US20180186742A1 - Picolinamides as fungicides - Google Patents

Picolinamides as fungicides Download PDF

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Publication number
US20180186742A1
US20180186742A1 US15/862,759 US201815862759A US2018186742A1 US 20180186742 A1 US20180186742 A1 US 20180186742A1 US 201815862759 A US201815862759 A US 201815862759A US 2018186742 A1 US2018186742 A1 US 2018186742A1
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colorless oil
compounds
mmol
compound according
clear
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US15/862,759
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Brian A. Loy
Jared W. RIGOLI
Brannon Sam
Kevin G. Meyer
Chenglin Yao
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Corteva Agriscience LLC
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Dow AgroSciences LLC
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Priority to US15/862,759 priority Critical patent/US20180186742A1/en
Assigned to DOW AGROSCIENCES LLC reassignment DOW AGROSCIENCES LLC ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: RIGOLI, JARED W, YAO, CHENGLIN, MEYER, KEVIN G, LOY, BRIAN A, SAM, BRANNON
Publication of US20180186742A1 publication Critical patent/US20180186742A1/en
Assigned to CORTEVA AGRISCIENCE LLC reassignment CORTEVA AGRISCIENCE LLC CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). Assignors: DOW AGROSCIENCES LLC
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/02—Saturated carboxylic acids or thio analogues thereof; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/02—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having no bond to a nitrogen atom
    • A01N47/06—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having no bond to a nitrogen atom containing —O—CO—O— groups; Thio analogues thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/10—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
    • A01N47/12—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof containing a —O—CO—N< group, or a thio analogue thereof, neither directly attached to a ring nor the nitrogen atom being a member of a heterocyclic ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C229/06—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton
    • C07C229/08—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to hydrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C53/00—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen
    • C07C53/15—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen containing halogen
    • C07C53/23—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen containing halogen containing rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/32—Sulfur atoms
    • C07D213/34—Sulfur atoms to which a second hetero atom is attached
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/83—Thioacids; Thioesters; Thioamides; Thioimides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/89—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
    • C07D265/12—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems
    • C07D265/14—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D265/24—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with hetero atoms directly attached in positions 2 and 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
    • C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
    • C07D317/54—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
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    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
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    • C07C2601/00—Systems containing only non-condensed rings
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

Definitions

  • Fungicides are compounds, of natural or synthetic origin, which act to protect and/or cure plants against damage caused by agriculturally relevant fungi. Generally, no single fungicide is useful in all situations. Consequently, research is ongoing to produce fungicides that may have better performance, are easier to use, and cost less.
  • the present disclosure relates to picolinamides and their use as fungicides.
  • the compounds of the present disclosure may offer protection against ascomycetes, basidiomycetes, deuteromycetes and oomycetes.
  • X is hydrogen or C(O)R 5 ;
  • Y is hydrogen, C(O)R 5 , or Q;
  • Z is N or N + ⁇ O ⁇ and W is O or S;
  • R 1 is hydrogen or alkyl, substituted with 0, 1 or multiple R 8 ;
  • R 2 is methyl
  • R 3 and R 3′ are independently chosen from C 2 -C 6 alkyl, C 3 -C 6 cycloalkyl, aryl or heteroaryl, each optionally substituted with 0, 1 or multiple R 8 ; Alternatively, R 3 and R 3′ may be taken together to form a 3-6 membered saturated or partially saturated carbocycle or heterocycle, optionally substituted with 0, 1 or multiple R 8 ;
  • R 4 is chosen from aryl or heteroaryl, each optionally substituted with 0, 1 or multiple R 8 ;
  • R 5 is chosen from alkoxy or benzyloxy, each optionally substituted with 0, 1, or multiple R 8 ;
  • R 6 is chosen from hydrogen, alkoxy, or halo, each optionally substituted with 0, 1, or multiple R 8 ;
  • R 7 is chosen from hydrogen, —C(O)R 9 , or —CH 2 OC(O)R 9 ;
  • R 8 is chosen from hydrogen, alkyl, aryl, acyl, halo, alkenyl, alkynyl, alkoxy, cyano, or heterocyclyl, each optionally substituted with 0, 1, or multiple R 10 ;
  • R 9 is chosen from alkyl, alkoxy, or aryl, each optionally substituted with 0, 1, or multiple R 8 ;
  • R 10 is chosen from hydrogen, alkyl, aryl, acyl, halo, alkenyl, alkoxy, or heterocyclyl;
  • R 11 is chosen from hydrogen or alkyl, each substituted with 0, 1 or multiple R 8 .
  • Another embodiment of the present disclosure may include a fungicidal composition for the control or prevention of fungal attack comprising the compounds described above and a phytologically acceptable carrier material.
  • Yet another embodiment of the present disclosure may include a method for the control or prevention of fungal attack on a plant, the method including the steps of applying a fungicidally effective amount of one or more of the compounds described above to at least one of the fungus, the plant, and an area adjacent to the plant.
  • alkyl refers to a branched, unbranched, or saturated cyclic carbon chain, including, but not limited to, methyl, ethyl, propyl, butyl, isopropyl, isobutyl, tertiary butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like.
  • alkenyl refers to a branched, unbranched or cyclic carbon chain containing one or more double bonds including, but not limited to, ethenyl, propenyl, butenyl, isopropenyl, isobutenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, and the like.
  • aryl and “Ar” refer to any aromatic ring, mono- or bi-cyclic, containing 0 heteroatoms.
  • heterocyclyl refers to any aromatic or non-aromatic ring, mono- or bi-cyclic, containing one or more heteroatoms
  • alkoxy refers to an —OR substituent.
  • acyloxy refers to an —OC(O)R substituent.
  • cyano refers to a —C ⁇ N substituent.
  • hydroxyl refers to a —OH substituent.
  • amino refers to an —N(R) 2 substituent.
  • arylalkoxy refers to —O(CH 2 ) n Ar where n is an integer selected from the list 1, 2, 3, 4, 5, or 6.
  • haloalkoxy refers to an —OR—X substituent, wherein X is Cl, F, Br, or I, or any combination thereof.
  • haloalkyl refers to an alkyl, which is substituted with Cl, F, I, or Br or any combination thereof.
  • halogen refers to one or more halogen atoms, defined as F, Cl, Br, and I.
  • nitro refers to a —NO 2 substituent.
  • thioalkyl refers to a —SR substituent.
  • Formula (I) is read as also including salts or hydrates thereof.
  • Exemplary salts include, but are not limited to: hydrochloride, hydrobromide, hydroiodide, trifluoroacetate, and trifluoromethane sulfonate.
  • Another embodiment of the present disclosure is a use of a compound of Formula I, for protection of a plant against attack by a phytopathogenic organism or the treatment of a plant infested by a phytopathogenic organism, comprising the application of a compound of Formula I, or a composition comprising the compound to soil, a plant, a part of a plant, foliage, and/or roots.
  • composition useful for protecting a plant against attack by a phytopathogenic organism and/or treatment of a plant infested by a phytopathogenic organism comprising a compound of Formula I and a phytologically acceptable carrier material.
  • the compounds of the present disclosure may be applied by any of a variety of known techniques, either as the compounds or as formulations comprising the compounds.
  • the compounds may be applied to the roots or foliage of plants for the control of various fungi, without damaging the commercial value of the plants.
  • the materials may be applied in the form of any of the generally used formulation types, for example, as solutions, dusts, wettable powders, flowable concentrate, or emulsifiable concentrates.
  • the compounds of the present disclosure are applied in the form of a formulation, comprising one or more of the compounds of Formula I with a phytologically acceptable carrier.
  • Concentrated formulations may be dispersed in water, or other liquids, for application, or formulations may be dust-like or granular, which may then be applied without further treatment.
  • the formulations can be prepared according to procedures that are conventional in the agricultural chemical art.
  • the present disclosure contemplates all vehicles by which one or more of the compounds may be formulated for delivery and used as a fungicide.
  • formulations are applied as aqueous suspensions or emulsions.
  • Such suspensions or emulsions may be produced from water-soluble, water-suspendable, or emulsifiable formulations which are solids, usually known as wettable powders; or liquids, usually known as emulsifiable concentrates, aqueous suspensions, or suspension concentrates.
  • any material to which these compounds may be added may be used, provided it yields the desired utility without significant interference with the activity of these compounds as antifungal agents.
  • Wettable powders which may be compacted to form water-dispersible granules, comprise an intimate mixture of one or more of the compounds of Formula I, an inert carrier and surfactants.
  • concentration of the compound in the wettable powder may be from about 10 percent to about 90 percent by weight based on the total weight of the wettable powder, more preferably about 25 weight percent to about 75 weight percent.
  • the compounds may be compounded with any finely divided solid, such as prophyllite, talc, chalk, gypsum, Fuller's earth, bentonite, attapulgite, starch, casein, gluten, montmorillonite clays, diatomaceous earths, purified silicates or the like.
  • the finely divided carrier and surfactants are typically blended with the compound(s) and milled.
  • Emulsifiable concentrates of the compounds of Formula I may comprise a convenient concentration, such as from about 1 weight percent to about 50 weight percent of the compound, in a suitable liquid, based on the total weight of the concentrate.
  • the compounds may be dissolved in an inert carrier, which is either a water-miscible solvent or a mixture of water-immiscible organic solvents, and emulsifiers.
  • the concentrates may be diluted with water and oil to form spray mixtures in the form of oil-in-water emulsions.
  • Useful organic solvents include aromatics, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic solvents may also be used, for example, terpenic solvents, including rosin derivatives, aliphatic ketones, such as cyclohexanone, and complex alcohols, such as 2-ethoxyethanol.
  • Emulsifiers which may be advantageously employed herein may be readily determined by those skilled in the art and include various nonionic, anionic, cationic and amphoteric emulsifiers, or a blend of two or more emulsifiers.
  • nonionic emulsifiers useful in preparing the emulsifiable concentrates include the polyalkylene glycol ethers and condensation products of alkyl and aryl phenols, aliphatic alcohols, aliphatic amines or fatty acids with ethylene oxide, propylene oxides such as the ethoxylated alkyl phenols and carboxylic esters solubilized with the polyol or polyoxyalkylene.
  • Cationic emulsifiers include quaternary ammonium compounds and fatty amine salts.
  • Anionic emulsifiers include the oil-soluble salts (e.g., calcium) of alkylaryl sulphonic acids, oil-soluble salts or sulfated polyglycol ethers and appropriate salts of phosphated polyglycol ether.
  • organic liquids which may be employed in preparing the emulsifiable concentrates of the compounds of the present disclosure are the aromatic liquids such as xylene, propyl benzene fractions; or mixed naphthalene fractions, mineral oils, substituted aromatic organic liquids such as dioctyl phthalate; kerosene; dialkyl amides of various fatty acids, particularly the dimethyl amides of fatty glycols and glycol derivatives such as the n-butyl ether, ethyl ether or methyl ether of diethylene glycol, the methyl ether of triethylene glycol, petroleum fractions or hydrocarbons such as mineral oil, aromatic solvents, paraffinic oils, and the like; vegetable oils such as soy bean oil, rape seed oil, olive oil, castor oil, sunflower seed oil, coconut oil, corn oil, cotton seed oil, linseed oil, palm oil, peanut oil, safflower oil, sesame oil, tung oil and the like; esters of
  • Organic liquids include xylene, and propyl benzene fractions, with xylene being most preferred in some cases.
  • Surface-active dispersing agents are typically employed in liquid formulations and in an amount of from 0.1 to 20 percent by weight based on the combined weight of the dispersing agent with one or more of the compounds.
  • the formulations can also contain other compatible additives, for example, plant growth regulators and other biologically active compounds used in agriculture.
  • Aqueous suspensions comprise suspensions of one or more water-insoluble compounds of Formula I, dispersed in an aqueous vehicle at a concentration in the range from about 1 to about 50 weight percent, based on the total weight of the aqueous suspension.
  • Suspensions are prepared by finely grinding one or more of the compounds, and vigorously mixing the ground material into a vehicle comprised of water and surfactants chosen from the same types discussed above.
  • Other components such as inorganic salts and synthetic or natural gums, may also be added to increase the density and viscosity of the aqueous vehicle.
  • the compounds of Formula I can also be applied as granular formulations, which are particularly useful for applications to the soil.
  • Granular formulations generally contain from about 0.5 to about 10 weight percent, based on the total weight of the granular formulation of the compound(s), dispersed in an inert carrier which consists entirely or in large part of coarsely divided inert material such as attapulgite, bentonite, diatomite, clay or a similar inexpensive substance.
  • Such formulations are usually prepared by dissolving the compounds in a suitable solvent and applying it to a granular carrier which has been preformed to the appropriate particle size, in the range of from about 0.5 to about 3 mm.
  • a suitable solvent is a solvent in which the compound is substantially or completely soluble.
  • Such formulations may also be prepared by making a dough or paste of the carrier and the compound and solvent, and crushing and drying to obtain the desired granular particle.
  • Dusts containing the compounds of Formula I may be prepared by intimately mixing one or more of the compounds in powdered form with a suitable dusty agricultural carrier, such as, for example, kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1 to about 10 weight percent of the compounds, based on the total weight of the dust.
  • a suitable dusty agricultural carrier such as, for example, kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1 to about 10 weight percent of the compounds, based on the total weight of the dust.
  • the formulations may additionally contain adjuvant surfactants to enhance deposition, wetting, and penetration of the compounds onto the target crop and organism.
  • adjuvant surfactants may optionally be employed as a component of the formulation or as a tank mix.
  • the amount of adjuvant surfactant will typically vary from 0.01 to 1.0 percent by volume, based on a spray-volume of water, preferably 0.05 to 0.5 volume percent.
  • Suitable adjuvant surfactants include, but are not limited to ethoxylated nonyl phenols, ethoxylated synthetic or natural alcohols, salts of the esters or sulphosuccinic acids, ethoxylated organosilicones, ethoxylated fatty amines, blends of surfactants with mineral or vegetable oils, crop oil concentrate (mineral oil (85%)+emulsifiers (15%)); nonylphenol ethoxylate; benzylcocoalkyldimethyl quaternary ammonium salt; blend of petroleum hydrocarbon, alkyl esters, organic acid, and anionic surfactant; C 9 -C 11 alkylpolyglycoside; phosphated alcohol ethoxylate; natural primary alcohol (C 12 -C 16 ) ethoxylate; di-sec-butylphenol EO-PO block copolymer; polysiloxane-methyl cap; nonylphenol ethoxylate+urea ammonium
  • the formulations may optionally include combinations that contain other pesticidal compounds.
  • additional pesticidal compounds may be fungicides, insecticides, herbicides, nematocides, miticides, arthropodicides, bactericides or combinations thereof that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds.
  • the other pesticidal compound is employed as a supplemental toxicant for the same or for a different pesticidal use.
  • the compounds of Formula I and the pesticidal compound in the combination can generally be present in a weight ratio of from 1:100 to 100:1.
  • the compounds of the present disclosure may also be combined with other fungicides to form fungicidal mixtures and synergistic mixtures thereof.
  • the fungicidal compounds of the present disclosure are often applied in conjunction with one or more other fungicides to control a wider variety of undesirable diseases.
  • the presently claimed compounds may be formulated with the other fungicide(s), tank-mixed with the other fungicide(s) or applied sequentially with the other fungicide(s).
  • Such other fungicides may include 2-(thiocyanatomethylthio)-benzothiazole, 2-phenylphenol, 8-hydroxyquinoline sulfate, ametoctradin, amisulbrom, antimycin, Ampelomyces quisqualis , azaconazole, Bacillus subtilis, Bacillus subtilis strain QST713, benalaxyl, benomyl, benthiavalicarb-isopropyl, benzovindiflupyr, benzylaminobenzene-sulfonate (BABS) salt, bicarbonates, biphenyl, bismerthiazol, bitertanol, bixafen, blasticidin-S, borax, Bordeaux mixture, boscalid, bromuconazole, bupirimate, calcium polysulfide, captafol, captan, carbendazim, carboxin, carpropamid, carvone, chlazafenone, chloroneb, chlor
  • the compounds described herein may be combined with other pesticides, including insecticides, nematocides, miticides, arthropodicides, bactericides or combinations thereof that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds to form pesticidal mixtures and synergistic mixtures thereof.
  • the fungicidal compounds of the present disclosure may be applied in conjunction with one or more other pesticides to control a wider variety of undesirable pests.
  • the presently claimed compounds may be formulated with the other pesticide(s), tank-mixed with the other pesticide(s) or applied sequentially with the other pesticide(s).
  • Typical insecticides include, but are not limited to: 1,2-dichloropropane, abamectin, acephate, acetamiprid, acethion, acetoprole, acrinathrin, acrylonitrile, alanycarb, aldicarb, aldoxycarb, aldrin, allethrin, allosamidin, allyxycarb, alpha-cypermethrin, alpha-ecdysone, alpha-endosulfan, amidithion, aminocarb, amiton, amiton oxalate, amitraz, anabasine, athidathion, azadirachtin, azamethiphos, azinphos-ethyl, azinphos-methyl, azothoate, barium hexafluorosilicate, barthrin, bendiocarb, benfuracarb, bensultap, beta-cyfluthr
  • the compounds described herein may be combined with herbicides that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds to form pesticidal mixtures and synergistic mixtures thereof.
  • the fungicidal compounds of the present disclosure may be applied in conjunction with one or more herbicides to control a wide variety of undesirable plants.
  • the presently claimed compounds may be formulated with the herbicide(s), tank-mixed with the herbicide(s) or applied sequentially with the herbicide(s).
  • Typical herbicides include, but are not limited to: 4-CPA; 4-CPB; 4-CPP; 2,4-D; 3,4-DA; 2,4-DB; 3,4-DB; 2,4-DEB; 2,4-DEP; 3,4-DP; 2,3,6-TBA; 2,4,5-T; 2,4,5-TB; acetochlor, acifluorfen, aclonifen, acrolein, alachlor, allidochlor, alloxydim, allyl alcohol, alorac, ametridione, ametryn, amibuzin, amicarbazone, amidosulfuron, aminocyclopyrachlor, aminopyralid, amiprofos-methyl, amitrole, ammonium sulfamate, anilofos, anisuron, asulam, atraton, atrazine, azafenidin, azimsulfuron, aziprotryne, barban, BCPC, beflubutamid, benazolin, ben
  • Another embodiment of the present disclosure is a method for the control or prevention of fungal attack.
  • This method comprises applying to the soil, plant, roots, foliage, or locus of the fungus, or to a locus in which the infestation is to be prevented (for example applying to cereal or grape plants), a fungicidally effective amount of one or more of the compounds of Formula I.
  • the compounds are suitable for treatment of various plants at fungicidal levels, while exhibiting low phytotoxicity.
  • the compounds may be useful both in a protectant and/or an eradicant fashion.
  • the compounds have been found to have significant fungicidal effect particularly for agricultural use. Many of the compounds are particularly effective for use with agricultural crops and horticultural plants.
  • the compounds have broad ranges of activity against fungal pathogens.
  • exemplary pathogens may include, but are not limited to, causing agent of wheat leaf blotch ( Zymoseptoria tritici ), wheat brown rust ( Puccinia triticina ), wheat stripe rust ( Puccinia striiformis ), scab of apple ( Venturia inaequalis ), powdery mildew of grapevine ( Uncinula necator ), barley scald ( Rhynchosporium secalis ), blast of rice ( Magnaporthe grisea ), rust of soybean ( Phakopsora pachyrhizi ), glume blotch of wheat ( Leptosphaeria nodorum ), powdery mildew of wheat ( Blumeria graminis f.
  • the exact amount of the active material to be applied is dependent not only on the specific active material being applied, but also on the particular action desired, the fungal species to be controlled, and the stage of growth thereof, as well as the part of the plant or other product to be contacted with the compound. Thus, all the compounds, and formulations containing the same, may not be equally effective at similar concentrations or against the same fungal species.
  • the compounds are effective in use with plants in a disease-inhibiting and phytologically acceptable amount.
  • disease-inhibiting and phytologically acceptable amount refers to an amount of a compound that kills or inhibits the plant disease for which control is desired, but is not significantly toxic to the plant. This amount will generally be from about 0.1 to about 1000 ppm (parts per million), with 1 to 500 ppm being preferred.
  • concentration of compound required varies with the fungal disease to be controlled, the type of formulation employed, the method of application, the particular plant species, climate conditions, and the like.
  • a suitable application rate is typically in the range from about 0.10 to about 4 pounds/acre (about 0.01 to 0.45 grams per square meter, g/m 2 ).
  • the compounds of Formula I may be made using well-known chemical procedures. Intermediates not specifically mentioned in this disclosure are either commercially available, may be made by routes disclosed in the chemical literature, or may be readily synthesized from commercial starting materials utilizing standard procedures.
  • Compounds of Formula 1.3 and 1.4 wherein R 4 is as originally defined can be prepared by the methods shown in Scheme 1, steps a-c.
  • Compounds of Formula 1.1, wherein R 4 is as originally defined can be prepared by treatment of halogens (X) of Formula 1.0, wherein R 4 is as originally defined, first under standard Grignard conditions, using magnesium metal and an alkali base, such as lithium chloride, in a polar, aprotic solvent such as tetrahydrofuran (THF) or diethyl ether (Et 2 O), at a temperature of about 0° C. to about 70° C., to afford the Grignard intermediate.
  • halogens (X) of Formula 1.0, wherein R 4 is as originally defined can be prepared by treatment of halogens (X) of Formula 1.0, wherein R 4 is as originally defined, first under standard Grignard conditions, using magnesium metal and an alkali base, such as lithium chloride, in a polar, aprotic solvent such as
  • the solution is then treated with a metal catalyst, such as iron (III) acetylacetonate, followed by allyl chloride, in a polar aprotic solvent, such as THF, at a temperature of about 0° C. to about 70° C., to give compounds of Formula 1.1, wherein R 4 is as previously defined, and shown in step a.
  • a metal catalyst such as iron (III) acetylacetonate
  • allyl chloride in a polar aprotic solvent, such as THF, at a temperature of about 0° C. to about 70° C.
  • Compounds of Formula 1.1, wherein R 4 is as previously defined, can be isomerized to compounds of Formula 1.2 by treating with a metal catalyst system, such as bis(dibenzylideneactone)palladium (0), a phosphine coordinating reagent, such as tri-tert-butylphosphine, and an acid chloride, such as isobutyryl chloride, in an aromatic hydrocarbon solvent such as toluene, at a temperature of about 25° C. to 100° C., to afford compounds of Formula 1.2, wherein R 4 is as originally defined, and shown in step b.
  • a metal catalyst system such as bis(dibenzylideneactone)palladium (0), a phosphine coordinating reagent, such as tri-tert-butylphosphine, and an acid chloride, such as isobutyryl chloride
  • compounds of Formula 1.2 can be isomerized using the conditions of Mayer, M.; Welther, A.; Jacobi von Wangelin, A. ChemCatChem. 2011, 3, 1567-1571, and shown in step b.
  • Epoxides of Formulas 1.3 and 1.4, wherein R 4 is as previously defined can be obtained by a catalytic asymmetric epoxidation method using oxone as oxidant and a fructose derived ketone as described by Wang, Z-X; Tu, Y.; Frohn, M.; Zhang, J-R.; Shi, Y. J. Am. Chem. Soc.
  • epoxides of Formulae 1.3 and 1.4, wherein R 4 is as previously defined can be prepared by other catalytic asymmetric epoxidation methods, including, but not limited to, dioxiranes derived from other chiral ketones; catalytic metal salen complexes using an oxidant, such
  • compounds of Formula 1.2 can be prepared by the oxo-metathesis method of Franzen ( Eur. J. Org. Chem. 2015, 1834) and shown in step d.
  • aldehydes of Formula 1.5 wherein R 4 is as previously defined, with an alkene, such as 2-methyl-2-butene, and a Lewis acidic catalyst, such as trityl tetrafluoroborate, in a polar, aprotic solvent, such as dichloromethane, at a temperature of about ⁇ 78° C. to about room temperature, affords trans-alkenes of Formula 1.2, wherein R 4 is as previously defined.
  • an alkene such as 2-methyl-2-butene
  • a Lewis acidic catalyst such as trityl tetrafluoroborate
  • organometallic nucleophile such as an alkyl magnesium halide
  • a metal halide such as copper iodide
  • a polar, aprotic solvent such as THF or Et 2 O
  • an alkenyl organometallic reagent as the carbon nucleophile and shown in Scheme 3.
  • Compounds of Formulas 3.1 and 3.3, wherein R 3 and R 4 are as previously defined can be prepared by treating epoxides of Formulas 1.3 and 1.4, wherein R 4 is as previously defined, with an alkenyl magnesium halide, such as prop-1-en-2-ylmagnesium bromide, in the presence of a metal halide, such as copper iodide, in a polar, aprotic solvent, such as THF or Et 2 O, at a temperature of about ⁇ 78° C. to 25° C., and shown in step a.
  • an alkenyl magnesium halide such as prop-1-en-2-ylmagnesium bromide
  • a metal halide such as copper iodide
  • aprotic solvent such as THF or Et 2 O
  • Formulas 3.2 and 3.4, wherein R 3 and R 4 are as previously defined can be prepared by treatment of compounds of Formulas 3.1 and 3.3, wherein R 3 and R 4 are as previously defined, with a metal hydrogenation catalyst, such as tris(triphenylphosphine)rhodium(I) chloride (Wilkinson's catalyst) in a polar, aprotic solvent, such as THF, in the presence of a hydrogen atmosphere (1-4 atm); or, alternatively, with palladium absorbed on carbon, in a polar solvent, such as THF, in the presence of a hydrogen atmosphere (1-4 atm), and shown in step b.
  • a metal hydrogenation catalyst such as tris(triphenylphosphine)rhodium(I) chloride (Wilkinson's catalyst) in a polar, aprotic solvent, such as THF, in the presence of a hydrogen atmosphere (1-4 atm); or, alternatively, with palladium absorbed on carbon, in a polar solvent,
  • compounds of Formula 4.2 wherein R 3 , R 3′ and R 4 are as previously defined and R 3 and R 3′ may or may not be equivalent, can be prepared by the procedure shown in Scheme 4, steps a and b.
  • Compounds of Formula 2.1, wherein R 3 , R 3′ and R 4 are as previously defined and R 3 and R 3′ may or may not be equivalent, can be treated with an oxidizing reagent, such as the Dess-Martin periodinane, in a polar solvent such as dichloromethane (CH 2 Cl 2 ), at a temperature of about 0° C.
  • an oxidizing reagent such as the Dess-Martin periodinane
  • compounds of Formula 4.1 can be enantioselective reduced by other chiral catalyst/hydride reducing agent combinations, including, but not limited to, chirally modified lithium aluminum hydride or sodium borohydride reagents, phosphoramide catalysts, transfer hydrogenation catalyzed by chiral metal complexes, phase transfer catalysts, or enantioselective hydrogenation of pro-chiral ketones by enzymatic catalysis.
  • chiral catalyst/hydride reducing agent combinations including, but not limited to, chirally modified lithium aluminum hydride or sodium borohydride reagents, phosphoramide catalysts, transfer hydrogenation catalyzed by chiral metal complexes, phase transfer catalysts, or enantioselective hydrogenation of pro-chiral ketones by enzymatic catalysis.
  • a racemic mixture of compounds of Formula 2.1 and 2.2, wherein R 3 , R 3′ and R 4 are as previously defined, and R 3 and R 3′ may or may not be equivalent, can be prepared by treating compounds of Formula 4A.3, wherein R 3 , R 3′ and R 4 are as originally defined, and R 3 and R 3′ may or may not be equivalent, with a hydride reducing agent, such as lithium aluminum hydride, in a polar, aprotic solvent, such as THF, at a temperature of about ⁇ 78° C.
  • a hydride reducing agent such as lithium aluminum hydride
  • a polar, aprotic solvent such as THF
  • a racemic mixture of compounds of Formula 2.1 and 2.2, wherein R 3 , R 3′ and R 4 are as previously defined, and R 3 and R 3′ may or may not be equivalent, can be separated by treatment of the mixture with an optically active carboxylic acid, such as (S)-2-methoxy-2-phenylacetic acid, a coupling reagent, such as 3-(ethyliminomethyleneamino)-N,N-dimethylpropan-1-amine hydrochloride (EDC) or a polymer-supported carbodiimide (PS-CDI), and a catalyst, such as N,N-dimethylpyridin-4-amine (DMAP), in a halogenated or polar, aprotic solvent, such as CH 2 Cl 2 or THF to afford compounds of Formula 4A.4 and 4A.5, wherein R 3 , R 3′ and R 4 are as originally defined, and R 3 and R 3′ may or may not be equivalent, as shown in step e.
  • the diastereomeric mixture can then separated into its individual components via silica gel chromatography using a mobile phase, such as 10% tert-butyl methyl ether in hexanes, as the eluant.
  • a mobile phase such as 10% tert-butyl methyl ether in hexanes
  • the individual diastereomers, compounds of Formula 4A.4 and 4A.5, wherein R 3 , R 3′ and R 4 are as originally defined, and R 3 and R 3′ may or may not be equivalent, can be treated with a carbonate base, such as potassium carbonate, in a polar, alcoholic solvent, such as methanol, at a temperature of about 25° C. to about 60° C., to give compounds of Formula 2.1 and 2.2, wherein R 3 , R 3′ and R 4 are as previously defined, and R 3 and R 3′ may or may not be equivalent, and shown in step f.
  • a carbonate base such as potassium carbonate
  • compounds of Formula 5.5 and 5.9 wherein R 3 , R 3′ and R 4 are as previously defined and R 3 and R 3′ may or may not be equivalent, can be prepared by the procedure shown in Scheme 5, steps a-i.
  • the compound of Formula 5.0 can be treated with an aryl or heteroaryl organometallic reagent, such as phenylmagnesium bromide, in a polar aprotic solvent, such as THF or Et 2 O, at a temperature of about 0° C. to room temperature, to afford compounds of Formula 5.1, wherein R 4 is as originally defined, and shown in step a.
  • an aryl or heteroaryl organometallic reagent such as phenylmagnesium bromide
  • a polar aprotic solvent such as THF or Et 2 O
  • R 3 and R 3′ may or may not be equivalent, can be obtained by treating compounds of Formula 5.2, wherein R 4 is as originally defined, with an organometallic nucleophile, such as isopropylmagnesium bromide, in a polar aprotic solvent, such as THF or Et 2 O, at a temperature of about 0° C. to room temperature, as depicted in step c.
  • organometallic nucleophile such as isopropylmagnesium bromide
  • a polar aprotic solvent such as THF or Et 2 O
  • Compounds of Formula 5.4 wherein R 3 , R 3′ , and R 4 are as previously defined and R 3 and R 3′ may or may not be equivalent, and R 4 is not an electron-deficient aryl or heteroaryl group, can be obtained by treating the compounds of Formula 5.3, wherein R 3 , R 3′ are as previously defined and may or may not be equivalent, and R 4 is not an electron-deficient aryl or heteroaryl group, with a mixture of a hydride reagent, such as triethylsilane (Et 3 SiH), and an acid, such as 2,2,2-trifluoroacetic acid (TFA) in a halogenated solvent such as dichloromethane (DCM) at a temperature of about 0° C.
  • a hydride reagent such as triethylsilane (Et 3 SiH)
  • an acid such as 2,2,2-trifluoroacetic acid (TFA)
  • DCM dichloromethane
  • Compounds of Formula 5.5, wherein R 3 , R 3′ , and R 4 are as originally defined and R 3 may or may not be equivalent to R 3′ can be prepared from compounds of Formula 5.4, wherein R 3 , R 3′ , and R 4 are as originally defined and R 3 may or may not be equivalent to R 3′ , by treating with a metal catalyst such as palladium on carbon (Pd/C) in a polar protic solvent, such as ethanol (EtOH), in a hydrogen atmosphere (1-4 atm) at a temperature of about 25° C.
  • a metal catalyst such as palladium on carbon (Pd/C)
  • a polar protic solvent such as ethanol (EtOH)
  • Compounds of Formula 5.8, wherein R 3 and R 4 are as previously defined, and R 4 is not an electron-deficient aryl or heteroaryl group can be obtained by treating the compounds of Formula 5.7, wherein R 3 and R 4 are as previously defined, and R 4 is not an electron-deficient aryl or heteroaryl group, with a mixture of a hydride reagent, such as triethylsilane (Et 3 SiH), and an acid, such as 2,2,2-trifluoroacetic acid (TFA) in a halogenated solvent such as dichloromethane (DCM) at a temperature of about 0° C. to 23° C., as depicted in h.
  • a hydride reagent such as triethylsilane (Et 3 SiH)
  • an acid such as 2,2,2-trifluoroacetic acid (TFA)
  • DCM dichloromethane
  • Compounds of Formula 5.9, wherein R 3 and R 4 are as previously defined can be prepared by treatment of compounds of Formula 5.8, wherein R 3 and R 4 are as previously defined, with a metal hydrogenation catalyst, such as tris(triphenylphosphine)rhodium(I) chloride (Wilkinson's catalyst) in a polar, aprotic solvent, such as THF, in the presence of a hydrogen atmosphere (1-4 atm); or, alternatively, with palladium absorbed on carbon, in a polar solvent, such as THF, in the presence of a hydrogen atmosphere (1-4 atm), and shown in step i.
  • a metal hydrogenation catalyst such as tris(triphenylphosphine)rhodium(I) chloride (Wilkinson's catalyst) in a polar, aprotic solvent, such as THF, in the presence of a hydrogen atmosphere (1-4 atm); or, alternatively, with palladium absorbed on carbon, in a polar solvent, such as THF,
  • compounds of Formula 5.5 wherein R 3 , R 3′ , and R 4 , are as originally defined, and R 3 and R 3′ may or may not be equivalent, may also be prepared according to the method outlined in Scheme 6, steps a and b.
  • step b compounds of Formula 6.1, wherein R 3 , R 3′ , and R 4 are as originally defined, and R 3 and R 3′ may or may not be equivalent, can be treated with an aqueous solution of an inorganic base, such as sodium hydroxide, in a polar aprotic solvent, such as THF, at a temperature of about 0° C. to about 40° C. to afford compounds of Formula 5.5, wherein R 3 , R 3′ , and R 4 are as originally defined, and R 3 and R 3′ may or may not be equivalent.
  • an inorganic base such as sodium hydroxide
  • a polar aprotic solvent such as THF
  • Alcohols of Formula 5.5, wherein R 3 , R 3′ , and R 4 , are as originally defined, and R 3 and R 3′ may or may not be equivalent, can be treated with compounds of Formula 7.1, wherein R 1 and R 11 are as originally defined, a coupling reagent, such as 3-(ethyliminomethyleneamino)-N,N-dimethylpropan-1-amine hydrochloride (EDC) or a polymer-supported carbodiimide (PS-CDI), and a catalyst, such as N,N-dimethylpyridin-4-amine (DMAP), in a halogenated or polar, aprotic solvent, such as CH 2 Cl 2 or THF to afford compounds of Formula 7.2, wherein R 1 , R 3 , R 3′ , R 4 , and R 11 , are as originally defined, and R 3 and R 3′ may or may not be equivalent, as shown in step a.
  • a coupling reagent such as 3-(ethyliminomethylene
  • R 3 and R 3′ may or may not be equivalent, can be treated with compounds of Formula 7.1, wherein R 1 and R 11 are as originally defined, a phosphine reagent, such as triphenylphosphine, and a diazine dicarboxylate electrophile, such as diisopropyl (E)-diazene-1,2-dicarboxylate (DIAD), in a polar aprotic solvent, such as THF, at a temperature of about 0° C. to 25° C. to afford compounds of Formula 7.2, wherein R 1 , R 3 , R 3′ , R 4 , and R 11 , are as originally defined, and R 3 and R 3′ may or may not be equivalent, as shown in step a.
  • a phosphine reagent such as triphenylphosphine
  • a diazine dicarboxylate electrophile such as diisopropyl (E)-diazene-1,2-dicarboxy
  • Compounds of Formula 9.5 wherein R 1 , R 2 , R 3 , R 3′ , R 4 , R 6 and R 11 , are as originally defined, and R 3 and R 3′ may or may not be equivalent, can be treated with an appropriate alkyl halide with or without a reagent such as sodium iodide (NaI) and an alkali carbonate base, such as sodium (Na 2 CO 3 ) or potassium carbonate (K 2 CO 3 ), in a solvent such as acetone, as shown in step a.
  • a reagent such as sodium iodide (NaI) and an alkali carbonate base, such as sodium (Na 2 CO 3 ) or potassium carbonate (K 2 CO 3 )
  • a solvent such as acetone
  • Compounds of Formula 9.5 wherein R 1 , R 2 , R 3 , R 3′ , R 4 , R 6 , and R 11 , are as originally defined, and R 3 and R 3′ may or may not be equivalent, can be treated with a thionating reagent such as phosphorus pentasulfide, an additive, such as hexamethyldisiloxane, optionally in a polar aprotic solvent such as acetonitrile (CH 3 CN), at a temperature of about 0° C. to 80° C.
  • a thionating reagent such as phosphorus pentasulfide
  • an additive such as hexamethyldisiloxane
  • a polar aprotic solvent such as acetonitrile (CH 3 CN)
  • R 1 , R 2 , R 3 , R 3′ , R 4 , R 6 , and R 11 are as originally defined, and R 3 and R 3′ may or may not be equivalent, and shown in step a.
  • compounds such as Formula 11.1 may also be prepared using other thionating agents including, but not limited to: sulfur, sulfhydric acid, sodium sulfide, sodium hydrosulfide, boron trisulfide, bis(diethylaluminum)sulfide, ammonium sulfide, Lawesson's reagent, ammonium O,O′-diethyl dithiophosphate, rhodanine, or a polymer supported thionating reagent.
  • thionating agents including, but not limited to: sulfur, sulfhydric acid, sodium sulfide, sodium hydrosulfide, boron trisulfide, bis(diethylaluminum)sulfide, ammonium sulfide, Lawesson's reagent, ammonium O,O′-diethyl dithiophosphate, rhodanine, or a polymer supported thionating reagent.
  • Additives can include, but not limited to, aluminum oxide (Al 2 O 3 ); inorganic bases, such as potassium carbonate and sodium bicarbonate; organic bases, such as triethylamine, diethylaniline, pyridine and morpholine.
  • Al 2 O 3 aluminum oxide
  • inorganic bases such as potassium carbonate and sodium bicarbonate
  • organic bases such as triethylamine, diethylaniline, pyridine and morpholine.
  • Optional solvents can include, but not limited to, aliphatic, alicyclic or aromatic hydrocarbons, such as hexane, cyclohexane or toluene; halogenated hydrocarbons, such as dichloromethane, 1,2-dichloroethane and chlorobenzene; ethers, such as diethyl ether, 1,4-dioxane, THF and 1,2-dimethoxyethane; and other polar aprotic solvents such as pyridine and hexamethylphosphoramide (HMPA).
  • aliphatic, alicyclic or aromatic hydrocarbons such as hexane, cyclohexane or toluene
  • halogenated hydrocarbons such as dichloromethane, 1,2-dichloroethane and chlorobenzene
  • ethers such as diethyl ether, 1,4-dioxane, THF and 1,2-dimethoxyethane
  • step b treatment of compounds of Formula 11.1, wherein R 1 , R 2 , R 3 , R 3′ , R 4 , R 6 , and R 11 , are as originally defined, and R 3 and R 3′ may or may not be equivalent, with an appropriate alkyl halide with or without a reagent such as sodium iodide (NaI) and an alkali carbonate base, such as sodium carbonate (Na 2 CO 3 ) or potassium carbonate (K 2 CO 3 ), in a solvent like acetone at a temperature of about 55° C., or by treatment with an acyl halide or anhydride in the presence of an amine base, such as pyridine, triethylamine (Et 3 N), DMAP, or mixtures thereof, in an optional aprotic solvent such as DCM, at a temperature of about 23° C., can afford compounds of Formula 11.2 wherein R 1 , R 2 , R 3 , R 3′ , R 4 , R 6 , R 7
  • Compounds of Formula 9.5 wherein R 1 , R 2 , R 3 , R 3′ , R 4 , R 6 , and R 11 , are as originally defined, and R 3 and R 3′ may or may not be equivalent, can be treated with a oxidizing reagent such as m-chloroperbenzoic acid (mCPBA) in a polar solvent such as dichloromethane (CH 2 Cl 2 ), at a temperature of about 0° C. to 50° C., to give compounds of Formula 12.1, as shown in a.
  • mCPBA m-chloroperbenzoic acid
  • CH 2 Cl 2 dichloromethane
  • Compounds of Formula 9.5 wherein R 1 , R 2 , R 3 , R 3′ , R 4 , R 6 , and R 11 , are as originally defined, and R 3 and R 3′ may or may not be equivalent, can be treated with a deactivated carbonyl reagent such as triphosgene, with a base, such as pyridine, in a polar solvent, such as dichloromethane (CH 2 Cl 2 ), at a temperature of about 0° C. to 50° C.
  • a deactivated carbonyl reagent such as triphosgene
  • a base such as pyridine
  • a polar solvent such as dichloromethane (CH 2 Cl 2 )
  • R 1 , R 2 , R 3 , R 3′ , R 4 , R 6 , and R 11 are as originally defined, and R 3 and R 3′ may or may not be equivalent, as depicted in a.
  • the mixture was warmed to room temperature over 1 hr and was heated at 70° C. overnight.
  • the reaction was cooled and diluted with petroleum ether (100 mL).
  • the reaction was then quenched by the addition of a saturated NH 4 Cl solution (100 mL).
  • the mixture was filtered through a Celite® pad and the layers were separated.
  • the aqueous layer was extracted with petroleum ether (2 ⁇ 100 mL) and the combined organic phases were dried over Na 2 SO 4 and carefully concentrated (25° C., 250 mbar).
  • This compound was prepared by the method of Franzen ( Eur. J. Org. Chem. 2015, 1834). To a solution of 2-methylbenzaldehyde (48.4 mL, 416 mmol) dissolved in CH 2 Cl 2 (300 mL) was added 2-methylbut-2-ene (8.82 mL, 83 mmol) and triphenylmethylium tetrafluoroborate (5.50 g, 16.65 mmol). The reaction was stirred at room temperature for 20 hr. The reaction was quenched by the addition of saturated NaHCO 3 and diluted with excess CH 2 Cl 2 . The organic layer was separated, dried over MgSO 4 , filtered and concentrated at low temperature and mild pressure.
  • Example 2A 2A Denotes that this Epoxide is Commercially Available
  • reaction mixture was cooled to 0° C. with an ice bath.
  • a solution of oxone (6.53 g, 10.61 mmol) in aqueous Na 2 (EDTA) (4 ⁇ 10 ⁇ 4 M, 50 mL) and a solution of potassium carbonate (6.17 g, 44.6 mmol) in water (50 mL) were added dropwise through two syringe pumps over a period of 1.5 h (under these conditions, the reaction pH is around 10.5; it is recommended that both oxone and K 2 CO 3 be added uniformly over 1.5 h).
  • the reaction was immediately quenched by the addition of 100 mL each of petroleum ether and water.
  • a suspension of magnesium (110 mg, 4.51 mmol) was prepared in THF (3 mL) and cooled to 0° C. After 5 min, bromocyclobutane (397 ⁇ L, 4.21 mmol) was added in one portion, and the resulting solution was vigorously stirred for 2 hr, slowly warming to room temperature. After 2 hr, the reaction was heated to 55° C. and stirred overnight. In a separate vial, a suspension of copper(I) iodide (401 mg, 2.106 mmol) in diethyl ether (7.5 mL) was cooled to ⁇ 30° C. in a dry ice/acetonitrile bath.
  • the oil was purified via silica gel Isco column chromatography (40 g silica gel column, 35 mL/min, 100% hexanes to 20% acetone:hexanes) to afford (2R,3S)-4-ethyl-3-(4-fluoro-2-methylphenyl)hexan-2-ol (116.7 mg, 0.490 mmol, 32.5% yield) as a yellow oil.
  • the oil was purified via silica gel Isco column chromatography (40 g silica gel column, 35 mL/min, 100% hexanes to 20% acetone:hexanes) to afford (2R,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpent-4-en-2-ol (120.2 mg, 0.577 mmol, 96% yield) as a pale yellow oil.
  • reaction was concentrated to a dark orange-brown oil, and the resulting oil was loaded directly onto a 25 g prepacked silica column in a minimal amount of dichloromethane and purified using Isco silica gel column chromatography (120 column, 85 mL/min, 100% hexanes to 30% ethyl acetate:hexanes) to afford (2R,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpentan-2-ol (880 mg, 4.18 mmol, 75% yield) as a clear, colorless oil.
  • reaction mixture was treated dropwise with triethylamine (3.76 mL, 27.0 mmol). The reaction mixture was stirred for 5 minutes and then allowed to warm to room temperature. The reaction was monitored by TLC (20% EtOAc in hexanes). The reaction mixture was poured into H 2 O and the phases were separated. The aqueous phase was extracted with CH 2 Cl 2 . The combined organics were dried with sodium sulfate and concentrated.
  • Step 2A Preparation of (S)-1-(benzo[d][1,3]dioxol-5-yl)-2-(benzyloxy)propan-1-one.
  • the resulting oil was loaded directly onto a 25 g prepacked silica column in a minimal amount of dichloromethane and purified using Isco silica gel column chromatography (40 column, 35 mL/min, 100% hexanes to 20% ethyl acetate:hexanes) to afford the title compound (659 mg, 98%) as a clear, colorless oil.
  • Step 4 Preparation of (2R,3S)-3-(2,5-dimethylphenyl)-4-methylpentan-2-ol and (2S,3R)-3-(2,5-dimethylphenyl)-4-methylpentan-7-ol
  • Lithium aluminum hydride (2.80 mL, 2.80 mmol) as a solution (1.0 M in THF) was added to a flask containing THF (28.0 mL) cooled to ⁇ 78° C.
  • a solution of 3-(2,5-dimethylphenyl)-4-methylpentan-2-one (0.573 g, 2.80 mmol) in THF (3 mL) was added dropwise.
  • the reaction was warmed to room temperature and stirred overnight.
  • the reaction was cooled to 0° C. and quenched by the addition of 0.1 mL H 2 O, 0.1 mL 1N NaOH, followed by an additional 0.3 mL of H 2 O.
  • the mixture was stirred vigorously for 15 min.
  • Step 5 Preparation of (2R,3S) and (2S,3R)-3-(2,5-dimethylphenyl)-4-methylpentan-2-yl (S)-2-methoxy-2-phenylacetate
  • the reaction was cooled to ambient temperature. The reaction was quenched by the addition of a saturated aqueous solution of NH 4 Cl (100 mL) and extracted with CH 2 Cl 2 (3 ⁇ 100 mL). Additional product remained in aqueous layer as evidenced by TLC, so 100 mL brine was added to aqueous layer, and the aqueous layer was extracted again with CH 2 Cl 2 (2 ⁇ 100 mL), after which no additional product was observed in the aqueous layer.
  • N 1 -((ethylimino)methylene)-N 3 ,N 3 -dimethylpropane-1,3-diamine hydrochloride EDC; 0.147 g, 0.764 mmol
  • the reaction was monitored until complete by TLC (25% EtOAc in hexanes).
  • the reaction was purified by automated column chromatography (0-10% EtOAc in hexanes) to provide (2S,3S)-3-(4-fluorophenyl)-4-methylpentan-2-yl (tert-butoxycarbonyl)-L-alaninate (137.5 mg, 0.370 mmol, 97% yield) as colorless oil.
  • Step 1 Preparation of (1R,2S)-1-cyclopentyl-1-phenylpropan-2-yl (3-hydroxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate
  • Step 2 Preparation of (1R,2S)-1-cyclopentyl-1-phenylpropan-2-yl (3-acetoxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate
  • Example A Evaluation of Fungicidal Activity: Leaf Blotch of Wheat ( Zymoseptoria tritici ; Bayer Code SEPTTR)
  • Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Zymoseptoria tritici either prior to or after fungicide treatments. After inoculation the plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two to three days in a lighted dew chamber at 20° C.) to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 20° C. for disease to develop. When disease symptoms were fully expressed on the 1 st leaves of untreated plants, infection levels were assessed on a scale of 0 to 100 percent disease severity. Percent disease control was calculated using the ratio of disease severity on treated plants relative to untreated plants.
  • Example B Evaluation of Fungicidal Activity: Wheat Brown Rust ( Puccinia triticina ; Synonym: Puccinia recondita f. Sp. Tritici ; Bayer Code PUCCRT)
  • Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Puccinia triticina either prior to or after fungicide treatments. After inoculation the plants were kept in a dark dew room at 22° C. with 100% relative humidity overnight to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 24° C. for disease to develop. Fungicide formulation, application and disease assessment followed the procedures as described in the Example A.
  • Example C Evaluation of Fungicidal Activity: Asian Soybean Rust ( Phakopsora pachyrhizi ; Bayer Code PHAKPA)
  • Soybean plants (variety Williams 82) were grown in soil-less Metro mix, with one plant per pot. Two week old seedlings were used for testing. Plants were inoculated either 3 days prior to or 1 day after fungicide treatments. Plants were incubated for 24 h in a dark dew room at 22° C. and 100% relative humidity then transferred to a growth room at 23° C. for disease to develop. Disease severity was assessed on the sprayed leaves.
  • Example D Evaluation of Fungicidal Activity: Tomato Early Blight ( Alternaria solani ; Bayer Code ALTESO)
  • Tomato plants (variety Outdoor Girl) were propagated in soil-less Metro mix, with each pot having one plant, and used when 12 to 14 days old. Test plants were inoculated with an aqueous spore suspension of Alternaria solani 24 hr after fungicide treatments. After inoculation the plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two to three days in a lighted dew chamber at 20° C.) to permit spores to germinate and infect the leaf. The plants were then transferred to a growth room at 22° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.
  • Example E Evaluation of Fungicidal Activity: Leaf Spot of Sugar Beets ( Cercospora beticola ; Bayer Code CERCBE)
  • Sugar beet plants (variety HH88) were grown in soil-less Metro mix and trimmed regularly to maintain a uniform plant size prior to test. Plants were inoculated with a spore suspension 24 hr after fungicide treatments. Inoculated plants were kept in a dew chamber at 22° C. for 48 hr then incubated in a greenhouse set at 24° C. under a clear plastic hood with bottom ventilation until disease symptoms were fully expressed. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.
  • Example F Evaluation of Fungicidal Activity: Cucumber Anthracnose ( Glomerella lagenarium ; Anamorph: Colletotrichum lagenarium ; Bayer Code COLLLA)
  • Cucumber seedlings (variety Bush Pickle) were propagated in soil-less Metro mix, with each pot having one plant, and used in the test when 12 to 14 days old. Test plants were inoculated with an aqueous spore suspension of Colletotrichum lagenarium 24 hr after fungicide treatments. After inoculation the plants were kept in a dew room at 22° C. with 100% relative humidity for 48 hr to permit spores to germinate and infect the leaf. The plants were then transferred to a growth room set at 22° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.
  • Example G Evaluation of Fungicidal Activity: Wheat Glume Blotch ( Parastagonospora nodorum ; Bayer Code LEPTNO)
  • Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Parastagonospora nodorum 24 hr after fungicide treatments. After inoculation the plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two days in a lighted dew chamber at 20° C.) to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 20° C. for disease to develop. Fungicide formulation, application and disease assessment followed the procedures as described in the Example A.
  • Example H Evaluation of Fungicidal Activity: Cucumber Downy Mildew ( Pseudoperonospora cubensis ; Bayer Code PSPECU)
  • Cucumber seedlings (variety Bush Pickle) were grown in soil-less Metro mix, with one plant per pot, and used in the test when 12 to 14 days old. Plants were inoculated with a spore suspension 24 hr following fungicide treatments. Test plants were inoculated with an aqueous spore suspension of Pseudoperonospora cubensis 24 hr after fungicide treatments. After inoculation the plants were kept in a dew room at 22° C. with 100% relative humidity for 24 hr to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 20° C. until disease was fully expressed. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.
  • Example I Evaluation of Fungicidal Activity: Rice Blast ( Magnaporthe grisea; Anamorph: Pyricularia oryzae ; Bayer Code PYRIOR)
  • Rice seedlings (variety Japonica ) were propagated in soil-less Metro mix, with each pot having 8 to 14 plants, and used in the test when 12 to 14 days old. Test plants were inoculated with an aqueous spore suspension of Pyricularia oryzae 24 hr after fungicide treatments. After inoculation, the plants were kept in a dew room at 22° C. with 100% relative humidity for 48 hr to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 24° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.
  • Example J Evaluation of Fungicidal Activity: Barley Scald ( Rhyncosporium secalis ; Bayer Code RHYNSE)
  • Barley seedlings (variety Harrington) were propagated in soil-less Metro mix, with each pot having 8 to 12 plants, and used in the test when first leaf was fully emerged.
  • Test plants were inoculated by an aqueous spore suspension of Rhyncosporium secalis 24 hr after fungicide treatments. After inoculation the plants were kept in a dew room at 20° C. with 100% relative humidity for 48 hr. The plants were then transferred to a greenhouse set at 20° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.
  • Example K Evaluation of Fungicidal Activity: Grape Powdery Mildew ( Uncinula necator ; Bayer Code UNCINE)
  • Grape seedlings (variety Carignane) were grown in soil-less Metro mix, with one plant per pot, and used in the test when approximately 1 month old. Plants were inoculated 24 hr after fungicide treatment by shaking spores from infected leaves over test plants. Plants were maintained in a greenhouse set at 20° C. until disease was fully developed. Fungicide formulation, application and disease assessment on sprayed leaves followed the procedures as described in the Example A.
  • Example 2B Example 8 Colorless Oil 2 Example 2A Example 3B Example 8 Colorless Oil 3 Example 2A Example 3B Example 9 Colorless Oil 4 Example 1A Example 2B Example 3B Example 8 Colorless Oil 5 Example 1A Example 2B Example 3B Example 8 Pale Yellow Oil 6 Example 1B Example 2B Example 3B Example 8 Colorless Oil 7 Example 2A Example 5 Example 8 Colorless Oil 8 Example 2A Example 5 Example 8 Colorless Oil 9 Example 1C; Step 1 Example 2B Example 3B Example 8 Clear, Colorless Oil 10 Example 1C; Step 1 Example 2B Example 3B Example 8 Clear, Colorless Oil 11 Example 1C; Step 1 Example 2B Example 3B Example 8 Clear, Colorless Oil 12 Example 1C; Step 1 Example 2B Example 3B Example 8 Clear, Colorless Oil 13 Example 1C; Step 1 Example 2B Example 3B Example 8 Clear, Colorless Oil 14 Example 1C; Step 1 Example 2B Example 3A Example 8 Clear, Colorless Oil

Abstract

This disclosure relates to picolinamides of Formula I and their use as fungicides.
Figure US20180186742A1-20180705-C00001

Description

    CROSS REFERENCE TO RELATED APPLICATIONS
  • This application claims priority under 35 U.S.C. § 119 of U.S. provisional patent application Ser. No. 62/442,904 filed Jan. 5, 2017, which application is hereby incorporated by reference in its entirety.
    • BACKGROUND & SUMMARY
  • Fungicides are compounds, of natural or synthetic origin, which act to protect and/or cure plants against damage caused by agriculturally relevant fungi. Generally, no single fungicide is useful in all situations. Consequently, research is ongoing to produce fungicides that may have better performance, are easier to use, and cost less.
  • The present disclosure relates to picolinamides and their use as fungicides. The compounds of the present disclosure may offer protection against ascomycetes, basidiomycetes, deuteromycetes and oomycetes.
  • One embodiment of the present disclosure may include compounds of Formula I:
  • Figure US20180186742A1-20180705-C00002
  • wherein:
  • X is hydrogen or C(O)R5;
  • Y is hydrogen, C(O)R5, or Q;
  • Q is
  • Figure US20180186742A1-20180705-C00003
  • wherein Z is N or N+→O− and W is O or S;
  • R1 is hydrogen or alkyl, substituted with 0, 1 or multiple R8;
  • R2 is methyl;
  • R3 and R3′ are independently chosen from C2-C6 alkyl, C3-C6 cycloalkyl, aryl or heteroaryl, each optionally substituted with 0, 1 or multiple R8; Alternatively, R3 and R3′ may be taken together to form a 3-6 membered saturated or partially saturated carbocycle or heterocycle, optionally substituted with 0, 1 or multiple R8;
  • R4 is chosen from aryl or heteroaryl, each optionally substituted with 0, 1 or multiple R8;
  • R5 is chosen from alkoxy or benzyloxy, each optionally substituted with 0, 1, or multiple R8;
  • R6 is chosen from hydrogen, alkoxy, or halo, each optionally substituted with 0, 1, or multiple R8;
  • R7 is chosen from hydrogen, —C(O)R9, or —CH2OC(O)R9;
  • R8 is chosen from hydrogen, alkyl, aryl, acyl, halo, alkenyl, alkynyl, alkoxy, cyano, or heterocyclyl, each optionally substituted with 0, 1, or multiple R10;
  • R9 is chosen from alkyl, alkoxy, or aryl, each optionally substituted with 0, 1, or multiple R8;
  • R10 is chosen from hydrogen, alkyl, aryl, acyl, halo, alkenyl, alkoxy, or heterocyclyl; and
  • R11 is chosen from hydrogen or alkyl, each substituted with 0, 1 or multiple R8.
  • Another embodiment of the present disclosure may include a fungicidal composition for the control or prevention of fungal attack comprising the compounds described above and a phytologically acceptable carrier material.
  • Yet another embodiment of the present disclosure may include a method for the control or prevention of fungal attack on a plant, the method including the steps of applying a fungicidally effective amount of one or more of the compounds described above to at least one of the fungus, the plant, and an area adjacent to the plant.
  • It will be understood by those skilled in the art that the following terms may include generic “R”-groups within their definitions, e.g., “the term alkoxy refers to an —OR substituent”. It is also understood that within the definitions for the following terms, these “R” groups are included for illustration purposes and should not be construed as limiting or being limited by substitutions about Formula I.
  • The term “alkyl” refers to a branched, unbranched, or saturated cyclic carbon chain, including, but not limited to, methyl, ethyl, propyl, butyl, isopropyl, isobutyl, tertiary butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and the like.
  • The term “alkenyl” refers to a branched, unbranched or cyclic carbon chain containing one or more double bonds including, but not limited to, ethenyl, propenyl, butenyl, isopropenyl, isobutenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, and the like.
  • The terms “aryl” and “Ar” refer to any aromatic ring, mono- or bi-cyclic, containing 0 heteroatoms.
  • The term “heterocyclyl” refers to any aromatic or non-aromatic ring, mono- or bi-cyclic, containing one or more heteroatoms
  • The term “alkoxy” refers to an —OR substituent.
  • The term “acyloxy” refers to an —OC(O)R substituent.
  • The term “cyano” refers to a —C≡N substituent.
  • The term “hydroxyl” refers to a —OH substituent.
  • The term “amino” refers to an —N(R)2 substituent.
  • The term “arylalkoxy” refers to —O(CH2)nAr where n is an integer selected from the list 1, 2, 3, 4, 5, or 6.
  • The term “haloalkoxy” refers to an —OR—X substituent, wherein X is Cl, F, Br, or I, or any combination thereof.
  • The term “haloalkyl” refers to an alkyl, which is substituted with Cl, F, I, or Br or any combination thereof.
  • The term “halogen” or “halo” refers to one or more halogen atoms, defined as F, Cl, Br, and I.
  • The term “nitro” refers to a —NO2 substituent.
  • The term thioalkyl refers to a —SR substituent.
  • Throughout the disclosure, reference to the compounds of Formula I is read as also including all stereoisomers, for example diastereomers, enantiomers, and mixtures thereof. In another embodiment, Formula (I) is read as also including salts or hydrates thereof. Exemplary salts include, but are not limited to: hydrochloride, hydrobromide, hydroiodide, trifluoroacetate, and trifluoromethane sulfonate.
  • It is also understood by those skilled in the art that additional substitution is allowable, unless otherwise noted, as long as the rules of chemical bonding and strain energy are satisfied and the product still exhibits fungicidal activity.
  • Another embodiment of the present disclosure is a use of a compound of Formula I, for protection of a plant against attack by a phytopathogenic organism or the treatment of a plant infested by a phytopathogenic organism, comprising the application of a compound of Formula I, or a composition comprising the compound to soil, a plant, a part of a plant, foliage, and/or roots.
  • Additionally, another embodiment of the present disclosure is a composition useful for protecting a plant against attack by a phytopathogenic organism and/or treatment of a plant infested by a phytopathogenic organism comprising a compound of Formula I and a phytologically acceptable carrier material.
    • DETAILED DESCRIPTION
  • The compounds of the present disclosure may be applied by any of a variety of known techniques, either as the compounds or as formulations comprising the compounds. For example, the compounds may be applied to the roots or foliage of plants for the control of various fungi, without damaging the commercial value of the plants. The materials may be applied in the form of any of the generally used formulation types, for example, as solutions, dusts, wettable powders, flowable concentrate, or emulsifiable concentrates.
  • Preferably, the compounds of the present disclosure are applied in the form of a formulation, comprising one or more of the compounds of Formula I with a phytologically acceptable carrier. Concentrated formulations may be dispersed in water, or other liquids, for application, or formulations may be dust-like or granular, which may then be applied without further treatment. The formulations can be prepared according to procedures that are conventional in the agricultural chemical art.
  • The present disclosure contemplates all vehicles by which one or more of the compounds may be formulated for delivery and used as a fungicide. Typically, formulations are applied as aqueous suspensions or emulsions. Such suspensions or emulsions may be produced from water-soluble, water-suspendable, or emulsifiable formulations which are solids, usually known as wettable powders; or liquids, usually known as emulsifiable concentrates, aqueous suspensions, or suspension concentrates. As will be readily appreciated, any material to which these compounds may be added may be used, provided it yields the desired utility without significant interference with the activity of these compounds as antifungal agents.
  • Wettable powders, which may be compacted to form water-dispersible granules, comprise an intimate mixture of one or more of the compounds of Formula I, an inert carrier and surfactants. The concentration of the compound in the wettable powder may be from about 10 percent to about 90 percent by weight based on the total weight of the wettable powder, more preferably about 25 weight percent to about 75 weight percent. In the preparation of wettable powder formulations, the compounds may be compounded with any finely divided solid, such as prophyllite, talc, chalk, gypsum, Fuller's earth, bentonite, attapulgite, starch, casein, gluten, montmorillonite clays, diatomaceous earths, purified silicates or the like. In such operations, the finely divided carrier and surfactants are typically blended with the compound(s) and milled.
  • Emulsifiable concentrates of the compounds of Formula I may comprise a convenient concentration, such as from about 1 weight percent to about 50 weight percent of the compound, in a suitable liquid, based on the total weight of the concentrate. The compounds may be dissolved in an inert carrier, which is either a water-miscible solvent or a mixture of water-immiscible organic solvents, and emulsifiers. The concentrates may be diluted with water and oil to form spray mixtures in the form of oil-in-water emulsions. Useful organic solvents include aromatics, especially the high-boiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic solvents may also be used, for example, terpenic solvents, including rosin derivatives, aliphatic ketones, such as cyclohexanone, and complex alcohols, such as 2-ethoxyethanol.
  • Emulsifiers which may be advantageously employed herein may be readily determined by those skilled in the art and include various nonionic, anionic, cationic and amphoteric emulsifiers, or a blend of two or more emulsifiers. Examples of nonionic emulsifiers useful in preparing the emulsifiable concentrates include the polyalkylene glycol ethers and condensation products of alkyl and aryl phenols, aliphatic alcohols, aliphatic amines or fatty acids with ethylene oxide, propylene oxides such as the ethoxylated alkyl phenols and carboxylic esters solubilized with the polyol or polyoxyalkylene. Cationic emulsifiers include quaternary ammonium compounds and fatty amine salts. Anionic emulsifiers include the oil-soluble salts (e.g., calcium) of alkylaryl sulphonic acids, oil-soluble salts or sulfated polyglycol ethers and appropriate salts of phosphated polyglycol ether.
  • Representative organic liquids which may be employed in preparing the emulsifiable concentrates of the compounds of the present disclosure are the aromatic liquids such as xylene, propyl benzene fractions; or mixed naphthalene fractions, mineral oils, substituted aromatic organic liquids such as dioctyl phthalate; kerosene; dialkyl amides of various fatty acids, particularly the dimethyl amides of fatty glycols and glycol derivatives such as the n-butyl ether, ethyl ether or methyl ether of diethylene glycol, the methyl ether of triethylene glycol, petroleum fractions or hydrocarbons such as mineral oil, aromatic solvents, paraffinic oils, and the like; vegetable oils such as soy bean oil, rape seed oil, olive oil, castor oil, sunflower seed oil, coconut oil, corn oil, cotton seed oil, linseed oil, palm oil, peanut oil, safflower oil, sesame oil, tung oil and the like; esters of the above vegetable oils; and the like. Mixtures of two or more organic liquids may also be employed in the preparation of the emulsifiable concentrate. Organic liquids include xylene, and propyl benzene fractions, with xylene being most preferred in some cases. Surface-active dispersing agents are typically employed in liquid formulations and in an amount of from 0.1 to 20 percent by weight based on the combined weight of the dispersing agent with one or more of the compounds. The formulations can also contain other compatible additives, for example, plant growth regulators and other biologically active compounds used in agriculture.
  • Aqueous suspensions comprise suspensions of one or more water-insoluble compounds of Formula I, dispersed in an aqueous vehicle at a concentration in the range from about 1 to about 50 weight percent, based on the total weight of the aqueous suspension. Suspensions are prepared by finely grinding one or more of the compounds, and vigorously mixing the ground material into a vehicle comprised of water and surfactants chosen from the same types discussed above. Other components, such as inorganic salts and synthetic or natural gums, may also be added to increase the density and viscosity of the aqueous vehicle.
  • The compounds of Formula I can also be applied as granular formulations, which are particularly useful for applications to the soil. Granular formulations generally contain from about 0.5 to about 10 weight percent, based on the total weight of the granular formulation of the compound(s), dispersed in an inert carrier which consists entirely or in large part of coarsely divided inert material such as attapulgite, bentonite, diatomite, clay or a similar inexpensive substance. Such formulations are usually prepared by dissolving the compounds in a suitable solvent and applying it to a granular carrier which has been preformed to the appropriate particle size, in the range of from about 0.5 to about 3 mm. A suitable solvent is a solvent in which the compound is substantially or completely soluble. Such formulations may also be prepared by making a dough or paste of the carrier and the compound and solvent, and crushing and drying to obtain the desired granular particle.
  • Dusts containing the compounds of Formula I may be prepared by intimately mixing one or more of the compounds in powdered form with a suitable dusty agricultural carrier, such as, for example, kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1 to about 10 weight percent of the compounds, based on the total weight of the dust.
  • The formulations may additionally contain adjuvant surfactants to enhance deposition, wetting, and penetration of the compounds onto the target crop and organism. These adjuvant surfactants may optionally be employed as a component of the formulation or as a tank mix. The amount of adjuvant surfactant will typically vary from 0.01 to 1.0 percent by volume, based on a spray-volume of water, preferably 0.05 to 0.5 volume percent. Suitable adjuvant surfactants include, but are not limited to ethoxylated nonyl phenols, ethoxylated synthetic or natural alcohols, salts of the esters or sulphosuccinic acids, ethoxylated organosilicones, ethoxylated fatty amines, blends of surfactants with mineral or vegetable oils, crop oil concentrate (mineral oil (85%)+emulsifiers (15%)); nonylphenol ethoxylate; benzylcocoalkyldimethyl quaternary ammonium salt; blend of petroleum hydrocarbon, alkyl esters, organic acid, and anionic surfactant; C9-C11 alkylpolyglycoside; phosphated alcohol ethoxylate; natural primary alcohol (C12-C16) ethoxylate; di-sec-butylphenol EO-PO block copolymer; polysiloxane-methyl cap; nonylphenol ethoxylate+urea ammonium nitrate; emulsified methylated seed oil; tridecyl alcohol (synthetic) ethoxylate (8EO); tallow amine ethoxylate (15 EO); PEG(400) dioleate-99. The formulations may also include oil-in-water emulsions such as those disclosed in U.S. patent application Ser. No. 11/495,228, the disclosure of which is expressly incorporated by reference herein.
  • The formulations may optionally include combinations that contain other pesticidal compounds. Such additional pesticidal compounds may be fungicides, insecticides, herbicides, nematocides, miticides, arthropodicides, bactericides or combinations thereof that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds. Accordingly, in such embodiments, the other pesticidal compound is employed as a supplemental toxicant for the same or for a different pesticidal use. The compounds of Formula I and the pesticidal compound in the combination can generally be present in a weight ratio of from 1:100 to 100:1.
  • The compounds of the present disclosure may also be combined with other fungicides to form fungicidal mixtures and synergistic mixtures thereof. The fungicidal compounds of the present disclosure are often applied in conjunction with one or more other fungicides to control a wider variety of undesirable diseases. When used in conjunction with other fungicide(s), the presently claimed compounds may be formulated with the other fungicide(s), tank-mixed with the other fungicide(s) or applied sequentially with the other fungicide(s). Such other fungicides may include 2-(thiocyanatomethylthio)-benzothiazole, 2-phenylphenol, 8-hydroxyquinoline sulfate, ametoctradin, amisulbrom, antimycin, Ampelomyces quisqualis, azaconazole, Bacillus subtilis, Bacillus subtilis strain QST713, benalaxyl, benomyl, benthiavalicarb-isopropyl, benzovindiflupyr, benzylaminobenzene-sulfonate (BABS) salt, bicarbonates, biphenyl, bismerthiazol, bitertanol, bixafen, blasticidin-S, borax, Bordeaux mixture, boscalid, bromuconazole, bupirimate, calcium polysulfide, captafol, captan, carbendazim, carboxin, carpropamid, carvone, chlazafenone, chloroneb, chlorothalonil, chlozolinate, Coniothyrium minitans, copper hydroxide, copper octanoate, copper oxychloride, copper sulfate, copper sulfate (tribasic), cuprous oxide, cyazofamid, cyflufenamid, cymoxanil, cyproconazole, cyprodinil, dazomet, debacarb, diammonium ethylenebis-(dithiocarbamate), dichlofluanid, dichlorophen, diclocymet, diclomezine, dichloran, diethofencarb, difenoconazole, difenzoquat ion, diflumetorim, dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, dinobuton, dinocap, diphenylamine, dithianon, dodemorph, dodemorph acetate, dodine, dodine free base, edifenphos, enestrobin, enestroburin, epoxiconazole, ethaboxam, ethoxyquin, etridiazole, famoxadone, fenamidone, fenarimol, fenbuconazole, fenfuram, fenhexamid, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fenpyrazamine, fentin, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, fluindapyr, flumorph, fluopicolide, fluopyram, fluoroimide, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutianil, flutolanil, flutriafol, fluxapyroxad, folpet, formaldehyde, fosetyl, fosetyl-aluminium, fuberidazole, furalaxyl, furametpyr, guazatine, guazatine acetates, GY-81, hexachlorobenzene, hexaconazole, hymexazol, imazalil, imazalil sulfate, imibenconazole, iminoctadine, iminoctadine triacetate, iminoctadine tris(albesilate), iodocarb, ipconazole, ipfenpyrazolone, iprobenfos, iprodione, iprovalicarb, isofetamide, isoprothiolane, isopyrazam, isotianil, kasugamycin, kasugamycin hydrochloride hydrate, kresoxium-methyl, laminarin, mancopper, mancozeb, mandipropamid, maneb, mefenoxam, mepanipyrim, mepronil, meptyl-dinocap, mercuric chloride, mercuric oxide, mercurous chloride, metalaxyl, metalaxyl-M, metam, metam-ammonium, metam-potassium, metam-sodium, metconazole, methasulfocarb, methyl iodide, methyl isothiocyanate, metiram, metominostrobin, metrafenone, mildiomycin, myclobutanil, nabam, nitrothal-isopropyl, nuarimol, octhilinone, ofurace, oleic acid (fatty acids), orysastrobin, oxadixyl, oxathiapiprolin, oxine-copper, oxpoconazole fumarate, oxycarboxin, pefurazoate, penconazole, pencycuron, penflufen, pentachlorophenol, pentachlorophenyl laurate, penthiopyrad, phenylmercury acetate, phosphonic acid, phthalide, picoxystrobin, polyoxin B, polyoxins, polyoxorim, potassium bicarbonate, potassium hydroxyquinoline sulfate, probenazole, prochloraz, procymidone, propamocarb, propamocarb hydrochloride, propiconazole, propineb, proquinazid, prothioconazole, pydiflumetofen, pyrametostrobin, pyraoxystrobin, pyraclostrobin, pyraziflumid, pyrazophos, pyribencarb, pyributicarb, pyrifenox, pyrimethanil, pyriofenone, pyroquilon, quinoclamine, quinoxyfen, quintozene, Reynoutria sachalinensis extract, sedaxane, silthiofam, simeconazole, sodium 2-phenylphenoxide, sodium bicarbonate, sodium pentachlorophenoxide, spiroxamine, sulfur, SYP-Z048, tar oils, tebuconazole, tebufloquin, tecnazene, tetraconazole, thiabendazole, thifluzamide, thiophanate-methyl, thiram, tiadinil, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triazoxide, tricyclazole, tridemorph, trifloxystrobin, triflumizole, triforine, triticonazole, validamycin, valifenalate, valiphenal, vinclozolin, zineb, ziram, zoxamide, Candida oleophila, Fusarium oxysporum, Gliocladium spp., Phlebiopsis gigantea, Streptomyces griseoviridis, Trichoderma spp., (RS)—N-(3,5-dichlorophenyl)-2-(methoxymethyl)-succinimide, 1,2-dichloropropane, 1,3-dichloro-1,1,3,3-tetrafluoroacetone hydrate, 1-chloro-2,4-dinitronaphthalene, 1-chloro-2-nitropropane, 2-(2-heptadecyl-2-imidazolin-1-yl)ethanol, 2,3-dihydro-5-phenyl-1,4-dithi-ine 1,1,4,4-tetraoxide, 2-methoxyethylmercury acetate, 2-methoxyethylmercury chloride, 2-methoxyethylmercury silicate, 3-(4-chlorophenyl)-5-methylrhodanine, 4-(2-nitroprop-1-enyl)phenyl thiocyanateme, ampropylfos, anilazine, azithiram, barium polysulfide, Bayer 32394, benodanil, benquinox, bentaluron, benzamacril; benzamacril-isobutyl, benzamorf, binapacryl, bis(methylmercury) sulfate, bis(tributyltin) oxide, buthiobate, cadmium calcium copper zinc chromate sulfate, carbamorph, CECA, chlobenthiazone, chloraniformethan, chlorfenazole, chlorquinox, climbazole, copper bis(3-phenylsalicylate), copper zinc chromate, coumoxystrobin, cufraneb, cupric hydrazinium sulfate, cuprobam, cyclafuramid, cypendazole, cyprofuram, decafentin, dichlobentiazox, dichlone, dichlozoline, diclobutrazol, dimethirimol, dinocton, dinosulfon, dinoterbon, dipymetitrone, dipyrithione, ditalimfos, dodicin, drazoxolon, EBP, enoxastrobin, ESBP, etaconazole, etem, ethirim, fenaminstrobin, fenaminosulf, fenapanil, fenitropan, fenpicoxamid, flufenoxystrobin, fluotrimazole, furcarbanil, furconazole, furconazole-cis, furmecyclox, furophanate, glyodine, griseofulvin, halacrinate, Hercules 3944, hexylthiofos, ICIA0858, ipfentrifluconazole, isopamphos, isovaledione, mandestrobin, mebenil, mecarbinzid, mefentrifluconazole, metazoxolon, methfuroxam, methylmercury dicyandiamide, metsulfovax, milneb, mucochloric anhydride, myclozolin, N-3,5-dichlorophenyl-succinimide, N-3-nitrophenylitaconimide, natamycin, N-ethylmercurio-4-toluenesulfonanilide, nickel bis(dimethyldithiocarbamate), OCH, phenylmercury dimethyldithiocarbamate, phenylmercury nitrate, phosdiphen, prothiocarb; prothiocarb hydrochloride, pyracarbolid, pyridinitril, pyrisoxazole, pyroxychlor, pyroxyfur, quinacetol; quinacetol sulfate, quinazamid, quinconazole, quinofumelin, rabenzazole, salicylanilide, SSF-109, sultropen, tecoram, thiadifluor, thicyofen, thiochlorfenphim, thiophanate, thioquinox, tioxymid, triamiphos, triarimol, triazbutil, trichlamide, triclopyricarb, triflumezopyrim, urbacid, zarilamid, and any combinations thereof.
  • Additionally, the compounds described herein may be combined with other pesticides, including insecticides, nematocides, miticides, arthropodicides, bactericides or combinations thereof that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds to form pesticidal mixtures and synergistic mixtures thereof. The fungicidal compounds of the present disclosure may be applied in conjunction with one or more other pesticides to control a wider variety of undesirable pests. When used in conjunction with other pesticides, the presently claimed compounds may be formulated with the other pesticide(s), tank-mixed with the other pesticide(s) or applied sequentially with the other pesticide(s). Typical insecticides include, but are not limited to: 1,2-dichloropropane, abamectin, acephate, acetamiprid, acethion, acetoprole, acrinathrin, acrylonitrile, alanycarb, aldicarb, aldoxycarb, aldrin, allethrin, allosamidin, allyxycarb, alpha-cypermethrin, alpha-ecdysone, alpha-endosulfan, amidithion, aminocarb, amiton, amiton oxalate, amitraz, anabasine, athidathion, azadirachtin, azamethiphos, azinphos-ethyl, azinphos-methyl, azothoate, barium hexafluorosilicate, barthrin, bendiocarb, benfuracarb, bensultap, beta-cyfluthrin, beta-cypermethrin, bifenthrin, bioallethrin, bioethanomethrin, biopermethrin, bistrifluron, borax, boric acid, bromfenvinfos, bromocyclen, bromo-DDT, bromophos, bromophos-ethyl, bufencarb, buprofezin, butacarb, butathiofos, butocarboxim, butonate, butoxycarboxim, cadusafos, calcium arsenate, calcium polysulfide, camphechlor, carbanolate, carbaryl, carbofuran, carbon disulfide, carbon tetrachloride, carbophenothion, carbosulfan, cartap, cartap hydrochloride, chlorantraniliprole, chlorbicyclen, chlordane, chlordecone, chlordimeform, chlordimeform hydrochloride, chlorethoxyfos, chlorfenapyr, chlorfenvinphos, chlorfluazuron, chlormephos, chloroform, chloropicrin, chlorphoxim, chlorprazophos, chlorpyrifos, chlorpyrifos-methyl, chlorthiophos, chromafenozide, cinerin I, cinerin II, cinerins, cismethrin, cloethocarb, closantel, clothianidin, copper acetoarsenite, copper arsenate, copper naphthenate, copper oleate, coumaphos, coumithoate, crotamiton, crotoxyphos, crufomate, cryolite, cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyclethrin, cycloprothrin, cyfluthrin, cyhalothrin, cypermethrin, cyphenothrin, cyromazine, cythioate, DDT, decarbofuran, deltamethrin, demephion, demephion-O, demephion-S, demeton, demeton-methyl, demeton-O, demeton-O-methyl, demeton-S, demeton-S-methyl, demeton-S-methylsulphon, diafenthiuron, dialifos, diatomaceous earth, diazinon, dicapthon, dichlofenthion, dichlorvos, dicresyl, dicrotophos, dicyclanil, dieldrin, diflubenzuron, dilor, dimefluthrin, dimefox, dimetan, dimethoate, dimethrin, dimethylvinphos, dimetilan, dinex, dinex-diclexine, dinoprop, dinosam, dinotefuran, diofenolan, dioxabenzofos, dioxacarb, dioxathion, disulfoton, dithicrofos, d-limonene, DNOC, DNOC-ammonium, DNOC-potassium, DNOC-sodium, doramectin, ecdysterone, emamectin, emamectin benzoate, EMPC, empenthrin, endosulfan, endothion, endrin, EPN, epofenonane, eprinomectin, esdepalléthrine, esfenvalerate, etaphos, ethiofencarb, ethion, ethiprole, ethoate-methyl, ethoprophos, ethyl formate, ethyl-DDD, ethylene dibromide, ethylene dichloride, ethylene oxide, etofenprox, etrimfos, EXD, famphur, fenamiphos, fenazaflor, fenchlorphos, fenethacarb, fenfluthrin, fenitrothion, fenobucarb, fenoxacrim, fenoxycarb, fenpirithrin, fenpropathrin, fensulfothion, fenthion, fenthion-ethyl, fenvalerate, fipronil, flonicamid, flubendiamide, flucofuron, flucycloxuron, flucythrinate, flufenerim, flufenoxuron, flufenprox, fluvalinate, fonofos, formetanate, formetanate hydrochloride, formothion, formparanate, formparanate hydrochloride, fosmethilan, fospirate, fosthietan, furathiocarb, furethrin, gamma-cyhalothrin, gamma-HCH, halfenprox, halofenozide, HCH, HEOD, heptachlor, heptenophos, heterophos, hexaflumuron, HHDN, hydramethylnon, hydrogen cyanide, hydroprene, hyquincarb, imidacloprid, imiprothrin, indoxacarb, iodomethane, IPSP, isazofos, isobenzan, isocarbophos, isodrin, isofenphos, isofenphos-methyl, isoprocarb, isoprothiolane, isothioate, isoxathion, ivermectin, jasmolin I, jasmolin II, jodfenphos, juvenile hormone I, juvenile hormone II, juvenile hormone III, kelevan, kinoprene, lambda-cyhalothrin, lead arsenate, lepimectin, leptophos, lindane, lirimfos, lufenuron, lythidathion, malathion, malonoben, mazidox, mecarbam, mecarphon, menazon, mephosfolan, mercurous chloride, mesulfenfos, metaflumizone, methacrifos, methamidophos, methidathion, methiocarb, methocrotophos, methomyl, methoprene, methoxychlor, methoxyfenozide, methyl bromide, methyl isothiocyanate, methylchloroform, methylene chloride, metofluthrin, metolcarb, metoxadiazone, mevinphos, mexacarbate, milbemectin, milbemycin oxime, mipafox, mirex, molosultap, monocrotophos, monomehypo, monosultap, morphothion, moxidectin, naftalofos, naled, naphthalene, nicotine, nifluridide, nitenpyram, nithiazine, nitrilacarb, novaluron, noviflumuron, omethoate, oxamyl, oxydemeton-methyl, oxydeprofos, oxydisulfoton, para-dichlorobenzene, parathion, parathion-methyl, penfluron, pentachlorophenol, permethrin, phenkapton, phenothrin, phenthoate, phorate, phosalone, phosfolan, phosmet, phosnichlor, phosphamidon, phosphine, phoxim, phoxim-methyl, pirimetaphos, pirimicarb, pirimiphos-ethyl, pirimiphos-methyl, potassium arsenite, potassium thiocyanate, pp′-DDT, prallethrin, precocene I, precocene II, precocene III, primidophos, profenofos, profluralin, promacyl, promecarb, propaphos, propetamphos, propoxur, prothidathion, prothiofos, prothoate, protrifenbute, pyraclofos, pyrafluprole, pyrazophos, pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins, pyridaben, pyridalyl, pyridaphenthion, pyrifluquinazon, pyrimidifen, pyrimitate, pyriprole, pyriproxyfen, quassia, quinalphos, quinalphos-methyl, quinothion, rafoxanide, resmethrin, rotenone, ryania, sabadilla, schradan, selamectin, silafluofen, silica gel, sodium arsenite, sodium fluoride, sodium hexafluorosilicate, sodium thiocyanate, sophamide, spinetoram, spinosad, spiromesifen, spirotetramat, sulcofuron, sulcofuron-sodium, sulfluramid, sulfotep, sulfoxaflor, sulfuryl fluoride, sulprofos, tau-fluvalinate, tazimcarb, TDE, tebufenozide, tebufenpyrad, tebupirimfos, teflubenzuron, tefluthrin, temephos, TEPP, terallethrin, terbufos, tetrachloroethane, tetrachlorvinphos, tetramethrin, tetramethylfluthrin, theta-cypermethrin, thiacloprid, thiamethoxam, thicrofos, thiocarboxime, thiocyclam, thiocyclam oxalate, thiodicarb, thiofanox, thiometon, thiosultap, thiosultap-disodium, thiosultap-monosodium, thuringiensin, tolfenpyrad, tralomethrin, transfluthrin, transpermethrin, triarathene, triazamate, triazophos, trichlorfon, trichlormetaphos-3, trichloronat, trifenofos, triflumuron, trimethacarb, triprene, vamidothion, vaniliprole, XMC, xylylcarb, zeta-cypermethrin, zolaprofos, and any combinations thereof.
  • Additionally, the compounds described herein may be combined with herbicides that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds to form pesticidal mixtures and synergistic mixtures thereof. The fungicidal compounds of the present disclosure may be applied in conjunction with one or more herbicides to control a wide variety of undesirable plants. When used in conjunction with herbicides, the presently claimed compounds may be formulated with the herbicide(s), tank-mixed with the herbicide(s) or applied sequentially with the herbicide(s). Typical herbicides include, but are not limited to: 4-CPA; 4-CPB; 4-CPP; 2,4-D; 3,4-DA; 2,4-DB; 3,4-DB; 2,4-DEB; 2,4-DEP; 3,4-DP; 2,3,6-TBA; 2,4,5-T; 2,4,5-TB; acetochlor, acifluorfen, aclonifen, acrolein, alachlor, allidochlor, alloxydim, allyl alcohol, alorac, ametridione, ametryn, amibuzin, amicarbazone, amidosulfuron, aminocyclopyrachlor, aminopyralid, amiprofos-methyl, amitrole, ammonium sulfamate, anilofos, anisuron, asulam, atraton, atrazine, azafenidin, azimsulfuron, aziprotryne, barban, BCPC, beflubutamid, benazolin, bencarbazone, benfluralin, benfuresate, bensulfuron, bensulide, bentazone, benzadox, benzfendizone, benzipram, benzobicyclon, benzofenap, benzofluor, benzoylprop, benzthiazuron, bicyclopyrone, bifenox, bilanafos, bispyribac, borax, bromacil, bromobonil, bromobutide, bromofenoxim, bromoxynil, brompyrazon, butachlor, butafenacil, butamifos, butenachlor, buthidazole, buthiuron, butralin, butroxydim, buturon, butylate, cacodylic acid, cafenstrole, calcium chlorate, calcium cyanamide, cambendichlor, carbasulam, carbetamide, carboxazole chlorprocarb, carfentrazone, CDEA, CEPC, chlomethoxyfen, chloramben, chloranocryl, chlorazifop, chlorazine, chlorbromuron, chlorbufam, chloreturon, chlorfenac, chlorfenprop, chlorflurazole, chlorflurenol, chloridazon, chlorimuron, chlornitrofen, chloropon, chlorotoluron, chloroxuron, chloroxynil, chlorpropham, chlorsulfuron, chlorthal, chlorthiamid, cinidon-ethyl, cinmethylin, cinosulfuron, cisanilide, clethodim, cliodinate, clodinafop, clofop, clomazone, clomeprop, cloprop, cloproxydim, clopyralid, cloransulam, CMA, copper sulfate, CPMF, CPPC, credazine, cresol, cumyluron, cyanatryn, cyanazine, cycloate, cyclosulfamuron, cycloxydim, cycluron, cyhalofop, cyperquat, cyprazine, cyprazole, cypromid, daimuron, dalapon, dazomet, delachlor, desmedipham, desmetryn, di-allate, dicamba, dichlobenil, dichloralurea, dichlormate, dichlorprop, dichlorprop-P, diclofop, diclosulam, diethamquat, diethatyl, difenopenten, difenoxuron, difenzoquat, diflufenican, diflufenzopyr, dimefuron, dimepiperate, dimethachlor, dimethametryn, dimethenamid, dimethenamid-P, dimexano, dimidazon, dinitramine, dinofenate, dinoprop, dinosam, dinoseb, dinoterb, diphenamid, dipropetryn, diquat, disul, dithiopyr, diuron, DMPA, DNOC, DSMA, EBEP, eglinazine, endothal, epronaz, EPTC, erbon, esprocarb, ethalfluralin, ethametsulfuron, ethidimuron, ethiolate, ethofumesate, ethoxyfen, ethoxysulfuron, etinofen, etnipromid, etobenzanid, EXD, fenasulam, fenoprop, fenoxaprop, fenoxaprop-P, fenoxasulfone, fenteracol, fenthiaprop, fentrazamide, fenuron, ferrous sulfate, flamprop, flamprop-M, flazasulfuron, florasulam, fluazifop, fluazifop-P, fluazolate, flucarbazone, flucetosulfuron, fluchloralin, flufenacet, flufenican, flufenpyr, flumetsulam, flumezin, flumiclorac, flumioxazin, flumipropyn, fluometuron, fluorodifen, fluoroglycofen, fluoromidine, fluoronitrofen, fluothiuron, flupoxam, flupropacil, flupropanate, flupyrsulfuron, fluridone, flurochloridone, fluroxypyr, flurtamone, fluthiacet, fomesafen, foramsulfuron, fosamine, furyloxyfen, glufosinate, glufosinate-P, glyphosate, halauxifen, halosafen, halosulfuron, haloxydine, haloxyfop, haloxyfop-P, hexachloroacetone, hexaflurate, hexazinone, imazamethabenz, imazamox, imazapic, imazapyr, imazaquin, imazethapyr, imazosulfuron, indanofan, indaziflam, iodobonil, iodomethane, iodosulfuron, ioxynil, ipazine, ipfencarbazone, iprymidam, isocarbamid, isocil, isomethiozin, isonoruron, isopolinate, isopropalin, isoproturon, isouron, isoxaben, isoxachlortole, isoxaflutole, isoxapyrifop, karbutilate, ketospiradox, lactofen, lenacil, linuron, MAA, MAMA, MCPA, MCPA-thioethyl, MCPB, mecoprop, mecoprop-P, medinoterb, mefenacet, mefluidide, mesoprazine, mesosulfuron, mesotrione, metam, metamifop, metamitron, metazachlor, metazosulfuron, metflurazon, methabenzthiazuron, methalpropalin, methazole, methiobencarb, methiozolin, methiuron, methometon, methoprotryne, methyl bromide, methyl isothiocyanate, methyldymron, metobenzuron, metobromuron, metolachlor, metosulam, metoxuron, metribuzin, metsulfuron, molinate, monalide, monisouron, monochloroacetic acid, monolinuron, monuron, morfamquat, MSMA, naproanilide, napropamide, naptalam, neburon, nicosulfuron, nipyraclofen, nitralin, nitrofen, nitrofluorfen, norflurazon, noruron, OCH, orbencarb, ortho-dichlorobenzene, orthosulfamuron, oryzalin, oxadiargyl, oxadiazon, oxapyrazon, oxasulfuron, oxaziclomefone, oxyfluorfen, parafluron, paraquat, pebulate, pelargonic acid, pendimethalin, penoxsulam, pentachlorophenol, pentanochlor, pentoxazone, perfluidone, pethoxamid, phenisopham, phenmedipham, phenmedipham-ethyl, phenobenzuron, phenylmercury acetate, picloram, picolinafen, pinoxaden, piperophos, potassium arsenite, potassium azide, potassium cyanate, pretilachlor, primisulfuron, procyazine, prodiamine, profluazol, profluralin, profoxydim, proglinazine, prometon, prometryn, propachlor, propanil, propaquizafop, propazine, propham, propisochlor, propoxycarbazone, propyrisulfuron, propyzamide, prosulfalin, prosulfocarb, prosulfuron, proxan, prynachlor, pydanon, pyraclonil, pyraflufen, pyrasulfotole, pyrazolynate, pyrazosulfuron, pyrazoxyfen, pyribenzoxim, pyributicarb, pyriclor, pyridafol, pyridate, pyriftalid, pyriminobac, pyrimisulfan, pyrithiobac, pyroxasulfone, pyroxsulam, quinclorac, quinmerac, quinoclamine, quinonamid, quizalofop, quizalofop-P, rhodethanil, rimsulfuron, saflufenacil, S-metolachlor, sebuthylazine, secbumeton, sethoxydim, siduron, simazine, simeton, simetryn, SMA, sodium arsenite, sodium azide, sodium chlorate, sulcotrione, sulfallate, sulfentrazone, sulfometuron, sulfosulfuron, sulfuric acid, sulglycapin, swep, TCA, tebutam, tebuthiuron, tefuryltrione, tembotrione, tepraloxydim, terbacil, terbucarb, terbuchlor, terbumeton, terbuthylazine, terbutryn, tetrafluron, thenylchlor, thiazafluron, thiazopyr, thidiazimin, thidiazuron, thiencarbazone-methyl, thifensulfuron, thiobencarb, tiocarbazil, tioclorim, topramezone, tralkoxydim, triafamone, tri-allate, triasulfuron, triaziflam, tribenuron, tricamba, triclopyr, tridiphane, trietazine, trifloxysulfuron, trifluralin, triflusulfuron, trifop, trifopsime, trihydroxytriazine, trimeturon, tripropindan, tritac, tritosulfuron, vernolate, and xylachlor.
  • Another embodiment of the present disclosure is a method for the control or prevention of fungal attack. This method comprises applying to the soil, plant, roots, foliage, or locus of the fungus, or to a locus in which the infestation is to be prevented (for example applying to cereal or grape plants), a fungicidally effective amount of one or more of the compounds of Formula I. The compounds are suitable for treatment of various plants at fungicidal levels, while exhibiting low phytotoxicity. The compounds may be useful both in a protectant and/or an eradicant fashion.
  • The compounds have been found to have significant fungicidal effect particularly for agricultural use. Many of the compounds are particularly effective for use with agricultural crops and horticultural plants.
  • It will be understood by those skilled in the art that the efficacy of the compound for the foregoing fungi establishes the general utility of the compounds as fungicides.
  • The compounds have broad ranges of activity against fungal pathogens. Exemplary pathogens may include, but are not limited to, causing agent of wheat leaf blotch (Zymoseptoria tritici), wheat brown rust (Puccinia triticina), wheat stripe rust (Puccinia striiformis), scab of apple (Venturia inaequalis), powdery mildew of grapevine (Uncinula necator), barley scald (Rhynchosporium secalis), blast of rice (Magnaporthe grisea), rust of soybean (Phakopsora pachyrhizi), glume blotch of wheat (Leptosphaeria nodorum), powdery mildew of wheat (Blumeria graminis f. sp. tritici), powdery mildew of barley (Blumeria graminis f. sp. hordei), powdery mildew of cucurbits (Erysiphe cichoracearum), anthracnose of cucurbits (Glomerella lagenarium), leaf spot of beet (Cercospora beticola), early blight of tomato (Alternaria solani), and spot blotch of barley (Cochliobolus sativus). The exact amount of the active material to be applied is dependent not only on the specific active material being applied, but also on the particular action desired, the fungal species to be controlled, and the stage of growth thereof, as well as the part of the plant or other product to be contacted with the compound. Thus, all the compounds, and formulations containing the same, may not be equally effective at similar concentrations or against the same fungal species.
  • The compounds are effective in use with plants in a disease-inhibiting and phytologically acceptable amount. The term “disease-inhibiting and phytologically acceptable amount” refers to an amount of a compound that kills or inhibits the plant disease for which control is desired, but is not significantly toxic to the plant. This amount will generally be from about 0.1 to about 1000 ppm (parts per million), with 1 to 500 ppm being preferred. The exact concentration of compound required varies with the fungal disease to be controlled, the type of formulation employed, the method of application, the particular plant species, climate conditions, and the like. A suitable application rate is typically in the range from about 0.10 to about 4 pounds/acre (about 0.01 to 0.45 grams per square meter, g/m2).
  • Any range or desired value given herein may be extended or altered without losing the effects sought, as is apparent to the skilled person for an understanding of the teachings herein.
  • The compounds of Formula I may be made using well-known chemical procedures. Intermediates not specifically mentioned in this disclosure are either commercially available, may be made by routes disclosed in the chemical literature, or may be readily synthesized from commercial starting materials utilizing standard procedures.
    • General Schemes
  • The following schemes illustrate approaches to generating picolinamide compounds of Formula (I). The following descriptions and examples are provided for illustrative purposes and should not be construed as limiting in terms of substituents or substitution patterns.
  • Compounds of Formula 1.3 and 1.4 wherein R4 is as originally defined, can be prepared by the methods shown in Scheme 1, steps a-c. Compounds of Formula 1.1, wherein R4 is as originally defined, can be prepared by treatment of halogens (X) of Formula 1.0, wherein R4 is as originally defined, first under standard Grignard conditions, using magnesium metal and an alkali base, such as lithium chloride, in a polar, aprotic solvent such as tetrahydrofuran (THF) or diethyl ether (Et2O), at a temperature of about 0° C. to about 70° C., to afford the Grignard intermediate. The solution is then treated with a metal catalyst, such as iron (III) acetylacetonate, followed by allyl chloride, in a polar aprotic solvent, such as THF, at a temperature of about 0° C. to about 70° C., to give compounds of Formula 1.1, wherein R4 is as previously defined, and shown in step a. Generally, the composition of compounds of Formula 1.1 derived from this process is a mixture of allyl and E, Z isomers of the styrene derived products. Compounds of Formula 1.1, wherein R4 is as previously defined, can be isomerized to compounds of Formula 1.2 by treating with a metal catalyst system, such as bis(dibenzylideneactone)palladium (0), a phosphine coordinating reagent, such as tri-tert-butylphosphine, and an acid chloride, such as isobutyryl chloride, in an aromatic hydrocarbon solvent such as toluene, at a temperature of about 25° C. to 100° C., to afford compounds of Formula 1.2, wherein R4 is as originally defined, and shown in step b. Alternatively, compounds of Formula 1.2, wherein R4 is as originally defined, can be isomerized using the conditions of Mayer, M.; Welther, A.; Jacobi von Wangelin, A. ChemCatChem. 2011, 3, 1567-1571, and shown in step b. Epoxides of Formulas 1.3 and 1.4, wherein R4 is as previously defined, can be obtained by a catalytic asymmetric epoxidation method using oxone as oxidant and a fructose derived ketone as described by Wang, Z-X; Tu, Y.; Frohn, M.; Zhang, J-R.; Shi, Y. J. Am. Chem. Soc. 1997, 119, 11224-11235, and depicted in step c. It will be understood by those skilled in the art that epoxides of Formulae 1.3 and 1.4, wherein R4 is as previously defined, can be prepared by other catalytic asymmetric epoxidation methods, including, but not limited to, dioxiranes derived from other chiral ketones; catalytic metal salen complexes using an oxidant, such
  • Figure US20180186742A1-20180705-C00004
  • as dioxygen or sodium hypochlorite; chiral iminium salts using oxone as the oxidizing species; chiral organic oxaziridine salts; and enzymatic epoxidation biocatalysts, such as monooxygenases and hydrolases. In certain other cases, compounds of Formula 1.2, wherein R4 is as previously defined, can be prepared by the oxo-metathesis method of Franzen (Eur. J. Org. Chem. 2015, 1834) and shown in step d. Treatment of aldehydes of Formula 1.5, wherein R4 is as previously defined, with an alkene, such as 2-methyl-2-butene, and a Lewis acidic catalyst, such as trityl tetrafluoroborate, in a polar, aprotic solvent, such as dichloromethane, at a temperature of about −78° C. to about room temperature, affords trans-alkenes of Formula 1.2, wherein R4 is as previously defined.
  • Compounds of Formulas 2.1 and 2.2, wherein R3, R3′ and R4 are as previously defined, and R3 and R3′ may or may not be equivalent, can be prepared by the method shown in Scheme 2, step a. Subjection of epoxides of Formulas 1.3 and 1.4, wherein R4 is as previously defined, to an
  • Figure US20180186742A1-20180705-C00005
  • organometallic nucleophile, such as an alkyl magnesium halide, in the presence of a metal halide, such as copper iodide, in a polar, aprotic solvent, such as THF or Et2O, at a temperature of about −78° C. to 55° C., affords compounds of Formulas 2.1 and 2.2, wherein R3, R3′ and R4 are as previously defined, and R3 and R3′ may or may not be equivalent, and shown in step a.
  • In certain cases, it is beneficial to employ an alkenyl organometallic reagent as the carbon nucleophile and shown in Scheme 3. Compounds of Formulas 3.1 and 3.3, wherein R3 and R4 are as previously defined, can be prepared by treating epoxides of Formulas 1.3 and 1.4, wherein R4 is as previously defined, with an alkenyl magnesium halide, such as prop-1-en-2-ylmagnesium bromide, in the presence of a metal halide, such as copper iodide, in a polar, aprotic solvent, such as THF or Et2O, at a temperature of about −78° C. to 25° C., and shown in step a. Compounds of
  • Figure US20180186742A1-20180705-C00006
  • Formulas 3.2 and 3.4, wherein R3 and R4 are as previously defined, can be prepared by treatment of compounds of Formulas 3.1 and 3.3, wherein R3 and R4 are as previously defined, with a metal hydrogenation catalyst, such as tris(triphenylphosphine)rhodium(I) chloride (Wilkinson's catalyst) in a polar, aprotic solvent, such as THF, in the presence of a hydrogen atmosphere (1-4 atm); or, alternatively, with palladium absorbed on carbon, in a polar solvent, such as THF, in the presence of a hydrogen atmosphere (1-4 atm), and shown in step b.
  • In certain additional examples, compounds of Formula 4.2, wherein R3, R3′ and R4 are as previously defined and R3 and R3′ may or may not be equivalent, can be prepared by the procedure shown in Scheme 4, steps a and b. Compounds of Formula 2.1, wherein R3, R3′ and R4 are as previously defined and R3 and R3′ may or may not be equivalent, can be treated with an oxidizing reagent, such as the Dess-Martin periodinane, in a polar solvent such as dichloromethane (CH2Cl2), at a temperature of about 0° C. to 50° C., to give compounds of Formula 4.1, wherein R3, R3′ and R4 are as previously defined and R3 and R3′ may or may not be equivalent, and shown in a. Compounds of Formula 4.1, wherein R3, R3′ and R4 are as previously defined and R3 and R3′ may or may not be equivalent, can be treated with a chiral oxazaborolidine catalyst, such as (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole, in the presence of a boron hydride reducing agent, such as borane-dimethyl sulfide complex, in an aprotic solvent, such as toluene or
  • Figure US20180186742A1-20180705-C00007
  • THF, at a temperature from about −78° C. to about room temperature, to afford compounds of Formula 4.2, wherein R3, R3′ and R4 are as previously defined and R3 and R3′ may or may not be equivalent, and shown in b. Typical diastereomeric ratios obtained in b are generally in the 2:1 to 5:1 range with the anti isomer being favored over the syn. It will be understood by those skilled in the art that compounds of Formula 4.1, wherein R3, R3′ and R4 are as previously defined and R3 and R3′ may or may not be equivalent, can be enantioselective reduced by other chiral catalyst/hydride reducing agent combinations, including, but not limited to, chirally modified lithium aluminum hydride or sodium borohydride reagents, phosphoramide catalysts, transfer hydrogenation catalyzed by chiral metal complexes, phase transfer catalysts, or enantioselective hydrogenation of pro-chiral ketones by enzymatic catalysis.
  • In yet other examples, it is beneficial to prepare compounds of Formula 2.1 and 2.2, wherein R3, R3′ and R4 are as previously defined, and R3 and R3′ may or may not be equivalent, by the method shown in Scheme 4A. Treatment of substituted acetic acids of Formula 4A.0, wherein R4 is as previously defined, with two equivalents of a strong base, such as isopropylmagnesium chloride, and an alkylating reagent, such as 2-iodopropane, in a polar aprotic solvent, such as THF, at a temperature of about 25° C. to about 70° C. gives compounds of Formula 4A.1, wherein R3, R3′ and R4 are as previously defined, and R3 and R3′ may or may not be equivalent, and shown in step a. Compounds of Formula 4A.1, wherein R3, R3′ and R4 are as previously defined and R3 and R3′ may or may not be equivalent, can be treated with an amine, such as N,O-dimethylhydroxylamine
  • Figure US20180186742A1-20180705-C00008
  • hydrochloride, a coupling reagent, such as 3-(ethyliminomethyleneamino)-N,N-dimethylpropan-1-amine hydrochloride (EDC) or a polymer-supported carbodiimide (PS-CDI), and a catalyst, such as N,N-dimethylpyridin-4-amine (DMAP), in a halogenated or polar, aprotic solvent, such as CH2Cl2 or THF to afford compounds of Formula 4A.2, wherein R3, R3′ and R4 are as originally defined, and R3 and R3′ may or may not be equivalent, as shown in step b. Treatment of amides of Formula 4A.2, wherein R3, R3′ and R4 are as originally defined, and R3 and R3′ may or may not be equivalent, with a Grignard reagent, such as methylmagnesium bromide, in a polar, aprotic solvent, such as THF, at a temperature of about 0° C. to about 60° C. yields compounds of Formula 4A.3, wherein R3, R3′ and R4 are as originally defined, and R3 and R3′ may or may not be equivalent, and shown in step c. A racemic mixture of compounds of Formula 2.1 and 2.2, wherein R3, R3′ and R4 are as previously defined, and R3 and R3′ may or may not be equivalent, can be prepared by treating compounds of Formula 4A.3, wherein R3, R3′ and R4 are as originally defined, and R3 and R3′ may or may not be equivalent, with a hydride reducing agent, such as lithium aluminum hydride, in a polar, aprotic solvent, such as THF, at a temperature of about −78° C. to about 30° C., to afford and inseparable mixture of compounds of Formula 2.1 and 2.2, wherein R3, R3′ and R4 are as previously defined, and R3 and R3′ may or may not be equivalent, and shown in step d. A racemic mixture of compounds of Formula 2.1 and 2.2, wherein R3, R3′ and R4 are as previously defined, and R3 and R3′ may or may not be equivalent, can be separated by treatment of the mixture with an optically active carboxylic acid, such as (S)-2-methoxy-2-phenylacetic acid, a coupling reagent, such as 3-(ethyliminomethyleneamino)-N,N-dimethylpropan-1-amine hydrochloride (EDC) or a polymer-supported carbodiimide (PS-CDI), and a catalyst, such as N,N-dimethylpyridin-4-amine (DMAP), in a halogenated or polar, aprotic solvent, such as CH2Cl2 or THF to afford compounds of Formula 4A.4 and 4A.5, wherein R3, R3′ and R4 are as originally defined, and R3 and R3′ may or may not be equivalent, as shown in step e. The diastereomeric mixture can then separated into its individual components via silica gel chromatography using a mobile phase, such as 10% tert-butyl methyl ether in hexanes, as the eluant. The individual diastereomers, compounds of Formula 4A.4 and 4A.5, wherein R3, R3′ and R4 are as originally defined, and R3 and R3′ may or may not be equivalent, can be treated with a carbonate base, such as potassium carbonate, in a polar, alcoholic solvent, such as methanol, at a temperature of about 25° C. to about 60° C., to give compounds of Formula 2.1 and 2.2, wherein R3, R3′ and R4 are as previously defined, and R3 and R3′ may or may not be equivalent, and shown in step f.
  • In certain additional examples, compounds of Formula 5.5 and 5.9, wherein R3, R3′ and R4 are as previously defined and R3 and R3′ may or may not be equivalent, can be prepared by the procedure shown in Scheme 5, steps a-i. The compound of Formula 5.0 can be treated with an aryl or heteroaryl organometallic reagent, such as phenylmagnesium bromide, in a polar aprotic solvent, such as THF or Et2O, at a temperature of about 0° C. to room temperature, to afford compounds of Formula 5.1, wherein R4 is as originally defined, and shown in step a. Subjection of compounds of Formula 5.1 to an oxidization procedure, such as the Swern process (oxalyl chloride, DMSO, Et3N, CH2Cl2), affords compounds of Formula 5.2, wherein R4 is as originally defined, depicted in b. Alternatively, compounds of Formula 5.2, wherein R4 is as originally defined, can be prepared by treatment of pyrolidine amide 5.15 with an arylmagnesium halide, such as phenylmagnesium bromide, in a polar, aprotic solvent, such as THF, at a temperature of about −20° C. to about 40° C. to give compounds of Formula 5.2, wherein R4 is as originally defined, and shown in step b2. Compounds of Formula 5.3, wherein R3, R3′ and R4 are as previously defined, and
  • Figure US20180186742A1-20180705-C00009
  • R3 and R3′ may or may not be equivalent, can be obtained by treating compounds of Formula 5.2, wherein R4 is as originally defined, with an organometallic nucleophile, such as isopropylmagnesium bromide, in a polar aprotic solvent, such as THF or Et2O, at a temperature of about 0° C. to room temperature, as depicted in step c. Compounds of Formula 5.4, wherein R3, R3′, and R4 are as previously defined and R3 and R3′ may or may not be equivalent, and R4 is not an electron-deficient aryl or heteroaryl group, can be obtained by treating the compounds of Formula 5.3, wherein R3, R3′ are as previously defined and may or may not be equivalent, and R4 is not an electron-deficient aryl or heteroaryl group, with a mixture of a hydride reagent, such as triethylsilane (Et3SiH), and an acid, such as 2,2,2-trifluoroacetic acid (TFA) in a halogenated solvent such as dichloromethane (DCM) at a temperature of about 0° C. to 23° C., as depicted in d. Compounds of Formula 5.5, wherein R3, R3′, and R4 are as originally defined and R3 may or may not be equivalent to R3′, can be prepared from compounds of Formula 5.4, wherein R3, R3′, and R4 are as originally defined and R3 may or may not be equivalent to R3′, by treating with a metal catalyst such as palladium on carbon (Pd/C) in a polar protic solvent, such as ethanol (EtOH), in a hydrogen atmosphere (1-4 atm) at a temperature of about 25° C. to 65° C., or with an alternate source of hydrogen, such as cyclohexene, in a polar solvent such as EtOH, and shown in step e. In certain other cases, it is beneficial to synthesize compounds of Formula 5.9, wherein R3 and R4 are as originally defined, by the method shown in steps f-i. Compounds of Formula 5.2, wherein R4 is as previously defined, can be treated with an alkenyl organometallic reagent, such as isopropenylmagnesium bromide, in a polar aprotic solvent, such as THF or Et2O, at a temperature of about 0° C. to room temperature, to afford compounds of Formula 5.6, wherein R3 and R4 are as originally defined, and shown in step f. Compounds of Formula 5.7, wherein R3 and R4 are as previously defined, can be prepared by treatment of compounds of Formula 5.6, wherein R3 and R4 are as previously defined, with a metal hydrogenation catalyst, such as tris(triphenylphosphine)rhodium(I) chloride (Wilkinson's catalyst) in a polar, aprotic solvent, such as THF, in the presence of a hydrogen atmosphere (1-4 atm), and shown in g. Compounds of Formula 5.8, wherein R3 and R4 are as previously defined, and R4 is not an electron-deficient aryl or heteroaryl group, can be obtained by treating the compounds of Formula 5.7, wherein R3 and R4 are as previously defined, and R4 is not an electron-deficient aryl or heteroaryl group, with a mixture of a hydride reagent, such as triethylsilane (Et3SiH), and an acid, such as 2,2,2-trifluoroacetic acid (TFA) in a halogenated solvent such as dichloromethane (DCM) at a temperature of about 0° C. to 23° C., as depicted in h. Compounds of Formula 5.9, wherein R3 and R4 are as previously defined, can be prepared by treatment of compounds of Formula 5.8, wherein R3 and R4 are as previously defined, with a metal hydrogenation catalyst, such as tris(triphenylphosphine)rhodium(I) chloride (Wilkinson's catalyst) in a polar, aprotic solvent, such as THF, in the presence of a hydrogen atmosphere (1-4 atm); or, alternatively, with palladium absorbed on carbon, in a polar solvent, such as THF, in the presence of a hydrogen atmosphere (1-4 atm), and shown in step i.
  • In certain other examples, compounds of Formula 5.5, wherein R3, R3′, and R4, are as originally defined, and R3 and R3′ may or may not be equivalent, may also be prepared according to the method outlined in Scheme 6, steps a and b. Treatment of compounds of Formula 2.1, wherein R3, R3′, and R4 are as originally defined, and R3 and R3′ may or may not be equivalent, with an
  • Figure US20180186742A1-20180705-C00010
  • electron deficient benzoic acid, such as p-nitrobenzoic acid, a phosphine nucleophile, such as triphenylphosphine; and a diazene coupling reagent, such as diethyl (E)-diazene-1,2-dicarboxylate, in a polar, aprotic solvent, such as THF, at a temperature of about 0° C. to about 25° C. affords compounds of Formula 6.1, wherein R3, R3′, and R4 are as originally defined, and R3 and R3′ may or may not be equivalent, as depicted in step a. In step b, compounds of Formula 6.1, wherein R3, R3′, and R4 are as originally defined, and R3 and R3′ may or may not be equivalent, can be treated with an aqueous solution of an inorganic base, such as sodium hydroxide, in a polar aprotic solvent, such as THF, at a temperature of about 0° C. to about 40° C. to afford compounds of Formula 5.5, wherein R3, R3′, and R4 are as originally defined, and R3 and R3′ may or may not be equivalent.
  • Compounds of Formula 7.2, wherein R1, R3, R3′, R4, and R11, are as originally defined, and R3 and R3′ may or may not be equivalent, may be prepared according to the method outlined in Scheme 7, step a. Alcohols of Formula 5.5, wherein R3, R3′, and R4, are as originally defined, and R3 and R3′ may or may not be equivalent, can be treated with compounds of Formula 7.1, wherein R1 and R11 are as originally defined, a coupling reagent, such as 3-(ethyliminomethyleneamino)-N,N-dimethylpropan-1-amine hydrochloride (EDC) or a polymer-supported carbodiimide (PS-CDI), and a catalyst, such as N,N-dimethylpyridin-4-amine (DMAP), in a halogenated or polar, aprotic solvent, such as CH2Cl2 or THF to afford compounds of Formula 7.2, wherein R1, R3, R3′, R4, and R11, are as originally defined, and R3 and R3′ may or may not be equivalent, as shown in step a.
  • Figure US20180186742A1-20180705-C00011
  • Compounds of Formula 7.2, wherein R1, R3, R3′, R4, and R11, are as originally defined, and R3 and R3′ may or may not be equivalent, may also be prepared according to the method outlined in Scheme 8, step a. Alcohols of Formula 2.1, wherein R3, R3′, and R4, are as originally
  • Figure US20180186742A1-20180705-C00012
  • defined, and R3 and R3′ may or may not be equivalent, can be treated with compounds of Formula 7.1, wherein R1 and R11 are as originally defined, a phosphine reagent, such as triphenylphosphine, and a diazine dicarboxylate electrophile, such as diisopropyl (E)-diazene-1,2-dicarboxylate (DIAD), in a polar aprotic solvent, such as THF, at a temperature of about 0° C. to 25° C. to afford compounds of Formula 7.2, wherein R1, R3, R3′, R4, and R11, are as originally defined, and R3 and R3′ may or may not be equivalent, as shown in step a.
  • Compounds of Formula 9.5, wherein R1, R2, R3, R3′, R4, R6, and R11, are as originally defined, and R3 and R3′ may or may not be equivalent, can be prepared according to the methods outlined in Scheme 9, steps a-d. Compounds of Formula 9.1, wherein R1, R2, R3, R3′, R4, and R11, are as originally defined, and R3 and R3′ may or may not be equivalent, but not alkenyl, can be treated with an acid, such as a 4 N solution of HCl in dioxane, in a halogenated solvent such as CH2Cl2 to afford compounds of Formula 9.2, wherein R1, R2, R3, R3′, R4, and R11, are as originally defined, and R3 and R3′ may or may not be equivalent, but not alkenyl, as shown in step a. Compounds of Formula 9.3, wherein R1, R2, R3, R3′, R4, and R11, are as originally defined, and R3 and R3′ may or may not be equivalent, can be prepared by treating compounds of Formula 9.1, wherein R1, R2, R3, R3′, R4, and R11, are as originally defined, and R3 and R3′ may or may not be equivalent, with an acid, such as 2,2,2-trifluoroacetic acid, in a halogenated solvent such as CH2Cl2, as shown in step c. Compounds of Formulas 9.2 and 9.3, wherein R1, R2, R3, R3′, R4, and R11, are as originally defined, and R3 and R3′ may or may not be equivalent, can be treated with compounds of Formula 9.4, wherein R6 is as originally defined, in the presence of a base, such as diisopropylethylamine, and a peptide coupling reagent, such as benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP) or O-(7-azabenzo-triazol-1-yl)-N,N,N′,N′tetramethyluronium hexafluorophosphate (HATU), in an halogenated solvent such as CH2Cl2, to afford compounds of Formula 9.5, wherein R1, R2, R3, R3′, R4, R6 and R11, are as originally defined, and R3 and R3′ may or may not be equivalent, as shown in steps b and d.
  • Figure US20180186742A1-20180705-C00013
  • Compounds of Formula 10.1, wherein R1, R2, R3, R3′, R4, R6, R7, and R11, are as originally defined, and R3 and R3′ may or may not be equivalent, can be prepared according to the method outlined in Scheme 10, steps a or b. Compounds of Formula 9.5, wherein R1, R2, R3, R3′, R4, R6 and R11, are as originally defined, and R3 and R3′ may or may not be equivalent, can be treated with an appropriate alkyl halide with or without a reagent such as sodium iodide (NaI) and an alkali carbonate base, such as sodium (Na2CO3) or potassium carbonate (K2CO3), in a solvent such as acetone, as shown in step a. Or, alternatively, by treatment with an acyl halide or anhydride in the presence of an amine base, such as pyridine, NEt3, DMAP, or mixtures thereof, in an aprotic solvent, such as CH2Cl2, to afford compounds of Formula 10.1, wherein R1, R2, R3, R3′, R4, R6, R7, and R11, are as originally defined, and R3 and R3′ may or may not be equivalent, as shown in step b.
  • Figure US20180186742A1-20180705-C00014
  • Compounds of Formula 11.1 and 11.2, wherein R1, R2, R3, R3′, R4, R6, R7, and R11, are as originally defined, and R3 and R3′ may or may not be equivalent, can be prepared according to the method outlined in Scheme 11, steps a and b. Compounds of Formula 9.5, wherein R1, R2, R3, R3′, R4, R6, and R11, are as originally defined, and R3 and R3′ may or may not be equivalent, can be treated with a thionating reagent such as phosphorus pentasulfide, an additive, such as hexamethyldisiloxane, optionally in a polar aprotic solvent such as acetonitrile (CH3CN), at a temperature of about 0° C. to 80° C. to afford compounds of Formula 11.1, wherein R1, R2, R3, R3′, R4, R6, and R11, are as originally defined, and R3 and R3′ may or may not be equivalent, and shown in step a. It will be understood by those skilled in the art that compounds such as Formula 11.1 may also be prepared using other thionating agents including, but not limited to: sulfur, sulfhydric acid, sodium sulfide, sodium hydrosulfide, boron trisulfide, bis(diethylaluminum)sulfide, ammonium sulfide, Lawesson's reagent, ammonium O,O′-diethyl dithiophosphate, rhodanine, or a polymer supported thionating reagent. Additives can include, but not limited to, aluminum oxide (Al2O3); inorganic bases, such as potassium carbonate and sodium bicarbonate; organic bases, such as triethylamine, diethylaniline, pyridine and morpholine. Optional solvents can include, but not limited to, aliphatic, alicyclic or aromatic hydrocarbons, such as hexane, cyclohexane or toluene; halogenated hydrocarbons, such as dichloromethane, 1,2-dichloroethane and chlorobenzene; ethers, such as diethyl ether, 1,4-dioxane, THF and 1,2-dimethoxyethane; and other polar aprotic solvents such as pyridine and hexamethylphosphoramide (HMPA). In step b, treatment of compounds of Formula 11.1, wherein R1, R2, R3, R3′, R4, R6, and R11, are as originally defined, and R3 and R3′ may or may not be equivalent, with an appropriate alkyl halide with or without a reagent such as sodium iodide (NaI) and an alkali carbonate base, such as sodium carbonate (Na2CO3) or potassium carbonate (K2CO3), in a solvent like acetone at a temperature of about 55° C., or by treatment with an acyl halide or anhydride in the presence of an amine base, such as pyridine, triethylamine (Et3N), DMAP, or mixtures thereof, in an optional aprotic solvent such as DCM, at a temperature of about 23° C., can afford compounds of Formula 11.2 wherein R1, R2, R3, R3′, R4, R6, R7, and R11, are as originally defined, and R3 and R3′ may or may not be equivalent.
  • Figure US20180186742A1-20180705-C00015
  • Compounds of Formula 12.1, wherein R1, R2, R3, R3′, R4, R6, and R11, are as originally defined, and R3 and R3′ may or may not be equivalent, can be prepared according to the method outlined in Scheme 12, step a. Compounds of Formula 9.5, wherein R1, R2, R3, R3′, R4, R6, and R11, are as originally defined, and R3 and R3′ may or may not be equivalent, can be treated with a oxidizing reagent such as m-chloroperbenzoic acid (mCPBA) in a polar solvent such as dichloromethane (CH2Cl2), at a temperature of about 0° C. to 50° C., to give compounds of Formula 12.1, as shown in a. It will be understood by those skilled in the art that compounds of Formula 12.1, wherein R1, R2, R3, R3′, R4, R6, and R11, are as originally defined, and R3 and R3′ may or may not be equivalent, may also be prepared using other oxidizing agents, including, bit not limited to:
  • Figure US20180186742A1-20180705-C00016
  • hydrogen peroxide, hydrogen peroxide-urea complex, magnesium monoperoxyphthalate hexahydrate (MMPP), peroxyacetic acid, oxone, sodium perchlorate or dimethyl dioxirane.
  • Compounds of Formula 13.1 wherein R1, R2, R3, R3′, R4, R6, and R11, are as originally defined, and R3 and R3′ may or may not be equivalent, can be prepared according to the method outlined in Scheme 13, step a. Compounds of Formula 9.5, wherein R1, R2, R3, R3′, R4, R6, and R11, are as originally defined, and R3 and R3′ may or may not be equivalent, can be treated with a deactivated carbonyl reagent such as triphosgene, with a base, such as pyridine, in a polar solvent, such as dichloromethane (CH2Cl2), at a temperature of about 0° C. to 50° C. to afford compounds of Formula 13.1, wherein R1, R2, R3, R3′, R4, R6, and R11, are as originally defined, and R3 and R3′ may or may not be equivalent, as depicted in a.
  • Figure US20180186742A1-20180705-C00017
    • EXAMPLES Example 1A: Preparation of (E)-1-methyl-4-(prop-1-en-1-yl)benzene
  • Figure US20180186742A1-20180705-C00018
  • This compound was prepared by the method of Mayer, M.; Welther, A.; Jacobi von Wangelin, A. ChemCatChem. 2011, 3, 1567-1571.
    • Example 1B: Preparation of (E)-1-fluoro-4-(prop-1-en-1-yl)benzene
  • Figure US20180186742A1-20180705-C00019
  • To a solution of 1-allyl-4-fluorobenzene (1.35 mL, 10 mmol) in toluene (20 mL) was added bis(dibenzylideneacetone)palladium (0.115 g, 0.200 mmol), tri-tert-butylphosphine (10% in hexane) (0.618 ml, 0.200 mmol) and isobutyryl chloride (0.021 ml, 0.200 mmol) in toluene (20.00 ml). The reaction was stirred at 80° C. overnight. The reaction mixture was purified by Isco chromatography (0 to 5% Et2O in pet ether) to provide the desired product as solution in toluene (20 mL) (1.36 g, 95%). 1H NMR (300 MHz, CDCl3) δ 7.32-7.10 (m, 6H), 2.35 (s, 3H). 19F NMR (376 MHz, CDCl3) δ −115.97.
    • Example 1C: Preparation of (E)-4-fluoro-2-methoxy-1-(prop-1-en-1-yl)benzene Step 1: Preparation of (E,Z)-4-fluoro-2-methoxy-1-(prop-1-en-1-yl)benzene
  • Figure US20180186742A1-20180705-C00020
  • To a mixture of magnesium (0.79 g, 32.5 mmol) and lithium chloride (1.52 g, 35.80 mmol) in THF (33 ml) at room temperature was added 1-bromo-4-fluoro-2-methoxybenzene (3.13 mL, 24.39 mmol) and the reaction was stirred at 70° C. for 1.5 hr. The reaction was then cooled to 0° C., and Fe(acac)3 (0.574 g, 1.63 mmol) was added. After 1 minute, allyl chloride (1.33 mL, 16.26 mmol) was added and the reaction was stirred at 0° C. for 30 min. The mixture was warmed to room temperature over 1 hr and was heated at 70° C. overnight. The reaction was cooled and diluted with petroleum ether (100 mL). The reaction was then quenched by the addition of a saturated NH4Cl solution (100 mL). The mixture was filtered through a Celite® pad and the layers were separated. The aqueous layer was extracted with petroleum ether (2×100 mL) and the combined organic phases were dried over Na2SO4 and carefully concentrated (25° C., 250 mbar). The residue was purified by Isco chromatography (100% pet ether as the eluent) to provide (E,Z)-4-fluoro-2-methoxy-1-(prop-1-en-1-yl)benzene (2.25 g, 83% yield) as a colorless oil. This mixture was approximately a 3:1 mixture of E and Z isomers with a trace of the allyl isomer present. This material was used directly in the next step. 1H NMR (400 MHz, CDCl3) δ 7.31 (dd, J=8.3, 6.8 Hz, 1H), 6.65-6.53 (m, 3H), 6.14 (dq, J=15.8, 6.6 Hz, 1H), 3.82 (s, 3H), 1.88 (dd, J=6.6, 1.7 Hz, 3H). 19F NMR (376 MHz, CDCl3) δ −113.30.
    • Step 2: Preparation of (E)-4-fluoro-2-methoxy-1-(prop-1-en-1-yl)benzene
  • Figure US20180186742A1-20180705-C00021
  • To a solution of (E,Z)-4-fluoro-2-methoxy-1-(prop-1-en-1-yl)benzene (2.25 g, 13.54 mmol) in toluene (27 mL) was added bis(dibenzylideneacetone)palladium (0.156 g, 0.271 mmol), tri-tert-butylphosphine (10% in hexane) (0.84 mL, 0.271 mmol) and isobutyryl chloride (0.028 mL, 0.271 mmol). The reaction was stirred at 80° C. overnight. The reaction mixture was purified by Isco chromatography (100% petroleum ether) to provide the title compound as a 20:1 mixture of E vs Z isomers (2.25 g, 100%). 1H NMR (400 MHz, CDCl3) δ 7.31 (dd, J=8.3, 6.8 Hz, 1H), 6.65-6.53 (m, 3H), 6.14 (dq, J=15.8, 6.6 Hz, 1H), 3.82 (s, 3H), 1.88 (dd, J=6.6, 1.7 Hz, 3H). 19F NMR (376 MHz, CDCl3) δ −113.30.
    • Example 1D: Preparation of (E)-2,4-dimethyl-1-(prop-1-en-1-yl)benzene Step 1: Preparation of 1-allyl-2,4-dimethylbenzene
  • Figure US20180186742A1-20180705-C00022
  • To a solution of magnesium (1.17 g, 48.0 mmol) and lithium chloride (2.20 g, 60.0 mmol) in THF (40 ml) at room temperature was added 1-bromo-2,4-dimethylbenzene (5.4 mL, 40.0 mmol) and the reaction was heated gently to reflux with a heat gun. The reaction was cooled to room temperature over 1 hr. The reaction was then cooled to 0° C., and Fe(acac)3 (0.71 g, 2.00 mmol) dissolved in 5 mL of THF was added. After 5 minutes, allyl chloride (4.23 mL, 52.0 mmol) was added and the reaction was stirred at 0° C. for 30 min. The mixture was warmed to room temperature over 1 hr and was heated at 70° C. overnight. The reaction was cooled to 0° C. and quenched by the addition of a saturated NaHCO3 solution (50 mL). The mixture was extracted with hexane (3×40 mL), the combined organic phases were washed with brine (50 mL), dried over Na2SO4 and carefully concentrated (25° C., 250 mbar). The residue was purified by Isco chromatography (100% hexane as the eluent) to provide 1-allyl-2,4-dimethylbenzene (2.75 g, 15.04 mmol, 38% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.11-6.87 (m, 3H), 5.93 (ddt, J=16.6, 10.1, 6.4 Hz, 1H), 5.19-4.85 (m, 2H), 3.33 (dd, J=6.4, 1.5 Hz, 2H), 2.29 (s, 3H), 2.25 (s, 3H).
    • Step 2: Preparation of (E)-2,4-dimethyl-1-(prop-1-en-1-yl)benzene
  • Figure US20180186742A1-20180705-C00023
  • To a 250 mL round bottom flask charged with 1-allyl-2,4-dimethylbenzene (2.75 g, 18.81 mmol) and tris(((Z)-4-oxopent-2-en-2-yl)oxy)iron (0.332 g, 0.940 mmol) in THF (38 mL) was added phenylmagnesium bromide (1.0 M in THF) (9.40 mL, 9.40 mmol) at room temperature. After stirring overnight, the reaction mixture was cooled to 0° C. and quenched by the addition of a saturated solution of NaHCO3 (50 mL). The combined organic layers were extracted with hexane (3×40 mL), washed with brine (50 mL) and dried over Na2SO4. Upon concentration in vacuo, the crude residue was purified via automated silica gel chromatography (100% hexanes as the eluent) to afford (E)-2,4-dimethyl-1-(prop-1-en-1-yl)benzene (2.71 g, 16.68 mmol, 89% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.30 (d, J=7.8 Hz, 1H), 7.05-6.86 (m, 2H), 6.56 (dd, J=15.6, 1.9 Hz, 1H), 6.06 (dq, J=15.6, 6.6 Hz, 1H), 2.30 (s, 3H), 2.29 (s, 3H), 1.89 (dd, J=6.6, 1.7 Hz, 3H).
    • Example 1E: Preparation of (E)-1-methyl-2-(prop-1-en-1-yl)benzene
  • Figure US20180186742A1-20180705-C00024
  • This compound was prepared by the method of Franzen (Eur. J. Org. Chem. 2015, 1834). To a solution of 2-methylbenzaldehyde (48.4 mL, 416 mmol) dissolved in CH2Cl2 (300 mL) was added 2-methylbut-2-ene (8.82 mL, 83 mmol) and triphenylmethylium tetrafluoroborate (5.50 g, 16.65 mmol). The reaction was stirred at room temperature for 20 hr. The reaction was quenched by the addition of saturated NaHCO3 and diluted with excess CH2Cl2. The organic layer was separated, dried over MgSO4, filtered and concentrated at low temperature and mild pressure. The resulting residue was purified by flash chromatography (ISCO, 330 g SiO2 column, 100% pet ether as the eluent) to give (E)-1-methyl-2-(prop-1-en-1-yl)benzene (10 g, 71.9 mmol, 86% yield) as a clear liquid. 1H NMR (400 MHz, CDCl3) δ 7.39 (d, J=7.0 Hz, 1H), 7.12 (qd, J=5.9, 2.1 Hz, 3H), 6.59 (dd, J=15.6, 1.9 Hz, 1H), 6.10 (dq, J=15.7, 6.6 Hz, 1H), 2.32 (s, 3H), 1.90 (dd, J=6.6, 1.8 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 137.08, 134.77, 130.11, 128.92, 126.93, 126.70, 125.99, 125.44. EIMS m/z 132.
    • Example 2A: 2A Denotes that this Epoxide is Commercially Available Example 2B: Preparation of (2S,3S)-2-methyl-3-(p-tolyl)oxirane
  • Figure US20180186742A1-20180705-C00025
  • To a 500 mL round-bottom flask containing 75 mL of a buffer solution containing 0.05 M Na2B4O7-10H2O in 4×10−4 M aqueous Na2(EDTA), was added acetonitrile (117 ml), (E)-1-methyl-4-(prop-1-en-1-yl)benzene (1.24 g, 7.69 mmol), tetrabutylammonium hydrogen sulfate (0.104 g, 0.308 mmol), and (3aS,4′R,7aS)-2,2,2′,2′-tetramethyldihydrospiro[[1,3]dioxolo-[4,5-c]pyran-6,4′-[1,3]dioxolan]-7(7aH)-one (0.596 g, 2.307 mmol). The reaction mixture was cooled to 0° C. with an ice bath. A solution of oxone (6.53 g, 10.61 mmol) in aqueous Na2(EDTA) (4×10−4 M, 50 mL) and a solution of potassium carbonate (6.17 g, 44.6 mmol) in water (50 mL) were added dropwise through two syringe pumps over a period of 1.5 h (under these conditions, the reaction pH is around 10.5; it is recommended that both oxone and K2CO3 be added uniformly over 1.5 h). At this point, the reaction was immediately quenched by the addition of 100 mL each of petroleum ether and water. The layers were separated and the aqueous layer was extracted with petroleum ether (3×150 mL). The combined organic layers were washed with brine (150 mL), dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by flash chromatography (0 to 10% acetone in hexanes as the eluent) to provide (2S,3S)-2-methyl-3-(p-tolyl)oxirane (1.09 g, 6.99 mmol, 91%) as a colorless oil. 1H NMR (300 MHz, CDCl3) δ 7.15 (s, 4H), 3.54 (d, J=2.1 Hz, 1H), 3.03 (qd, J=5.1, 2.1 Hz, 1H), 2.34 (s, 3H), 1.44 (d, J=5.1 Hz, 3H). EIMS m/z 148.
    • Example 3A: Preparation of (1S,2R)-1-cyclobutyl-1-(4-fluoro-2-methylphenyl)propan-2-ol
  • Figure US20180186742A1-20180705-C00026
  • A suspension of magnesium (110 mg, 4.51 mmol) was prepared in THF (3 mL) and cooled to 0° C. After 5 min, bromocyclobutane (397 μL, 4.21 mmol) was added in one portion, and the resulting solution was vigorously stirred for 2 hr, slowly warming to room temperature. After 2 hr, the reaction was heated to 55° C. and stirred overnight. In a separate vial, a suspension of copper(I) iodide (401 mg, 2.106 mmol) in diethyl ether (7.5 mL) was cooled to −30° C. in a dry ice/acetonitrile bath. After −5 min, the grignard solution was added via syringe over 30 seconds, and the resulting solution was stirred at −30° C. for 30 min, yielding a turbid dark grey/brown mixture. After 30 min, the reaction was cooled to −78° C. in a dry ice/acetone bath, and (2R,3R)-2-(4-fluoro-2-methylphenyl)-3-methyloxirane (250 mg, 1.504 mmol) was added dropwise via syringe as a solution in diethyl ether (1.5 mL with 2×0.5 mL washes). The reaction was then stirred overnight, slowly warming to room temperature. TLC indicated consumption of starting material. The reaction was quenched with sat. aq. NH4Cl (20 mL) and extracted with diethyl ether (3×20 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated to afford an oil. The oil was purified via silica gel Isco column chromatography (40 g silica gel column, 35 mL/min, 100% hexanes to 20% acetone:hexanes) to afford (1S,2R)-1-cyclobutyl-1-(4-fluoro-2-methylphenyl)propan-2-ol (133.4 mg, 0.600 mmol, 40% yield) as a clear, colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.14 (dd, J=8.2, 6.1 Hz, 1H), 6.86 (t, J=8.5 Hz, 2H), 3.89 (p, J=6.4 Hz, 1H), 2.84 (dd, J=10.4, 6.0 Hz, 1H), 2.77-2.64 (m, 1H), 2.35 (s, 3H), 2.24-2.12 (m, 1H), 1.86-1.58 (m, 4H), 1.44-1.24 (m, 2H), 1.13 (d, J=6.3 Hz, 3H). 19F NMR (376 MHz, CDCl3) δ −117.58, −117.59. 13C NMR (101 MHz, CDCl3) δ 160.94 (d, J=244.2 Hz), 139.81 (d, J=7.3 Hz), 134.60 (d, J=3.3 Hz), 128.53 (d, J=8.0 Hz), 116.78 (d, J=20.7 Hz), 112.84 (d, J=20.6 Hz), 70.25, 53.68, 38.03, 29.54, 27.08, 21.55, 20.55 (d, J=1.7 Hz), 18.16. IR (thin film) 3413, 2967, 1495, 1252, 1021, 955, 860 cm−1.
    • Example 3B: Preparation of (2R,3S)-4-ethyl-3-(4-fluoro-2-methylphenyl)hexan-2-ol
  • Figure US20180186742A1-20180705-C00027
  • A suspension of copper(I) iodide (401 mg, 2.106 mmol) in anhydrous diethyl ether (7.5 mL) was cooled to −30° C. in a dry ice/acetonitrile bath. After −5 min, pentan-3-ylmagnesium bromide (2M in Et2O) (2106 μL, 4.21 mmol) was added via syringe over 30 seconds, and the resulting solution was stirred at −30° C. for 30 min, yielding a turbid dark grey/brown mixture. After 30 min, the reaction was cooled to −78° C. in a dry ice/acetone bath, and (2R,3R)-2-(4-fluoro-2-methylphenyl)-3-methyloxirane (250 mg, 1.504 mmol) was added dropwise via syringe as a solution in diethyl ether (1.5 mL with 2×0.5 mL washes). The reaction was then stirred overnight, slowly warming to room temperature. TLC indicated consumption of starting material. The reaction was quenched with sat. aq. NH4Cl (20 mL) and extracted with diethyl ether (3×20 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated to afford an oil. The oil was purified via silica gel Isco column chromatography (40 g silica gel column, 35 mL/min, 100% hexanes to 20% acetone:hexanes) to afford (2R,3S)-4-ethyl-3-(4-fluoro-2-methylphenyl)hexan-2-ol (116.7 mg, 0.490 mmol, 32.5% yield) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.34 (dd, J=9.6, 6.1 Hz, 1H), 6.92-6.81 (m, 2H), 4.27 (dq, J=8.8, 4.7 Hz, 1H), 2.74 (dd, J=10.2, 3.6 Hz, 1H), 2.28 (s, 3H), 1.87 (qt, J=8.2, 3.6 Hz, 1H), 1.64 (dtd, J=14.9, 7.3, 4.4 Hz, 1H), 1.53 (tt, J=14.0, 6.7 Hz, 1H), 1.30-1.09 (m, 2H), 1.08-0.98 (m, 1H), 0.96 (d, J=6.4 Hz, 3H), 0.92 (t, J=7.5 Hz, 3H), 0.71 (t, J=7.4 Hz, 3H). 19F NMR (376 MHz, CDCl3) d −118.01. 13C NMR (101 MHz, CDCl3) δ 160.91 (d, J=243.7 Hz), 139.73 (d, J=7.1 Hz), 135.03 (d, J=3.3 Hz), 129.46 (d, J=7.9 Hz), 116.60 (d, J=20.5 Hz), 112.57 (d, J=20.4 Hz), 67.19, 47.45, 41.41, 22.08, 21.91, 21.53, 20.67 (d, J=1.6 Hz), 10.82, 9.78. IR (thin film) 3430, 2962, 1496, 1455, 1380, 1256, 956, 860, 801 cm−1.
    • Example 4A: Preparation of (2R,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpent-4-en-2-ol
  • Figure US20180186742A1-20180705-C00028
  • A suspension of copper(I) iodide (0.160 g, 0.842 mmol) in anhydrous diethyl ether (4.0 mL) was cooled to −20° C. After ˜5 min, prop-1-en-2-ylmagnesium bromide (1M in 2-Me-THF) (1.685 mL, 1.685 mmol) was added via syringe over 30 seconds, and the resulting solution was stirred at −20° C. for 30 min. After 30 min, the reaction was cooled to −78° C. and (2R,3R)-2-(4-fluoro-2-methylphenyl)-3-methyloxirane (0.100 g, 0.602 mmol) was added dropwise via syringe as a solution in diethyl ether (1.0 mL with 2×0.5 mL washes). The reaction was then stirred overnight, slowly warming to room temperature. TLC indicated consumption of starting material. The reaction was quenched with sat. aq. NH4Cl (20 mL) and extracted with diethyl ether (3×20 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated to afford an oil. The oil was purified via silica gel Isco column chromatography (40 g silica gel column, 35 mL/min, 100% hexanes to 20% acetone:hexanes) to afford (2R,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpent-4-en-2-ol (120.2 mg, 0.577 mmol, 96% yield) as a pale yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.37-7.30 (m, 1H), 6.93-6.86 (m, 2H), 4.89 (s, 2H), 4.32 (dq, J=8.8, 6.1 Hz, 1H), 3.42 (d, J=8.7 Hz, 1H), 2.34 (s, 3H), 1.59 (s, 3H), 1.52 (s, 1H), 1.30 (d, J=6.1 Hz, 3H). 19F NMR (376 MHz, CDCl3) δ −116.95. 13C NMR (101 MHz, CDCl3) δ 161.27 (d, J=244.8 Hz), 144.85, 140.40 (d, J=7.5 Hz), 133.79 (d, J=3.2 Hz), 128.19 (d, J=8.2 Hz), 117.47 (d, J=20.6 Hz), 113.12, 112.76 (d, J=20.8 Hz), 68.13, 56.04, 21.28, 21.22, 20.03 (d, J=1.5 Hz). IR (thin film) 3373, 2970, 1495, 1240, 958, 861 cm−1.
    • Example 4B: Preparation of (2R,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpentan-2-ol
  • Figure US20180186742A1-20180705-C00029
  • To a 20 mL vial containing (2R,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpent-4-en-2-ol (120.2 mg, 0.577 mmol) and palladium on carbon (5%) (184 mg, 0.087 mmol) was added ethyl acetate (2886 μL). The black reaction mixture was flushed with H2 gas via balloon. The resulting reaction was stirred at room temperature for 2 h, at which point TLC/UPLC indicated consumption of starting material. The reaction was filtered through a plug of celute, eluting with ethyl acetate (2×10 mL). The resulting solution was concentrated to afford an oil that was loaded directly onto a 25 g prepacked silica column in a minimal amount of dichloromethane and purified using Isco silica gel column chromatography (40 column, 40 mL/min, 100% hexanes to 30% ethyl acetate:hexanes) to afford (2R,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpentan-2-ol (44.9 mg, 0.214 mmol, 37.0% yield) as a clear, colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.32 (dd, J=9.5, 6.1 Hz, 1H), 6.93-6.84 (m, 2H), 4.28 (qd, J=6.3, 4.4 Hz, 1H), 2.50 (dd, J=9.2, 4.4 Hz, 1H), 2.28 (s, 3H), 2.15 (dp, J=9.1, 6.6 Hz, 1H), 1.42-1.13 (m, 1H), 1.06 (d, J=6.6 Hz, 3H), 1.01 (d, J=6.3 Hz, 3H), 0.70 (d, J=6.7 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 160.93 (d, J=243.8 Hz), 139.78 (d, J=7.2 Hz), 134.96 (d, J=3.3 Hz), 129.17 (d, J=8.0 Hz), 116.64 (d, J=20.4 Hz), 112.57 (d, J=20.4 Hz), 67.70, 52.62, 30.26, 21.76, 21.32, 20.77. 19F NMR (376 MHz, CDCl3) δ −117.97.
    • Example 4C: Preparation of (2R,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpentan-2-ol
  • Figure US20180186742A1-20180705-C00030
  • To a 250 mL round bottom flask containing (2R,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpent-4-en-2-ol (1.16 g, 5.57 mmol) and Wilkinson's catalyst (1.288 g, 1.392 mmol) was added THF (55.7 ml). The reddish-brown reaction mixture was flushed with H2 gas via balloon. The resulting reaction was stirred at room temperature overnight. The reaction was concentrated to a dark orange-brown oil, and the resulting oil was loaded directly onto a 25 g prepacked silica column in a minimal amount of dichloromethane and purified using Isco silica gel column chromatography (120 column, 85 mL/min, 100% hexanes to 30% ethyl acetate:hexanes) to afford (2R,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpentan-2-ol (880 mg, 4.18 mmol, 75% yield) as a clear, colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.32 (dd, J=9.5, 6.0 Hz, 1H), 6.92-6.84 (m, 2H), 4.28 (qd, J=6.3, 4.4 Hz, 1H), 2.50 (dd, J=9.2, 4.4 Hz, 1H), 2.28 (s, 3H), 2.15 (ddd, J=13.2, 6.8, 2.3 Hz, 1H), 1.31-1.17 (m, 1H), 1.06 (d, J=6.6 Hz, 3H), 1.01 (d, J=6.3 Hz, 3H), 0.70 (d, J=6.7 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 160.92 (d, J=243.8 Hz), 139.78 (d, J=7.2 Hz), 134.95 (d, J=3.2 Hz), 129.16 (d, J=7.8 Hz), 116.64 (d, J=20.4 Hz), 112.57 (d, J=20.3 Hz), 67.70, 52.62, 30.26, 21.76, 21.31, 20.76. 19F NMR (376 MHz, CDCl3) δ −117.97.
    • Example 5: Preparation of (3S)-4-ethyl-3-phenylhexan-2-ol Step 1: Preparation of (2R,3S)-4-ethyl-3-phenylhexan-2-ol
  • Figure US20180186742A1-20180705-C00031
  • To a suspension of copper (I) iodide (667 mg, 3.50 mmol) in Et2O (12.5 mL) cooled to −78° C. was added pentan-3-ylmagnesium bromide (2M in THF) (3.5 mL, 7.00 mmol). The reaction was warmed to −20° C. and stirred at that temperature for 30 min. The reaction was then cooled to −78° C. followed by the addition of (2R,3R)-2-methyl-3-phenyloxirane (335 mg, 2.5 mmol). The reaction was slowly warmed to room temperature and stirred overnight. The reaction was quenched by the addition of aqueous saturated NH4Cl. The mixture was filtered through a pad of Celite, and the solution was extracted with Et2O. The combined organic phases were dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography using a 0-10% acetone/hexane mixture as the eluent to provide the title compound as colorless oil (200 mg, 27%). 1H NMR (400 MHz, CDCl3) δ 7.37-7.18 (m, 5H), 4.38-4.19 (m, 1H), 2.47 (dd, J=8.5, 5.1 Hz, 1H), 1.81 (ttd, J=8.8, 5.9, 3.2 Hz, 1H), 1.55-1.25 (m, 3H), 1.20 (d, J=5.6 Hz, 1H), 1.05 (d, J=6.3 Hz, 3H), 1.03-0.94 (m, 1H), 0.93 (t, J=7.4 Hz, 3H), 0.76 (t, J=7.4 Hz, 3H). ESIMS (m/z) 413 [2M+H]+.
    • Step 2: Preparation of (S)-4-ethyl-3-phenylhexan-2-one
  • Figure US20180186742A1-20180705-C00032
  • To a solution containing (2R,3S)-4-ethyl-3-phenylhexan-2-ol (190 mg, 0.921 mmol) dissolved in CH2Cl2 (4.6 mL) at 0° C. was added sodium bicarbonate (774 mg, 9.21 mmol) followed by Dess-Martin periodinane (781 mg, 1.842 mmol). The reaction was slowly warmed to room temperature over 3 hr. The reaction was quenched by the addition of aqueous saturated NaHCO3 solution followed by extraction with CH2Cl2. The combined organic phases were dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography using a 0-5% acetone/hexane mixture as the eluent to provide the title compound as colorless oil (124 mg, 63%). 1H NMR (400 MHz, CDCl3) δ 7.54-7.10 (m, 5H), 3.61 (d, J=10.8 Hz, 1H), 2.21 (dtt, J=11.1, 7.5, 3.9 Hz, 1H), 2.09 (s, 3H), 1.49-1.32 (m, 2H), 1.31-1.15 (m, 1H), 1.05-0.94 (m, 1H), 0.89 (t, J=7.4 Hz, 3H), 0.69 (t, J=7.4 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 208.87, 137.71, 128.98, 128.66, 127.12, 63.12, 41.13, 30.15, 22.76, 21.03, 10.46, 9.47.
    • Step 3: Preparation of (3S)-4-ethyl-3-phenylhexan-2-ol
  • Figure US20180186742A1-20180705-C00033
  • To a stirred solution containing (S)-4-ethyl-3-phenylhexan-2-one (120 mg, 0.587 mmol) and (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole (1 M in toluene) (58.7 μL, 0.059 mmol) dissolved in toluene (5.9 mL) at −78° C. was added BH3—SMe2 complex (61.3 μL, 0.646 mmol) dropwise. The reaction was slowly warmed to room temperature and stirred overnight. The reaction was then quenched carefully with methanol (475 μL, 11.75 mmol). The mixture was diluted with H2O and extracted with Et2O. The combined organic phases were dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography using a 0-10% acetone/hexane mixture as the eluent to provide the title compound as colorless oil (110 mg, 86%). 1H NMR shows a 3.3:1 mixture of diastereomers with the desired product being the major diastereomer. 1H NMR (major diastereomer) (300 MHz, CDCl3) δ 7.37-7.04 (m, 5H), 4.22 (dt, J=13.8, 6.3 Hz, 1H), 2.75 (t, J=7.5 Hz, 1H), 1.85-1.73 (m, 1H), 1.55-1.21 (m, 3H), 1.18 (d, J=7.8 Hz, 1H), 1.05 (d, J=6.3 Hz, 3H), 1.03-0.97 (m, 1H), 0.94 (t, J=7.4 Hz, 3H), 0.81 (t, J=7.4 Hz, 3H). ESIMS (m/z) 413 [2M+H]+.
    • Example 6: Preparation of (2S,3S)-3-(4-fluorophenyl)-4-methylpentan-2-ol Step 1: Preparation of (2S)-2-(benzyloxy)-1-(4-fluorophenyl)propan-1-ol
  • Figure US20180186742A1-20180705-C00034
  • A round bottom flask was charged with (S)-2-(benzyloxy)propanal (1.0 g, 6.09 mmol) dissolved in anhydrous THF (6.77 mL). This solution was cooled in an ice bath under an atmosphere of N2 and was treated dropwise with (4-fluorophenyl)magnesium bromide (6.70 mL, 6.70 mmol). The reaction was monitored by TLC (20% EtOAc in hexanes) until the reaction was complete. The reaction mixture was poured into saturated NH4Cl and the phases separated. The aqueous phase was extracted with EtOAc. The organic fractions were dried with magnesium sulfate and concentrated under reduced pressure. The crude residue was purified by automated silica gel chromatography (0-25% EtOAc in hexanes) to provide (2S)-2-(benzyloxy)-1-(4-fluorophenyl)propan-1-ol (1.404 g, 5.34 mmol, 88% yield) as a colorless oil. 1H NMR analysis showed the mixture to be a 2:1 mixture of diastereomers. HRMS-ESI (m/z) [M+Na]+ calcd for C16H17FO2Na, 283.1105; found, 283.1105.
    • Step 2: Preparation of (S)-2-(benzyloxy)-1-(4-fluorophenyl)propan-1-one
  • Figure US20180186742A1-20180705-C00035
  • A 100 mL round bottom flask was charged with CH2Cl2 (12.26 mL), and oxalyl chloride (0.519 mL, 5.93 mmol). This solution was cooled in a dry ice/acetone bath under an atmosphere of N2 and treated dropwise with DMSO (0.842 mL, 11.87 mmol). The resultant mixture was stirred for ˜2 minutes and then treated dropwise with a solution of (2S)-2-(benzyloxy)-1-(4-fluorophenyl)propan-1-ol (1.404 g, 5.39 mmol) in 3 mL of CH2Cl2 (extra rinse with 1 mL). After stirring for ˜15 minutes, the reaction mixture was treated dropwise with triethylamine (3.76 mL, 27.0 mmol). The reaction mixture was stirred for 5 minutes and then allowed to warm to room temperature. The reaction was monitored by TLC (20% EtOAc in hexanes). The reaction mixture was poured into H2O and the phases were separated. The aqueous phase was extracted with CH2Cl2. The combined organics were dried with sodium sulfate and concentrated. The crude residue was purified by silica gel chromatography (0-15% EtOAc in hexanes) to provide (S)-2-(benzyloxy)-1-(4-fluorophenyl)propan-1-one (1.1475 g, 4.44 mmol, 82% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 8.20-8.04 (m, 2H), 7.40-7.24 (m, 5H), 7.19-7.02 (m, 2H), 4.70 (q, J=6.9 Hz, 1H), 4.61 (d, J=11.6 Hz, 1H), 4.45 (d, J=11.6 Hz, 1H), 1.54 (d, J=6.9 Hz, 3H). 19F NMR (376 MHz, CDCl3) δ −104.39. 13C NMR (126 MHz, CDCl3) δ 199.27, 165.83 (d, J=255.3 Hz), 137.41, 131.69 (d, J=9.2 Hz), 131.08 (d, J=2.9 Hz), 128.46, 127.98, 127.93, 115.71 (d, J=21.8 Hz), 78.72, 71.65, 18.81. HRMS-ESI (m/z) [M+Na]+ calcd for C16H15FO2Na, 281.0948; found, 281.0950.
  • Step 2A: Preparation of (S)-1-(benzo[d][1,3]dioxol-5-yl)-2-(benzyloxy)propan-1-one.
  • Figure US20180186742A1-20180705-C00036
  • To a vial charged with (S)-2-(benzyloxy)-1-(pyrrolidin-1-yl)propan-1-one (1 g, 4.29 mmol) dissolved in anhydrous THF (12 mL) was added dropwise benzo[d][1,3]dioxol-5-ylmagnesium bromide (1M in 1:1 toluene/THF, 4.29 mL, 4.29 mmol) at −5° C. The mixture was allowed to warm to ambient temperature and stirred overnight. The mixture was quenched by the addition of 1 N HCl. The layers were separated, followed by extraction with ethyl ether (3×10 mL). The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated in vacuo. The residue was purified via automated silica gel chromatography (Isco, 0-25% EtOAc/hexanes as the eluent) to afford (S)-1-(benzo[d][1,3]dioxol-5-yl)-2-(benzyloxy)propan-1-one (0.39 g, 30%) as yellow oil. 1H NMR (500 MHz, CDCl3) δ 7.73 (dd, J=8.2, 1.7 Hz, 1H), 7.55 (d, J=1.6 Hz, 1H), 7.39-7.27 (m, 5H), 6.84 (d, J=8.2 Hz, 1H), 6.04 (s, 2H), 4.70 (q, J=6.9 Hz, 1H), 4.53 (dd, J=103.5, 11.6 Hz, 2H), 1.52 (d, J=6.9 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 198.8, 152.0, 148.1, 137.6, 129.4, 128.4, 127.9, 127.8, 125.2, 108.6, 107.9, 101.8, 78.4, 71.5, 19.1. HRMS-ESI (m/z) [M+H]+ calcd for C17H17O4, 285.1121; found, 285.1121.
    • Step 3: Preparation of (2S)-2-(benzyloxy)-3-(4-fluorophenyl)-4-methylpentan-3-ol
  • Figure US20180186742A1-20180705-C00037
  • A solution of isopropylmagnesium bromide (1.936 mL, 3.87 mmol) was added to anhydrous THF (6.45 ml) cooled to 0° C. in an ice bath. A solution of (S)-2-(benzyloxy)-1-(4-fluorophenyl)propan-1-one (0.5 g, 1.936 mmol) in THF (2 mL+1 mL to rinse the syringe) was added dropwise. The reaction was stirred until complete by consumption of starting material by TLC (20% EtOAc in hexanes). The reaction was quenched by the addition of saturated ammonium chloride and the mixture was extracted with EtOAc. The combined organic fractions were dried over MgSO4, filtered and concentrated. The crude residue was purified by automated silica gel chromatography (0-10% EtOAc in hexanes) to provide (2S)-2-(benzyloxy)-3-(4-fluorophenyl)-4-methylpentan-3-ol (201.9 mg, 0.634 mmol, 33% yield) as a white foam. 1H NMR data showed a 9.2:1 ratio of diastereomers. 1H NMR (400 MHz, CDCl3) δ 7.43-7.20 (m, 7H), 7.00 (t, J=8.8 Hz, 2H), 4.72 (d, J=11.4 Hz, 1H), 4.49 (d, J=11.5 Hz, 1H), 4.09 (q, J=6.2 Hz, 1H), 2.46 (s, 1H), 2.35 (p, J=6.8 Hz, 1H), 1.00 (d, J=6.2 Hz, 3H), 0.77 (dd, J=8.8, 6.8 Hz, 6H). 19F NMR (376 MHz, CDCl3) δ −117.13. 13C NMR (126 MHz, CDCl3) δ 161.55 (d, J=244.4 Hz), 138.28, 136.60 (d, J=3.2 Hz), 128.45, 128.14 (d, J=7.7 Hz), 127.80, 114.09 (d, J=20.9 Hz), 80.56, 70.91, 34.79, 17.93, 16.87, 13.63. HRMS-ESI (m/z) [M+Na]+ calcd for C19H23FO2Na, 325.1574; found, 325.1574.
    • Step 4: Preparation of 1-((2S,3S)-2-(benzyloxy)-4-methylpentan-3-yl)-4-fluorobenzene
  • Figure US20180186742A1-20180705-C00038
  • To a solution of (2S)-2-(benzyloxy)-3-(4-fluorophenyl)-4-methylpentan-3-ol (0.2 g, 0.661 mmol) dissolved in CH2Cl2 (2.205 ml) at 0° C. was added triethylsilane (1.056 mL, 6.61 mmol) followed by trifluoroacetic acid (0.510 mL, 6.61 mmol). The mixture was stirred at 0° C. for 1 hr. The mixture was then allowed to slowly warm to room temperature and stirred overnight. The reaction was carefully quenched by the addition of a saturated sodium bicarbonate solution and extracted with CH2Cl2. The combined organic layers were then dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude residue was purified by automated silica gel chromatography (0-5% EtOAc in hexanes) to provide 1-((2S,3S)-2-(benzyloxy)-4-methylpentan-3-yl)-4-fluorobenzene (152.2 mg, 0.505 mmol, 76% yield) as a colorless oil. 1H NMR data revealed a 7.2:1 ratio of diastereomers. 1H NMR (400 MHz, CDCl3) δ 7.39-7.26 (m, 5H), 7.07-6.91 (m, 4H), 4.66 (d, J=11.6 Hz, 1H), 4.50 (d, J=11.6 Hz, 1H), 3.88 (dq, J=8.5, 6.1 Hz, 1H), 2.61 (d, J=14.4 Hz, 1H), 2.37 (dq, J=13.4, 6.7 Hz, 1H), 1.01 (d, J=6.1 Hz, 3H), 0.80 (d, J=6.8 Hz, 3H), 0.74 (d, J=6.8 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 161.48 (d, J=243.8 Hz), 138.84, 135.66 (d, J=3.3 Hz), 131.08 (d, J=7.6 Hz), 128.35, 127.71, 127.49, 114.48 (d, J=20.8 Hz), 75.31, 70.71, 57.21, 27.57, 21.59, 18.36, 17.35. HRMS-ESI (m/z) [M+Na]+ calcd for C19H23FONa, 309.1625; found, 309.1629.
    • Step 5: Preparation of (2S,3S)-3-(4-fluorophenyl)-4-methylpentan-2-ol
  • Figure US20180186742A1-20180705-C00039
  • A flask containing 1-((2S)-2-(benzyloxy)-4-methylpentan-3-yl)-4-fluorobenzene (0.15 g, 0.524 mmol) was charged with 5% palladium on carbon (0.056 g, 0.026 mmol) and then suspended in ethanol (2.62 mL). The reaction atmosphere was replaced with hydrogen gas via a balloon (1 atm) and monitored until complete by TLC (25% EtOAc in hexanes). The reaction was filtered through a pad of Celite© and the pad was washed with ethyl acetate. The filtrate was concentrated under reduced pressure. The crude residue was purified by automated column chromatography (0-20% EtOAc in hexanes as the eluent) to provide (2S,3S)-3-(4-fluorophenyl)-4-methylpentan-2-ol (76.9 mg, 0.388 mmol, 74.1% yield) as a white foam. 1H NMR (500 MHz, CDCl3) δ 7.11-7.05 (m, 2H), 7.03-6.97 (m, 2H), 4.17 (dq, J=7.5, 6.2 Hz, 1H), 2.47 (t, J=7.5 Hz, 1H), 2.18 (dp, J=13.6, 6.8 Hz, 1H), 1.19 (d, J=7.2 Hz, 1H), 1.03 (d, J=6.3 Hz, 3H), 0.90 (d, J=6.7 Hz, 3H), 0.79 (d, J=6.7 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 161.65 (d, J=244.4 Hz), 135.15 (d, J=3.4 Hz), 131.11 (d, J=7.6 Hz), 114.76 (d, J=20.9 Hz), 68.13, 59.08, 28.28, 21.34, 20.53, 19.47. IR (thin film) 3348, 2960, 2929, 2872, 1604, 1508, 1465, 1368, 1223, 1160, 833 cm−1.
    • Step 6: Preparation of (4S)-4-(benzyloxy)-3-(4-fluorophenyl)-2-methylpent-1-en-3-ol
  • Figure US20180186742A1-20180705-C00040
  • To a solution containing prop-1-en-2-ylmagnesium bromide (1 M in 2-Me-THF) (4.29 mL, 4.29 mmol) dissolved in THF (21.44 mL) and cooled to 0° C. in an ice/water bath was added (S)-2-(benzyloxy)-1-(4-fluoro-3-methylphenyl)propan-1-one (0.584 g, 2.144 mmol) dropwise over 5 minutes as a solution in THF (3 mL). The resulting solution was stirred for 1 hr, at which point an additional 2.1 mL (1 equivalent) of the Grignard reagent was added, and the reaction was stirred for an additional hour. The reaction was quenched with saturated aqueous NH4Cl (50 mL) solution and extracted with EtOAc (3×50 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated to an oil. The oil was loaded onto a prepacked 25 g silica gel column and purified using Isco silica gel column chromatography (40 column, 35 mL/min, 100% hexanes to 20% ethyl acetate:hexanes) to afford the title compound (671 mg, 100%) as a clear, colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.40-7.23 (m, 6H), 7.16 (ddd, J=7.9, 4.9, 2.4 Hz, 1H), 6.92 (t, J=9.0 Hz, 1H), 5.17 (t, J=1.0 Hz, 1H), 4.98 (p, J=1.4 Hz, 1H), 4.69 (d, J=11.4 Hz, 1H), 4.51 (d, J=11.4 Hz, 1H), 4.21 (q, J=6.1 Hz, 1H), 2.81 (s, 1H), 2.26 (d, J=1.9 Hz, 3H), 1.63 (t, J=1.0 Hz, 3H), 0.99 (d, J=6.1 Hz, 3H). 19F NMR (376 MHz, CDCl3) d −120.68. IR (thin film) 3500, 2977, 2923, 1499, 1242, 1114, 1097, 894, 818, 733, 697 cm−1. HRMS-ESI (m/z) [M+H]+ calcd for C20H23FNaO2, 337.1574; found, 337.1584.
    • Step 7: Preparation of (2S)-2-(benzyloxy)-3-(4-fluorophenyl)-4-methylpentan-3-ol
  • Figure US20180186742A1-20180705-C00041
  • A solution containing (3S,4S)-4-(benzyloxy)-3-(4-fluoro-3-methylphenyl)-2-methylpent-1-en-3-ol (0.6713 g, 2.135 mmol) and Wilkinson's catalyst (0.593 g, 0.641 mmol) dissolved in THF (14.23 mL) was flushed with hydrogen gas via balloon. The resulting reaction was stirred at room temperature overnight. The reaction mixture was concentrated to a dark orange-brown oil under reduced pressure. The resulting oil was loaded directly onto a 25 g prepacked silica column in a minimal amount of dichloromethane and purified using Isco silica gel column chromatography (40 column, 35 mL/min, 100% hexanes to 20% ethyl acetate:hexanes) to afford the title compound (659 mg, 98%) as a clear, colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.41-7.28 (m, 5H), 7.16 (dd, J=7.6, 2.3 Hz, 1H), 7.05 (ddd, J=7.8, 5.0, 2.4 Hz, 1H), 6.92 (t, J=9.0 Hz, 1H), 4.72 (d, J=11.4 Hz, 1H), 4.49 (d, J=11.4 Hz, 1H), 4.08 (q, J=6.2 Hz, 1H), 2.44 (s, 1H), 2.34 (p, J=6.8 Hz, 1H), 2.27 (d, J=1.9 Hz, 3H), 1.01 (d, J=6.1 Hz, 3H), 0.77 (dd, J=10.6, 6.8 Hz, 6H). 19F NMR (376 MHz, CDCl3) δ −121.44. 13C NMR (101 MHz, CDCl3) δ 160.12 (d, J=243.5 Hz), 138.39, 136.31 (d, J=3.5 Hz), 129.74 (d, J=4.9 Hz), 128.45, 127.79, 127.75, 125.35 (d, J=7.8 Hz), 123.40 (d, J=17.0 Hz), 113.69 (d, J=22.1 Hz), 80.55, 77.07, 70.95, 34.84, 18.01, 16.94, 14.80 (d, J=3.5 Hz), 13.71. IR (thin film) 3564, 2962, 2935, 1501, 1374, 1243, 1105, 1089, 817, 757, 697 cm−1. HRMS-ESI (m/z) [M+H]+ calcd for C20H25FNaO2, 339.1731; found, 339.1728.
    • Example 6A: Preparation of (2R,3S)-3-(2,5-dimethylphenyl)-4-methylpentan-2-ol Step 1: Preparation of 2-(2,5-dimethylphenyl)-3-methylbutanoic acid
  • Figure US20180186742A1-20180705-C00042
  • A solution of isopropylmagnesium chloride (2 M in THF, 5.79 mL, 11.57 mmol) was added slowly to a solution of 2-(2,5-dimethylphenyl)acetic acid (0.95 g, 5.79 mmol) in THF (11.57 mL) at room temperature. The resulting thick suspension was stirred for 1 hr and treated with 2-iodopropane (1.736 mL, 17.36 mmol). The reaction was heated to 70° C. and stirred overnight. The reaction was quenched by the addition of 1N HCl and extracted with EtOAc. The organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by automated column chromatography (Isco, 0-30% EtOAc in hexanes as the eluent) to provide 2-(2,5-dimethylphenyl)-3-methylbutanoic acid (670 mg, 53.3%) as a white solid. 1H NMR (500 MHz, CDCl3) δ 11.32 (bs, 1H), 7.21 (s, 1H), 7.04 (d, J=7.7 Hz, 1H), 6.95 (d, J=8.5 Hz, 1H), 3.46 (d, J=10.9 Hz, 1H), 2.40-2.34 (m, 1H), 2.33 (s, 3H), 2.29 (s, 3H), 1.11 (d, J=6.4 Hz, 3H), 0.69 (d, J=6.7 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 179.72, 136.08, 135.79, 133.69, 130.22, 127.82, 127.67, 54.23, 31.46, 21.62, 21.12, 19.75, 19.69. HRMS-ESI (m/z) [2M+H]+ calcd for C13H18O2, 413.2686; found, 413.2674.
    • Step 2: Preparation of 2-(2,5-dimethylphenyl)-N-methoxy-N,3-dimethylbutanamide
  • Figure US20180186742A1-20180705-C00043
  • To a solution containing 2-(2,5-dimethylphenyl)-3-methylbutanoic acid (0.66 g, 3.20 mmol) dissolved in 32 mL of CH2Cl2 at 0° C. was added 4-methylmorpholine (0.70 mL, 6.40 mmol) and N,O-dimethylhydroxylamine hydrochloride (0.624 g, 5.71 mmol). 3-(((Ethylimino)methylene)amino)-N,N-dimethylpropan-1-amine hydrochloride (EDC, 1.23 g, 6.40 mmol) was added and the reaction was warmed to room temperature and stirred overnight. The reaction was concentrated under reduced pressure and the residue was purified by automated silica gel chromatography (Isco, 0-25% EtOAc in hexanes as the eluent) to provide 2-(2,5-dimethylphenyl)-N-methoxy-N,3-dimethylbutanamide (694 mg, 83%) as a colorless oil. 1H NMR (500 MHz, CDCl3) δ 7.27 (s, 1H), 7.01 (d, J=7.7 Hz, 1H), 6.93-6.89 (m, 1H), 3.84 (d, J=10.3 Hz, 1H), 3.48 (s, 3H), 3.14 (s, 3H), 2.41-2.35 (m, 1H), 2.34 (s, 3H), 2.27 (s, 3H), 1.05 (d, J=6.4 Hz, 3H), 0.68 (d, J=6.8 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 137.49, 135.69, 133.14, 129.89, 127.88, 127.23, 60.95, 49.90, 32.65, 32.21, 22.25, 21.11, 19.51. HRMS-ESI (m/z) [M+H]+ calcd for C15H23NO2, 250.1802; found, 250.1799.
    • Step 3: Preparation of 3-(2,5-dimethylphenyl)-4-methylpentan-2-one
  • Figure US20180186742A1-20180705-C00044
  • A solution containing 2-(2,5-dimethylphenyl)-N-methoxy-N,3-dimethylbutanamide (0.685 g, 2.75 mmol) dissolved in THF (18.31 mL) was cooled to 0° C. Methylmagnesium bromide (3.0 M in diethyl ether, 2.75 ml, 8.24 mmol) was added dropwise and the reaction was allowed to warm to room temperature and stirred overnight. The reaction was quenched by the addition of saturated ammonium chloride solution and was extracted with EtOAc. The organic layer was dried over magnesium sulfate, filtered and concentrated under reduced pressure to provide 3-(2,5-dimethylphenyl)-4-methylpentan-2-one (573.3 mg, 97%) as a yellow oil. 1H NMR (500 MHz, CDCl3) δ 7.27 (s, 1H), 7.06 (d, J=7.6 Hz, 1H), 6.94 (d, J=7.7 Hz, 1H), 3.58 (d, J=10.5 Hz, 1H), 2.44-2.38 (m, 1H), 2.37 (s, 3H), 2.27 (s, 3H), 2.02 (s, 3H), 1.01 (d, J=6.4 Hz, 3H), 0.65 (d, J=6.8 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 208.55, 136.24, 135.95, 133.52, 130.48, 127.83, 127.61, 62.29, 30.53, 30.09, 21.86, 21.04, 19.91, 19.51. HRMS-ESI (m/z) [M+H]+ calcd for C14H20O, 205.1587; found, 205.1578.
    • Step 4: Preparation of (2R,3S)-3-(2,5-dimethylphenyl)-4-methylpentan-2-ol and (2S,3R)-3-(2,5-dimethylphenyl)-4-methylpentan-7-ol
  • Figure US20180186742A1-20180705-C00045
  • Lithium aluminum hydride (2.80 mL, 2.80 mmol) as a solution (1.0 M in THF) was added to a flask containing THF (28.0 mL) cooled to −78° C. A solution of 3-(2,5-dimethylphenyl)-4-methylpentan-2-one (0.573 g, 2.80 mmol) in THF (3 mL) was added dropwise. The reaction was warmed to room temperature and stirred overnight. The reaction was cooled to 0° C. and quenched by the addition of 0.1 mL H2O, 0.1 mL 1N NaOH, followed by an additional 0.3 mL of H2O. The mixture was stirred vigorously for 15 min. The reaction was filtered and the solids were washed with EtOAc. The filtrate was concentrated under reduced pressure to provide a racemic mixture of (2R,3S)-3-(2,5-dimethylphenyl)-4-methylpentan-2-ol and (2S,3R)-3-(2,5-dimethylphenyl)-4-methylpentan-2-ol (491 mg, 72%) as a colorless oil. The syn product is the exclusive product as predicted by Cram's rule. 1H NMR (500 MHz, CDCl3) δ 7.12 (s, 1H), 7.05 (d, J=7.7 Hz, 1H), 6.94-6.91 (m, 1H), 4.32-4.20 (m, 1H), 2.55 (dd, J=8.9, 4.7 Hz, 1H), 2.31 (s, 3H), 2.25 (s, 3H), 2.17 (ddt, J=13.3, 8.8, 6.7 Hz, 1H), 1.26 (d, J=6.1 Hz, 1H), 1.05 (d, J=2.3 Hz, 3H), 1.04 (d, J=2.0 Hz, 3H), 0.72 (d, J=6.7 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 138.84, 135.13, 134.66, 130.18, 128.14, 126.71, 67.91, 62.20, 53.16, 30.01, 21.76, 21.36, 20.75, 20.29. ESIMS (m/z) 207 [M+H]+.
    • Step 5: Preparation of (2R,3S) and (2S,3R)-3-(2,5-dimethylphenyl)-4-methylpentan-2-yl (S)-2-methoxy-2-phenylacetate
  • Figure US20180186742A1-20180705-C00046
  • To a racemic mixture containing (2R,3S) and (2S,3R)-3-(2,5-dimethylphenyl)-4-methylpentan-2-ol (0.491 g, 2.380 mmol) dissolved in 16 mL of CH2Cl2 was added N,N-dimethylpyridin-4-amine (0.029 g, 0.238 mmol) and (S)-2-methoxy-2-phenylacetic acid (0.514 g, 3.09 mmol). The reaction was cooled to 0° C. followed by addition of 3-(((ethylimino)methylene)amino)-N,N-dimethylpropan-1-amine hydrochloride (0.912 g, 4.76 mmol) was added and the reaction was warmed to room temperature and stirred overnight. The mixture was concentrated under reduced pressure. The residue was purified by automated silica gel chromatography (Isco, 80 g SiO2 column, 0-10% MTBE in hexanes as the eluent) to provide (2R,3S)-3-(2,5-dimethylphenyl)-4-methylpentan-2-yl (S)-2-methoxy-2-phenylacetate (284.7 mg 32%) and (2S,3R)-3-(2,5-dimethylphenyl)-4-methylpentan-2-yl (S)-2-methoxy-2-phenylacetate as colorless oils. Only the desired (2R,3S) diastereomer was characterized. 1H NMR (500 MHz, CDCl3) δ 7.44-7.37 (m, 2H), 7.36-7.27 (m, 3H), 7.18 (s, 1H), 7.00 (d, J=7.7 Hz, 1H), 6.93-6.80 (m, 1H), 5.42-5.34 (m, 1H), 4.74 (s, 1H), 3.40 (s, 3H), 2.62 (dd, J=9.7, 4.3 Hz, 1H), 2.30 (s, 3H), 2.21 (s, 3H), 2.05-1.92 (m, 1H), 0.93 (d, J=6.5 Hz, 3H), 0.87 (d, J=6.3 Hz, 3H), 0.68 (d, J=6.7 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 170.32, 139.03, 136.46, 134.96, 133.92, 129.67, 128.80, 128.51, 126.90, 126.67, 82.86, 72.23, 57.31, 51.06, 30.54, 21.31, 21.00, 20.93, 20.23, 17.82. HRMS-ESI (m/z) [M+Na]+ calcd for C23H30O3, 377.2087; found, 377.2089.
    • Step 6: Preparation of (2R,3S)-3-(2,5-dimethylphenyl)-4-methylpentan-2-ol
  • Figure US20180186742A1-20180705-C00047
  • To a solution containing (2R,3S)-3-(2,5-dimethylphenyl)-4-methylpentan-2-yl(S)-2-methoxy-2-phenylacetate (0.28 g, 0.790 mmol) dissolved in MeOH (7.90 mL) was added potassium carbonate (0.327 g, 2.370 mmol). The reaction was heated to 55° C. and stirred overnight. The reaction was cooled to room temperature, diluted with water and extracted with CH2Cl2. The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by automated silica gel chromatography (Isco, 0-20% EtOAc in hexanes as the eluent) to provide (2R,3S)-3-(2,5-dimethylphenyl)-4-methylpentan-2-ol (139 mg, 81%) as a colorless oil. 1H NMR (500 MHz, CDCl3) δ 7.12 (s, 1H), 7.05 (d, J=7.7 Hz, 1H), 6.96-6.87 (m, 1H), 4.33-4.19 (m, 1H), 2.55 (dd, J=8.9, 4.7 Hz, 1H), 2.31 (s, 3H), 2.25 (s, 3H), 2.17 (ddt, J=13.4, 8.8, 6.7 Hz, 1H), 1.26 (d, J=6.1 Hz, 1H), 1.05 (d, J=2.1 Hz, 3H), 1.04 (d, J=1.8 Hz, 3H), 0.72 (d, J=6.7 Hz, 3H). IR (thin film) 3429 (b), 2956, 2925, 2868, 1500, 1457, 1382, 1151, 1027, 905, 806, 787 cm−1. HRMS-ESI (m/z) [M+NH4]+ calcd for C14H22O, 224.2009; found, 224.2001.
    • Example 7: Preparation of (2S,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpentan-2-ol Step 1: Preparation of (2S,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpentan-2-yl 4-nitrobenzoate
  • Figure US20180186742A1-20180705-C00048
  • In a 250 mL round bottom flask, a solution of (2R,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpentan-2-ol (0.880 g, 4.18 mmol), triphenylphosphine (4.17 g, 15.90 mmol) and 4-nitrobenzoic acid (2.87 g, 17.16 mmol) was prepared in anhydrous THF (41.8 ml) and cooled to 0° C. in an ice/water bath. After ˜5 min, diethyl (E)-diazene-1,2-dicarboxylate (2.97 ml, 18.83 mmol) was added dropwise, and the mixture was allowed to slowly warm to room temperature overnight. After 18 hr, TLC indicated ˜75% conversion to a single higher Rf spot. The reaction was then heated to 40° C. and stirred for an additional 12 hr. The mixture was cooled to room temperature and quenched with a saturated aqueous solution of NH4Cl (40 mL) and extracted with CH2Cl2 (3×40 mL). The combined organic layers were passed through a phase separator and concentrated to an oil. The residue was purified via silica gel Isco column chromatography (80 g silica gel column, 60 mL/min, 100% hexanes to 20% acetone:hexanes) to afford (2S,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpentan-2-yl 4-nitrobenzoate (1.34 g, 3.73 mmol, 89% yield) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.33-8.26 (m, 2H), 8.17-8.11 (m, 2H), 7.14 (dd, J=9.5, 5.9 Hz, 1H), 6.98-6.86 (m, 2H), 5.65 (dq, J=8.2, 6.3 Hz, 1H), 3.18 (t, J=7.8 Hz, 1H), 2.30 (s, 3H), 2.19-2.09 (m, 1H), 1.19 (d, J=6.3 Hz, 3H), 0.98 (d, J=6.7 Hz, 3H), 0.80 (d, J=6.8 Hz, 3H). 19F NMR (376 MHz, CDCl3) δ −117.11. IR (thin film) 3353, 2961, 1719, 1528, 1277, 1102, 720 cm−1. ESIMS (m/z) 359.1 [M+H]+.
    • Step 2: Preparation of (2S,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpentan-2-ol
  • Figure US20180186742A1-20180705-C00049
  • In a 250 mL round-bottom flask, a solution of (2S,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpentan-2-yl 4-nitrobenzoate (1.34 g, 3.73 mmol) was prepared in THF (49.7 mL) and cooled to 0° C. in an ice/water bath. After ˜5 min, sodium hydroxide (10% aqueous solution) (44 mL, 3.73 mmol) (39.7 mL water+4.4 mL 50% w/w/NaOH) was added dropwise, and the mixture was allowed to slowly warm to room temperature over 1 hr and then heated to 40° C. and stirred for 2 days. The reaction was cooled to ambient temperature. The reaction was quenched by the addition of a saturated aqueous solution of NH4Cl (100 mL) and extracted with CH2Cl2 (3×100 mL). Additional product remained in aqueous layer as evidenced by TLC, so 100 mL brine was added to aqueous layer, and the aqueous layer was extracted again with CH2Cl2 (2×100 mL), after which no additional product was observed in the aqueous layer. The combined organic layers were then passed through a phase separator and concentrated to afford an oil that was purified via silica gel Isco column chromatography (120 g silica gel column, 85 mL/min, 100% hexanes to 30% acetone:hexanes) to afford (2S,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpentan-2-ol (460 mg, 2.187 mmol, 58.7% yield) (52% over 2 steps) as a clear, colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.02 (dd, J=8.6, 6.0 Hz, 1H), 6.94-6.81 (m, 2H), 4.25-4.12 (m, 1H), 2.88 (t, J=7.6 Hz, 1H), 2.35 (s, 3H), 2.25-2.12 (m, 1H), 1.21 (d, J=6.0 Hz, 1H), 1.04 (d, J=6.3 Hz, 3H), 0.94 (d, J=6.7 Hz, 3H), 0.80 (d, J=6.7 Hz, 3H). 19F NMR (376 MHz, CDCl3) δ −117.86. 13C NMR (101 MHz, CDCl3) δ 160.86 (d, J=243.9 Hz), 140.35 (d, J=7.4 Hz), 134.42 (d, J=3.1 Hz), 129.29 (d, J=6.8 Hz), 116.88 (d, J=20.3 Hz), 112.20 (d, J=20.6 Hz), 69.48, 29.72, 21.12, 21.00, 20.99, 20.65, 19.98. IR (thin film) 3382, 2960, 2927, 1716, 1497, 1365, 1225, 736 cm−1.
    • Example 8: (2S,3S)-3-(4-fluorophenyl)-4-methylpentan-2-yl(tert-butoxycarbonyl)-L-alaninate
  • Figure US20180186742A1-20180705-C00050
  • To a stirred solution of (2S,3S)-3-(4-fluorophenyl)-4-methylpentan-2-ol (0.075 g, 0.382 mmol), (tert-butoxycarbonyl)-L-alanine (0.108 g, 0.573 mmol) and DMAP (4.67 mg, 0.038 mmol) dissolved in CH2Cl2 (3.82 mL) at 0° C. in an ice bath was added N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (EDC; 0.147 g, 0.764 mmol) and the reaction was monitored until complete by TLC (25% EtOAc in hexanes). The reaction was purified by automated column chromatography (0-10% EtOAc in hexanes) to provide (2S,3S)-3-(4-fluorophenyl)-4-methylpentan-2-yl (tert-butoxycarbonyl)-L-alaninate (137.5 mg, 0.370 mmol, 97% yield) as colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.06 (dd, J=8.7, 5.6 Hz, 2H), 7.02-6.92 (m, 2H), 5.36 (dq, J=8.7, 6.3 Hz, 1H), 5.05 (s, 1H), 4.37-4.19 (m, 1H), 2.69 (dd, J=8.7, 6.4 Hz, 1H), 2.08 (h, J=6.7 Hz, 1H), 1.45 (s, 9H), 1.38 (d, J=7.2 Hz, 3H), 1.06 (d, J=6.2 Hz, 3H), 0.86 (d, J=6.8 Hz, 3H), 0.74 (d, J=6.8 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 172.79, 161.75 (d, J=244.8 Hz), 155.03, 134.29, 131.03 (d, J=7.6 Hz), 114.82 (d, J=21.0 Hz), 79.79, 72.32, 55.88, 49.50, 28.34, 28.18, 21.30, 18.81, 18.41, 17.74. IR (thin film) 3352, 2964, 2932, 1712, 1605, 1509, 1452, 1366, 1224, 1160, 835 cm−1. HRMS-ESI (m/z) [M+Na]+ calcd for C20H30FNNaO4, 390.2051; found, 390.2044.
    • Example 9: Preparation of (2S,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpentan-2-yl (tert-butoxycarbonyl)-L-alaninate
  • Figure US20180186742A1-20180705-C00051
  • In a small vial, (2R,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpentan-2-ol (115.5 mg, 0.549 mmol), (tert-butoxycarbonyl)-L-alanine (125 mg, 0.659 mmol) and triphenylphosphine (173 mg, 0.659 mmol) were dissolved in THF (2.75 mL) under a N2 atmosphere and cooled to 0° C. in an ice/water bath. After ˜5 min, diisopropyl (E)-diazene-1,2-dicarboxylate (130 μL, 0.659 mmol) was added in dropwise via syringe over 3 min, and the resulting pale orange reaction was stirred overnight, slowly warming to room temperature as the ice melted. After 18 hr, the reaction was concentrated under reduced pressure to afford an oil. The oil was loaded directly onto a 12 g prepacked silica column in a minimal amount of dichloromethane and purified using Isco silica gel column chromatography (120 column, 85 mL/min, 100% pet ether to 40% MTBE:pet ether) to afford (2S,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpentan-2-yl (tert-butoxycarbonyl)-L-alaninate (35.0 mg, 0.092 mmol, 17% yield) as a clear, colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.05 (dd, J=8.5, 6.0 Hz, 1H), 6.87 (ddt, J=11.6, 8.3, 4.1 Hz, 2H), 5.33 (dq, J=9.1, 6.2 Hz, 1H), 5.05 (d, J=8.1 Hz, 1H), 4.28 (d, J=7.6 Hz, 1H), 3.08 (dd, J=9.2, 6.2 Hz, 1H), 2.32 (s, 3H), 2.18-2.06 (m, 1H), 1.45 (s, 9H), 1.39 (d, J=7.2 Hz, 3H), 1.03 (d, J=6.2 Hz, 3H), 0.85 (d, J=6.8 Hz, 3H), 0.78 (d, J=6.9 Hz, 3H). 19F NMR (376 MHz, CDCl3) δ −117.34. IR (thin film) 3355, 2965, 1714, 1499, 1366, 1167, 1052, 735 cm−1. HRMS-ESI (m/z) [M+Na]+ calcd for C21H32FNNaO4, 404.2208; found, 404.2201.
    • Example 10: Preparation of (2S,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpentan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate Step 1: Preparation of (2S,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpentan-2-yl-L-alaninate Hydrochloride
  • Figure US20180186742A1-20180705-C00052
  • In a small vial, (2S,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpentan-2-yl-(tert-butoxycarbonyl)-L-alaninate (35.0 mg, 0.092 mmol) was dissolved in CH2Cl2 (2 mL). Hydrogen chloride (4M in dioxane) (0.344 mL, 1.376 mmol) was added in one portion via syringe. The resulting clear, colorless reaction was stirred at room temperature for 3 hr. After 3 hr, TLC indicated complete consumption of the starting material and conversion to a baseline product by TLC. The reaction was concentrated under a stream of N2 and dried in a vacuum oven to provide (2S,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpentan-2-yl-L-alaninate (26.1 mg, 0.092 mmol, 100% yield) as a clear, colorless oil. ESIMS (m/z) 282.1 [M+H]+. This material was used directly in the next step without further purification.
    • Step 2: Preparation of (2S,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpentan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate
  • Figure US20180186742A1-20180705-C00053
  • To a vial containing (2S,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpentan-2-yl-L-alaninate (26.1 mg, 0.093 mmol) was added 3-hydroxy-4-methoxypicolinic acid (23.53 mg, 0.139 mmol) and ((1H-benzo[d][1,2,3]triazol-1-yl)oxy)tri(pyrrolidin-1-yl)phosphonium hexafluorophosphate(V) (72.4 mg, 0.139 mmol). Dichloromethane (1.86 mL) was added followed by N-ethyl-N-isopropylpropan-2-amine (121 μL, 0.696 mmol) dropwise over 45 seconds. After 10 min, most of the solids solubilized and the resultant pale pink colored reaction was stirred at room temperature overnight. TLC/UPLC indicated consumption of the starting material and formation of a major spot that glowed blue under UV. The reaction was then concentrated under reduced pressure to yield an orange oil. The oil was loaded directly onto a 12 g prepacked silica column in a minimal amount of dichloromethane and purified using Isco silica gel column chromatography (24 column, 30 mL/min, 100% hexanes to 50% acetone:hexanes) to afford (2S,3S)-3-(4-fluoro-2-methylphenyl)-4-methylpentan-2-yl-(3-hydroxy-4-methoxypicolinoyl)-L-alaninate (24.4 mg, 0.056 mmol, 60.8% yield) as a clear, colorless oil. 1H NMR (400 MHz, CDCl3) δ 12.13 (s, 1H), 8.45 (d, J=8.0 Hz, 1H), 7.99 (d, J=5.2 Hz, 1H), 7.05 (dd, J=8.6, 5.9 Hz, 1H), 6.93-6.77 (m, 3H), 5.38 (dq, J=8.9, 6.3 Hz, 1H), 4.76-4.65 (m, 1H), 3.95 (s, 3H), 3.09 (dd, J=8.9, 6.5 Hz, 1H), 2.29 (s, 3H), 2.11 (h, J=6.8 Hz, 1H), 1.55 (d, J=7.2 Hz, 3H), 1.08 (d, J=6.2 Hz, 3H), 0.86 (d, J=6.8 Hz, 3H), 0.78 (d, J=6.7 Hz, 3H). 19F NMR (376 MHz, CDCl3) δ −117.30. IR (thin film) 3366, 2961, 1734, 1650, 1529, 1264, 1183, 1049, 955, 801, 735 cm−1. HRMS-ESI (m/z) [M+H]+ calcd for C23H30FN2O5, 433.2133; found, 433.2129.
    • Example 11A: Preparation of (2S,3R)-3-(2,4-dimethylphenyl)-4-methylpentan-2-yl (3-acetoxy-4-methoxypicolinoyl)-L-alaninate
  • Figure US20180186742A1-20180705-C00054
  • To a 20 mL vial charged with (2S,3R)-3-(2,4-dimethylphenyl)-4-methylpentan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate (30 mg, 0.070 mmol) dissolved in pyridine (1 mL, 12.36 mmol) was added acetic anhydride (25 μL, 2.65 mmol) at room temperature. After stirring for 45 min, the mixture was concentrated in vacuo and purified via automated silica gel chromatography (0-40% acetone/hexanes as the eluent) to afford (2S,3R)-3-(2,4-dimethylphenyl)-4-methylpentan-2-yl (3-acetoxy-4-methoxypicolinoyl)-L-alaninate (32 mg, 0.061 mmol, 87% yield) as colorless oil. 1H NMR (500 MHz, CDCl3) δ 8.56 (s, 1H), 8.35 (d, J=5.4 Hz, 1H), 7.19 (d, J=7.9 Hz, 1H), 7.00 (d, J=5.4 Hz, 1H), 6.94 (d, J=1.9 Hz, 1H), 6.90 (dd, J=7.9, 1.9 Hz, 1H), 5.41 (qd, J=6.3, 4.7 Hz, 1H), 4.77-4.61 (m, 1H), 3.91 (s, 3H), 2.68 (dd, J=9.3, 4.8 Hz, 1H), 2.39 (s, 3H), 2.27 (s, 3H), 2.25 (s, 3H), 2.03 (dp, J=9.2, 6.6 Hz, 1H), 1.38 (d, J=7.2 Hz, 3H), 1.05 (d, J=6.3 Hz, 3H), 0.99 (d, J=6.6 Hz, 3H), 0.69 (d, J=6.8 Hz, 3H). IR (thin film) 3383, 2969, 1772, 1733, 1679, 1200, 1176 cm−1. HRMS-ESI (m/z) [M+H]+ calcd for C26H35N2O6, 471.2490; found, 471.2485.
    • Example 11B: Preparation of (2S,3R)-3-(2,4-dimethylphenyl)-4-methylpentan-2-yl (3-(acetoxymethoxy)-4-methoxypicolinoyl)-L-alaninate
  • Figure US20180186742A1-20180705-C00055
  • To a 20 mL vial charged with in (2S,3R)-3-(2,4-dimethylphenyl)-4-methylpentan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate (30 mg, 0.070 mmol) and potassium carbonate (19.35 mg, 0.140 mmol) dissolved in acetone (1.5 mL) was added bromomethyl acetate (0.014 mL, 0.140 mmol) at room temperature. After stirring for 2 hr at 50° C., the mixture was concentrated in vacuo and purified via automated silica gel chromatography (0-40% acetone/hexanes as the eluent) to afford (2S,3R)-3-(2,4-dimethylphenyl)-4-methylpentan-2-yl(3-(acetoxymethoxy)-4-methoxypicolinoyl)-L-alaninate (21 mg, 0.038 mmol, 54% yield) as colorless oil. 1H NMR (500 MHz, CDCl3) δ 8.38 (d, J=7.9 Hz, 1H), 8.29 (d, J=5.4 Hz, 1H), 7.20 (d, J=7.9 Hz, 1H), 7.00-6.87 (m, 3H), 5.80-5.69 (m, 2H), 5.42 (qd, J=6.2, 4.7 Hz, 1H), 4.71 (p, J=7.2 Hz, 1H), 3.91 (s, 3H), 2.69 (dd, J=9.2, 4.9 Hz, 1H), 2.27 (s, 3H), 2.25 (s, 3H), 2.10-1.97 (m, 1H), 2.06 (s, 3H), 1.39 (d, J=7.2 Hz, 3H), 1.07 (d, J=6.3 Hz, 3H), 0.99 (d, J=6.6 Hz, 3H), 0.70 (d, J=6.7 Hz, 3H). IR (thin film) 3380, 2969, 1732, 1675, 1502, 1200, 1003, 967, 829 cm−1. HRMS-ESI (m/z) [M+H]+ calcd for C27H37N2O7, 501.2595; found, 501.2589.
    • Example 11C: Preparation of (2S,3S)-3-(3-fluoro-4-methoxyphenyl)-4-methylpentan-2-yl (4-methoxy-3-((3-methoxypropanoyl)oxy)picolinoyl)-L-alaninate
  • Figure US20180186742A1-20180705-C00056
  • To a stirred solution of (2S,3S)-3-(3-fluoro-4-methoxyphenyl)-4-methylpentan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate (59.3 mg, 0.132 mmol) and 4-(dimethylamino)pyridine (3.23 mg, 0.026 mmol) dissolved in CH2Cl2 (2.0 mL) was added triethylamine (0.037 mL, 0.264 mmol) followed by 3-methoxypropanoyl chloride (0.022 mL, 0.198 mmol). The reaction was allowed to stir at room temperature overnight. The reaction was concentrated under a stream of nitrogen. The residue was loaded directly onto a 12 g prepacked silica column in a minimal amount of dichloromethane and purified using Isco silica gel column chromatography (24 g column, 35 mL/min, 100% hexanes to 50% acetone:hexanes as the eluent) to afford the title compound (58.5 mg, 83% yield) as a pale yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J=7.9 Hz, 1H), 8.34 (d, J=5.4 Hz, 1H), 7.01 (d, J=5.5 Hz, 1H), 6.92-6.75 (m, 3H), 5.34 (dq, J=8.3, 6.2 Hz, 1H), 4.66 (dt, J=8.1, 7.1 Hz, 1H), 3.90 (s, 3H), 3.86 (s, 3H), 3.81 (t, J=6.6 Hz, 2H), 3.40 (s, 3H), 2.99 (t, J=6.6 Hz, 2H), 2.64 (dd, J=8.6, 6.5 Hz, 1H), 2.05 (h, J=6.8 Hz, 1H), 1.49 (d, J=7.2 Hz, 3H), 1.09 (d, J=6.3 Hz, 3H), 0.87 (d, J=6.7 Hz, 3H), 0.75 (d, J=6.7 Hz, 3H). 13C NMR (101 MHz, CDCl3) δ 172.19, 169.42, 162.36, 159.51, 151.94 (d, J=245.0 Hz), 146.73, 146.25 (d, J=10.8 Hz), 141.62, 137.42, 131.84 (d, J=5.6 Hz), 125.47 (d, J=3.6 Hz), 117.15 (d, J=18.2 Hz), 113.05-112.84 (m), 109.77, 72.51, 67.62, 58.76, 56.33, 56.24, 55.74, 48.21, 34.67, 28.35, 21.25, 18.77, 18.63, 17.47. 19F NMR (376 MHz, CDCl3) δ −135.76. HRMS-ESI (m/z) [M+H]+ calcd for C27H36FN2O8, 535.2450; found, 535.2444.
    • Example 12: Preparation of (1R,2S)-1-cyclopentyl-1-phenylpropan-2-yl(3-acetoxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate Step 1: Preparation of (1R,2S)-1-cyclopentyl-1-phenylpropan-2-yl (3-hydroxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate
  • Figure US20180186742A1-20180705-C00057
  • To a 30 mL vial charged with (1R,2S)-1-cyclopentyl-1-phenylpropan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate (99 mg, 0.232 mmol) dissolved in acetonitrile (2.32 mL) was added phosphorous pentasulfide (103 mg, 0.464 mmol) and 1,1,1,3,3,3-hexamethyldisiloxane (248 μL, 1.161 mmol). After stirring for 45 min at 45° C., sat. NaHCO3 (15 mL) was added followed by aqueous extraction with dichloromethane (3×15 mL). The organics were dried over MgSO4, filtered, and concentrated in vacuo. The crude residue was purified via flash chromatography (0-45% acetone/hexanes as the eluent) to furnish (1R,2S)-1-cyclopentyl-1-phenylpropan-2-yl (3-hydroxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate (72 mg, 0.155 mmol, 66.6% yield) as a yellow oil. 1H NMR (500 MHz, CDCl3) δ 12.94 (s, 1H), 10.71 (s, 1H), 8.01 (d, J=15.0 Hz, 1H), 7.22-7.17 (m, 3H), 7.15 (dd, J=6.7, 3.0 Hz, 2H), 6.89 (d, J=5.0 Hz, 1H), 5.39 (qd, J=6.4, 4.0 Hz, 1H), 5.12-5.03 (m, 1H), 3.97 (s, 3H), 2.41 (dd, J=10.4, 4.0 Hz, 1H), 2.25-2.14 (m, 1H), 1.95-1.84 (m, 1H), 1.69-1.59 (m, 1H), 1.56 (d, J=7.2 Hz, 3H), 1.54-1.45 (m, 2H), 1.44-1.28 (m, 2H), 1.19 (dq, J=12.3, 9.1 Hz, 1H), 1.09 (d, J=6.4 Hz, 3H), 0.92 (ddt, J=12.5, 10.0, 8.5 Hz, 1H). IR (thin film) 2951, 2868, 1733, 1581, 1514, 1480, 1454, 1377, 1342, 1274, 1249, 1211, 1131, 1095, 992, 913, 860, 801, 736, 703 cm−1. HRMS-ESI (m/z) [M+Na]+ calcd for C24H30N2O4SNa, 465.1818; found, 465.1830.
    • Step 2: Preparation of (1R,2S)-1-cyclopentyl-1-phenylpropan-2-yl (3-acetoxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate
  • Figure US20180186742A1-20180705-C00058
  • To a solution of (1R,2S)-1-cyclopentyl-1-phenylpropan-2-yl (3-hydroxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate (55 mg, 0.124 mmol) dissolved in pyridine (1 mL, 0.124 mmol) was added acetic anhydride (0.25 mL, 0.124 mmol). After stirring for 1 hr at room temperature, the mixture was concentrated in vacuo and purified via automated column chromatography (0-50% acetone/hexanes as the eluent) to furnish (1R,2S)-1-cyclopentyl-1-phenylpropan-2-yl (3-acetoxy-4-methoxypyridine-2-carbonothioyl)-L-alaninate (34 mg, 0.060 mmol, 48.0% yield) as a brown oil. 1H NMR (500 MHz, CDCl3) δ 9.98 (d, J=7.3 Hz, 1H), 8.35 (d, J=5.4 Hz, 1H), 7.25-7.13 (m, 5H), 7.01 (d, J=5.5 Hz, 1H), 5.39 (qd, J=6.3, 4.1 Hz, 1H), 5.16 (p, J=7.2 Hz, 1H), 3.91 (s, 3H), 2.42 (dd, J=10.3, 4.0 Hz, 1H), 2.35 (s, 3H), 2.28-2.19 (m, 1H), 1.93-1.83 (m, 1H), 1.68-1.59 (m, 1H), 1.52 (d, J=7.2 Hz, 3H), 1.50-1.31 (m, 4H), 1.20 (dq, J=12.5, 9.1 Hz, 1H), 1.08 (d, J=6.4 Hz, 3H), 0.97-0.90 (m, 1H). IR (thin film) 2950, 2868, 1770, 1731, 1585, 1496, 1438, 1365, 1311, 1278, 1193, 1175, 1131, 1102, 1040, 1010, 909, 847, 824, 759, 703 cm−1. HRMS-ESI (m/z) [M+Na]+ calcd for C26H32N2O5SNa, 507.1924; found, 507.1920.
    • Example 13: Preparation of 2-(((S)-1-(((2S,3R)-3-(2,4-dimethylphenyl)-4-methylpentan-2-yl)oxy)-1-oxopropan-2-yl)carbamoyl)-3-hydroxy-4-methoxypyridine 1-oxide
  • Figure US20180186742A1-20180705-C00059
  • To a 25 mL vial charged with (2S,3R)-3-(2,4-dimethylphenyl)-4-methylpentan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate (38 mg, 0.089 mmol) dissolved in CH2Cl2 (1182 μL) was added 3-chlorobenzoperoxoic acid (mCPBA, 43.7 mg, 0.177 mmol) at room temperature. After stirring overnight, the reaction mixture was concentrated in vacuo and purified via automated silica gel chromatography (0-50% acetone/hexanes as the eluent) to afford 2-(((S)-1-(((2S,3R)-3-(2,4-dimethylphenyl)-4-methylpentan-2-yl)oxy)-1-oxopropan-2-yl)carbamoyl)-3-hydroxy-4-methoxypyridine 1-oxide (27 mg, 0.055 mmol, 61.6% yield) as colorless oil. 1H NMR (500 MHz, CDCl3) δ 14.37 (s, 1H), 12.78 (d, J=7.0 Hz, 1H), 7.88 (d, J=7.1 Hz, 1H), 7.15 (d, J=7.7 Hz, 1H), 6.90 (d, J=8.0 Hz, 2H), 6.77 (d, J=7.2 Hz, 1H), 5.42 (qd, J=6.3, 5.0 Hz, 1H), 4.69-4.61 (m, 1H), 3.96 (s, 3H), 2.69 (dd, J=9.1, 5.0 Hz, 1H), 2.25 (s, 3H), 2.23 (s, 3H), 2.00 (dp, J=8.8, 6.6 Hz, 1H), 1.44 (d, J=7.2 Hz, 3H), 1.08 (d, J=6.3 Hz, 3H), 0.98 (d, J=6.6 Hz, 3H), 0.69 (d, J=6.8 Hz, 3H). IR (thin film) 2964, 1734, 1644, 1571, 1480, 1302, 1216 cm−1. HRMS-ESI (m/z) [M+H]+ calcd for C24H33N2O6, 445.2333; found, 445.2370.
    • Example 14: Preparation of (2S,3R)-3-(2,4-dimethylphenyl)-4-methylpentan-2-yl (S)-2-(8-methoxy-2,4-dioxo-2H-pyrido[2,3-e][1,3]oxazin-3(4H)-yl)propanoate
  • Figure US20180186742A1-20180705-C00060
  • To a 20 mL vial charged with (2S,3R)-3-(2,4-dimethylphenyl)-4-methylpentan-2-yl (3-hydroxy-4-methoxypicolinoyl)-L-alaninate (30 mg, 0.070 mmol) and triphosgene (41.5 mg, 0.140 mmol) dissolved in CH2Cl2 (0.75 mL) was added pyridine (0.1 mL, 1.236 mmol) at room temperature. After stirring for 45 min at room temperature, the crude LCMS revealed a complete conversion to the desired mass. The reaction mixture was quenched by the addition of a saturated NaHCO3 solution and was extracted with EtOAc (3×10 mL). The combined organic layers were washed with brine (10 mL). The organic solution was dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified via automated silica gel chromatography (0-40% acetone/hexanes as the eluent) to afford (2S,3R)-3-(2,4-dimethylphenyl)-4-methylpentan-2-yl(S)-2-(8-methoxy-2,4-dioxo-2H-pyrido[2,3-e][1,3]oxazin-3(4H)-yl)propanoate (28 mg, 0.059 mmol, 84% yield) as orange oil. 1H NMR (500 MHz, CDCl3) δ 8.62 (d, J=5.3 Hz, 1H), 7.15 (d, J=5.4 Hz, 1H), 6.90 (d, J=7.9 Hz, 1H), 6.87-6.83 (m, 1H), 6.32-6.24 (m, 1H), 5.65 (q, J=7.1 Hz, 1H), 5.43 (qd, J=6.4, 3.2 Hz, 1H), 4.05 (s, 3H), 2.53 (dd, J=10.4, 3.2 Hz, 1H), 2.18 (s, 3H), 2.10 (s, 3H), 2.06-1.96 (m, 1H), 1.71 (d, J=7.0 Hz, 3H), 1.04 (d, J=6.5 Hz, 3H), 0.95 (d, J=6.3 Hz, 3H), 0.60 (d, J=6.6 Hz, 3H). IR (thin film) 2958, 1770, 1715, 1371, 1244, 734 cm−1. HRMS-ESI (m/z) [M+H]+ calcd for C25H31N2O6, 455.2177; found, 455.2171.
    • Example A: Evaluation of Fungicidal Activity: Leaf Blotch of Wheat (Zymoseptoria tritici; Bayer Code SEPTTR)
  • Technical grades of materials were dissolved in acetone, which were then mixed with nine volumes of water containing 110 ppm Triton X-100. The fungicide solutions were applied onto wheat seedlings using an automated booth sprayer to run-off. All sprayed plants were allowed to air dry prior to further handling. All fungicides were evaluated using the aforementioned method for their activity vs. all target diseases, unless stated otherwise. Wheat leaf blotch and brown rust activity were also evaluated using track spray applications, in which case the fungicides were formulated as EC formulations, containing 0.1% Trycol 5941 in the spray solutions.
  • Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Zymoseptoria tritici either prior to or after fungicide treatments. After inoculation the plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two to three days in a lighted dew chamber at 20° C.) to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 20° C. for disease to develop. When disease symptoms were fully expressed on the 1st leaves of untreated plants, infection levels were assessed on a scale of 0 to 100 percent disease severity. Percent disease control was calculated using the ratio of disease severity on treated plants relative to untreated plants.
    • Example B: Evaluation of Fungicidal Activity: Wheat Brown Rust (Puccinia triticina; Synonym: Puccinia recondita f. Sp. Tritici; Bayer Code PUCCRT)
  • Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Puccinia triticina either prior to or after fungicide treatments. After inoculation the plants were kept in a dark dew room at 22° C. with 100% relative humidity overnight to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 24° C. for disease to develop. Fungicide formulation, application and disease assessment followed the procedures as described in the Example A.
    • Example C: Evaluation of Fungicidal Activity: Asian Soybean Rust (Phakopsora pachyrhizi; Bayer Code PHAKPA)
  • Technical grades of materials were dissolved in acetone, which were then mixed with nine volumes of water containing 0.011% Tween 20. The fungicide solutions were applied onto soybean seedlings using an automated booth sprayer to run-off. All sprayed plants were allowed to air dry prior to further handling.
  • Soybean plants (variety Williams 82) were grown in soil-less Metro mix, with one plant per pot. Two week old seedlings were used for testing. Plants were inoculated either 3 days prior to or 1 day after fungicide treatments. Plants were incubated for 24 h in a dark dew room at 22° C. and 100% relative humidity then transferred to a growth room at 23° C. for disease to develop. Disease severity was assessed on the sprayed leaves.
    • Example D: Evaluation of Fungicidal Activity: Tomato Early Blight (Alternaria solani; Bayer Code ALTESO)
  • Tomato plants (variety Outdoor Girl) were propagated in soil-less Metro mix, with each pot having one plant, and used when 12 to 14 days old. Test plants were inoculated with an aqueous spore suspension of Alternaria solani 24 hr after fungicide treatments. After inoculation the plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two to three days in a lighted dew chamber at 20° C.) to permit spores to germinate and infect the leaf. The plants were then transferred to a growth room at 22° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.
    • Example E: Evaluation of Fungicidal Activity: Leaf Spot of Sugar Beets (Cercospora beticola; Bayer Code CERCBE)
  • Sugar beet plants (variety HH88) were grown in soil-less Metro mix and trimmed regularly to maintain a uniform plant size prior to test. Plants were inoculated with a spore suspension 24 hr after fungicide treatments. Inoculated plants were kept in a dew chamber at 22° C. for 48 hr then incubated in a greenhouse set at 24° C. under a clear plastic hood with bottom ventilation until disease symptoms were fully expressed. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.
    • Example F: Evaluation of Fungicidal Activity: Cucumber Anthracnose (Glomerella lagenarium; Anamorph: Colletotrichum lagenarium; Bayer Code COLLLA)
  • Cucumber seedlings (variety Bush Pickle) were propagated in soil-less Metro mix, with each pot having one plant, and used in the test when 12 to 14 days old. Test plants were inoculated with an aqueous spore suspension of Colletotrichum lagenarium 24 hr after fungicide treatments. After inoculation the plants were kept in a dew room at 22° C. with 100% relative humidity for 48 hr to permit spores to germinate and infect the leaf. The plants were then transferred to a growth room set at 22° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.
    • Example G: Evaluation of Fungicidal Activity: Wheat Glume Blotch (Parastagonospora nodorum; Bayer Code LEPTNO)
  • Wheat plants (variety Yuma) were grown from seed in a greenhouse in 50% mineral soil/50% soil-less Metro mix until the first leaf was fully emerged, with 7-10 seedlings per pot. These plants were inoculated with an aqueous spore suspension of Parastagonospora nodorum 24 hr after fungicide treatments. After inoculation the plants were kept in 100% relative humidity (one day in a dark dew chamber followed by two days in a lighted dew chamber at 20° C.) to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 20° C. for disease to develop. Fungicide formulation, application and disease assessment followed the procedures as described in the Example A.
    • Example H: Evaluation of Fungicidal Activity: Cucumber Downy Mildew (Pseudoperonospora cubensis; Bayer Code PSPECU)
  • Cucumber seedlings (variety Bush Pickle) were grown in soil-less Metro mix, with one plant per pot, and used in the test when 12 to 14 days old. Plants were inoculated with a spore suspension 24 hr following fungicide treatments. Test plants were inoculated with an aqueous spore suspension of Pseudoperonospora cubensis 24 hr after fungicide treatments. After inoculation the plants were kept in a dew room at 22° C. with 100% relative humidity for 24 hr to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 20° C. until disease was fully expressed. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.
    • Example I: Evaluation of Fungicidal Activity: Rice Blast (Magnaporthe grisea; Anamorph: Pyricularia oryzae; Bayer Code PYRIOR)
  • Rice seedlings (variety Japonica) were propagated in soil-less Metro mix, with each pot having 8 to 14 plants, and used in the test when 12 to 14 days old. Test plants were inoculated with an aqueous spore suspension of Pyricularia oryzae 24 hr after fungicide treatments. After inoculation, the plants were kept in a dew room at 22° C. with 100% relative humidity for 48 hr to permit spores to germinate and infect the leaf. The plants were then transferred to a greenhouse set at 24° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.
    • Example J: Evaluation of Fungicidal Activity: Barley Scald (Rhyncosporium secalis; Bayer Code RHYNSE)
  • Barley seedlings (variety Harrington) were propagated in soil-less Metro mix, with each pot having 8 to 12 plants, and used in the test when first leaf was fully emerged. Test plants were inoculated by an aqueous spore suspension of Rhyncosporium secalis 24 hr after fungicide treatments. After inoculation the plants were kept in a dew room at 20° C. with 100% relative humidity for 48 hr. The plants were then transferred to a greenhouse set at 20° C. for disease to develop. Fungicide formulation, application and disease assessment on the sprayed leaves followed the procedures as described in the Example A.
    • Example K: Evaluation of Fungicidal Activity: Grape Powdery Mildew (Uncinula necator; Bayer Code UNCINE)
  • Grape seedlings (variety Carignane) were grown in soil-less Metro mix, with one plant per pot, and used in the test when approximately 1 month old. Plants were inoculated 24 hr after fungicide treatment by shaking spores from infected leaves over test plants. Plants were maintained in a greenhouse set at 20° C. until disease was fully developed. Fungicide formulation, application and disease assessment on sprayed leaves followed the procedures as described in the Example A.
  • TABLE 1
    Compound Structure, Appearance, and Preparation Method
    As
    Prepared
    Cmpd. According
    No. Structure To Appearance
    1
    Figure US20180186742A1-20180705-C00061
         		Example 2A Example 3B Example 8 Colorless Oil
    2
    Figure US20180186742A1-20180705-C00062
         		Example 2A Example 3B Example 8 Colorless Oil
    3
    Figure US20180186742A1-20180705-C00063
         		Example 2A Example 3B Example 9 Colorless Oil
    4
    Figure US20180186742A1-20180705-C00064
         		Example 1A Example 2B Example 3B Example 8 Colorless Oil
    5
    Figure US20180186742A1-20180705-C00065
         		Example 1A Example 2B Example 3B Example 8 Pale Yellow Oil
    6
    Figure US20180186742A1-20180705-C00066
         		Example 1B Example 2B Example 3B Example 8 Colorless Oil
    7
    Figure US20180186742A1-20180705-C00067
         		Example 2A Example 5 Example 8 Colorless Oil
    8
    Figure US20180186742A1-20180705-C00068
         		Example 2A Example 5 Example 8 Colorless Oil
    9
    Figure US20180186742A1-20180705-C00069
         		Example 1C; Step 1 Example 2B Example 3B Example 8 Clear, Colorless Oil
    10
    Figure US20180186742A1-20180705-C00070
         		Example 1C; Step 1 Example 2B Example 3B Example 8 Clear, Colorless Oil
    11
    Figure US20180186742A1-20180705-C00071
         		Example 1C; Step 1 Example 2B Example 3B Example 8 Clear, Colorless Oil
    12
    Figure US20180186742A1-20180705-C00072
         		Example 1C; Step 1 Example 2B Example 3B Example 8 Clear, Colorless Oil
    13
    Figure US20180186742A1-20180705-C00073
         		Example 1C; Step 1 Example 2B Example 3B Example 8 Clear, Colorless Oil
    14
    Figure US20180186742A1-20180705-C00074
         		Example 1C; Step 1 Example 2B Example 3A Example 8 Clear, Colorless Oil
    15
    Figure US20180186742A1-20180705-C00075
         		Example 1C; Step 1 Example 2B Example 3B Example 9 Clear, Colorless Oil
    16
    Figure US20180186742A1-20180705-C00076
         		Example 1C; Step 1 Example 2B Example 3B Example 9 Clear, Colorless Oil
    17
    Figure US20180186742A1-20180705-C00077
         		Example 1C; Step 1 Example 2B Example 4A Example 4C Example 9 Clear, Colorless Oil
    18
    Figure US20180186742A1-20180705-C00078
         		Example 1C; Step 1 Example 2B Example 3B Example 9 Clear, Colorless Oil
    19
    Figure US20180186742A1-20180705-C00079
         		Example 1C; Step 1 Example 2B Example 3B Example 9 Clear, Colorless Oil
    20
    Figure US20180186742A1-20180705-C00080
         		Example 1C; Step 1 Example 2B Example 3A Example 9 Clear, Colorless Oil
    21
    Figure US20180186742A1-20180705-C00081
         		Example 1C; Step 1 Example 2B Example 3B Example 8 Clear, Colorless Oil
    22
    Figure US20180186742A1-20180705-C00082
         		Example 1C; Step 1 Example 2B Example 3B Example 8 Clear, Colorless Oil
    23
    Figure US20180186742A1-20180705-C00083
         		Example 1C; Step 1 Example 2B Example 4A Example 4B Example 8 Clear, Colorless Oil
    24
    Figure US20180186742A1-20180705-C00084
         		Example 1D Example 2B Example 3B Example 8 Yellow Oil
    25
    Figure US20180186742A1-20180705-C00085
         		Example 1D Example 2B Example 3B Example 8 Colorless Oil
    26
    Figure US20180186742A1-20180705-C00086
         		Example 1D Example 2B Example 3B Example 8 Colorless Oil
    27
    Figure US20180186742A1-20180705-C00087
         		Example 1D Example 2B Example 3B Example 8 Colorless Oil
    28
    Figure US20180186742A1-20180705-C00088
         		Example 1C Example 2B Example 3B Example 8 Clear, Colorless Oil
    29
    Figure US20180186742A1-20180705-C00089
         		Example 1C Example 2B Example 3B Example 8 Clear, Colorless Oil
    30
    Figure US20180186742A1-20180705-C00090
         		Example 1C Example 2B Example 3B Example 8 Clear, Colorless Oil
    31
    Figure US20180186742A1-20180705-C00091
         		Example 1C Example 2B Example 3B Example 8 Clear, Colorless Oil
    32
    Figure US20180186742A1-20180705-C00092
         		Example 1C Example 2B Example 3B Example 8 Clear, Colorless Oil
    33
    Figure US20180186742A1-20180705-C00093
         		Example 6 Steps 1, 2, 3, 4, 5 Example 8 Colorless Oil
    34
    Figure US20180186742A1-20180705-C00094
         		Example 1C Example 2B Example 3A Example 8 Clear, Colorless Oil
    35
    Figure US20180186742A1-20180705-C00095
         		Example 1C Example 2B Example 3B Example 7 Example 8 Clear, Colorless Oil
    36
    Figure US20180186742A1-20180705-C00096
         		Example 1C Example 2B Example 3B Example 7 Example 8 Clear, Colorless Oil
    37
    Figure US20180186742A1-20180705-C00097
         		Example 1C Example 2B Example 3B Example 7 Example 8 Clear, Colorless Oil
    38
    Figure US20180186742A1-20180705-C00098
         		Example 1C Example 2B Example 3B Example 7 Example 8 Clear, Colorless Oil
    39
    Figure US20180186742A1-20180705-C00099
         		Example 1C Example 2B Example 3A Example 7 Example 8 Clear, Colorless Oil
    40
    Figure US20180186742A1-20180705-C00100
         		Example 1C Example 2B Example 4A Example 4C Example 7 Example 8 Clear, Colorless Oil
    41
    Figure US20180186742A1-20180705-C00101
         		Example 1D Example 2B Example 3A Example 8 Colorless Oil
    42
    Figure US20180186742A1-20180705-C00102
         		Example 6 Steps 1, 2, 6, 7, 4, 5 Example 8 Colorless Oil
    43
    Figure US20180186742A1-20180705-C00103
         		Example 6 Steps 1, 2, 6, 7, 4, 5 Example 8 Colorless Oil
    44
    Figure US20180186742A1-20180705-C00104
         		Example 6 Steps 1, 2, 6, 7, 4, 5 Example 8 Colorless Oil
    45
    Figure US20180186742A1-20180705-C00105
         		Example 6 Steps 1, 2, 6, 7, 4, 5 Example 8 Pale Yellow Oil
    46
    Figure US20180186742A1-20180705-C00106
         		Example 6 Steps 1, 2, 6, 7, 4, 5 Example 8 Clear, Colorless Oil
    47
    Figure US20180186742A1-20180705-C00107
         		Example 6 Steps 1, 2, 6, 7, 4, 5 Example 8 Clear, Colorless Oil
    48
    Figure US20180186742A1-20180705-C00108
         		Example 6 Steps 1, 2, 6, 7, 4, 5 Example 8 Pale Yellow Oil
    49
    Figure US20180186742A1-20180705-C00109
         		Example 6 Steps 1, 2, 6, 7, 4, 5 Example 8 Clear, Colorless Oil
    50
    Figure US20180186742A1-20180705-C00110
         		Example 6 Steps 1, 2, 6, 7, 4, 5 Example 8 Colorless Oil
    51
    Figure US20180186742A1-20180705-C00111
         		Example 6 Steps 1, 2, 6, 7, 4, 5 Example 8 Colorless Oil
    52
    Figure US20180186742A1-20180705-C00112
         		Example 10 Step 1 Colorless Oil
    53
    Figure US20180186742A1-20180705-C00113
         		Example 10 Step 1 Colorless Oil
    54
    Figure US20180186742A1-20180705-C00114
         		Example 10 Step 1 Colorless Oil
    55
    Figure US20180186742A1-20180705-C00115
         		Example 10 Step 1 Colorless Oil
    56
    Figure US20180186742A1-20180705-C00116
         		Example 10 Step 1 White Semisolid
    57
    Figure US20180186742A1-20180705-C00117
         		Example 10 Step 1 Colorless Oil
    58
    Figure US20180186742A1-20180705-C00118
         		Example 10 Step 1 Colorless Oil
    59
    Figure US20180186742A1-20180705-C00119
         		Example 10 Step 1 Colorless Oil
    60
    Figure US20180186742A1-20180705-C00120
         		Example 10 Step 1 Colorless Oil
    61
    Figure US20180186742A1-20180705-C00121
         		Example 10 Step 1 Colorless Oil
    62
    Figure US20180186742A1-20180705-C00122
         		Example 10 Step 1 Clear, Colorless Oil
    63
    Figure US20180186742A1-20180705-C00123
         		Example 10 Step 1 Clear, Colorless Oil
    64
    Figure US20180186742A1-20180705-C00124
         		Example 10 Step 1 Pale Yellow Oil
    65
    Figure US20180186742A1-20180705-C00125
         		Example 10 Step 1 Clear, Colorless Oil
    66
    Figure US20180186742A1-20180705-C00126
         		Example 10 Step 1 Clear, Colorless Oil
    67
    Figure US20180186742A1-20180705-C00127
         		Example 10 Step 1 Clear, Colorless Oil
    68
    Figure US20180186742A1-20180705-C00128
         		Example 10 Step 1 Pale Yellow Oil
    69
    Figure US20180186742A1-20180705-C00129
         		Example 10 Step 1 Clear, Colorless Oil
    70
    Figure US20180186742A1-20180705-C00130
         		Example 10 Step 1 Clear, Colorless Oil
    71
    Figure US20180186742A1-20180705-C00131
         		Example 10 Step 1 Pale Yellow Oil
    72
    Figure US20180186742A1-20180705-C00132
         		Example 10 Step 1 Pale Yellow Oil
    73
    Figure US20180186742A1-20180705-C00133
         		Example 10 Step 1 Pale Yellow Oil
    74
    Figure US20180186742A1-20180705-C00134
         		Example 10 Step 1 Clear, Colorless Oil
    75
    Figure US20180186742A1-20180705-C00135
         		Example 10 Step 1 Clear, Colorless Oil
    76
    Figure US20180186742A1-20180705-C00136
         		Example 10 Step 1 Clear, Colorless Oil
    77
    Figure US20180186742A1-20180705-C00137
         		Example 10 Step 1 Yellow Oil
    78
    Figure US20180186742A1-20180705-C00138
         		Example 10 Step 1 Yellow Oil
    79
    Figure US20180186742A1-20180705-C00139
         		Example 10 Step 1 Yellow Oil
    80
    Figure US20180186742A1-20180705-C00140
         		Example 10 Step 1 Yellow Oil
    81
    Figure US20180186742A1-20180705-C00141
         		Example 10 Step 1 Thick Oil
    82
    Figure US20180186742A1-20180705-C00142
         		Example 10 Step 1 Pale Yellow Oil
    83
    Figure US20180186742A1-20180705-C00143
         		Example 10 Step 1 Clear, Colorless Oil
    84
    Figure US20180186742A1-20180705-C00144
         		Example 10 Step 1 Clear, Colorless Oil
    85
    Figure US20180186742A1-20180705-C00145
         		Example 10 Step 1 Clear, Colorless Oil
    86
    Figure US20180186742A1-20180705-C00146
         		Example 10 Step 1 Clear, Colorless Oil
    87
    Figure US20180186742A1-20180705-C00147
         		Example 10 Step 1 Clear, Colorless Oil
    88
    Figure US20180186742A1-20180705-C00148
         		Example 10 Step 1 Clear, Colorless Oil
    89
    Figure US20180186742A1-20180705-C00149
         		Example 10 Step 1 White Semisolid
    90
    Figure US20180186742A1-20180705-C00150
         		Example 10 Step 1 Off-White Semisolid
    91
    Figure US20180186742A1-20180705-C00151
         		Example 10 Step 1 Clear, Colorless Oil
    92
    Figure US20180186742A1-20180705-C00152
         		Example 10 Step 1 Clear, Colorless Oil
    93
    Figure US20180186742A1-20180705-C00153
         		Example 10 Step 1 Clear, Colorless Oil
    94
    Figure US20180186742A1-20180705-C00154
         		Example 10 Step 1 Yellow Oil
    95
    Figure US20180186742A1-20180705-C00155
         		Example 10 Step 1 Thick Oil
    96
    Figure US20180186742A1-20180705-C00156
         		Example 10 Step 1 Thick Oil
    97
    Figure US20180186742A1-20180705-C00157
         		Example 10 Step 1 Thick Oil
    98
    Figure US20180186742A1-20180705-C00158
         		Example 10 Step 1 Pale Yellow Oil
    99
    Figure US20180186742A1-20180705-C00159
         		Example 10 Step 1 White Semisolid
    100
    Figure US20180186742A1-20180705-C00160
         		Example 10 Step 1 Clear, Colorless Oil
    101
    Figure US20180186742A1-20180705-C00161
         		Example 10 Step 1 Pale Yellow Oil
    102
    Figure US20180186742A1-20180705-C00162
         		Example 10 Step 1 Clear, Colorless Oil
    103
    Figure US20180186742A1-20180705-C00163
         		Example 10 Step 1 Yellow Oil
    104
    Figure US20180186742A1-20180705-C00164
         		Example 10 Step 1 Yellow Oil
    105
    Figure US20180186742A1-20180705-C00165
         		Example 10 Step 2 Colorless Gel
    106
    Figure US20180186742A1-20180705-C00166
         		Example 10 Step 2 Colorless Gel
    107
    Figure US20180186742A1-20180705-C00167
         		Example 10 Step 2 Colorless Oil
    108
    Figure US20180186742A1-20180705-C00168
         		Example 10 Step 2 Colorless Oil
    109
    Figure US20180186742A1-20180705-C00169
         		Example 10 Step 2 Clear, Colorless Oil
    110
    Figure US20180186742A1-20180705-C00170
         		Example 10 Step 2 Colorless Oil
    111
    Figure US20180186742A1-20180705-C00171
         		Example 10 Step 2 Colorless Oil
    112
    Figure US20180186742A1-20180705-C00172
         		Example 10 Step 2 Colorless Oil
    113
    Figure US20180186742A1-20180705-C00173
         		Example 10 Step 2 Colorless Oil
    114
    Figure US20180186742A1-20180705-C00174
         		Example 10 Step 2 Yellow Solid
    115
    Figure US20180186742A1-20180705-C00175
         		Example 10 Step 2 Yellow Oil
    116
    Figure US20180186742A1-20180705-C00176
         		Example 10 Step 2 Clear, Colorless Oil
    117
    Figure US20180186742A1-20180705-C00177
         		Example 10 Step 2 Clear, Colorless Oil
    118
    Figure US20180186742A1-20180705-C00178
         		Example 10 Step 2 Clear, Colorless Oil
    119
    Figure US20180186742A1-20180705-C00179
         		Example 10 Step 2 Clear, Colorless Oil
    120
    Figure US20180186742A1-20180705-C00180
         		Example 10 Step 2 Clear, Colorless Oil
    121
    Figure US20180186742A1-20180705-C00181
         		Example 10 Step 2 Clear, Colorless Oil
    122
    Figure US20180186742A1-20180705-C00182
         		Example 10 Step 2 Clear, Colorless Oil
    123
    Figure US20180186742A1-20180705-C00183
         		Example 10 Step 2 Clear, Colorless Oil
    124
    Figure US20180186742A1-20180705-C00184
         		Example 10 Step 2 Clear, Colorless Oil
    125
    Figure US20180186742A1-20180705-C00185
         		Example 10 Step 2 Clear, Colorless Oil
    126
    Figure US20180186742A1-20180705-C00186
         		Example 10 Step 2 Clear, Colorless Oil
    127
    Figure US20180186742A1-20180705-C00187
         		Example 10 Step 2 Clear, Colorless Oil
    128
    Figure US20180186742A1-20180705-C00188
         		Example 10 Step 2 Clear, Colorless Oil
    129
    Figure US20180186742A1-20180705-C00189
         		Example 10 Step 2 Clear, Colorless Oil
    130
    Figure US20180186742A1-20180705-C00190
         		Example 10 Step 2 Clear, Colorless Oil
    131
    Figure US20180186742A1-20180705-C00191
         		Example 10 Step 2 Colorless Oil
    132
    Figure US20180186742A1-20180705-C00192
         		Example 10 Step 2 Colorless Oil
    133
    Figure US20180186742A1-20180705-C00193
         		Example 10 Step 2 White Wax
    134
    Figure US20180186742A1-20180705-C00194
         		Example 10 Step 2 White Wax
    135
    Figure US20180186742A1-20180705-C00195
         		Example 10 Step 2 Thick Oil
    136
    Figure US20180186742A1-20180705-C00196
         		Example 10 Step 2 Bright Yellow Semisolid
    137
    Figure US20180186742A1-20180705-C00197
         		Example 10 Step 2 Yellow Oil
    138
    Figure US20180186742A1-20180705-C00198
         		Example 10 Step 2 Pale Yellow Oil
    139
    Figure US20180186742A1-20180705-C00199
         		Example 10 Step 2 Yellow Oil
    140
    Figure US20180186742A1-20180705-C00200
         		Example 10 Step 2 Pale Yellow Oil
    141
    Figure US20180186742A1-20180705-C00201
         		Example 10 Step 2 Clear, Colorless Oil
    142
    Figure US20180186742A1-20180705-C00202
         		Example 10 Step 2 Clear, Colorless Oil
    143
    Figure US20180186742A1-20180705-C00203
         		Example 10 Step 2 Clear, Colorless Oil
    144
    Figure US20180186742A1-20180705-C00204
         		Example 10 Step 2 Clear, Colorless Oil
    145
    Figure US20180186742A1-20180705-C00205
         		Example 10 Step 2 Clear, Colorless Oil
    146
    Figure US20180186742A1-20180705-C00206
         		Example 10 Step 2 Clear, Colorless Oil
    147
    Figure US20180186742A1-20180705-C00207
         		Example 10 Step 2 Clear, Colorless Oil
    148
    Figure US20180186742A1-20180705-C00208
         		Example 10 Step 2 Clear, Colorless Oil
    149
    Figure US20180186742A1-20180705-C00209
         		Example 10 Step 2 Colorless Oil
    150
    Figure US20180186742A1-20180705-C00210
         		Example 10 Step 2 Colorless Oil
    151
    Figure US20180186742A1-20180705-C00211
         		Example 10 Step 2 Thick Oil
    152
    Figure US20180186742A1-20180705-C00212
         		Example 10 Step 2 Thick Oil
    153
    Figure US20180186742A1-20180705-C00213
         		Example 10 Step 2 Clear, Colorless Oil
    154
    Figure US20180186742A1-20180705-C00214
         		Example 10 Step 2 Clear, Colorless Oil
    155
    Figure US20180186742A1-20180705-C00215
         		Example 10 Step 2 Clear, Colorless Oil
    156
    Figure US20180186742A1-20180705-C00216
         		Example 10 Step 2 Clear, Colorless Oil
    157
    Figure US20180186742A1-20180705-C00217
         		Example 10 Step 2 Clear, Colorless Oil
    158
    Figure US20180186742A1-20180705-C00218
         		Example 10 Step 2 Colorless Oil
    159
    Figure US20180186742A1-20180705-C00219
         		Example 10 Step 2 Colorless Oil
    160
    Figure US20180186742A1-20180705-C00220
         		Example 11A Colorless Oil
    161
    Figure US20180186742A1-20180705-C00221
         		Example 11A Colorless Oil
    162
    Figure US20180186742A1-20180705-C00222
         		Example 11B Colorless Oil
    163
    Figure US20180186742A1-20180705-C00223
         		Example 11B Colorless Oil
    164
    Figure US20180186742A1-20180705-C00224
         		Example 11B Colorless Oil
    165
    Figure US20180186742A1-20180705-C00225
         		Example 11A Colorless Oil
    166
    Figure US20180186742A1-20180705-C00226
         		Example 11A Colorless Oil
    167
    Figure US20180186742A1-20180705-C00227
         		Example 11B Colorless Oil
    168
    Figure US20180186742A1-20180705-C00228
         		Example 11A Clear, Colorless Oil
    169
    Figure US20180186742A1-20180705-C00229
         		Example 11A Colorless Oil
    170
    Figure US20180186742A1-20180705-C00230
         		Example 11A Colorless Oil
    171
    Figure US20180186742A1-20180705-C00231
         		Example 11B Colorless Oil
    172
    Figure US20180186742A1-20180705-C00232
         		Example 11A Colorless Oil
    173
    Figure US20180186742A1-20180705-C00233
         		Example 11A Colorless Oil
    174
    Figure US20180186742A1-20180705-C00234
         		Example 11B Colorless Oil
    175
    Figure US20180186742A1-20180705-C00235
         		Example 11B Colorless Oil
    176
    Figure US20180186742A1-20180705-C00236
         		Example 12 Orange Wax
    177
    Figure US20180186742A1-20180705-C00237
         		Example 12 Brown Oil
    178
    Figure US20180186742A1-20180705-C00238
         		Example 11A Clear, Colorless Oil
    179
    Figure US20180186742A1-20180705-C00239
         		Example 11A Clear, Colorless Oil
    180
    Figure US20180186742A1-20180705-C00240
         		Example 11A Clear, Colorless Oil
    181
    Figure US20180186742A1-20180705-C00241
         		Example 11A Pale Yellow Oil
    182
    Figure US20180186742A1-20180705-C00242
         		Example 11A Clear, Colorless Oil
    183
    Figure US20180186742A1-20180705-C00243
         		Example 11A Clear, Colorless Oil
    184
    Figure US20180186742A1-20180705-C00244
         		Example 11A Clear, Colorless Oil
    185
    Figure US20180186742A1-20180705-C00245
         		Example 11A Clear, Colorless Oil
    186
    Figure US20180186742A1-20180705-C00246
         		Example 11A Clear, Colorless Oil
    187
    Figure US20180186742A1-20180705-C00247
         		Example 11A Clear, Colorless Oil
    188
    Figure US20180186742A1-20180705-C00248
         		Example 11A Clear, Colorless Oil
    189
    Figure US20180186742A1-20180705-C00249
         		Example 11A Clear, Colorless Oil
    190
    Figure US20180186742A1-20180705-C00250
         		Example 11A Clear, Colorless Oil
    191
    Figure US20180186742A1-20180705-C00251
         		Example 11A Clear, Colorless Oil
    192
    Figure US20180186742A1-20180705-C00252
         		Example 11A Clear, Colorless Oil
    193
    Figure US20180186742A1-20180705-C00253
         		Example 11B Clear, Colorless Oil
    194
    Figure US20180186742A1-20180705-C00254
         		Example 11B Clear, Colorless Oil
    195
    Figure US20180186742A1-20180705-C00255
         		Example 11B Clear, Colorless Oil
    196
    Figure US20180186742A1-20180705-C00256
         		Example 11B Clear, Colorless Oil
    197
    Figure US20180186742A1-20180705-C00257
         		Example 11B Clear, Colorless Oil
    198
    Figure US20180186742A1-20180705-C00258
         		Example 11B White Semisolid
    199
    Figure US20180186742A1-20180705-C00259
         		Example 11B Clear, Colorless Oil
    200
    Figure US20180186742A1-20180705-C00260
         		Example 11A Colorless Oil
    201
    Figure US20180186742A1-20180705-C00261
         		Example 11A Colorless Oil
    202
    Figure US20180186742A1-20180705-C00262
         		Example 11A Colorless Oil
    203
    Figure US20180186742A1-20180705-C00263
         		Example 11A Colorless Oil
    204
    Figure US20180186742A1-20180705-C00264
         		Example 11B Colorless Oil
    205
    Figure US20180186742A1-20180705-C00265
         		Example 11B Colorless Oil
    206
    Figure US20180186742A1-20180705-C00266
         		Example 11B Colorless Oil
    207
    Figure US20180186742A1-20180705-C00267
         		Example 11B Colorless Oil
    208
    Figure US20180186742A1-20180705-C00268
         		Example 14 Orange Oil
    209
    Figure US20180186742A1-20180705-C00269
         		Example 14 Orange Oil
    210
    Figure US20180186742A1-20180705-C00270
         		Example 14 Orange Foam
    211
    Figure US20180186742A1-20180705-C00271
         		Example 13 Colorless Oil
    212
    Figure US20180186742A1-20180705-C00272
         		Example 13 Colorless Oil
    213
    Figure US20180186742A1-20180705-C00273
         		Example 13 Colorless Oil
    214
    Figure US20180186742A1-20180705-C00274
         		Example 11A White Foam
    215
    Figure US20180186742A1-20180705-C00275
         		Example 11B Pale Yellow Oil
    216
    Figure US20180186742A1-20180705-C00276
         		Example 11C Clear, Colorless Oil
    217
    Figure US20180186742A1-20180705-C00277
         		Example 14 Pale Yellow Oil
    218
    Figure US20180186742A1-20180705-C00278
         		Example 13 Clear, Colorless Oil
    219
    Figure US20180186742A1-20180705-C00279
         		Example 12 Yellow Oil
    220
    Figure US20180186742A1-20180705-C00280
         		Example 11C Pale Yellow Oil
    221
    Figure US20180186742A1-20180705-C00281
         		Example 11A Pale Yellow Oil
    222
    Figure US20180186742A1-20180705-C00282
         		Example 11A Yellow Oil
    223
    Figure US20180186742A1-20180705-C00283
         		Example 11A Clear, Colorless Oil
    224
    Figure US20180186742A1-20180705-C00284
         		Example 11A Clear, Colorless Oil
    225
    Figure US20180186742A1-20180705-C00285
         		Example 11A Clear, Colorless Oil
    226
    Figure US20180186742A1-20180705-C00286
         		Example 11A Clear, Colorless Oil
    227
    Figure US20180186742A1-20180705-C00287
         		Example 11A Clear, Colorless Oil
    228
    Figure US20180186742A1-20180705-C00288
         		Example 11A Clear, Colorless Oil
    229
    Figure US20180186742A1-20180705-C00289
         		Example 11A Clear, Colorless Oil
    230
    Figure US20180186742A1-20180705-C00290
         		Example 11A Clear, Colorless Oil
    231
    Figure US20180186742A1-20180705-C00291
         		Example 11A Clear, Colorless Oil
    232
    Figure US20180186742A1-20180705-C00292
         		Example 11A Clear, Colorless Oil
    233
    Figure US20180186742A1-20180705-C00293
         		Example 11B Clear, Colorless Oil
    234
    Figure US20180186742A1-20180705-C00294
         		Example 11B Clear, Colorless Oil
    235
    Figure US20180186742A1-20180705-C00295
         		Example 11B Clear, Colorless Oil
    236
    Figure US20180186742A1-20180705-C00296
         		Example 11B Clear, Colorless Oil
    237
    Figure US20180186742A1-20180705-C00297
         		Example 11B Clear, Colorless Oil
    238
    Figure US20180186742A1-20180705-C00298
         		Example 11C Clear, Colorless Oil
    239
    Figure US20180186742A1-20180705-C00299
         		Example 11C Clear, Colorless Oil
    240
    Figure US20180186742A1-20180705-C00300
         		Example 11B Yellow Oil
    241
    Figure US20180186742A1-20180705-C00301
         		Example 11A Colorless Oil
    242
    Figure US20180186742A1-20180705-C00302
         		Example 11A Thick Oil
    243
    Figure US20180186742A1-20180705-C00303
         		Example 11A White Foam
    244
    Figure US20180186742A1-20180705-C00304
         		Example 11A Thick Oil
    245
    Figure US20180186742A1-20180705-C00305
         		Example 11C Pale Yellow Oil
    246
    Figure US20180186742A1-20180705-C00306
         		Example 11C Clear, Colorless Oil
    247
    Figure US20180186742A1-20180705-C00307
         		Example 11C Pale Yellow Oil
    248
    Figure US20180186742A1-20180705-C00308
         		Example 11C Pale Yellow Oil
    249
    Figure US20180186742A1-20180705-C00309
         		Example 11C Clear, Colorless Oil
    250
    Figure US20180186742A1-20180705-C00310
         		Example 11A Clear, Colorless Oil
    251
    Figure US20180186742A1-20180705-C00311
         		Example 11A Clear, Colorless Oil
    252
    Figure US20180186742A1-20180705-C00312
         		Example 11A Clear, Colorless Oil
    253
    Figure US20180186742A1-20180705-C00313
         		Example 11A Clear, Colorless Oil
    254
    Figure US20180186742A1-20180705-C00314
         		Example 11A Clear, Colorless Oil
    255
    Figure US20180186742A1-20180705-C00315
         		Example 11B Clear, Colorless Oil
    256
    Figure US20180186742A1-20180705-C00316
         		Example 11B Clear, Colorless Oil
    257
    Figure US20180186742A1-20180705-C00317
         		Example 11B Clear, Colorless Oil
    258
    Figure US20180186742A1-20180705-C00318
         		Example 11B Clear, Colorless Oil
    259
    Figure US20180186742A1-20180705-C00319
         		Example 11B Clear, Colorless Oil
    260
    Figure US20180186742A1-20180705-C00320
         		Example 11B Clear, Colorless Oil
    261
    Figure US20180186742A1-20180705-C00321
         		Example 11A Colorless Oil
    262
    Figure US20180186742A1-20180705-C00322
         		Example 11A Colorless Oil
    263
    Figure US20180186742A1-20180705-C00323
         		Example 11B Yellow Oil
    264
    Figure US20180186742A1-20180705-C00324
         		Example 11B Yellow Oil
    265
    Figure US20180186742A1-20180705-C00325
         		Example 10 Step 1 Clear, Colorless Oil
    266
    Figure US20180186742A1-20180705-C00326
         		Example 10 Step 1 Clear, Colorless Oil
    267
    Figure US20180186742A1-20180705-C00327
         		Example 10 Step 1 Clear, Colorless Oil
    268
    Figure US20180186742A1-20180705-C00328
         		Example 10 Step 1 White Semisolid
    269
    Figure US20180186742A1-20180705-C00329
         		Example 10 Step 1 White Solid
    270
    Figure US20180186742A1-20180705-C00330
         		Example 10 Step 1 White Solid
    271
    Figure US20180186742A1-20180705-C00331
         		Example 10 Step 1 White Solid
    272
    Figure US20180186742A1-20180705-C00332
         		Example 10 Step 1 White Solid
    273
    Figure US20180186742A1-20180705-C00333
         		Example 10 Step 1 White Solid
    274
    Figure US20180186742A1-20180705-C00334
         		Example 10 Step 1 White Solid
    275
    Figure US20180186742A1-20180705-C00335
         		Example 10 Step 1 White Solid
    276
    Figure US20180186742A1-20180705-C00336
         		Example 10 Step 1 Thick Oil
    277
    Figure US20180186742A1-20180705-C00337
         		Example 10 Step 1 Thick Oil
    278
    Figure US20180186742A1-20180705-C00338
         		Example 10 Step 1 Thick Oil
    279
    Figure US20180186742A1-20180705-C00339
         		Example 10 Step 1 Thick Oil
    280
    Figure US20180186742A1-20180705-C00340
         		Example 10 Step 1 Thick Oil
    281
    Figure US20180186742A1-20180705-C00341
         		Example 10 Step 1 Thick Oil
    282
    Figure US20180186742A1-20180705-C00342
         		Example 10 Step 1 Yellow Oil
    283
    Figure US20180186742A1-20180705-C00343
         		Example 10 Step 1 Colorless Semi-Solid
    284
    Figure US20180186742A1-20180705-C00344
         		Example 10 Step 1 Yellow Oil
    285
    Figure US20180186742A1-20180705-C00345
         		Example 10 Step 1 Yellow Oil
    286
    Figure US20180186742A1-20180705-C00346
         		Example 10 Step 1 Colorless Oil
    287
    Figure US20180186742A1-20180705-C00347
         		Example 10 Step 1 Residue
    288
    Figure US20180186742A1-20180705-C00348
         		Example 1D Example 2B Example 4A Example 4B Example 7 Example 8 Clear, Colorless Oil
    289
    Figure US20180186742A1-20180705-C00349
         		Example 1D Example 2B Example 4A Example 4B Example 7 Example 8 Clear, Colorless Oil
    290
    Figure US20180186742A1-20180705-C00350
         		Example 1D Example 2B Example 4A Example 4B Example 7 Example 8 White Semisolid
    291
    Figure US20180186742A1-20180705-C00351
         		Example 1D Example 2B Example 4A Example 4B Example 7 Example 8 Clear, Colorless Oil
    292
    Figure US20180186742A1-20180705-C00352
         		Example 6A Example 7 Example 8 Colorless Oil
    293
    Figure US20180186742A1-20180705-C00353
         		Example 6A Example 7 Example 8 Colorless Oil
    294
    Figure US20180186742A1-20180705-C00354
         		Example 6A Example 7 Example 8 Colorless Oil
    295
    Figure US20180186742A1-20180705-C00355
         		Example 6A Example 7 Example 8 Colorless Oil
    296
    Figure US20180186742A1-20180705-C00356
         		Example 6A Example 7 Example 8 Colorless Oil
    297
    Figure US20180186742A1-20180705-C00357
         		Example 6A Example 7 Example 8 Colorless Oil
    298
    Figure US20180186742A1-20180705-C00358
         		Example 6A Example 7 Example 8 Colorless Oil
    299
    Figure US20180186742A1-20180705-C00359
         		Example 6A Example 7 Example 8 Oil
    300
    Figure US20180186742A1-20180705-C00360
         		Example 6A Example 7 Example 8 Oil
    301
    Figure US20180186742A1-20180705-C00361
         		Example 6A Example 7 Example 8 Oil
    302
    Figure US20180186742A1-20180705-C00362
         		Example 6A Example 7 Example 8 Colorless Oil
    303
    Figure US20180186742A1-20180705-C00363
         		Example 6A Example 7 Example 8 Oil
    304
    Figure US20180186742A1-20180705-C00364
         		Example 6A Example 7 Example 8 Oil
    305
    Figure US20180186742A1-20180705-C00365
         		Example 6 Steps 2A, 6, 7, 4, 5 Example 7 Example 8 Colorless Oil
    306
    Figure US20180186742A1-20180705-C00366
         		Example 6 Steps 2A, 6, 7, 4, 5 Example 7 Example 8 Colorless Oil
    307
    Figure US20180186742A1-20180705-C00367
         		Example 6 Steps 2A, 6, 7, 4, 5 Example 7 Example 8 White Wax
    308
    Figure US20180186742A1-20180705-C00368
         		Example 6 Steps 2A, 6, 7, 4, 5 Example 7 Example 8 Colorless Oil
    309
    Figure US20180186742A1-20180705-C00369
         		Example 6 Steps 1, 2, 6, 7, 4, 5 Example 8 Colorless Oil
    310
    Figure US20180186742A1-20180705-C00370
         		Example 1E Example 2B Example 3B Example 7 Example 8 Residue
    311
    Figure US20180186742A1-20180705-C00371
         		Example 1E Example 2B Example 3B Example 7 Example 8 Residue
    312
    Figure US20180186742A1-20180705-C00372
         		Example 6A Example 7 Example 8 Residue
    313
    Figure US20180186742A1-20180705-C00373
         		Example 6A Example 7 Example 8 Residue
    314
    Figure US20180186742A1-20180705-C00374
         		Example 6A Example 7 Example 8 Residue
    315
    Figure US20180186742A1-20180705-C00375
         		Example 6A Example 7 Example 8 Residue
    316
    Figure US20180186742A1-20180705-C00376
         		Example 6A Example 7 Example 8 Residue
    317
    Figure US20180186742A1-20180705-C00377
         		Example 10 Step 2 Clear, Colorless Oil
    318
    Figure US20180186742A1-20180705-C00378
         		Example 10 Step 2 Clear, Colorless Oil
    319
    Figure US20180186742A1-20180705-C00379
         		Example 10 Step 2 Clear, Colorless Oil
    320
    Figure US20180186742A1-20180705-C00380
         		Example 10 Step 2 Clear, Colorless Oil
    321
    Figure US20180186742A1-20180705-C00381
         		Example 10 Step 2 Colorless Oil
    322
    Figure US20180186742A1-20180705-C00382
         		Example 10 Step 2 Colorless Oil
    323
    Figure US20180186742A1-20180705-C00383
         		Example 10 Step 2 Colorless Oil
    324
    Figure US20180186742A1-20180705-C00384
         		Example 10 Step 2 Colorless Oil
    325
    Figure US20180186742A1-20180705-C00385
         		Example 10 Step 2 Colorless Oil
    326
    Figure US20180186742A1-20180705-C00386
         		Example 10 Step 2 Colorless Oil
    327
    Figure US20180186742A1-20180705-C00387
         		Example 10 Step 2 Off-White Wax
    328
    Figure US20180186742A1-20180705-C00388
         		Example 10 Step 2 White Foam
    329
    Figure US20180186742A1-20180705-C00389
         		Example 10 Step 2 White Foam
    330
    Figure US20180186742A1-20180705-C00390
         		Example 10 Step 2 Thick Oil
    331
    Figure US20180186742A1-20180705-C00391
         		Example 10 Step 2 Thick Oil
    332
    Figure US20180186742A1-20180705-C00392
         		Example 10 Step 2 Thick Oil
    333
    Figure US20180186742A1-20180705-C00393
         		Example 10 Step 2 Thick Oil
    334
    Figure US20180186742A1-20180705-C00394
         		Example 10 Step 2 Yellow Oil
    335
    Figure US20180186742A1-20180705-C00395
         		Example 10 Step 2 Yellow Oil
    336
    Figure US20180186742A1-20180705-C00396
         		Example 10 Step 2 Yellow Oil
    337
    Figure US20180186742A1-20180705-C00397
         		Example 10 Step 2 Colorless Oil
    338
    Figure US20180186742A1-20180705-C00398
         		Example 10 Step 2 Colorless Oil
    339
    Figure US20180186742A1-20180705-C00399
         		Example 10 Step 2 Residue
    340
    Figure US20180186742A1-20180705-C00400
         		Example 10 Step 2 Residue
    341
    Figure US20180186742A1-20180705-C00401
         		Example 10 Step 2 Residue
    342
    Figure US20180186742A1-20180705-C00402
         		Example 10 Step 2 Residue
    343
    Figure US20180186742A1-20180705-C00403
         		Example 10 Step 2 Residue
    344
    Figure US20180186742A1-20180705-C00404
         		Example 10 Step 2 Residue
    345
    Figure US20180186742A1-20180705-C00405
         		Example 10 Step 2 Residue
    346
    Figure US20180186742A1-20180705-C00406
         		Example 11A Clear, Colorless Oil
    347
    Figure US20180186742A1-20180705-C00407
         		Example 11A Clear, Colorless Oil
    348
    Figure US20180186742A1-20180705-C00408
         		Example 11A Clear, Colorless Oil
    349
    Figure US20180186742A1-20180705-C00409
         		Example 11A Clear, Colorless Oil
    350
    Figure US20180186742A1-20180705-C00410
         		Example 11C Clear, Colorless Oil
    351
    Figure US20180186742A1-20180705-C00411
         		Example 11C Clear, Colorless Oil
    352
    Figure US20180186742A1-20180705-C00412
         		Example 11C Clear, Colorless Oil
    353
    Figure US20180186742A1-20180705-C00413
         		Example 11C Clear, Colorless Oil
    354
    Figure US20180186742A1-20180705-C00414
         		Example 11C Clear, Colorless Oil
    355
    Figure US20180186742A1-20180705-C00415
         		Example 11C Pale Yellow Oil
    356
    Figure US20180186742A1-20180705-C00416
         		Example 11C Clear, Colorless Oil
    357
    Figure US20180186742A1-20180705-C00417
         		Example 11C Clear, Colorless Oil
    358
    Figure US20180186742A1-20180705-C00418
         		Example 11A White Foam
    359
    Figure US20180186742A1-20180705-C00419
         		Example 11A White Foam
    360
    Figure US20180186742A1-20180705-C00420
         		Example 11A Colorless Oil
    361
    Figure US20180186742A1-20180705-C00421
         		Example 11A Colorless Oil
    362
    Figure US20180186742A1-20180705-C00422
         		Example 11A Colorless Oil
    363
    Figure US20180186742A1-20180705-C00423
         		Example 11A Colorless Oil
    364
    Figure US20180186742A1-20180705-C00424
         		Example 11A Colorless Oil
    365
    Figure US20180186742A1-20180705-C00425
         		Example 11A White Foam
    366
    Figure US20180186742A1-20180705-C00426
         		Example 11A White Foam
    367
    Figure US20180186742A1-20180705-C00427
         		Example 11A White Foam
    368
    Figure US20180186742A1-20180705-C00428
         		Example 11A White Foam
    369
    Figure US20180186742A1-20180705-C00429
         		Example 11A Thick Oil
    370
    Figure US20180186742A1-20180705-C00430
         		Example 11A Thick Oil
    371
    Figure US20180186742A1-20180705-C00431
         		Example 11C White Foam
    372
    Figure US20180186742A1-20180705-C00432
         		Example 11C Thick Oil
    373
    Figure US20180186742A1-20180705-C00433
         		Example 11C Colorless Oil
    374
    Figure US20180186742A1-20180705-C00434
         		Example 11C Thick Oil
    375
    Figure US20180186742A1-20180705-C00435
         		Example 11C Colorless Oil
    376
    Figure US20180186742A1-20180705-C00436
         		Example 11A Colorless Oil
    377
    Figure US20180186742A1-20180705-C00437
         		Example 11A Colorless Oil
    378
    Figure US20180186742A1-20180705-C00438
         		Example 11B Yellow Oil
    379
    Figure US20180186742A1-20180705-C00439
         		Example 11B Yellow Oil
    380
    Figure US20180186742A1-20180705-C00440
         		Example 11A Glassy White Solid
    381
    Figure US20180186742A1-20180705-C00441
         		Example 11A Colorless Oil
    382
    Figure US20180186742A1-20180705-C00442
         		Example 11B Yellow Oil
    383
    Figure US20180186742A1-20180705-C00443
         		Example 11A Colorless Oil
    384
    Figure US20180186742A1-20180705-C00444
         		Example 11A Residue
    385
    Figure US20180186742A1-20180705-C00445
         		Example 11A Residue
    386
    Figure US20180186742A1-20180705-C00446
         		Example 11C Residue
    387
    Figure US20180186742A1-20180705-C00447
         		Example 11C Residue
    388
    Figure US20180186742A1-20180705-C00448
         		Example 11A Residue
    389
    Figure US20180186742A1-20180705-C00449
         		Example 11A Residue
    390
    Figure US20180186742A1-20180705-C00450
         		Example 11A Residue
    391
    Figure US20180186742A1-20180705-C00451
         		Example 11A Residue
    392
    Figure US20180186742A1-20180705-C00452
         		Example 11A Residue
    *Cmpd. No.—Compound Number
  • TABLE 2
    Analytical Data
    Melting
    Cmpd. Point
    No. (° C.) IR (cm−1) MASS SPEC NMR
    1 ESIMS m/z 350.5 1H NMR (400 MHz, CDCl3) δ
    ([M + H]+) 7.31-7.12 (m, 5H), 5.50-5.38 (m, 1H),
    5.02 (d, J = 7.8 Hz, 1H), 4.29-4.17 (m, 1H),
    2.36 (dd, J = 8.4, 5.6 Hz, 1H),
    2.13-1.96 (m, 1H), 1.44 (s, 9H), 1.14 (d, J = 7.2 Hz,
    3H), 1.11 (d, J = 6.3 Hz, 3H),
    0.94 (d, J = 6.6 Hz, 3H), 0.72 (d, J = 6.7 Hz,
    3H).
    13C NMR (101 MHz, CDCl3) δ 172.83,
    157.91, 139.85, 129.62, 127.92, 126.50,
    79.70, 71.92, 58.00, 49.41, 29.18,
    28.33, 21.29, 20.19, 18.97, 18.54.
    2 ESIMS m/z 376.6 1H NMR (400 MHz, CDCl3) δ
    ([M + H]+) 7.38-7.14 (m, 5H), 5.33 (qd, J = 6.4, 3.9 Hz,
    1H), 5.07 (d, J = 8.0 Hz, 1H),
    4.40-4.23 (m, 1H), 2.41 (dd, J = 10.3, 4.0 Hz,
    1H), 2.29-2.13 (m, 1H),
    1.92-1.79 (m, 1H), 1.70-1.61 (m, 1H),
    1.59-1.48 (m, 2H), 1.45 (s, 9H),
    1.45-1.32 (m, 2H), 1.31 (d, J = 7.2 Hz, 3H),
    1.27-1.13 (m, 1H), 1.06 (d, J = 6.3 Hz, 3H),
    1.04-0.88 (m, 1H).
    13C NMR (101 MHz, CDCl3) δ 172.79,
    155.00, 140.76, 129.49, 127.96, 126.49,
    79.75, 73.15, 56.65, 49.52, 42.13,
    31.61, 31.47, 28.34, 25.12, 24.53,
    18.81.
    3 ESIMS m/z 350.5 1H NMR (300 MHz, CDCl3) δ
    ([M + H]+) 7.36-7.20 (m, 3H), 7.16-7.03 (m, 2H),
    5.40 (dq, J = 8.8, 6.2 Hz, 1H), 5.09 (d, J = 8.0 Hz,
    1H), 4.39-4.15 (m, 1H),
    2.70 (dd, J = 8.9, 6.3 Hz, 1H),
    2.20-2.01 (m, 1H), 1.45 (s, 9H), 1.39 (d, J = 7.2 Hz,
    3H), 1.08 (d, J = 6.2 Hz, 3H),
    0.86 (d, J = 6.8 Hz, 3H), 0.76 (d, J = 6.8 Hz,
    3H).
    4 ESIMS m/z 365 ([M + H]+) 1H NMR (400 MHz, CDCl3) δ
    7.18-7.02 (m, 4H), 5.36-5.22 (m, 1H),
    5.07 (s, 1H), 4.36-4.19 (m, 1H), 2.33 (s,
    3H), 1.97 (dd, J = 10.0, 7.1 Hz, 1H),
    1.45 (s, 9H), 1.36 (d, J = 7.2 Hz, 3H),
    1.15 (d, J = 6.3 Hz, 3H), 1.12-1.00 (m,
    1H), 0.73-0.57 (m, 1H),
    0.47-0.27 (m, 2H), −0.01-−0.15 (m, 1H).
    13C NMR (101 MHz, CDCl3) δ 172.79,
    155.03, 138.55, 136.15, 128.94, 128.28,
    75.73, 68.48, 55.27, 49.50, 28.35,
    21.01, 18.87, 18.19, 13.04, 6.90, 2.83.
    5 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ
    film) 3358, calcd for C21H33NNaO4, 7.13-7.05 (m, 2H), 7.00-6.94 (m, 2H),
    2976, 386.2302; found, 386.2306 5.38 (dq, J = 8.9, 6.3 Hz, 1H), 5.13 (d, J = 7.9 Hz,
    1715, 1H), 4.28 (p, J = 7.5 Hz, 1H),
    1514, 2.66 (dd, J = 8.9, 6.2 Hz, 1H), 2.33 (s,
    1366, 3H), 2.09 (h, J = 6.8 Hz, 1H), 1.45 (s,
    1167, 1052 cm−1 9H), 1.39 (d, J = 7.2 Hz, 3H), 1.07 (d, J = 6.3 Hz,
    3H), 0.85 (d, J = 6.8 Hz, 3H),
    0.76 (d, J = 6.7 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 172.82,
    155.03, 136.11, 135.47, 129.67, 128.65,
    79.66, 72.59, 56.29, 49.56, 28.36,
    28.16, 21.39, 21.00, 18.81, 18.42,
    17.98.
    6 ESIMS m/z 366 ([M + H]+) 1H NMR (400 MHz, CDCl3) δ
    7.22-7.12 (m, 2H), 7.03-6.94 (m, 2H),
    5.32-5.20 (m, 1H), 5.04 (d, J = 8.0 Hz, 1H),
    4.40-4.22 (m, 1H), 2.01 (dd, J = 10.1,
    6.7 Hz, 1H), 1.45 (s, 9H), 1.34 (d, J = 7.2 Hz,
    3H), 1.16 (d, J = 6.4 Hz, 3H),
    1.13-1.07 (m, 1H), 0.76-0.63 (m,
    1H), 0.46-0.31 (m, 2H),
    −0.03-−0.10 (m, 1H).
    19F NMR (376 MHz, CDCl3) δ −116.47.
    7 ESIMS m/z 378 ([M + H]+) 1H NMR (400 MHz, CDCl3) δ
    7.32-7.02 (m, 5H), 5.48-5.34 (m, 1H),
    5.10 (bs, 1H), 4.35-4.21 (m, 1H), 2.94 (dd,
    J = 8.6, 6.3 Hz, 1H), 1.64-1.55 (m,
    1H), 1.45 (s, 9H), 1.66-1.54 (m, 2H),
    1.30-1.12 (m, 2H), 1.39 (d, J = 7.2 Hz,
    3H), 1.08 (d, J = 6.3 Hz, 3H),
    0.96 (t, J = 7.4 Hz, 3H), 0.78 (t, J = 7.3 Hz,
    3H).
    13C NMR (101 MHz, CDCl3) δ 172.72,
    154.99, 138.99, 129.76, 127.94, 126.61,
    72.12, 51.91, 49.49, 41.54, 28.35,
    22.30, 19.03, 17.95, 11.68, 11.13.
    8 ESIMS m/z 376 ([M + H]+) 1H NMR (400 MHz, CDCl3) δ
    7.36-7.04 (m, 5H), 5.34-5.26 (m, 1H),
    5.14-4.97 (m, 1H), 4.28 (m, 1H), 2.76 (dd,
    J = 9.9, 6.1 Hz, 1H), 2.35-2.10 (m,
    2H), 1.96-1.83 (m, 2H), 1.45 (s, 9H),
    1.36 (d, J = 7.2 Hz, 3H), 1.33-0.98 m,
    5H), 1.10 (d, J = 6.5 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 172.62,
    140.75, 140.10, 129.62, 127.90, 126.55,
    74.02, 55.12, 41.77, 31.46, 31.26,
    28.35, 25.30, 24.45, 18.88, 16.30.
    9 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.27 (q,
    film) 3358, calcd for C21H32FNNaO4, J = 3.3 Hz, 1H), 6.91-6.82 (m, 2H),
    2975, 404.2208; found, 404.2202 5.45-5.33 (m, 1H), 5.03 (d, J = 7.9 Hz,
    1712, 1H), 4.35-4.18 (m, 1H), 2.69 (dd,
    1498, J = 9.2, 5.0 Hz, 1H), 2.28 (s, 3H),
    1165, 862 cm−1 2.02 (dp, J = 9.1, 6.7 Hz, 1H), 1.44 (s, 9H),
    1.34-1.17 (m, 4H), 1.06 (d, J = 6.3 Hz,
    3H), 0.98 (d, J = 6.5 Hz, 3H),
    0.70 (d, J = 6.7 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 172.75,
    160.98 (d, J = 243.9 Hz), 155.01,
    139.40 (d, J = 7.3 Hz), 134.70 (d, J = 2.9 Hz),
    129.37 (d, J = 8.1 Hz),
    116.46 (d, J = 20.4 Hz), 112.69 (d, J = 20.5 Hz),
    79.81, 72.22, 50.66, 49.49, 30.41,
    28.34, 20.99, 20.73 (d, J = 1.5 Hz),
    20.44, 18.65, 18.40.
    19F NMR (376 MHz, CDCl3) δ −117.64.
    10 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.31 (dd,
    film) 3358, calcd for C23H36FNNaO4, J = 8.4, 6.1 Hz, 1H), 6.86 (dd, J = 9.2,
    2966, 432.2521; found, 432.2515 7.4 Hz, 2H), 5.36 (qd, J = 6.3, 4.5 Hz,
    1715, 1H), 5.05 (d, J = 8.0 Hz, 1H),
    1498, 1167 cm−1 4.39-4.21 (m, 1H), 2.91 (dd, J = 10.0, 4.3 Hz,
    1H), 2.30 (s, 3H), 1.74 (ddq, J = 14.1,
    10.2, 4.6 Hz, 1H), 1.52 (ddt, J = 14.5,
    7.4, 4.0 Hz, 1H), 1.44 (d, J = 2.1 Hz,
    9H), 1.42-1.34 (m, 2H),
    1.34-1.28 (m, 2H), 1.26-1.03 (m, 2H),
    1.01 (d, J = 6.2 Hz, 3H), 0.88 (t, J = 7.4 Hz,
    3H), 0.76 (q, J = 7.7 Hz, 1H), 0.70 (t, J = 7.4 Hz,
    2H).
    13C NMR (101 MHz, CDCl3) δ 172.82,
    160.98 (d, J = 244.1 Hz), 154.98,
    139.43 (d, J = 7.3 Hz), 134.74 (d, J = 3.3 Hz),
    129.78 (d, J = 8.0 Hz),
    116.45 (d, J = 20.6 Hz), 112.75 (d, J = 20.7 Hz),
    79.82, 71.95, 49.49, 45.70, 41.63,
    28.36, 21.76, 21.12, 20.61, 18.83,
    18.39, 10.77, 9.56.
    19F NMR (376 MHz, CDCl3) δ −117.60.
    11 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.30 (dd,
    film) 3357, calcd for C23H34FNNaO4, J = 8.5, 6.1 Hz, 1H), 6.86 (t, J = 8.2 Hz,
    2954, 430.2364; found, 430.2361 2H), 5.31 (td, J = 6.5, 4.4 Hz, 1H),
    1711, 5.06 (d, J = 7.8 Hz, 1H), 4.39-4.20 (m,
    1497, 1H), 2.80 (dd, J = 10.3, 4.3 Hz, 1H),
    1164, 860, 2.30 (s, 3H), 2.26-2.10 (m, 1H),
    732 cm−1 1.88 (dtd, J = 11.0, 6.9, 3.3 Hz, 1H),
    1.74-1.48 (m, 2H), 1.48-1.33 (m, 11H),
    1.33-1.13 (m, 4H), 1.11-1.00 (m,
    4H), 0.96-0.81 (m, 1H).
    13C NMR (101 MHz, CDCl3) δ 172.69,
    160.94 (d, J = 243.9 Hz), 155.01,
    138.84 (d, J = 7.2 Hz), 135.28 (d, J = 3.1 Hz),
    129.66 (d, J = 8.1 Hz),
    116.43 (d, J = 20.2 Hz), 112.70 (d, J = 20.4 Hz),
    79.82, 73.45, 49.55, 49.41, 42.93,
    31.61, 31.35, 28.35, 25.13, 24.42,
    20.61, 18.72, 18.22.
    19F NMR (376 MHz, CDCl3) δ −117.66.
    12 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ
    film) 3357, calcd for C24H36FNNaO4, 7.32-7.26 (m, 1H), 6.90-6.81 (m, 2H),
    2928, 444.2521; found, 444.2514 5.47-5.35 (m, 1H), 5.07 (d, J = 7.9 Hz,
    1709, 1H), 4.31 (q, J = 7.4 Hz, 1H), 2.76 (dd,
    1497, J = 9.2, 4.9 Hz, 1H), 2.27 (s, 3H),
    1206, 860, 1.84 (dt, J = 12.6, 3.2 Hz, 1H),
    731 cm−1 1.79-1.53 (m, 3H), 1.45 (s, 9H), 1.41-1.30 (m,
    1H), 1.30-1.25 (m, 3H),
    1.25-0.87 (m, 8H), 0.80 (qt, J = 12.1, 6.1 Hz, 1H).
    13C NMR (101 MHz, CDCl3) δ 172.81,
    160.94 (d, J = 243.9 Hz), 154.99,
    139.46 (d, J = 7.2 Hz), 134.70 (d, J = 3.2 Hz),
    129.43 (d, J = 7.9 Hz),
    116.39 (d, J = 20.5 Hz), 112.73 (d, J = 20.5 Hz),
    79.78, 71.54, 49.67, 49.44, 40.28,
    31.31, 30.73, 28.38, 26.45, 26.40,
    26.34, 20.73, 18.79, 18.29.
    19F NMR (376 MHz, CDCl3) δ −117.65.
    13 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.27 (d,
    film) 3357, calcd for C22H34FNNaO4, J = 6.3 Hz, 1H), 6.91-6.80 (m, 2H),
    2971, 418.2364; found, 418.2360 5.50-5.32 (m, 1H), 5.03 (s, 1H),
    1712, 4.27 (dt, J = 13.6, 7.2 Hz, 1H), 2.79 (ddd, J = 43.4,
    1498, 9.2, 5.1 Hz, 1H), 2.28 (d, J = 1.8 Hz,
    1164, 860 cm−1 3H), 1.81 (dtdd, J = 19.1, 9.5, 6.3,
    3.1 Hz, 1H), 1.68-1.50 (m, 1H),
    1.44 (d, J = 3.1 Hz, 9H), 1.36-1.13 (m,
    3H), 1.13-0.57 (m, 10H).
    19F NMR (376 MHz, CDCl3) δ −117.61,
    −117.68.
    14 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.09 (dd,
    film) 3355, calcd for C22H32FNNaO4, J = 8.3, 6.0 Hz, 1H), 6.82 (t, J = 8.4 Hz,
    2976, 416.2208; found, 416.2203 2H), 5.11 (t, J = 6.4 Hz, 1H), 4.95 (d, J = 8.0 Hz,
    1713 1H), 4.17 (t, J = 7.5 Hz, 1H),
    1498, 1166 cm−1 3.02 (dd, J = 10.4, 6.7 Hz, 1H), 2.65 (q,
    J = 8.6, 7.8 Hz, 1H), 2.35 (s, 3H),
    2.15 (dp, J = 7.4, 5.1, 4.1 Hz, 1H),
    1.92-1.75 (m, 2H), 1.75-1.55 (m, 2H),
    1.49-1.32 (m, 10H), 1.17 (d, J = 6.3 Hz,
    3H), 1.06 (d, J = 7.2 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −117.57.
    15 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.09 (dd,
    film) 3356, calcd for C23H34FNNaO4, J = 9.5, 5.9 Hz, 1H), 6.91-6.82 (m,
    2954, 430.2364; found, 430.2360 2H), 5.26 (p, J = 6.5 Hz, 1H), 5.03 (s,
    1711, 1H), 4.35-4.19 (m, 1H), 3.10 (t, J = 8.3 Hz,
    1497, 1H), 2.30 (s, 3H),
    1163, 2.21-2.06 (m, 1H), 1.85 (dtd, J = 11.2, 7.3, 3.5 Hz,
    1056, 860, 1H), 1.72-1.46 (m, 2H), 1.44 (s,
    732 cm−1 9H), 1.42-1.14 (m, 6H), 1.08 (d, J = 6.4 Hz,
    3H), 1.03 (dd, J = 9.1, 6.4 Hz,
    1H), 0.91 (dtt, J = 15.2, 7.8, 4.4 Hz,
    1H).
    19F NMR (376 MHz, CDCl3) δ −117.51.
    16 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.05 (dd,
    film) 2928, calcd for C24H36FNNaO4, J = 8.3, 5.9 Hz, 1H), 6.91-6.81 (m,
    1714, 444.2521; found, 444.2516 2H), 5.36 (dq, J = 9.2, 6.3 Hz, 1H),
    1497, 5.08 (d, J = 7.8 Hz, 1H), 4.31 (d, J = 9.1 Hz,
    1450, 1H), 3.11 (dd, J = 9.2, 6.0 Hz, 1H),
    1366, 2.31 (s, 3H), 1.82-1.50 (m, 6H), 1.45 (s,
    1166, 9H), 1.40 (d, J = 7.1 Hz, 3H),
    1029, 861, 1.35-1.06 (m, 2H), 1.02 (d, J = 6.3 Hz, 3H),
    733 cm−1 1.00-0.77 (m, 3H).
    19F NMR (376 MHz, CDCl3) δ −117.40.
    17 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.05 (dd,
    film) 3355, calcd for C21H32FNNaO4, J = 8.5, 6.0 Hz, 1H), 6.87 (ddt, J = 11.6,
    2965, 404.2208; found, 404.2201 8.3, 4.1 Hz, 2H), 5.33 (dq, J = 9.1, 6.2 Hz,
    1714, 1H), 5.05 (d, J = 8.1 Hz, 1H),
    1499, 4.28 (d, J = 7.6 Hz, 1H), 3.08 (dd, J = 9.2,
    1366, 6.2 Hz, 1H), 2.32 (s, 3H),
    1167, 2.18-2.06 (m, 1H), 1.45 (s, 9H), 1.39 (d, J = 7.2 Hz,
    1052, 735 cm−1 3H), 1.03 (d, J = 6.2 Hz, 3H),
    0.85 (d, J = 6.8 Hz, 3H), 0.78 (d, J = 6.9 Hz,
    3H).
    19F NMR (376 MHz, CDCl3) δ −117.34.
    18 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ
    film) 2963, calcd for C23H36FNNaO4, 7.34 (dd, J = 9.7, 6.0 Hz, 1H), 6.86 (ddd, J = 8.3,
    1714, 432.2521; found, 432.2516 5.8, 2.9 Hz, 2H), 5.38 (dq, J = 8.1,
    1497, 6.3 Hz, 1H), 5.05 (d, J = 8.2 Hz, 1H),
    1453, 4.27 (qd, J = 6.4, 3.6 Hz, 1H), 2.74 (dd,
    1367, J = 10.2, 3.6 Hz, 1H), 2.28 (s, 3H),
    1166, 1.88 (ddq, J = 10.1, 6.2, 4.0, 3.2 Hz, 1H),
    1055, 860 cm−1 1.69-1.48 (m, 1H), 1.44 (s, 9H),
    1.36 (d, J = 7.2 Hz, 1H), 1.35-1.11 (m,
    2H), 1.10-0.83 (m, 6H), 0.74 (dt, J = 25.4,
    7.3 Hz, 6H).
    19F NMR (376 MHz, CDCl3) δ −117.41,
    −118.02.
    19 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.33 (dd,
    film) 3442, calcd for C22H34FNNaO4, J = 9.5, 6.0 Hz, 1H), 6.86 (ddt, J = 12.5,
    2965, 418.2364; found, 418.2360 8.4, 3.6 Hz, 2H), 5.36 (ddq, J = 15.7,
    1713, 9.5, 6.2 Hz, 1H), 5.08 (s, 1H), 4.28 (p, J = 6.3 Hz,
    1497, 1H), 2.28 (d, J = 3.9 Hz, 3H),
    1453, 2.04-1.57 (m, 1H), 1.45 (d, J = 1.9 Hz,
    1367, 9H), 1.42-1.11 (m, 2H),
    1165, 1.09-0.99 (m, 3H), 0.99-0.83 (m, 6H),
    1055, 954, 0.83-0.74 (m, 3H), 0.68 (d, J = 6.8 Hz,
    860 cm−1 1H).
    19F NMR (376 MHz, CDCl3) δ −117.94,
    −118.00.
    20 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.01 (dd,
    film) 3356, calcd for C22H32FNNaO4, J = 8.4, 5.9 Hz, 1H), 6.85 (ddt, J = 11.3,
    2977, 416.2208; found, 416.2202 8.3, 4.1 Hz, 2H), 5.08 (dd, J = 14.2, 7.6 Hz,
    1708, 2H), 4.36-4.05 (m, 1H),
    1498, 3.23-3.03 (m, 1H), 2.70 (tt, J = 19.6, 9.3 Hz,
    1163, 909 1H), 2.35 (s, 3H), 2.19-2.04 (m, 2H),
    731 cm−1 1.94-1.72 (m, 2H), 1.72-1.54 (m,
    1H), 1.44 (s, 9H), 1.37 (d, J = 7.1 Hz,
    4H), 1.05 (d, J = 6.3 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −117.31.
    21 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.33 (dd,
    film) 3355, calcd for C23H34FNNaO4, J = 8.4, 6.1 Hz, 1H), 6.86 (tt, J = 9.8,
    2954, 430.2364; found, 430.2360 2.8 Hz, 2H), 5.30 (qd, J = 6.1, 3.3 Hz,
    1711, 1H), 5.05 (d, J = 7.7 Hz, 1H),
    1497, 4.42-4.22 (m, 1H), 2.77 (dd, J = 10.8, 3.4 Hz,
    1163, 1H), 2.30 (s, 3H), 2.28-2.10 (m,
    1066, 2H), 1.93 (dtd, J = 11.5, 7.3, 3.4 Hz,
    1019, 860, 1H), 1.75-1.46 (m, 2H),
    733 cm−1 1.46-1.42 (m, 10H), 1.42-1.16 (m, 5H), 1.02 (d,
    J = 6.4 Hz, 3H), 0.86 (tdd, J = 12.0, 8.6,
    6.0 Hz, 1H).
    13C NMR (101 MHz, CDCl3) δ 172.72,
    160.92 (d, J = 243.9 Hz), 155.10,
    138.76 (d, J = 7.3 Hz), 135.17 (d, J = 3.3 Hz),
    129.94 (d, J = 7.8 Hz),
    116.33 (d, J = 20.5 Hz), 112.67 (d, J = 20.6 Hz),
    79.77, 73.09, 49.53, 42.66, 31.71,
    28.31, 25.19, 24.50, 20.59, 18.55,
    17.80.
    19F NMR (376 MHz, CDCl3) δ −117.74.
    22 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.33 (dd,
    film) 3357, calcd for C24H36FNNaO4, J = 8.6, 6.1 Hz, 1H), 6.86 (ddt, J = 9.8,
    2928, 444.2521; found, 444.2515 7.1, 4.0 Hz, 2H), 5.47-5.36 (m, 1H),
    1711, 5.10-4.94 (m, 1H), 4.37-4.21 (m,
    1497, 1H), 2.72 (dd, J = 9.9, 4.0 Hz, 1H),
    1165, 860, 2.27 (s, 3H), 1.93 (d, J = 12.7 Hz, 1H),
    733 cm−1 1.80-1.48 (m, 4H), 1.44 (s, 10H), 1.29 (dd,
    J = 18.3, 7.7 Hz, 4H), 1.16-0.87 (m,
    6H), 0.87-0.68 (m, 1H).
    13C NMR (101 MHz, CDCl3) δ 172.73,
    160.93 (d, J = 244.0 Hz), 155.06,
    139.41 (d, J = 7.3 Hz), 134.65 (d, J = 3.3 Hz),
    129.67 (d, J = 7.8 Hz),
    116.33 (d, J = 20.6 Hz), 112.74 (d, J = 20.5 Hz),
    79.80, 71.03, 49.68, 39.93, 31.35,
    28.35, 26.51, 26.37, 26.28, 20.74,
    18.54, 17.99.
    19F NMR (376 MHz, CDCl3) δ −117.76.
    23 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.32 (dd,
    film) 3356, calcd for C21H32FNNaO4, J = 8.4, 6.1 Hz, 1H), 6.92-6.82 (m,
    2975, 404.2208; found, 404.2202 2H), 5.40 (qd, J = 6.3, 3.9 Hz, 1H),
    1712, 5.00 (d, J = 7.8 Hz, 1H), 4.41-4.18 (m,
    1498, 1H), 2.63 (dd, J = 9.5, 4.3 Hz, 1H),
    1366, 2.28 (s, 3H), 2.03 (dp, J = 9.7, 6.4 Hz, 1H),
    1165, 1.44 (d, J = 3.7 Hz, 9H),
    1063, 862, 1.41-1.12 (m, 3H), 1.10-0.95 (m, 5H),
    735 cm−1 0.92-0.74 (m, 1H), 0.67 (d, J = 6.7 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −117.72.
    24 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (500 MHz, CDCl3) δ
    film) 3355, calcd for C22H35NO4Na, 7.21-6.94 (m, 3H), 5.44-5.34 (m, 1H),
    2973, 400.2458; found, 400.2452 5.06 (d, J = 7.8 Hz, 1H), 4.33-4.23 (m,
    2871, 1H), 2.68 (dd, J = 9.2, 4.9 Hz, 1H),
    1713, 2.28 (s, 3H), 2.25 (s, 3H), 2.03 (dp, J = 9.0,
    1366, 6.6 Hz, 1H), 1.44 (s, 9H), 1.25 (d, J = 7.3 Hz,
    1163, 733 cm−1 3H), 1.05 (d, J = 6.3 Hz, 3H),
    0.98 (d, J = 6.6 Hz, 3H), 0.70 (d, J = 6.7 Hz,
    3H).
    25 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (500 MHz, CDCl3) δ
    film) 3366, calcd for C24H37NO4Na, 7.24-6.91 (m, 3H), 5.30 (dq, J = 6.5, 3.4, 2.2 Hz,
    2953, 426.2615; found, 426.2608 1H), 5.08 (d, J = 8.2 Hz, 1H),
    1712, 4.34-4.25 (m, 1H), 2.79 (dd, J = 10.3, 4.1 Hz,
    1161, 731 cm−1 1H), 2.29 (s, 3H), 2.27 (s, 3H),
    2.25-2.14 (m, 1H), 1.97-1.80 (m, 1H),
    1.70-1.61 (m, 1H), 1.58-1.35 (m,
    12H), 1.34-1.17 (m, 5H), 1.07 (d, J = 6.3 Hz,
    3H), 0.93-0.87 (m, 1H).
    26 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (500 MHz, CDCl3) δ 7.21 (d,
    film) 3360, calcd for C25H39NO4Na, J = 7.9 Hz, 1H), 6.98-6.94 (m, 2H),
    2924, 440.2771; found, 440.2765 5.48-5.30 (m, 1H), 5.08 (d, J = 7.9 Hz,
    1712, 1H), 4.38-4.23 (m, 1H), 2.75 (dd, J = 9.3,
    1162, 732 cm−1 4.8 Hz, 1H), 2.28 (s, 3H), 2.24 (s,
    3H), 1.90-1.83 (m, 1H)
    1.79-1.53 (m, 3H), 1.45 (s, 9H), 1.42-1.05 (m,
    8H), 1.03 (d, J = 6.2 Hz, 3H),
    1.01-0.73 (m, 2H).
    27 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (500 MHz, CDCl3) δ
    film) 3358, calcd for C23H37NO4Na, 7.23-6.90 (m, 3H), 5.40 (dd, J = 7.7, 4.7 Hz,
    2970, 414.2615; found, 414.2610 1H), 5.06 (t, J = 9.1 Hz, 1H),
    2931, 4.35-4.21 (m, 1H), 2.87-2.70 (m, 1H),
    1713, 2.30-2.24 (m, 6H), 1.92-1.75 (m, 1H),
    1163, 733 cm−1 1.64-1.53 (m, 1H), 1.44 (d, J = 4.3 Hz,
    9H), 1.35-1.14 (m, 3H),
    1.15-0.62 (m, 10H).
    28 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.21 (dd,
    film) 3358, calcd for C21H32FNNaO5, J = 8.5, 6.9 Hz, 1H), 6.69-6.53 (m,
    2973, 420.2157; found, 420.2149 2H), 5.39 (p, J = 5.9 Hz, 1H), 5.05 (d, J = 7.8 Hz,
    1711, 1H), 4.33-4.17 (m, 1H),
    1501, 1163 cm−1 3.78 (s, 3H), 3.06 (dd, J = 9.4, 5.0 Hz,
    1H), 1.97 (dp, J = 9.2, 6.6 Hz, 1H),
    1.44 (s, 9H), 1.27-1.20 (m, 3H), 1.05 (d, J = 6.2 Hz,
    3H), 0.95 (d, J = 6.6 Hz, 3H),
    0.68 (d, J = 6.7 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −114.15.
    29 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.24 (dd,
    film) 3358, calcd for C23H36FNNaO5, J = 8.6, 6.9 Hz, 1H), 6.68-6.50 (m,
    2965, 448.2470; found, 448.2464 2H), 5.44-5.30 (m, 1H), 5.05 (d, J = 8.1 Hz,
    1714, 1H), 4.37-4.18 (m, 1H),
    1501, 1165 cm−1 3.78 (s, 3H), 3.31 (dd, J = 9.7, 4.7 Hz, 1H),
    1.76-1.56 (m, 2H), 1.44 (s, 9H),
    1.41-1.17 (m, 5H), 1.02 (d, J = 6.2 Hz,
    3H), 0.96 (ddd, J = 11.8, 9.1, 6.1 Hz,
    1H), 0.88 (t, J = 7.4 Hz, 3H), 0.69 (t, J = 7.4 Hz,
    3H).
    13C NMR (101 MHz, CDCl3) δ 172.81,
    162.06 (d, J = 244.1 Hz), 159.15 (d, J = 9.2 Hz),
    154.95, 130.14 (d, J = 9.1 Hz),
    124.35 (d, J = 3.5 Hz), 106.70 (d, J = 20.5 Hz),
    98.44 (d, J = 25.3 Hz), 79.73,
    77.21, 72.04, 55.59, 49.46, 40.99,
    28.34, 21.70, 21.48, 18.84, 18.42,
    10.26, 10.03.
    19F NMR (376 MHz, CDCl3) δ −114.14.
    30 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.23 (t, J = 7.8 Hz,
    film) 3356, calcd for C24H36FNNaO5, 1H), 6.69-6.48 (m, 2H),
    2929, 460.2470; found, 460.2466 5.47-5.33 (m, 1H), 5.07 (d, J = 8.2 Hz,
    1714, 1H), 4.35-4.21 (m, 1H), 3.77 (s,
    1502, 1165 cm−1 3H), 3.13 (s, 1H), 1.87-1.53 (m, 6H),
    1.44 (s, 9H), 1.39-1.16 (m, 4H),
    1.16-0.85 (m, 6H), 0.78 (qd, J = 12.2, 3.2 Hz,
    1H).
    19F NMR (376 MHz, CDCl3) δ −114.17.
    31 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ
    film) 3358, calcd for C23H34FNNaO5, 7.29-7.22 (m, 1H), 6.68-6.55 (m, 2H),
    2954, 446.2313; found, 446.2309 5.38-5.24 (m, 1H), 5.08 (d, J = 7.9 Hz,
    1713, 1H), 4.38-4.21 (m, 1H), 3.78 (s, 3H),
    1502, 1165 cm−1 3.12 (d, J = 10.7 Hz, 1H), 2.16 (qd, J = 10.0,
    7.8, 2.9 Hz, 1H), 1.85 (ddt, J = 14.5,
    11.1, 5.0 Hz, 1H), 1.74-1.59 (m,
    1H), 1.52 (dtd, J = 15.4, 8.4, 3.7 Hz,
    1H), 1.44 (d, J = 2.3 Hz, 9H),
    1.43-1.14 (m, 6H), 1.03 (d, J = 6.3 Hz, 3H),
    1.00-0.81 (m, 2H).
    19F NMR (376 MHz, CDCl3) δ −114.20.
    32 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ
    film) 3358, calcd for C22H34FNNaO5, 7.21 (ddd, J = 14.6, 8.6, 6.9 Hz, 1H),
    2968, 434.2313; found, 434.2306 6.61 (dddd, J = 15.1, 10.8, 4.4, 2.5 Hz, 2H),
    1711, 5.47-5.33 (m, 1H), 5.05 (dd, J = 16.0,
    1501, 1163 cm−1 7.7 Hz, 1H), 4.25 (dt, J = 23.5, 7.3 Hz,
    1H), 3.78 (d, J = 1.3 Hz, 3H),
    3.31-3.08 (m, 1H), 1.78 (ttd, J = 7.9, 6.3, 5.9,
    3.5 Hz, 1H), 1.55-1.35 (m, 10H),
    1.34-1.18 (m, 2H), 1.10 (td, J = 15.7, 14.1,
    6.9 Hz, 3H), 1.04-0.81 (m, 5H),
    0.77-0.61 (m, 3H).
    19F NMR (376 MHz, CDCl3) δ −114.11,
    −114.21.
    33 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.06 (dd,
    film) 3352, calcd for C20H30FNO4Na, J = 8.7, 5.6 Hz, 2H), 7.02-6.92 (m,
    2964, 390.2051; found, 390.2044 2H), 5.36 (dq, J = 8.7, 6.3 Hz, 1H),
    2932, 5.05 (s, 1H), 4.37-4.19 (m, 1H), 2.69 (dd, J = 8.7,
    1712, 6.4 Hz, 1H), 2.08 (h, J = 6.7 Hz,
    1605, 1H), 1.45 (s, 8H), 1.38 (d, J = 7.2 Hz,
    1509, 3H), 1.06 (d, J = 6.2 Hz, 3H), 0.86 (d, J = 6.8 Hz,
    1452, 3H), 0.74 (d, J = 6.8 Hz, 3H).
    1366, 13C NMR (126 MHz, CDCl3) δ 172.79,
    1224, 161.75 (d, J = 244.8 Hz), 155.03,
    1160, 134.29, 131.03 (d, J = 7.6 Hz),
    1052, 835 cm−1 114.82 (d, J = 21.0 Hz), 79.79, 72.32, 55.88,
    49.50, 28.34, 28.18, 21.30, 18.81,
    18.41, 17.74.
    34 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.07 (dd,
    film) 3358, calcd for C22H32FNNaO5, J = 8.3, 6.8 Hz, 1H), 6.63-6.53 (m,
    2976, 432.2157; found, 432.2159 2H), 5.19 (q, J = 6.2 Hz, 1H), 5.00 (d, J = 7.8 Hz,
    1710, 1H), 4.18 (d, J = 7.4 Hz, 1H),
    1501, 3.79 (s, 3H), 3.24 (s, 1H), 2.64 (h, J = 8.6 Hz,
    1276, 1H), 2.11 (ddt, J = 11.6, 6.9, 4.3 Hz,
    1164, 1H), 1.88-1.55 (m, 4H),
    1035, 954, 1.51-1.35 (m, 10H), 1.16 (d, J = 7.4 Hz, 3H),
    833 cm−1 1.11 (d, J = 6.4 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −114.07.
    35 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.00 (dd,
    film) 3358, calcd for C24H36FNNaO5, J = 8.3, 6.8 Hz, 1H), 6.60 (ddt, J = 10.7,
    2928, 460.2470; found, 460.2470 7.4, 4.1 Hz, 2H), 5.41 (s, 1H), 5.10 (d, J = 8.0 Hz,
    1712, 1H), 4.37-4.17 (m, 1H),
    1502, 3.76 (s, 3H), 3.36 (s, 1H),
    1450, 1.76-1.48 (m, 5H), 1.45 (s, 9H), 1.38 (d, J = 7.1 Hz,
    1163, 3H), 1.32-1.16 (m, 2H),
    1033, 955, 1.16-0.92 (m, 5H), 0.92-0.72 (m, 2H).
    834 cm−1 19F NMR (376 MHz, CDCl3) δ −113.94.
    36 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.05 (t, J = 7.7 Hz,
    film) 3358, calcd for C32H34FNNaO5, 1H), 6.67-6.53 (m, 2H),
    2954, 446.2313; found, 446.2313 5.29 (s, 1H), 5.07 (s, 1H), 4.23 (d, J = 7.9 Hz,
    1710, 1H), 3.76 (s, 3H), 3.49 (d, J = 67.4 Hz,
    1502, 1H), 2.11 (d, J = 53.5 Hz, 1H),
    1450, 1.84 (dtd, J = 10.9, 7.1, 3.4 Hz, 1H),
    1366, 1.70-1.58 (m, 1H), 1.58-1.37 (m,
    1164, 12H), 1.34 (d, J = 7.1 Hz, 3H),
    1033, 953, 1.30-1.18 (m, 2H), 1.09 (d, J = 6.4 Hz, 3H),
    834, 732 cm−1 0.99-0.83 (m, 1H).
    19F NMR (376 MHz, CDCl3) δ −114.07.
    37 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.04 (dd,
    film) 3359, calcd for C23H36FNNaO5, J = 8.3, 6.8 Hz, 1H), 6.60 (ddt, J = 11.0,
    2965, 448.2470; found, 448.2469 7.6, 2.5 Hz, 2H), 5.40 (dt, J = 12.5, 6.3 Hz,
    1713, 1H), 5.20-5.02 (m, 1H), 4.27 (s,
    1501, 1H), 3.77 (s, 2H), 3.57 (d, J = 10.1 Hz,
    1165, 1H), 1.55 (dt, J = 9.8, 6.7 Hz, 1H),
    1054, 1.50-1.42 (m, 10H), 1.42-1.30 (m, 4H),
    1035, 955, 1.29-1.09 (m, 2H), 1.06 (d, J = 6.3 Hz,
    834 cm−1 3H), 0.94 (t, J = 7.4 Hz, 3H),
    0.91-0.78 (m, 1H), 0.75 (t, J = 7.2 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −113.91.
    38 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.02 (t, J = 7.6 Hz,
    film) 3358, calcd for C22H34FNNaO5, 1H), 6.66-6.56 (m, 2H),
    2966, 434.2313; found, 434.2312 5.40 (tt, J = 10.1, 5.5 Hz, 1H), 5.11 (s,
    1711, 1H), 4.29 (dd, J = 15.4, 7.9 Hz, 1H),
    1600, 3.77 (d, J = 2.3 Hz, 3H), 3.42 (d, J = 27.2 Hz,
    1502, 1H), 1.80 (ddt, J = 8.9, 6.8, 4.4 Hz,
    1452, 1H), 1.45 (d, J = 2.2 Hz, 9H),
    1366, 1.36 (ddd, J = 14.4, 12.6, 6.9 Hz, 4H),
    1164, 1.05 (dd, J = 8.1, 6.2 Hz, 3H),
    1053, 0.97-0.82 (m, 4H), 0.76 (dd, J = 11.5, 7.0 Hz,
    1035, 954, 3H).
    834 cm−1 19F NMR (376 MHz, CDCl3) δ −113.85,
    −113.92.
    39 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ
    film) 3359, calcd for C22H32FNNaO5, 7.00-6.93 (m, 1H), 6.58 (ddd, J = 10.0, 6.6,
    2976, 432.2157; found, 432.2147 2.0 Hz, 2H), 5.21-4.97 (m, 2H),
    1709, 4.24 (d, J = 7.9 Hz, 1H), 3.79 (s, 3H),
    1501, 3.31 (s, 1H), 2.76 (h, J = 8.5 Hz, 1H),
    1164, 2.12 (dddd, J = 22.7, 20.7, 11.3, 6.7 Hz, 1H),
    1035, 954, 1.97-1.74 (m, 2H), 1.74-1.57 (m,
    834, 732 cm−1 2H), 1.50-1.37 (m, 10H), 1.34 (d, J = 7.1 Hz,
    3H), 1.06 (d, J = 6.4 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −113.90.
    40 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.01 (dd,
    film) 3359, calcd for C21H32FNNaO5, J = 8.2, 6.7 Hz, 1H), 6.66-6.57 (m,
    2964, 420.2157; found, 420.2154 2H), 5.38 (t, J = 7.4 Hz, 1H), 5.09 (d, J = 7.7 Hz,
    1710, 1H), 4.38-4.20 (m, 1H),
    1502, 3.77 (s, 3H), 3.32 (s, 1H),
    1164, 2.14-2.01 (m, 1H), 1.45 (s, 9H), 1.37 (d, J = 7.2 Hz,
    1050, 3H), 1.05 (d, J = 6.2 Hz, 3H),
    1034, 954, 0.84 (d, J = 6.8 Hz, 3H), 0.73 (d, J = 6.7 Hz,
    834, 732 cm−1 3H).
    19F NMR (376 MHz, CDCl3) δ −113.87.
    41 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (500 MHz, CDCl3) δ
    film) 3358, calcd for C23H35NO4Na, 7.09-6.87 (m, 3H), 5.21-5.07 (m, 1H),
    2975, 412.2458; found, 412.2463 4.98 (d, J = 7.9 Hz, 1H), 4.29-4.07 (m, 1H),
    2935, 3.02 (dd, J = 10.5, 6.3 Hz, 1H),
    1713, 2.68 (hept, J = 8.0, 7.1 Hz, 1H), 2.32 (s, 3H),
    1164, 1021 cm−1 2.26 (s, 3H), 2.19-2.08 (m, 1H),
    1.88-1.62 (m, 4H), 1.43 (s, 9H),
    1.32-1.22 (m, 1H), 1.16 (d, J = 6.4 Hz, 3H),
    1.07 (d, J = 7.1 Hz, 3H).
    42 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.27 (d,
    film) 3365, calcd for C20H30ClNO4, J = 9.9 Hz, 2H), 7.03 (d, J = 8.5 Hz,
    2969, 409.1763; found, 409.1764 2H), 5.42-5.31 (m, 1H),
    2932, 5.13-4.95 (m, 1H), 4.27 (t, 1H), 2.68 (dd, J = 8.6,
    2875, 6.5 Hz, 1H), 2.16-1.98 (m, 1H),
    1714, 1.45 (s, 9H), 1.38 (d, J = 7.2 Hz, 3H),
    1492, 1.07 (d, J = 6.3 Hz, 3H), 0.86 (d, J = 6.8 Hz,
    1366, 3H), 0.74 (d, J = 6.8 Hz, 3H).
    1166, 1053 cm−1 13C NMR (126 MHz, CDCl3) δ 172.76,
    137.14, 132.52, 131.02, 128.15, 77.21,
    72.15, 56.07, 49.49, 28.35, 28.15,
    25.29, 21.27, 18.81, 18.47, 17.70,
    14.13.
    43 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.09 (t, J = 8.0 Hz,
    film) 3353, calcd for C21H32FNO4, 1H), 6.80-6.71 (m, 2H),
    2969, 406.2268; found, 406.2269 5.40-5.25 (m, 1H), 5.06 (s, 1H),
    2931, 4.33-4.22 (m, 1H), 2.65 (dd, J = 8.7, 6.5 Hz,
    1714, 1H), 2.25 (d, J = 1.8 Hz, 3H),
    1506, 2.13-1.98 (m, 1H), 1.45 (s, 9H), 1.38 (d, J = 7.2 Hz,
    1366, 3H), 1.08 (d, J = 6.3 Hz, 3H),
    1163, 1052 cm−1 0.86 (d, J = 6.8 Hz, 3H), 0.76 (d, J = 6.8 Hz,
    3H).
    13C NMR (126 MHz, CDCl3) δ 172.79,
    161.92, 159.98, 138.35, 138.30, 130.82,
    130.78, 125.20, 125.17, 123.01, 122.88,
    116.22, 116.04, 79.77, 77.21, 72.28,
    56.12, 49.50, 34.67, 31.59, 28.34,
    28.19, 25.28, 21.29, 18.81, 18.51,
    17.74, 14.21, 14.18, 14.13.
    44 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.09 (dt,
    film) 3351, calcd for C20H29F2NO4, J = 10.1, 8.3 Hz, 1H), 6.92 (ddd, J = 11.7,
    2976, 408.1957; found, 408.1956 7.6, 2.2 Hz, 1H), 6.86-6.76 (m,
    1709, 1H), 5.31 (dt, J = 8.5, 6.3 Hz, 1H),
    1515, 5.03 (s, 1H), 4.27 (s, 1H), 2.72-2.62 (m,
    1280, 1H), 2.13-1.96 (m, 1H), 1.45 (s, 9H),
    1163, 1.37 (d, J = 7.2 Hz, 3H), 1.08 (d, J = 6.3 Hz,
    1053, 771 cm−1 3H), 0.88 (d, J = 6.8 Hz, 3H),
    0.75 (d, J = 6.8 Hz, 3H).
    13C NMR (126 MHz, CDCl3) δ 172.72,
    125.58, 118.35, 118.21, 116.77, 116.63,
    79.84, 77.21, 71.98, 55.92, 49.48,
    28.33, 28.24, 21.20, 18.75, 18.57,
    17.51.
    45 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ
    film) 2965, calcd for C21H32FNNaO4, 6.96-6.84 (m, 3H), 5.35 (dq, J = 8.8, 6.2 Hz,
    1714, 404.2208; found, 404.2208 1H), 5.11 (d, J = 7.8 Hz, 1H), 4.28 (p, J = 7.5 Hz,
    1503, 1H), 2.65 (dd, J = 8.9, 6.3 Hz,
    1366, 1H), 2.26 (d, J = 1.9 Hz, 3H),
    1211, 2.13-2.03 (m, 1H), 1.45 (s, 9H), 1.39 (d, J = 7.2 Hz,
    1164, 1052 cm−1 3H), 1.07 (d, J = 6.3 Hz, 3H),
    0.85 (d, J = 6.8 Hz, 3H), 0.75 (d, J = 6.8 Hz,
    3H).
    13C NMR (101 MHz, CDCl3) δ 172.82,
    160.30 (d, J = 243.6 Hz), 155.04,
    134.03 (d, J = 3.9 Hz), 132.62 (d, J = 4.9 Hz),
    128.31 (d, J = 7.7 Hz),
    124.13 (d, J = 17.1 Hz), 114.42 (d, J = 22.0 Hz),
    79.75, 72.46, 55.89, 49.56, 28.36,
    28.19, 21.34, 18.76, 18.46, 17.87,
    14.64 (d, J = 3.5 Hz).
    19F NMR (376 MHz, CDCl3) δ −120.77.
    46 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.03 (t, J = 8.5 Hz,
    film) 3369, calcd for C21H32FNNaO5, 1H), 6.67 (ddd, J = 8.6, 2.6,
    2965, 420.2157; found, 420.2158 0.8 Hz, 1H), 6.60 (dd, J = 12.0, 2.6 Hz,
    1714, 1H), 5.44-5.34 (m, 1H), 5.13 (d, J = 8.0 Hz,
    1508, 1H), 4.28 (dd, J = 11.1, 4.2 Hz,
    1366, 1H), 3.79 (s, 3H), 3.08 (dd, J = 8.5, 6.8 Hz,
    1293, 1H), 2.15-2.05 (m, 1H), 1.45 (s,
    1165, 9H), 1.38 (d, J = 7.2 Hz, 3H), 1.09 (d, J = 6.3 Hz,
    1053, 1032 cm−1 3H), 0.90 (dd, J = 6.7, 1.0 Hz,
    3H), 0.76 (d, J = 6.7 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 172.80,
    162.10 (d, J = 244.2 Hz), 159.37 (d, J = 11.4 Hz),
    155.06, 130.68 (d, J = 6.6 Hz),
    117.55 (d, J = 15.5 Hz), 109.59 (d,
    J = 3.0 Hz), 101.42 (d, J = 27.9 Hz),
    79.66, 72.25, 55.44, 49.55, 47.97,
    28.35, 21.11, 18.84, 18.60, 17.55.
    19F NMR (376 MHz, CDCl3) δ −113.07.
    47 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ
    film) 3369, calcd for C21H32FNNaO5, 6.93-6.77 (m, 3H), 5.32 (dq, J = 8.6, 6.2 Hz,
    2965, 420.2157; found, 420.2160 1H), 5.17-5.04 (m, 1H), 4.28 (dd, J = 11.1,
    1712, 4.1 Hz, 1H), 3.88 (s, 3H),
    1515, 2.63 (dd, J = 8.7, 6.4 Hz, 1H),
    1273, 2.13-2.00 (m, 1H), 1.45 (s, 9H), 1.38 (d, J = 7.2 Hz,
    1221, 3H), 1.08 (d, J = 6.3 Hz, 3H),
    1164, 0.86 (d, J = 6.8 Hz, 3H), 0.76 (d, J = 6.8 Hz,
    1052, 1028 cm−1 3H).
    13C NMR (101 MHz, CDCl3) δ 172.78,
    155.04, 151.97 (d, J = 245.2 Hz),
    146.32 (d, J = 10.6 Hz), 131.77 (d, J = 5.7 Hz),
    125.40 (d, J = 3.6 Hz),
    117.21 (d, J = 18.3 Hz), 112.98 (d, J = 2.1 Hz),
    79.75, 72.30, 56.25, 55.81, 49.53,
    28.35, 28.25, 21.30, 18.75, 18.51,
    17.72.
    19F NMR (376 MHz, CDCl3) δ −135.65.
    48 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 6.94 (d,
    film) 3355, calcd for C22H35NNaO5, J = 7.7 Hz, 1H), 6.72 (dd, J = 7.6, 1.5 Hz,
    2963, 416.2407; found, 416.2410 1H), 6.68 (d, J = 1.6 Hz, 1H),
    1714, 5.40 (t, J = 7.7 Hz, 1H), 5.14 (d, J = 7.4 Hz,
    1506, 1H), 4.35-4.20 (m, 1H), 3.76 (s, 3H),
    1454, 3.32 (s, 1H), 2.33 (s, 3H), 2.08 (dq, J = 12.5,
    1366, 6.3, 5.8 Hz, 1H), 1.45 (s, 9H),
    1256, 1.38 (d, J = 7.2 Hz, 3H), 1.05 (d, J = 6.2 Hz,
    1163, 3H), 0.84 (d, J = 6.8 Hz, 3H),
    1050 cm−1 0.74 (d, J = 6.8 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 172.75,
    158.09, 155.01, 137.18, 129.51, 124.60,
    120.74, 111.75, 79.60, 73.28, 55.34,
    53.89, 49.67, 29.30, 28.76, 28.37,
    21.44, 21.12, 18.79, 18.12.
    49 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ
    film) 3364, calcd for C22H35NNaO5, 7.03-6.95 (m, 1H), 6.71 (d, J = 7.9 Hz, 2H),
    2961, 416.2407; found, 416.2404 5.33 (dq, J = 9.4, 6.2 Hz, 1H), 5.12 (d, J = 7.9 Hz,
    1712, 1H), 4.38-4.20 (m, 1H),
    1502, 3.78 (s, 3H), 3.05 (dd, J = 9.4, 5.9 Hz,
    1453, 1H), 2.31 (s, 3H), 2.12 (dq, J = 13.4,
    1366, 6.7 Hz, 1H), 1.45 (s, 9H), 1.40 (d, J = 7.2 Hz,
    1250, 3H), 1.03 (d, J = 6.2 Hz, 3H),
    1162, 0.84 (d, J = 6.8 Hz, 3H), 0.79 (d, J = 6.9 Hz,
    1048, 732 cm−1 3H).
    13C NMR (101 MHz, CDCl3) δ 172.89,
    157.60, 155.00, 138.86, 129.96, 128.86,
    115.89, 110.91, 79.71, 73.89, 55.04,
    49.60, 49.24, 29.58, 28.35, 21.08,
    20.98, 18.72, 18.64, 18.33.
    50 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ
    film) 3363, calcd for C22H35NO6Na, 7.04-6.82 (m, 1H), 6.50-6.30 (m, 2H),
    2962, 432.2357; found, 432.2347 5.50-5.28 (m, 1H), 5.11 (d, J = 7.4 Hz, 1H),
    1712, 4.36-4.17 (m, 1H), 3.80 (s, 3H),
    1505, 3.76 (s, 3H), 3.44-3.00 (m, 1H), 2.06 (h, J = 6.7 Hz,
    1207, 1H), 1.45 (s, 9H), 1.38 (d, J = 7.1 Hz,
    1157, 3H), 1.05 (d, J = 6.2 Hz, 3H),
    1045, 732 cm−1 0.83 (d, J = 6.8 Hz, 3H), 0.73 (d, J = 6.8 Hz,
    3H).
    51 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ
    film) 3359, calcd for C21H33NO5Na, 7.25-7.13 (m, 1H), 7.07 (dd, J = 7.6, 1.8 Hz,
    2968, 402.23; found, 402.2194 1H), 6.95-6.81 (m, 2H),
    1713, 5.58-5.36 (m, 1H), 5.20-5.02 (m, 1H),
    1493, 4.38-4.17 (m, 1H), 3.78 (s, 3H),
    1242, 3.55-3.08 (m, 1H), 2.10 (h, J = 6.7 Hz, 1H),
    1163, 1.45 (s, 9H), 1.38 (d, J = 7.1 Hz, 3H),
    1051, 755 cm−1 1.06 (d, J = 6.2 Hz, 3H), 0.85 (d, J = 6.8 Hz,
    3H), 0.74 (d, J = 6.8 Hz, 3H).
    52 ESIMS m/z 250.4
    ([M + H]+)
    53 ESIMS m/z 375.5
    ([M + Boc]+)
    54 ESIMS m/z 250.4
    ([M + H]+)
    55 ESIMS m/z 262 ([M + H]+)
    56 ESIMS m/z 264.3
    ([M + H]+)
    57 ESIMS m/z 264.4
    ([M + H]+)
    58 ESIMS m/z 268 ([M + H]+)
    59 ESIMS m/z 266 ([M + H]+)
    60 HRMS-ESI (m/z) [M + H]+
    calcd for C17H28NO2,
    278.2120; found, 278.2115
    61 HRMS-ESI (m/z) [M + H]+
    calcd for C17H26NO2,
    276.1963; found, 276.1960
    62 ESIMS m/z 282.2
    ([M + H]+)
    63 ESIMS m/z 310.2
    ([M + H]+)
    64 ESIMS m/z 308.2
    ([M + H]+)
    65 ESIMS m/z 322.2
    ([M + H]+)
    66 ESIMS m/z 296.2
    ([M + H]+)
    67 ESIMS m/z 294.2
    ([M + H]+)
    68 ESIMS m/z 308.2
    ([M + H]+)
    69 ESIMS m/z 322.2
    ([M + H]+)
    70 ESIMS m/z 282.1
    ([M + H]+)
    71 ESIMS m/z 310.2
    ([M + H]+)
    72 ESIMS m/z 296.2
    ([M + H]+)
    73 ESIMS m/z 294.2
    ([M + H]+)
    74 ESIMS m/z 308.1
    ([M + H]+)
    75 ESIMS m/z 322.2
    ([M + H]+)
    76 ESIMS m/z 282.2
    ([M + H]+)
    77 HRMS-ESI (m/z) [M + H]+
    calcd for C18H30NO2,
    292.2271; found, 292.2268
    78 HRMS-ESI (m/z) [M + H]+
    calcd for C20H32NO2,
    318.2428; found, 318.2525
    79 HRMS-ESI (m/z) [M + H]+
    calcd for C19H30NO2,
    304.2271; found, 304.2267
    80 HRMS-ESI (m/z) [M + H]+
    calcd for C17H28NO2,
    278.2115; found, 278.2112
    81 IR (thin HRMS-ESI (m/z) [M + H]+
    film) 3383, calcd for C15H23FNO2,
    2960, 268.1707; found, 268.1717
    1737,
    1603,
    1509,
    1460,
    1386,
    1223,
    1117, 834 cm−1
    82 ESIMS m/z 298.3
    ([M + H]+)
    83 EIMS m/z 324.9
    84 ESIMS m/z 338.3
    ([M + H]+)
    85 EIMS m/z 324.2
    86 EIMS m/z 311.1
    87 EIMS m/z 310.2
    88 EIMS m/z 337.3
    89 EIMS m/z 323.0
    90 EIMS m/z 326.2
    91 EIMS m/z 311.9
    92 ESIMS m/z 310.0
    ([M + H]+)
    93 EIMS m/z 298.2
    94 HRMS-ESI (m/z) [M + H]+
    calcd for C18H28NO2,
    290.2115; found, 290.2116
    95 IR (thin ESIMS m/z 284.1
    film) 3451, ([M + H]+)
    3381,
    2957,
    2751,
    2626,
    2506,
    1757,
    1515,
    1492,
    1240,
    1214,
    1092, 832 cm−1
    96 IR (thin ESIMS m/z 282.2
    film) 2959, ([M + H]+)
    2928,
    1738,
    1507,
    1235,
    1117, 731 cm−1
    97 IR (thin ESIMS m/z 286.2
    film) 3386, ([M + H]+)
    2961,
    1739,
    1515,
    1238,
    1210, 1115 cm−1
    98 ESIMS m/z 282.3
    ([M + H]+)
    99 ESIMS m/z 298.3
    ([M + H]+)
    100 ESIMS m/z 298.3
    ([M + H]+)
    101 ESIMS m/z 294.3
    ([M + H]+)
    102 ESIMS m/z 294.3
    ([M + H]+)
    103 HRMS-ESI (m/z) [M + H]+
    calcd for C16H26NO3,
    280.1907; found, 280.1908
    104 HRMS-ESI (m/z) [M + Na]+
    calcd for C17H27NO4Na,
    382.1832; found, 332.1811
    105 HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.15 (s,
    calcd for C22H29N2O5, 1H), 8.46 (d, J = 8.0 Hz, 1H), 8.01 (d, J = 5.2 Hz,
    401.2076; found, 401.2078 1H), 7.27-7.08 (m, 5H),
    6.88 (d, J = 5.2 Hz, 1H), 5.56-5.43 (m, 1H),
    4.74-4.54 (m, 1H), 3.94 (s, 3H),
    2.37 (dd, J = 8.4, 5.7 Hz, 1H), 2.03 (dh, J = 8.4,
    6.6 Hz, 1H), 1.32 (d, J = 7.2 Hz,
    3H), 1.13 (d, J = 6.3 Hz, 3H), 0.95 (d, J = 6.6 Hz,
    3H), 0.71 (d, J = 6.7 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 171.67,
    168.64, 155.38, 148.77, 140.46, 139.69,
    130.49, 129.58, 127.91, 126.49, 109.45,
    72.39, 57.96, 56.07, 48.05, 29.19,
    21.30, 20.17, 18.93, 18.06.
    106 HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.17 (s,
    calcd for C24H31N2O5, 1H), 8.52 (d, J = 8.0 Hz, 1H), 8.01 (d, J = 5.2 Hz,
    427.2233; found, 427.2235 1H), 7.31-7.12 (m, 5H), 6.88 (d,
    J = 5.2 Hz, 1H), 5.37 (qd, J = 6.3, 3.9 Hz,
    1H), 4.81-4.58 (m, 1H), 3.94 (s, 3H),
    2.42 (dd, J = 10.3, 4.1 Hz, 1H),
    2.25-2.16 (m, 1H), 1.88 (dtd, J = 11.2, 7.2, 3.3 Hz,
    1H), 1.69-1.50 (m, 3H), 1.49 (d, J = 7.2 Hz,
    3H), 1.47-1.30 (m, 2H),
    1.24-1.13 (m, 1H), 1.08 (d, J = 6.4 Hz, 3H),
    0.99-0.85 (m, 1H).
    13C NMR (101 MHz, CDCl3) δ 171.60,
    168.73, 155.39, 148.80, 140.63, 140.49,
    130.45, 129.44, 127.93, 126.45, 109.49,
    73.59, 56.60, 56.07, 48.21, 42.11, 31.63,
    31.45, 25.07, 24.52, 18.73, 18.22.
    107 HRMS-ESI (m/z) [M + H]+ 1H NMR (300 MHz, CDCl3) δ 12.16 (s,
    calcd for C22H29N2O5, 1H), 8.50 (d, J = 7.9 Hz, 1H), 8.00 (d, J = 5.2 Hz,
    401.2076; found, 401.2073 1H), 7.38-7.17 (m, 3H),
    7.13-7.04 (m, 2H), 6.88 (d, J = 5.2 Hz, 1H),
    5.44 (dq, J = 8.6, 6.3 Hz, 1H),
    4.81-4.59 (m, 1H), 3.95 (s, 3H), 2.72 (dd, J = 8.6,
    6.5 Hz, 1H), 2.24-2.00 (m, 1H),
    1.55 (d, J = 7.2 Hz, 3H), 1.11 (d, J = 6.3 Hz
    3H), 0.86 (d, J = 6.8 Hz, 3H),
    0.76 (d, J = 6.7 Hz, 3H).
    13C NMR (75 MHz, CDCl3) δ 171.73,
    168.72, 155.37, 148.75, 140.50, 138.53,
    130.49, 129.78, 127.93, 126.66, 109.45,
    73.04, 56.60, 56.11, 48.21, 28.31,
    21.31, 18.65, 18.35, 17.76.
    108 HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.18 (s,
    calcd for C23H29N2O5 1H), 8.50 (d, J = 8.1 Hz, 1H), 8.00 (d, J = 5.2 Hz,
    413.2071; found, 413.2070 1H), 7.12-7.05 (m, 4H),
    6.88 (d, J = 5.2 Hz, 1H), 5.42-5.24 (m, 1H),
    4.82-4.63 (m, 1H), 3.95 (s, 3H),
    2.32 (s, 3H), 1.99 (dd, J = 10.1, 7.0 Hz, 1H),
    1.52 (d, J = 7.2 Hz, 3H), 1.18 (d, J = 6.4 Hz,
    3H), 1.15-1.06 (m, 1H),
    0.70-0.61 (m, 1H), 0.44-0.29 (m, 2H),
    −0.01-−0.10 (m, 1H).
    13C NMR (101 MHz, CDCl3) δ 171.66,
    168.63, 155.40, 148.79, 140.43, 138.48,
    136.16, 130.58, 128.94, 128.25, 109.44,
    76.20, 56.06, 55.24, 48.15, 21.01,
    18.39, 18.13, 12.99, 6.94, 2.89.
    109 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.17 (d,
    film) 3370, calcd for C23H31N2O5, J = 0.6 Hz, 1H), 8.51 (d, J = 7.9 Hz,
    2960, 415.2227; found, 415.2222 1H), 8.00 (d, J = 5.2 Hz, 1H),
    1732, 7.11-7.05 (m, 2H), 7.00-6.95 (m, 2H),
    1649, 6.88 (d, J = 5.2 Hz, 1H), 5.42 (dq, J = 8.6,
    1527, 6.3 Hz, 1H), 4.75-4.65 (m, 1H),
    1481, 3.94 (s, 3H), 2.68 (dd, J = 8.6, 6.5 Hz, 1H),
    1451, 2.31 (s, 3H), 2.09 (h, J = 6.7 Hz, 1H),
    1263, 1.56 (d, J = 7.2 Hz, 3H), 1.11 (d, J = 6.2 Hz,
    1150, 3H), 0.85 (d, J = 6.8 Hz, 3H),
    1048, 799, 0.76 (d, J = 6.8 Hz, 3H).
    730 cm−1 13C NMR (101 MHz, CDCl3) δ 171.72,
    168.74, 155.39, 148.79, 140.47, 136.11,
    135.40, 130.54, 129.64, 128.64, 109.47,
    73.12, 56.22, 56.07, 48.23, 28.28,
    21.32, 20.99, 18.65, 18.33, 17.75.
    110 HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.15 (s,
    calcd for C22H28FN2O5, 1H), 8.61-8.38 (m, 1H),
    419.1977; found, 419.1978 8.06-7.94 (m, 1H), 7.12-6.82 (m, 5H),
    5.51-5.33 (m, 1H), 4.75-4.60 (m, 1H),
    3.95 (s, 3H), 2.77-2.63 (m, 1H),
    2.16-1.99 (m, 1H), 1.59-1.47 (m, 3H),
    1.16-1.04 (m, 3H), 0.94-0.83 (m, 3H),
    0.79-0.71 (m, 3H).
    19F NMR (376 MHz, CDCl3) δ −116.41,
    −116.47.
    111 HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.15 (s,
    calcd for C22H26FN2O5, 1H), 8.46 (d, J = 8.1 Hz, 1H), 8.00 (d, J = 5.2 Hz,
    417.1821; found, 417.1813 1H), 7.21-7.07 (m, 2H),
    7.02-6.92 (m, 2H), 6.88 (d, J = 5.2 Hz, 1H),
    5.37-5.25 (m, 1H), 4.85-4.60 (m,
    1H), 3.95 (s, 3H), 2.03 (dd, J = 10.2,
    6.6 Hz, 1H), 1.51 (d, J = 7.2 Hz, 3H),
    1.19 (d, J = 6.4 Hz, 3H), 1.16-1.03 (m,
    1H), 0.74-0.62 (m, 1H),
    0.49-0.29 (m, 2H), −0.02-−0.12 (m, 1H).
    19F NMR (376 MHz, CDCl3) δ −116.42.
    112 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (300 MHz, CDCl3) δ 12.16 (s,
    film) 3372, calcd for C24H33N2O5, 1H), 8.51 (d, J = 7.9 Hz, 1H), 8.00 (d, J = 5.2 Hz,
    2962, 429.2389; found, 429.2385 1H), 7.38-7.00 (m, 5H),
    2934, 6.88 (d, J = 5.2 Hz, 1H),
    2879, 5.59-5.37 (m, 1H), 4.70 (p, J = 7.2 Hz, 1H),
    1734, 3.95 (s, 3H), 2.97 (dd, J = 8.5, 6.4 Hz, 1H),
    1650, 1.55 (d, J = 7.2 Hz, 3H),
    1576, 1.51-1.31 (m, 5H), 1.12 (d, J = 6.3 Hz, 3H),
    1528, 0.93 (t, J = 7.4 Hz, 3H), 0.77 (t, J = 7.2 Hz,
    1481, 3H).
    1452,
    1324,
    1280,
    1264,
    1213,
    1149,
    1059, 954,
    802, 737,
    705 cm−1.
    113 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (300 MHz, CDCl3) δ 12.17 (s,
    film) 3370, calcd for C24H31N2O5, 1H), 8.48 (t, J = 8.9 Hz, 1H), 8.00 (d, J = 5.9 Hz,
    2943, 427.2233; found, 427.2237 1H), 7.33-7.03 (m, 5H),
    2868, 6.93-6.83 (m, 1H), 5.41-5.26 (m,
    1731, 1H), 4.80-4.58 (m, 1H), 3.95 (s, 3H),
    1648, 2.78 (dd, J = 10.1, 5.9 Hz, 1H),
    1527, 2.33-2.11 (m, 2H), 1.99-1.80 (m, 2H),
    1450, 1.69-1.56 (m, 2H), 1.52 (dd, J = 7.2 Hz,
    1263, 3H), 1.44-1.16 (m, 4H), 1.13 (d, J = 6.5 Hz,
    1144, 2H).
    1038, 799,
    734, 702 cm−1.
    114 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.94 (s,
    film) 3254, calcd for C24H31N2O4S, 1H), 10.69 (s, 1H), 7.98 (s, 1H),
    2947, 443.1999; found, 443.2026 7.26-7.18 (m, 4H), 7.14-7.08 (m, 1H),
    2867, 6.88 (s, 1H), 5.43-5.25 (m, 1H), 5.07 (dp, J = 17.6,
    1729, 7.2 Hz, 1H), 3.97 (d, J = 3.1 Hz,
    1512, 3H), 2.79 (dd, J = 9.9, 6.0 Hz, 1H),
    1485, 2.45-2.27 (m, 1H), 2.27-2.12 (m, 1H),
    1273, 2.00-1.77 (m, 1H), 1.61 (d, J = 7.1 Hz,
    1207, 730 cm−1 3H), 1.57-1.39 (m, 4H),
    1.35-1.23 (m, 2H), 1.14 (d, J = 6.4 Hz, 3H).
    115 IR HRMS-ESI (m/z) [M + Na]+ 1H NMR (500 MHz, CDCl3) δ 12.94 (s,
    (CDCl3) calcd for C24H30N2O4S, 1H), 10.71 (s, 1H), 8.01 (d, J = 15.0 Hz,
    2951, 465.1818; found, 465.1830 1H), 7.22-7.17 (m, 3H), 7.15 (dd, J = 6.7,
    2868, 3.0 Hz, 2H), 6.89 (d, J = 5.0 Hz,
    1733, 1H), 5.39 (qd, J = 6.4, 4.0 Hz, 1H),
    1581, 5.12-5.03 (m, 1H), 3.97 (s, 3H), 2.41 (dd, J = 10.4,
    1514, 4.0 Hz, 1H), 2.25-2.14 (m,
    1486, 1H), 1.95-1.84 (m, 1H),
    1454, 1.69-1.59 (m, 1H), 1.56 (d, J = 7.2 Hz, 3H),
    1377, 1.54-1.45 (m, 2H), 1.44-1.28 (m, 2H),
    1342, 1.19 (dq, J = 12.3, 9.1 Hz, 1H), 1.09 (d,
    1274, J = 6.4 Hz, 3H), 0.92 (ddt, J = 12.5,
    1249, 10.0, 8.5 Hz, 1H).
    1211,
    1131,
    1095, 992,
    913, 860,
    801, 736,
    703 cm−1
    116 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 12.13 (s,
    film) 3369, calcd for C23H29FN2NaO5, 1H), 8.46 (d, J = 8.0 Hz, 1H), 8.02 (d, J = 5.2 Hz,
    2967, 455.1953; found, 455.1947 1H), 7.22 (dd, J = 8.7, 6.0 Hz,
    1733, 1H), 6.89 (d, J = 5.2 Hz, 1H), 6.83 (dd,
    1650, J = 9.9, 2.7 Hz, 1H), 6.73 (td, J = 8.5,
    1529, 2.9 Hz, 1H), 5.49-5.41 (m, 1H),
    1481, 4.69 (p, J = 7.3 Hz, 1H), 3.95 (s, 3H),
    1264, 954, 2.69 (dd, J = 9.2, 5.0 Hz, 1H), 2.27 (s, 3H),
    801, 733 cm−1 2.07-1.86 (m, 1H), 1.43 (d, J = 7.2 Hz,
    3H), 1.07 (d, J = 6.3 Hz, 3H),
    0.99 (d, J = 6.6 Hz, 3H), 0.68 (d, J = 6.7 Hz,
    3H).
    13C NMR (101 MHz, CDCl3) δ 171.56,
    168.72, 160.94 (d, J = 244.1 Hz),
    155.46, 148.86, 140.50, 139.36 (d, J = 7.2 Hz),
    134.57 (d, J = 3.3 Hz), 130.48,
    129.32 (d, J = 8.2 Hz), 116.44 (d, J = 20.5 Hz),
    112.67 (d, J = 20.5 Hz),
    109.54, 72.65, 56.10, 50.65, 48.12,
    30.45, 21.00, 20.72, 20.47, 18.37,
    18.16.
    19F NMR (376 MHz, CDCl3) δ −117.61.
    117 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 12.14 (s,
    film) 3372, calcd for C25H33FN2NaO5, 1H), 8.47 (d, J = 8.1 Hz, 1H), 8.03 (d, J = 5.2 Hz,
    2963, 483.2266; found, 483.2262 1H), 7.28-7.21 (m, 1H),
    1732, 6.89 (d, J = 5.2 Hz, 1H), 6.82 (dd, J = 9.9,
    1649, 2.8 Hz, 1H), 6.73 (td, J = 8.5, 2.9 Hz,
    1528, 1H), 5.40 (qt, J = 6.2, 3.0 Hz, 1H),
    1450, 4.71 (p, J = 7.3 Hz, 1H), 3.95 (s, 3H),
    1263, 2.90 (dd, J = 10.0, 4.3 Hz, 1H), 2.27 (s,
    1060, 954, 3H), 1.63-1.46 (m, 4H),
    800, 731 cm−1 1.46-1.32 (m, 1H), 1.15-0.83 (m, 9H), 0.65 (t, J = 7.4 Hz,
    3H).
    13C NMR (101 MHz, CDCl3) δ 171.62,
    168.78, 160.93 (d, J = 244.2 Hz),
    155.49, 148.90, 140.52, 139.40 (d, J = 7.2 Hz),
    134.65 (d, J = 3.2 Hz), 130.47,
    129.74 (d, J = 7.9 Hz), 116.41 (d, J = 20.6 Hz),
    112.73 (d, J = 20.5 Hz),
    109.57, 72.33, 56.11, 48.24, 41.62,
    29.30, 21.72, 21.09, 20.60, 18.28,
    18.20, 10.79, 9.43.
    19F NMR (376 MHz, CDCl3) δ −117.60.
    118 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 12.14 (s,
    film) 3372, calcd for C25H31FN2NaO5, 1H), 8.47 (d, J = 8.1 Hz, 1H), 8.02 (d, J = 5.2 Hz,
    2951, 481.2109; found, 481.2106 1H), 7.22 (dd, J = 8.7, 6.0 Hz,
    1732, 1H), 6.89 (d, J = 5.2 Hz, 1H), 6.82 (dd,
    1649, J = 9.8, 2.9 Hz, 1H), 6.71 (td, J = 8.5,
    1528, 2.9 Hz, 1H), 5.34 (qd, J = 6.4, 4.1 Hz,
    1263, 1H), 4.71 (p, J = 7.3 Hz, 1H), 3.95 (s,
    1060, 952, 3H), 2.79 (dd, J = 10.3, 4.3 Hz, 1H),
    911, 800, 2.28 (s, 3H), 2.20-2.08 (m, 1H),
    730 cm−1 1.90 (dtd, J = 11.3, 7.2, 3.6 Hz, 1H),
    1.77-1.14 (m, 9H), 1.08 (d, J = 6.3 Hz, 3H),
    0.85 (ddt, J = 12.4, 10.2, 8.4 Hz, 1H).
    13C NMR (101 MHz, CDCl3) δ 171.50,
    168.76, 160.89 (d, J = 244.1 Hz),
    155.47, 148.87, 140.51, 138.79 (d, J = 7.3 Hz),
    135.16 (d, J = 3.3 Hz), 130.47,
    129.60 (d, J = 8.0 Hz), 116.40 (d, J = 20.4 Hz),
    112.67 (d, J = 20.6 Hz),
    109.56, 73.88, 56.11, 49.39, 48.22,
    42.94, 31.60, 31.38, 25.08, 24.42,
    20.60, 18.19, 18.13.
    19F NMR (376 MHz, CDCl3) δ −117.66.
    119 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.14 (s,
    film) 3372, calcd for C26H34FN2O5, 1H), 8.47 (d, J = 8.1 Hz, 1H), 8.02 (d, J = 5.2 Hz,
    2928, 473.2446; found, 473.2440 1H), 7.23 (dd, J = 8.7, 6.0 Hz,
    1732, 1H), 6.89 (d, J = 5.2 Hz, 1H), 6.82 (dd,
    1649, J = 9.9, 2.9 Hz, 1H), 6.74 (td, J = 8.5,
    1528, 2.9 Hz, 1H), 5.50-5.39 (m, 1H),
    1448, 4.70 (p, J = 7.3 Hz, 1H), 3.95 (s, 3H),
    1263, 2.75 (dd, J = 9.3, 4.8 Hz, 1H), 2.26 (s, 3H),
    1060, 954, 1.87 (dt, J = 12.7, 3.2 Hz, 1H),
    910, 730 cm−1 1.80-1.70 (m, 1H), 1.70-1.52 (m, 3H),
    1.45 (d, J = 7.2 Hz, 3H), 1.35-1.15 (m,
    2H), 1.15-0.85 (m, 6H), 0.76 (qd, J = 12.2,
    3.6 Hz, 1H).
    13C NMR (101 MHz, CDCl3) δ 171.59,
    168.75, 160.90 (d, J = 243.9 Hz),
    155.48, 148.86, 140.51, 139.44 (d, J = 7.2 Hz),
    134.60 (d, J = 3.3 Hz), 130.48,
    129.40 (d, J = 8.0 Hz), 116.37 (d, J = 20.5 Hz),
    112.71 (d, J = 20.5 Hz),
    109.56, 71.90, 56.11, 49.65, 48.16,
    40.26, 31.30, 30.80, 26.44, 26.40,
    26.30, 20.72, 18.19, 18.19.
    19F NMR (376 MHz, CDCl3) δ −117.64.
    120 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.13 (d,
    film) 3372, calcd for C24H32FN2O5, J = 3.1 Hz, 1H), 8.45 (t, J = 6.7 Hz,
    2965, 447.2290; found, 447.2296 1H), 8.02 (dd, J = 5.2, 3.5 Hz, 1H),
    1734, 7.22 (ddd, J = 8.8, 6.1, 4.0 Hz, 1H), 6.89 (dd,
    1650, J = 5.3, 1.7 Hz, 1H), 6.82 (dd, J = 10.0,
    1529, 2.9 Hz, 1H), 6.73 (qd, J = 8.7, 2.9 Hz,
    1265, 954, 1H), 5.44 (tdd, J = 9.1, 6.4, 3.5 Hz, 1H),
    801, 734 cm−1 4.68 (dp, J = 10.9, 7.3 Hz, 1H), 3.95 (s,
    3H), 2.78 (ddd, J = 48.5, 9.2, 4.9 Hz,
    1H), 2.27 (d, J = 3.9 Hz, 3H),
    1.87-1.33 (m, 4H), 1.26 (s, 1H),
    1.23-0.76 (m, 7H), 0.76-0.60 (m, 3H).
    19F NMR (376 MHz, CDCl3) δ −117.60,
    −117.64.
    121 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.12 (s,
    film) 3368, calcd for C24H30FN2O5, 1H), 8.38 (d, J = 8.1 Hz, 1H), 7.99 (d, J = 5.1 Hz,
    2938, 445.2133; found, 445.2130 1H), 7.06 (dd, J = 8.6, 5.9 Hz,
    1733, 1H), 6.87 (d, J = 5.2 Hz, 1H), 6.80 (dd,
    1648, J = 9.9, 2.8 Hz, 1H), 6.74 (td, J = 8.5,
    1528, 2.9 Hz, 1H), 5.16 (p, J = 6.3 Hz, 1H),
    1481, 4.58 (p, J = 7.3 Hz, 1H), 3.94 (s, 3H),
    1439, 3.03 (dd, J = 10.4, 6.6 Hz, 1H),
    1263, 953, 2.70-2.57 (m, 1H), 2.34 (s, 3H),
    800, 730 cm−1 2.23-2.10 (m, 1H), 1.86-1.55 (m, 4H),
    1.45-1.34 (m, 1H), 1.28-1.22 (m, 3H),
    1.19 (d, J = 6.3 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 171.39,
    168.64, 160.91 (d, J = 243.9 Hz),
    155.43, 148.81, 140.45, 139.10 (d, J = 6.7 Hz),
    134.12 (d, J = 3.2 Hz), 130.49,
    128.52 (d, J = 5.2 Hz), 116.50 (d, J = 20.4 Hz),
    112.72 (d, J = 20.7 Hz),
    109.49, 74.20, 56.09, 50.86, 47.99,
    37.76, 29.39, 26.99, 20.45, 18.51,
    18.19, 17.92.
    19F NMR (376 MHz, CDCl3) δ −117.49.
    122 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.13 (s,
    film) 3369, calcd for C25H32FN2O5, 1H), 8.41 (d, J = 8.2 Hz, 1H), 7.98 (d, J = 5.2 Hz,
    2946, 459.2290; found, 459.2318 1H), 7.09 (dd, J = 8.6, 5.9 Hz,
    1732, 1H), 6.92-6.80 (m, 2H), 6.77 (dd, J = 9.9,
    1648, 2.8 Hz, 1H), 5.31 (p, J = 6.4 Hz,
    1528, 1H), 4.75-4.64 (m, 1H), 3.95 (s, 3H),
    1262, 3.10 (dt, J = 7.1, 5.4 Hz, 1H), 2.26 (s,
    1153, 953, 3H), 2.20-2.06 (m, 1H), 1.87 (qdd, J = 11.1,
    800, 730 cm−1 8.9, 7.1, 3.8 Hz, 1H),
    1.69-1.06 (m, 12H), 0.98-0.82 (m, 1H).
    13C NMR (101 MHz, CDCl3) δ 171.59,
    168.65, 160.84 (d, J = 244.2 Hz),
    155.41, 148.81, 140.44, 139.16 (d, J = 7.4 Hz),
    134.99 (d, J = 3.0 Hz), 130.48,
    129.07 (d, J = 8.3 Hz), 116.78 (d, J = 20.4 Hz),
    112.48 (d, J = 20.6 Hz),
    109.49, 75.73, 56.09, 48.21, 48.21,
    43.47, 31.50, 31.09, 25.12, 24.13,
    20.72, 18.23, 17.26.
    19F NMR (376 MHz, CDCl3) δ −117.47.
    123 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.14 (s,
    film) 3371, calcd for C26H34FN2O5, 1H), 8.47 (d, J = 8.1 Hz, 1H), 7.99 (d, J = 5.2 Hz,
    2928, 473.2446; found, 473.2467 1H), 7.05 (dd, J = 8.6, 5.9 Hz,
    1733, 1H), 6.92-6.75 (m, 4H), 5.40 (dq, J = 9.0,
    1650, 6.3 Hz, 1H), 4.77-4.68 (m, 1H),
    1528, 3.95 (s, 3H), 3.12 (dd, J = 9.0, 6.1 Hz,
    1450, 1H), 2.29 (s, 3H), 1.82-1.59 (m, 3H),
    1264, 1.53 (dd, J = 21.9, 7.2 Hz, 5H),
    1155, 954, 1.28-0.78 (m, 8H).
    800, 732 cm−1 13C NMR (101 MHz, CDCl3) δ 171.67,
    168.67, 160.89 (d, J = 244.6 Hz),
    155.42, 148.82, 140.47, 139.76 (d, J = 7.6 Hz),
    133.87 (d, J = 3.3 Hz),
    130.50, 129.20 (d, J = 7.2 Hz), 116.93 (d, J = 20.6 Hz),
    112.37 (d, J = 20.7 Hz),
    109.50, 73.49, 56.10, 49.06, 48.20,
    40.18, 31.47, 29.14, 26.60, 26.55,
    26.32, 20.95, 18.38, 17.98.
    19F NMR (376 MHz, CDCl3) δ −117.35.
    124 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.13 (s,
    film) 3366, calcd for C23H30FN2O5, 1H), 8.45 (d, J = 8.0 Hz, 1H), 7.99 (d, J = 5.2 Hz,
    2961, 433.2133; found, 433.2129 1H), 7.05 (dd, J = 8.6, 5.9 Hz,
    1734, 1H), 6.93-6.77 (m, 3H), 5.38 (dq, J = 8.9,
    1650, 6.3 Hz, 1H), 4.76-4.65 (m, 1H),
    1529, 3.95 (s, 3H), 3.09 (dd, J = 8.9, 6.5 Hz,
    1264, 1H), 2.29 (s, 3H), 2.11 (h, J = 6.8 Hz,
    1153, 1H), 1.55 (d, J = 7.2 Hz, 3H), 1.08 (d, J = 6.2 Hz,
    1049, 955, 3H), 0.86 (d, J = 6.8 Hz, 3H),
    801, 735 cm−1 0.78 (d, J = 6.7 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −117.30.
    125 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.13 (s,
    film) 3368, calcd for C25H34FN2O5, 1H), 8.42 (d, J = 8.2 Hz, 1H), 7.98 (d, J = 5.3 Hz,
    2962, 461.2446; found, 461.2442 1H), 7.10 (dd, J = 8.7, 5.9 Hz,
    1733, 1H), 6.88 (d, J = 5.1 Hz, 1H), 6.83 (td,
    1650, J = 8.3, 2.8 Hz, 1H), 6.77 (dd, J = 9.9,
    1528, 2.9 Hz, 1H), 5.46-5.40 (m, 1H),
    1263, 4.75-4.66 (m, 1H), 3.95 (d, J = 2.2 Hz, 3H),
    1154, 3.27 (t, J = 7.7 Hz, 1H), 2.27 (s, 2H),
    1057, 954, 1.67-1.24 (m, 8H), 1.14-0.82 (m,
    800, 733 cm−1 7H), 0.76 (t, J = 7.4 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −117.38.
    126 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.13 (d,
    film) 3369, calcd for C24H32FN2O5, J = 4.6 Hz, 1H), 8.50-8.39 (m, 1H),
    2964, 447.2290; found, 447.2302 7.99 (dd, J = 5.3, 2.8 Hz, 1H),
    1733, 7.07 (ddd, J = 8.9, 5.9, 3.1 Hz, 1H),
    1649, 6.93-6.75 (m, 3H), 5.40 (ddq, J = 21.8, 9.3,
    1528, 6.3 Hz, 1H), 4.77-4.64 (m, 1H),
    1262, 3.95 (s, 3H), 3.16 (ddd, J = 24.5, 8.9, 6.4 Hz,
    1056, 953, 1H), 2.35-2.26 (m, 3H),
    800, 730 cm−1 1.94-1.73 (m, 1H), 1.55 (t, J = 6.9 Hz, 3H),
    1.52-1.33 (m, 1H), 1.08 (dd, J = 9.4, 6.2 Hz,
    3H), 1.01-0.72 (m, 7H).
    19F NMR (376 MHz, CDCl3) δ −117.29,
    −117.34.
    127 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 12.14 (s,
    film) 3369, calcd for C24H29FN2O5, 1H), 8.46 (d, J = 8.1 Hz, 1H), 8.00 (dd,
    2939, 467.1953; found, 467.1940 J = 8.2, 5.2 Hz, 1H), 7.01 (ddd, J = 9.3,
    1733, 4.6, 2.2 Hz, 1H), 6.88 (d, J = 5.2 Hz,
    1649, 1H), 6.82 (dd, J = 8.0, 3.4 Hz, 2H),
    1438, 5.12 (p, J = 6.3 Hz, 1H), 4.78-4.64 (m,
    1261, 1H), 3.95 (s, 3H), 3.14 (dd, J = 10.0,
    1039, 953, 7.4 Hz, 1H), 2.74 (h, J = 8.3 Hz, 1H),
    800, 729 cm−1 2.33 (s, 3H), 2.23-2.06 (m, 1H),
    2.05-1.57 (m, 4H), 1.54 (d, J = 7.1 Hz,
    3H), 1.45-1.33 (m, 1H), 1.09 (d, J = 6.3 Hz,
    3H).
    19F NMR (376 MHz, CDCl3) δ −117.25.
    128 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 12.14 (s,
    film) 3369, calcd for C25H31FN2NaO5, 1H), 8.45 (d, J = 7.7 Hz, 1H), 8.02 (d, J = 5.1 Hz,
    2951, 481.2109; found, 481.2105 1H), 7.30 (dd, J = 8.7, 6.1 Hz,
    1735, 1H), 6.90 (d, J = 5.2 Hz, 1H), 6.82 (dd,
    1650, J = 9.9, 2.9 Hz, 1H), 6.71 (td, J = 8.5,
    1529, 2.9 Hz, 1H), 5.33 (qd, J = 6.3, 3.4 Hz,
    1264, 953, 1H), 4.71 (p, J = 7.3 Hz, 1H), 3.96 (s,
    733 cm−1 3H), 2.78 (dd, J = 10.5, 3.7 Hz, 1H),
    2.29 (s, 3H), 2.28-2.16 (m, 1H),
    1.92 (ddq, J = 10.8, 7.1, 3.4 Hz, 1H),
    1.73-1.60 (m, 1H), 1.60-1.47 (m, 5H),
    1.47-1.31 (m, 2H), 1.31-1.15 (m, 1H),
    1.04 (d, J = 6.4 Hz, 3H),
    0.92-0.77 (m, 1H).
    19F NMR (376 MHz, CDCl3) δ −117.71.
    129 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.15 (s,
    film) 3372, calcd for C26H34FN2O5, 1H), 8.42 (d, J = 7.7 Hz, 1H), 8.02 (d, J = 5.2 Hz,
    2928, 473.2446; found, 473.2455 1H), 7.30 (dd, J = 8.7, 6.1 Hz,
    1733, 1H), 6.90 (d, J = 5.2 Hz, 1H), 6.81 (dd,
    1527, J = 9.9, 2.8 Hz, 1H), 6.68 (td, J = 8.5,
    1263, 955, 2.9 Hz, 1H), 5.45 (qd, J = 6.2, 4.0 Hz,
    800, 730 cm−1 1H), 4.70 (p, J = 7.2 Hz, 1H), 3.96 (s,
    3H), 2.73 (dd, J = 9.9, 4.1 Hz, 1H),
    2.26 (s, 3H), 1.92 (dt, J = 12.9, 3.2 Hz, 1H),
    1.80-1.53 (m, 4H), 1.51 (d, J = 7.2 Hz,
    3H), 1.35-1.03 (m, 4H), 1.00 (d, J = 6.3 Hz,
    3H), 0.95 (td, J = 12.1, 3.7 Hz,
    1H), 0.74 (qd, J = 12.2, 3.6 Hz,
    1H).
    19F NMR (376 MHz, CDCl3) δ −117.72.
    130 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.12 (s,
    film) 3372, calcd for C23H30FN2O5, 1H), 8.43 (d, J = 8.3 Hz, 1H), 8.02 (d, J = 5.2 Hz,
    2964, 433.2133; found, 433.2130 1H), 7.33-7.23 (m, 1H),
    1734, 6.90 (d, J = 5.2 Hz, 1H), 6.82 (dd, J = 10.0,
    1528, 3.0 Hz, 1H), 6.66 (td, J = 8.5, 2.9 Hz,
    1264, 954, 1H), 5.44 (qd, J = 6.3, 4.0 Hz, 1H),
    801, 732 cm−1 4.70 (p, J = 7.3 Hz, 1H), 3.96 (s, 3H),
    2.68-2.62 (m, 1H), 2.27 (s, 3H),
    2.15-1.82 (m, 1H), 1.50 (d, J = 7.2 Hz,
    3H), 1.02 (dd, J = 6.4, 2.1 Hz, 6H),
    0.67 (d, J = 6.7 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −117.67.
    131 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 12.16 (s,
    film) 3369, calcd for C24H33N2O5, 1H), 8.49 (d, J = 8.0 Hz, 1H), 8.01 (d, J = 5.2 Hz,
    2968, 451.2203; found, 451.2190 1H), 7.15 (d, J = 7.9 Hz, 1H),
    1732, 6.93 (d, J = 1.8 Hz, 1H),
    1649, 6.92-6.85 (m, 2H), 5.44 (qd, J = 6.2, 4.1 Hz, 1H),
    1527, 4.76-4.60 (m, 1H), 3.94 (s, 3H),
    1263, 800, 2.70 (dd, J = 9.2, 5.0 Hz, 1H), 2.27 (s, 3H),
    730 cm−1 2.24 (s, 3H), 2.02 (dp, J = 9.1, 6.7 Hz,
    1H), 1.42 (d, J = 7.2 Hz, 3H), 1.09 (d, J = 6.3 Hz,
    3H), 0.99 (d, J = 6.6 Hz, 3H),
    0.70 (d, J = 6.7 Hz, 3H).
    132 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 12.17 (s,
    film) 3369, calcd for C26H35N2O5, 1H), 8.50 (d, J = 8.0 Hz, 1H), 8.02 (d, J = 5.2 Hz,
    2947, 455.2540; found, 455.2536 1H), 7.16 (d, J = 7.9 Hz, 1H),
    2868, 6.93 (d, J = 1.8 Hz, 1H),
    2256, 6.91-6.85 (m, 2H), 5.33 (qd, J = 6.3, 4.2 Hz, 1H),
    1713, 4.70 (p, J = 7.4 Hz, 1H), 3.94 (s, 3H),
    1527, 2.80 (dd, J = 10.2, 4.2 Hz, 1H), 2.26 (s,
    1263, 730 cm−1 3H), 2.26 (s, 3H), 2.17 (dddd, J = 17.0,
    10.2, 6.8, 3.1 Hz, 1H), 1.89 (dtd, J = 11.0,
    7.1, 3.3 Hz, 1H), 1.69-1.31 (m,
    8H), 1.21 (dq, J = 12.3, 9.2 Hz, 1H),
    1.09 (d, J = 6.4 Hz, 3H),
    0.92-0.81 (m, 1H).
    133 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 12.17 (d,
    film) 3369, calcd for C27H37N2O5, J = 0.6 Hz, 1H), 8.50 (d, J = 8.0 Hz,
    2925, 491.2516; found, 491.2520 1H), 8.02 (d, J = 5.2 Hz, 1H), 7.16 (d, J = 7.9 Hz,
    2850, 1H), 6.92 (d, J = 1.9 Hz, 1H),
    1731, 6.91-6.86 (m, 2H), 5.44 (qd, J = 6.3,
    1527, 4.7 Hz, 1H), 4.75-4.64 (m, 1H),
    1262, 729 cm−1 3.94 (s, 3H), 2.76 (dd, J = 9.3, 4.8 Hz, 1H),
    2.27 (s, 3H), 2.23 (s, 3H), 1.87 (dt, J = 12.5,
    3.3 Hz, 1H), 1.78-1.47 (m, 4H),
    1.44 (d, J = 7.2 Hz, 3H),
    1.39-1.14 (m, 2H), 1.05 (d, J = 6.3 Hz, 3H),
    1.03-0.69 (m, 4H).
    134 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ
    film) 3369, calcd for C25H35N2O5, 12.15 (dd, J = 3.6, 0.6 Hz, 1H),
    2964, 443.2540; found, 443.2562 8.52-8.44 (m, 1H), 8.01 (t, J = 5.1 Hz, 1H),
    2933, 7.15 (dd, J = 7.9, 2.0 Hz, 1H),
    2875, 6.95-6.91 (m, 1H), 6.91-6.85 (m, 2H),
    1732, 5.49-5.40 (m, 1H), 4.73-4.61 (m, 1H),
    1527, 3.94 (s, 3H), 2.88-2.70 (m, 1H),
    1263, 800, 2.28-2.22 (m, 6H), 1.91-1.68 (m, 1H),
    730 cm−1 1.49-1.33 (m, 3H), 1.14-0.64 (m, 11H).
    135 IR (thin ESIMS m/z 419.1 1H NMR (400 MHz, CDCl3) δ 12.14 (s,
    film) 3370, ([M + H]+) 1H), 8.45 (d, J = 8.0 Hz, 1H), 8.00 (d, J = 5.2 Hz,
    2961, 1H), 7.09-6.99 (m, 2H),
    1733, 6.99-6.90 (m, 2H), 6.89 (d, J = 5.2 Hz,
    1648, 1H), 5.40 (dq, J = 8.4, 6.3 Hz, 1H),
    1575, 4.69 (p, J = 7.3 Hz, 1H), 3.96 (s, 3H),
    1528, 3.71 (t, J = 6.9 Hz, 1H), 2.70 (dd, J = 8.3,
    1509, 6.8 Hz, 1H), 1.54 (d, J = 7.1 Hz,
    1480, 3H), 1.10 (d, J = 6.3 Hz, 3H), 0.87 (d, J = 6.8 Hz,
    1453, 3H), 0.74 (d, J = 6.7 Hz, 3H).
    1437, 13C NMR (126 MHz, CDCl3) δ 171.63,
    1307, 168.72, 168.30, 161.72 (d, J = 244.8 Hz),
    1280, 155.40, 155.06, 150.14, 148.78,
    1261, 140.49, 139.14, 134.23 (d, J = 3.3 Hz),
    1241, 131.01 (d, J = 7.7 Hz), 130.46,
    1150, 801 cm−1 114.80 (d, J = 21.1 Hz), 109.47, 108.37, 72.80,
    56.10, 55.83, 50.65, 48.19, 47.95,
    28.35, 27.05, 23.40, 21.21, 18.75,
    18.32, 17.41.
    136 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.92 (s,
    film) 3131, calcd for C23H30FN2O4S, 1H), 10.79-10.61 (m, 1H), 7.98 (d, J = 5.1 Hz,
    2959, 449.1905; found, 449.1906 1H), 7.05 (dd, J = 8.6, 5.9 Hz,
    1748, 1H), 6.85 (ddt, J = 17.1, 9.5, 4.7 Hz,
    1511, 3H), 5.40 (dq, J = 13.0, 6.4 Hz, 1H),
    1479, 5.09 (p, J = 7.2 Hz, 1H), 3.97 (s, 3H),
    1280, 3.11 (dd, J = 9.0, 6.3 Hz, 1H), 2.30 (s,
    1207, 3H), 2.13 (dt, J = 13.5, 6.8 Hz, 1H),
    1142, 797 cm−1 1.64 (d, J = 7.1 Hz, 3H), 1.09 (d, J = 6.3 Hz,
    3H), 0.86 (d, J = 6.7 Hz, 3H),
    0.79 (d, J = 6.8 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −117.20.
    137 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.15 (d,
    film) 3372, calcd for C25H34FN2O6, J = 0.6 Hz, 1H), 8.47 (d, J = 8.1 Hz,
    2963, 477.2395; found, 477.2392 1H), 8.02 (d, J = 5.3 Hz, 1H), 7.18 (dd,
    1731, J = 8.5, 6.9 Hz, 1H), 6.89 (d, J = 5.1 Hz,
    1649, 1H), 6.57 (dd, J = 11.0, 2.5 Hz,
    1528, 1H), 6.51 (td, J = 8.4, 2.6 Hz, 1H),
    1450, 5.40 (qd, J = 6.2, 4.5 Hz, 1H),
    1263, 4.75-4.62 (m, 1H), 3.95 (s, 3H), 3.77 (s, 4H),
    1149, 3.31 (dd, J = 9.9, 4.5 Hz, 1H), 1.63 (d, J = 12.1 Hz,
    1036, 953 cm−1 1H), 1.45 (d, J = 7.2 Hz, 3H),
    1.42-1.27 (m, 1H), 1.24-1.08 (m,
    1H), 1.03 (d, J = 6.2 Hz, 3H),
    1.01-0.91 (m, 1H), 0.88 (t, J = 7.4 Hz, 3H),
    0.65 (t, J = 7.4 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −114.13.
    138 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.15 (s,
    film) 3370, calcd for C23H30FN2O6, 1H), 8.46 (d, J = 8.0 Hz, 1H), 8.01 (d, J = 5.2 Hz,
    2964, 449.2082; found, 449.2079 1H), 7.16 (dd, J = 8.5, 6.9 Hz,
    1731, 1H), 6.89 (d, J = 5.2 Hz, 1H), 6.57 (dd,
    1649, J = 11.1, 2.5 Hz, 1H), 6.51 (td, J = 8.3,
    1528, 2.5 Hz, 1H), 5.49-5.40 (m, 1H),
    1263, 4.74-4.61 (m, 1H), 3.95 (s, 3H), 3.77 (s, 3H),
    1149, 953, 3.06 (dd, J = 9.4, 5.0 Hz, 1H),
    731 cm−1 1.96 (ddq, J = 13.1, 9.1, 6.6 Hz, 1H), 1.42 (d,
    J = 7.2 Hz, 3H), 1.07 (d, J = 6.3 Hz,
    3H), 0.97 (d, J = 6.6 Hz, 3H), 0.66 (d, J = 6.6 Hz,
    3H).
    19F NMR (376 MHz, CDCl3) δ −114.12.
    139 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.16 (s,
    film) 3371, calcd for C26H34FN2O6, 1H), 8.47 (d, J = 8.1 Hz, 1H), 8.02 (d, J = 5.2 Hz,
    2928, 489.2395; found, 489.2401 1H), 7.17 (t, J = 7.7 Hz, 1H),
    1731, 6.89 (d, J = 5.2 Hz, 1H),
    1649, 6.61-6.46 (m, 2H), 5.44 (p, J = 6.1 Hz, 1H),
    1528, 4.69 (p, J = 7.3 Hz, 1H), 3.95 (s, 3H),
    1449, 3.76 (s, 3H), 3.12 (d, J = 6.7 Hz, 1H),
    1262, 1.84 (d, J = 13.0 Hz, 1H), 1.78-1.48 (m,
    1150, 4H), 1.45 (d, J = 7.2 Hz, 3H),
    1128, 1.37-1.05 (m, 4H), 1.04 (d, J = 6.3 Hz, 3H),
    1035, 953, 1.01-0.86 (m, 1H), 0.75 (qd, J = 12.1,
    729 cm−1 3.6 Hz, 1H).
    19F NMR (376 MHz, CDCl3) δ −114.15.
    140 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.17 (s,
    film) 3370, calcd for C25H32FN2O6, 1H), 8.48 (d, J = 8.0 Hz, 1H), 8.02 (d, J = 5.2 Hz,
    2944, 475.2239; found, 475.2233 1H), 7.21-7.13 (m, 1H),
    1732, 6.89 (d, J = 5.2 Hz, 1H), 6.57 (dd, J = 11.1,
    1649, 2.5 Hz, 1H), 6.48 (td, J = 8.3, 2.5 Hz,
    1528, 1H), 5.34 (qd, J = 6.2, 3.3 Hz, 1H),
    1450, 4.71 (p, J = 7.4 Hz, 1H), 3.95 (s, 3H),
    1263, 3.77 (s, 3H), 3.18-3.06 (m, 1H),
    1149, 2.21-2.05 (m, 1H), 1.87 (dtd, J = 11.2, 7.1,
    1036, 952, 3.5 Hz, 1H), 1.74-1.59 (m, 1H),
    731 cm−1 1.58-1.45 (m, 4H), 1.37 (dddd, J = 26.9,
    11.8, 7.7, 3.1 Hz, 1H), 1.28-1.16 (m,
    2H), 1.04 (d, J = 6.3 Hz, 3H),
    1.02-0.97 (m, 1H), 0.95-0.82 (m, 1H).
    19F NMR (376 MHz, CDCl3) δ −114.21.
    141 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.15 (d,
    film) 3371, calcd for C24H32FN2O6, J = 5.4 Hz, 1H), 8.45 (dd, J = 13.9, 8.0 Hz,
    2964, 463.2239; found, 463.2234 1H), 8.01 (dd, J = 6.2, 5.2 Hz, 1H),
    1731, 7.16 (ddd, J = 8.5, 6.9, 4.0 Hz, 1H),
    1649, 6.88 (dd, J = 5.2, 3.9 Hz, 1H),
    1451, 6.63-6.47 (m, 2H), 5.50-5.39 (m, 1H),
    1263, 4.75-4.59 (m, 1H), 3.95 (d, J = 0.9 Hz,
    1149, 3H), 3.77 (s, 3H), 3.29-3.06 (m, 1H),
    1036, 952, 1.82-1.66 (m, 1H), 1.49 (dd, J = 12.2,
    730 cm−1 7.1 Hz, 2H), 1.33 (d, J = 7.2 Hz, 1H),
    1.20-1.00 (m, 4H), 1.00-0.78 (m,
    4H), 0.74-0.63 (m, 3H).
    19F NMR (376 MHz, CDCl3) δ −114.11,
    −114.15.
    142 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.16 (s,
    film) 3371, calcd for C24H30FN2O6, 1H), 8.41 (d, J = 8.0 Hz, 1H), 8.00 (d, J = 5.2 Hz,
    2938, 461.2082; found, 461.2073 1H), 7.03 (dd, J = 8.5, 6.8 Hz,
    1732, 1H), 6.88 (d, J = 5.2 Hz, 1H), 6.55 (dd,
    1649, J = 11.0, 2.5 Hz, 1H), 6.47 (td, J = 8.3,
    1529, 2.5 Hz, 1H), 5.24 (q, J = 6.5 Hz, 1H),
    1451, 4.61 (p, J = 7.3 Hz, 1H), 3.95 (s, 3H),
    1264, 3.79 (s, 3H), 3.25 (s, 1H),
    1148, 953, 2.69-2.58 (m, 1H), 2.16-2.04 (m, 1H),
    732 cm−1 1.89-1.57 (m, 4H), 1.51-1.37 (m, 1H),
    1.34 (d, J = 7.2 Hz, 3H), 1.13 (d, J = 6.4 Hz,
    3H).
    19F NMR (376 MHz, CDCl3) δ −114.03.
    143 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.18 (s,
    film) 3369, calcd for C26H34FN2O6, 1H), 8.50 (d, J = 8.1 Hz, 1H), 7.98 (d, J = 5.2 Hz,
    2927, 489.2395; found, 489.2399 1H), 7.01 (dd, J = 8.5, 6.8 Hz,
    1732, 1H), 6.88 (d, J = 5.2 Hz, 1H), 6.60 (td,
    1649, J = 8.2, 2.6 Hz, 1H), 6.54 (dd, J = 11.0,
    1528, 2.5 Hz, 1H), 5.46 (s, 1H),
    1450, 4.76-4.62 (m, 1H), 3.95 (s, 3H), 3.75 (s, 3H),
    1278, 3.39 (s, 1H), 1.80-1.59 (m, 5H),
    1263, 1.59-1.46 (m, 4H), 1.17 (qt, J = 13.4, 3.6 Hz,
    1035, 954, 1H), 1.08 (d, J = 6.3 Hz, 3H),
    731 cm−1 1.07-0.91 (m, 2H), 0.82 (qt, J = 15.4, 7.4 Hz,
    2H).
    19F NMR (376 MHz, CDCl3) δ −113.87.
    144 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.18 (s,
    film) 3370, calcd for C25H32FN2O6, 1H), 8.46 (d, J = 8.1 Hz, 1H), 7.96 (d, J = 5.2 Hz,
    2943, 475.2239; found, 475.2223 1H), 7.05 (t, J = 7.6 Hz, 1H),
    1731, 6.87 (d, J = 5.2 Hz, 1H), 6.59 (td, J = 8.3,
    1528, 2.5 Hz, 1H), 6.50 (dd, J = 11.1, 2.5 Hz,
    1450, 1H), 5.34 (s, 1H), 4.77-4.59 (m,
    1279, 1H), 3.95 (s, 3H), 3.73 (s, 3H),
    1263, 3.65-3.13 (m, 1H), 2.30-2.02 (m, 1H),
    1148, 1.84 (td, J = 11.6, 10.9, 6.8 Hz, 1H),
    1034, 953, 1.69-1.54 (m, 2H), 1.54-1.33 (m, 6H),
    731 cm−1 1.33-1.21 (m, 1H), 1.13 (d, J = 6.4 Hz,
    3H), 0.98-0.81 (m, 1H).
    19F NMR (376 MHz, CDCl3) δ −114.03.
    145 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.18 (s,
    film) 3370, calcd for C25H34FN2O6, 1H), 8.48 (d, J = 7.9 Hz, 1H), 7.97 (d, J = 5.3 Hz,
    2962, 477.2395; found, 477.2389 1H), 7.04 (dd, J = 8.6, 6.8 Hz,
    1762, 1H), 6.87 (d, J = 5.2 Hz, 1H), 6.59 (td,
    1649, J = 8.2, 2.5 Hz, 1H), 6.52 (dd, J = 11.0,
    1528, 2.6 Hz, 1H), 5.50-5.41 (m, 1H),
    1451, 4.74-4.64 (m, 1H), 3.95 (s, 3H), 3.74 (s, 3H),
    1262, 3.57 (d, J = 10.4 Hz, 1H),
    1150, 1.65-1.55 (m, 1H), 1.53 (d, J = 7.2 Hz, 3H),
    1034, 954, 1.51-1.23 (m, 2H), 1.17 (dq, J = 14.2, 7.2 Hz,
    731 cm−1 1H), 1.10 (d, J = 6.2 Hz, 3H),
    1.01-0.83 (m, 4H), 0.82-0.68 (m, 3H).
    19F NMR (376 MHz, CDCl3) δ −113.85.
    146 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.17 (s,
    film) 3370, calcd for C24H32FN2O6, 1H), 8.50 (q, J = 10.0, 8.1 Hz, 1H),
    2963, 463.2239; found, 463.2227 7.98 (t, J = 5.5 Hz, 1H), 7.02 (dd, J = 8.4,
    1732, 6.8 Hz, 1H), 6.88 (d, J = 5.2 Hz, 1H),
    1649, 6.66-6.48 (m, 2H), 5.45 (dd, J = 13.7,
    1527, 7.1 Hz, 1H), 4.79-4.63 (m, 1H),
    1451, 3.95 (s, 3H), 3.82-3.70 (m, 3H), 3.46 (s,
    1278, 1H), 1.87-1.72 (m, 1H), 1.54 (dd, J = 14.3,
    1263, 7.1 Hz, 3H), 1.43-1.23 (m, 1H),
    1149, 1.09 (dd, J = 11.6, 6.2 Hz, 3H),
    1035, 730 cm−1 0.99-0.80 (m, 4H), 0.80-0.69 (m, 3H).
    19F NMR (376 MHz, CDCl3) δ −113.79,
    −113.87.
    147 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.18 (s,
    film) 3371, calcd for C24H30FN2O6, 1H), 8.47 (d, J = 8.1 Hz, 1H), 7.98 (d, J = 5.2 Hz,
    2939, 461.2082; found, 461.2060 1H), 6.97 (dd, J = 8.5, 6.7 Hz,
    1733, 1H), 6.87 (d, J = 5.2 Hz, 1H),
    1529, 6.61-6.50 (m, 2H), 5.19 (s, 1H),
    1280, 4.74-4.60 (m, 1H), 3.95 (s, 3H), 3.78 (s, 3H),
    1264, 3.34 (s, 1H), 2.79 (hept, J = 8.8, 7.9 Hz, 1H),
    11748, 954 cm−1 2.20-2.06 (m, 1H), 2.00-1.83 (m,
    1H), 1.83-1.71 (m, 1H),
    1.71-1.59 (m, 2H), 1.51 (dd, J = 7.2, 2.7 Hz, 3H),
    1.42 (qd, J = 9.6, 1.7 Hz, 1H), 1.10 (d, J = 6.4 Hz,
    3H).
    19F NMR (376 MHz, CDCl3) δ −113.83.
    148 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ
    film) 3371, calcd for C23H30FN2O6, 12.18-12.16 (m, 1H), 8.50 (d, J = 7.9 Hz, 1H),
    2961, 449.2082; found, 449.2063 7.98 (d, J = 5.2 Hz, 1H), 7.01 (dd, J = 8.5,
    1732, 6.7 Hz, 1H), 6.88 (d, J = 5.2 Hz,
    1528, 1H), 6.61 (td, J = 8.3, 2.6 Hz, 1H),
    1280, 6.55 (dd, J = 11.0, 2.5 Hz, 1H), 5.44 (d, J = 7.5 Hz,
    1262, 1H), 4.76-4.64 (m, 1H),
    1149, 4.12 (q, J = 7.2 Hz, 0H), 3.95 (s, 3H),
    1034, 953, 3.75 (s, 3H), 3.34 (s, 1H), 2.14-2.02 (m,
    730 cm−1 1H), 1.54 (d, J = 7.2 Hz, 3H), 1.09 (d, J = 6.3 Hz,
    3H), 0.85 (d, J = 6.7 Hz, 3H),
    0.73 (d, J = 6.8 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −113.80.
    149 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 12.15 (d,
    film) 2937, calcd for C25H33F4N2O5, J = 0.6 Hz, 1H), 8.40 (d, J = 8.0 Hz,
    1732, 441.2384; found, 441.2378 1H), 7.99 (d, J = 5.2 Hz, 1H), 7.00 (d, J = 7.8 Hz,
    1689, 1H), 6.93-6.83 (m, 3H),
    1527, 5.24-5.12 (m, 1H), 4.65-4.51 (m,
    1439, 910, 1H), 3.94 (s, 3H), 3.04 (dd, J = 10.5,
    800, 729 cm−1 6.5 Hz, 1H), 2.75-2.60 (m, 1H),
    2.31 (s, 3H), 2.24 (s, 3H), 2.21-2.09 (m,
    1H), 1.88-1.61 (m, 4H), 1.41 (pd, J = 10.1,
    3.5 Hz, 1H), 1.24 (d, J = 7.2 Hz,
    3H), 1.19 (d, J = 6.3 Hz, 3H).
    150 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.14 (s,
    film) 3370, calcd for C22H28ClN2O5, 1H), 8.44 (d, J = 8.0 Hz, 1H), 8.00 (d, J = 5.2 Hz,
    2962, 435.1681; found, 435.168 1H), 7.22 (d, J = 8.4 Hz, 2H),
    1735, 7.02 (d, J = 8.4 Hz, 2H), 6.89 (d, J = 5.2 Hz,
    1649, 1H), 5.45-5.34 (m, 1H),
    1529, 4.76-4.61 (m, 1H), 3.96 (s, 3H), 2.69 (t, J = 7.6 Hz,
    1481, 1H), 2.13-2.00 (m, 1H),
    1264, 1.54 (d, J = 6.6 Hz, 3H), 1.10 (d, J = 6.3 Hz,
    1152, 3H), 0.88 (d, J = 6.7 Hz, 3H), 0.74 (d, J = 6.7 Hz,
    1052, 826, 3H).
    801 cm−1 13C NMR (126 MHz, CDCl3) δ 171.59,
    168.72, 155.41, 148.78, 140.51, 137.11,
    132.47, 130.99, 130.44, 128.13, 109.49,
    77.21, 72.62, 56.11, 56.01, 48.18,
    28.32, 21.17, 18.86, 18.31, 17.31.
    151 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.14 (s,
    film) 3370, calcd for C23H30FN2O5, 1H), 8.48 (d, J = 7.9 Hz, 1H), 8.00 (d, J = 5.2 Hz,
    2961, 434.2165; found, 434.2169 1H), 7.06 (t, J = 7.9 Hz, 1H),
    1734, 6.88 (d, J = 5.2 Hz, 1H),
    1649, 6.81-6.71 (m, 2H), 5.43-5.32 (m, 1H),
    1576, 4.73-4.63 (m, 1H), 3.95 (s, 3H), 2.67 (t, 1H),
    1528, 2.24 (s, 3H), 2.12-1.99 (m, 1H),
    1481, 1.55 (d, 3H), 1.11 (d, J = 6.3 Hz, 3H),
    1280, 0.87 (d, J = 6.7 Hz, 3H), 0.76 (d, J = 6.8 Hz,
    1262, 800 cm−1 3H).
    13C NMR (126 MHz, CDCl3) δ 171.66,
    168.71, 161.91, 159.97, 155.38, 148.76,
    140.49, 138.29, 138.23, 130.83, 130.79,
    130.48, 125.23, 125.20, 123.02, 122.88,
    116.15, 115.98, 109.44, 77.22, 72.79,
    56.09, 56.07, 48.17, 34.67, 31.59,
    28.33, 25.28, 22.66, 21.22, 20.71,
    18.75, 18.34, 17.51, 14.20, 14.17,
    14.13.
    152 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.12 (s,
    film) 2963, calcd for 1H), 8.43 (d, J = 8.1 Hz, 1H), 8.00 (d, J = 5.2 Hz,
    1736, C22H27F2N2O5, 438.1915; 1H), 7.09-6.98 (m, 1H),
    1649, found, 438.1921 6.95-6.86 (m, 2H), 6.84-6.75 (m,
    1517, 1H), 5.43-5.33 (m, 1H),
    1481, 4.74-4.60 (m, 1H), 3.96 (s, 3H), 2.68 (t, J = 7.6 Hz,
    1281, 1H), 2.11-2.00 (m, 1H), 1.53 (d,
    1264, 3H), 1.12 (d, J = 6.3 Hz, 3H), 0.89 (d, J = 6.7 Hz,
    1212, 3H), 0.75 (d, J = 6.7 Hz, 3H).
    1053, 801 cm−1 13C NMR (126 MHz, CDCl3) δ 171.54,
    168.73, 155.41, 148.78, 140.52, 130.40,
    118.11, 109.49, 77.21, 72.45, 56.11,
    55.86, 48.16, 28.43, 21.11, 18.94,
    18.28, 17.15.
    153 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.15 (d,
    film) 2962, calcd for C23H31FN2O5, J = 0.6 Hz, 1H), 8.49 (d, J = 7.9 Hz,
    1734, 433.2133; found, 433.2129 1H), 8.00 (d, J = 5.2 Hz, 1H),
    1715, 6.93-6.82 (m, 4H), 5.38 (dq, J = 8.6, 6.3 Hz,
    1530, 1H), 4.73-4.63 (m, 1H), 3.95 (s, 3H),
    1481, 2.66 (dd, J = 8.6, 6.6 Hz, 1H), 2.24 (d, J = 1.9 Hz,
    1282, 3H), 2.06 (hept, J = 6.8 Hz,
    1264, 1H), 1.55 (d, J = 7.2 Hz, 3H), 1.10 (d, J = 6.3 Hz,
    1244, 3H), 0.85 (d, J = 6.7 Hz, 3H),
    1220, 801 cm−1 0.75 (d, J = 6.8 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 171.65,
    168.73, 160.27 (d, J = 243.5 Hz),
    155.40, 148.79, 140.47, 133.95 (d, J = 3.8 Hz),
    132.52 (d, J = 4.9 Hz), 130.50,
    128.31 (d, J = 7.7 Hz), 124.11 (d, J = 17.0 Hz),
    114.39 (d, J = 22.0 Hz),
    109.48, 72.95, 56.07, 55.82, 48.20,
    28.32, 21.25, 18.68, 18.29, 17.62,
    14.61 (d, J = 3.5 Hz).
    19F NMR (376 MHz, CDCl3) δ −120.75.
    154 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.16 (d,
    film) 3367, calcd for C23H30FN2O6, J = 0.6 Hz, 1H), 8.50 (d, J = 7.9 Hz,
    2963, 449.2082; found, 449.2076 1H), 7.99 (d, J = 5.2 Hz, 1H), 7.03 (t, J = 8.5 Hz,
    1734, 1H), 6.91-6.84 (m, 1H),
    1649, 6.66 (ddd, J = 8.6, 2.6, 0.8 Hz, 1H),
    1530, 6.57 (dd, J = 12.0, 2.6 Hz, 1H),
    1508, 5.44 (dqd, J = 7.6, 6.3, 1.2 Hz, 1H),
    1282, 4.75-4.63 (m, 1H), 3.94 (s, 3H), 3.78 (s, 3H),
    1264, 3.10 (t, J = 7.7 Hz, 1H), 2.09 (tt, J = 13.5,
    1149, 801, 6.6 Hz, 1H), 1.55 (d, J = 7.2 Hz,
    731 cm−1 3H), 1.12 (d, J = 6.3 Hz, 3H),
    0.94-0.87 (m, 3H), 0.76 (d, J = 6.7 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 171.68,
    168.74, 162.09 (d, J = 244.2 Hz),
    159.37 (d, J = 11.4 Hz), 155.38, 148.78,
    140.47, 130.67 (d, J = 6.6 Hz), 130.56,
    117.46 (d, J = 15.4 Hz), 109.59 (d, J = 3.0 Hz),
    109.46, 101.41 (d, J = 27.9 Hz),
    72.76, 56.07, 55.44, 48.21, 47.95,
    28.41, 21.06, 19.09, 18.15, 17.30.
    19F NMR (376 MHz, CDCl3) δ −113.05.
    155 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.15 (d,
    film) 3367, calcd for C23H30FN2O6, J = 0.6 Hz, 1H), 8.48 (d, J = 7.9 Hz,
    2962, 449.2082; found, 449.2082 1H), 8.00 (d, J = 5.2 Hz, 1H),
    1715, 6.90-6.77 (m, 4H), 5.36 (dq, J = 8.4, 6.3 Hz,
    1518, 1H), 4.73-4.64 (m, 1H), 3.95 (s, 3H),
    1273, 3.87 (s, 3H), 2.68-2.60 (m, 1H),
    1222, 801 cm−1 2.05 (h, J = 6.7 Hz, 1H), 1.55 (d, J = 7.2 Hz,
    3H), 1.11 (d, J = 6.3 Hz, 3H), 0.87 (d, J = 6.7 Hz,
    3H), 0.76 (d, J = 6.7 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 171.63,
    168.76, 155.40, 151.94 (d, J = 245.1 Hz),
    148.79, 146.29 (d, J = 10.7 Hz),
    140.51, 131.69 (d, J = 5.6 Hz), 130.50,
    125.45 (d, J = 3.5 Hz), 117.10 (d, J = 18.2 Hz),
    112.94 (d, J = 2.2 Hz),
    109.50, 72.80, 56.21, 56.08, 55.73,
    48.21, 28.40, 21.21, 18.79, 18.30,
    17.45.
    19F NMR (376 MHz, CDCl3) δ −135.65.
    156 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.19 (d,
    film) 3367, calcd for C24H33N2O6, J = 0.6 Hz, 1H), 8.53 (d, J = 7.9 Hz,
    2960, 445.2333; found, 445.2332 1H), 7.98 (d, J = 5.2 Hz, 1H), 6.94 (d, J = 7.7 Hz,
    1732, 1H), 6.87 (d, J = 5.1 Hz, 1H),
    1649, 6.71 (dt, J = 7.7, 1.1 Hz, 1H), 6.66 (d, J = 1.5 Hz,
    1528, 1H), 5.51-5.35 (m, 1H),
    1262, 4.75-4.64 (m, 1H), 3.94 (s, 3H),
    1041, 800, 3.76 (s, 3H), 3.34 (s, 1H), 2.32 (s, 3H),
    730 cm−1 2.09 (h, J = 6.7 Hz, 1H), 1.55 (d, J = 7.2 Hz,
    3H), 1.09 (d, J = 6.2 Hz, 3H), 0.84 (d, J = 6.7 Hz,
    3H), 0.74 (d, J = 6.8 Hz, 3H).
    157 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.15 (d,
    film) 2960, calcd for C24H33N2O6, J = 0.6 Hz, 1H), 8.51 (d, J = 7.9 Hz,
    1715, 445.2333; found, 445.2328 1H), 7.99 (d, J = 5.2 Hz, 1H), 7.00 (dd,
    1529, J = 8.1, 0.8 Hz, 1H), 6.90-6.85 (m,
    1281, 1H), 6.70 (d, J = 8.2 Hz, 2H), 5.37 (dq,
    1222, J = 9.2, 6.2 Hz, 1H), 4.76-4.66 (m,
    1048, 801, 1H), 3.95 (s, 3H), 3.78 (s, 3H),
    732 cm−1 3.07 (dd, J = 9.2, 6.1 Hz, 1H), 2.29 (s, 3H),
    2.11 (dq, J = 13.4, 6.8 Hz, 1H), 1.56 (d,
    J = 7.1 Hz, 3H), 1.07 (d, J = 6.2 Hz,
    3H), 0.84 (d, J = 6.8 Hz, 3H), 0.79 (d, J = 6.8 Hz,
    3H).
    13C NMR (101 MHz, CDCl3) δ 171.80,
    168.71, 157.59, 155.39, 148.79, 140.47,
    138.86, 130.54, 129.90, 128.80, 115.92,
    110.88, 109.47, 74.41, 56.08, 55.04,
    48.26, 29.71, 29.29, 21.08, 20.96,
    18.76, 18.27, 18.23.
    158 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.18 (d,
    film) 3370, calcd for C23H31N2O6, J = 0.6 Hz, 1H), 8.52 (d, J = 7.9 Hz,
    2961, 431.2177; found, 431.2155 1H), 7.99 (d, J = 5.2 Hz, 1H),
    1732, 7.22-6.77 (m, 5H), 5.55-5.36 (m, 1H),
    1649, 4.76-4.59 (m, 1H), 3.94 (s, 3H), 3.77 (s,
    1528, 3H), 3.55-3.22 (m, 1H),
    1241, 2.18-2.05 (m, 1H), 1.55 (d, J = 7.2 Hz, 3H),
    1050, 755, 1.09 (d, J = 6.3 Hz, 3H), 0.85 (d, J = 6.8 Hz,
    731 cm−1 3H), 0.74 (d, J = 6.8 Hz, 3H).
    159 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.19 (s,
    film) 3369, calcd for C24H33N2O7, 1H), 8.53 (d, J = 7.9 Hz, 1H), 7.99 (d, J = 5.2 Hz,
    2960, 461.2282; found, 461.2266 1H), 6.96 (d, J = 8.2 Hz, 1H),
    1732, 6.87 (d, J = 5.3 Hz, 1H),
    1649, 6.52-6.38 (m, 2H), 5.43 (s, 1H), 4.77-4.60 (m,
    1528, 1H), 3.95 (s, 3H), 3.79 (s, 3H), 3.75 (s,
    1262, 3H), 3.41-3.14 (m, 1H), 2.07 (dq, J = 13.4,
    1207, 6.7 Hz, 1H), 1.55 (d, J = 7.1 Hz,
    1156, 3H), 1.09 (d, J = 6.2 Hz, 3H), 0.83 (d, J = 6.7 Hz,
    1042, 730 cm−1 3H), 0.73 (d, J = 6.8 Hz, 3H).
    160 HRMS-ESI (m/z) [M + H]+ 1H NMR (300 MHz, CDCl3) δ 8.54 (d,
    calcd for C24H31N2O6, J = 8.0 Hz, 1H), 8.34 (d, J = 5.4 Hz,
    443.2182; found, 443.2187 1H), 7.33-7.10 (m, 5H), 7.00 (d, J = 5.4 Hz,
    1H), 5.56-5.34 (m, 1H),
    4.79-4.54 (m, 1H), 3.89 (s, 3H), 2.39 (s, 3H),
    2.34 (dd, J = 8.7, 5.4 Hz, 1H),
    2.14-1.95 (m, 1H), 1.29 (d, J = 7.2 Hz, 3H),
    1.09 (d, J = 6.2 Hz, 3H), 0.95 (d, J = 6.6 Hz,
    3H), 0.71 (d, J = 6.7 Hz, 3H).
    13C NMR (75 MHz, CDCl3) δ 172.24,
    168.91, 162.34, 159.46, 146.68, 141.49,
    139.86, 137.49, 129.63, 127.90, 126.47,
    109.79, 72.07, 58.01, 56.30, 56.26,
    48.08, 29.24, 21.24, 20.74, 20.42,
    18.92, 18.49.
    161 HRMS-ESI (m/z) [M + H]+ 1H NMR (300 MHz, CDCl3) δ 8.58 (d,
    calcd for C26H33N2O6, J = 8.0 Hz, 1H), 8.34 (d, J = 5.4 Hz,
    469.2338; found, 469.2345 1H), 7.33-7.09 (m, 5H), 7.01 (d, J = 5.5 Hz,
    1H), 5.35 (qd, J = 6.3, 3.8 Hz,
    1H), 4.83-4.65 (m, 1H), 3.89 (s, 3H),
    2.43-2.38 (m, 1H), 2.40 (s, 3H),
    2.29-2.14 (m, 1H), 1.93-1.78 (m, 1H),
    1.70-1.50 (m, 3H), 1.45 (d, J = 7.2 Hz, 3H),
    1.41-1.26 (m, 2H), 1.24-1.14 (m,
    1H), 1.06 (d, J = 6.3 Hz, 3H),
    0.95-0.77 (m, 1H).
    13C NMR (75 MHz, CDCl3) δ 172.20,
    168.90, 162.36, 159.49, 146.67, 141.47,
    140.72, 137.53, 129.49, 127.92, 126.44,
    109.82, 73.34, 56.66, 56.31, 56.27,
    48.20, 42.11, 31.70, 31.45, 25.11,
    24.51, 20.74, 18.72.
    162 HRMS-ESI (m/z) [M + H]+ 1H NMR (300 MHz, CDCl3) δ 8.36 (d,
    calcd for C25H33N2O7, J = 7.9 Hz, 1H), 8.29 (d, J = 5.3 Hz,
    473.2288; found, 473.2294 1H), 7.28-7.11 (m, 5H), 6.96 (d, J = 5.4 Hz,
    1H), 5.83-5.67 (m, 2H),
    5.60-5.35 (m, 1H), 4.83-4.55 (m, 1H),
    3.90 (s, 3H), 2.37 (dd, J = 8.5, 5.6 Hz, 1H),
    2.12-2.00 (m, 1H), 2.06 (s, 3zH),
    1.29 (d, J = 7.2 Hz, 3H), 1.12 (d, J = 6.2 Hz,
    3H), 0.95 (d, J = 6.6 Hz, 3H), 0.72 (d, J = 6.7 Hz,
    3H).
    13C NMR (75 MHz, CDCl3) δ 172.35,
    170.26, 162.90, 160.29, 145.71, 143.99,
    142.47, 139.82, 129.61, 127.90, 126.46,
    109.58, 89.54, 72.07, 57.98, 56.20,
    56.17, 48.26, 29.22, 21.27, 20.88,
    20.85, 20.28, 18.93, 18.32.
    163 HRMS-ESI (m/z) [M + H]+ 1H NMR (300 MHz, CDCl3) δ 8.41 (d,
    calcd for C27H35N2O7, J = 7.8 Hz, 1H), 8.30 (d, J = 5.3 Hz,
    499.2444; found, 499.2449 1H), 7.30-7.15 (m, 5H), 6.97 (d, J = 5.4 Hz,
    1H), 5.87-5.65 (m, 2H),
    5.36 (qd, J = 6.4, 3.9 Hz, 1H),
    4.94-4.63 (m, 1H), 3.91 (s, 3H), 2.42 (dd, J = 10.3,
    3.9 Hz, 1H), 2.34-2.14 (m, 1H),
    2.07 (s, 3H), 1.96-1.79 (m, 1H),
    1.75-1.49 (m, 3H), 1.46 (d, J = 7.1 Hz, 3H),
    1.45-1.28 (m, 2H), 1.27-1.16 (m,
    1H), 1.08 (d, J = 6.3 Hz, 3H),
    0.95-0.73 (m, 1H).
    13C NMR (75 MHz, CDCl3) δ 172.32,
    170.28, 162.93, 160.32, 145.71, 144.05,
    142.45, 140.73, 129.48, 127.94, 126.44,
    109.60, 89.58, 73.34, 56.64, 56.22,
    56.18, 48.39, 42.14, 31.64, 31.45,
    25.10, 24.50, 20.89, 20.86, 18.76,
    18.57.
    164 HRMS-ESI (m/z) [M + H]+ 1H NMR (300 MHz, CDCl3) δ 8.38 (d,
    calcd for C25H33N2O7, J = 7.7 Hz, 1H), 8.29 (d, J = 5.4 Hz,
    473.2288; found, 473.2279 1H), 7.30-7.19 (m, 3H),
    7.17-7.06 (m, 2H), 6.96 (d, J = 5.4 Hz, 1H),
    5.75 (s, 2H), 5.43 (dq, J = 8.7, 6.2 Hz, 1H),
    4.90-4.52 (m, 1H), 3.92 (s, 3H),
    2.72 (dd, J = 8.8, 6.4 Hz, 1H),
    2.19-2.09 (m, 1H), 2.08 (s, 3H), 1.53 (d, J = 7.2 Hz,
    3H), 1.10 (d, J = 6.3 Hz, 3H),
    0.86 (d, J = 6.7 Hz, 3H), 0.77 (d, J = 6.8 Hz,
    3H).
    13C NMR (75 MHz, CDCl3) δ 172.39,
    170.32, 162.98, 160.29, 145.73, 144.03,
    142.52, 138.62, 129.81, 127.90, 126.61,
    109.56, 89.60, 72.72, 56.61, 56.22,
    56.18, 48.41, 28.24, 21.34, 20.89,
    18.54, 17.86.
    165 HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.54 (d,
    calcd for C24H31N2O6, J = 8.1 Hz, 1H), 8.33 (d, J = 5.4 Hz,
    443.2182; found, 443.2177 1H), 7.30-7.17 (m, 3H),
    7.14-7.05 (m, 2H), 7.00 (d, J = 5.4 Hz, 1H),
    5.42 (dq, J = 8.7, 6.3 Hz, 1H), 4.69 (p, J = 7.3 Hz,
    1H), 3.90 (s, 3H), 2.71 (dd, J = 8.6,
    6.5 Hz, 1H), 2.39 (s, 3H),
    2.17-2.03 (m, 1H), 1.50 (d, J = 7.2 Hz, 3H),
    1.09 (d, J = 6.3 Hz, 3H), 0.86 (d, J = 6.8 Hz,
    3H), 0.76 (d, J = 6.7 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 172.22,
    168.83, 162.38, 159.48, 146.63, 141.63,
    138.69, 137.54, 129.79, 127.88, 126.58,
    109.74, 72.74, 56.64, 56.26, 48.21,
    28.26, 21.32, 20.72, 18.64, 18.62,
    17.80.
    166 HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.60 (d,
    calcd for C25H31N2O6, J = 8.0 Hz, 1H), 8.37 (d, J = 5.4 Hz,
    455.2177; found, 455.2169 1H), 7.18-7.10 (m, 4H), 7.05 (d, J = 5.5 Hz,
    1H), 5.50-5.31 (m, 1H),
    4.91-4.66 (m, 1H), 3.94 (s, 3H), 2.44 (s, 3H),
    2.36 (s, 3H), 2.03 (dd, J = 10.0, 7.0 Hz,
    1H), 1.52 (d, J = 7.1 Hz, 3H), 1.20 (d, J = 6.4 Hz,
    3H), 1.19-1.08 (m, 1H),
    0.76-0.62 (m, 1H), 0.51-0.34 (m, 2H),
    0.05-−0.08 (m, 1H).
    13C NMR (101 MHz, CDCl3) δ 172.21,
    168.85, 162.33, 159.48, 146.64, 141.64,
    138.58, 137.52, 136.08, 128.92, 128.29,
    109.76, 75.92, 56.27, 55.25, 48.18,
    21.01, 20.73, 18.68, 18.12, 13.03, 6.93,
    2.87.
    167 HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.43 (d,
    calcd for C26H33N2O7, J = 7.9 Hz, 1H), 8.33 (d, J = 5.3 Hz,
    485.2283; found, 485.2281 1H), 7.18-7.10 (m, 4H), 7.01 (d, J = 5.4 Hz,
    1H), 5.80 (s, 2H),
    5.46-5.25 (m, 1H), 4.90-4.72 (m, 1H), 3.96 (s,
    3H), 2.37 (s, 3H), 2.12 (s, 3H),
    2.05 (dd, J = 10.0, 7.0 Hz, 1H), 1.55 (d, J = 7.1 Hz,
    3H), 1.22 (d, J = 6.3 Hz, 3H),
    1.20-1.09 (m, 1H), 0.75-0.65 (m,
    1H), 0.51-0.37 (m, 2H),
    0.08-−0.06 (m, 1H).
    13C NMR (101 MHz, CDCl3) δ 172.32,
    170.20, 162.91, 160.30, 145.68, 143.99,
    142.61, 138.58, 136.07, 128.91, 128.28,
    109.57, 89.55, 75.89, 56.17, 55.24,
    48.37, 21.00, 20.83, 18.53, 18.14,
    13.01, 6.94, 2.87.
    168 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.55 (d,
    film) 3380, calcd for C25H33N2O6, J = 8.0 Hz, 1H), 8.34 (d, J = 5.4 Hz,
    2961, 457.2333; found, 457.2328 1H), 7.06 (t, J = 6.4 Hz, 2H),
    1771, 7.03-6.94 (m, 3H), 5.40 (dq, J = 8.7, 6.3 Hz,
    1732, 1H), 4.74-4.62 (m, 1H), 3.91 (s, 3H),
    1676, 2.67 (dd, J = 8.8, 6.3 Hz, 1H), 2.40 (s,
    1508, 3H), 2.32 (s, 3H), 2.14-2.05 (m, 1H),
    1199, 1.50 (d, J = 7.2 Hz, 3H), 1.08 (d, J = 6.3 Hz,
    1175, 908, 3H), 0.85 (d, J = 6.7 Hz, 3H),
    823, 802, 0.75 (d, J = 6.7 Hz, 3H).
    731 cm−1 13C NMR (101 MHz, CDCl3) δ 172.28,
    168.90, 162.39, 159.49, 146.65, 141.67,
    137.55, 136.06, 135.51, 129.68, 128.62,
    109.73, 72.85, 56.29, 56.23, 48.23,
    28.21, 21.36, 21.01, 20.75, 18.69,
    18.56, 17.85.
    169 HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.51 (d,
    calcd for C24H30FN2O6, J = 7.9 Hz, 1H), 8.39-8.28 (m, 1H),
    461.2083; found, 461.2082 7.12-6.89 (m, 5H), 5.50-5.32 (m,
    1H), 4.78-4.60 (m, 1H), 3.91 (s, 3H),
    2.77-2.64 (m, 1H), 2.41 (s, 3H),
    2.14-2.02 (m, 1H), 1.54-1.35 (m, 3H),
    1.12-0.97 (m, 3H), 0.94-0.83 (m, 3H),
    0.79-0.68 (m, 3H).
    19F NMR (376 MHz, CDCl3) δ −116.57,
    −116.61.
    170 HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.51 (d,
    calcd for C24H28FN2O6, J = 8.3 Hz, 1H), 8.32 (d, J = 5.4 Hz,
    459.1926; found, 459.1923 1H), 7.22-7.10 (m, 2H),
    7.09-6.86 (m, 3H), 5.39-5.19 (m, 1H), 4.71 (dq,
    J = 8.2, 7.2 Hz, 1H), 3.90 (s, 3H),
    2.40 (s, 3H), 2.02 (dd, J = 10.1, 6.5 Hz, 1H),
    1.46 (d, J = 7.2 Hz, 3H), 1.17 (d, J = 6.4 Hz,
    3H), 1.12-1.03 (m, 1H),
    0.73-0.62 (m, 1H), 0.47-0.31 (m, 2H),
    −0.01-−0.14 (m, 1H).
    19F NMR (376 MHz, CDCl3) δ −116.54.
    171 HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.35 (d,
    calcd for C25H30FN2O7, J = 8.0 Hz, 1H), 8.31-8.19 (m, 1H),
    489.2032; found, 489.2027 7.23-7.14 (m, 2H), 7.03-6.82 (m,
    3H), 5.75 (s, 2H), 5.36-5.19 (m, 1H),
    4.82-4.65 (m, 1H), 3.92 (s, 3H),
    2.07 (s, 3H), 2.03 (dd, J = 10.2, 6.5 Hz, 1H),
    1.48 (d, J = 7.2 Hz, 3H), 1.18 (d, J = 6.4 Hz,
    3H), 1.15-1.06 (m, 1H),
    0.75-0.63 (m, 1H), 0.48-0.33 (m, 2H),
    −0.03-−0.12 (m, 1H).
    19F NMR (376 MHz, CDCl3) δ −116.54.
    172 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (300 MHz, CDCl3) δ 8.57 (d,
    film) 3382, calcd for C26H35N2O6, J = 7.3 Hz, 1H), 8.33 (d, J = 5.4 Hz,
    2962, 471.2495; found, 471.2494 1H), 7.33-7.06 (m, 5H), 7.01 (d, J = 5.5 Hz,
    2933, 1H), 5.52-5.36 (m, 1H),
    2875, 4.70 (p, J = 7.1 Hz, 1H), 3.90 (s, 3H),
    1771, 2.96 (dd, J = 8.6, 6.3 Hz, 1H), 2.40 (s, 3H),
    1732, 1.50 (d, J = 7.2 Hz, 3H),
    1676, 1.46-1.22 (m, 3H), 1.10 (d, J = 6.2 Hz, 3H),
    1505, 0.99-0.82 (m, 5H), 0.78 (t, J = 7.2 Hz,
    1309, 3H).
    1193,
    1174,
    1040, 826,
    734, 703 cm−1.
    173 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (300 MHz, CDCl3) δ 8.53 (d,
    film) 3381, calcd for C26H33N2O6, J = 7.8 Hz, 1H), 8.32 (d, J = 4.6 Hz,
    2950, 469.2338; found, 469.2342 1H), 7.33-7.06 (m, 5H), 7.01 (d, J = 5.5 Hz,
    1771, 1H), 5.48-5.16 (m, 1H),
    1732, 4.85-4.55 (m, 1H), 3.89 (s, 3H), 2.78 (dd, J = 10.0,
    1676, 5.9 Hz, 1H), 2.39 (s, 3H),
    1505, 1.98-1.80 (m, 1H), 1.73-1.19 (m, 11H),
    1309, 1.11 (d, J = 6.5 Hz, 3H).
    1195,
    1174,
    1038, 826,
    802, 734,
    702 cm−1.
    174 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (300 MHz, CDCl3) δ 8.40 (d,
    film) 3380, calcd for C27H37N2O7, J = 7.9 Hz, 1H), 8.29 (d, J = 5.4 Hz,
    2962, 501.2601; found, 501.2606 1H), 7.34-7.06 (m, 5H), 6.96 (d, J = 5.4 Hz,
    2933, 1H), 5.75 (s, 2H),
    1734, 5.57-5.35 (m, 1H), 4.81-4.54 (m, 1H), 3.91 (s,
    1676, 3H), 2.97 (dd, J = 8.6, 6.3 Hz, 1H),
    1502, 2.07 (s, 3H), 1.53 (d, J = 7.2 Hz, 3H),
    1452, 1.49-1.34 (m, 3H), 1.11 (d, J = 6.3 Hz, 3H),
    1310, 0.95 (t, J = 7.3 Hz, 3H), 0.91-0.82 (m,
    1200, 2H), 0.78 (t, J = 7.2 Hz, 3H).
    1041,
    1002, 967,
    829, 735,
    704 cm−1.
    175 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (300 MHz, CDCl3) δ 8.36 (d,
    film) 3382, calcd for C27H35N2O7, J = 7.8 Hz, 1H), 8.28 (d, J = 5.2 Hz,
    2948, 499.2444; found, 499.2447 1H), 7.32-7.02 (m, 5H), 6.97 (dd, J = 5.4,
    2869, 2.6 Hz, 1H), 5.75 (s, 2H),
    1733, 5.45-5.17 (m, 1H), 4.85-4.40 (m, 1H),
    1501, 3.91 (s, 3H), 2.79 (dd, J = 10.0, 5.9 Hz, 1H),
    1437, 2.07 (s, 3H), 2.02-1.77 (m, 2H),
    1310, 1.67-1.19 (m, 7H), 1.13-0.86 (m, 6H).
    1200,
    1040,
    1002, 967,
    829, 734,
    703 cm−1.
    176 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3, major) δ
    film) 2950, calcd for C26H33N2O5S, 9.94 (d, J = 6.5 Hz, 1H), 8.33 (d, J = 5.5 Hz,
    1769, 485.2105; found, 485.2171 1H), 7.26-7.20 (m, 3H),
    1732, 7.14-7.10 (m, 2H), 7.00 (d, J = 5.5 Hz, 1H),
    1192, 5.38-5.31 (m, 1H), 5.17-5.08 (m,
    1175, 730 cm−1 1H), 3.91 (s, 3H), 2.79 (dd, J = 9.9, 6.0 Hz,
    1H), 2.36 (s, 3H), 2.28-2.12 (m,
    1H), 1.98-1.82 (m, 2H), 1.57 (d, J = 7.2 Hz,
    3H), 1.53-1.36 (m, 4H),
    1.34-1.20 (m, 2H), 1.13 (d, J = 6.5 Hz, 3H).
    177 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (500 MHz, CDCl3) δ 9.98 (d,
    film) 2950, calcd for C26H32N2O5S, J = 7.3 Hz, 1H), 8.35 (d, J = 5.4 Hz,
    2868, 507.1924; found, 507.1920 1H), 7.25-7.13 (m, 5H), 7.01 (d, J = 5.5 Hz,
    1770, 1H), 5.39 (qd, J = 6.3, 4.1 Hz,
    1731, 1H), 5.16 (p, J = 7.2 Hz, 1H), 3.91 (s,
    1585, 3H), 2.42 (dd, J = 10.3, 4.0 Hz, 1H),
    1496, 2.35 (s, 3H), 2.28-2.19 (m, 1H),
    1438, 1.93-1.83 (m, 1H), 1.68-1.59 (m, 1H),
    1365, 1.52 (d, J = 7.2 Hz, 3H), 1.50-1.31 (m, 4H),
    1311, 1.20 (dq, J = 12.5, 9.1 Hz, 1H), 1.08 (d,
    1278, J = 6.4 Hz, 3H), 0.97-0.90 (m, 1H).
    1193,
    1175,
    1131,
    1102,
    1040,
    1010, 909,
    847, 824,
    759, 703 cm−1
    178 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 8.52 (s,
    film) 3384, calcd for C25H31FN2NaO6, 1H), 8.35 (d, J = 5.4 Hz, 1H),
    2968, 497.2058; found, 497.2056 7.31-7.22 (m, 1H), 7.02 (d, J = 5.5 Hz, 1H),
    1772, 6.84 (dd, J = 9.9, 2.9 Hz, 1H), 6.76 (td,
    1733, J = 8.5, 2.8 Hz, 1H), 5.48-5.36 (m,
    1677, 1H), 4.76-4.62 (m, 1H), 3.91 (s, 3H),
    1499, 2.67 (dd, J = 9.4, 4.8 Hz, 1H), 2.39 (s,
    1176, 825, 3H), 2.27 (s, 3H), 2.01 (dp, J = 9.2, 6.6 Hz,
    734 cm−1 1H), 1.39 (d, J = 7.2 Hz, 3H),
    1.05 (d, J = 6.3 Hz, 3H), 0.99 (d, J = 6.6 Hz,
    3H), 0.68 (d, J = 6.7 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −117.72.
    179 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 8.54 (d,
    film) 3384, calcd for C27H35FN2NaO6, J = 7.6 Hz, 1H), 8.35 (d, J = 5.5 Hz,
    2963, 525.2371; found, 525.2364 1H), 7.30 (dd, J = 8.8, 6.2 Hz, 1H),
    1771, 7.02 (dd, J = 5.5, 2.6 Hz, 1H), 6.83 (dd, J = 9.9,
    1732, 2.9 Hz, 1H), 6.75 (td, J = 8.6, 2.9 Hz,
    1676, 1H), 5.38 (qd, J = 6.3, 4.0 Hz, 1H),
    1498, 4.79-4.65 (m, 1H), 3.91 (s, 3H),
    1174, 825, 2.90 (dd, J = 10.1, 4.2 Hz, 1H), 2.39 (s, 3H),
    731 cm−1 2.27 (d, J = 3.5 Hz, 3H),
    1.82-1.67 (m, 1H), 1.58-1.28 (m, 4H), 1.26 (s,
    1H), 1.19-1.05 (m, 1H), 0.99 (dd, J = 10.0,
    6.3 Hz, 3H), 0.94-0.81 (m, 4H),
    0.72-0.63 (m, 3H).
    19F NMR (376 MHz, CDCl3) δ −117.69.
    180 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 8.54 (d,
    film) 3384, calcd for C27H33FN2NaO6, J = 8.0 Hz, 1H), 8.35 (d, J = 5.4 Hz,
    2950, 523.2215; found, 523.2210 1H), 7.31-7.22 (m, 1H), 7.02 (d, J = 5.4 Hz,
    1771, 1H), 6.83 (dd, J = 9.9, 2.8 Hz,
    1731, 1H), 6.73 (td, J = 8.5, 2.8 Hz, 1H),
    1675, 5.32 (qd, J = 6.4, 3.9 Hz, 1H), 4.72 (p, J = 7.3 Hz,
    1498, 1H), 3.91 (s, 3H), 2.78 (dd, J = 10.4,
    1175, 907, 4.2 Hz, 1H), 2.39 (s, 3H), 2.29 (s,
    730 cm−1 3H), 2.25-2.10 (m, 1H), 1.89 (ddt, J = 14.4,
    10.9, 5.2 Hz, 1H), 1.74-1.30 (m,
    7H), 1.30-1.13 (m, 2H), 1.06 (d, J = 6.3 Hz,
    3H), 1.00-0.78 (m, 1H).
    13C NMR (101 MHz, CDCl3) δ 172.09,
    168.86, 162.37, 160.90 (d, J = 243.9 Hz),
    159.56, 146.64, 141.54, 138.75 (d,
    J = 7.2 Hz), 137.63, 135.25 (d, J = 3.2 Hz),
    129.77 (d, J = 8.1 Hz), 116.34 (d, J = 20.2 Hz),
    112.67 (d, J = 20.5 Hz),
    109.82, 73.60, 56.31, 49.43, 48.20,
    42.91, 31.62, 31.42, 25.12, 24.42,
    20.73, 20.61, 18.63, 18.13.
    19F NMR (376 MHz, CDCl3) δ −117.78.
    181 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.54 (d,
    film) 3383, calcd for C28H36FN2O6, J = 7.5 Hz, 1H), 8.35 (d, J = 5.4 Hz,
    2928, 515.2552; found, 515.2557 1H), 7.31-7.27 (m, 1H), 7.02 (d, J = 5.4 Hz,
    1771, 1H), 6.87-6.73 (m, 2H),
    1675, 5.42 (qd, J = 6.3, 4.3 Hz, 1H),
    1498, 4.77-4.66 (m, 1H), 3.91 (s, 3H), 2.74 (dd, J = 9.5,
    1174, 4.7 Hz, 1H), 2.40 (s, 3H),
    1038, 825, 2.31-2.21 (m, 3H), 1.86 (d, J = 12.9 Hz, 1H),
    732 cm−1 1.78-1.49 (m, 3H), 1.41 (d, J = 7.2 Hz,
    3H), 1.36-1.15 (m, 3H),
    1.15-0.84 (m, 6H), 0.84-0.70 (m, 1H).
    13C NMR (101 MHz, CDCl3) δ 172.20,
    168.87, 162.36, 160.91 (d, J = 243.8 Hz),
    159.55, 146.65, 141.55, 139.40 (d,
    J = 7.1 Hz), 137.60, 134.70 (d, J = 3.4 Hz),
    129.50 (d, J = 7.7 Hz), 116.32 (d, J = 20.6 Hz),
    112.74 (d, J = 20.2 Hz),
    109.82, 71.63, 56.31, 49.64, 48.13,
    40.27, 31.28, 30.87, 29.30, 26.47,
    26.37, 26.27, 20.74, 18.66, 18.19.
    19F NMR (376 MHz, CDCl3) δ −117.74.
    182 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ
    film) 3384, calcd for C26H33FN2NaO6, 8.59-8.45 (m, 1H), 8.35 (dd, J = 5.4, 1.3 Hz,
    2965, 511.2215; found, 511.2207 1H), 7.31-7.23 (m, 1H),
    1771, 7.04-6.95 (m, 1H), 6.83 (dd, J = 9.9, 2.7 Hz, 1H),
    1732, 6.76 (dtd, J = 8.5, 5.3, 2.6 Hz, 1H),
    1674, 5.42 (ddt, J = 8.6, 6.1, 3.5 Hz, 1H),
    1498, 4.76-4.64 (m, 1H), 3.91 (s, 3H), 2.77 (ddd, J = 42.7,
    1175, 908, 9.3, 4.8 Hz, 1H), 2.39 (d, J = 2.0 Hz,
    731 cm−1 3H), 2.33-2.23 (m, 3H),
    1.97-1.50 (m, 2H), 1.48-1.31 (m, 3H),
    1.26 (s, 1H), 1.23-0.93 (m, 4H),
    0.94-0.58 (m, 5H).
    19F NMR (376 MHz, CDCl3) δ −117.69,
    −117.74.
    183 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ
    film) 3380, calcd for C26H31FN2NaO6, 8.49-8.39 (m, 1H), 8.33 (d, J = 5.4 Hz, 1H),
    2938, 509.2058; found, 509.2056 7.09 (dd, J = 8.6, 6.0 Hz, 1H), 7.00 (d, J = 5.5 Hz,
    1771, 1H), 6.81 (dd, J = 9.9, 2.9 Hz,
    1732, 1H), 6.74 (td, J = 8.4, 2.8 Hz, 1H),
    1674, 5.14 (p, J = 6.4 Hz, 1H), 4.59 (p, J = 7.4 Hz,
    1498, 1H), 3.90 (s, 3H), 3.02 (dd, J = 10.4,
    1175, 908, 6.4 Hz, 1H), 2.70-2.59 (m, 1H),
    730 cm−1 2.39 (s, 3H), 2.34 (s, 3H), 2.17 (d, J = 6.0 Hz,
    1H), 1.88-1.59 (m, 4H),
    1.42-1.33 (m, 1H), 1.20 (d, J = 7.2 Hz, 3H),
    1.17 (d, J = 6.3 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −117.62.
    184 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 8.47 (d,
    film) 3379, calcd for C27H33FN2NaO6, J = 8.1 Hz, 1H), 8.31 (d, J = 5.4 Hz,
    2949, 523.2215; found, 523.2202 1H), 7.09 (dd, J = 8.7, 5.9 Hz, 1H),
    1770, 7.01 (d, J = 5.5 Hz, 1H), 6.84 (td, J = 8.3,
    1731, 3.1 Hz, 1H), 6.76 (dd, J = 9.9, 2.8 Hz,
    1675, 1H), 5.29 (p, J = 6.7 Hz, 1H),
    1499, 4.74-4.63 (m, 1H), 3.91 (s, 3H), 3.10 (dd, J = 9.2,
    1175, 907, 7.1 Hz, 1H), 2.40 (d, J = 2.6 Hz,
    730 cm−1 3H), 2.21-2.07 (m, 1H), 1.86 (dtd, J = 14.8,
    7.9, 7.1, 4.5 Hz, 1H),
    1.67-1.30 (m, 9H), 1.30-1.16 (m, 2H),
    1.16-1.08 (m, 4H), 0.98-0.81 (m, 1H).
    19F NMR (376 MHz, CDCl3) δ −117.62.
    185 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.52 (d,
    film) 3379, calcd for C28H36FN2O6, J = 8.0 Hz, 1H), 8.33 (d, J = 5.4 Hz,
    2928, 515.2552; found, 515.2568 1H), 7.05 (dd, J = 8.6, 5.9 Hz, 1H),
    1771, 7.01 (d, J = 5.5 Hz, 1H), 6.88-6.78 (m,
    1733, 2H), 5.41-5.36 (m, 1H),
    1676, 4.77-4.67 (m, 1H), 3.91 (s, 3H), 3.11 (dd, J = 9.0,
    1499, 6.1 Hz, 1H), 2.40 (s, 3H), 2.28 (s, 3H),
    1193, 1.83-1.39 (m, 10H), 1.31-0.95 (m,
    1175, 825, 5H), 0.95-0.81 (m, 2H).
    732 cm−1 19F NMR (376 MHz, CDCl3) δ −117.48.
    186 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 8.51 (d,
    film) 3381, calcd for C25H31FN2NaO6, J = 8.0 Hz, 1H), 8.33 (d, J = 5.4 Hz,
    2961, 497.2058; found, 497.2048 1H), 7.05 (dd, J = 8.5, 6.0 Hz, 1H),
    1771, 7.01 (d, J = 5.5 Hz, 1H), 6.84 (qd, J = 10.0,
    1732, 9.2, 2.8 Hz, 2H), 5.36 (dq, J = 9.3, 6.2 Hz,
    1675, 1H), 4.75-4.65 (m, 1H), 3.91 (d, J = 1.9 Hz,
    1499, 3H), 3.08 (dd, J = 8.9, 6.5 Hz,
    1174, 1H), 2.40 (d, J = 2.1 Hz, 3H), 2.29 (s,
    1045, 908, 3H), 2.12 (h, J = 6.8 Hz, 1H), 1.50 (dd,
    731 cm−1 J = 7.2, 2.0 Hz, 3H), 1.06 (d, J = 6.2 Hz,
    3H), 0.86 (dd, J = 6.9, 1.9 Hz, 3H),
    0.77 (d, J = 6.8 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 172.23,
    168.88, 162.36, 160.94 (d, J = 244.3 Hz),
    159.51, 146.65, 141.57, 139.90 (d,
    J = 6.5 Hz), 137.56, 133.65 (d, J = 2.9 Hz),
    129.31-129.08 (m), 116.96 (d, J = 20.5 Hz),
    112.33 (d, J = 20.7 Hz),
    109.77, 73.76, 56.30, 48.22, 29.69,
    29.30, 20.93, 20.91, 20.75, 18.92,
    18.59, 17.91.
    19F NMR (376 MHz, CDCl3) δ −117.42.
    187 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.47 (d,
    film) 3379, calcd for C27H36FN2O6, J = 8.3 Hz, 1H), 8.31 (d, J = 5.5 Hz,
    2963, 503.2552; found, 503.2557 1H), 7.09 (dd, J = 8.7, 5.9 Hz, 1H),
    1771, 7.01 (dd, J = 5.4, 2.2 Hz, 1H), 6.83 (td, J = 8.5,
    1732, 3.3 Hz, 1H), 6.76 (dd, J = 9.9, 2.9 Hz,
    1675, 1H), 5.41 (dq, J = 7.8, 6.2 Hz, 1H),
    1499, 4.70 (dt, J = 8.0, 6.0 Hz, 1H), 3.91 (d, J = 1.7 Hz,
    1175, 907, 3H), 3.25 (q, J = 8.0 Hz, 1H),
    730 cm−1 2.40 (s, 3H), 2.27 (s, 2H), 1.62 (d, J = 10.7 Hz,
    2H), 1.54-1.24 (m, 6H),
    1.09 (d, J = 6.2 Hz, 3H), 1.07-0.81 (m,
    4H), 0.81-0.64 (m, 3H).
    19F NMR (376 MHz, CDCl3) δ −117.52.
    188 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ
    film) 3379, calcd for C26H33FN2NaO6, 8.56-8.45 (m, 1H), 8.32 (dd, J = 5.4, 3.2 Hz,
    2964, 511.2215; found, 511.2209 1H), 7.06 (ddd, J = 9.1, 5.8, 3.2 Hz,
    1771, 1H), 7.01 (d, J = 5.5 Hz, 1H), 6.83 (qd,
    1733, J = 10.4, 9.3, 5.1 Hz, 2H), 5.38 (ddt, J = 18.2,
    1676, 9.3, 6.3 Hz, 1H), 4.76-4.63 (m,
    1500, 1H), 3.91 (s, 3H), 3.22-3.07 (m, 1H),
    1176, 2.40 (d, J = 1.3 Hz, 3H),
    1059, 732 cm−1 2.35-2.25 (m, 3H), 1.95-1.75 (m, 1H),
    1.54-1.33 (m, 4H), 1.06 (dd, J = 8.1, 6.2 Hz,
    3H), 1.00-0.81 (m, 4H), 0.78 (dt, J = 7.1,
    3.7 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −117.43,
    −117.48.
    189 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 8.49 (d,
    film) 3379, calcd for C26H31FN2NaO6, J = 8.1 Hz, 1H), 8.33 (d, J = 5.5 Hz,
    2939, 509.2059; found, 509.2039 1H), 7.05-6.97 (m, 2H),
    1770, 6.87-6.77 (m, 2H), 5.17-5.04 (m, 1H),
    1732, 4.74-4.62 (m, 1H), 3.91 (s, 3H), 3.13 (t, J = 8.7 Hz,
    1674, 1H), 2.72 (dt, J = 19.2, 9.6 Hz,
    1499, 1H), 2.40 (s, 3H), 2.33 (s, 3H),
    1175, 908, 2.19-2.06 (m, 1H), 1.92-1.71 (m, 2H),
    730 cm−1 1.71-1.56 (m, 2H), 1.48 (d, J = 7.1 Hz,
    3H), 1.44-1.20 (m, 1H), 1.07 (d, J = 6.3 Hz,
    3H).
    19F NMR (376 MHz, CDCl3) δ −117.38.
    190 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ
    film) 3383, calcd for C27H33FN2NaO6, 8.61-8.49 (m, 1H), 8.35 (d, J = 5.4 Hz, 1H),
    2951, 523.2215; found, 523.2201 7.33 (dd, J = 8.7, 6.1 Hz, 1H), 7.02 (d, J = 5.5 Hz,
    1771, 1H), 6.86-6.72 (m, 2H),
    1732, 5.32 (qd, J = 6.4, 3.5 Hz, 1H), 4.74 (p, J = 7.2 Hz,
    1675, 1H), 3.92 (s, 3H), 2.77 (dd, J = 10.6,
    1498, 3.5 Hz, 1H), 2.40 (s, 3H),
    1175, 908, 2.29 (s, 3H), 2.27-2.15 (m, 1H),
    730 cm−1 1.99-1.86 (m, 1H), 1.74-1.29 (m, 7H),
    1.29-1.15 (m, 2H), 1.03 (d, J = 6.4 Hz,
    3H), 0.93-0.78 (m, 1H).
    13C NMR (101 MHz, CDCl3) δ 172.03,
    168.89, 162.41, 160.91 (d, J = 243.8 Hz),
    159.55, 146.65, 141.52, 138.75 (d,
    J = 7.2 Hz), 137.62, 135.15 (d, J = 3.2 Hz),
    129.97 (d, J = 8.1 Hz), 116.32 (d, J = 20.6 Hz),
    112.63 (d, J = 20.5 Hz),
    109.81, 73.36, 56.31, 49.51, 48.10,
    42.71, 31.73, 31.70, 25.18, 24.52,
    20.74, 20.62, 18.55, 17.78.
    19F NMR (376 MHz, CDCl3) δ −117.80.
    191 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 8.53 (s,
    film) 3380, calcd for C28H35FN2NaO6, 1H), 8.35 (d, J = 5.4 Hz, 1H), 7.33 (dd,
    2928, 537.2371; found, 537.2380 J = 8.7, 6.1 Hz, 1H), 7.03 (d, J = 5.4 Hz,
    1771, 1H), 6.88-6.69 (m, 2H), 5.42 (pd,
    1732, J = 8.5, 7.4, 3.3 Hz, 1H),
    1675, 4.78-4.67 (m, 1H), 3.92 (s, 3H), 2.71 (dd, J = 9.9,
    1498, 3.9 Hz, 1H), 2.40 (s, 3H), 2.26 (s, 3H),
    1173, 909, 1.92 (d, J = 12.8 Hz, 1H),
    730 cm−1 1.79-1.49 (m, 4H), 1.44 (d, J = 7.2 Hz, 3H),
    1.38-1.16 (m, 3H), 1.16-0.84 (m, 5H),
    0.82-0.66 (m, 1H).
    13C NMR (101 MHz, CDCl3) δ 172.01,
    168.88, 162.37, 160.90 (d, J = 243.9 Hz),
    159.57, 146.64, 141.51, 139.38 (d,
    J = 7.3 Hz), 137.64, 134.61 (d, J = 3.1 Hz),
    129.69 (d, J = 7.8 Hz), 116.28 (d, J = 20.6 Hz),
    112.68 (d, J = 20.6 Hz),
    109.82, 71.31, 56.32, 49.62, 48.11,
    39.95, 31.32, 31.20, 29.29, 26.51,
    26.37, 26.24, 20.74, 18.52, 17.93.
    19F NMR (376 MHz, CDCl3) δ −117.81.
    192 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ
    film) 3380, calcd for C25H31FN2NaO6, 8.57-8.43 (m, 1H), 8.35 (d, J = 5.4 Hz, 1H),
    2963, 497.2058; found, 497.2059 7.32 (dd, J = 8.7, 6.1 Hz, 1H), 7.02 (d, J = 5.4 Hz,
    1771, 1H), 6.83 (dd, J = 9.9, 2.9 Hz,
    1732, 1H), 6.79-6.71 (m, 1H), 5.43 (qd, J = 6.4,
    1676, 3.9 Hz, 1H), 4.76-4.68 (m, 1H),
    1499, 3.92 (s, 3H), 2.67-2.60 (m, 1H),
    1176, 733 cm−1 2.40 (s, 3H), 2.27 (s, 3H), 2.12-1.94 (m,
    1H), 1.44 (d, J = 7.2 Hz, 3H), 1.01 (dd,
    J = 6.4, 3.0 Hz, 6H), 0.67 (d, J = 6.7 Hz,
    3H).
    19F NMR (376 MHz, CDCl3) δ −117.77.
    193 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 8.37 (d,
    film) 3378, calcd for C28H35FN2NaO7, J = 7.9 Hz, 1H), 8.30 (d, J = 5.4 Hz,
    2951, 553.2321; found, 553.2310 1H), 7.31-7.27 (m, 1H), 6.97 (d, J = 5.4 Hz,
    1732, 1H), 6.83 (dd, J = 9.9, 2.8 Hz,
    1674, 1H), 6.75 (td, J = 8.5, 2.9 Hz, 1H),
    1497, 5.75 (d, J = 2.4 Hz, 2H), 5.33 (qd, J = 6.3,
    1201, 4.0 Hz, 1H), 4.74 (p, J = 7.3 Hz, 1H),
    1003, 968, 3.92 (s, 3H), 2.80 (dd, J = 10.3, 4.2 Hz,
    730 cm−1 1H), 2.29 (s, 3H), 2.25-2.11 (m, 1H),
    2.07 (s, 3H), 1.89 (dtd, J = 10.9, 7.1, 3.4 Hz,
    1H), 1.77-1.29 (m, 7H),
    1.29-1.13 (m, 2H), 1.08 (d, J = 6.3 Hz, 3H),
    0.96-0.79 (m, 1H).
    13C NMR (101 MHz, CDCl3) δ 172.21,
    170.25, 162.95, 160.90 (d, J = 243.9 Hz),
    160.39, 145.69, 144.14, 142.51,
    138.78 (d, J = 7.2 Hz), 135.27 (d, J = 3.2 Hz),
    129.70 (d, J = 8.1 Hz),
    116.37 (d, J = 20.5 Hz), 112.69 (d, J = 20.6 Hz),
    109.63, 89.63, 73.62, 56.21, 49.42,
    48.41, 42.95, 31.62, 31.38, 25.11,
    24.41, 20.86, 20.62, 18.50, 18.17.
    19F NMR (376 MHz, CDCl3) δ −117.76.
    194 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.37 (d,
    film) 3379, calcd for C29H38FN2O7, J = 7.8 Hz, 1H), 8.29 (d, J = 5.4 Hz,
    2929, 545.2658; found, 545.2652 1H), 7.30 (dd, J = 8.7, 6.1 Hz, 1H),
    1733, 6.96 (d, J = 5.4 Hz, 1H), 6.87-6.76 (m,
    1675, 2H), 5.75 (d, J = 1.6 Hz, 2H),
    1498, 5.48-5.38 (m, 1H), 4.73 (p, J = 7.3 Hz, 1H),
    1202, 3.91 (s, 3H), 2.76 (dd, J = 9.3, 4.8 Hz,
    1004, 969, 1H), 2.27 (s, 3H), 2.07 (s, 3H), 1.86 (d,
    829, 731 cm−1 J = 12.8 Hz, 1H), 1.81-1.51 (m, 3H),
    1.42 (d, J = 7.1 Hz, 3H), 1.33 (d, J = 12.7 Hz,
    1H), 1.28-0.89 (m, 8H),
    0.85-0.72 (m, 1H).
    13C NMR (101 MHz, CDCl3) δ 172.32,
    170.25, 162.94, 160.91 (d, J = 244.0 Hz),
    160.37, 145.69, 144.10, 142.54,
    139.42 (d, J = 7.3 Hz), 134.70 (d, J = 3.3 Hz),
    129.47 (d, J = 8.1 Hz),
    116.34 (d, J = 20.3 Hz), 112.75 (d, J = 20.5 Hz),
    109.62, 89.62, 71.67, 56.21, 49.66,
    48.34, 40.30, 31.30, 30.79, 26.45,
    26.40, 26.32, 20.86, 20.74, 18.54,
    18.23.
    19F NMR (376 MHz, CDCl3) δ −117.73.
    195 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.31 (d,
    film) 3379, calcd for C28H35FN2NaO7, J = 8.1 Hz, 1H), 8.26 (d, J = 5.4 Hz,
    2950, 553.2321; found, 553.2326 1H), 7.09 (dd, J = 8.6, 5.9 Hz, 1H),
    1756, 6.96 (d, J = 5.4 Hz, 1H), 6.89-6.72 (m,
    1676, 2H), 5.74 (s, 2H), 5.36-5.22 (m, 1H),
    1498, 4.71 (p, J = 7.2 Hz, 1H), 3.92 (s, 3H),
    1201, 3.11 (dd, J = 9.2, 7.2 Hz, 1H), 2.27 (s,
    1003, 969, 2H), 2.20-2.10 (m, 2H), 2.07 (s, 4H),
    829, 731 cm−1 1.87 (dtd, J = 14.8, 7.1, 3.4 Hz, 1H),
    1.75-1.30 (m, 7H), 1.30-1.16 (m,
    1H), 1.11 (d, J = 6.4 Hz, 3H),
    0.99-0.81 (m, 1H).
    19F NMR (376 MHz, CDCl3) δ −117.60.
    196 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 8.34 (t, J = 8.5 Hz,
    film) 3379, calcd for C27H35FN2NaO7, 1H), 8.28 (dd, J = 5.4, 2.6 Hz,
    2964, 541.2321; found, 541.2306 1H), 7.07 (ddd, J = 9.0, 6.0, 3.1 Hz,
    1734, 1H), 6.96 (d, J = 5.4 Hz, 1H),
    1675, 6.90-6.75 (m, 2H), 5.75 (d, J = 2.7 Hz, 2H),
    1498, 5.39 (ddq, J = 18.7, 9.3, 6.2 Hz, 1H),
    1202, 4.72 (td, J = 7.4, 6.2 Hz, 1H), 3.92 (s,
    1003, 968, 3H), 3.16 (ddd, J = 24.9, 9.0, 6.3 Hz,
    829, 731 cm−1 1H), 2.35-2.20 (m, 3H), 2.07 (d, J = 0.9 Hz,
    3H), 1.97-1.72 (m, 1H),
    1.58-1.34 (m, 4H), 1.07 (dd, J = 7.7, 6.2 Hz,
    3H), 1.02-0.82 (m, 4H), 0.78 (dd, J = 7.3,
    5.2 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −117.41,
    −117.46.
    197 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.33 (d,
    film) 3379, calcd for C27H34FN2O7, J = 7.9 Hz, 1H), 8.28 (d, J = 5.4 Hz,
    2977, 517.2345; found, 517.2340 1H), 7.06-6.98 (m, 1H), 6.95 (d, J = 5.4 Hz,
    1733, 1H), 6.83 (dd, J = 9.5, 2.3 Hz,
    1674, 2H), 5.75 (s, 2H), 5.17-5.01 (m, 1H),
    1498, 4.71 (p, J = 7.2 Hz, 1H), 3.91 (s, 3H),
    1201, 3.14 (t, J = 8.7 Hz, 1H), 2.73 (p, J = 8.8 Hz,
    1041, 1H), 2.34 (s, 3H), 2.23-2.09 (m,
    1003, 968, 1H), 2.07 (s, 3H), 1.95-1.72 (m, 2H),
    829, 730 cm−1 1.72-1.55 (m, 2H), 1.50 (d, J = 7.1 Hz,
    3H), 1.37 (p, J = 10.0 Hz, 1H),
    1.08 (d, J = 6.3 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −117.38.
    198 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 8.37 (d,
    film) 3384, calcd for C28H35FN2NaO7, J = 7.7 Hz, 1H), 8.30 (d, J = 5.3 Hz,
    2951, 553.2321; found, 553.2313 1H), 7.34 (dd, J = 8.7, 6.1 Hz, 1H),
    1734, 6.97 (d, J = 5.4 Hz, 1H), 6.83 (dd, J = 9.9,
    1677, 2.8 Hz, 1H), 6.74 (td, J = 8.5, 3.0 Hz,
    1499, 1H), 5.77 (d, J = 6.4 Hz, 1H), 5.71 (d, J = 6.4 Hz,
    1202, 1H), 5.32 (qd, J = 6.4, 3.2 Hz,
    1005, 970, 1H), 4.76 (p, J = 7.3 Hz, 1H), 3.92 (s,
    830 cm−1 3H), 2.77 (dd, J = 10.7, 3.5 Hz, 1H),
    2.34-2.20 (m, 4H), 2.08 (s, 3H),
    1.99-1.86 (m, 1H), 1.74-1.30 (m, 8H),
    1.30-1.16 (m, 1H), 1.10-0.99 (m,
    3H), 0.84 (ddt, J = 12.2, 10.3, 5.9 Hz,
    1H).
    13C NMR (101 MHz, CDCl3) δ 172.14,
    170.25, 162.99, 160.92 (d, J = 243.9 Hz),
    160.41, 145.70, 144.13, 142.50,
    138.76 (d, J = 7.3 Hz), 135.17 (d, J = 3.4 Hz),
    129.97 (d, J = 8.1 Hz),
    116.32 (d, J = 20.7 Hz), 112.61 (d, J = 20.6 Hz),
    109.63, 89.62, 73.34, 56.22, 49.52,
    48.31, 42.72, 31.73, 31.70, 25.20,
    24.53, 20.86, 20.61, 18.46, 17.80.
    19F NMR (376 MHz, CDCl3) δ −117.78.
    199 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 8.36 (d,
    film) 3379, calcd for C29H37FN2NaO7, J = 7.6 Hz, 1H), 8.30 (d, J = 5.4 Hz,
    2928, 567.2477; found, 567.2486 1H), 7.33 (dd, J = 8.7, 6.1 Hz, 1H),
    1733, 6.98 (d, J = 5.5 Hz, 1H), 6.82 (dd, J = 9.9,
    1675, 2.8 Hz, 1H), 6.71 (td, J = 8.5, 2.9 Hz,
    1497, 1H), 5.77 (d, J = 6.4 Hz, 1H), 5.70 (d, J = 6.4 Hz,
    1201, 1H), 5.43 (qd, J = 6.2, 3.8 Hz,
    1003, 969, 1H), 4.74 (p, J = 7.2 Hz, 1H), 3.92 (s,
    911, 829, 3H), 2.72 (dd, J = 9.9, 4.0 Hz, 1H),
    730 cm−1 2.26 (s, 3H), 2.07 (s, 3H), 1.99-1.87 (m,
    1H), 1.82-1.51 (m, 3H),
    1.51-1.39 (m, 3H), 1.37-1.01 (m, 6H), 0.99 (d, J = 6.3 Hz,
    3H), 0.84-0.67 (m, 1H).
    13C NMR (101 MHz, CDCl3) δ 172.12,
    170.24, 162.93, 160.90 (d, J = 243.7 Hz),
    160.44, 145.68, 144.17, 142.45,
    139.38 (d, J = 7.2 Hz), 134.63 (d, J = 2.9 Hz),
    129.67 (d, J = 8.0 Hz),
    116.28 (d, J = 20.5 Hz), 112.64 (d, J = 20.5 Hz),
    109.64, 89.64, 71.28, 56.22, 49.62,
    48.34, 39.99, 31.31, 31.21, 26.51,
    26.37, 26.27, 20.86, 20.73, 18.45,
    17.94.
    19F NMR (376 MHz, CDCl3) δ −117.79.
    200 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 8.56 (s,
    film) 3383, calcd for C26H35N2O6, 1H), 8.35 (d, J = 5.4 Hz, 1H), 7.19 (d, J = 7.9 Hz,
    2969, 471.2490; found, 471.2485 1H), 7.00 (d, J = 5.4 Hz, 1H),
    1772, 6.94 (d, J = 1.9 Hz, 1H), 6.90 (dd, J = 7.9,
    1733, 1.9 Hz, 1H), 5.41 (qd, J = 6.3, 4.7 Hz,
    1679, 1H), 4.77-4.61 (m, 1H), 3.91 (s,
    1200, 1176 cm−1 3H), 2.68 (dd, J = 9.3, 4.8 Hz, 1H),
    2.39 (s, 3H), 2.27 (s, 3H), 2.25 (s, 3H),
    2.03 (dp, J = 9.2, 6.6 Hz, 1H), 1.38 (d, J = 7.2 Hz,
    3H), 1.05 (d, J = 6.3 Hz, 3H),
    0.99 (d, J = 6.6 Hz, 3H), 0.69 (d, J = 6.8 Hz,
    3H).
    201 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 8.58 (s,
    film) 3383, calcd for C28H37N2O6, 1H), 8.35 (d, J = 5.5 Hz, 1H), 7.20 (d, J = 7.9 Hz,
    2950, 497.2646; found, 497.2640 1H), 7.01 (d, J = 5.4 Hz, 1H),
    1773, 6.97-6.86 (m, 2H), 5.31 (qd, J = 6.3,
    1734, 3.9 Hz, 1H), 4.78-4.64 (m, 1H),
    1679, 3.91 (s, 3H), 2.79 (dd, J = 10.4, 4.1 Hz, 1H),
    1507, 2.40 (s, 3H), 2.27 (s, 3H), 2.26 (s, 3H),
    1201, 1177 cm−1 2.26-2.16 (m, 1H), 1.93-1.82 (m,
    1H), 1.71-1.59 (m, 1H),
    1.59-1.23 (m, 7H), 1.29-1.15 (m, 1H), 1.07 (d, J = 6.4 Hz,
    3H), 0.92-0.83 (m, 1H).
    202 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (500 MHz, CDCl3) δ 8.58 (s,
    film) 3382, calcd for C29H38N2O6Na, 1H), 8.35 (d, J = 5.4 Hz, 1H), 7.21 (d, J = 7.8 Hz,
    2929, 533.2622; found, 533.2615 1H), 7.01 (d, J = 5.5 Hz, 1H),/
    1173, 6.96-6.88 (m, 2H), 5.42 (qd, J = 6.3,
    1735, 4.5 Hz, 1H), 4.76-4.67 (m, 1H),
    1679, 3.91 (s, 3H), 2.75 (dd, J = 9.4, 4.6 Hz, 1H),
    1508, 2.40 (s, 3H), 2.28 (s, 3H), 2.24 (s, 3H),
    1201, 1.90-1.50 (m, 5H), 1.41 (d, J = 7.2 Hz,
    1176, 735 cm−1 3H), 1.39-1.31 (m, 1H),
    1.29-1.14 (m, 1H), 1.14-1.04 (m, 2H), 1.03 (d, J = 6.3 Hz,
    3H), 1.01-0.86 (m, 1H),
    0.84-0.73 (m, 1H).
    203 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 8.56 (s,
    film) 2968, calcd for C27H37N2O6, 1H), 8.35 (dd, J = 5.4, 2.6 Hz, 1H),
    29333, 485.2646; found, 485.2643 7.20 (t, J = 7.2 Hz, 1H), 7.06-6.87 (m, 3H),
    1773, 5.42 (dtd, J = 10.6, 6.3, 4.5 Hz, 1H),
    1734, 4.77-4.62 (m, 1H), 3.91 (s, 3H),
    1679, 2.88-2.68 (m, 1H), 2.39 (s, 3H),
    1507, 2.29-2.24 (m, 6H), 1.94-1.53 (m, 1H),
    1200, 1177 cm−1 1.46-0.62 (m, 14H).
    204 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 8.38 (d,
    film) 3380, calcd for C27H37N2O7, J = 7.9 Hz, 1H), 8.29 (d, J = 5.4 Hz,
    2969, 501.2595; found, 501.2589 1H), 7.20 (d, J = 7.9 Hz, 1H),
    1732, 7.00-6.87 (m, 3H), 5.80-5.69 (m, 2H),
    1675, 5.42 (qd, J = 6.2, 4.7 Hz, 1H), 4.71 (p, J = 7.2 Hz,
    1502, 1H), 3.91 (s, 3H), 2.69 (dd, J = 9.2,
    1200, 4.9 Hz, 1H), 2.27 (s, 3H), 2.25 (s,
    1003, 967, 3H), 2.10-1.97 (m, 1H), 2.06 (s, 3H),
    829 cm−1 1.39 (d, J = 7.2 Hz, 3H), 1.07 (d, J = 6.3 Hz,
    3H), 0.99 (d, J = 6.6 Hz, 3H),
    0.70 (d, J = 6.7 Hz, 3H).
    205 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 8.39 (d,
    film) 3380, calcd for C29H39N2O7, J = 7.9 Hz, 1H), 8.29 (d, J = 5.4 Hz,
    2950, 527.2752; found, 527.2744 1H), 7.21 (d, J = 7.9 Hz, 1H),
    1756, 6.98-6.86 (m, 3H), 5.82-5.69 (m, 2H),
    1735, 5.32 (qd, J = 6.3, 4.1 Hz, 1H), 4.73 (p, J = 7.3 Hz,
    1678, 1H), 3.91 (s, 3H), 2.81 (dd, J = 10.3,
    1504, 4.2 Hz, 1H), 2.27 (s, 3H), 2.27 (s,
    1202, 1005 cm−1 3H), 2.25-2.19 (m, 1H), 2.07 (s, 3H),
    1.95-1.82 (m, 1H), 1.69-1.60 (m,
    1H), 1.57-1.34 (m, 7H),
    1.29-1.15 (m, 1H), 1.08 (d, J = 6.3 Hz, 3H),
    0.89 (tdd, J = 11.7, 9.4, 7.6 Hz, 1H).
    206 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (500 MHz, CDCl3) δ 8.39 (d,
    film) 3380, calcd for C30H40N2O7Na, J = 7.9 Hz, 1H), 8.29 (d, J = 5.3 Hz,
    2963, 563.2728; found, 563.2725 1H), 7.23 (d, J = 7.7 Hz, 1H),
    1756, 6.97-6.90 (m, 3H), 5.81-5.68 (m, 2H),
    1735, 5.42 (qd, J = 6.2, 4.6 Hz, 1H),
    1678, 4.77-4.69 (m, 1H), 3.91 (s, 3H), 2.76 (dd, J = 9.4,
    1504, 4.7 Hz, 1H), 2.28 (s, 3H), 2.24 (s, 3H),
    1202, 2.06 (s, 3H), 1.91-1.51z (m, 5H),
    1005, 970 cm−1 1.42 (d, J = 7.2 Hz, 3H), 1.40-1.33 (m, 1H),
    1.25-0.91 (m, 7H), 0.85-0.73 (m,
    1H).
    207 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 8.38 (d,
    film) 3381, calcd for C28H39N2O7, J = 16.9, 7.8 Hz, 1H), 8.32-8.26 (m,
    2968, 515.2752; found, 515.2746 1H), 7.21 (t, J = 8.3 Hz, 1H),
    2933, 7.00-6.86 (m, 3H), 5.81-5.66 (m, 2H),
    1757, 5.48-5.37 (m, 1H), 4.77-4.63 (m, 1H),
    1735, 3.91 (s, 3H), 2.88-2.70 (m, 1H),
    1678, 2.32-2.23 (m, 6H), 2.06 (s, 3H),
    1504, 1.90-1.52 (m, 1H), 1.46-0.66 (m, 14H).
    1202, 1005 cm−1
    208 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 8.62 (d,
    film) 2958, calcd for C25H31N2O6, J = 5.3 Hz, 1H), 7.15 (d, J = 5.4 Hz,
    1770, 455.2177; found, 455.2171 1H), 6.90 (d, J = 7.9 Hz, 1H),
    1715, 6.87-6.83 (m, 1H), 6.32-6.24 (m, 1H),
    1371, 5.65 (q, J = 7.1 Hz, 1H), 5.43 (qd, J = 6.4,
    1244, 734 cm−1 3.2 Hz, 1H), 4.05 (s, 3H), 2.53 (dd, J = 10.4,
    3.2 Hz, 1H), 2.18 (s, 3H), 2.10 (s,
    3H), 2.06-1.96 (m, 1H), 1.71 (d, J = 7.0 Hz,
    3H), 1.04 (d, J = 6.5 Hz, 3H),
    0.95 (d, J = 6.3 Hz, 3H), 0.60 (d, J = 6.6 Hz,
    3H).
    209 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 8.62 (d,
    film) 2949, calcd for C27H33N2O6, J = 5.3 Hz, 1H), 7.15 (d, J = 5.4 Hz,
    1770, 481.2333; found, 481.2325 1H), 6.93 (d, J = 7.9 Hz, 1H),
    1715, 6.87-6.82 (m, 1H), 6.33-6.28 (m, 1H),
    1502, 5.67 (q, J = 7.0 Hz, 1H), 5.29 (qd, J = 6.5,
    1371, 1243 cm−1 2.9 Hz, 1H), 4.05 (s, 3H), 2.68 (dd, J = 10.9,
    2.8 Hz, 1H), 2.30-2.18 (m, 4H),
    2.09 (s, 3H), 1.93 (dtd, J = 11.2, 7.2, 3.4 Hz,
    1H), 1.71 (d, J = 7.1 Hz, 3H),
    1.68-1.05 (m, 6H), 0.98 (d, J = 6.4 Hz,
    3H), 0.83-0.72 (m, 1H).
    210 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 8.63 (d,
    film) 2928, calcd for C28H35N2O6, J = 5.3 Hz, 1H), 7.15 (d, J = 5.3 Hz,
    1771, 495.2490; found, 495.2485 1H), 6.90 (d, J = 7.9 Hz, 1H),
    1715, 6.86-6.83 (m, 1H), 6.29-6.24 (m, 1H),
    1502, 5.67 (q, J = 7.0 Hz, 1H), 5.43 (qd, J = 6.3,
    1371, 1243 cm−1 3.1 Hz, 1H), 4.06 (s, 3H),
    2.66-2.60 (m, 1H), 2.17 (s, 3H), 2.10 (s, 3H),
    2.01-1.94 (m, 1H), 1.78-1.54 (m, 6H),
    1.53-1.43 (m, 1H), 1.34-1.19 (m,
    2H), 1.14-0.88 (m, 6H),
    0.76-0.58 (m, 1H).
    211 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 14.37 (s,
    film) 2964, calcd for C24H33N2O6, 1H), 12.78 (d, J = 7.0 Hz, 1H), 7.88 (d,
    1734, 445.2333; found, 445.2370 J = 7.1 Hz, 1H), 7.15 (d, J = 7.7 Hz,
    1644, 1H), 6.90 (d, J = 8.0 Hz, 2H), 6.77 (d, J = 7.2 Hz,
    1571, 1H), 5.42 (qd, J = 6.3, 5.0 Hz,
    1480, 1H), 4.69-4.61 (m, 1H), 3.96 (s, 3H),
    1302, 1216 cm−1 2.69 (dd, J = 9.1, 5.0 Hz, 1H), 2.25 (s,
    3H), 2.23 (s, 3H), 2.00 (dp, J = 8.8, 6.6 Hz,
    1H), 1.44 (d, J = 7.2 Hz, 3H),
    1.08 (d, J = 6.3 Hz, 3H), 0.98 (d, J = 6.6 Hz,
    3H), 0.69 (d, J = 6.8 Hz, 3H).
    212 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 14.38 (s,
    film) 2948, calcd for C26H35N2O6, 1H), 12.79 (d, J = 7.2 Hz, 1H), 7.90 (d,
    2868, 471.2490; found, 471.2515 J = 7.1 Hz, 1H), 7.17 (d, J = 7.9 Hz,
    1734, 1H), 6.96-6.85 (m, 2H), 6.77 (d, J = 7.1 Hz,
    1570, 1H), 5.31 (qd, J = 6.3, 4.0 Hz,
    1480, 1H), 4.72-4.60 (m, 1H), 3.96 (s, 3H),
    1301, 1218 cm−1 2.80 (dd, J = 10.3, 4.2 Hz, 1H),
    2.28-2.24 (m, 6H), 2.21-2.10 (m, 1H),
    1.95-1.85 (m, 1H), 1.69-1.30 (m, 8H),
    1.20 (dq, J = 12.3, 9.2 Hz, 1H), 1.08 (d,
    J = 6.3 Hz, 3H), 0.94-0.81 (m, 1H).
    213 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 14.37 (d,
    film) 2963, calcd for C25H35N2O6, J = 6.2 Hz, 1H), 12.75 (dd, J = 15.8, 7.1 Hz,
    2931, 459.2490; found, 459.2527 1H), 7.98-7.81 (m, 1H),
    1733, 7.21-6.71 (m, 4H), 5.50-5.33 (m, 1H),
    1569, 4.72-4.58 (m, 1H), 3.96 (s, 3H),
    1479, 2.92-2.70 (m, 1H), 2.31-2.19 (m, 6H),
    1453, 1.88-1.69 (m, 1H), 1.44 (dd, J = 48.4, 7.2 Hz,
    1301, 3H), 1.25-0.58 (m, 11H).
    1213, 729 cm−1
    214 IR (thin ESIMS m/z 461.1 1H NMR (500 MHz, CDCl3) δ 8.50 (d,
    film) 3382, ([M + H]+) J = 8.0 Hz, 1H), 8.33 (d, J = 5.4 Hz,
    2962, 1H), 7.17-6.99 (m, 3H),
    1770, 6.99-6.86 (m, 2H), 5.38 (dq, J = 8.2, 6.2 Hz, 1H),
    1731, 4.75-4.60 (m, 1H), 3.92 (s, 3H),
    1674, 2.69 (dd, J = 8.3, 6.9 Hz, 1H), 2.40 (s, 3H),
    1590, 2.14-2.00 (m, 1H), 1.49 (d, J = 7.2 Hz,
    1571, 3H), 1.08 (d, J = 6.3 Hz, 3H),
    1507, 0.87 (d, J = 6.7 Hz, 3H), 0.74 (d, J = 6.7 Hz,
    1452, 3H).
    1435, 13C NMR (126 MHz, CDCl3) δ 172.15,
    1309, 168.93, 162.38, 161.69 (d, J = 244.5 Hz),
    1198, 159.48, 146.65, 141.52, 137.54,
    1174, 134.34 (d, J = 3.3 Hz), 131.04 (d, J = 7.7 Hz),
    1159, 114.75 (d, J = 20.9 Hz), 109.77,
    1045, 906, 72.50, 56.31, 55.80, 48.17, 28.29,
    833, 803, 21.24, 20.77, 18.75, 18.65, 17.41.
    729 cm−1
    215 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.34 (d,
    film) 3381, calcd for C26H34FN2O7, J = 7.8 Hz, 1H), 8.28 (d, J = 5.3 Hz,
    2962, 505.2345; found, 505.2345 1H), 7.05 (dd, J = 8.5, 5.9 Hz, 1H),
    1756, 6.96 (d, J = 5.4 Hz, 1H), 6.91-6.77 (m,
    1677, 2H), 5.75 (s, 2H), 5.36 (dq, J = 9.0, 6.2 Hz,
    1499, 1H), 4.72 (p, J = 7.2 Hz, 1H),
    1203, 3.92 (s, 3H), 3.09 (dd, J = 9.0, 6.4 Hz, 1H),
    1044, 2.30 (s, 3H), 2.13 (q, J = 6.8 Hz, 1H),
    1004, 971, 2.08 (s, 3H), 1.52 (d, J = 7.2 Hz, 3H),
    830 cm−1 1.07 (d, J = 6.3 Hz, 3H), 0.86 (d, J = 6.7 Hz,
    3H), 0.78 (d, J = 6.8 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 172.35,
    170.26, 162.95, 160.94 (d, J = 244.4 Hz),
    160.33, 145.69, 144.07, 142.53,
    139.88 (d, J = 7.3 Hz), 133.64 (d, J = 3.0 Hz),
    129.16 (d, J = 6.0 Hz),
    116.96 (d, J = 20.5 Hz), 112.34 (d, J = 20.7 Hz),
    109.59, 89.61, 73.75, 56.20, 48.43,
    29.70, 29.30, 20.92, 20.87, 18.88,
    18.44, 17.99.
    19F NMR (376 MHz, CDCl3) δ −117.40.
    216 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.45 (d,
    film) 3382, calcd for C27H36FN2O6, J = 7.7 Hz, 1H), 8.32 (d, J = 5.4 Hz,
    2971, 503.2552; found, 503.2553 1H), 7.05 (dd, J = 8.6, 5.9 Hz, 1H),
    1733, 6.99 (d, J = 5.4 Hz, 1H), 6.90-6.73 (m,
    1678, 2H), 5.35 (dq, J = 8.9, 6.2 Hz, 1H),
    1499, 4.78-4.64 (m, 1H), 3.90 (s, 3H), 3.08 (dd, J = 8.9,
    1210, 6.5 Hz, 1H), 2.95 (p, J = 7.0 Hz,
    1153, 1H), 2.29 (s, 3H), 2.11 (h, J = 6.7 Hz,
    1123, 1H), 1.49 (d, J = 7.2 Hz, 3H), 1.37 (s,
    1045, 731 cm−1 3H), 1.35 (s, 3H), 1.06 (d, J = 6.2 Hz,
    3H), 0.86 (d, J = 6.8 Hz, 3H), 0.77 (d, J = 6.8 Hz,
    3H).
    13C NMR (101 MHz, CDCl3) δ 174.67,
    172.31, 162.33, 160.93 (d, J = 244.3 Hz),
    159.48, 146.54, 141.94, 139.89 (d,
    J = 7.3 Hz), 137.73, 133.69 (d, J = 2.9 Hz),
    129.15 (d, J = 7.1 Hz), 116.95 (d, J = 20.5 Hz),
    112.31 (d, J = 20.7 Hz),
    109.62, 73.70, 56.30, 48.19, 33.97,
    29.70, 20.93, 20.90, 20.89, 18.95,
    18.82, 18.62, 17.90.
    19F NMR (376 MHz, CDCl3) δ −117.44.
    217 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.60 (d,
    film) 2960, calcd for C24H28FN2O6, J = 5.3 Hz, 1H), 7.14 (d, J = 5.3 Hz,
    1714, 459.1926; found, 459.1926 1H), 6.97 (dd, J = 8.7, 6.0 Hz, 1H),
    1500, 6.62 (td, J = 8.5, 2.9 Hz, 1H), 6.23 (dd, J = 10.0,
    1371, 2.8 Hz, 1H), 5.49 (q, J = 7.0 Hz,
    1243, 1H), 5.34 (p, J = 6.3 Hz, 1H), 4.07 (s,
    1083, 731 cm−1 3H), 2.87 (dd, J = 9.9, 6.1 Hz, 1H),
    2.12 (s, 3H), 1.95 (dp, J = 9.8, 6.6 Hz, 1H),
    1.63 (d, J = 7.0 Hz, 3H), 1.15 (d, J = 6.3 Hz,
    3H), 1.00 (d, J = 6.5 Hz, 3H),
    0.63 (d, J = 6.6 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −117.44,
    −117.49.
    218 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 14.33 (s,
    film) 2962, calcd for C23H30FN2O6, 1H), 12.78 (d, J = 7.0 Hz, 1H), 7.88 (d,
    1736, 449.2082; found, 449.2085 J = 7.2 Hz, 1H), 7.05 (dd, J = 8.3, 5.9 Hz,
    1533, 1H), 6.88-6.75 (m, 3H), 5.37 (dq,
    1481, J = 8.9, 6.3 Hz, 1H), 4.66 (p, J = 7.1 Hz,
    1302, 1H), 3.98 (s, 3H), 3.08 (dd, J = 9.0,
    1241, 6.5 Hz, 1H), 2.30 (s, 3H), 2.09 (hept, J = 6.9 Hz,
    1155, 1H), 1.57 (d, J = 7.2 Hz, 3H),
    1030, 953, 1.07 (d, J = 6.2 Hz, 3H), 0.85 (d, J = 6.8 Hz,
    815, 758 cm−1 3H), 0.77 (d, J = 6.8 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 171.09,
    165.57, 160.90 (d, J = 244.3 Hz),
    152.59, 149.34, 139.86 (d, J = 7.3 Hz),
    133.66 (d, J = 3.1 Hz), 130.96,
    129.20 (d, J = 7.4 Hz), 123.74, 116.84 (d, J = 20.5 Hz),
    112.33 (d, J = 20.8 Hz),
    107.74, 73.95, 56.55, 48.90, 29.73,
    29.30, 20.93, 20.92, 18.96, 17.83,
    17.59.
    19F NMR (376 MHz, CDCl3) δ −117.36.
    219 IR (thin ESIMS m/z 491.2 1H NMR (400 MHz, CDCl3) δ 9.94 (d,
    film) 3281, ([M + H]+) J = 7.5 Hz, 1H), 8.32 (d, J = 5.4 Hz,
    2962, 1H), 7.05 (dd, J = 8.4, 5.9 Hz, 1H),
    1770, 7.00 (d, J = 5.5 Hz, 1H), 6.90-6.80 (m,
    1733, 2H), 5.39 (dq, J = 9.1, 6.3 Hz, 1H),
    1498, 5.18 (p, J = 7.1 Hz, 1H), 3.91 (s, 3H),
    1192, 3.10 (dd, J = 9.1, 6.3 Hz, 1H), 2.36 (s, 3H),
    1175, 2.30 (s, 3H), 2.19-2.09 (m, 1H),
    1104, 821, 1.60 (d, J = 7.1 Hz, 3H), 1.08 (d, J = 6.2 Hz,
    730 cm−1 3H), 0.86 (d, J = 6.7 Hz, 3H), 0.79 (d, J = 6.8 Hz,
    3H).
    13C NMR (101 MHz, CDCl3) δ 189.28,
    171.51, 168.58, 160.96 (d, J = 244.5 Hz),
    159.87, 146.29, 145.03, 139.87 (d,
    J = 7.4 Hz), 136.90, 133.53 (d, J = 2.9 Hz),
    129.16 (d, J = 6.9 Hz), 117.00 (d, J = 20.5 Hz),
    112.38 (d, J = 20.7 Hz),
    109.27, 74.11, 56.43, 53.08, 29.66,
    29.29, 21.26, 20.94, 20.91, 18.78,
    18.10, 16.84.
    19F NMR (376 MHz, CDCl3) δ −117.27.
    220 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.49 (d,
    film) 3382, calcd for C27H36FN2O7, J = 7.9 Hz, 1H), 8.32 (d, J = 5.4 Hz,
    2961, 519.2501; found, 519.2497 1H), 7.05 (dd, J = 8.6, 5.9 Hz, 1H),
    1732, 7.01 (d, J = 5.5 Hz, 1H), 6.89-6.77 (m,
    1676, 2H), 5.36 (dp, J = 8.9, 6.2 Hz, 1H),
    1499, 4.74-4.64 (m, 1H), 3.91 (s, 3H), 3.81 (t, J = 6.6 Hz,
    1151, 2H), 3.41 (s, 3H), 3.08 (dd, J = 8.9,
    1110, 6.5 Hz, 1H), 2.99 (t, J = 6.6 Hz,
    1049, 730 cm−1 2H), 2.29 (s, 3H), 2.11 (h, J = 6.7 Hz,
    1H), 1.49 (d, J = 7.1 Hz, 3H), 1.06 (d, J = 6.3 Hz,
    3H), 0.86 (d, J = 6.8 Hz, 3H),
    0.77 (d, J = 6.8 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 172.23,
    169.40, 162.30, 160.93 (d, J = 244.3 Hz),
    159.51, 146.69, 141.58, 139.89 (d,
    J = 7.4 Hz), 137.41, 133.65 (d, J = 3.2 Hz),
    129.15 (d, J = 9.6 Hz), 116.96 (d, J = 20.5 Hz),
    112.32 (d, J = 20.8 Hz),
    109.77, 73.74, 67.62, 58.76, 56.33,
    48.22, 34.67, 29.70, 20.93, 20.90,
    18.95, 18.58, 17.90.
    19F NMR (376 MHz, CDCl3) δ −117.42.
    221 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.53 (s,
    film) 3375, calcd for C25H32FN2O7, 1H), 8.35 (d, J = 5.4 Hz, 1H), 7.21 (dd,
    2964, 491.2188; found, 491.2184 J = 8.5, 6.9 Hz, 1H), 7.01 (d, J = 5.4 Hz,
    1771, 1H), 6.62-6.48 (m, 2H),
    1676, 5.46-5.37 (m, 1H), 4.74-4.64 (m, 1H),
    1502, 3.91 (s, 3H), 3.77 (s, 3H), 3.04 (dd, J = 9.5,
    1193, 4.8 Hz, 1H), 2.39 (s, 3H), 1.61 (s, 1H),
    1035, 953, 1.39 (d, J = 7.2 Hz, 3H), 1.03 (d, J = 6.3 Hz,
    832 cm−1 3H), 0.97 (d, J = 6.6 Hz, 3H),
    0.67 (d, J = 6.7 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −114.24.
    222 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.54 (s,
    film) 3379, calcd for C27H36FN2O7, 1H), 8.35 (d, J = 5.5 Hz, 1H), 7.23 (dd,
    2963, 519.2501; found, 519.2499 J = 8.5, 6.9 Hz, 1H), 7.01 (d, J = 5.5 Hz,
    1772, 1H), 6.60-6.49 (m, 2H),
    1733, 5.43-5.33 (m, 1H), 4.75-4.65 (m, 1H),
    1677, 3.91 (s, 3H), 3.77 (s, 3H), 3.30 (dd, J = 10.0,
    1502, 4.4 Hz, 1H), 2.39 (s, 3H),
    1194, 1.77-1.59 (m, 2H), 1.51-1.39 (m, 3H), 1.33 (dq,
    1177, J = 14.4, 7.2 Hz, 1H), 1.19 (dtd, J = 14.9,
    1036, 954, 7.5, 3.3 Hz, 1H), 1.01 (d, J = 6.2 Hz,
    834 cm−1 3H), 0.99-0.91 (m, 1H), 0.88 (t, J = 7.4 Hz,
    3H), 0.67 (t, J = 7.4 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −114.23.
    223 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.54 (d,
    film) 3381, calcd for C28H36FN2O7, J = 7.8 Hz, 1H), 8.35 (d, J = 5.4 Hz,
    2929, 531.2501; found, 531.2496 1H), 7.22 (t, J = 7.7 Hz, 1H), 7.01 (d, J = 5.4 Hz,
    1771, 1H), 6.56 (ddd, J = 9.5, 7.3,
    1731, 4.1 Hz, 2H), 5.42 (t, J = 5.8 Hz, 1H),
    1675, 4.70 (p, J = 7.3 Hz, 1H), 3.91 (s, 3H),
    1501, 3.76 (s, 3H), 3.11 (s, 1H), 2.40 (s, 3H),
    1193, 1.78 (dd, J = 46.1, 13.0 Hz, 2H),
    1175, 953, 1.59 (dd, J = 20.5, 8.6 Hz, 3H), 1.42 (dd, J = 11.2,
    731 cm−1 7.1 Hz, 3H), 1.37-0.85 (m, 8H),
    0.83-0.67 (m, 1H).
    19F NMR (376 MHz, CDCl3) δ −114.25.
    224 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.55 (s,
    film) 3382, calcd for C27H34FN2O7, 1H), 8.35 (d, J = 5.4 Hz, 1H), 7.23 (t, J = 7.7 Hz,
    2946, 517.2345; found, 517.2341 1H), 7.02 (d, J = 5.4 Hz, 1H),
    1771, 6.57 (dd, J = 11.1, 2.6 Hz, 1H),
    1731, 6.50 (td, J = 8.4, 2.5 Hz, 1H), 5.32 (dt, J = 10.1,
    1675, 5.0 Hz, 1H), 4.72 (p, J = 7.2 Hz,
    1501, 1H), 3.92 (s, 3H), 3.77 (s, 3H), 3.11 (d,
    1192, J = 10.7 Hz, 1H), 2.40 (s, 3H),
    1176, 2.22-2.06 (m, 1H), 1.86 (dtd, J = 11.2, 6.9,
    1149, 951, 3.4 Hz, 1H), 1.71-1.59 (m, 2H),
    731 cm−1 1.59-1.29 (m, 5H), 1.29-1.16 (m, 2H),
    1.02 (d, J = 6.3 Hz, 3H), 0.88 (dq, J = 11.9,
    8.4, 8.0 Hz, 1H).
    19F NMR (376 MHz, CDCl3) δ −114.34.
    225 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.52 (s,
    film) 3378, calcd for C26H34FN2O7, 1H), 8.34 (dd, J = 5.5, 3.2 Hz, 1H),
    2964, 505.2345; found, 505.2341 7.21 (ddd, J = 11.8, 8.4, 6.9 Hz, 1H),
    1771, 7.01 (dd, J = 5.5, 3.5 Hz, 1H), 6.55 (dddt, J = 13.6,
    1731, 8.1, 5.3, 2.7 Hz, 2H),
    1675, 5.48-5.36 (m, 1H), 4.75-4.58 (m, 1H),
    1501, 3.94-3.87 (m, 3H), 3.77 (d, J = 1.1 Hz,
    1193, 3H), 3.16 (ddd, J = 47.2, 9.4, 4.9 Hz,
    1175, 1H), 2.39 (d, J = 2.9 Hz, 3H),
    1035, 952, 1.86-1.71 (m, 1H), 1.61-1.36 (m, 2H),
    833, 732 cm−1 1.34-1.21 (m, 3H), 1.11-0.93 (m, 4H),
    0.89 (td, J = 7.3, 3.6 Hz, 2H),
    0.75-0.61 (m, 3H).
    19F NMR (376 MHz, CDCl3) δ −114.21,
    −114.28.
    226 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.47 (s,
    film) 3379, calcd for C26H32FN2O7, 1H), 8.33 (d, J = 5.4 Hz, 1H), 7.06 (dd,
    2938, 503.2188; found, 503.2181 J = 8.5, 6.8 Hz, 1H), 7.01 (d, J = 5.4 Hz,
    1771, 1H), 6.55 (dd, J = 11.0, 2.6 Hz,
    1731, 1H), 6.48 (td, J = 8.3, 2.5 Hz, 1H),
    1675, 5.21 (q, J = 6.1 Hz, 1H), 4.62 (p, J = 7.3 Hz,
    1502, 1H), 3.91 (s, 3H), 3.78 (s, 3H), 3.25 (s,
    1193, 1H), 2.65 (d, J = 14.9 Hz, 1H), 2.40 (s,
    1176, 3H), 2.15-2.06 (m, 1H),
    1035, 953, 1.87-1.58 (m, 4H), 1.43 (dt, J = 17.2, 8.4 Hz, 1H),
    733 cm−1 1.30 (d, J = 7.1 Hz, 3H), 1.11 (d, J = 6.3 Hz,
    3H).
    19F NMR (376 MHz, CDCl3) δ −114.16.
    227 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.54 (d,
    film) 3381, calcd for C28H36FN2O7, J = 7.8 Hz, 1H), 8.31 (d, J = 5.4 Hz,
    2927, 531.2501; found, 531.2493 1H), 7.00 (q, J = 4.9 Hz, 2H), 6.60 (td,
    1770, J = 8.3, 2.5 Hz, 1H), 6.53 (dd, J = 11.0,
    1732, 2.5 Hz, 1H), 5.54-5.31 (m, 1H),
    1675, 4.78-4.63 (m, 1H), 3.91 (s, 3H), 3.73 (s, 3H),
    1502, 3.47 (d, J = 69.3 Hz, 1H), 2.40 (s, 3H),
    1192, 1.81-1.51 (m, 5H), 1.49 (d, J = 7.1 Hz,
    1175, 3H), 1.37-1.08 (m, 2H),
    1034, 953, 1.08-1.04 (m, 4H), 1.04-0.70 (m, 3H).
    908, 730 cm−1 19F NMR (376 MHz, CDCl3) δ −114.00.
    228 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.50 (s,
    film) 3379, calcd for C27H34FN2O7, 1H), 8.28 (d, J = 5.4 Hz, 1H), 7.05 (t, J = 7.7 Hz,
    2944, 517.2345; found, 517.2333 1H), 7.00 (d, J = 5.5 Hz, 1H),
    1770, 6.58 (td, J = 8.2, 2.5 Hz, 1H), 6.49 (dd,
    1732, J = 11.1, 2.5 Hz, 1H), 5.32 (s, 1H),
    1675, 4.71-4.59 (m, 1H), 3.91 (s, 3H), 3.71 (s,
    1502, 3H), 3.48 (d, J = 40.6 Hz, 1H), 2.40 (s,
    1192, 3H), 2.18 (s, 1H), 1.92-1.78 (m, 1H),
    1176, 1.63 (s, 1H), 1.56-1.34 (m, 6H),
    1149, 1.34-1.20 (m, 2H), 1.11 (d, J = 6.4 Hz,
    1033, 952, 3H), 0.89 (td, J = 9.3, 8.3, 3.7 Hz, 1H).
    732 cm−1 19F NMR (376 MHz, CDCl3) δ −114.18.
    229 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.53 (s,
    film) 2963, calcd for C27H36FN2O7, 1H), 8.30 (d, J = 5.4 Hz, 1H),
    1772, 519.2501; found, 519.2499 7.09-6.97 (m, 2H), 6.58 (td, J = 8.2, 2.5 Hz,
    1733, 1H), 6.51 (dd, J = 11.0, 2.6 Hz, 1H),
    1677, 5.49-5.37 (m, 1H), 4.74-4.63 (m,
    1503, 1H), 3.91 (s, 3H), 3.73 (s, 3H), 3.58 (s,
    1194, 1H), 2.40 (s, 3H), 1.61 (d, J = 18.5 Hz,
    1177, 1H), 1.48 (d, J = 7.1 Hz, 3H),
    1035, 954 cm−1 1.45-1.28 (m, 2H), 1.27-1.12 (m, 1H),
    1.09 (d, J = 6.2 Hz, 3H), 1.00-0.83 (m,
    4H), 0.74 (t, J = 7.3 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −113.98.
    230 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.55 (s,
    film) 2964, calcd for C26H34FN2O7, 1H), 8.31 (dd, J = 8.1, 5.4 Hz, 1H),
    1770, 505.2345; found, 505.2333 7.08-6.97 (m, 2H), 6.65-6.55 (m, 1H),
    1732, 6.55-6.48 (m, 1H), 5.45 (d, J = 11.2 Hz,
    1675, 1H), 4.69 (ddd, J = 14.1, 8.0, 7.1 Hz,
    1502, 1H), 3.91 (s, 3H), 3.74 (d, J = 9.6 Hz,
    1193, 3H), 3.51 (d, J = 44.9 Hz, 1H),
    1175, 2.40 (d, J = 1.8 Hz, 3H), 1.90-1.58 (m,
    1034, 953, 1H), 1.55-1.44 (m, 3H),
    834, 731 cm−1 1.41-1.26 (m, 1H), 1.07 (dd, J = 11.1, 6.2 Hz,
    3H), 0.99-0.80 (m, 4H), 0.75 (t, J = 7.4 Hz,
    3H).
    19F NMR (376 MHz, CDCl3) δ −113.91,
    −114.00.
    231 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.51 (d,
    film) 3381, calcd for C26H32FN2O7, J = 7.6 Hz, 1H), 8.31 (d, J = 5.4 Hz,
    2939, 503.2188; found, 503.2173 1H), 7.02-6.94 (m, 2H),
    1770, 6.65-6.49 (m, 2H), 5.16 (s, 1H), 4.73-4.59 (m,
    1731, 1H), 3.91 (s, 3H), 3.77 (s, 3H), 3.33 (s,
    1674, 1H), 2.78 (hept, J = 8.6, 7.8 Hz, 1H),
    1502, 2.40 (s, 3H), 2.17-2.04 (m, 1H),
    1193, 1.97-1.56 (m, 4H), 1.45 (d, J = 7.1 Hz,
    1175, 3H), 1.43-1.36 (m, 1H), 1.08 (d, J = 6.4 Hz,
    1148, 3H).
    1035, 953, 19F NMR (376 MHz, CDCl3) δ −113.98.
    731 cm−1
    232 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.54 (d,
    film) 3379, calcd for C25H32FN2O7, J = 7.3 Hz, 1H), 8.31 (d, J = 5.4 Hz,
    2962, 491.2188; found, 491.2179 1H), 7.05-6.97 (m, 2H), 6.60 (td, J = 8.3,
    1770, 2.6 Hz, 1H), 6.54 (dd, J = 11.1, 2.5 Hz,
    1732, 1H), 5.48-5.31 (m, 1H),
    1674, 4.77-4.64 (m, 1H), 3.91 (s, 3H), 3.74 (s, 3H),
    1502, 3.33 (s, 1H), 2.40 (s, 3H),
    1192, 2.14-2.01 (m, 1H), 1.66 (s, 1H), 1.49 (d, J = 7.1 Hz,
    1175, 2H), 1.07 (d, J = 6.2 Hz, 3H),
    1150, 0.85 (d, J = 6.7 Hz, 3H), 0.72 (d, J = 6.8 Hz,
    1034, 953, 3H).
    731 cm−1 19F NMR (376 MHz, CDCl3) δ −113.95.
    233 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.36 (d,
    film) 3381, calcd for C29H38FN2O8, J = 7.9 Hz, 1H), 8.29 (d, J = 5.4 Hz,
    2928, 561.2607; found, 561.2602 1H), 7.26-7.22 (m, 1H), 6.96 (d, J = 5.4 Hz,
    1733, 1H), 6.61-6.52 (m, 2H),
    1675, 5.78-5.72 (m, 2H), 5.42 (q, J = 5.9 Hz, 1H),
    1501, 4.72 (p, J = 7.1 Hz, 1H), 3.91 (s, 3H),
    1201, 3.77 (s, 3H), 3.13 (s, 1H), 2.07 (s, 3H),
    1004, 953, 1.89-1.51 (m, 7H), 1.42 (d, J = 7.1 Hz,
    831, 730 cm−1 3H), 1.37-1.05 (m, 3H), 1.03 (d, J = 6.2 Hz,
    2H), 1.01-0.68 (m, 2H).
    19F NMR (376 MHz, CDCl3) δ −114.24.
    234 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.37 (d,
    film) 3381, calcd for C28H36FN2O8, J = 7.9 Hz, 1H), 8.29 (d, J = 5.4 Hz,
    2948, 547.2450; found, 547.2445 1H), 7.28-7.21 (m, 1H), 6.96 (d, J = 5.4 Hz,
    1732, 1H), 6.57 (dd, J = 11.1, 2.5 Hz,
    1674, 1H), 6.52 (td, J = 8.4, 2.5 Hz, 1H),
    1501, 5.81-5.71 (m, 2H), 5.33 (qd, J = 6.4, 3.8 Hz,
    1200, 1H), 4.73 (p, J = 7.2 Hz, 1H),
    1004, 951, 3.92 (s, 3H), 3.77 (s, 3H), 3.12 (d, J = 10.4 Hz,
    831 cm−1 1H), 2.18 (s, 1H), 2.07 (s, 3H),
    1.98-1.80 (m, 1H), 1.64 (d, J = 6.5 Hz,
    2H), 1.58-1.29 (m, 5H),
    1.29-1.15 (m, 2H), 1.02 (dd, J = 14.6, 6.3 Hz,
    3H), 0.94-0.83 (m, 1H).
    19F NMR (376 MHz, CDCl3) δ −114.31.
    235 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.32 (d,
    film) 3379, calcd for C28H36FN2O8, J = 7.8 Hz, 1H), 8.25 (d, J = 5.4 Hz,
    2945, 547.2450; found, 547.2444 1H), 7.05 (t, J = 7.7 Hz, 1H), 6.95 (d, J = 5.4 Hz,
    1733, 1H), 6.59 (td, J = 8.2, 2.5 Hz,
    1674, 1H), 6.50 (dd, J = 11.1, 2.5 Hz, 1H),
    1501, 5.74 (s, 2H), 5.32 (s, 1H), 4.68 (p, J = 7.2 Hz,
    1200, 1H), 3.91 (s, 3H), 3.73 (s, 3H),
    1035, 3.49 (d, J = 46.2 Hz, 1H), 2.07 (s, 3H),
    1003, 953, 1.90-1.78 (m, 1H), 1.63 (d, J = 24.2 Hz,
    831, 731 cm−1 1H), 1.55-1.31 (m, 8H),
    1.31-1.19 (m, 1H), 1.12 (d, J = 6.4 Hz, 3H),
    0.90 (td, J = 9.4, 8.3, 3.6 Hz, 1H).
    19F NMR (376 MHz, CDCl3) δ −114.15.
    236 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.33 (d,
    film) 3381, calcd for C27H34FN2O8, J = 7.9 Hz, 1H), 8.27 (d, J = 5.4 Hz,
    2939, 533.2294; found, 533.2286 1H), 7.02-6.92 (m, 2H),
    1733, 6.60-6.47 (m, 2H), 5.80-5.70 (m, 2H), 5.16 (s,
    1674, 1H), 4.78-4.63 (m, 1H), 3.91 (s, 3H),
    1501, 3.78 (s, 3H), 3.34 (s, 1H), 2.79 (h, J = 8.6 Hz,
    1200, 1H), 2.20-2.09 (m, 1H),
    1147, 2.07 (s, 3H), 1.99-1.57 (m, 4H), 1.48 (dd, J = 7.1,
    1037, 3.0 Hz, 3H), 1.45-1.37 (m, 1H),
    1003, 953, 1.09 (d, J = 6.4 Hz, 3H).
    831, 731 cm−1 19F NMR (376 MHz, CDCl3) δ −113.97.
    237 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.36 (d,
    film) 3379, calcd for C26H34FN2O8, J = 7.8 Hz, 1H), 8.27 (d, J = 5.3 Hz,
    2962, 521.2294; found, 521.2284 1H), 7.01 (dd, J = 8.5, 6.8 Hz, 1H),
    1733, 6.95 (d, J = 5.4 Hz, 1H), 6.60 (td, J = 8.3,
    1674, 2.5 Hz, 1H), 6.55 (dd, J = 11.1, 2.5 Hz,
    1501, 1H), 5.75 (s, 2H), 5.56-5.31 (m, 1H),
    1200, 4.71 (p, J = 7.3 Hz, 1H), 3.92 (s, 3H),
    1036, 3.75 (s, 3H), 3.34 (s, 1H), 2.07 (s, 3H),
    1003, 953, 1.67 (s, 1H), 1.51 (d, J = 7.1 Hz, 3H),
    831, 731 cm−1 1.08 (d, J = 6.3 Hz, 3H), 0.85 (d, J = 6.8 Hz,
    3H), 0.73 (d, J = 6.8 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −113.93.
    238 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.49 (s,
    film) 3380, calcd for C28H36FN2O8, 1H), 8.31 (d, J = 5.4 Hz, 1H), 6.98 (dd,
    2937, 547.2450; found, 547.2439 J = 15.2, 6.2 Hz, 2H), 6.61-6.46 (m,
    1768, 2H), 5.16 (s, 1H), 4.70-4.59 (m, 1H),
    1732, 3.90 (s, 3H), 3.82 (t, J = 6.6 Hz, 2H),
    1675, 3.77 (s, 3H), 3.41 (s, 3H),
    1502, 3.37-3.23 (m, 1H), 2.99 (t, J = 6.7 Hz, 2H),
    1146, 2.77 (h, J = 8.8, 8.4 Hz, 1H), 2.16-2.05 (m,
    1110, 1H), 1.97-1.55 (m, 5H), 1.44 (d, J = 7.2 Hz,
    1035, 953, 3H), 1.08 (d, J = 6.4 Hz, 3H).
    833, 731 cm−1 19F NMR (376 MHz, CDCl3) δ −113.97.
    239 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.52 (s,
    film) 3377, calcd for C27H36FN2O8, 1H), 8.31 (d, J = 5.4 Hz, 1H),
    2961, 535.2450; found, 535.2441 7.07-6.97 (m, 2H), 6.60 (td, J = 8.3, 2.6 Hz,
    1768, 1H), 6.54 (dd, J = 11.0, 2.5 Hz, 1H),
    1675, 5.49-5.35 (m, 1H), 4.72-4.60 (m,
    1502, 1H), 3.90 (s, 3H), 3.81 (t, J = 6.6 Hz,
    1310, 2H), 3.74 (s, 3H), 3.41 (s, 3H), 3.28 (d,
    1148, J = 41.3 Hz, 1H), 2.99 (t, J = 6.6 Hz,
    1112, 2H), 2.08 (dp, J = 13.6, 7.0 Hz, 1H),
    1034, 953, 1.48 (d, J = 7.1 Hz, 3H), 1.07 (d, J = 6.2 Hz,
    833, 732 cm−1 3H), 0.85 (d, J = 6.7 Hz, 3H),
    0.72 (d, J = 6.9 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −113.94.
    240 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ
    film) 1733, calcd for C28H37N2O7, 8.35-8.23 (m, 2H), 7.02 (d, J = 7.9 Hz, 1H),
    1674, 513.2595; found, 513.2591 6.95-6.84 (m, 3H), 5.79-5.68 (m,
    1503, 2H), 5.20-5.08 (m, 1H),
    1201, 4.66-4.55 (m, 1H), 3.90 (s, 3H), 3.04 (dd, J = 10.5,
    1003, 968, 6.3 Hz, 1H), 2.70 (dh, J = 16.8,
    911, 729 cm−1 8.8, 8.2 Hz, 1H), 2.32 (s, 3H), 2.24 (s,
    3H), 2.19-2.10 (m, 1H), 2.06 (s, 3H),
    1.89-1.63 (m, 4H), 1.46-1.36 (m,
    1H), 1.21 (d, J = 7.2 Hz, 3H), 1.18 (d, J = 6.3 Hz,
    3H).
    241 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 8.48 (s,
    film) 2938, calcd for C27H35N2O6, 1H), 8.33 (d, J = 5.5 Hz, 1H),
    1771, 483.2490; found, 483.2484 7.04-6.85 (m, 4H), 5.20-5.10 (m, 1H),
    1675, 4.65-4.52 (m, 1H), 3.90 (s, 3H), 3.03 (dd, J = 10.5,
    1505, 6.3 Hz, 1H), 2.69 (h, J = 9.1 Hz,
    1199, 1H), 2.39 (s, 3H), 2.32 (s, 3H), 2.25 (s,
    1175, 908, 3H), 2.20-2.10 (m, 1H),
    730 cm−1 1.88-1.63 (m, 4H), 1.46-1.35 (m, 1H), 1.20 (d, J = 7.1 Hz,
    3H), 1.16 (d, J = 6.4 Hz, 3H).
    242 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.49 (d,
    film) 3380, calcd for J = 8.1 Hz, 1H), 8.34 (d, J = 5.5 Hz,
    2961, C24H30ClN2O6, 479.1769; 1H), 7.21 (d, J = 8.4 Hz, 2H),
    1771, found, 479.1772 7.07-6.97 (m, 3H), 5.46-5.33 (m, 1H),
    1734, 4.75-4.61 (m, 1H), 3.92 (s, 3H), 2.68 (t, J = 7.6 Hz,
    1676, 1H), 2.40 (s, 3H),
    1508, 2.12-2.02 (m, 1H), 1.49 (d, J = 7.1 Hz, 3H),
    1310, 1.08 (d, J = 6.3 Hz, 3H), 0.88 (d, J = 6.6 Hz,
    1200, 3H), 0.73 (d, J = 6.8 Hz, 3H).
    1175,
    1061, 827 cm−1
    243 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.54 (s,
    film) 3380, calcd for C25H32FN2O6, 1H), 8.34 (d, J = 5.4 Hz, 1H),
    2962, 476.2271; found, 476.2275 7.11-6.97 (m, 2H), 6.83-6.64 (m, 2H),
    1772, 5.44-5.29 (m, 1H), 4.77-4.60 (m, 1H),
    1735, 3.92 (s, 3H), 2.71-2.60 (m, 1H),
    1677, 2.40 (s, 3H), 2.24 (d, J = 1.8 Hz, 3H),
    1508, 2.13-2.00 (m, 1H), 1.49 (d, J = 7.1 Hz, 3H),
    1202, 1.09 (d, J = 6.3 Hz, 3H), 0.86 (d, J = 6.8 Hz,
    1176, 1061 cm−1 3H), 0.75 (d, J = 6.7 Hz, 3H).
    244 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.48 (d,
    film) 3382, calcd for C24H29F2N2O6, J = 8.1 Hz, 1H), 8.33 (d, J = 5.4 Hz,
    2963, 480.202; found, 480.202 1H), 7.08-6.97 (m, 2H), 6.92 (ddd, J = 11.7,
    1771, 7.6, 2.2 Hz, 1H), 6.85-6.72 (m,
    1734, 1H), 5.41-5.26 (m, 1H),
    1676, 4.75-4.63 (m, 1H), 3.92 (s, 3H), 2.73-2.57 (m,
    1513, 1H), 2.40 (s, 3H), 2.12-1.99 (m, 1H),
    1203, 1.48 (d, J = 7.1 Hz, 3H), 1.09 (d, J = 6.3 Hz,
    1175, 1061 cm−1 3H), 0.89 (d, J = 6.5 Hz, 3H),
    0.74 (d, J = 6.7 Hz, 3H).
    245 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.53 (d,
    film) 3380, calcd for C27H37N2O7, J = 8.0 Hz, 1H), 8.34 (d, J = 5.5 Hz,
    2960, 501.2595; found, 501.2589 1H), 7.06 (t, J = 7.0 Hz, 2H),
    1769, 7.02-6.95 (m, 3H), 5.39 (dq, J = 8.7, 6.2 Hz,
    1732, 1H), 4.74-4.63 (m, 1H), 3.90 (s, 3H),
    1676, 3.81 (t, J = 6.6 Hz, 2H), 3.40 (s, 3H),
    1508, 2.99 (t, J = 6.6 Hz, 2H), 2.67 (dd, J = 8.7,
    1210, 6.3 Hz, 1H), 2.32 (s, 3H), 2.09 (h, J = 6.7 Hz,
    1111, 1H), 1.50 (d, J = 7.1 Hz, 3H),
    1061, 823 cm−1 1.08 (d, J = 6.3 Hz, 3H), 0.85 (d, J = 6.8 Hz,
    3H), 0.75 (d, J = 6.8 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 172.29,
    169.42, 162.35, 159.50, 146.71, 141.69,
    137.40, 136.06, 135.51, 129.68, 128.62,
    109.74, 72.83, 67.62, 58.76, 56.32,
    56.24, 48.23, 34.66, 28.22, 21.36,
    21.01, 18.68, 18.57, 17.84.
    246 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.51 (d,
    film) 3380, calcd for C27H36FN2O7, J = 7.7 Hz, 1H), 8.33 (d, J = 5.5 Hz,
    2961, 519.2501; found, 519.2498 1H), 7.01 (d, J = 5.5 Hz, 1H),
    1733, 6.93-6.80 (m, 3H), 5.36 (dq, J = 8.6, 6.3 Hz,
    1676, 1H), 4.73-4.62 (m, 1H), 3.91 (s, 3H),
    1503, 3.81 (t, J = 6.6 Hz, 2H), 3.40 (s, 3H),
    1208, 2.99 (t, J = 6.6 Hz, 2H), 2.65 (dd, J = 8.6,
    1115, 6.6 Hz, 1H), 2.24 (d, J = 1.9 Hz,
    1051, 731 cm−1 3H), 2.08 (hept, J = 6.7 Hz, 1H),
    1.49 (d, J = 7.2 Hz, 3H), 1.08 (d, J = 6.3 Hz,
    3H), 0.85 (d, J = 6.7 Hz, 3H), 0.74 (d, J = 6.8 Hz,
    3H).
    13C NMR (101 MHz, CDCl3) δ 172.24,
    169.42, 162.36, 160.27 (d, J = 243.5 Hz),
    159.52, 146.72, 141.64, 137.42,
    134.08 (d, J = 3.9 Hz), 132.56 (d, J = 5.0 Hz),
    128.37 (d, J = 7.7 Hz),
    124.07 (d, J = 17.1 Hz), 114.38 (d, J = 22.0 Hz),
    109.78, 72.67, 67.62, 58.76, 56.33,
    55.84, 48.22, 34.67, 28.28, 21.30,
    18.67, 18.63, 17.67, 14.63 (d, J = 3.6 Hz).
    19F NMR (376 MHz, CDCl3) δ −120.90.
    247 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.53 (d,
    film) 3377, calcd for C27H36FN2O8, J = 7.7 Hz, 1H), 8.33 (d, J = 5.4 Hz,
    2962, 535.2450; found, 535.2446 1H), 7.06-6.97 (m, 2H),
    1734, 6.69-6.62 (m, 1H), 6.58 (dd, J = 12.0, 2.6 Hz,
    1676, 1H), 5.40 (ddt, J = 8.6, 6.8, 3.4 Hz, 1H),
    1507, 4.75-4.60 (m, 1H), 3.90 (s, 3H),
    1209, 3.81 (t, J = 6.6 Hz, 2H), 3.78 (s, 3H), 3.40 (s,
    1113, 3H), 3.09 (t, J = 7.6 Hz, 1H), 2.99 (t, J = 6.6 Hz,
    1061, 833, 2H), 2.10 (h, J = 6.8 Hz, 1H),
    731 cm−1 1.49 (d, J = 7.1 Hz, 3H), 1.10 (d, J = 6.3 Hz,
    3H), 0.93-0.87 (m, 3H), 0.75 (d, J = 6.7 Hz,
    3H).
    13C NMR (101 MHz, CDCl3) δ 172.25,
    169.41, 162.33, 162.10 (d, J = 244.3 Hz),
    159.48, 159.32 (d, J = 11.2 Hz),
    146.71, 141.67, 137.38, 130.69 (d, J = 6.6 Hz),
    117.57 (d, J = 15.3 Hz),
    109.73, 109.58 (d, J = 2.9 Hz),
    101.39 (d, J = 28.0 Hz), 72.48, 67.62, 58.76,
    56.31, 55.44, 48.21, 34.66, 29.29,
    28.36, 21.10, 18.97, 18.50, 17.43.
    19F NMR (376 MHz, CDCl3) δ −112.98.
    248 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.51 (d,
    film) 3380, calcd for C27H36FN2O8, J = 7.9 Hz, 1H), 8.34 (d, J = 5.4 Hz,
    2962, 535.2450; found, 535.2444 1H), 7.01 (d, J = 5.5 Hz, 1H),
    1732, 6.92-6.75 (m, 3H), 5.34 (dq, J = 8.3, 6.2 Hz,
    1676, 1H), 4.66 (dt, J = 8.1, 7.1 Hz, 1H),
    1511, 3.90 (s, 3H), 3.86 (s, 3H), 3.81 (t, J = 6.6 Hz,
    1273, 2H), 3.40 (s, 3H), 2.99 (t, J = 6.6 Hz,
    1210, 2H), 2.64 (dd, J = 8.6, 6.5 Hz, 1H),
    1113, 731 cm−1 2.05 (h, J = 6.8 Hz, 1H), 1.49 (d, J = 7.2 Hz,
    3H), 1.09 (d, J = 6.3 Hz, 3H), 0.87 (d, J = 6.7 Hz,
    3H), 0.75 (d, J = 6.7 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 172.19,
    169.42, 162.36, 159.51, 151.94 (d, J = 245.0 Hz),
    146.73, 146.25 (d, J = 10.8 Hz),
    141.62, 137.42, 131.84 (d, J = 5.6 Hz),
    125.47 (d, J = 3.6 Hz), 117.15 (d, J = 18.2 Hz),
    113.05-112.84 (m),
    109.77, 72.51, 67.62, 58.76, 56.33,
    56.24, 55.74, 48.21, 34.67, 28.35,
    21.25, 18.77, 18.63, 17.47.
    19F NMR (376 MHz, CDCl3) δ −135.76.
    249 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.55 (s,
    film) 3379, calcd for C28H39N2O8, 1H), 8.32 (d, J = 5.4 Hz, 1H), 6.99 (d, J = 5.5 Hz,
    2960, 531.2701; found, 531.2703 1H), 6.94 (d, J = 7.7 Hz, 1H),
    1769, 6.75-6.69 (m, 1H), 6.65 (d, J = 1.6 Hz,
    1732, 1H), 5.41 (d, J = 7.8 Hz, 1H),
    1678, 4.73-4.62 (m, 1H), 3.90 (s, 3H), 3.82 (t, J = 6.6 Hz,
    1506, 2H), 3.75 (s, 3H), 3.40 (s, 3H),
    1311, 2.99 (t, J = 6.7 Hz, 2H), 2.31 (s, 3H),
    1210, 2.09 (h, J = 6.7 Hz, 1H), 1.69 (s, 1H),
    1111, 1.49 (d, J = 7.1 Hz, 3H), 1.07 (d, J = 6.2 Hz,
    1041, 808 cm−1 3H), 0.84 (d, J = 6.7 Hz, 3H),
    0.74 (d, J = 6.8 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 172.30,
    169.43, 162.30, 159.47, 158.10, 146.70,
    141.75, 137.36, 137.15, 124.61, 120.69,
    111.71, 109.69, 73.50, 67.63, 58.76,
    56.31, 55.31, 48.32, 34.67, 29.30,
    28.80, 21.43, 21.12, 18.87, 18.61,
    18.11.
    250 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.53 (d,
    film) 3381, calcd for C25H32FN2O6, J = 8.0 Hz, 1H), 8.34 (d, J = 5.4 Hz,
    2962, 475.2239; found, 475.2236 1H), 7.01 (d, J = 5.5 Hz, 1H),
    1771, 6.92-6.84 (m, 3H), 5.36 (dq, J = 8.6, 6.3 Hz,
    1733, 1H), 4.69 (dq, J = 8.1, 7.1 Hz, 1H),
    1677, 3.91 (s, 3H), 2.70-2.62 (m, 1H), 2.40 (s,
    1503, 3H), 2.24 (d, J = 1.9 Hz, 3H), 2.07 (h, J = 6.7 Hz,
    1311, 1H), 1.50 (d, J = 7.1 Hz, 3H),
    1203, 1.08 (d, J = 6.2 Hz, 3H), 0.85 (d, J = 6.7 Hz,
    1176, 3H), 0.74 (d, J = 6.8 Hz, 3H).
    1049, 733 cm−1 13C NMR (101 MHz, CDCl3) δ 172.23,
    168.89, 162.41, 160.27 (d, J = 243.4 Hz),
    159.51, 146.66, 141.63, 137.57,
    134.08 (d, J = 3.8 Hz), 132.56 (d, J = 4.9 Hz),
    128.37 (d, J = 7.7 Hz),
    124.08 (d, J = 17.2 Hz), 114.38 (d, J = 22.0 Hz),
    109.78, 72.69, 56.30, 55.84, 48.22,
    28.28, 21.30, 20.75, 18.67, 18.64,
    17.67, 14.63 (d, J = 3.6 Hz).
    19F NMR (376 MHz, CDCl3) δ −120.91.
    251 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.55 (d,
    film) 3376, calcd for C25H32FN2O7, J = 7.7 Hz, 1H), 8.33 (d, J = 5.4 Hz,
    2963, 491.2188; found, 491.2183 1H), 7.06-6.97 (m, 2H), 6.65 (ddd, J = 8.6,
    1771, 2.6, 0.8 Hz, 1H), 6.58 (dd, J = 12.0,
    1733, 2.6 Hz, 1H), 5.41 (dqd, J = 7.6, 6.2, 1.2 Hz,
    1675, 1H), 4.68 (dq, J = 8.1, 7.2 Hz, 1H),
    1507, 3.91 (s, 3H), 3.78 (s, 3H),
    1195, 3.15-3.03 (m, 1H), 2.40 (s, 3H), 2.14-2.05 (m,
    1175, 1H), 1.50 (d, J = 7.2 Hz, 3H), 1.10 (d, J = 6.3 Hz,
    1150, 3H), 0.90 (dd, J = 6.7, 0.8 Hz,
    1033, 833, 3H), 0.75 (d, J = 6.7 Hz, 3H).
    731 cm−1 13C NMR (101 MHz, CDCl3) δ 172.24,
    168.89, 162.39, 162.11 (d, J = 244.3 Hz),
    159.49, 159.34 (d, J = 11.2 Hz),
    146.66, 141.67, 137.54, 130.71 (d, J = 6.5 Hz),
    117.58 (d, J = 15.5 Hz),
    109.73, 109.59 (d, J = 3.0 Hz),
    101.40 (d, J = 27.9 Hz), 72.50, 56.29, 55.45,
    48.22, 29.30, 28.37, 21.10, 20.75,
    18.98, 18.51, 17.42.
    19F NMR (376 MHz, CDCl3) δ −112.96.
    252 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.53 (d,
    film) 3379, calcd for C25H32FN2O7, J = 8.0 Hz, 1H), 8.34 (d, J = 5.4 Hz,
    2962, 491.2188; found, 491.2182 1H), 7.01 (d, J = 5.5 Hz, 1H),
    1770, 6.90-6.76 (m, 3H), 5.34 (dq, J = 8.4, 6.3 Hz,
    1732, 1H), 4.73-4.63 (m, 1H), 3.91 (s, 3H),
    1675, 3.86 (s, 3H), 2.68-2.61 (m, 1H),
    1512, 2.40 (s, 3H), 2.05 (dq, J = 13.5, 6.8 Hz, 1H),
    1202, 1.49 (d, J = 7.2 Hz, 3H), 1.09 (d, J = 6.3 Hz,
    1176, 3H), 0.87 (d, J = 6.7 Hz, 3H),
    1030, 731 cm−1 0.75 (d, J = 6.7 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 172.17,
    168.90, 162.41, 159.50, 151.94 (d, J = 245.0 Hz),
    146.68, 146.25 (d, J = 10.6 Hz),
    141.59, 137.56, 131.84 (d, J = 5.7 Hz),
    125.48 (d, J = 3.6 Hz), 117.13 (d, J = 18.2 Hz),
    112.94 (d, J = 1.6 Hz),
    109.77, 72.53, 56.27 (d, J = 6.4 Hz),
    55.73, 48.21, 29.29, 28.35, 21.25,
    20.75, 18.76, 18.64, 17.47.
    19F NMR (376 MHz, CDCl3) δ −135.76.
    253 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.57 (d,
    film) 3381, calcd for C26H35N2O7, J = 7.9 Hz, 1H), 8.32 (d, J = 5.4 Hz,
    2961, 487.2439; found, 487.2430 1H), 7.00 (d, J = 5.5 Hz, 1H), 6.94 (d, J = 7.7 Hz,
    1772, 1H), 6.75-6.68 (m, 1H),
    1732, 6.65 (d, J = 1.6 Hz, 1H),
    1678, 5.51-5.39 (m, 1H), 4.76-4.60 (m, 1H), 3.90 (s,
    1507, 3H), 3.75 (s, 3H), 3.33 (s, 1H), 2.40 (s,
    1201, 3H), 2.31 (s, 3H), 2.09 (h, J = 6.7 Hz,
    1176, 1H), 1.50 (d, J = 7.1 Hz, 3H), 1.07 (d, J = 6.2 Hz,
    1041, 733 cm−1 3H), 0.84 (d, J = 6.8 Hz, 3H),
    0.74 (d, J = 6.8 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 172.29,
    168.90, 162.35, 159.46, 158.10, 146.65,
    141.73, 137.51, 137.15, 124.61, 120.69,
    111.71, 109.69, 73.52, 56.28, 55.31,
    48.33, 29.30, 28.80, 21.43, 21.13,
    20.75, 18.85, 18.62, 18.11.
    254 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.55 (d,
    film) 3379, calcd for C26H35N2O7, J = 8.0 Hz, 1H), 8.33 (d, J = 5.4 Hz,
    2959, 487.2439; found, 487.2436 1H), 7.06-6.92 (m, 2H), 6.70 (d, J = 8.1 Hz,
    1771, 2H), 5.35 (dq, J = 9.2, 6.2 Hz,
    1731, 1H), 4.70 (dq, J = 8.1, 7.1 Hz, 1H),
    1677, 3.91 (s, 3H), 3.78 (s, 3H), 3.06 (dd, J = 9.3,
    1503, 6.0 Hz, 1H), 2.40 (s, 3H), 2.29 (s, 3H),
    1201, 2.12 (dq, J = 13.4, 6.7 Hz, 1H), 1.51 (d,
    1175, J = 7.1 Hz, 3H), 1.05 (d, J = 6.2 Hz,
    1046, 733 cm−1 3H), 0.84 (d, J = 6.8 Hz, 3H), 0.79 (d, J = 6.9 Hz,
    3H).
    13C NMR (101 MHz, CDCl3) δ 172.34,
    168.88, 162.37, 159.49, 157.56, 146.65,
    141.65, 138.91, 137.54, 130.04, 128.84,
    115.90, 110.86, 109.74, 74.13, 56.29,
    55.05, 48.27, 29.64, 29.30, 21.09,
    20.99, 20.75, 18.74, 18.61, 18.26.
    255 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.37 (d,
    film) 3379, calcd for C26H35N2O7, J = 7.8 Hz, 1H), 8.29 (d, J = 5.3 Hz,
    2961, 487.2439; found, 487.2433 1H), 7.11-7.03 (m, 2H),
    1756, 7.03-6.93 (m, 3H), 5.75 (d, J = 0.6 Hz, 2H),
    1675, 5.40 (dq, J = 8.8, 6.3 Hz, 1H),
    1503, 4.79-4.66 (m, 1H), 3.91 (s, 3H), 2.68 (dd, J = 8.8,
    1201, 6.3 Hz, 1H), 2.32 (s, 3H),
    1042, 2.16-2.03 (m, 4H), 1.53 (d, J = 7.1 Hz, 3H),
    1003, 969, 1.09 (d, J = 6.3 Hz, 3H), 0.85 (d, J = 6.8 Hz,
    827, 731 cm−1 3H), 0.76 (d, J = 6.8 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 172.40,
    170.26, 162.98, 160.32, 145.70, 144.04,
    142.66, 136.08, 135.50, 129.69, 128.62,
    109.55, 89.63, 72.83, 56.26, 56.19,
    48.44, 28.23, 21.36, 21.01, 20.87,
    18.57, 18.54, 17.89.
    256 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.36 (d,
    film) 3380, calcd for C26H34FN2O7, J = 7.7 Hz, 1H), 8.29 (d, J = 5.4 Hz,
    2962, 505.2345; found, 505.2339 1H), 6.96 (d, J = 5.4 Hz, 1H),
    1735, 6.93-6.85 (m, 3H), 5.75 (s, 2H), 5.37 (dq, J = 8.6,
    1674, 6.2 Hz, 1H), 4.78-4.65 (m, 1H),
    1503, 3.92 (s, 3H), 2.67 (dd, J = 8.6, 6.5 Hz,
    1203, 1H), 2.24 (d, J = 2.0 Hz, 3H), 2.07 (s,
    1043, 4H), 1.52 (d, J = 7.2 Hz, 3H), 1.09 (d, J = 6.3 Hz,
    1004, 969, 3H), 0.85 (d, J = 6.7 Hz, 3H),
    829, 731 cm−1 0.75 (d, J = 6.8 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 172.35,
    170.27, 163.00, 160.33, 160.28 (d, J = 243.4 Hz),
    145.71, 144.07, 142.60,
    134.07 (d, J = 3.8 Hz), 132.59 (d, J = 4.9 Hz),
    128.35 (d, J = 7.7 Hz),
    124.09 (d, J = 17.2 Hz), 114.38 (d, J = 22.1 Hz),
    109.59, 89.62, 72.67, 56.20, 55.85,
    48.43, 28.28, 21.31, 20.87, 18.62,
    18.51, 17.74, 14.63 (d, J = 3.5 Hz).
    19F NMR (376 MHz, CDCl3) δ −120.87.
    257 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.37 (d,
    film) 3380, calcd for C26H34FN2O8, J = 7.8 Hz, 1H), 8.28 (d, J = 5.4 Hz,
    2963, 521.2294; found, 521.2286 1H), 7.03 (t, J = 8.5 Hz, 1H), 6.95 (d = 5.4 Hz,
    1736, 1H), 6.66 (ddd, J = 8.6, 2.6,
    1676, 0.7 Hz, 1H), 6.58 (dd, J = 12.0, 2.6 Hz,
    1507, 1H), 5.78-5.68 (m, 2H),
    1200, 5.47-5.36 (m, 1H), 4.75-4.65 (m, 1H), 3.91 (s,
    1040, 3H), 3.79 (s, 3H), 3.10 (t, J = 7.7 Hz,
    1004, 969, 1H), 2.07 (s, 4H), 1.52 (d, J = 7.2 Hz,
    831 cm−1 3H), 1.11 (d, J = 6.3 Hz, 3H), 0.90 (dd,
    J = 6.7, 0.8 Hz, 3H), 0.76 (d, J = 6.7 Hz,
    3H).
    13C NMR (101 MHz, CDCl3) δ 172.36,
    170.27, 162.99, 162.11 (d, J = 244.3 Hz),
    160.32, 159.34 (d, J = 11.2 Hz),
    145.70, 144.04, 142.64, 130.70 (d, J = 5.5 Hz),
    117.58 (d, J = 15.5 Hz),
    109.58 (d, J = 3.3 Hz), 109.55, 101.40 (d, J = 27.9 Hz),
    89.63, 72.58-72.37 (m),
    56.19, 55.45, 48.42, 29.30, 28.39,
    21.10, 20.87, 18.98, 18.37, 17.44.
    19F NMR (376 MHz, CDCl3) δ −112.98.
    258 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.36 (d,
    film) 3378, calcd for C26H34FN2O8, J = 7.8 Hz, 1H), 8.29 (d, J = 5.4 Hz,
    2962, 521.2294; found, 521.2288 1H), 6.96 (d, J = 5.4 Hz, 1H),
    1736, 6.90-6.76 (m, 3H), 5.75 (s, 2H), 5.35 (dq, J = 8.5,
    1674, 6.3 Hz, 1H), 4.70 (p, J = 7.2 Hz,
    1513, 1H), 3.92 (s, 3H), 3.87 (s, 3H),
    1203, 2.69-2.60 (m, 1H), 2.13-2.01 (m, 4H),
    1043, 1.52 (d, J = 7.1 Hz, 3H), 1.10 (d, J = 6.3 Hz,
    1004, 969, 3H), 0.87 (d, J = 6.7 Hz, 3H), 0.76 (d, J = 6.7 Hz,
    732 cm−1 3H).
    13C NMR (101 MHz, CDCl3) δ 172.31,
    170.27, 163.01, 160.33, 151.95 (d, J = 245.4 Hz),
    146.27 (d, J = 10.8 Hz),
    145.72, 144.07, 142.57, 131.82 (d, J = 5.8 Hz),
    125.46 (d, J = 3.5 Hz),
    117.16 (d, J = 18.0 Hz), 113.05-112.84 (m),
    109.59, 89.62, 72.51, 56.22 (d, J = 5.0 Hz),
    55.76, 48.41, 29.30, 28.35, 21.26,
    20.87, 18.70, 18.51, 17.55.
    19F NMR (376 MHz, CDCl3) δ −135.75.
    259 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.39 (d,
    film) 3376, calcd for C27H37N2O8, J = 7.7 Hz, 1H), 8.28 (d, J = 5.4 Hz,
    2960, 517.2544; found, 517.2539 1H), 6.97-6.92 (m, 2H),
    1737, 6.76-6.68 (m, 1H), 6.66 (d, J = 1.6 Hz, 1H),
    1678, 5.80-5.72 (m, 2H), 5.42 (d, J = 8.1 Hz,
    1505, 1H), 4.76-4.65 (m, 1H), 3.91 (s, 3H),
    1203, 3.76 (s, 3H), 3.34 (s, 1H), 2.32 (s, 3H),
    1042, 2.15-2.02 (m, 4H), 1.52 (d, J = 7.1 Hz,
    1004, 971, 3H), 1.07 (d, J = 6.2 Hz, 3H),
    736 cm−1 0.84 (d, J = 6.8 Hz, 3H), 0.74 (d, J = 6.8 Hz,
    3H).
    13C NMR (101 MHz, CDCl3) δ 172.43,
    170.26, 162.95, 160.30, 158.11, 145.71,
    143.99, 142.75, 137.16, 124.61, 120.70,
    111.72, 109.51, 89.64, 73.51, 56.18,
    55.32, 48.52, 29.30, 28.82, 21.43,
    21.14, 20.87, 18.83, 18.49, 18.17.
    260 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.37 (d,
    film) 3379, calcd for C27H37N2O8, J = 7.8 Hz, 1H), 8.28 (d, J = 5.4 Hz,
    2960, 517.2544; found, 517.2536 1H), 7.04-6.97 (m, 1H), 6.95 (d, J = 5.4 Hz,
    1732, 1H), 6.70 (d, J = 7.5 Hz, 2H),
    1674, 5.75 (d, J = 0.7 Hz, 2H), 5.36 (dq, J = 9.3,
    1502, 6.2 Hz, 1H), 4.77-4.65 (m, 1H),
    1201, 3.91 (s, 3H), 3.78 (s, 3H), 3.07 (dd, J = 9.3,
    1043, 6.0 Hz, 1H), 2.30 (s, 3H),
    1003, 969, 2.18-2.09 (m, 1H), 2.07 (s, 3H), 1.53 (d, J = 7.1 Hz,
    830, 730 cm−1 3H), 1.06 (d, J = 6.2 Hz, 3H),
    0.84 (d, J = 6.8 Hz, 3H), 0.79 (d, J = 6.8 Hz,
    3H).
    13C NMR (101 MHz, CDCl3) δ 172.47,
    170.26, 162.97, 160.31, 157.57, 145.70,
    144.04, 142.62, 138.90, 130.02, 128.86,
    115.89, 110.88, 109.56, 89.62, 74.11,
    56.19, 55.05, 48.48, 29.65, 29.30,
    21.09, 20.99, 20.87, 18.71, 18.47,
    18.31.
    261 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.58 (d,
    film) 3379, calcd for C25H33N2O7, J = 7.7 Hz, 1H), 8.32 (d, J = 5.4 Hz,
    2961, 473.2282; found, 473.2264 1H), 7.22-7.13 (m, 1H), 7.07 (dd, J = 7.6,
    1770, 1.8 Hz, 1H), 7.00 (d, J = 5.6 Hz,
    1732, 1H), 6.97-6.80 (m, 2H),
    1675, 5.64-5.28 (m, 1H), 4.77-4.57 (m, 1H), 3.91 (s,
    1508, 3H), 3.77 (s, 3H), 3.55-3.28 (m, 1H),
    1175, 731 cm−1 2.40 (s, 3H), 2.12 (dq, J = 13.4, 6.7 Hz,
    1H), 1.50 (d, J = 7.1 Hz, 3H), 1.08 (d, J = 6.3 Hz,
    3H), 0.85 (d, J = 6.8 Hz, 3H),
    0.74 (d, J = 6.7 Hz, 3H).
    262 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.58 (s,
    film) 3379, calcd for C26H35N2O8, 1H), 8.32 (d, J = 5.4 Hz, 1H), 7.00 (d, J = 5.5 Hz,
    2960, 503.2388; found, 503.2374 1H), 6.96 (d, J = 8.2 Hz, 1H),
    1770, 6.47-6.39 (m, 2H), 5.42 (d, J = 9.2 Hz,
    1732, 1H), 4.79-4.61 (m, 1H), 3.91 (s,
    1676, 3H), 3.78 (s, 3H), 3.74 (s, 3H),
    1505, 3.45-3.16 (m, 1H), 2.40 (s, 3H),
    1205, 730 cm−1 2.13-2.01 (m, 1H), 1.50 (d, J = 7.1 Hz, 3H),
    1.07 (d, J = 6.3 Hz, 3H), 0.83 (d, J = 6.7 Hz,
    3H), 0.73 (d, J = 6.8 Hz, 3H).
    263 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.38 (d,
    film) 3379, calcd for C26H35N2O8, J = 7.8 Hz, 1H), 8.27 (d, J = 5.4 Hz,
    2961, 503.2388; found, 503.2359 1H), 7.22-7.13 (m, 1H), 7.07 (dd, J = 7.6,
    1735, 1.8 Hz, 1H), 6.94 (d, J = 5.4 Hz,
    1674, 1H), 6.92-6.75 (m, 2H),
    1493, 5.82-5.69 (m, 2H), 5.45 (s, 1H), 4.81-4.59 (m,
    1203, 969, 1H), 3.91 (s, 3H), 3.77 (s, 3H),
    733 cm−1 3.53-3.23 (m, 1H), 2.16-2.05 (m, 4H),
    1.52 (d, J = 7.1 Hz, 3H), 1.08 (d, J = 6.2 Hz,
    3H), 0.85 (d, J = 6.7 Hz, 3H), 0.74 (d, J = 6.8 Hz,
    3H).
    264 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.38 (d,
    film) 3379, calcd for C27H37N2O9, J = 7.8 Hz, 1H), 8.27 (d, J = 5.4 Hz,
    2960, 533.2494; found, 533.2488 1H), 7.03-6.84 (m, 2H), 6.43 (d, J = 7.8 Hz,
    1734, 2H), 5.74 (d, J = 1.2 Hz, 2H),
    1675, 5.46-5.34 (m, 1H), 4.78-4.62 (m,
    1505, 1H), 3.90 (s, 3H), 3.78 (s, 3H), 3.74 (s,
    1204, 3H), 3.42-2.96 (m, 1H),
    1041, 830, 2.15-2.04 (m, 4H), 1.51 (d, J = 7.2 Hz, 3H),
    731 cm−1 1.07 (d, J = 6.2 Hz, 3H), 0.82 (d, J = 6.7 Hz,
    3H), 0.73 (d, J = 6.8 Hz, 3H).
    265 ESIMS m/z 268.3
    ([M + H]+)
    266 ESIMS m/z 310.3
    ([M + H]+)
    267 ESIMS m/z 324.3
    ([M + H]+)
    268 ESIMS m/z 324.3
    ([M + H]+)
    269 IR (thin HRMS-ESI (m/z) [M + H]+
    film) 2969, calcd for C17H28NO2,
    1743, 278.2115; found, 278.2108
    1502,
    1449,
    1365,
    1230,
    1216,
    1203,
    1120,
    1053, 805 cm−1
    270 IR (thin HRMS-ESI (m/z) [M + H]+
    film) 2961, calcd for C16H25FNO2,
    2826, 282.1864; found, 282.1877
    1739,
    1578,
    1508,
    1466,
    1368,
    1253,
    1235,
    1197,
    1166,
    1094,
    1044, 786,
    754 cm−1
    271 IR (thin HRMS-ESI (m/z) [M + H]+
    film) 2959, calcd for C15H23FNO2,
    2851, 268.1707; found, 268.1718
    1739,
    1583,
    1491,
    1454,
    1248,
    1231,
    1197,
    1120,
    1051, 761 cm−1
    272 IR (thin HRMS-ESI (m/z) [M + H]+
    film) 2959, calcd for C16H25FNO2,
    2873, 282.1864; found, 282.1869
    1737,
    1587,
    1530,
    1498,
    1457,
    1284,
    1238,
    1190,
    1114,
    1047, 873,
    813 cm−1
    273 IR (thin HRMS-ESI (m/z) [M + H]+
    film) 2870, calcd for C17H28NO2,
    1742, 278.2115; found, 278.2119
    1594,
    1502,
    1454,
    1377,
    1251,
    1226,
    1199,
    1118,
    1048, 887,
    818 cm−1
    274 IR (thin HRMS-ESI (m/z) [M + H]+
    film) 2871, calcd for C17H28NO2,
    1740, 278.2115; found, 278.2110
    1588,
    1407,
    1455,
    1384,
    1252,
    1239,
    1200,
    1117,
    1044, 783 cm−1
    275 IR (thin HRMS-ESI (m/z) [M + H]+
    film) 2871, calcd for C16H26NO2,
    1738, 264.1958; found, 264.1953
    1586,
    1505,
    1455,
    1244,
    1196,
    1162,
    1119,
    1053, 754 cm−1
    276 IR (thin HRMS-ESI (m/z) [M + H]+
    film) 2961, calcd for C15H22F2NO2,
    2872, 286.1613; found, 286.1628
    1754,
    1740,
    1602,
    1501,
    1244,
    1116,
    1082, 967,
    846 cm−1
    277 IR (thin HRMS-ESI (m/z) [M + H]+
    film) 2960, calcd for C16H25FNO2,
    1757, 282.1864; found, 282.1871
    1508,
    1458,
    1269,
    1236,
    1212,
    1124,
    1050, 853,
    819 cm−1
    278 IR (thin
    film) 2967,
    2873,
    1737,
    1589,
    1476,
    1382,
    1251,
    1229,
    1121,
    1107,
    1043, 871,
    845, 824 cm−1
    279 IR (thin HRMS-ESI (m/z) [M + H]+
    film) 2963, calcd for C15H22F2NO2,
    1740, 286.1613; found, 286.1637
    1602,
    1501,
    1458,
    1234,
    1207,
    1172,
    1113, 964,
    846 cm−1
    280 IR (thin HRMS-ESI (m/z) [M + H]+
    film) 2961, calcd for C16H25FNO2,
    1740, 282.1864; found, 282.1878
    1506,
    1456,
    1235,
    1207,
    1115, 939 cm−1
    281 IR (thin HRMS-ESI (m/z) [M + H]+
    film) 2962, calcd for C15H22Cl2NO2,
    1739, 318.1022; found, 318.1022
    1470,
    1381,
    1233,
    1192,
    1109,
    1044,
    1007, 806 cm−1
    282 IR (thin
    film) 3391,
    2959,
    2875,
    1736,
    1488,
    1231,
    1196,
    1114, 1035 cm−1
    283 HRMS-ESI (m/z) [M + H]+
    calcd for C16H23F3NO3,
    334.1625; found, 334.1616
    284 IR (thin
    film) 2973,
    1738,
    1509,
    1237,
    1117, 831 cm−1
    285 HRMS-ESI (m/z) [M + H]+
    calcd for C18H30NO3,
    308.2226; found, 308.2074
    286 HRMS-ESI (m/z) [M + Na]+
    calcd for C16H25NO3Na,
    302.1727; found, 302.1723
    287
    288 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.04 (dd,
    film) 3367, calcd for C20H30FNNaO4, J = 8.5, 5.9 Hz, 1H), 6.87 (ddt, J = 11.6,
    2964, 390.2051; found, 390.2053 8.3, 4.1 Hz, 2H), 5.40 (dq, J = 8.3, 6.3 Hz,
    1713, 1H), 5.02 (s, 1H), 3.93-3.85 (m,
    1498, 2H), 3.02 (t, J = 7.7 Hz, 1H), 2.31 (s,
    1366, 3H), 2.07 (h, J = 6.8 Hz, 1H), 1.46 (s,
    1164, 9H), 1.04 (d, J = 6.3 Hz, 3H), 0.91 (d, J = 6.7 Hz,
    1052, 954, 3H), 0.77 (d, J = 6.8 Hz, 3H).
    862 cm−1 13C NMR (101 MHz, CDCl3) δ 169.85,
    160.98 (d, J = 244.6 Hz), 155.63,
    139.89 (d, J = 8.0 Hz), 133.68 (d, J = 2.8 Hz),
    129.24 (d, J = 7.3 Hz),
    117.01 (d, J = 20.5 Hz), 112.37 (d, J = 20.8 Hz),
    79.96, 73.61, 49.56, 42.78, 29.85,
    28.33, 20.96, 20.78, 19.55, 17.64.
    19F NMR (376 MHz, CDCl3) δ −117.37.
    289 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.04 (dd,
    film) 2964, calcd for C23H36FNNaO4, J = 8.6, 6.0 Hz, 1H), 6.87 (qd, J = 9.3,
    1712, 432.2521; found, 432.2521 8.4, 2.8 Hz, 2H), 5.33 (dq, J = 9.5, 6.2 Hz,
    1498, 1H), 4.97 (d, J = 9.4 Hz, 1H),
    1366, 4.24 (dd, J = 9.3, 4.4 Hz, 1H), 3.09 (dd, J = 9.5,
    1158, 5.7 Hz, 1H), 2.33 (s, 3H),
    1049, 863 cm−1 2.26-2.07 (m, 2H), 1.46 (s, 9H), 1.02 (d, J = 6.2 Hz,
    3H), 1.00 (d, J = 6.9 Hz, 3H),
    0.88 (d, J = 6.9 Hz, 3H), 0.83 (d, J = 6.8 Hz,
    3H), 0.80 (d, J = 6.9 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 171.82,
    160.99 (d, J = 244.4 Hz), 155.66,
    139.90 (d, J = 7.6 Hz), 133.39 (d, J = 2.7 Hz),
    129.26 (d, J = 7.4 Hz),
    117.04 (d, J = 20.5 Hz), 112.37 (d, J = 20.6 Hz),
    79.70, 73.46, 58.88, 49.31, 31.26,
    29.27, 28.34, 20.91, 19.38, 18.39, 17.03.
    19F NMR (376 MHz, CDCl3) δ −117.33.
    290 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.04 (dd,
    film) 2964, calcd for C24H38FNNaO4, J = 8.6, 5.9 Hz, 1H), 6.93-6.81 (m,
    1712, 446.2677; found, 446.2681 2H), 5.33 (dq, J = 9.5, 6.2 Hz, 1H),
    1498, 4.96 (d, J = 9.3 Hz, 1H), 4.28 (dd, J = 9.3,
    1366, 4.5 Hz, 1H), 3.10 (dd, J = 9.6, 5.5 Hz,
    1158, 1H), 2.33 (s, 3H), 2.14 (dt, J = 13.5, 6.7 Hz,
    1049, 863 cm−1 1H), 1.99-1.83 (m, 1H),
    1.54-1.32 (m, 10H), 1.21-1.08 (m, 1H),
    1.02 (d, J = 6.2 Hz, 3H), 0.97 (d, J = 6.8 Hz,
    3H), 0.91 (t, J = 7.4 Hz, 3H),
    0.82 (d, J = 6.9 Hz, 3H), 0.80 (d, J = 6.9 Hz,
    3H).
    13C NMR (101 MHz, CDCl3) δ 171.79,
    161.00 (d, J = 244.4 Hz), 155.59,
    139.90 (d, J = 7.3 Hz), 133.33 (d, J = 2.9 Hz),
    129.28 (d, J = 7.6 Hz),
    117.05 (d, J = 20.5 Hz), 112.37 (d, J = 20.7 Hz),
    79.69, 73.41, 58.61, 49.35, 37.97,
    29.19, 28.35, 24.40, 20.92, 18.45, 18.21,
    15.71, 11.56.
    19F NMR (376 MHz, CDCl3) δ −117.32.
    291 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (400 MHz, CDCl3) δ 7.05 (dd,
    film) 3365, calcd for C24H38FNNaO4, J = 8.5, 5.9 Hz, 1H), 6.93-6.82 (m,
    2960, 446.2677; found, 446.2675 2H), 5.31 (dq, J = 9.2, 6.2 Hz, 1H),
    1714, 4.85 (d, J = 8.8 Hz, 1H), 4.29 (td, J = 9.1, 4.8 Hz,
    1499, 1H), 3.08 (dd, J = 9.2, 6.1 Hz, 1H),
    1367, 2.33 (s, 3H), 2.12 (h, J = 6.7 Hz, 1H),
    1165, 1.70 (dq, J = 13.1, 6.8 Hz, 1H),
    1049, 863 cm−1 1.58 (ddd, J = 13.5, 8.4, 5.1 Hz, 1H),
    1.52-1.36 (m, 10H), 1.03 (d, J = 6.2 Hz, 3H),
    0.95 (dd, J = 6.6, 3.0 Hz, 6H), 0.85 (d, J = 6.8 Hz,
    3H), 0.78 (d, J = 6.8 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 172.88,
    160.98 (d, J = 244.5 Hz), 155.31,
    139.86 (d, J = 7.3 Hz), 133.62 (d, J = 2.9 Hz),
    129.25 (d, J = 8.4 Hz),
    116.99 (d, J = 20.5 Hz), 112.37 (d, J = 20.6 Hz),
    79.73, 73.45, 52.55, 49.36, 41.84,
    29.51, 28.33, 24.82, 23.05, 21.82, 20.95,
    18.75, 18.09.
    19F NMR (376 MHz, CDCl3) δ −117.42.
    292 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (500 MHz, CDCl3) δ 7.04 (d, J = 7.6 Hz,
    film) 3357, calcd for C22H35NO4Na, 1H), 6.92 (dd, J = 7.7, 1.7 Hz,
    2963, 400.2458; found, 400.2450 1H), 6.89 (s, 1H), 5.35 (dq, J = 9.4, 6.2 Hz,
    2874, 1H), 5.08 (d, J = 7.9 Hz, 1H),
    1712, 4.30 (t, J = 7.6 Hz, 1H), 3.09 (dd, J = 9.4, 6.0 Hz,
    1501, 1H), 2.29 (s, 3H), 2.28 (s, 3H),
    1451, 2.14 (dq, J = 13.5, 6.7 Hz, 1H), 1.45 (s, 9H),
    1365, 1.40 (d, J = 7.1 Hz, 3H), 1.04 (d, J = 6.2 Hz,
    1160, 1049 cm−1 3H), 0.84 (d, J = 6.8 Hz, 3H),
    0.81 (d, J = 6.9 Hz, 3H).
    293 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (500 MHz, CDCl3) δ 7.11 (td,
    film) 3356, calcd for C21H32FNO4Na, J = 7.9, 5.9 Hz, 1H), 6.99-6.82 (m,
    2965, 404.2208; found, 404.2208 2H), 5.36 (dq, J = 9.1, 6.2 Hz, 1H),
    1712, 5.05 (d, J = 7.8 Hz, 1H), 4.29 (t, J = 7.5 Hz,
    1500, 1H), 3.14 (dd, J = 9.0, 6.4 Hz, 1H),
    1455, 2.24 (d, J = 2.3 Hz, 3H), 2.14 (dq, J = 13.4,
    1365, 6.7 Hz, 1H), 1.45 (s, 9H), 1.39 (d, J = 7.2 Hz,
    1245, 3H), 1.04 (d, J = 6.2 Hz, 3H),
    1161, 0.86 (d, J = 6.8 Hz, 3H), 0.79 (d, J = 6.8 Hz,
    1045, 820 cm−1 3H).
    294 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (500 MHz, CDCl3) δ
    film) 3363, calcd for C20H30FNO4Na, 7.25-7.19 (m, 1H), 7.12 (dtd, J = 22.9, 7.6,
    2965, 390.2051; found, 390.2053 1.6 Hz, 2H), 7.03 (ddd, J = 9.7, 8.1, 1.3 Hz,
    2933, 1H), 5.43 (dqd, J = 7.5, 6.3, 1.3 Hz,
    1712, 1H), 5.06 (d, J = 7.9 Hz, 1H),
    1491, 4.39-4.15 (m, 1H), 3.18 (t, J = 7.7 Hz, 1H),
    1453, 2.22-2.03 (m, 1H), 1.45 (s, 9H),
    1365, 1.38 (d, J = 7.2 Hz, 3H), 1.10 (d, J = 6.3 Hz,
    1162, 3H), 1.04-0.86 (m, 3H), 0.77 (d, J = 6.7 Hz,
    1052, 757 cm−1 3H).
    295 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (500 MHz, CDCl3) δ 7.12 (dd,
    film) 3356, calcd for C21H32FNO4Na, J = 8.5, 6.0 Hz, 1H), 6.88-6.75 (m,
    2969, 404.2208; found, 404.2204 2H), 5.31 (dq, J = 9.0, 6.3 Hz, 1H),
    1712, 5.05 (d, J = 7.9 Hz, 1H), 4.43-4.15 (m, 1H),
    1497, 3.10 (t, J = 7.4 Hz, 1H), 2.29 (s, 3H),
    1365, 2.12 (h, J = 6.8 Hz, 1H), 1.45 (s, 9H),
    1243, 1.38 (d, J = 7.2 Hz, 3H), 1.06 (d, J = 6.3 Hz,
    1161, 3H), 0.87 (d, J = 6.7 Hz, 3H),
    1051, 731 cm−1 0.81 (d, J = 6.8 Hz, 3H).
    296 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (500 MHz, CDCl3) δ
    film) 3356, calcd for C22H35NO4Na, 7.04-6.91 (m, 3H), 5.35 (dq, J = 9.3, 6.3 Hz,
    2962, 400.2458; found, 400.2462 1H), 5.07 (s, 1H), 4.29 (t, J = 7.6 Hz,
    1713, 1H), 3.08 (dd, J = 9.4, 6.0 Hz, 1H),
    1501, 2.29 (s, 3H), 2.29 (s, 3H), 2.12 (dq, J = 13.4,
    1451, 6.8 Hz, 1H), 1.45 (s, 9H), 1.39 (d, J = 7.2 Hz,
    1365, 3H), 1.03 (d, J = 6.2 Hz, 3H),
    1160, 0.84 (d, J = 6.7 Hz, 3H), 0.80 (d, J = 6.9 Hz,
    1049, 732 cm−1 3H).
    297 IR (thin HRMS-ESI (m/z) 1H NMR (500 MHz, CDCl3) δ
    film) 3352, [M + NH4]+ calcd for 7.07-7.01 (m, 2H), 6.95 (dd, J = 7.0, 2.3 Hz,
    2964, C22H35NO4NH4, 395.2904; 1H), 5.37 (dq, J = 9.2, 6.3 Hz, 1H),
    1712, found, 395.2889 5.08 (s, 1H), 4.30 (t, J = 7.8 Hz, 1H),
    1499, 3.23 (dd, J = 9.3, 6.0 Hz, 1H), 2.30 (s, 3H),
    1452, 2.24 (s, 3H), 2.13 (dq, J = 13.4, 6.7 Hz,
    1365, 1H), 1.45 (s, 9H), 1.40 (d, J = 7.1 Hz,
    1160, 3H), 1.03 (d, J = 6.2 Hz, 3H), 0.84 (d, J = 6.8 Hz,
    1050, 731 cm−1 3H), 0.79 (d, J = 6.9 Hz, 3H).
    298 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (500 MHz, CDCl3) δ
    film) 3359, calcd for C21H33NO4Na, 7.20-7.06 (m, 4H), 5.37 (dq, J = 9.3, 6.2 Hz,
    2965, 386.2302; found, 386.2301 1H), 5.07 (d, J = 7.8 Hz, 1H), 4.29 (t, J = 7.2 Hz,
    2875, 1H), 3.13 (dd, J = 9.2, 6.1 Hz,
    1714, 1H), 2.34 (s, 3H), 2.15 (dq, J = 13.4, 6.8 Hz,
    1161, 1054 cm−1 1H), 1.45 (s, 9H), 1.39 (d, J = 7.2 Hz,
    3H), 1.04 (d, J = 6.2 Hz, 3H),
    0.86 (d, J = 6.8 Hz, 3H), 0.81 (d, J = 6.8 Hz,
    3H).
    299 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (500 MHz, CDCl3) δ 7.10 (td,
    film) 3365, calcd for C20H29F2NO4Na, J = 8.4, 6.4 Hz, 1H), 6.93-6.74 (m,
    2966, 408.1957; found, 408.1955 2H), 5.39 (tt, J = 7.0, 5.5 Hz, 1H),
    1712, 5.04 (d, J = 7.9 Hz, 1H), 4.26 (t, J = 7.6 Hz,
    1503, 1H), 3.13 (t, J = 7.7 Hz, 1H), 2.10 (h, J = 6.8 Hz,
    1454, 1H), 1.45 (s, 9H), 1.37 (d, J = 7.2 Hz,
    1366, 3H), 1.09 (d, J = 6.3 Hz, 3H),
    1165, 0.91 (d, J = 6.8 Hz, 3H), 0.75 (d, J = 6.7 Hz,
    1053, 966, 3H).
    849 cm−1
    300 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (500 MHz, CDCl3) δ 7.00 (t, J = 7.7 Hz,
    film) 2969, calcd for C21H32FNO4Na, 1H), 6.90 (dd, J = 7.9, 1.7 Hz,
    1716, 404.2208; found, 404.2202 1H), 6.87-6.74 (m, 1H), 5.40 (tt, J = 6.9,
    1506, 5.5 Hz, 1H), 5.07 (d, J = 8.1 Hz,
    1456, 1H), 4.33-4.16 (m, 1H), 3.11 (t, J = 7.7 Hz,
    1365, 1H), 2.33 (s, 3H), 2.10 (h, J = 6.8 Hz,
    1164, 1053 cm−1 1H), 1.45 (s, 9H), 1.38 (d, J = 7.2 Hz,
    3H), 1.09 (d, J = 6.3 Hz, 3H),
    0.90 (d, J = 6.7 Hz, 3H), 0.76 (d, J = 6.7 Hz,
    3H).
    301 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (500 MHz, CDCl3) δ 7.42 (d, J = 2.3 Hz,
    film) 3358, calcd for 1H), 7.23 (dd, J = 8.5, 2.2 Hz,
    2966, C20H29Cl2NO4Na, 1H), 7.13 (d, J = 8.5 Hz, 1H),
    1712, 440.1366; found, 440.1366 5.47-5.25 (m, 1H), 5.03 (d, J = 7.6 Hz, 1H),
    1500, 4.28 (d, J = 7.7 Hz, 1H), 3.51 (s, 1H),
    1474, 2.24-1.99 (m, 1H), 1.45 (s, 9H),
    1453, 1.39 (d, J = 7.2 Hz, 3H), 1.08 (d, J = 6.4 Hz,
    1365, 3H), 0.92 (d, J = 6.8 Hz, 3H), 0.77 (d, J = 6.8 Hz,
    1162, 1045 cm−1 3H).
    302 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (500 MHz, CDCl3) δ
    film) 3346, calcd for C20H29F2NO4Na, 7.27 (m, 1H), 6.90-6.82 (m, 1H),
    2975, 408.1957; found, 408.1956 6.82-6.75 (m, 1H), 5.54-5.30 (m, 1H),
    1710, 5.01 (d, J = 8.6 Hz, 1H), 4.35-4.18 (m,
    1502, 1H), 2.84 (dd, J = 9.1, 5.2 Hz, 1H),
    1366, 2.09-1.87 (m, 1H), 1.44 (s, 9H), 1.24 (d, J = 7.3 Hz,
    1249, 3H), 1.10 (d, J = 6.3 Hz, 3H),
    1163, 0.97 (d, J = 6.5 Hz, 3H), 0.72 (d, J = 6.8 Hz,
    1064, 965 3H).
    847 cm−1
    303 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (500 MHz, CDCl3) δ 7.17 (t, J = 7.8 Hz,
    film) 3364, calcd for C21H32FNO4Na, 1H), 6.90 (d, J = 7.6 Hz, 1H),
    2974, 404.2208; found, 404.2206 6.84 (dd, J = 11.0, 1.8 Hz, 1H),
    2932, 5.44-5.38 (m, 1H), 5.04 (d, J = 7.4 Hz, 1H),
    1714 4.46-4.15 (m, 1H) 2.83 (dd, J = 9.0,
    1506, 5.1 Hz, 1H), 2.33 (d, J = 3.0 Hz, 3H),
    1454, 2.11-1.97 (m, 1H), 1.44 (s, 9H),
    1336, 1.22 (d, J = 7.2 Hz, 3H), 1.10 (d, J = 6.3 Hz,
    1167, 1065 cm−1 3H), 0.97 (d, J = 6.6 Hz, 3H), 0.73 (d, J = 6.9 Hz,
    3H).
    304 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (500 MHz, CDCl3) δ 7.40 (d, J = 2.2 Hz,
    film) 3353, calcd for 1H), 7.36 (d, J = 8.5 Hz, 1H),
    2975, C20H29Cl2NO4Na, 7.24-7.06 (m, 1H), 5.62-5.20 (m,
    1710, 440.1366; found, 440.1360 1H), 5.02 (d, J = 8.1 Hz, 1H),
    1475, 4.46-4.13 (m, 1H), 3.13 (dd, J = 9.6, 4.6 Hz,
    1366, 1H), 2.20-1.92 (m, 1H), 1.44 (s, 9H),
    1163, 1.37-1.26 (m, 3H), 1.06 (d, J = 6.3 Hz,
    1111, 3H), 1.01 (d, J = 6.6 Hz, 3H), 0.70 (d, J = 6.8 Hz,
    1020, 863, 3H).
    809 cm−1
    305 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (500 MHz, CDCl3) δ 6.74 (d, J = 7.9 Hz,
    film) 3375, calcd for C21H31NO6Na, 1H), 6.60 (d, J = 1.8 Hz, 1H),
    2969, 416.2044; found, 416.2040 6.54 (dd, J = 8.0, 1.7 Hz, 1H), 5.94 (s,
    1711, 2H), 5.31 (dq, J = 8.8, 6.3 Hz, 1H),
    1504, 5.07 (d J = 7.8 Hz, 1H), 4.33-4.20 (m, 1H),
    1488, 2.61 (dd, J = 8.8, 6.4 Hz, 1H),
    1160, 2.12-1.98 (m, J = 6.8 Hz, 1H), 1.45 (s, 9H),
    1038, 731 cm−1 1.38 (d, J = 7.2 Hz, 3H), 1.08 (d, J = 6.2 Hz,
    3H), 0.85 (d, J = 6.7 Hz, 3H),
    0.76 (d, J = 6.7 Hz, 3H).
    306 IR (thin 1H NMR (500 MHz, CDCl3) δ 7.13 (q, J = 8.8 Hz,
    film) 3361, 4H), 5.37 (dq, J = 8.7, 6.3 Hz,
    2970, 1H), 5.04 (d, J = 8.0 Hz, 1H),
    1715, 4.37-4.22 (m, 1H), 2.72 (dd, J = 8.6, 6.6 Hz,
    1366, 1H), 2.10 (h, J = 6.7 Hz, 1H), 1.45 (s,
    1262, 9H), 1.37 (d, J = 7.2 Hz, 3H), 1.07 (d, J = 6.3 Hz,
    1218, 1165 cm−1 3H), 0.87 (d, J = 6.8 Hz, 3H),
    0.75 (d, J = 6.7 Hz, 3H).
    19F NMR (471 MHz, CDCl3) δ −57.9.
    307 IR (thin 1H NMR (500 MHz, CDCl3) δ
    film) 3363, 7.06-6.91 (m, 2H), 6.90-6.75 (m, 2H),
    2976, 5.35 (dq, J = 8.9, 6.3 Hz, 1H), 5.08 (d, J = 8.0 Hz,
    2933, 1H), 4.52 (hept, J = 6.1 Hz, 1H),
    2875, 4.36-4.22 (m, 1H), 2.63 (dd, J = 9.0,
    1712, 6.1 Hz, 1H), 2.14-2.00 (m, 1H),
    1508, 1.45 (s, 9H), 1.38 (d, J = 7.2 Hz, 3H),
    1238, 1.33 (d, J = 6.1 Hz, 6H), 1.06 (d, J = 6.2 Hz,
    1165, 1050 cm−1 3H), 0.84 (d, J = 6.8 Hz, 3H), 0.75 (d, J = 6.7 Hz,
    3H).
    13C NMR (126 MHz, CDCl3) δ 172.8,
    156.6, 155.0, 130.6, 130.3, 115.2, 79.7,
    72.7, 69.7, 60.4, 55.8, 49.5, 28.3, 28.2,
    22.1, 21.4, 18.9, 18.3, 18.0.
    308 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (500 MHz, CDCl3) δ
    film) 3357, calcd for C23H37NO5Na, 7.23-7.11 (m, 1H), 7.06 (dd, J = 7.8, 1.8 Hz,
    2976, 430.2569; found, 430.2431 1H), 6.92-6.78 (m, 2H), 5.42 (s, 1H),
    2933, 5.13 (d, J = 7.7 Hz, 1H), 4.56 (hept, J = 6.1 Hz,
    2874, 1H), 4.30 (t, J = 7.5 Hz, 1H),
    1712, 3.44 (s, 1H), 2.12 (h, J = 6.7 Hz, 1H),
    1489, 1.45 (s, 9H), 1.40 (d, J = 7.2 Hz, 3H),
    1238, 1.39-1.26 (m, 6H), 1.04 (d, J = 6.2 Hz,
    1160, 3H), 0.83 (d, J = 6.8 Hz, 3H), 0.76 (d, J = 6.8 Hz,
    1050, 732 cm−1 3H).
    309 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (500 MHz, CDCl3) δ
    film) 3361, calcd for C21H33NO5Na, 7.09-6.90 (m, 2H), 6.90-6.77 (m, 2H),
    2962, 402.2251; found, 402.2221 5.35 (dq, J = 8.9, 6.3 Hz, 1H), 5.07 (s, 1H),
    1713, 4.28 (t, J = 7.6 Hz, 1H), 3.80 (s, 3H),
    1512, 2.64 (dd, J = 8.9, 6.2 Hz, 1H), 2.07 (h, J = 6.7 Hz,
    1246, 1H), 1.45 (s, 9H), 1.38 (d, J = 7.2 Hz,
    1165, 1050 cm−1 3H), 1.06 (d, J = 6.2 Hz, 3H),
    0.84 (d, J = 6.8 Hz, 3H), 0.75 (d, J = 6.8 Hz,
    3H).
    310 ESIMS m/z 400 1H NMR (400 MHz, CDCl3) δ
    ([M + Na]+) 7.23-7.04 (m, 4H), 5.38 (dq, J = 9.6, 6.1 Hz,
    1H), 5.09 (s, 1H), 4.41-4.22 (m, 1H),
    3.32-3.07 (m, 1H), 2.34 (d, J = 2.6 Hz,
    3H), 1.89 (dtd, J = 12.5, 6.2, 5.6, 3.2 Hz,
    1H), 1.54-1.33 (m, 12H),
    1.32-1.20 (m, 1H), 1.14-0.69 (m, 10H).
    311 ESIMS m/z 392 ([M + H]+) 1H NMR (400 MHz, CDCl3) δ
    7.20-7.03 (m, 4H), 5.41 (dq, J = 8.3, 6.2 Hz,
    1H), 5.06 (s, 1H), 4.27 (s, 1H), 3.30 (t, J = 7.6 Hz,
    1H), 2.33 (s, 3H),
    1.72-1.58 (m, 1H), 1.44 (s, 10H), 1.36 (dd, J = 10.9,
    7.2 Hz, 5H), 1.08 (d, J = 6.3 Hz,
    4H), 0.93 (t, J = 7.4 Hz, 3H), 0.78 (t, J = 7.3 Hz,
    3H).
    312 1H NMR (400 MHz, CDCl3) δ 6.67 (d, J = 9.3 Hz,
    2H), 5.54 (ddt, J = 8.1, 6.3,
    2.0 Hz, 1H), 5.04 (s, 1H), 4.27 (d, J = 8.5 Hz,
    1H), 3.17 (t, J = 7.7 Hz, 1H),
    2.30-2.15 (m, 1H), 1.45 (s, 9H),
    1.37 (d, J = 7.3 Hz, 3H), 1.12 (dt, J = 6.3, 1.2 Hz,
    3H), 0.95 (d, J = 6.6 Hz, 3H),
    0.77 (dt, J = 6.8, 1.4 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −103.51,
    −108.05, −110.09.
    313 1H NMR (400 MHz, CDCl3) δ 7.09 (dtt,
    J = 8.3, 5.6, 2.7 Hz, 3H),
    5.47-5.32 (m, 1H), 5.03 (s, 1H), 4.26 (s, 1H),
    3.13 (t, J = 7.7 Hz, 1H), 2.10 (q, J = 6.8 Hz,
    1H), 1.45 (s, 9H), 1.37 (d, J = 7.2 Hz,
    3H), 1.09 (d, J = 6.3 Hz, 3H),
    0.99-0.85 (m, 3H), 0.75 (d, J = 6.8 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −112.35.
    314 1H NMR (400 MHz, CDCl3) δ 7.23 (dd,
    J = 8.4, 1.2 Hz, 1H), 7.16 (td, J = 8.0,
    5.6 Hz, 1H), 6.96 (ddd, J = 10.9, 8.1,
    1.5 Hz, 1H), 5.58 (ddq, J = 12.5, 9.1,
    3.1 Hz, 1H), 5.07 (s, 1H), 4.30 (d, J = 8.5 Hz,
    1H), 3.60-3.48 (m, 1H),
    2.24 (dqd, J = 13.7, 6.8, 2.1 Hz, 1H), 1.45 (s,
    9H), 1.40 (d, J = 7.2 Hz, 3H), 1.08 (dd,
    J = 6.3, 1.8 Hz, 3H), 0.99 (d, J = 6.8 Hz,
    3H), 0.78 (dd, J = 6.8, 2.8 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −105.00
    315 1H NMR (400 MHz, CDCl3) δ 7.17 (t, J = 7.8 Hz,
    1H), 7.05 (d, J = 7.6 Hz, 1H),
    6.89 (s, 2H), 5.45-5.32 (m, 1H),
    5.08 (s, 1H), 4.28 (s, 1H), 2.65 (dd, J = 8.9,
    6.2 Hz, 1H), 2.33 (s, 3H),
    2.14-2.04 (m, 1H), 1.45 (s, 9H), 1.39 (d, J = 7.3 Hz,
    3H), 1.07 (d, J = 6.2 Hz, 3H),
    0.85 (d, J = 6.8 Hz, 3H), 0.76 (d, J = 6.8 Hz,
    3H).
    316 ESIMS m/z 386 ([M + H]+) 1H NMR (400 MHz, CDCl3) δ 7.00 (td,
    J = 9.1, 4.7 Hz, 1H), 6.88 (dddd, J = 24.6,
    8.9, 6.3, 3.3 Hz, 2H),
    5.49-5.28 (m, 1H), 5.04 (s, 1H), 4.26 (d, J = 9.3 Hz,
    1H), 3.15 (t, J = 7.7 Hz, 1H),
    2.09 (h, J = 6.9 Hz, 1H), 1.45 (s, 9H),
    1.37 (d, J = 7.3 Hz, 3H), 1.12 (d, J = 6.3 Hz,
    3H), 0.94 (d, J = 6.7 Hz, 3H), 0.78 (d, J = 6.7 Hz,
    3H).
    19F NMR (376 MHz, CDCl3) δ
    −118.45-−122.20 (m).
    317 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ
    film) 3374, calcd for C22H28FN2O5, 12.06-12.02 (m, 1H), 8.47 (t, J = 5.8 Hz, 1H),
    2961, 419.1977; found, 419.1976 7.99 (d, J = 5.3 Hz, 1H), 7.05 (dd, J = 8.3,
    1740, 5.9 Hz, 1H), 6.90-6.81 (m, 3H),
    1650, 5.45 (dq, J = 8.2, 6.3 Hz, 1H), 4.19 (d, J = 5.7 Hz,
    1533, 2H), 3.95 (s, 3H), 3.04 (t, J = 7.7 Hz,
    1497, 1H), 2.30 (s, 3H), 2.08 (h, J = 6.8 Hz,
    1437, 1H), 1.09 (d, J = 6.3 Hz, 3H),
    1262, 0.93 (d, J = 6.7 Hz, 3H), 0.77 (d, J = 6.8 Hz,
    1240, 3H).
    1215, 13C NMR (101 MHz, CDCl3) δ 169.35,
    1188, 801, 168.66, 160.95 (d, J = 244.4 Hz),
    729 cm−1 155.42, 148.73, 140.59, 139.90 (d, J = 7.5 Hz),
    133.63 (d, J = 3.3 Hz), 130.43,
    129.20 (d, J = 6.9 Hz), 116.98 (d, J = 20.5 Hz),
    112.35 (d, J = 20.7 Hz),
    109.57, 74.06, 56.09, 49.55, 41.17,
    29.95, 20.95, 20.80, 19.71, 17.46.
    19F NMR (376 MHz, CDCl3) δ −117.31.
    318 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.16 (s,
    film) 3371, calcd for C25H34FN2O5, 1H), 8.43 (d, J = 9.5 Hz, 1H), 7.99 (d, J = 5.2 Hz,
    2963, 461.2466; found, 461.2453 1H), 7.03 (dd, J = 8.7, 5.9 Hz,
    1731, 1H), 6.89 (d, J = 5.2 Hz, 1H), 6.83 (td, J = 8.4,
    1651, 2.9 Hz, 1H), 6.77 (dd, J = 9.9, 2.8 Hz,
    1527, 1H), 5.37 (dq, J = 9.1, 6.1 Hz, 1H),
    1262, 4.66 (dd, J = 9.5, 4.9 Hz, 1H), 3.96 (s,
    1240, 730 cm−1 3H), 3.09 (dd, J = 9.2, 6.1 Hz, 1H),
    2.42-2.29 (m, 1H), 2.27 (s, 3H),
    2.20-2.06 (m, 1H), 1.07 (d, J = 6.2 Hz, 3H),
    1.06 (d, J = 6.9 Hz, 3H), 1.01 (d, J = 6.9 Hz,
    3H), 0.82 (d, J = 6.8 Hz, 3H), 0.76 (d, J = 6.9 Hz,
    3H).
    13C NMR (101 MHz, CDCl3) δ 170.53,
    169.10, 160.93 (d, J = 244.6 Hz),
    155.43, 148.78, 140.48, 139.88 (d, J = 7.3 Hz),
    133.35 (d, J = 3.3 Hz), 130.52,
    129.15 (d, J = 7.9 Hz), 116.98 (d, J = 20.5 Hz),
    112.31 (d, J = 20.6 Hz),
    109.50, 73.81, 57.39, 56.10, 49.30,
    31.34, 29.46, 20.88, 19.48, 18.63, 18.11,
    17.43.
    19F NMR (376 MHz, CDCl3) δ −117.29.
    319 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.17 (s,
    film) 3374, calcd for C26H36FN2O5, 1H), 8.42 (d, J = 9.5 Hz, 1H), 7.98 (d, J = 5.2 Hz,
    2963, 475.2603; found, 475.2599 1H), 7.03 (dd, J = 8.7, 5.9 Hz,
    1731, 1H), 6.89 (d, J = 5.3 Hz, 1H), 6.83 (td, J = 8.4,
    1651, 2.9 Hz, 1H), 6.77 (dd, J = 9.9, 2.8 Hz,
    1526, 1H), 5.37 (dq, J = 9.2, 6.2 Hz, 1H),
    1261, 4.71 (dd, J = 9.5, 4.9 Hz, 1H), 3.96 (s,
    1240, 3H), 3.09 (dd, J = 9.3, 6.0 Hz, 1H),
    1046, 800, 2.27 (s, 3H), 2.19-2.03 (m, 2H), 1.54 (dddd,
    730 cm−1 J = 14.9, 11.4, 6.8, 4.0 Hz, 1H),
    1.28 (tdd, J = 14.3, 9.8, 7.3 Hz, 1H), 1.07 (d,
    J = 6.2 Hz, 3H), 1.04 (d, J = 6.8 Hz,
    3H), 1.01-0.87 (m, 3H), 0.81 (d, J = 6.8 Hz,
    3H), 0.76 (d, J = 6.9 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 170.48,
    168.99, 160.93 (d, J = 244.4 Hz),
    155.43, 148.77, 140.47, 139.89 (d, J = 7.3 Hz),
    133.30 (d, J = 3.3 Hz), 130.53,
    129.16 (d, J = 7.8 Hz), 116.98 (d, J = 20.5 Hz),
    112.30 (d, J = 20.6 Hz),
    109.49, 73.77, 56.98, 56.10, 49.29,
    37.88, 29.40, 24.69, 20.88, 18.48, 18.15,
    15.83, 11.48.
    19F NMR (376 MHz, CDCl3) δ −117.28.
    320 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.15 (s,
    film) 3367, calcd for C26H36FN2O5, 1H), 8.28 (d, J = 9.0 Hz, 1H), 7.98 (d, J = 5.2 Hz,
    2959, 475.2603; found, 475.2600 1H), 7.04 (dd, J = 8.7, 5.9 Hz,
    1733, 1H), 6.89 (d, J = 5.2 Hz, 1H), 6.83 (td, J = 8.4,
    1650, 2.9 Hz, 1H), 6.77 (dd, J = 9.9, 2.8 Hz,
    1529, 1H), 5.35 (dq, J = 8.8, 6.2 Hz, 1H),
    1263, 4.79-4.68 (m, 1H), 3.95 (s, 3H),
    1244, 3.07 (dd, J = 8.8, 6.6 Hz, 1H), 2.27 (s, 3H),
    1049, 800, 2.08 (h, J = 6.8 Hz, 1H), 1.80-1.66 (m,
    731 cm−1 2H), 1.08 (d, J = 6.2 Hz, 3H),
    1.05-0.86 (m, 7H), 0.84 (d, J = 6.7 Hz, 3H),
    0.75 (d, J = 6.8 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 171.49,
    168.88, 160.90 (d, J = 244.3 Hz),
    155.43, 148.80, 140.41, 139.83 (d, J = 7.3 Hz),
    133.54 (d, J = 3.3 Hz), 130.45,
    129.10 (d, J = 7.1 Hz), 116.91 (d, J = 20.4 Hz),
    112.28 (d, J = 20.7 Hz),
    109.48, 73.83, 56.08, 50.94, 49.28,
    41.40, 29.68, 24.91, 23.00, 21.70, 20.89,
    18.98, 17.74.
    19F NMR (376 MHz, CDCl3) δ −117.37.
    321 IR (thin ESIMS m/z 429.2 1H NMR (500 MHz, CDCl3) δ 12.15 (s,
    film) 3370, ([M + H]+) 1H), 8.50 (d, J = 7.9 Hz, 1H), 8.00 (d, J = 5.2 Hz,
    2959, 1H), 7.02 (d, J = 7.6 Hz, 1H),
    2873, 6.95-6.86 (m, 3H), 5.39 (dq, J = 9.3,
    1731, 6.2 Hz, 1H), 4.81-4.60 (m, 1H),
    1648, 3.95 (s, 3H), 3.20-2.96 (m, 1H), 2.30 (s,
    1576, 3H), 2.27 (s, 3H), 2.14 (dq, J = 13.4, 6.7 Hz,
    1526, 1H), 1.57 (d, J = 7.2 Hz, 3H),
    1480, 1.07 (d, J = 6.2 Hz, 3H), 0.84 (d, J = 6.8 Hz,
    1450, 3H), 0.81 (d, J = 6.8 Hz, 3H).
    1325,
    1280,
    1262,
    1241,
    1149,
    1046, 953,
    800, 730 cm−1
    322 IR (thin ESIMS m/z 433.2 1H NMR (500 MHz, CDCl3) δ 12.12 (s,
    film) 3370, ([M + H]+) 1H), 8.48 (d, J = 7.9 Hz, 1H), 8.00 (d, J = 5.2 Hz,
    2962, 1H), 7.12 (td, J = 8.0, 5.9 Hz,
    2875, 1H), 6.94-6.85 (m, 3H), 5.40 (dq, J = 9.0,
    1734, 6.2 Hz, 1H), 4.70 (p, J = 7.3 Hz,
    1649, 1H), 3.95 (s, 3H), 3.15 (t, J = 7.7 Hz,
    1576, 1H), 2.22 (d, J = 2.4 Hz, 3H), 2.14 (h, J = 6.8 Hz,
    1527, 1H), 1.56 (d, J = 7.2 Hz, 3H),
    1480, 1.08 (d, J = 6.2 Hz, 3H), 0.86 (d, J = 6.8 Hz,
    1453, 3H), 0.79 (d, J = 6.9 Hz, 3H).
    1324,
    1280,
    1263,
    1241,
    1163,
    1043, 786,
    732 cm−1
    323 IR (thin ESIMS m/z 419.2 1H NMR (500 MHz, CDCl3) δ 12.15 (s,
    film) 3370, ([M + H]+) 1H), 8.49 (d, J = 7.9 Hz, 1H), 8.00 (d, J = 5.2 Hz,
    2962, 1H), 7.24-7.18 (m, 1H),
    1733, 7.15 (td, J = 7.4, 1.9 Hz, 1H), 7.09 (td, J = 7.5,
    1648, 1.3 Hz, 1H), 7.00 (ddd, J = 10.3,
    1576, 8.2, 1.2 Hz, 1H), 6.88 (d, J = 5.2 Hz,
    1527, 1H), 5.47 (dqd, J = 7.6, 6.4, 1.2 Hz,
    1480, 1H), 4.73-4.62 (m, 1H), 3.95 (s, 3H),
    1452, 3.20 (t, J = 7.7 Hz, 1H), 2.18-2.08 (m,
    1280, 1H), 1.55 (d, J = 7.3 Hz, 3H), 1.13 (d, J = 6.3 Hz,
    1262, 3H), 0.92 (d, J = 6.8 Hz, 3H),
    1241, 0.77 (d, J = 6.7 Hz, 3H).
    1216,
    1148,
    1049, 849,
    800, 757,
    730 cm−1
    324 IR (thin ESIMS m/z 433.2 1H NMR (500 MHz, CDCl3) δ 12.12 (s,
    film) 3370, ([M + H]+) 1H), 8.46 (d, J = 8.0 Hz, 1H), 7.99 (d, J = 5.2 Hz,
    2959, 1H), 7.07 (dd, J = 8.3, 6.2 Hz,
    1731, 1H), 6.88 (d, J = 5.2 Hz, 1H),
    1648, 6.84-6.76 (m, 2H), 5.36 (dq, J = 8.7, 6.2 Hz,
    1576, 1H), 4.75-4.61 (m, 1H), 3.95 (s, 3H),
    1526, 3.11 (t, J = 7.9 Hz, 1H), 2.27 (s, 3H),
    1480, 2.11 (h, J = 6.7 Hz, 1H), 1.55 (d, J = 7.2 Hz,
    1450, 3H), 1.10 (d, J = 6.3 Hz, 3H),
    1438, 0.88 (d, J = 6.8 Hz, 3H), 0.80 (d, J = 6.8 Hz,
    1280, 3H).
    1262,
    1241,
    1149,
    1046, 953,
    819, 799,
    730 cm−1
    325 IR (thin ESIMS m/z 429.2 1H NMR (500 MHz, CDCl3) δ 12.15 (s,
    film) 3370, ([M + H]+) 1H), 8.50 (d, J = 7.9 Hz, 1H), 8.00 (d, J = 5.2 Hz,
    2961, 1H), 7.02-6.94 (m, 3H),
    1733, 6.88 (d, J = 5.2 Hz, 1H), 5.39 (dq, J = 9.2,
    1648, 6.2 Hz, 1H), 4.71 (p, J = 7.3 Hz, 1H),
    1576, 3.95 (s, 3H), 3.10 (dd, J = 9.3, 6.1 Hz,
    1527, 1H), 2.28 (s, 6H), 2.12 (dq, J = 13.4, 6.8 Hz,
    1497, 1H), 1.56 (d, J = 7.2 Hz, 3H),
    1451, 1.07 (d, J = 6.2 Hz, 3H), 0.84 (d, J = 6.8 Hz,
    1280, 3H), 0.80 (d, J = 6.8 Hz, 3H).
    1261,
    1240,
    1148,
    1048, 952,
    800, 730 cm−1
    326 IR (thin ESIMS m/z 429.2 1H NMR (500 MHz, CDCl3) δ 12.15 (s,
    film) 3369, ([M + H]+) 1H), 8.51 (d, J = 7.7 Hz, 1H), 8.00 (d, J = 5.2 Hz,
    2961, 1H), 7.09-7.00 (m, 2H),
    2873, 6.95 (dd, J = 7.4, 1.8 Hz, 1H), 6.88 (d, J = 5.3 Hz,
    1732, 1H), 5.41 (dq, J = 9.0, 6.2 Hz,
    1648, 1H), 4.76-4.63 (m, 1H), 3.95 (s, 3H),
    1576, 3.25 (dd, J = 9.2, 6.1 Hz, 1H), 2.28 (s,
    1526, 3H), 2.23 (s, 3H), 2.18-2.08 (m, 1H),
    1480, 1.57 (d, J = 7.2 Hz, 3H), 1.06 (d, J = 6.3 Hz,
    1451, 3H), 0.84 (d, J = 6.7 Hz, 3H),
    1384, 0.79 (d, J = 6.8 Hz, 3H).
    1359,
    1262,
    1241,
    1213,
    1150,
    1045, 849,
    800, 779,
    729 cm−1
    327 IR (thin ESIMS m/z 415 ([M + H]+) 1H NMR (500 MHz, CDCl3) δ 12.15 (d,
    film) 3369, J = 0.6 Hz, 1H), 8.50 (d, J = 7.9 Hz,
    2960, 1H), 8.00 (d, J = 5.2 Hz, 1H),
    2932, 7.19-7.06 (m, 4H), 6.88 (d, J = 5.2 Hz, 1H),
    2874, 5.41 (dq, J = 9.2, 6.2 Hz, 1H),
    1732, 4.76-4.66 (m, 1H), 3.95 (s, 3H), 3.15 (dd, J = 9.2,
    1649, 6.2 Hz, 1H), 2.32 (s, 3H), 2.15 (dq,
    1527, J = 13.4, 6.7 Hz, 1H), 1.56 (d, J = 7.2 Hz,
    1451, 3H), 1.08 (d, J = 6.2 Hz, 3H),
    1150, 0.86 (d, J = 6.8 Hz, 3H), 0.81 (d, J = 6.8 Hz,
    1053, 731 cm−1 3H).
    328 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 12.14 (d,
    film) 2964, calcd for C22H27F2N2O5, J = 0.6 Hz, 1H), 8.45 (d, J = 7.9 Hz,
    1733, 437.1883; found, 437.1879 1H), 7.99 (d, J = 5.2 Hz, 1H), 7.10 (td, J = 8.4,
    1714, 6.4 Hz, 1H), 6.88 (d, J = 5.2 Hz,
    1652, 1H), 6.86-6.81 (m, 1H), 6.74 (ddd, J = 10.2,
    1528, 8.9, 2.6 Hz, 1H), 5.52-5.31 (m,
    1503, 1H), 4.79-4.55 (m, 1H), 3.95 (s, 3H),
    1280, 3.14 (t, J = 7.7 Hz, 1H), 2.09 (h, J = 6.8 Hz,
    1263, 966, 1H), 1.58-1.53 (m, 3H), 1.12 (d, J = 6.3 Hz,
    848 cm−1 3H), 0.93 (d, J = 6.7 Hz, 3H),
    0.75 (d, J = 6.7 Hz, 3H).
    329 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 12.16 (d,
    film) 2962, calcd for C23H30FN2O5, J = 0.7 Hz, 1H), 8.49 (d, J = 8.0 Hz,
    1733, 433.2133; found, 433.2129 1H), 8.00 (d, J = 5.2 Hz, 1H), 7.01 (t, J = 7.7 Hz,
    1650, 1H), 6.93-6.84 (m, 2H),
    1576, 6.83-6.78 (m, 1H), 5.45 (dqd, J = 7.6, 6.3,
    1528, 1.2 Hz, 1H), 4.73-4.60 (m, 1H),
    1481, 3.95 (s, 3H), 3.14 (t, J = 7.7 Hz, 1H), 2.32 (s,
    1450, 3H), 2.10 (h, J = 6.8 Hz, 1H), 1.55 (d, J = 7.2 Hz,
    1362, 3H), 1.12 (d, J = 6.3 Hz, 3H),
    1327, 1.01-0.88 (m, 3H), 0.76 (d, J = 6.7 Hz,
    1263, 3H).
    1242,
    1149,
    1050, 800 cm−1
    330 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 12.13 (d,
    film) 2963, calcd for C22H27Cl2N2O5, J = 0.6 Hz, 1H), 8.44 (d, J = 8.0 Hz,
    1734, 469.1292; found, 469.1293 1H), 7.99 (d, J = 5.2 Hz, 1H), 7.34 (d, J = 2.2 Hz,
    1648, 1H), 7.22 (dd, J = 8.4, 2.2 Hz,
    1576, 1H), 7.13 (d, J = 8.4 Hz, 1H), 6.88 (d, J = 5.2 Hz,
    1527, 1H), 5.45-5.32 (m, 1H),
    1478, 4.78-4.61 (m, 1H), 3.95 (s, 3H), 3.52 (s,
    1451, 1H), 2.09 (dt, J = 13.7, 6.9 Hz, 1H),
    1438, 1.55 (d, J = 7.2 Hz, 3H), 1.12 (d, J = 6.3 Hz,
    1262, 3H), 0.93 (d, J = 6.7 Hz, 3H),
    1150, 0.76 (d, J = 6.8 Hz, 3H).
    1044, 799,
    730 cm−1
    331 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ
    film) 2965, calcd for C22H27F2N2O5, 12.24-11.76 (m, 1H), 8.42 (d, J = 8.0 Hz, 1H),
    1734, 437.1883; found, 437.1887 8.01 (d, J = 5.2 Hz, 1H), 7.25-7.10 (m,
    1648, 1H), 6.89 (d, J = 5.1 Hz, 1H),
    1576, 6.74 (dddd, J = 14.1, 11.6, 7.5, 1.9 Hz, 2H),
    1528, 5.50-5.41 (m, 1H), 4.78-4.62 (m,
    1502, 1H), 3.95 (s, 3H), 2.84 (dd, J = 9.1, 5.1 Hz,
    1480, 1H), 2.00 (dq, J = 9.0, 6.9 Hz, 1H),
    1438, 1.42 (d, J = 7.2 Hz, 3H), 1.12 (d, J = 6.3 Hz,
    1322, 3H), 0.99 (d, J = 6.6 Hz, 3H),
    1263, 0.70 (d, J = 6.7 Hz, 3H).
    1241,
    1150,
    1060, 964,
    848, 800,
    731 cm−1
    332 IR (thin 1H NMR (500 MHz, CDCl3) δ 12.14 (d,
    film) 2964, J = 0.7 Hz, 1H), 8.46 (d, J = 8.0 Hz,
    1733, 1H), 8.01 (d, J = 5.2 Hz, 1H), 7.13 (t, J = 7.9 Hz,
    1648, 1H), 6.88 (d, J = 5.3 Hz, 1H),
    1576, 6.86-6.71 (m, 2H), 5.55-5.40 (m,
    1527, 1H), 4.80-4.59 (m, 1H), 3.95 (s, 3H),
    1438, 2.85 (dd, J = 8.9, 5.3 Hz, 1H), 2.30 (s,
    1323, 3H), 2.02 (dp, J = 13.6, 6.8 Hz, 1H),
    1262, 1.40 (d, J = 7.2 Hz, 3H), 1.13 (d, J = 6.2 Hz,
    1132, 800, 3H), 1.01-0.89 (m, 3H), 0.72 (d, J = 6.6 Hz,
    730 cm−1 3H).
    13C NMR (126 MHz, CDCl3) δ 171.60,
    168.63, 161.50 (d, J = 243.0 Hz),
    155.39, 148.77, 140.46, 138.17, 130.49,
    124.61, 123.34 (d, J = 14.9 Hz),
    115.43 (d, J = 23.9 Hz), 109.44, 72.12, 56.09,
    48.06, 34.67, 31.59, 29.04, 20.91, 18.19.
    333 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 12.11 (d,
    film) 2964, calcd for C22H27Cl2N2O5, J = 0.6 Hz, 1H), 8.43 (d, J = 7.9 Hz,
    2872, 469.1292; found, 469.1282 1H), 8.02 (d, J = 5.3 Hz, 1H), 7.37 (d, J = 2.2 Hz,
    1734, 1H), 7.28 (d, J = 8.5 Hz, 1H),
    1649, 7.05 (dd, J = 8.5, 2.3 Hz, 1H), 6.90 (d, J = 5.1 Hz,
    1576, 1H), 5.46 (qd, J = 6.3, 4.7 Hz,
    1528, 1H), 4.77-4.65 (m, 1H), 3.96 (s, 3H),
    1472, 3.12 (dd, J = 9.6, 4.5 Hz, 1H),
    1438, 2.02-1.92 (m, 1H), 1.48 (d, J = 7.2 Hz, 3H),
    1323, 1.08 (d, J = 6.3 Hz, 3H), 1.02 (d, J = 6.6 Hz,
    1263, 3H), 0.68 (d, J = 6.7 Hz, 3H).
    1241, 13C NMR (126 MHz, CDCl3) δ 171.40,
    1129, 800 cm−1 168.71, 155.48, 148.85, 140.54, 136.78,
    136.31, 132.55, 130.48, 130.37, 128.95,
    127.06, 109.56, 72.00, 56.13, 51.39,
    48.06, 34.53, 30.14, 20.75, 20.47, 18.22.
    334 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 12.14 (s,
    film) 3368, calcd for C23H29N2O7, 1H), 8.48 (d, J = 7.9 Hz, 1H), 7.99 (d, J = 5.2 Hz,
    2961, 445.1969; found, 445.1961 1H), 6.87 (d, J = 5.2 Hz, 1H),
    1731, 6.69 (d, J = 8.0 Hz, 1H), 6.59 (d, J = 1.7 Hz,
    1648, 1H), 6.53 (dd, J = 8.0, 1.7 Hz, 1H),
    1528, 5.92 (q, J = 1.6 Hz, 2H), 5.34 (dq, J = 8.5,
    1482, 6.3 Hz, 1H), 4.75-4.60 (m, 1H),
    1438, 3.94 (s, 3H), 2.63 (dd, J = 8.5, 6.6 Hz,
    1240, 1H), 2.03 (dq, J = 13.5, 6.8 Hz, 1H),
    1037, 729 cm−1 1.54 (d, J = 7.2 Hz, 3H), 1.11 (d, J = 6.3 Hz,
    3H), 0.85 (d, J = 6.7 Hz, 3H),
    0.76 (d, J = 6.7 Hz, 3H).
    335 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 12.13 (d,
    film) 3370, calcd for C23H28F3N2O6, J = 0.6 Hz, 1H), 8.44 (d, J = 7.9 Hz,
    2964, 485.1894; found, 485.1896 1H), 7.99 (d, J = 5.2 Hz, 1H),
    1735, 7.15-7.05 (m, 4H), 6.88 (d, J = 5.2 Hz, 1H),
    1649, 5.41 (dq, J = 8.2, 6.3 Hz, 1H),
    1528, 4.76-4.59 (m, 1H), 3.95 (s, 3H), 2.73 (dd, J = 8.2,
    1258, 7.0 Hz, 1H), 2.09 (h, J = 6.8 Hz,
    1217, 1153 cm−1 1H), 1.54 (d, J = 7.2 Hz, 3H), 1.10 (d, J = 6.4 Hz,
    3H), 0.88 (d, J = 6.7 Hz, 3H),
    0.74 (d, J = 6.7 Hz, 3H).
    19F NMR (471 MHz, CDCl3) δ −57.8.
    336 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 12.16 (s,
    film) 3369, calcd for C25H35N2O6, 1H), 8.50 (d, J = 7.8 Hz, 1H), 8.00 (d, J = 5.2 Hz,
    2974, 459.2490; found, 459.2468 1H), 7.08-6.94 (m, 2H),
    1732, 6.87 (d, J = 5.2 Hz, 1H), 6.84-6.75 (m, 2H),
    1649, 5.38 (dq, J = 8.7, 6.3 Hz, 1H),
    1527, 4.79-4.58 (m, 1H), 4.50 (hept, J = 6.1 Hz,
    1509, 1H), 3.95 (s, 3H), 2.65 (dd, J = 8.7, 6.3 Hz,
    1239, 953, 1H), 2.15-1.97 (m, 1H), 1.55 (d, J = 7.2 Hz,
    730 cm−1 3H), 1.33 (d, J = 6.0 Hz, 6H),
    1.10 (d, J = 6.3 Hz, 3H), 0.84 (d, J = 6.7 Hz,
    3H), 0.75 (d, J = 6.7 Hz, 3H).
    337 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 12.19 (s,
    film) 3369, calcd for C25H35N2O6, 1H), 8.54 (d, J = 7.9 Hz, 1H), 7.99 (d, J = 5.2 Hz,
    2972, 459.2490; found, 459.2476 1H), 7.14 (ddd, J = 8.5, 7.5,
    1733, 1.7 Hz, 1H), 7.06 (dd, J = 7.6, 1.8 Hz,
    1649, 1H), 6.93-6.74 (m, 3H), 5.47 (s, 1H),
    1527, 4.84-4.62 (m, 1H), 4.54 (hept, J = 6.0 Hz,
    1450, 1H), 3.94 (s, 3H), 3.45 (s, 1H),
    1238, 953, 2.12 (hept, J = 6.8 Hz, 1H), 1.57 (d, J = 7.2 Hz,
    752, 732 cm−1 3H), 1.33 (d, J = 6.0 Hz, 3H),
    1.31 (d, J = 6.0 Hz, 3H), 1.08 (d, J = 6.2 Hz,
    3H), 0.83 (d, J = 6.8 Hz, 3H), 0.76 (d, J = 6.8 Hz,
    3H).
    338 IR (thin HRMS-ESI (m/z) [M + Na]+ 1H NMR (500 MHz, CDCl3) δ 12.16 (s,
    film) 3368, calcd for C23H30N2O6Na, 1H), 8.49 (d, J = 7.9 Hz, 1H), 8.00 (d, J = 5.2 Hz,
    2960, 453.1996; found, 453.1983 1H), 7.00 (d, J = 8.6 Hz, 2H),
    1732, 6.88 (d, J = 5.2 Hz, 1H), 6.84-6.75 (m,
    1649, 2H), 5.39 (dq, J = 8.6, 6.3 Hz, 1H),
    1512, 4.76-4.63 (m, 1H), 3.95 (s, 3H), 3.79 (s,
    1453, 3H), 2.66 (dd, J = 8.7, 6.4 Hz, 1H),
    1241, 800, 2.07 (h, J = 6.8 Hz, 1H), 1.55 (d, J = 7.2 Hz,
    730 cm−1 3H), 1.10 (d, J = 6.2 Hz, 3H), 0.85 (d, J = 6.8 Hz,
    3H), 0.75 (d, J = 6.7 Hz, 3H).
    339 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.15 (s,
    film) 2963, calcd for C24H33N2O5, 1H), 8.50 (d, J = 7.8 Hz, 1H), 8.00 (d, J = 5.2 Hz,
    1734, 429.2310; found, 429.2381 1H), 7.21-7.02 (m, 4H),
    1650, 6.88 (d, J = 5.2 Hz, 1H), 5.43 (ddq, J = 12.3,
    1528, 9.6, 6.2 Hz, 1H), 4.77-4.59 (m, 1H),
    1452, 1264 cm−1 3.95 (s, 3H), 3.31-3.11 (m, 1H),
    2.33 (d, J = 4.9 Hz, 3H), 2.00-1.79 (m, 1H),
    1.55 (d, J = 6.6 Hz, 2H), 1.41 (ddd, J = 12.2,
    7.3, 4.5 Hz, 1H), 1.34-1.19 (m,
    1H), 1.12-0.67 (m, 10H).
    340 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 12.15 (s,
    film) 3370, calcd for C25H35N2O5, 1H), 8.47 (d, J = 8.1 Hz, 1H), 7.99 (d, J = 5.2 Hz,
    2961, 443.2465; found, 443.2536 1H), 7.19-7.04 (m, 4H),
    1528, 6.88 (d, J = 5.2 Hz, 1H), 5.46 (dq, J = 8.5,
    1263, 1057 cm−1 6.2 Hz, 1H), 4.70 (p, J = 7.5 Hz, 1H),
    3.95 (s, 3H), 3.32 (t, J = 7.6 Hz, 1H),
    2.31 (s, 3H), 1.75-1.59 (m, 1H),
    1.54 (d, J = 7.2 Hz, 3H), 1.49-1.17 (m, 3H),
    1.14-0.97 (m, 4H), 0.90 (t, J = 7.4 Hz,
    3H), 0.77 (t, J = 7.3 Hz, 3H).
    341 ESIMS m/z 455 ([M + H]+) 1H NMR (400 MHz, CDCl3) δ 12.14 (s,
    1H), 8.47 (d, J = 8.0 Hz, 1H), 7.99 (d, J = 5.2 Hz,
    1H), 6.88 (d, J = 5.2 Hz, 1H),
    6.62 (s, 2H), 5.58 (ddt, J = 8.0, 6.4, 1.9 Hz,
    1H), 4.68 (dq, J = 9.3, 7.3 Hz, 1H),
    3.95 (s, 3H), 3.19 (t, J = 7.7 Hz, 1H),
    2.35-2.19 (m, 1H), 1.54 (d, J = 7.2 Hz,
    3H), 1.15 (dt, J = 6.4, 1.3 Hz, 3H),
    0.96 (d, J = 6.7 Hz, 3H), 0.78 (dt, J = 6.8, 1.3 Hz,
    3H).
    19F NMR (376 MHz, CDCl3) δ
    −105.84 (d, J = 1667.9 Hz), −110.02.
    342 1H NMR (400 MHz, CDCl3) δ 12.13 (s,
    1H), 8.44 (d, J = 8.0 Hz, 1H), 7.99 (d, J = 5.2 Hz,
    1H), 7.08 (dd, J = 3.8, 2.0 Hz,
    2H), 7.04-6.96 (m, 1H), 6.86 (dd, J = 19.5,
    5.2 Hz, 1H), 5.44 (ddd, J = 7.7,
    6.4, 1.3 Hz, 1H), 4.80-4.49 (m, 1H),
    3.95 (s, 3H), 3.14 (t, J = 7.8 Hz, 1H),
    2.09 (q, J = 6.9 Hz, 1H), 1.54 (d, J = 7.2 Hz,
    3H), 1.12 (d, J = 6.3 Hz, 3H),
    0.93 (d, J = 6.6 Hz, 3H), 0.75 (d, J = 6.7 Hz,
    3H).
    19F NMR (376 MHz, CDCl3) δ −112.37.
    343 1H NMR (400 MHz, CDCl3) δ 12.15 (s,
    1H), 8.50 (d, J = 8.0 Hz, 1H), 7.99 (d, J = 5.2 Hz,
    1H), 7.24-7.07 (m, 3H),
    6.96 (dddd, J = 9.5, 8.1, 2.8, 1.5 Hz, 1H),
    6.87 (d, J = 5.2 Hz, 1H), 5.82-5.37 (m,
    1H), 4.71 (dd, J = 7.9, 7.1 Hz, 1H),
    3.62-3.24 (m, 1H), 2.31-2.21 (m, 1H),
    1.57 (d, J = 7.2 Hz, 3H), 1.36 (s, 1H),
    1.18-0.96 (m, 7H), 0.78 (ddd, J = 6.8,
    2.7, 0.9 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 171.59,
    168.70, 155.38, 148.78, 140.43,
    137.03 (d, J = 9.3 Hz), 129.07-127.37 (m),
    125.68 (d, J = 3.5 Hz), 114.81 (dd, J = 24.5,
    2.1 Hz), 109.43, 73.22 (d, J = 5.4 Hz),
    72.04 (d, J = 5.2 Hz), 56.06,
    52.18-50.01 (m), 48.25, 29.65 (d, J = 3.2 Hz),
    21.72 (d, J = 3.8 Hz), 20.38,
    18.59 (d, J = 2.4 Hz), 18.16.
    19F NMR (376 MHz, CDCl3) δ
    −105.04 (d, J = 14.1 Hz).
    344 ESIMS m/z 415 ([M + H]+) 1H NMR (400 MHz, CDCl3) δ 12.16 (s,
    1H), 8.51 (d, J = 7.9 Hz, 1H), 8.01 (dd,
    J = 5.2, 3.5 Hz, 1H), 7.17 (q, J = 8.2 Hz,
    1H), 7.04 (t, J = 6.0 Hz, 1H), 6.89 (td, J = 5.2,
    4.7, 2.6 Hz, 3H), 5.41 (ddt, J = 17.9,
    8.7, 6.2 Hz, 1H), 4.69 (p, J = 7.3 Hz,
    1H), 3.94 (d, J = 5.1 Hz, 2H),
    2.66 (ddd, J = 12.1, 8.8, 6.4 Hz, 1H), 2.33 (d,
    J = 4.2 Hz, 3H), 1.70-1.48 (m, 6H),
    1.09 (dd, J = 16.5, 6.2 Hz, 2H),
    0.86 (dd, J = 8.0, 6.8 Hz, 3H), 0.76 (d, J = 6.8 Hz,
    3H).
    13C NMR (101 MHz, CDCl3) δ 171.75,
    168.73, 155.40, 148.81, 140.46, 137.37,
    130.65, 130.57, 127.73, 127.39, 126.82,
    109.45, 108.39, 73.18, 72.02, 56.07,
    48.22, 28.31, 21.49, 21.33, 18.66, 18.33,
    17.89.
    345 ESIMS m/z 431 ([M + H]+) 1H NMR (400 MHz, CDCl3) δ 12.13 (s,
    1H), 8.46 (d, J = 8.0 Hz, 1H), 8.00 (dd,
    J = 8.4, 5.2 Hz, 1H), 7.09-6.65 (m,
    4H), 5.59-5.25 (m, 1H),
    4.85-4.56 (m, 1H), 3.94 (d, J = 5.0 Hz, 4H),
    3.27-3.08 (m, 1H), 1.54 (d, J = 7.2 Hz, 3H),
    1.15 (d, J = 6.3 Hz, 3H), 0.95 (d, J = 6.7 Hz,
    3H), 0.78 (d, J = 6.7 Hz, 3H).
    346 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.48 (t, J = 5.4 Hz,
    film) 3391, calcd for C24H30FN2O6, 1H), 8.34 (d, J = 5.4 Hz, 1H),
    2962, 461.2082; found, 461.2077 7.08-6.97 (m, 2H), 6.86 (ddd, J = 9.5,
    1770, 6.3, 2.4 Hz, 2H), 5.43 (dq, J = 8.5, 6.4 Hz,
    1743, 1H), 4.16 (d, J = 5.4 Hz, 2H),
    1677, 3.92 (s, 3H), 3.03 (t, J = 7.7 Hz, 1H), 2.40 (s,
    1513, 3H), 2.30 (s, 3H), 2.13-2.02 (m, 1H),
    1499, 1.07 (d, J = 6.3 Hz, 3H), 0.92 (d, J = 6.7 Hz,
    1311, 3H), 0.76 (d, J = 6.7 Hz, 3H).
    1192, 19F NMR (376 MHz, CDCl3) δ −117.43.
    1175,
    1009, 732 cm−1
    347 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.46 (d, J = 9.5 Hz,
    film) 3382, calcd for C27H36FN2O6, 1H), 8.32 (d, J = 5.5 Hz, 1H),
    2963, 503.2552; found, 503.2554 7.03 (dd, J = 9.1, 5.7 Hz, 2H), 6.83 (td,
    1771, J = 8.4, 2.9 Hz, 1H), 6.77 (dd, J = 10.0,
    1730, 2.8 Hz, 1H), 5.35 (dq, J = 9.1, 6.2 Hz,
    1681, 1H), 4.66 (dd, J = 9.6, 4.8 Hz, 1H),
    1499, 3.92 (s, 3H), 3.07 (dd, J = 9.1, 6.1 Hz, 1H),
    1311, 2.40 (s, 3H), 2.36-2.22 (m, 4H),
    1191, 2.14 (td, J = 13.4, 12.6, 5.9 Hz, 1H), 1.05 (d,
    1173, 907, J = 6.2 Hz, 3H), 1.02 (d, J = 6.8 Hz,
    731 cm−1 3H), 0.97 (d, J = 6.9 Hz, 3H), 0.82 (d, J = 6.8 Hz,
    3H), 0.76 (d, J = 6.8 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 171.03,
    168.84, 162.69, 160.91 (d, J = 244.3 Hz),
    159.51, 146.61, 141.66, 139.97 (d,
    J = 7.3 Hz), 137.57, 133.48 (d, J = 3.2 Hz),
    129.19 (d, J = 7.8 Hz), 116.95 (d, J = 20.4 Hz),
    112.24 (d, J = 20.7 Hz),
    109.74, 73.47, 57.33, 56.31, 49.32,
    31.55, 29.38, 20.91, 20.89-20.83 (m),
    20.77, 19.38, 18.63, 18.10, 17.51.
    19F NMR (376 MHz, CDCl3) δ −117.47.
    348 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.45 (d, J = 9.5 Hz,
    film) 3383, calcd for C28H37FN2O6, 1H), 8.31 (d, J = 5.4 Hz, 1H),
    2963, 517.2708; found, 517.2715 7.03 (dd, J = 9.5, 5.6 Hz, 2H), 6.83 (td,
    1771, J = 8.4, 2.9 Hz, 1H), 6.77 (dd, J = 9.9,
    1730, 2.8 Hz, 1H), 5.35 (dq, J = 9.2, 6.2 Hz,
    1680, 1H), 4.71 (dd, J = 9.5, 4.9 Hz, 1H),
    1499, 3.92 (s, 3H), 3.08 (dd, J = 9.2, 6.0 Hz, 1H),
    1191, 2.40 (s, 3H), 2.26 (s, 3H), 2.14 (td, J = 13.3,
    1173, 731 cm−1 12.8, 6.1 Hz, 1H), 2.09-1.98 (m,
    1H), 1.51 (dtd, J = 16.7, 7.4, 3.6 Hz,
    1H), 1.30-1.18 (m, 1H), 1.04 (d, J = 6.2 Hz,
    3H), 1.00 (d, J = 6.8 Hz, 3H),
    0.93 (t, J = 7.4 Hz, 3H), 0.82 (d, J = 6.8 Hz,
    3H), 0.76 (d, J = 6.9 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 170.99,
    168.84, 162.59, 160.91 (d, J = 244.3 Hz),
    159.51, 146.60, 141.67, 139.98 (d,
    J = 7.5 Hz), 137.58, 133.44 (d, J = 3.3 Hz),
    129.21 (d, J = 7.6 Hz), 116.95 (d, J = 20.5 Hz),
    112.23 (d, J = 20.8 Hz),
    109.72, 73.43, 56.98, 56.31, 49.32,
    38.12, 29.31, 24.73, 20.92,
    20.90-20.83 (m), 20.78, 18.48, 18.16, 15.72,
    11.56.
    19F NMR (376 MHz, CDCl3) δ −117.47.
    349 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.31 (t, J = 5.8 Hz,
    film) 3378, calcd for C28H38FN2O6, 2H), 7.08-6.96 (m, 2H),
    2959, 517.2708; found, 517.2707 6.84 (td, J = 8.4, 2.9 Hz, 1H), 6.78 (dd, J = 9.9,
    1772, 2.8 Hz, 1H), 5.33 (dq, J = 8.9, 6.3 Hz,
    1733, 1H), 4.72 (dt, J = 9.0, 7.0 Hz, 1H),
    1679, 3.91 (s, 3H), 3.06 (dd, J = 8.9, 6.5 Hz,
    1499, 1H), 2.39 (s, 3H), 2.26 (s, 3H),
    1191, 2.15-2.04 (m, 1H), 1.78-1.59 (m, 3H),
    1173, 1.05 (d, J = 6.2 Hz, 3H), 0.99-0.93 (m, 6H),
    1049, 825 cm−1 0.84 (d, J = 6.8 Hz, 3H), 0.75 (d, J = 6.8 Hz,
    3H).
    13C NMR (101 MHz, CDCl3) δ 172.05,
    168.83, 162.46, 160.90 (d, J = 244.3 Hz),
    159.52, 146.57, 141.63, 139.94 (d,
    J = 7.5 Hz), 137.58, 133.69 (d, J = 3.3 Hz),
    129.18 (d, J = 6.9 Hz), 116.90 (d, J = 20.5 Hz),
    112.25 (d, J = 20.6 Hz),
    109.74, 73.52, 56.30, 51.04, 49.33,
    41.69, 29.59, 24.93, 23.03, 21.98, 20.94,
    20.92-20.86 (m), 20.76, 18.94, 17.82.
    19F NMR (376 MHz, CDCl3) δ −117.54.
    350 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.46 (t, J = 5.4 Hz,
    film) 3387, calcd for C26H34FN2O7, 1H), 8.33 (d, J = 5.4 Hz, 1H),
    2961, 505.2345; found, 505.2339 7.08-6.99 (m, 2H), 6.90-6.80 (m,
    1767, 2H), 5.43 (dq, J = 8.2, 6.3 Hz, 1H),
    1742, 4.15 (d, J = 5.4 Hz, 2H), 3.91 (s, 3H), 3.82 (t,
    1678, J = 6.6 Hz, 2H), 3.41 (s, 3H),
    1498, 3.09-2.95 (m, 3H), 2.30 (s, 3H), 2.07 (h, J = 6.8 Hz,
    1208, 1H), 1.07 (d, J = 6.3 Hz, 3H),
    1112, 0.92 (d, J = 6.7 Hz, 3H), 0.76 (d, J = 6.8 Hz,
    1047, 3H).
    1009, 730 cm−1 19F NMR (376 MHz, CDCl3) δ −117.43.
    351 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.44 (d, J = 9.5 Hz,
    film) 3383, calcd for C29H40FN2O7, 1H), 8.32 (d, J = 5.4 Hz, 1H),
    2963, 547.2814; found, 547.2813 7.09-6.98 (m, 2H), 6.83 (td, J = 8.4,
    1769, 2.9 Hz, 1H), 6.77 (dd, J = 10.0, 2.8 Hz,
    1730, 1H), 5.35 (dq, J = 9.1, 6.2 Hz, 1H),
    1681, 4.65 (dd, J = 9.5, 4.8 Hz, 1H), 3.91 (s, 3H),
    1499, 3.81 (t, J = 6.6 Hz, 2H), 3.40 (s, 3H),
    1311, 3.07 (dd, J = 9.1, 6.1 Hz, 1H), 2.99 (t, J = 6.7 Hz,
    1110, 826 cm−1 2H), 2.34-2.21 (m, 4H),
    2.14 (dq, J = 13.4, 6.5 Hz, 1H), 1.05 (d, J = 6.2 Hz,
    3H), 1.01 (d, J = 6.8 Hz, 3H),
    0.97 (d, J = 6.9 Hz, 3H), 0.82 (d, J = 6.8 Hz,
    3H), 0.76 (d, J = 6.9 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −117.47.
    352 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.43 (d, J = 9.4 Hz,
    film) 3382, calcd for C30H42FN2O7, 1H), 8.31 (d, J = 5.4 Hz, 1H),
    2963, 561.2971; found, 561.2969 7.06-6.96 (m, 2H), 6.83 (td, J = 8.4,
    1769, 2.9 Hz, 1H), 6.77 (dd, J = 10.0, 2.8 Hz,
    1730, 1H), 5.35 (dq, J = 9.1, 6.2 Hz, 1H),
    1681, 4.69 (dd, J = 9.5, 4.9 Hz, 1H), 3.91 (s, 3H),
    1499, 3.81 (t, J = 6.6 Hz, 2H), 3.41 (s, 3H),
    1111, 3.07 (dd, J = 9.2, 6.0 Hz, 1H), 2.99 (t, J = 6.7 Hz,
    1046, 825, 2H), 2.26 (s, 3H),
    731 cm−1 2.18-2.08 (m, 1H), 2.08-1.97 (m, 1H),
    1.50 (dddd, J = 13.3, 11.3, 6.8, 3.8 Hz, 1H),
    1.29-1.17 (m, 1H), 1.04 (d, J = 6.2 Hz,
    3H), 0.99 (d, J = 6.9 Hz, 3H), 0.93 (t, J = 7.4 Hz,
    3H), 0.82 (d, J = 6.8 Hz, 3H),
    0.76 (d, J = 6.8 Hz, 3H).
    13C NMR (101 MHz, CDCl3) δ 170.99,
    169.35, 162.55, 160.91 (d, J = 243.9 Hz),
    159.52, 146.64, 141.69, 139.97 (d,
    J = 7.5 Hz), 137.44, 133.44 (d, J = 3.1 Hz),
    129.20 (d, J = 8.2 Hz), 116.95 (d, J = 20.3 Hz),
    112.24 (d, J = 20.7 Hz),
    109.72, 73.43, 67.65, 58.75, 56.97,
    56.34, 49.30, 38.13, 34.69, 29.32, 24.73,
    20.92, 20.90-20.86 (m), 18.49, 18.15,
    15.72, 11.55.
    19F NMR (376 MHz, CDCl3) δ −117.46.
    353 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.31 (t, J = 3.9 Hz,
    film) 3377, calcd for C30H42FN2O7, 2H), 7.08-6.98 (m, 2H),
    2958, 561.2971; found, 561.2974 6.84 (td, J = 8.4, 2.9 Hz, 1H), 6.78 (dd, J = 10.0,
    1769, 2.8 Hz, 1H), 5.37-5.27 (m, 1H),
    1733, 4.79-4.63 (m, 1H), 3.91 (s, 3H),
    1679, 3.81 (t, J = 6.7 Hz, 2H), 3.40 (s, 3H),
    1499, 3.06 (dd, J = 8.9, 6.5 Hz, 1H), 2.98 (t, J = 6.7 Hz,
    1309, 2H), 2.26 (s, 3H), 2.09 (h, J = 6.8 Hz,
    1110, 1H), 1.75-1.62 (m, 3H), 1.05 (d, J = 6.2 Hz,
    1049, 826 cm−1 3H), 0.99-0.93 (m, 6H),
    0.84 (d, J = 6.8 Hz, 3H), 0.74 (d, J = 6.8 Hz,
    3H).
    13C NMR (101 MHz, CDCl3) δ 172.06,
    169.33, 162.42, 160.91 (d, J = 244.3 Hz),
    159.53, 146.61, 141.64, 139.93 (d,
    J = 7.6 Hz), 137.45, 133.69 (d, J = 3.1 Hz),
    129.19 (d, J = 8.0 Hz), 116.91 (d, J = 20.5 Hz),
    112.25 (d, J = 20.6 Hz),
    109.74, 73.51, 67.65, 58.74, 56.33,
    51.03, 49.32, 41.74, 34.69, 29.60, 24.91,
    23.05, 21.97, 21.01-20.80 (m), 20.94,
    18.95, 17.82.
    19F NMR (376 MHz, CDCl3) δ −117.54.
    354 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.45 (d, J = 8.1 Hz,
    film) 3383, calcd for C29H38FN2O6, 1H), 8.31 (d, J = 5.4 Hz, 1H),
    2960, 529.2708; found, 529.2705 7.05 (dd, J = 8.6, 5.9 Hz, 1H), 6.99 (d, J = 5.5 Hz,
    1736, 1H), 6.90-6.77 (m, 2H),
    1499, 5.35 (dq, J = 8.9, 6.2 Hz, 1H),
    1208, 4.77-4.64 (m, 1H), 3.89 (s, 3H), 3.15 (q, J = 8.0 Hz,
    1122, 730 cm−1 1H), 3.11-3.03 (m, 1H), 2.29 (s,
    3H), 2.21-1.97 (m, 6H),
    1.83-1.70 (m, 2H), 1.70-1.57 (m, 1H), 1.49 (d, J = 7.2 Hz,
    3H), 1.06 (d, J = 6.2 Hz, 3H),
    0.86 (d, J = 6.8 Hz, 3H), 0.77 (d, J = 6.8 Hz,
    3H).
    19F NMR (376 MHz, CDCl3) δ −117.44.
    355 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.42 (d, J = 10.8 Hz,
    film) 3382, calcd for C28H38FN2O6, 1H), 8.32 (d, J = 5.4 Hz,
    2968, 517.2708; found, 517.2702 1H), 7.05 (dd, J = 8.6, 5.9 Hz, 1H),
    1734, 6.99 (d, J = 5.5 Hz, 1H), 6.91-6.77 (m, 2H),
    1679, 5.35 (dq, J = 8.7, 6.2 Hz, 1H),
    1499, 4.77-4.66 (m, 1H), 3.89 (s, 3H), 3.07 (dd, J = 8.8,
    1155, 6.5 Hz, 1H), 2.77 (q, J = 6.9 Hz,
    1109, 1H), 2.29 (s, 3H), 2.11 (h, J = 6.7 Hz,
    1059, 731 cm−1 1H), 1.92 (dp, J = 14.2, 7.0 Hz, 1H),
    1.65 (dt, J = 13.9, 7.2 Hz, 1H), 1.49 (d,
    J = 7.2 Hz, 3H), 1.37-1.30 (m, 3H),
    1.05 (dd, J = 7.8, 7.0 Hz, 6H), 0.86 (d, J = 6.8 Hz,
    3H), 0.77 (d, J = 6.8 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −117.44.
    356 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.47 (d, J = 8.1 Hz,
    film) 3380, calcd for C28H38FN2O6, 1H), 8.32 (d, J = 5.4 Hz, 1H),
    2960, 517.2708; found, 517.2706 7.05 (dd, J = 8.6, 5.9 Hz, 1H), 7.00 (d, J = 5.4 Hz,
    1678, 1H), 6.88-6.77 (m, 2H),
    1499, 5.36 (dq, J = 8.9, 6.3 Hz, 1H), 4.70 (dq, J = 8.2,
    1311, 7.2 Hz, 1H), 3.90 (s, 3H), 3.08 (dd,
    1149, J = 8.9, 6.5 Hz, 1H), 2.58 (d, J = 7.1 Hz,
    1049, 731 cm−1 2H), 2.35-2.20 (m, 4H),
    2.17-2.05 (m, 1H), 1.49 (d, J = 7.2 Hz, 3H),
    1.09-1.03 (m, 9H), 0.86 (d, J = 6.7 Hz, 3H),
    0.77 (d, J = 6.8 Hz, 3H).
    19F NMR (376 MHz, CDCl3) δ −117.43.
    357 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.50 (d, J = 8.0 Hz,
    film) 3379, calcd for C26H34FN2O6, 1H), 8.32 (d, J = 5.5 Hz, 1H),
    2961, 489.2395; found, 489.2389 7.05 (dd, J = 8.6, 5.9 Hz, 1H), 7.01 (d, J = 5.4 Hz,
    1734, 1H), 6.89-6.78 (m, 2H),
    1676, 5.36 (dq, J = 8.9, 6.2 Hz, 1H),
    1499, 4.76-4.64 (m, 1H), 3.91 (s, 3H), 3.08 (dd, J = 8.9,
    1310, 6.5 Hz, 1H), 2.73 (q, J = 7.5 Hz, 2H),
    1211, 2.29 (s, 3H), 2.11 (h, J = 6.8 Hz, 1H),
    1125, 1.50 (d, J = 7.2 Hz, 3H), 1.28 (t, J = 7.5 Hz,
    1049, 731 cm−1 3H), 1.06 (d, J = 6.3 Hz, 3H),
    0.86 (d, J = 6.8 Hz, 3H), 0.77 (d, J = 6.8 Hz,
    3H).
    19F NMR (376 MHz, CDCl3) δ −117.43.
    358 IR (thin ESIMS m/z 471.2 1H NMR (500 MHz, CDCl3) δ 8.56 (s,
    film) 3378, ([M + H]+) 1H), 8.34 (d, J = 5.5 Hz, 1H),
    2959, 7.04-6.98 (m, 2H), 6.95-6.84 (m, 2H),
    1770, 5.37 (dq, J = 9.4, 6.2 Hz, 1H),
    1731, 4.76-4.65 (m, 1H), 3.91 (s, 3H), 3.10 (dd, J = 9.1,
    1675, 5.9 Hz, 1H), 2.40 (s, 3H), 2.29 (s, 3H),
    1504, 2.27 (s, 3H), 2.14 (dp, J = 14.1, 7.4, 6.9 Hz,
    1451, 1H), 1.52 (d, J = 7.1 Hz, 3H),
    1435, 1.05 (d, J = 6.2 Hz, 3H), 0.84 (d, J = 6.8 Hz,
    1365, 3H), 0.80 (d, J = 6.8 Hz, 3H).
    1309,
    1199,
    1174,
    1044, 907,
    804, 729 cm−1
    359 IR (thin ESIMS m/z 475.2 1H NMR (500 MHz, CDCl3) δ 8.53 (s,
    film) 3381, ([M + H]+) 1H), 8.34 (d, J = 5.5 Hz, 1H), 7.11 (td, J = 8.0,
    2961, 5.9 Hz, 1H), 7.01 (d, J = 5.5 Hz,
    1770, 1H), 6.90 (dt, J = 8.8, 4.9 Hz, 2H),
    1732, 5.38 (dq, J = 8.9, 6.2 Hz, 1H),
    1675, 4.75-4.63 (m, 1H), 3.91 (s, 3H), 3.14 (t, J = 7.7 Hz,
    1506, 1H), 2.40 (s, 3H), 2.22 (d, J = 2.4 Hz,
    1457, 3H), 2.14 (dq, J = 13.5, 6.9 Hz, 1H),
    1436, 1.51 (d, J = 7.1 Hz, 3H), 1.06 (d, J = 6.3 Hz,
    1366, 3H), 0.86 (d, J = 6.8 Hz, 3H),
    1310, 0.78 (d, J = 6.9 Hz, 3H).
    1199,
    1164,
    1041, 907,
    785, 731 cm−1
    360 IR (thin ESIMS m/z 461.2 1H NMR (500 MHz, CDCl3) δ 8.55 (s,
    film) 3381, ([M + H]+) 1H), 8.34 (d, J = 5.4 Hz, 1H),
    2963, 7.22-7.17 (m, 1H), 7.14 (td, J = 7.5, 1.9 Hz,
    1771, 1H), 7.08 (td, J = 7.5, 1.2 Hz, 1H),
    1734, 7.00 (d, J = 5.4 Hz, 2H), 5.52-5.37 (m, 1H),
    1676, 4.75-4.60 (m, 1H), 3.91 (s, 3H),
    1508, 3.19 (t, J = 7.7 Hz, 1H), 2.40 (s, 3H),
    1490, 2.18-2.09 (m, 1H), 1.50 (d, J = 7.2 Hz, 3H),
    1453, 1.11 (d, J = 6.3 Hz, 3H), 0.91 (d, J = 6.7 Hz,
    1436, 3H), 0.77 (d, J = 6.7 Hz, 3H).
    1366,
    1310,
    1202,
    1175,
    1050, 907,
    759, 732 cm−1
    361 IR (thin ESIMS m/z 475.2 1H NMR (500 MHz, CDCl3) δ 8.53 (s,
    film) 3377, ([M + H]+) 1H), 8.33 (d, J = 5.4 Hz, 1H), 7.07 (dd,
    2961, J = 8.2, 6.2 Hz, 1H), 7.01 (d, J = 5.4 Hz,
    1770, 1H), 6.88-6.73 (m, 2H),
    1734, 5.41-5.24 (m, 1H), 4.76-4.64 (m, 1H), 3.91 (s,
    1676, 3H), 3.10 (t, J = 7.8 Hz, 1H), 2.40 (s,
    1500, 3H), 2.27 (s, 3H), 2.16-2.08 (m, 1H),
    1453, 1.50 (d, J = 7.2 Hz, 3H), 1.08 (d, J = 6.3 Hz,
    1436, 3H), 0.88 (d, J = 6.8 Hz, 3H),
    1365, 0.80 (d, J = 6.8 Hz, 3H).
    1310,
    1201,
    1175,
    1048, 907,
    805, 731 cm−1
    362 IR (thin ESIMS m/z 471.2 1H NMR (400 MHz, CDCl3) δ 8.56 (s,
    film) 3376, ([M + H]+) 1H), 8.34 (d, J = 5.5 Hz, 1H), 7.01 (d, J = 5.5 Hz,
    2959, 1H), 6.96 (d, J = 2.9 Hz, 3H),
    1771, 5.46-5.29 (m, 1H), 4.77-4.65 (m,
    1731, 1H), 3.91 (s, 3H), 3.09 (dd, J = 9.2, 5.9 Hz,
    1676, 1H), 2.36 (s, 3H), 2.28 (s, 6H),
    1505, 2.19-2.07 (m, 1H), 1.51 (d, J = 7.1 Hz, 3H),
    1452, 1.04 (d, J = 6.2 Hz, 3H), 0.84 (d, J = 6.8 Hz,
    1437, 3H), 0.79 (d, J = 6.8 Hz, 3H).
    1200,
    1175,
    1045, 823 cm−1
    363 IR (thin ESIMS m/z 471.2 1H NMR (400 MHz, CDCl3) δ 8.57 (s,
    film) 3377, ([M + H]+) 1H), 8.34 (d, J = 5.4 Hz, 1H),
    2961, 7.06-6.99 (m, 3H), 6.97-6.92 (m, 1H),
    1771, 5.39 (dq, J = 12.5, 6.5 Hz, 1H), 4.69 (dt, J = 8.1,
    1733, 7.1 Hz, 1H), 3.91 (s, 3H), 3.25 (dd,
    1677, J = 9.2, 6.0 Hz, 1H), 2.36 (s, 3H),
    1507, 2.28 (s, 3H), 2.23 (s, 3H), 2.13 (dt, J = 14.1,
    1452, 7.1 Hz, 1H), 1.52 (d, J = 7.2 Hz, 3H),
    1437, 1.04 (d, J = 6.2 Hz, 3H), 0.84 (d, J = 6.7 Hz,
    1365, 3H), 0.79 (d, J = 6.9 Hz, 3H).
    1310,
    1202,
    1175, 1043 cm−1
    364 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 8.55 (s,
    film) 3382, calcd for C25H33N2O6, 1H), 8.34 (d, J = 5.5 Hz, 1H),
    2960, 457.2333; found, 457.2332 7.18-7.06 (m, 4H), 7.01 (d, J = 5.4 Hz, 1H),
    1771, 5.39 (dq, J = 9.3, 6.2 Hz, 1H),
    1732, 4.75-4.66 (m, 1H), 3.91 (s, 3H), 3.14 (dd, J = 9.3,
    1676, 6.2 Hz, 1H), 2.40 (s, 3H), 2.32 (s,
    1507, 3H), 2.21-2.10 (m, 1H), 1.51 (d, J = 7.1 Hz,
    1200, 3H), 1.05 (d, J = 6.2 Hz, 3H),
    1175, 731 cm−1 0.86 (d, J = 6.9 Hz, 3H), 0.80 (d, J = 6.9 Hz,
    3H).
    365 IR (thin ESIMS m/z 479.2 1H NMR (500 MHz, CDCl3) δ 8.52 (s,
    film) 2964, ([M + H]+) 1H), 8.33 (d, J = 5.4 Hz, 1H), 7.10 (td, J = 8.4,
    1770, 6.4 Hz, 1H), 7.01 (d, J = 5.5 Hz,
    1734, 1H), 6.85-6.79 (m, 1H), 6.75 (ddd, J = 10.2,
    1675, 8.9, 2.6 Hz, 1H), 5.41 (tt, J = 7.1,
    1502, 5.8 Hz, 1H), 4.83-4.58 (m, 1H),
    1453, 3.91 (s, 3H), 3.13 (t, J = 7.7 Hz, 1H), 2.40 (s,
    1309, 3H), 2.09 (td, J = 13.3, 6.5 Hz, 1H),
    1192, 1.49 (d, J = 7.2 Hz, 3H), 1.10 (d, J = 6.3 Hz,
    1174, 3H), 0.92 (d, J = 6.8 Hz, 3H),
    1049, 965, 0.75 (d, J = 6.7 Hz, 3H).
    907, 846,
    730 cm−1
    366 IR (thin ESIMS m/z 475.2 1H NMR (500 MHz, CDCl3) δ 8.55 (s,
    film) 2962, ([M + H]+) 1H), 8.34 (d, J = 5.5 Hz, 1H),
    1770, 7.05-6.95 (m, 2H), 6.89 (dd, J = 7.6, 1.5 Hz,
    1733, 1H), 6.85-6.77 (m, 1H),
    1676, 5.50-5.38 (m, 1H), 4.83-4.55 (m, 1H), 3.91 (s,
    1506, 3H), 3.13 (t, J = 7.7 Hz, 1H), 2.40 (s,
    1452, 3H), 2.32 (s, 3H), 2.10 (dt, J = 13.5, 6.8 Hz,
    1310, 1H), 1.50 (d, J = 7.1 Hz, 3H),
    1197, 1.10 (d, J = 6.3 Hz, 3H), 0.90 (d, J = 6.7 Hz,
    1174, 3H), 0.76 (d, J = 6.7 Hz, 3H).
    1049, 907, 13C NMR (126 MHz, CDCl3) δ 172.25,
    823, 731 cm−1 168.92, 162.36, 160.50, 159.45, 146.65,
    141.61, 138.33 (d, J = 8.2 Hz), 137.50,
    130.10, 124.31 (d, J = 3.0 Hz),
    122.50 (d, J = 15.0 Hz), 115.94 (d, J = 23.8 Hz),
    109.70, 72.47, 56.28, 48.17, 28.32,
    21.07, 20.90, 20.77, 18.96, 18.52, 17.42.
    367 IR (thin ESIMS m/z 511.1 ([M]+) 1H NMR (500 MHz, CDCl3) δ 8.51 (s,
    film) 2963, 1H), 8.33 (d, J = 5.4 Hz, 1H), 7.36 (d, J = 2.2 Hz,
    1771, 1H), 7.22 (dd, J = 8.5, 2.2 Hz,
    1735, 1H), 7.13 (d, J = 8.4 Hz, 1H), 7.01 (d, J = 5.4 Hz,
    1677, 1H), 5.37 (t, J = 7.3 Hz, 1H),
    1508, 4.83-4.56 (m, 1H), 3.91 (s, 3H),
    1365, 3.51 (s, 1H), 2.40 (s, 3H), 2.16-1.99 (m,
    1310, 1H), 1.50 (d, J = 7.2 Hz, 3H), 1.10 (d, J = 6.3 Hz,
    1200, 3H), 0.92 (d, J = 6.7 Hz, 3H),
    1175, 0.76 (d, J = 6.8 Hz, 3H).
    1044, 825,
    732 cm−1
    368 IR (thin ESIMS m/z 479.2 1H NMR (500 MHz, CDCl3) δ 8.49 (s,
    film) 3379, ([M + H]+) 1H), 8.34 (d, J = 5.4 Hz, 1H), 7.26 (s,
    2967, 1H), 7.02 (dd, J = 5.5, 2.3 Hz, 1H),
    1770, 6.82-6.71 (m, 2H), 5.45 (td, J = 6.2, 4.7 Hz,
    1733, 1H), 4.75-4.59 (m, 1H), 3.92 (d, J = 2.5 Hz,
    1675, 3H), 2.82 (dd, J = 9.3, 4.8 Hz,
    1502, 1H), 2.39 (s, 3H), 2.01 (ddt, J = 15.8,
    1192, 13.3, 6.8 Hz, 1H), 1.39 (d, J = 7.1 Hz,
    1173, 965, 3H), 1.08 (d, J = 6.3 Hz, 3H), 0.99 (d, J = 6.6 Hz,
    846, 731 cm−1 3H), 0.70 (d, J = 6.6 Hz, 3H).
    369 IR (thin ESIMS m/z 475.2 1H NMR (500 MHz, CDCl3) δ 8.62 (dt,
    film) 2965, ([M + H]+) J = 4.3, 1.8 Hz, 1H), 8.35 (d, J = 5.5 Hz,
    1771, 1H), 7.70 (tt, J = 7.7, 1.8 Hz, 1H),
    1732, 7.31 (dd, J = 7.7, 5.8 Hz, 1H), 7.01 (d, J = 5.5 Hz,
    1676, 1H), 6.82 (dd, J = 9.4, 7.0 Hz,
    1506, 2H), 5.53-5.33 (m, 1H),
    1437, 4.76-4.54 (m, 1H), 3.91 (s, 3H), 2.83 (dd, J = 9.2,
    1310, 5.0 Hz, 1H), 2.39 (s, 3H), 2.31 (s, 3H),
    1190, 1.36 (d, J = 7.1 Hz, 3H), 1.10 (d, J = 6.3 Hz,
    1175, 3H), 0.98 (d, J = 6.6 Hz, 3H),
    1061, 0.72 (d, J = 6.8 Hz, 3H).
    1008, 821,
    803 cm−1
    370 IR (thin ESIMS m/z 511.1 1H NMR (500 MHz, CDCl3) δ 8.50 (s,
    film) 2964, ([M + H]+) 1H), 8.35 (d, J = 5.4 Hz, 1H),
    1771, 7.41-7.30 (m, 2H), 7.07 (dd, J = 8.5, 2.2 Hz,
    1733, 1H), 7.03 (d, J = 5.4 Hz, 1H), 5.44 (qd,
    1714, J = 6.2, 4.3 Hz, 1H), 4.80-4.61 (m,
    1676, 1H), 3.92 (d, J = 1.9 Hz, 3H), 3.10 (dd,
    1506, J = 9.8, 4.3 Hz, 1H), 2.40 (s, 3H),
    1472, 2.04-1.88 (m, 1H), 1.44 (d, J = 7.2 Hz, 3H),
    1365, 1.05 (d, J = 6.3 Hz, 3H), 1.02 (d, J = 6.6 Hz,
    1310, 3H), 0.68 (d, J = 6.7 Hz, 3H).
    1192, 13C NMR (126 MHz, CDCl3) δ 171.98,
    1175, 826, 168.88, 162.37, 159.57, 149.73, 146.66,
    804, 734 cm−1 141.41, 137.63, 136.93, 136.28, 132.49,
    130.70, 128.86, 127.08, 123.76, 109.88,
    71.68, 56.33, 48.10, 30.13, 20.73, 20.64,
    18.62, 18.30.
    371 IR (thin ESIMS m/z 577.3 1H NMR (400 MHz, CDCl3) δ 8.33 (d, J = 5.5 Hz,
    film) 2961, ([M + H]+) 1H), 7.04 (dd, J = 8.6, 5.9 Hz,
    1773, 1H), 6.95 (d, J = 5.6 Hz, 1H),
    1742, 6.91-6.79 (m, 2H), 5.44-5.31 (m, 1H),
    1685, 5.25 (q, J = 7.0 Hz, 1H), 4.31 (q, J = 7.1 Hz,
    1594, 2H), 3.98-3.85 (m, 5H), 3.01 (t, J = 7.6 Hz,
    1490, 1H), 2.31 (s, 3H),
    1441, 2.15-2.04 (m, 1H), 1.63 (d, J = 7.0 Hz, 3H),
    1375, 1.36 (t, J = 7.2 Hz, 3H), 1.01 (d, J = 6.3 Hz,
    1342, 3H), 0.90 (d, J = 6.8 Hz, 3H), 0.87 (t, J = 7.2 Hz,
    1306, 3H), 0.77 (d, J = 6.7 Hz, 3H).
    1246,
    1217,
    1201, 1090 cm−1
    372 IR (thin ESIMS m/z 505.3 1H NMR (500 MHz, CDCl3) δ 8.47 (d, J = 8.1 Hz,
    film) 3379, ([M + H]+) 1H), 8.34 (d, J = 5.5 Hz, 1H),
    2962, 7.08-6.99 (m, 2H), 6.88-6.79 (m,
    1767, 2H), 5.36 (dq, J = 8.9, 6.3 Hz, 1H),
    1734, 4.81-4.69 (m, 1H), 4.36 (q, J = 7.1 Hz, 2H),
    1678, 3.94 (s, 3H), 3.08 (dd, J = 8.9, 6.5 Hz,
    1499, 1H), 2.29 (m, 3H), 2.15-2.05 (m, 1H),
    1312, 1.50 (d, J = 7.1 Hz, 3H), 1.41 (t, J = 7.1 Hz,
    1251, 3H), 1.06 (d, J = 6.3 Hz, 3H),
    1215, 0.86 (d, J = 6.8 Hz, 3H), 0.77 (d, J = 6.8 Hz,
    1051, 731 cm−1 3H).
    373 IR (thin ESIMS m/z 519.3 1H NMR (400 MHz, CDCl3) δ 8.44 (d, J = 8.1 Hz,
    film) 3384, ([M + H]+) 1H), 8.33 (d, J = 5.4 Hz, 1H),
    2981, 7.08-6.97 (m, 2H), 6.91-6.75 (m,
    1764, 2H), 5.44-5.31 (m, 1H), 4.98 (dq, J = 12.9,
    1736, 6.4 Hz, 1H), 4.81-4.61 (m, 1H),
    1681, 3.93 (s, 3H), 3.08 (dd, J = 8.9, 6.5 Hz,
    1500, 1H), 2.29 (s, 3H), 2.11 (dt, J = 13.5, 6.8 Hz,
    1313, 1H), 1.50 (d, J = 7.1 Hz, 3H),
    1259, 1.41 (d, J = 6.3 Hz, 6H), 1.06 (d, J = 6.3 Hz,
    1217, 3H), 0.86 (d, J = 6.8 Hz, 3H), 0.77 (d, J = 6.8 Hz,
    1180, 3H).
    1100, 915 cm−1
    374 IR (thin ESIMS m/z 517.3 1H NMR (400 MHz, CDCl3) δ 8.40 (s,
    film) 3382, ([M + H]+) 1H), 8.31 (d, J = 5.4 Hz, 1H), 7.05 (dd,
    2968, J = 8.5, 5.9 Hz, 1H), 6.98 (d, J = 5.5 Hz,
    2874, 1H), 6.91-6.72 (m, 2H), 5.35 (dq, J = 8.9,
    1756, 6.3 Hz, 1H), 4.77-4.62 (m, 1H),
    1735, 3.89 (s, 3H), 3.07 (dd, J = 8.8, 6.6 Hz,
    1681, 1H), 2.29 (s, 3H), 2.11 (h, J = 6.7 Hz,
    1611, 1H), 1.49 (d, J = 7.1 Hz, 3H), 1.41 (s,
    1500, 9H), 1.05 (d, J = 6.3 Hz, 3H), 0.86 (d, J = 6.8 Hz,
    1311, 3H), 0.77 (d, J = 6.8 Hz, 3H).
    1274, 13C NMR (126 MHz, CDCl3) δ 176.05,
    1208, 172.39, 162.25, 160.89 (d, J = 244.3 Hz),
    1154, 159.38, 146.49, 142.15, 139.92,
    1108, 137.85, 133.67, 116.93 (d, J = 20.4 Hz),
    1060, 819, 112.29 (d, J = 20.6 Hz), 109.49, 73.65,
    730 cm−1 56.29, 53.43, 49.29, 48.13, 39.15, 29.67,
    27.17, 20.92, 18.92, 18.66, 17.87.
    375 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 8.49 (s,
    film) 3382, calcd for C27H37N2O6, 1H), 8.33 (d, J = 5.4 Hz, 1H),
    2970, 485.2646; found, 485.2642 7.18-7.06 (m, 4H), 6.99 (d, J = 5.5 Hz, 1H),
    2875, 5.39 (dq, J = 9.2, 6.2 Hz, 1H),
    1762, 4.76-4.66 (m, 1H), 3.89 (s, 3H), 3.13 (dd, J = 9.2,
    1733, 6.2 Hz, 1H), 2.95 (p, J = 7.0 Hz,
    1678, 1H), 2.32 (s, 3H), 2.21-2.10 (m, 1H),
    1504, 1.50 (d, J = 7.1 Hz, 3H), 1.36 (dd, J = 7.0,
    1208, 730 cm−1 0.9 Hz, 6H), 1.05 (d, J = 6.2 Hz,
    3H), 0.86 (d, J = 6.8 Hz, 3H), 0.80 (d, J = 6.8 Hz,
    3H).
    376 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 8.59 (s,
    film) calcd for C27H37N2O7, 1H), 8.33 (d, J = 5.5 Hz, 1H), 7.14 (td, J = 7.8,
    3383, 2974, 501.2601; found, 501.2515 1.7 Hz, 1H), 7.06 (dd, J = 7.5, 1.7 Hz,
    1771, 1H), 7.00 (d, J = 5.5 Hz, 1H),
    1732, 6.94-6.73 (m, 2H), 5.45 (s, 1H),
    1676, 4.86-4.64 (m, 1H), 4.54 (hept, J = 6.0 Hz, 1H),
    1506, 3.90 (s, 3H), 3.44 (s, 1H), 2.40 (s, 3H),
    1193, 2.14 (dq, J = 13.3, 6.4 Hz, 1H), 1.52 (d,
    1174, 751 cm−1 J = 7.1 Hz, 3H), 1.33 (d, J = 6.0 Hz,
    3H), 1.31 (d, J = 6.0 Hz, 3H), 1.05 (d, J = 6.1 Hz,
    3H), 0.83 (d, J = 6.8 Hz, 3H),
    0.76 (d, J = 6.8 Hz, 3H).
    377 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 8.56 (s,
    film) 3381, calcd for C27H37N2O7, 1H), 8.34 (d, J = 5.4 Hz, 1H), 7.00 (d, J = 5.5 Hz,
    2975, 501.2601; found, 501.2493 1H), 6.99-6.96 (m, 2H),
    1771, 6.81-6.76 (m, 2H), 5.36 (dq, J = 8.6, 6.2 Hz,
    1732, 1H), 4.75-4.62 (m, 1H),
    1676, 4.51 (hept, J = 6.0 Hz, 1H), 3.91 (s, 3H),
    1507, 2.64 (dd, J = 8.8, 6.3 Hz, 1H), 2.40 (s,
    1175, 730 cm−1 3H), 2.12-2.02 (m, 1H), 1.50 (d, J = 7.1 Hz,
    3H), 1.33 (d, J = 6.0 Hz, 6H),
    1.08 (d, J = 6.3 Hz, 3H), 0.84 (d, J = 6.8 Hz,
    3H), 0.75 (d, J = 6.7 Hz, 3H).
    378 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 8.33 (d, J = 7.8 Hz,
    film) 3381, calcd for C26H32F3N2O8, 1H), 8.28 (d, J = 5.3 Hz, 1H),
    2964, 557.2107; found, 557.2107 7.15-7.04 (m, 4H), 6.96 (d, J = 5.4 Hz,
    1737, 1H), 5.75 (s, 2H), 5.40 (dq, J = 8.3, 6.3 Hz,
    1677, 1H), 4.70 (p, J = 7.3 Hz, 1H),
    1506, 3.92 (s, 3H), 2.73 (dd, J = 8.3, 6.9 Hz, 1H),
    1256, 2.15-2.04 (m, 4H), 1.51 (d, J = 7.2 Hz,
    1201, 3H), 1.09 (d, J = 6.3 Hz, 3H), 0.88 (d, J = 6.7 Hz,
    1160, 1004 cm−1 3H), 0.74 (d, J = 6.8 Hz, 3H).
    379 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 8.38 (d, J = 7.8 Hz,
    film) 3382, calcd for C28H39N2O8, 1H), 8.29 (d, J = 5.3 Hz, 1H),
    2976, 531.2701; found, 531.2688 6.98 (d, J = 8.7 Hz, 2H), 6.95 (d, J = 5.4 Hz,
    1755, 1H), 6.79 (d, J = 8.6 Hz, 2H),
    1733, 5.80-5.71 (m, 2H), 5.37 (dq, J = 8.8, 6.3 Hz,
    1675, 1H), 4.80-4.64 (m, 1H), 4.51 (hept, J = 6.1 Hz,
    1506, 1H), 3.91 (s, 3H), 2.65 (dd, J = 8.8,
    1236, 6.3 Hz, 1H), 2.15-2.00 (m, 4H),
    1201, 955, 1.52 (d, J = 7.2 Hz, 3H), 1.33 (d, J = 6.1 Hz,
    829 cm−1 6H), 1.08 (d, J = 6.3 Hz, 3H),
    0.84 (d, J = 6.7 Hz, 3H), 0.75 (d, J = 6.8 Hz,
    3H).
    380 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 8.54 (s,
    film) 3380, calcd for C25H31N2O8, 1H), 8.34 (d, J = 5.5 Hz, 1H), 7.01 (d, J = 5.5 Hz,
    2961, 487.2080; found, 487.2065 1H), 6.70 (d, J = 7.9 Hz, 1H),
    1770, 6.60 (d, J = 1.6 Hz, 1H), 6.54 (dd, J = 8.0,
    1731, 1.7 Hz, 1H), 5.93 (q, J = 1.5 Hz,
    1675, 2H), 5.33 (dq, J = 8.6, 6.3 Hz, 1H),
    1504, 4.75-4.63 (m, 1H), 3.91 (s, 3H), 2.63 (dd, J = 8.5,
    1488, 6.6 Hz, 1H), 2.40 (s, 3H),
    1192, 2.09-2.00 (m, 1H), 1.49 (d, J = 7.2 Hz, 3H),
    1175, 1.09 (d, J = 6.3 Hz, 3H), 0.86 (d, J = 6.7 Hz,
    1037, 730 cm−1 3H), 0.76 (d, J = 6.8 Hz, 3H).
    381 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 8.49 (d, J = 7.5 Hz,
    film) 3385, calcd for C25H30F3N2O7, 1H), 8.33 (d, J = 5.5 Hz, 1H),
    2964, 527.2000; found, 527.2000 7.16-7.05 (m, 4H), 7.01 (d, J = 5.5 Hz,
    1772, 1H), 5.39 (dq, J = 8.2, 6.3 Hz, 1H),
    1734, 4.74-4.60 (m, 1H), 3.91 (s, 3H), 2.72 (dd, J = 8.1,
    1677, 7.0 Hz, 1H), 2.40 (s, 3H),
    1507, 2.15-2.02 (m, 1H), 1.48 (d, J = 7.2 Hz, 3H),
    1258, 1.08 (d, J = 6.3 Hz, 3H), 0.88 (d, J = 6.7 Hz,
    1199, 1162 cm−1 3H), 0.74 (d, J = 6.8 Hz, 3H).
    382 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (300 MHz, CDCl3) δ 8.38 (d, J = 7.7 Hz,
    film) 3378, calcd for C26H35N2O8, 1H), 8.29 (d, J = 5.4 Hz, 1H),
    2960, 503.2388; found, 503.2356 7.05-6.98 (m, 2H), 6.96 (d, J = 5.4 Hz,
    1733, 1H), 6.87-6.75 (m, 2H), 5.75 (s, 2H),
    1675, 5.45-5.30 (m, 1H), 4.80-4.60 (m,
    1511, 1H), 3.92 (s, 3H), 3.79 (s, 3H), 2.67 (dd,
    1201, J = 8.8, 6.3 Hz, 1H), 2.19-1.98 (m,
    1038, 968, 4H), 1.53 (d, J = 7.2 Hz, 3H), 1.09 (d, J = 6.3 Hz,
    829 cm−1 3H), 0.85 (d, J = 6.8 Hz, 3H),
    0.75 (d, J = 6.8 Hz, 3H).
    383 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (500 MHz, CDCl3) δ 8.55 (s,
    film) 3378, calcd for C25H33N2O7, 1H), 8.34 (d, J = 5.4 Hz, 1H),
    2960, 473.2282; found, 473.2259 7.07-6.95 (m, 3H), 6.88-6.74 (m, 2H),
    1770, 5.37 (dq, J = 8.7, 6.3 Hz, 1H),
    1732, 4.75-4.61 (m, 1H), 3.91 (s, 3H), 3.79 (s, 3H),
    1675, 2.66 (dd, J = 8.7, 6.4 Hz, 1H), 2.40 (s, 3H),
    1511, 2.08 (dq, J = 13.4, 6.7 Hz, 1H), 1.50 (d,
    1176, J = 7.2 Hz, 3H), 1.07 (d, J = 6.2 Hz,
    1035, 730 cm−1 3H), 0.84 (d, J = 6.8 Hz, 3H), 0.75 (d, J = 6.8 Hz,
    3H).
    384 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.56 (s,
    film) 2963, calcd for C26H35N2O6, 1H), 8.34 (dd, J = 5.4, 2.0 Hz, 1H),
    1772, 471.2416; found, 471.2487 7.19-7.06 (m, 4H), 7.01 (d, J = 5.5 Hz, 1H),
    1678, 5.40 (dq, J = 12.1, 6.6 Hz, 1H), 4.72 (p,
    1507, J = 7.3 Hz, 1H), 3.91 (s, 3H),
    1200, 733 cm−1 3.39-3.05 (m, 1H), 2.40 (d, J = 1.7 Hz, 3H),
    2.33 (d, J = 5.7 Hz, 3H), 1.90 (s, 1H),
    1.55-1.18 (m, 5H), 1.04 (d, J = 6.3 Hz,
    3H), 1.01-0.71 (m, 6H).
    385 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.53 (s,
    film) 2961, calcd for C27H37N2O6, 1H), 8.33 (d, J = 5.4 Hz, 1H),
    1771, 485.2572; found, 485.2643 7.22-7.05 (m, 4H), 7.01 (d, J = 5.5 Hz, 1H),
    1732, 5.43 (dq, J = 8.3, 6.2 Hz, 1H), 4.69 (p, J = 7.3 Hz,
    1677, 1H), 3.91 (s, 3H), 3.31 (t, J = 7.6 Hz,
    1506, 1H), 2.39 (s, 3H), 2.31 (s, 3H),
    1198, 1.63 (d, J = 6.2 Hz, 1H), 1.54-1.17 (m,
    1175, 731 cm−1 6H), 1.17-0.85 (m, 7H), 0.77 (t, J = 7.3 Hz,
    3H).
    386 IR (thin HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.49 (s,
    film) 2970, calcd for C28H39N2O6, 1H), 8.33 (dd, J = 5.4, 2.1 Hz, 1H),
    1736, 499.2729; found, 499.2729 7.22-7.05 (m, 4H), 6.99 (d, J = 5.5 Hz, 1H),
    1506, 5.39 (dq, J = 9.6, 6.7, 6.2 Hz, 1H),
    1210, 733 cm−1 4.72 (p, J = 7.3 Hz, 1H), 3.89 (s, 3H),
    3.30-3.12 (m, 1H), 2.95 (tt, J = 7.0, 6.0 Hz,
    1H), 2.33 (s, 3H), 1.88 (d, J = 13.8 Hz,
    1H), 1.43 (dd, J = 59.5, 7.0 Hz, 11H),
    1.04 (d, J = 6.3 Hz, 3H), 0.83 (qd, J = 15.1,
    13.7, 7.1 Hz, 6H).
    387 IR (thin
    film) 2964, HRMS-ESI (m/z) [M + H]+ 1H NMR (400 MHz, CDCl3) δ 8.46 (s,
    1681, calcd for C29H41N2O6, 1H), 8.32 (d, J = 5.5 Hz, 1H),
    1505, 513.2883; found, 513.2953 7.17-7.03 (m, 5H), 6.99 (d, J = 5.5 Hz, 1H),
    1211, 1111 cm−1 5.50-5.36 (m, 1H), 4.69 (p, J = 7.3 Hz,
    1H), 3.89 (s, 3H), 3.31 (t, J = 7.6 Hz,
    1H), 2.94 (p, J = 7.0 Hz, 1H), 2.31 (s,
    3H), 1.61 (s, 1H), 1.51-0.94 (m, 15H),
    0.90 (t, J = 7.4 Hz, 3H), 0.77 (t, J = 7.3 Hz,
    3H).
    388 ESIMS m/z 497 ([M + H]+) 1H NMR (400 MHz, CDCl3) δ 8.53 (d, J = 8.0 Hz,
    1H), 8.43-8.20 (m, 1H),
    7.01 (d, J = 5.5 Hz, 1H), 6.62 (t, J = 9.0 Hz,
    2H), 5.65-5.47 (m, 1H), 4.68 (dq, J = 8.3,
    7.2 Hz, 1H), 3.91 (s, 3H), 3.19 (t, J = 7.7 Hz,
    1H), 2.40 (s, 3H),
    2.31-2.13 (m, 1H), 1.49 (d, J = 7.2 Hz, 3H),
    1.13 (dt, J = 6.4, 1.2 Hz, 3H), 0.96 (dd, J = 6.7,
    3.5 Hz, 3H), 0.77 (dt, J = 6.7, 1.3 Hz,
    3H).
    19F NMR (376 MHz, CDCl3) δ
    −105.79 (d, J = 1613.0 Hz), −110.18 (t, J = 6.4 Hz).
    389 ESIMS m/z 495 ([M + H]+) 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J = 6.7 Hz,
    1H), 8.33 (d, J = 5.4 Hz, 1H),
    7.13-6.92 (m, 4H), 5.42 (dqd, J = 7.6,
    6.4, 1.2 Hz, 1H), 4.75-4.51 (m, 1H),
    3.91 (s, 3H), 3.13 (t, J = 7.7 Hz, 1H),
    2.40 (s, 3H), 2.20-2.01 (m, 1H),
    1.49 (d, J = 7.2 Hz, 3H), 1.10 (d, J = 6.3 Hz,
    3H), 0.93 (d, J = 6.5 Hz, 3H), 0.75 (d, J = 6.7 Hz,
    3H).
    19F NMR (376 MHz, CDCl3) δ −112.27.
    390 ESIMS m/z 495 ([M + H]+) 1H NMR (400 MHz, CDCl3) δ
    8.40-8.29 (m, 1H), 7.25-7.08 (m, 3H),
    7.06-6.90 (m, 2H), 5.75-5.47 (m, 1H),
    4.89-4.39 (m, 1H), 3.91 (s, 3H),
    3.62-3.47 (m, 1H), 2.40 (s, 3H),
    2.33-2.17 (m, 1H), 1.47 (dd, J = 38.1, 7.2 Hz, 3H),
    1.14-1.06 (m, 3H), 0.99 (dd, J = 6.8,
    5.6 Hz, 3H), 0.78 (dt, J = 6.9, 2.4 Hz,
    3H).
    19F NMR (376 MHz, CDCl3) δ
    −105.07 (d, J = 18.2 Hz).
    391 ESIMS m/z 457 ([M + H]+) 1H NMR (400 MHz, CDCl3) δ 8.57 (d, J = 8.1 Hz,
    1H), 8.34 (d, J = 5.4 Hz, 1H),
    7.22-7.10 (m, 1H), 7.09-6.98 (m,
    2H), 6.89 (d, J = 6.0 Hz, 2H),
    5.47-5.24 (m, 1H), 4.62 (dp, J = 51.8, 7.2 Hz,
    1H), 3.91 (s, 3H), 2.67 (dt, J = 8.7, 6.9 Hz,
    1H), 2.40 (s, 3H), 2.33 (d, J = 5.2 Hz,
    3H), 2.10 (dt, J = 13.6, 6.8 Hz, 1H),
    1.46 (dd, J = 37.4, 7.2 Hz, 3H), 1.09 (d,
    J = 6.3 Hz, 3H), 0.86 (t, J = 7.0 Hz,
    3H), 0.76 (d, J = 6.7 Hz, 3H).
    392 ESIMS m/z 479 ([M + H]+) 1H NMR (400 MHz, CDCl3) δ 8.53 (d, J = 7.8 Hz,
    1H), 8.33 (d, J = 5.5 Hz, 1H),
    7.07-6.78 (m, 4H), 5.45-5.34 (m,
    1H), 4.76-4.62 (m, 1H), 3.91 (s, 3H),
    3.22-3.08 (m, 1H), 2.40 (s, 3H),
    2.09 (dt, J = 13.5, 6.8 Hz, 1H), 1.49 (d, J = 7.1 Hz,
    3H), 1.13 (d, J = 6.3 Hz, 3H),
    0.95 (t, J = 5.2 Hz, 3H), 0.77 (d, J = 6.7 Hz,
    3H).
    19F NMR (376 MHz, CDCl3) δ −119.17,
    −120.97.
    *Cmpd. No.—Compound Number
  • TABLE 3
    Biological Testing Rating Scale
    Rating Table for Fungal Pathogens
    % Control Rating
    >80 A
    ≤80 B
    Not Tested C
    ≤0 D
  • TABLE 4
    Biological Activity - PUCCRT and SEPTTR Disease
    Control in High and Low Volume Applications
    HV activity at 100 ppm LV activity at 121.5 g/H
    Cmpd. PUCCRT* SEPTTR* PUCCRT* SEPTTR*
    No. 1DP* 3DC* 1DP* 3DC* 1DP* 3DC* 1DP* 3DC*
    105 A D B B C C C C
    106 B D D D C C C C
    112 A A A A C C C C
    113 A A A A C C C C
    114 A B A B C C C C
    115 D D B D C C C C
    116 A D D B C C C C
    117 A D A A C C C C
    118 A B B B C C C C
    119 A B A A C C C C
    120 A D D B C C C C
    121 A B B A C C C C
    122 A A A B C C C C
    123 A A A A C C C C
    124 A A A A C C C C
    125 A B A A C C C C
    126 A B A A C C C C
    127 A A A B C C C C
    128 B D D B C C C C
    129 A D A B C C C C
    130 A B B B C C C C
    131 A A B B C C C C
    132 A A A B C C C C
    133 A B A B C C C C
    134 B B B B C C C C
    135 B A B A C C C C
    136 A A A A C C C C
    138 A A D D C C C C
    139 A B A D C C C C
    140 A A D B C C C C
    141 B A D A C C C C
    142 A A D B C C C C
    143 A A A B C C C C
    144 A A B A C C C C
    145 A A B A C C C C
    146 A A B A C C C C
    147 A A D B C C C C
    148 B A D B C C C C
    149 B B B A C C C C
    160 C C C C A B B A
    161 C C C C A B B A
    162 C C C C A A B A
    163 C C C C A B B A
    164 C C C C A A A A
    165 C C C C A A A A
    166 C C C C A A B A
    167 C C C C A A A A
    168 C C C C A A B B
    169 C C C C A A B A
    170 C C C C A A A A
    171 C C C C A A A A
    172 C C C C A A A A
    173 C C C C A B A A
    174 C C C C A A A A
    175 C C C C A A A A
    176 C C C C A B A A
    177 C C C C B D B D
    178 C C C C A B D B
    179 C C C C A D A A
    180 C C C C A B B B
    181 C C C C B B B A
    182 C C C C A B B A
    183 C C C C B B B A
    184 C C C C A A A A
    185 C C C C A B A A
    186 C C C C A A A A
    187 C C C C A B A A
    188 C C C C A B A A
    189 C C C C A B A A
    190 C C C C D D D B
    191 C C C C D B B B
    192 C C C C A B D A
    193 C C C C B B D B
    194 C C C C B D B A
    195 C C C C A A A A
    196 C C C C A A A A
    197 C C C C A A A A
    198 C C C C B D B B
    199 C C C C B D A B
    200 C C C C B B D B
    201 C C C C A B B B
    202 C C C C A D B B
    203 C C C C B B B B
    204 C C C C A B D B
    205 C C C C A D B B
    206 C C C C B D B B
    207 C C C C A B B A
    208 C C C C B B D B
    209 C C C C D D B B
    210 C C C C B D A B
    211 B D B B D D B D
    212 A B B A B D D D
    213 C C C C B D B B
    214 C C C C A A A A
    215 C C C C A A A A
    216 C C C C A A A A
    217 C C C C A A A A
    218 C C C C A B A B
    219 C C C C A A B A
    220 C C C C A A A A
    221 C C C C B B B A
    222 C C C C A B A A
    223 C C C C B B A A
    224 C C C C B B B D
    225 C C C C A B A A
    226 C C C C B B B B
    227 C C C C A A A A
    228 C C C C A B A B
    229 C C C C A B A A
    230 C C C C A A A B
    231 C C C C B B B B
    232 C C C C A A A B
    233 C C C C B B A A
    234 C C C C A B B B
    235 C C C C A B B B
    236 C C C C B B B B
    237 C C C C A A B B
    238 C C C C B B B B
    239 C C C C A A A B
    240 C C C C A A B A
    241 C C C C B B D A
    242 C C C C A A A A
    243 C C C C A B D B
    244 C C C C A A A B
    245 C C C C A A B C
    246 C C C C A A A C
    247 C C C C A A B C
    248 C C C C B B B C
    249 C C C C A A B C
    250 C C C C A A A C
    251 C C C C A A B C
    252 C C C C A B B C
    253 C C C C A A B C
    254 C C C C A A A C
    255 C C C C A A B C
    256 C C C C A A A C
    257 C C C C A A A C
    258 C C C C A B B C
    259 C C C C A A B C
    260 C C C C A A A C
    261 C C C C A B B B
    262 C C C C A B B B
    263 C C C C A A B A
    264 C C C C A A B B
    317 A A B B C C C C
    318 A A B B C C C C
    319 B B B B C C C C
    320 B B B B C C C C
    321 A A B B C C C C
    322 A A B B C C C C
    323 A A B A C C C C
    324 A A B B C C C C
    325 A A A B C C C C
    326 A A B A C C C C
    327 A A B A C C C C
    328 A A A A C C C C
    329 A A B B C C C C
    330 A A B B C C C C
    331 B B B B C C C C
    332 B B B B C C C C
    333 A B B B C C C C
    334 A A B D C C C C
    335 A A A B C C C C
    336 A B B B C C C C
    337 A A B D C C C C
    338 A A B B C C C C
    339 C C C C
    340 C C C C C C C C
    341 A A A A C C C C
    342 C C C C C C C C
    343 A A A A C C C C
    344 C C C C C C C C
    345 C C C C C C C C
    346 C C C C A A B B
    347 C C C C A B A A
    348 C C C C A B B B
    349 C C C C A B B B
    350 C C C C A A B B
    351 C C C C A B A B
    352 C C C C A B B B
    353 C C C C B B B B
    354 C C C C A B A A
    355 C C C C A B A A
    356 C C C C A B A A
    357 C C C C A A A A
    358 C C C C A B B B
    359 C C C C A A B A
    360 C C C C A A B A
    361 C C C C A B B B
    362 C C C C A A A A
    363 C C C C A A B B
    364 C C C C A B B B
    365 C C C C A A A A
    366 C C C C A A B B
    367 C C C C A A A B
    368 C C C C B D B B
    369 C C C C A B B B
    370 C C C C B D B B
    371 C C C C C C C C
    372 C C C C C C C C
    373 C C C C A B A A
    374 C C C C A B A A
    375 C C C C A A B A
    376 C C C C A B B B
    377 C C C C A B B B
    378 C C C C A A A A
    379 C C C C A B B B
    380 C C C C A A B B
    381 C C C C A B A A
    382 C C C C A A B A
    383 C C C C A B B B
    384 C C C C A A A A
    385 C C C C A A A A
    386 C C C C A A B A
    387 C C C C A B B A
    388 C C C C A A A A
    389 C C C C A A A A
    390 C C C C A A A A
    391 C C C C A B B B
    392 C C C C A A B A
    *Cmpd. No.—Compound Number
    *PUCCRT—Wheat Brown Rust (Puccinia triticina)
    *SEPTTR—Wheat Leaf Blotch (Zymoseptoria tritici)
    *1DP—1 Day Protectant
    *3DC—3 Day Curative
    *ppm—Parts Per Million
  • TABLE 5
    Biological Activity - High Volume Disease Control at 25 ppm
    PHAKPA*
    Cmpd. No.* 1DP* 3DC*
    162 A B
    164 A B
    177 A D
    178 D B
    179 B B
    180 B B
    181 D B
    182 B B
    183 B B
    184 A B
    185 A B
    186 A A
    187 A B
    188 A A
    189 A B
    190 B B
    191 B D
    192 A B
    193 B B
    194 B B
    195 A B
    196 A B
    197 A A
    198 B B
    199 B B
    200 B D
    201 B D
    202 B D
    203 A D
    204 B D
    205 B D
    206 B D
    207 A D
    208 B D
    209 B D
    210 B B
    211 B D
    212 B B
    213 D D
    214 A B
    215 A A
    216 A A
    217 A A
    218 B B
    219 A A
    220 A A
    221 B B
    222 A B
    223 B D
    224 B D
    225 A B
    226 B D
    227 A B
    228 A B
    229 A B
    230 A B
    231 A B
    232 A A
    233 B B
    234 A D
    235 A B
    236 A B
    237 A A
    238 B B
    239 A A
    240 A B
    241 B B
    242 A B
    243 A B
    244 A B
    346 A B
    347 A A
    348 A B
    349 A B
    350 A A
    351 A B
    352 A B
    353 A B
    354 A A
    355 A A
    356 A A
    357 A A
    358 A B
    359 A A
    360 A A
    361 A A
    362 A A
    363 A A
    364 A A
    365 A A
    366 A B
    367 A A
    368 B B
    369 B B
    370 B B
    371 A A
    372 A A
    373 A A
    374 A B
    375 A A
    376 A B
    377 B B
    378 B B
    379 B B
    380 B B
    381 B B
    382 A B
    383 A B
    *Cmpd. No.—Compound Number
    *PHAKPA—Asian Soybean Rust (Phakopsora pachyrhizi)
    *1DP—1 Day Protectant
    *3DC—3 Day Curative
  • TABLE 6
    Biological Activity - Disease Control in 1DP* test at 100 ppm
    Cmpd. No.* ALTESO* CERCBE* COLLLA* LEPTNO*
    186 A A D A
    187 B A A B
    216 B A B A
    217 B A D A
    218 D A B A
    219 B A B A
    220 B A B A
    354 B A A A
    355 A A A A
    356 A A B A
    357 B A A A
    359 B A A A
    363 D A B B
    364 B A A B
    371 B A A A
    372 A A A A
    373 B A A A
    374 B A B A
    375 B A A A
    *Cmpd. No.—Compound Number
    *ALTESO—Tomato Early Blight (Alternaria solani)
    *CERCBE—Leaf Spot of Sugar Beets (Cercospora beticola)
    *COLLLA—Cucumber Anthracnose (Glomerella lagenarium; Anamorph: Colletotricum lagenarium)
    *LEPTNO—Wheat Glume Blotch (Parastagonospora nodorum)
  • TABLE 7
    Biological Activity - Disease Control in 1DP* Test at 100 ppm
    Cmpd. No.* PSPECU* PYRIOR* RHYNSE* UNCINE*
    186 B A B A
    187 D A A A
    216 B A B A
    217 D A B A
    218 D A B A
    219 B A B A
    220 D A B A
    354 A B B A
    355 B B B A
    356 B B B A
    357 B B B A
    359 B A A A
    363 D A B A
    364 B A B A
    371 B B B A
    372 A B B A
    373 B B B A
    374 B B B A
    375 B A B A
    *Cmpd. No.—Compound Number
    *PSPECU—Cucumber Downy Midlew (Pseudoperonospora cubensis)
    *PYRIOR—Rice Blast (Magnaporthe grisea; Anamorph: Pyricularia oryzae)
    *RHYNSE—Barley Scald (Rhyncosporium secalis)
    *UNCINE—Grape Powdery Mildew (Uncinula necator)
    *1DP—1 Day Protectant

Claims (30)

What is claimed is:
1. A compound of Formula I
Figure US20180186742A1-20180705-C00453
wherein:
X is hydrogen or C(O)R5;
Y is hydrogen, C(O)R5, or Q;
Q is
Figure US20180186742A1-20180705-C00454
wherein Z is N or N+→O− and W is O or S;
R1 is hydrogen or alkyl, substituted with 0, 1 or multiple R8;
R2 is methyl;
R3 and R3′ are independently chosen from C2-C6 alkyl, C3-C6 cycloalkyl, aryl or heteroaryl, each optionally substituted with 0, 1 or multiple R8; Alternatively, R3 and R3′ may be taken together to form a 3-6 membered saturated or partially saturated carbocycle or heterocycle, optionally substituted with 0, 1 or multiple R8;
R4 is chosen from aryl or heteroaryl, each optionally substituted with 0, 1 or multiple R8;
R5 is chosen from alkoxy or benzyloxy, each optionally substituted with 0, 1, or multiple R8;
R6 is chosen from hydrogen, alkoxy, or halo, each optionally substituted with 0, 1, or multiple R8;
R7 is chosen from hydrogen, —C(O)R9, or —CH2OC(O)R9;
R8 is chosen from hydrogen, alkyl, aryl, acyl, halo, alkenyl, alkynyl, alkoxy, cyano, or heterocyclyl, each optionally substituted with 0, 1, or multiple R10,
R9 is chosen from alkyl, alkoxy, or aryl, each optionally substituted with 0, 1, or multiple R8;
R10 is chosen from hydrogen, alkyl, aryl, acyl, halo, alkenyl, alkoxy, or heterocyclyl; and
R11 is chosen from hydrogen or alkyl, each substituted with 0, 1 or multiple R8.
2. The compound according to claim 1, wherein X and Y are hydrogen.
3. The compound according to claim 2, wherein R1 and R11 are independently chosen from hydrogen or alkyl.
4. The compound according to claim 2, wherein R3 and R3′ are independently chosen from C2-C6 alkyl or taken together to form a 3-6 membered saturated carbocycle, each optionally substituted with 0, 1 or multiple R8.
5. The compound according to claim 2, wherein R4 is aryl, optionally substituted with 0, 1 or multiple R8.
6. The compound according to claim 2, wherein R1 and R11 are independently chosen from hydrogen or alkyl, R3 and R3′ are independently chosen from C2-C6 alkyl or taken together to form a 3-6 membered saturated carbocycle, each optionally substituted with 0, 1 or multiple R8, and R4 is aryl, optionally substituted with 0, 1 or multiple R8.
7. The compound according to claim 1, wherein X is C(O)R5 and Y is hydrogen.
8. The compound according to claim 7, wherein R1 and R11 are independently chosen from hydrogen or alkyl.
9. The compound according to claim 7, wherein R3 and R3′ are independently chosen from C2-C6 alkyl or taken together to form a 3-6 membered saturated carbocycle, each optionally substituted with 0, 1 or multiple R8.
10. The compound according to claim 7, wherein R4 is aryl, optionally substituted with 0, 1 or multiple R8.
11. The compound according to claim 7, wherein R1 and R11 are independently chosen from hydrogen or alkyl, R3 and R3′ are independently chosen from C2-C6 alkyl or taken together to form a 3-6 membered saturated carbocycle, each optionally substituted with 0, 1 or multiple R8, and R4 is aryl, optionally substituted with 0, 1 or multiple R8.
12. The compound according to claim 1, wherein X is hydrogen and Y is Q.
13. The compound according to claim 12 wherein Z is N.
14. The compound according to claim 13 wherein W is O.
15. The compound according to claim 14, wherein R6 is alkoxy.
16. The compound according to claim 15, wherein R7 is hydrogen.
17. The compound according to claim 16, wherein R1 and R11 are independently chosen from hydrogen or alkyl.
18. The compound according to claim 16, wherein R3 and R3′ are independently chosen from C2-C6 alkyl or taken together to form a 3-6 membered saturated carbocycle, each optionally substituted with 0, 1 or multiple R8.
19. The compound according to claim 16, wherein R4 is aryl, optionally substituted with 0, 1 or multiple R8.
20. The compound according to claim 16, wherein R1 and R11 are independently chosen from hydrogen or alkyl, R3 and R3′ are independently chosen from C2-C6 alkyl or taken together to form a 3-6 membered saturated carbocycle, each optionally substituted with 0, 1 or multiple R8, and R4 is aryl, optionally substituted with 0, 1 or multiple R8.
21. The compound according to claim 15, wherein R7 is chosen from —C(O)R9, or —CH2OC(O)R9.
22. The compound according to claim 21, wherein R1 and R11 are independently chosen from hydrogen or alkyl.
23. The compound according to claim 21, wherein R3 and R3′ are independently chosen from C2-C6 alkyl or taken together to form a 3-6 membered saturated carbocycle, each optionally substituted with 0, 1 or multiple R8.
24. The compound according to claim 21, wherein R4 is aryl, optionally substituted with 0, 1 or multiple R8.
25. The compound according to claim 21, wherein R1 and R11 are independently chosen from hydrogen or alkyl, R3 and R3′ are independently chosen from C2-C6 alkyl or taken together to form a 3-6 membered saturated carbocycle, each optionally substituted with 0, 1 or multiple R8, and R4 is aryl, optionally substituted with 0, 1 or multiple R8.
26. A composition for the control of a fungal pathogen including mixtures of at least one of the compounds of claim 1 and another pesticide including fungicides, insecticides, nematocides, miticides, arthropodicides, bactericides and combinations thereof.
27. A composition for the control of a fungal pathogen including mixtures of at least one of the compounds of claim 16 and another pesticide including fungicides, insecticides, nematocides, miticides, arthropodicides, bactericides and combinations thereof.
28. A composition for the control of a fungal pathogen including mixtures of at least one of the compounds of claim 21 and another pesticide including fungicides, insecticides, nematocides, miticides, arthropodicides, bactericides and combinations thereof.
29. A method for the control and prevention of fungal attack on a plant, the method including the step of:
applying a fungicidally effective amount of at least one of the compounds of claim 1 to at least one of the plant, an area adjacent to the plant, soil adapted to support growth of the plant, a root of the plant, and foliage of the plant.
30. A method for the control and prevention of fungal attack on a plant, the method including the step of:
applying a fungicidally effective amount of at least one of the compounds of any of claim 26 to at least one of the plant, an area adjacent to the plant, soil adapted to support growth of the plant, a root of the plant, and foliage of the plant.
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