WO2015031725A1 - Imidation d'arènes catalysée par des métaux de transition - Google Patents

Imidation d'arènes catalysée par des métaux de transition Download PDF

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WO2015031725A1
WO2015031725A1 PCT/US2014/053357 US2014053357W WO2015031725A1 WO 2015031725 A1 WO2015031725 A1 WO 2015031725A1 US 2014053357 W US2014053357 W US 2014053357W WO 2015031725 A1 WO2015031725 A1 WO 2015031725A1
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substituted
unsubstituted
instance
certain embodiments
heteroaryl
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Ming-Yu NGAI
Gregory Bagrad BOURSALIAN
Eric Andrew MCNEILL
Tobias Ritter
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President And Fellows Of Harvard College
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
    • C07D207/48—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
    • C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members 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
    • 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
    • C07D213/72—Nitrogen atoms
    • C07D213/76—Nitrogen atoms to which a second hetero atom is attached
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
    • C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
    • C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
    • C07D221/04—Ortho- or peri-condensed ring systems
    • C07D221/06—Ring systems of three rings
    • C07D221/10—Aza-phenanthrenes
    • C—CHEMISTRY; METALLURGY
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur 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
    • C07D333/30—Hetero atoms other than halogen
    • C07D333/36—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
    • C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
    • C07D333/62—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes 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 carbon atoms of the hetero ring
    • C07D333/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
    • C07D333/70—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 2
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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
    • C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
    • C07F15/006—Palladium compounds
    • C07F15/0066—Palladium compounds without a metal-carbon linkage
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    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
    • C—CHEMISTRY; METALLURGY
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    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/40—Esters thereof
    • C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/4021—Esters of aromatic acids (P-C aromatic linkage)
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    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/05—Isotopically modified compounds, e.g. labelled

Definitions

  • the present invention provides novel transition metal complexes (e.g., complexes of any one of Formulae (CI) to (C25)) that include an amine-N-oxide motif.
  • the invention also provides methods of using the inventive transition metal complexes in preparing N-aryl or N-heteroaryl sulfonimides (e.g., compounds of Formula (I)) and aryl or heteroaryl amines (e.g., compounds of Formula (II)).
  • the inventive methods involve imidation of arenes and heteroarenes (e.g., compounds of Formula (A)) using an imidating agent (e.g.
  • a compound of Formula (B) such as N-fluorobenzenesulfonimide (NFBS or NFSI)) in the presence of a single-electron reductant (e.g., an Ag(I) or Ru(II) salt).
  • NFBS N-fluorobenzenesulfonimide
  • a single-electron reductant e.g., an Ag(I) or Ru(II) salt
  • the present invention provides methods for preparing an N-aryl or N-heteroaryl sulfonimide (e.g. , a compound of Formula (I), or a salt thereof).
  • the method typically involves contacting a compound of Formula (A), or a salt thereof, with a compound of Formula (B), or a salt thereof, in the presence of a transition metal complex of any one of Formula (CI) to (C25) and a single-electron reductant to provide the compound of Formula (I), or a salt thereof.
  • the compound of Formula (B) is N- fluorobenzenesulfonimide (NFBS or NFSI).
  • the transition metal complex is of Formula (CI).
  • the transition metal complex is of Formula (C2).
  • the transition metal complex is of Formula (C3).
  • the transition metal complex is of Formula (C4).
  • the transition metal complex is of any one of Formulae (C5) to (C25).
  • the single-electron reductant is an Ag(I) or Ru(II) salt.
  • a transition metal complex of Formula (CI) for use in the imidation reactions described herein is prepared by contacting a ligand of Formula (Dl), or a salt thereof, with a transition metal salt of Formula (E) to provide the complex of Formula (CI):
  • a transition metal complex of Formula (C2) is prepared by contacting a ligand of Formula (D2), or a salt thereof, with a transition metal salt of Formula (E) to provide the complex of Formula (C2):
  • the inventive methods of further include the step of deprotecting a compound of Formula (I), or a salt thereof, with a reductant (e.g. , a mixture of an alkaline earth metal and an alcohol; or a mixture of zinc and an acid), a strong acid, or a nucleophile (e.g. , an alkyl lithium, phenyl lithium, or a Grignard reagent), to provide a compound of Formula (II), or a salt thereof.
  • a reductant e.g. , a mixture of an alkaline earth metal and an alcohol; or a mixture of zinc and an acid
  • a strong acid e.g. , an alkyl lithium, phenyl lithium, or a Grignard reagent
  • the present invention provides complexes of any one of Formulae (CI) to (C25).
  • the complex of the invention is of Formula (CI).
  • the complex of the invention is of Formula (C2).
  • the complex of the invention is of Formula (C3).
  • the complex of the invention is of Formula (C4).
  • the complex of the invention is of any one of Formulae (C5) to (C25).
  • kits are useful.
  • the kits are useful for preparing the compounds (e.g. , N-aryl or N-heteroaryl sulfonimides and aryl or heteroaryl amines) described herein.
  • the kits are useful for preparing compounds of Formula (I), and salts thereof.
  • the kits are useful for preparing compounds of Formula (II), and salts thereof.
  • a kit of the invention includes a compound of Formula (B) (e.g., N-fluorobenzenesulfonimide (NFBS or NFSI)), or a salt thereof; a transition metal complex of any one of Formulae (Cl)- (C25); and a single-electron reductant (e.g., an Au(I) or Ru(II) salt).
  • a kit further includes an arene or heteroarene described herein (e.g., a compound of Formula (A), or a salt thereof).
  • a kit further includes a deprotecting agent (e.g., a reductant, a strong acid, or a nucleophile).
  • a kit of the invention may also include a container, solvent, organic or inorganic agent, and/or solid support, as described herein.
  • a kit of the invention may further include instructions for using the kit.
  • Compounds described herein can comprise one or more asymmetric centers, and thus can exist in various isomeric forms, e.g., enantiomers and/or diastereomers.
  • the compounds described herein can be in the form of an individual enantiomer, diastereomer or geometric isomer, or can be in the form of a mixture of stereoisomers, including racemic mixtures and mixtures enriched in one or more stereoisomer.
  • Isomers can be isolated from mixtures by methods known to those skilled in the art, including chiral high pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts; or preferred isomers can be prepared by asymmetric syntheses.
  • HPLC high pressure liquid chromatography
  • C ⁇ is intended to encompass, C 1 ; C 2 , C 3 , C 4 , C5, C 6 , Ci_6, Ci-5, Ci ⁇ , Ci-3, Ci-2, C 2 -6, C 2 _5, C 2 _4, C 2 _ 3 , C 3 _6, C 3 _ 5 , C 3 ⁇ , C 4 _ 6 , C 4 _ 5 , and C 5 _6.
  • aliphatic includes both saturated and unsaturated, straight chain (i.e. , unbranched), branched, acyclic, cyclic, or polycyclic aliphatic hydrocarbons, which are optionally substituted with one or more functional groups.
  • aliphatic is intended herein to include, but is not limited to, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, and cycloalkynyl moieties.
  • alkyl includes straight, branched and cyclic alkyl groups.
  • alkyl alkenyl
  • alkynyl alkynyl
  • lower alkyl is used to indicate those alkyl groups (cyclic, acyclic, substituted, unsubstituted, branched or unbranched) having 1-6 carbon atoms.
  • the alkyl, alkenyl, and alkynyl groups employed in the invention contain 1-20 aliphatic carbon atoms. In certain other embodiments, the alkyl, alkenyl, and alkynyl groups employed in the invention contain 1- 10 aliphatic carbon atoms. In yet other embodiments, the alkyl, alkenyl, and alkynyl groups employed in the invention contain 1-8 aliphatic carbon atoms. In still other embodiments, the alkyl, alkenyl, and alkynyl groups employed in the invention contain 1-6 aliphatic carbon atoms. In yet other
  • the alkyl, alkenyl, and alkynyl groups employed in the invention contain 1-4 carbon atoms.
  • Illustrative aliphatic groups thus include, but are not limited to, for example, methyl, ethyl, n-propyl, isopropyl, cyclopropyl, -CH 2 -cyclopropyl, vinyl, allyl, n-butyl, sec- butyl, isobutyl, tert-butyl, cyclobutyl, -CH 2 -cyclobutyl, n-pentyl, sec-pentyl, isopentyl, tert- pentyl, cyclopentyl, -CH 2 -cyclopentyl, n-hexyl, sec-hexyl, cyclohexyl, -CH 2 -cyclohexyl moieties and the like, which again, may bear one or more substituents.
  • Alkenyl groups include, but are not limited to, for example, ethenyl, propenyl, butenyl, l-methyl-2-buten- l- yl, and the like.
  • Representative alkynyl groups include, but are not limited to, ethynyl, 2- propynyl (propargyl), 1-propynyl, and the like.
  • alkyl refers to a radical of a straight-chain or branched saturated hydrocarbon group having from 1 to 10 carbon atoms (“Ci-w alkyl”). In some embodiments, an alkyl group has 1 to 9 carbon atoms ("Q-9 alkyl”). In some embodiments, an alkyl group has 1 to 8 carbon atoms ("Q-e alkyl”). In some embodiments, an alkyl group has 1 to 7 carbon atoms (“C ⁇ alkyl”). In some embodiments, an alkyl group has 1 to 6 carbon atoms (“Ci_6 alkyl”). In some embodiments, an alkyl group has 1 to 5 carbon atoms (“Q-s alkyl”).
  • an alkyl group has 1 to 4 carbon atoms ("Ci ⁇ alkyl”). In some embodiments, an alkyl group has 1 to 3 carbon atoms ("C ⁇ alkyl”). In some embodiments, an alkyl group has 1 to 2 carbon atoms ("C ⁇ alkyl”). In some embodiments, an alkyl group has 1 carbon atom (“Q alkyl”). In some embodiments, an alkyl group has 2 to 6 carbon atoms (“C 2 -6 alkyl”).
  • Q-6 alkyl groups include methyl (CO, ethyl (C 2 ), n-propyl (C 3 ), isopropyl (C 3 ), n-butyl (C 4 ), tert-butyl (C 4 ), sec-butyl (C 4 ), iso-butyl (C 4 ), n-pentyl (C 5 ), 3-pentanyl (C 5 ), amyl (C 5 ), neopentyl (C 5 ), 3-methyl-2-butanyl (C 5 ), tertiary amyl (C 5 ), and n-hexyl (C 6 ).
  • Additional examples of alkyl groups include n-heptyl (C 7 ), n-octyl (C 8 ), and the like. Unless otherwise specified, each instance of an alkyl group is
  • the alkyl group is an unsubstituted Q_ 10 alkyl (e.g., -CH 3 ). In certain embodiments, the alkyl group is a substituted C ⁇ o alkyl.
  • haloalkyl is a substituted alkyl group, wherein one or more of the hydrogen atoms are independently replaced by a halogen, e.g., fluoro, bromo, chloro, or iodo.
  • a halogen e.g., fluoro, bromo, chloro, or iodo.
  • Perhaloalkyl is a subset of haloalkyl, and refers to an alkyl group wherein all of the hydrogen atoms are independently replaced by a halogen, e.g., fluoro, bromo, chloro, or iodo.
  • the haloalkyl moiety has 1 to 8 carbon atoms ("Q-s haloalkyl").
  • the haloalkyl moiety has 1 to 6 carbon atoms ("C ⁇ haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 4 carbon atoms ("C ⁇ haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 3 carbon atoms (“Ci_ 3 haloalkyl”). In some embodiments, the haloalkyl moiety has 1 to 2 carbon atoms (“C ⁇ haloalkyl”). In some embodiments, all of the haloalkyl hydrogen atoms are replaced with fluoro to provide a perfluoroalkyl group.
  • haloalkyl hydrogen atoms are replaced with chloro to provide a "perchloroalkyl" group.
  • haloalkyl groups include -CF , -CF 2 CF 3 , -CF 2 CF 2 CF 3 , -CCI 3 , -CFC1 2 , -CF 2 C1, and the like.
  • alkenyl refers to a radical of a straight-chain or branched hydrocarbon group having from 2 to 20 carbon atoms, one or more carbon-carbon double bonds, and no triple bonds (“C2-20 alkenyl”).
  • an alkenyl group has 2 to 10 carbon atoms ("C 2 -io alkenyl”).
  • an alkenyl group has 2 to 9 carbon atoms ("C2-9 alkenyl”).
  • an alkenyl group has 2 to 8 carbon atoms (“C 2 - 8 alkenyl”).
  • an alkenyl group has 2 to 7 carbon atoms (“C 2 _ 7 alkenyl”).
  • an alkenyl group has 2 to 6 carbon atoms ("C 2 -6 alkenyl”). In some embodiments, an alkenyl group has 2 to 5 carbon atoms (“C 2 _5 alkenyl”). In some embodiments, an alkenyl group has 2 to 4 carbon atoms (“C 2 ⁇ alkenyl”). In some embodiments,
  • an alkenyl group has 2 to 3 carbon atoms ("C 2 _3 alkenyl").
  • an alkenyl group has 2 carbon atoms ("C 2 alkenyl").
  • the one or more carbon- carbon double bonds can be internal (such as in 2-butenyl) or terminal (such as in 1-butenyl).
  • Examples of C 2 ⁇ alkenyl groups include ethenyl (C 2 ), 1-propenyl (C 3 ), 2-propenyl (C 3 ), 1- butenyl (C 4 ), 2-butenyl (C 4 ), butadienyl (C 4 ), and the like.
  • C 2 -6 alkenyl groups include the aforementioned C 2 ⁇ alkenyl groups as well as pentenyl (C 5 ), pentadienyl (C 5 ), hexenyl (C 6 ), and the like. Additional examples of alkenyl include heptenyl (C 7 ), octenyl (Cg), octatrienyl (Cg), and the like. Unless otherwise specified, each instance of an alkenyl group is independently optionally substituted, i.e. , unsubstituted (an "unsubstituted alkenyl") or substituted (a "substituted alkenyl”) with one or more substituents. In certain
  • Alkynyl refers to a radical of a straight-chain or branched hydrocarbon group having from 2 to 20 carbon atoms, one or more carbon-carbon triple bonds, and optionally one or more double bonds ("C 2 - 2 o alkynyl").
  • an alkynyl group has 2 to 10 carbon atoms ("C 2 -io alkynyl”).
  • an alkynyl group has 2 to 9 carbon atoms (“C 2 _9 alkynyl”).
  • an alkynyl group has 2 to 8 carbon atoms (“C 2 _8 alkynyl”).
  • an alkynyl group has 2 to 7 carbon atoms ("C 2 _ 7 alkynyl”). In some embodiments, an alkynyl group has 2 to 6 carbon atoms ("C 2 -6 alkynyl”). In some embodiments, an alkynyl group has 2 to 5 carbon atoms (“C 2 _5 alkynyl”). In some embodiments, an alkynyl group has 2 to 4 carbon atoms ("C 2 ⁇ alkynyl”). In some
  • an alkynyl group has 2 to 3 carbon atoms ("C 2 _ 3 alkynyl").
  • an alkynyl group has 2 carbon atoms ("C 2 alkynyl").
  • the one or more carbon- carbon triple bonds can be internal (such as in 2-butynyl) or terminal (such as in 1-butynyl).
  • Examples of C 2 - alkynyl groups include, without limitation, ethynyl (C 2 ), 1-propynyl (C 3 ), 2-propynyl (C 3 ), 1-butynyl (C 4 ), 2-butynyl (C 4 ), and the like.
  • C 2 -6 alkenyl groups include the aforementioned C 2 - alkynyl groups as well as pentynyl (C 5 ), hexynyl (C 6 ), and the like. Additional examples of alkynyl include heptynyl (C 7 ), octynyl (Cg), and the like. Unless otherwise specified, each instance of an alkynyl group is independently optionally substituted, i.e., unsubstituted (an "unsubstituted alkynyl") or substituted (a "substituted alkynyl") with one or more substituents. In certain embodiments, the alkynyl group is unsubstituted C 2 _ 10 alkynyl. In certain embodiments, the alkynyl group is substituted C2-10 alkynyl.
  • Carbocyclyl or “carbocyclic” refers to a radical of a non-aromatic cyclic hydrocarbon group having from 3 to 10 ring carbon atoms (" -io carbocyclyl") and zero heteroatoms in the non-aromatic ring system.
  • a carbocyclyl group has 3 to 8 ring carbon atoms ("C 3 _ 8 carbocyclyl”).
  • a carbocyclyl group has 3 to 6 ring carbon atoms ("C 3 _6 carbocyclyl”).
  • a carbocyclyl group has 3 to 6 ring carbon atoms (“C 3 _6 carbocyclyl”).
  • a carbocyclyl group has 5 to 10 ring carbon atoms ("Cs-io carbocyclyl").
  • Exemplary C 3 _ 6 carbocyclyl groups include, without limitation, cyclopropyl (C 3 ), cyclopropenyl (C 3 ), cyclobutyl (C 4 ), cyclobutenyl (C 4 ), cyclopentyl (C 5 ), cyclopentenyl (C 5 ), cyclohexyl (C 6 ), cyclohexenyl (C 6 ), cyclohexadienyl (C 6 ), and the like.
  • Exemplary C 3 _ 8 carbocyclyl groups include, without limitation, the aforementioned C 3 _ 6 carbocyclyl groups as well as cycloheptyl (C 7 ), cycloheptenyl (C 7 ), cycloheptadienyl (C 7 ), cycloheptatrienyl (C 7 ), cyclooctyl (C 8 ), cyclooctenyl (C 8 ),
  • C 3 _io carbocyclyl groups include, without limitation, the aforementioned C 3 _ 8 carbocyclyl groups as well as cyclononyl (C 9 ), cyclononenyl (C 9 ), cyclodecyl (C 10 ), cyclodecenyl (C 10 ), octahydro-lH-indenyl (C 9 ), decahydronaphthalenyl (C 10 ), spiro[4.5]decanyl (C 10 ), and the like.
  • the carbocyclyl group is either monocyclic (“monocyclic carbocyclyl”) or contain a fused, bridged or spiro ring system such as a bicyclic system (“bicyclic carbocyclyl”) and can be saturated or can be partially unsaturated.
  • “Carbocyclyl” also includes ring systems wherein the carbocyclic ring, as defined above, is fused with one or more aryl or heteroaryl groups wherein the point of attachment is on the carbocyclic ring, and in such instances, the number of carbons continue to designate the number of carbons in the carbocyclic ring system.
  • each instance of a carbocyclyl group is independently optionally substituted, i.e., unsubstituted (an "unsubstituted carbocyclyl") or substituted (a "substituted carbocyclyl") with one or more substituents.
  • the carbocyclyl group is unsubstituted C 3 _io carbocyclyl. In certain embodiments, the carbocyclyl group is substituted C 3 _ 10 carbocyclyl.
  • “carbocyclyl” is a monocyclic, saturated carbocyclyl group having from 3 to 10 ring carbon atoms ("C 3 _io cycloalkyl”). In some embodiments, a cycloalkyl group has 3 to 8 ring carbon atoms ("C 3 _ 8 cycloalkyl”). In some embodiments, a cycloalkyl group has 3 to 6 ring carbon atoms ("C 3 _6 cycloalkyl”). In some embodiments, a cycloalkyl group has 5 to 6 ring carbon atoms ("Cs_6 cycloalkyl").
  • a cycloalkyl group has 5 to 10 ring carbon atoms ("Cs-io cycloalkyl").
  • C 5 _6 cycloalkyl groups include cyclopentyl (C 5 ) and cyclohexyl (C 5 ).
  • C 3 _ 6 cycloalkyl groups include the aforementioned C 5 _6 cycloalkyl groups as well as cyclopropyl (C 3 ) and cyclobutyl (C 4 ).
  • C 3 _ 8 cycloalkyl groups include the aforementioned C 3 _6 cycloalkyl groups as well as cycloheptyl (C 7 ) and cyclooctyl (C 8 ).
  • each instance of a cycloalkyl group is independently unsubstituted (an "unsubstituted cycloalkyl") or substituted (a "substituted cycloalkyl”) with one or more substituents.
  • the cycloalkyl group is unsubstituted C 3 _ 10 cycloalkyl.
  • the cycloalkyl group is substituted C 3 _ 10 cycloalkyl.
  • Heterocyclyl or “heterocyclic” refers to a radical of a 3- to 10-membered non- aromatic ring system having ring carbon atoms and 1 to 4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, sulfur, boron, phosphorus, and silicon ("3-10 membered heterocyclyl").
  • the point of attachment can be a carbon or nitrogen atom, as valency permits.
  • a heterocyclyl group can either be monocyclic ("monocyclic heterocyclyl”) or a fused, bridged, or spiro ring system, such as a bicyclic system ("bicyclic heterocyclyl”), and can be saturated or can be partially unsaturated.
  • Heterocyclyl bicyclic ring systems can include one or more heteroatoms in one or both rings.
  • Heterocyclyl also includes ring systems wherein the heterocyclic ring, as defined above, is fused with one or more carbocyclyl groups wherein the point of attachment is either on the carbocyclyl or heterocyclic ring, or ring systems wherein the heterocyclic ring, as defined above, is fused with one or more aryl or heteroaryl groups, wherein the point of attachment is on the heterocyclic ring, and in such instances, the number of ring members continue to designate the number of ring members in the
  • heterocyclic ring system Unless otherwise specified, each instance of heterocyclyl is independently optionally substituted, i.e., unsubstituted (an “unsubstituted heterocyclyl”) or substituted (a "substituted heterocyclyl”) with one or more substituents.
  • each instance of heterocyclyl is independently optionally substituted, i.e., unsubstituted (an “unsubstituted heterocyclyl”) or substituted (a "substituted heterocyclyl”) with one or more substituents.
  • the heterocyclyl group is unsubstituted 3-10 membered heterocyclyl. In certain embodiments, the heterocyclyl group is substituted 3-10 membered heterocyclyl.
  • a heterocyclyl group is a 5-10 membered non-aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, sulfur, boron, phosphorus, and silicon ("5-10 membered heterocyclyl").
  • a heterocyclyl group is a 5-8 membered non-aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-8 membered heterocyclyl").
  • a heterocyclyl group is a 5-6 membered non-aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-6 membered heterocyclyl").
  • the 5-6 membered heterocyclyl has 1-3 ring heteroatoms selected from nitrogen, oxygen, and sulfur.
  • the 5-6 membered heterocyclyl has 1-2 ring heteroatoms selected from nitrogen, oxygen, and sulfur.
  • the 5-6 membered heterocyclyl has one ring heteroatom selected from nitrogen, oxygen, and sulfur.
  • Exemplary 3-membered heterocyclyl groups containing one heteroatom include, without limitation, azirdinyl, oxiranyl, and thiiranyl.
  • Exemplary 4-membered heterocyclyl groups containing one heteroatom include, without limitation, azetidinyl, oxetanyl, and thietanyl.
  • Exemplary 5-membered heterocyclyl groups containing one heteroatom include, without limitation, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl,
  • Exemplary 5- membered heterocyclyl groups containing two heteroatoms include, without limitation, dioxolanyl, oxasulfuranyl, disulfuranyl, and oxazolidin-2-one.
  • Exemplary 5-membered heterocyclyl groups containing three heteroatoms include, without limitation, triazolinyl, oxadiazolinyl, and thiadiazolinyl.
  • Exemplary 6-membered heterocyclyl groups containing one heteroatom include, without limitation, piperidinyl, tetrahydropyranyl, dihydropyridinyl, and thianyl.
  • Exemplary 6-membered heterocyclyl groups containing two heteroatoms include, without limitation, piperazinyl, morpholinyl, dithianyl, and dioxanyl.
  • Exemplary 6- membered heterocyclyl groups containing three heteroatoms include, without limitation, triazinanyl.
  • Exemplary 7-membered heterocyclyl groups containing one heteroatom include, without limitation, azepanyl, oxepanyl and thiepanyl.
  • Exemplary 8-membered heterocyclyl groups containing one heteroatom include, without limitation, azocanyl, oxecanyl and thiocanyl.
  • Exemplary 5-membered heterocyclyl groups fused to a C 6 aryl ring include, without limitation, indolinyl, isoindolinyl, dihydrobenzofuranyl, dihydrobenzothienyl, benzoxazolinonyl, and the like.
  • Exemplary 6-membered heterocyclyl groups fused to an aryl ring include, without limitation, tetrahydroquinolinyl,
  • Aryl refers to a radical of a monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n+2 aromatic ring system (e.g. , having 6, 10, or 14 pi electrons shared in a cyclic array) having 6-14 ring carbon atoms and zero heteroatoms provided in the aromatic ring system ("C6-14 aryl").
  • an aryl group has six ring carbon atoms ("C 6 aryl”; e.g., phenyl).
  • an aryl group has ten ring carbon atoms ("Cio aryl”; e.g., naphthyl such as 1-naphthyl and 2-naphthyl). In some embodiments, an aryl group has fourteen ring carbon atoms ("Cw aryl”; e.g. , anthracyl).
  • Aryl also includes ring systems wherein the aryl ring, as defined above, is fused with one or more carbocyclyl or heterocyclyl groups wherein the radical or point of attachment is on the aryl ring, and in such instances, the number of carbon atoms continue to designate the number of carbon atoms in the aryl ring system. Unless otherwise specified, each instance of an aryl group is independently optionally substituted, i.e. , unsubstituted (an "unsubstituted aryl”) or substituted (a
  • substituted aryl with one or more substituents.
  • the aryl group is unsubstituted C 6 -i4 aryl.
  • the aryl group is substituted C 6 -i4 aryl.
  • Alkyl is a subset of alkyl and aryl and refers to an optionally substituted alkyl group substituted by an optionally substituted aryl group. In certain embodiments, the aralkyl is optionally substituted benzyl. In certain embodiments, the aralkyl is benzyl. In certain embodiments, the aralkyl is optionally substituted phenethyl. In certain embodiments, the aralkyl is phenethyl.
  • Heteroaryl refers to a radical of a 5-10 membered monocyclic or bicyclic 4n+2 aromatic ring system (e.g., having 6 or 10 pi electrons shared in a cyclic array) having ring carbon atoms and 1-4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-10 membered heteroaryl").
  • the point of attachment can be a carbon or nitrogen atom, as valency permits.
  • Heteroaryl bicyclic ring systems can include one or more heteroatoms in one or both rings.
  • Heteroaryl includes ring systems wherein the heteroaryl ring, as defined above, is fused with one or more carbocyclyl or heterocyclyl groups wherein the point of attachment is on the heteroaryl ring, and in such instances, the number of ring members continue to designate the number of ring members in the heteroaryl ring system.
  • Heteroaryl also includes ring systems wherein the heteroaryl ring, as defined above, is fused with one or more aryl groups wherein the point of attachment is either on the aryl or heteroaryl ring, and in such instances, the number of ring members designates the number of ring members in the fused (aryl/heteroaryl) ring system.
  • Bicyclic heteroaryl groups wherein one ring does not contain a heteroatom e.g. , indolyl, quinolinyl, carbazolyl, and the like
  • the point of attachment can be on either ring, i.e., either the ring bearing a heteroatom (e.g., 2-indolyl) or the ring that does not contain a heteroatom (e.g., 5- indolyl).
  • a heteroaryl group is a 5-10 membered aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-10 membered heteroaryl").
  • a heteroaryl group is a 5-8 membered aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-8 membered heteroaryl").
  • a heteroaryl group is a 5-6 membered aromatic ring system having ring carbon atoms and 1-4 ring heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from nitrogen, oxygen, and sulfur ("5-6 membered heteroaryl").
  • the 5-6 membered heteroaryl has 1-3 ring heteroatoms selected from nitrogen, oxygen, and sulfur.
  • the 5-6 membered heteroaryl has 1-2 ring heteroatoms selected from nitrogen, oxygen, and sulfur.
  • the 5-6 membered heteroaryl has 1 ring heteroatom selected from nitrogen, oxygen, and sulfur.
  • each instance of a heteroaryl group is independently optionally substituted, i.e., unsubstituted (an "unsubstituted heteroaryl") or substituted (a "substituted heteroaryl") with one or more substituents.
  • the heteroaryl group is unsubstituted 5-14 membered heteroaryl. In certain embodiments, the heteroaryl group is substituted 5-14 membered heteroaryl.
  • Exemplary 5-membered heteroaryl groups containing one heteroatom include, without limitation, pyrrolyl, furanyl, and thiophenyl.
  • Exemplary 5-membered heteroaryl groups containing two heteroatoms include, without limitation, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl.
  • Exemplary 5-membered heteroaryl groups containing three heteroatoms include, without limitation, triazolyl, oxadiazolyl, and thiadiazolyl.
  • Exemplary 5-membered heteroaryl groups containing four heteroatoms include, without limitation, tetrazolyl.
  • Exemplary 6-membered heteroaryl groups containing one heteroatom include, without limitation, pyridinyl.
  • Exemplary 6-membered heteroaryl groups containing two heteroatoms include, without limitation, pyridazinyl, pyrimidinyl, and pyrazinyl.
  • Exemplary 6-membered heteroaryl groups containing three or four heteroatoms include, without limitation, triazinyl and tetrazinyl, respectively.
  • Exemplary 7-membered heteroaryl groups containing one heteroatom include, without limitation, azepinyl, oxepinyl, and thiepinyl.
  • Exemplary 5,6-bicyclic heteroaryl groups include, without limitation, indolyl, isoindolyl, indazolyl, benzotriazolyl, benzothiophenyl, isobenzothiophenyl, benzofuranyl, benzoisofuranyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzoxadiazolyl, benzthiazolyl, benzisothiazolyl, benzthiadiazolyl, indolizinyl, and purinyl.
  • Exemplary 6,6- bicyclic heteroaryl groups include, without limitation, naphthyridinyl, pteridinyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl, phthalazinyl, and quinazolinyl.
  • Heteroaralkyl is a subset of alkyl and heteroaryl and refers to an optionally substituted alkyl group substituted by an optionally substituted heteroaryl group.
  • Unsaturated or “partially unsaturated” refers to a group that includes at least one double or triple bond.
  • a “partially unsaturated” ring system is further intended to encompass rings having multiple sites of unsaturation, but is not intended to include aromatic groups
  • saturated refers to a group that does not contain a double or triple bond, i.e., contains all single bonds.
  • Alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl groups, which are divalent bridging groups, are further referred to using the suffix -ene, e.g., alkylene, alkenylene, alkynylene, carbocyclylene, heterocyclylene, arylene, and
  • Alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl groups are optionally substituted (e.g., "substituted” or “unsubstituted” alkyl, "substituted” or
  • substituted carbocyclyl, "substituted” or “unsubstituted” heterocyclyl, "substituted” or “unsubstituted” aryl or “substituted” or “unsubstituted” heteroaryl group).
  • substituted whether preceded by the term “optionally” or not, means that at least one hydrogen present on a group (e.g. , a carbon or nitrogen atom) is replaced with a permissible substituent, e.g. , a substituent which upon substitution results in a stable compound, e.g., a compound which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, or other reaction.
  • a "substituted" group has a substituent at one or more substitutable positions of the group, and when more than one position in any given structure is substituted, the substituent is either the same or different at each position.
  • substituted is contemplated to include substitution with all permissible substituents of organic compounds, any of the substituents described herein that results in the formation of a stable compound.
  • the present invention contemplates any and all such combinations in order to arrive at a stable compound.
  • heteroatoms such as nitrogen may have hydrogen substituents and/or any suitable substituent as described herein which satisfy the valencies of the heteroatoms and results in the formation of a stable moiety.
  • the substituent is a carbon atom substituent. In certain embodiments, the substituent is a nitrogen atom substituent. In certain embodiments, the substituent is an oxygen atom substituent. In certain embodiments, the substituent is a sulfur atom substituent.
  • each instance of R aa is, independently, selected from C ⁇ o alkyl, C ⁇ o perhaloalkyl, C 2 _ 10 alkenyl, C 2 _ 10 alkynyl, C 3 _ 10 carbocyclyl, 3-14 membered heterocyclyl, C 6 -i4 aryl, and 5-14 membered heteroaryl, or two R aa groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R dd groups;
  • each instance of R cc is, independently, selected from hydrogen, Ci-io alkyl, Q_ io perhaloalkyl, C 2 _ 10 alkenyl, C 2 _ 10 alkynyl, C 3 _ 10 carbocyclyl, 3-14 membered heterocyclyl, C 6 -i4 aryl, and 5-14 membered heteroaryl, or two R cc groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R dd groups;
  • each instance of R ee is, independently, selected from Q_6 alkyl, C ⁇
  • each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R gg groups;
  • each instance of R is, independently, selected from hydrogen, Q_6 alkyl, Q_6 perhaloalkyl, C 2 _ 6 alkenyl, C 2 _ 6 alkynyl, C 3 _ 10 carbocyclyl, 3-10 membered heterocyclyl, C 6 - ff
  • io aryl and 5-10 membered heteroaryl, or two R groups are joined to form a 3-14 membered heterocyclyl or 5-14 membered heteroaryl ring, wherein each alkyl, alkenyl, alkynyl, carbocyclyl, heterocyclyl, aryl, and heteroaryl is independently substituted with 0, 1, 2, 3, 4, or 5 R gg groups; and
  • Halo or "halogen” refers to fluorine (fluoro, -F), chlorine (chloro, -CI), bromine (bromo, -Br), or iodine (iodo, -I).
  • Nitrogen atoms can be substituted or unsubstituted as valency permits, and include primary, secondary, tertiary, and quatemarynitrogen atoms.
  • the substituent present on a nitrogen atom is a nitrogen protecting group (also referred to as an amino protecting group).
  • Nitrogen protecting groups such as carbamate groups include, but are not limited to, methyl carbamate, ethyl carbamante, 9-fluorenylmethyl carbamate (Fmoc), 9-(2-sulfo)fluorenylmethyl carbamate, 9-(2,7-dibromo)fluoroenylmethyl carbamate, 2,7-di-i-butyl-[9-( 10,10-dioxo-l 0, 10,10,10-tetrahydrothioxanthyl)]methyl carbamate (DBD-Tmoc), 4-methoxyphenacyl carbamate (Phenoc), 2,2,2-trichloroethyl carbamate (Troc), 2-trimethylsilylethyl carbamate (Teoc), 2-phenylethyl carbamate (hZ), 1- (l-adamantyl)-l-methylethyl
  • Nitrogen protecting groups such as sulfonamide groups include, but are not limited to, p-toluenesulfonamide (Ts), benzenesulfonamide, 2,3,6,-trimethyl-4- methoxybenzenesulfonamide (Mtr), 2,4,6-trimethoxybenzenesulfonamide (Mtb), 2,6- dimethyl-4-methoxybenzenesulfonamide (Pme), 2,3,5, 6-tetramethyl-4- methoxybenzenesulfonamide (Mte), 4-methoxybenzenesulfonamide (Mbs), 2,4,6- trimethylbenzenesulfonamide (Mts), 2,6-dimethoxy-4-methylbenzenesulfonamide (iMds), 2,2,5,7, 8-pentamethylchroman-6-sulfonamide (Pmc), methanes
  • Ts p-toluenesulfonamide
  • Mtr 2,3,
  • nitrogen protecting groups include, but are not limited to, phenothiazinyl- (lO)-acyl derivative, N'-p-toluenesulfonylaminoacyl derivative, N'-phenylaminothioacyl derivative, N-benzoylphenylalanyl derivative, N-acetylmethionine derivative, 4,5-diphenyl- 3-oxazolin-2-one, N-phthalimide, N-dithiasuccinimide (Dts), N-2,3-diphenylmaleimide, N-2,5-dimethylpyrrole, N-l,l,4,4-tetramethyldisilylazacyclopentane adduct (STABASE), 5-substituted l,3-dimethyl-l,3,5-triazacyclohexan-2-one, 5-substituted 1,3-dibenzyl- l,3,5-triazacyclohexan-2-one
  • benzenesulfenamide o-nitrobenzenesulfenamide (Nps), 2,4-dinitrobenzenesulfenamide, pentachlorobenzenesulfenamide, 2-nitro-4-methoxybenzenesulfenamide,
  • oxygen protecting groups include, but are not limited to, methyl, i-butyloxycarbonyl (BOC or Boc), methoxylmethyl (MOM), methylthiomethyl (MTM), i-butylthiomethyl, (phenyldimethylsilyl)methoxymethyl (SMOM), benzyloxymethyl (BOM), p-methoxybenzyloxymethyl (PMBM), (4- methoxyphenoxy)methyl (p-AOM), guaiacolmethyl (GUM), i-butoxymethyl, 4- pentenyloxymethyl (POM), siloxymethyl, 2-methoxyethoxymethyl (MEM), 2,2,2- trichloroethoxymethyl, bis(2-chloroethoxy)methyl, 2-(trimethylsilyl)ethoxymethyl
  • DPMS diphenylmethylsilyl
  • TMPS i-butylmethoxyphenylsilyl
  • the sulfur atom substituent present on a sulfur atom is a sulfur protecting group (also referred to as a thiol protecting group).
  • Sulfur protecting groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3 r edition, John Wiley & Sons, 1999, incorporated herein by reference.
  • salt refers to ionic compounds that result from the neutralization reaction of an acid and a base.
  • a salt is composed of one or more cations (positively charged ions) and one or more anions (negative ions) so that the salt is electrically neutral (without a net charge).
  • Salts of the compounds of this invention include those derived from inorganic and organic acids and bases.
  • acid addition salts are salts of an amino group formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid, or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid or by using other methods known in the art such as ion exchange.
  • Other salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate,
  • ethanesulfonate formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2- naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, picrate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate salts, and the like.
  • Salts derived from appropriate bases include alkali metal, alkaline earth metal, ammonium and N + (Ci ⁇ alkyl) 4 salts.
  • Representative alkali or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, and the like.
  • Further salts include ammonium, quaternary ammonium, and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, lower alkyl sulfonate, and aryl sulfonate.
  • tautomers refers to two or more interconvertable compounds resulting from at least one formal migration of a hydrogen atom and at least one change in valency (e.g., a single bond to a double bond, a triple bond to a single bond, or vice versa).
  • the exact ratio of the tautomers depends on several factors, including temperature, solvent, and pH. Tautomerizations (i.e., the reaction providing a tautomeric pair) may catalyzed by acid or base.
  • Exemplary tautomerizations include keto-to-enol, amide-to-imide, lactam- to-lactim, enamine-to-imine, and enamine-to-(a different enamine) tautomerizations.
  • isomers compounds that have the same molecular formula but differ in the nature or sequence of bonding of their atoms or the arrangement of their atoms in space are termed "isomers”. Isomers that differ in the arrangement of their atoms in space are termed "stereoisomers”.
  • enantiomers and those that are non-superimposable mirror images of each other are termed "enantiomers".
  • An enantiomer can be characterized by the absolute configuration of its asymmetric center and is described by the R- and S-sequencing rules of Cahn and Prelog, or by the manner in which the molecule rotates the plane of polarized light and designated as dextrorotatory or levorotatory (i.e., as (+) or (-)-isomers respectively).
  • a chiral compound can exist as either individual enantiomer or as a mixture thereof. A mixture containing equal proportions of the enantiomers is called a "racemic mixture".
  • solvate refers to forms of the compound that are associated with a solvent, usually by a solvolysis reaction. This physical association may include hydrogen bonding.
  • solvents include water, methanol, ethanol, acetic acid, DMSO, THF, diethyl ether, and the like.
  • the compounds described herein may be prepared, e.g., in crystalline form, and may be solvated.
  • Suitable solvates include pharmaceutically acceptable solvates and further include both stoichiometric solvates and non- stoichiometric solvates. In certain instances, the solvate will be capable of isolation, for example, when one or more solvent molecules are incorporated in the crystal lattice of a crystalline solid.
  • “Solvate” encompasses both solution-phase and isolatable solvates. Representative solvates include hydrates, ethanolates, and methanolates.
  • hydrate refers to a compound that is associated with water.
  • the number of the water molecules contained in a hydrate of a compound is in a definite ratio to the number of the compound molecules in the hydrate. Therefore, a hydrate of a compound may be represented, for example, by the general formula R x H 2 0, wherein R is the compound, and x is a number greater than 0.
  • a given compound may form more than one type of hydrate, including, e.g., monohydrates (x is 1), lower hydrates (x is a number greater than 0 and smaller than 1, e.g., hemihydrates (R-0.5 H 2 0)), and polyhydrates (x is a number greater than 1, e.g., dihydrates (R-2 H 2 0) and hexahydrates (R-6 H 2 0)).
  • polymorph refers to a crystalline form of a compound (or a salt, hydrate, or solvate thereof) in a particular crystal packing arrangement. All polymorphs have the same elemental composition. Different crystalline forms usually have different X-ray diffraction patterns, infrared spectra, melting points, density, hardness, crystal shape, optical and electrical properties, stability, and solubility. Recrystallization solvent, rate of
  • crystallization, storage temperature, and other factors may cause one crystal form to dominate.
  • Various polymorphs of a compound can be prepared by crystallization under different conditions.
  • complex refers to an association of at least one atom or ion (which is referred to as a "central atom,” “central ion,” or “acceptor,” and is usually a metallic cation) and a surrounding array of bound ligands or donors).
  • Ligands are generally bound to a central atom or central ion by a coordinate covalent bond (e.g. , ligands may donate electrons from a lone electron pair into an empty orbital of the central atom or central ion) and are referred to as being “coordinated" to the central atom or central ion.
  • a complex may include one or more donors, which can be the same or different.
  • a complex may also include one or more acceptors, which can be the same or different.
  • ligand refers to an ion or molecule that binds to a central atom or ion (e.g., a central metal atom or ion) to form a coordination complex.
  • Ligands are usually electron donors, and the central atom or ion is electron acceptors.
  • the bonding between the central atom or ion and the ligand typically involves formal donation of one or more of the ligand' s electron pairs. The nature of such bonding can range from covalent to ionic, and the bond order can range from one to three.
  • One central atom or ion may bind to one or more ligands of the same or different type.
  • a ligand may be capable of binding a central atom or ion through multiple sites, usually because the ligand includes lone pairs on more than one atom of the ligand.
  • Ligands in a complex may affect the reactivity (e.g. , ligand substitution rates and redox) of the central atom or ion.
  • Exemplary ligands include charge-neutral ligands ("ligand molecules," e.g. , CH 3 CN, amides (e.g.
  • N,N-dimethylformamide (DMF), N,N- dimethylacetamide (DMA), or N-methyl-2-pyrrolidone (NMP)
  • dimethyl sulfoxide (DMSO)
  • amines e.g., ammonia; ethylenediamine (en); pyridine (py); 2,2'-bipyridine (bipy); and 1,10- phenanthroline (phen)
  • phosphines e.g., PPh 3
  • ethers e.g. , tetrahydrofuran (THF), 2- methly-tetrahydrofuran, tetrahydropyran, dioxane, diethyl ether, methyl t-butyl ether
  • ketones e.g., acetone and butanone
  • chlorohydrocarbons e.g. , dichloromethane (DCM), chloroform, carbon tetrachloride, and 1,2-dichloroethane (DCE)
  • esters e.g., propylene carbonate and ethyl acetate
  • CO N 2
  • water water
  • alkenes anionic ligands
  • transition metal refers to elements that are in the d-block and f-block of the Periodic Chart of the Elements, which may exhibit a variety of oxidation states, and which may form numerous complex ions.
  • d-block refers to those elements that have electrons filling the 3d, 4d, 5d, and 6d orbitals
  • f-block refers to those elements (including lanthanides and the actinides) that have electrons filling the 4f and 5f orbitals.
  • Exemplary transition metals include palladium, nickel, cobalt, copper, platinum, silver, manganese, zinc, iridium, rhodium, iron, and ruthenium.
  • Transition metal also includes alloys, metal/metal composites, metal ceramic composites, and metal polymer composites, as well as other metal composites.
  • catalysis refers to the increase in rate of a chemical reaction due to the participation of a substance called a "catalyst.”
  • the amount and nature of a catalyst remains essentially unchanged during a reaction.
  • a catalyst is regenerated, or the nature of a catalyst is essentially restored after a reaction.
  • a catalyst may participate in multiple chemical transformations. The effect of a catalyst may vary due to the presence of other substances known as inhibitors or poisons (which reduce the catalytic activity) or promoters (which increase the activity).
  • Catalyzed reactions have lower activation energy (rate-limiting free energy of activation) than the corresponding uncatalyzed reaction, resulting in a higher reaction rate at the same temperature.
  • Catalysts may affect the reaction environment favorably, bind to the reagents to polarize bonds, form specific intermediates that are not typically produced by a uncatalyzed reaction, or cause dissociation of reagents to reactive forms.
  • arene refers to a compound including an aryl moiety, wherein at least one carbon atom of the aryl ring system is directly attached to a hydrogen atom.
  • heteroaryl refers to a compound including a heteroaryl moiety, wherein at least one carbon atom of the heteroaryl ring system is directly attached to a hydrogen atom.
  • a "counterion” or “anionic counterion” is a negatively charged group associated with a positively charged group in order to maintain electronic neutrality.
  • An anionic counterion may be monovalent (i.e., including one formal negative charge).
  • An anionic counterion may also be multivalent (i.e., including more than one formal negative charge), such as divalent or trivalent.
  • Exemplary counterions include halide ions (e.g., F , CT, Br , ⁇ ), NO 3 , CIO 4 , OH , H 2 PO 4 , HSO 4 , sulfonate ions (e.g., methansulfonate,
  • non-coordinating anionic counterion refers to an anion that interacts weakly with cations.
  • exemplary non-coordinating anions include, but are not limited to, C10 4 , ⁇ , BF 4 , PF 4 , PF 6 , and SbF 6 ⁇ .
  • Other examples of non-coordinating anions include, but are not limited to, B[3,5-(CF ) 2 C 6 H ] 4 ] ⁇ , BPh 4 , Al(OC(CF ) ) 4 ⁇ , or a carborane anion (e.g., CB U H 12 or (HCBnMe 5 Br 6 ) ).
  • Figure 1 depicts an X-ray structure of complex 1 (elipsoids drawn at 50% probability).
  • Figure 2 shows a proposed mechanism of a catalytic imidation reaction of the invention.
  • Figure 3 shows calculated valence orbitals of complex 1.
  • Figure 4 illustrates the rate law for the reduction of N-fluorobenzenesulfonimide (NFBS or NFSI) catalyzed by complex 1.
  • NFBS N-fluorobenzenesulfonimide
  • Figure 5 illustrates the rate law for an imidation reaction of the invention catalyzed by 1 and in the presence of Ag(bipy) 2 C10 4 .
  • Figure 6 illustrates the rate law showing the order in Ag(bipy) 2 C10 4 .
  • Figure 7 shows the results of experiments for the determination of the order in an arene substrate.
  • Figure 8 shows the results of experiments for the determination of the order in NFBS.
  • Figure 9 shows the results of experiments for the determination of the order in complex 1.
  • Figure 10 shows the results of experiments for the determination of the resting state.
  • Figure 11 shows the 1H NMR spectra of Solution A (left panels) and Solution B (right panels) after 10 minutes (top panels) and 4 hours (bottom panels) of oxidation of Ru(bipy) (PF 6 )2 mediated by complex 1.
  • Figure 12 shows 1 H NMR peak broadness at 23 °C, -20 °C, and -40 °C during oxidation of Ru(bipy) 3 (PF 6 )2 mediated by complex 1.
  • Figure 13 shows EPR (electron paramagnetic resonance) spectra of Solution B and pure Ru(bipy) 3 (PF 6 ) 3 .
  • Figure 14 shows the rates of NFBS consumption by Ru(bipy) 3 (PF 6 )2 or by
  • Figure 15 shows the EPR spectra of Solutions E and F.
  • Figure 16 shows the optimized structure of complex 1 with the B3PW91 functional with the BS I basis set.
  • the present invention provides novel transition metal complexes (e.g., complexes of any one of Formulae (CI) to (C25)) that include an amine-N-oxide motif. These transition metal complexes have been found useful in the imidation of arenes and heteroarenes.
  • the invention also provides methods of using the transition metal complexes as catalysts in the preparation of N-aryl or N-heteroaryl sulfonimides (e.g., compounds of Formula (I), and salts thereof) and aryl or heteroaryl amines (e.g., compounds of Formula (II), and salts thereof) through imidation of arenes or heteroarenes (e.g., compounds of Formula (A), and salts thereof).
  • the methods of the invention involves an imidating agent (e.g., a compound of Formula (B), such as N-fluorobenzenesulfonimide (NFBS or NFSI)) in the presence of a transition metal complex of the invention and a single-electron reductant (e.g., an Ag(I) or Ru(II) salt).
  • an imidating agent e.g., a compound of Formula (B), such as N-fluorobenzenesulfonimide (NFBS or NFSI)
  • NFBS or NFSI N-fluorobenzenesulfonimide
  • a single-electron reductant e.g., an Ag(I) or Ru(II) salt
  • inventive methods may involve a catalytic, intermolecular C-H imidation that proceeds via a mechanism different from the conventional metallation-functionalization sequence and may enable the transfer of the imido group without the formation of conventionally targeted organometallic
  • oxidation of the catalyst e.g., complexes of any one of Formulae (CI) to (C25)
  • the methods of the invention may be practiced at or below room temperature.
  • the imidation methods of the invention do not require coordinating directing groups on the starting material and give synthetically useful yields with the arene or heteroarene starting material as the limiting reagent (e.g., one equivalent of arene or heteroarene and more than one equivalents of imidating agent is typically used).
  • the present invention provides methods of preparing N-aryl sulfonimides or N-heteroaryl sulfonimides through a catalytic imidation of an arene or heteroarene (e.g., a compound of Formula (A), or a salt thereof) using an imidating agent in the presence of a catalyst and a single-electron reductant.
  • the imidating agent employed in the methods of the invention may be an N-fluorosulfonimide, such as a compound of Formula (B) (e.g., N-fluorobenzenesulfonimide (NFBS or NFSI)), or a salt thereof.
  • the catalyst useful in the inventive methods may be a transition metal complex, such as a complex of any one of Formulae (CI) to (C25).
  • the invention provides methods of preparing compounds of Formula (I):
  • inventive methods typically include contacting a compound of Formula (A), or a salt thereof, with a compound of Formula (B), or a salt thereof, in the presence of a transition metal complex of any one of Formulae (CI) to (C25) and a single-electron reductant to provide the compound of Formula (I), or the salt thereof:
  • each instance of R A1 is independently hydrogen, substituted or unsubstituted acyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom, or two instances of R A1 are joined to form a substituted or unsubstituted heterocyclic ring;
  • k 0, 1, 2, 3, 4, or 5;
  • each instance of m is independently 0, 1, 2, 3, 4, or 5;
  • each instance of M is a transition metal ion
  • each instance of Ring B is independently substituted or unsubstituted heteroaryl; each instance of is independently a single or double bond;
  • each instance of r is independently 0, 1, 2, 3, or 4;
  • each instance of R D is independently substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or a nitrogen protecting group, or two instances of R D are joined to form a substituted or unsubstituted heterocyclic ring;
  • each instance of R is independently absent, hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or a nitrogen protecting group, or p
  • n 0 or 1 ;
  • p 1 or 2;
  • each instance of X is an anionic counterion
  • q is 1, 2, or 3.
  • the arene or heteroarene involved in the inventive methods may be a compound of Formula (A), or a salt thereof.
  • Compounds of Formula (A) include substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl as Ring A.
  • Ring A is substituted aryl. In certain embodiments, Ring A is unsubstituted aryl. In certain embodiments, Ring A is 6- to 14-membered aryl. In certain embodiments, Ring A is 6- to 10-membered aryl. In certain embodiments, Ring A is monocyclic aryl. In certain embodiments, Ring A is unsubstituted phenyl. In certain embo Ring A is
  • Ring A is of the formula: . In certain . In certain embodiments, Ring A is of
  • Ring A is of the formula: .
  • Ring A is of the formula: . In certain embodiments, Ring A is
  • Ring A is of the formula:
  • n certa n em o ments ng s o t e ormu a: . n certa n em o ments,
  • Rin A is of the formula: .
  • Ring A is of the formula:
  • Ring A is bicyclic aryl. In certain embodiments, Ring A is substituted naphthyl. In certain embodiments, Ring A is unsubstituted naphthyl. In certain embodiments, Ring A is substituted or unsubstituted aryl fused with one or more substituted or
  • Ring A of Formula (I) may also be substituted or unsubstituted heteroaryl.
  • Ring A is substituted heteroaryl.
  • Ring A is unsubstituted heteroaryl.
  • Ring A is 5- or 6-membered, monocyclic heteroaryl, wherein one, two, or three atoms in the heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • Ring A is 6-membered, monocyclic heteroaryl.
  • Ring A is of the formula: .
  • Ring A is of
  • Ring A is of the formula:
  • Ring A is of the
  • Ring A is of the formula:
  • Ring A is of the formula:
  • Ring A is 5-membered, monocyclic heteroaryl. In certain embodiments, Ring A is 5-membered, monocyclic heteroaryl, wherein one atom in the heteroaryl ring system is nitrogen, ox en, or sulfur. In certain embodiments, Ring A is of
  • Ring A is of the
  • Ring A is 5-membered, monocyclic heteroaryl, wherein two atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur. In certain embodiments, Ring A is of the formula: , or . In certain embodiments, Ring A is of the
  • Ring A is of th e f . In certain embodiments, Ring A is of
  • Ring A is of the formula In certain embodiments, Ring A
  • Ring A is 5-membered, monocyclic heteroaryl, wherein three atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur.
  • three atoms in the heteroaryl ring system are independently nitrogen, oxygen, or sulfur.
  • Ring A is of the or ⁇ * . n certa n em o ments, Ring A is of the formula:
  • Ring A is 5-membered, monocyclic heteroaryl, wherein four atoms in the heteroaryl ring system are nitrogen, oxygen, or sulfur.
  • Ring A is of the formula:
  • Ring A is bicyclic heteroaryl, wherein the point of attachment may be on any atom of the bicyclic heteroaryl ring system, as valency permits.
  • the bicyclic heteroaryl described herein may be substituted or unsubstituted.
  • Ring A is 9- or 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the bicyclic heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • Ring A is 5- or 6- membered, monocyclic heteroaryl fused with phenyl, wherein one, two, or three atoms in the bicyclic heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • Ring A is 5- or 6-membered, monocyclic heteroaryl fused with another 5- or 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the bicyclic heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • Ring A is substituted or unsubstituted indole.
  • Ring A is substituted or unsubstituted isoindole.
  • Ring A is substituted or unsubstituted indazole. In certain embodiments, Ring A is substituted or unsubstituted benzothiophene. In certain embodiments, Ring A is substituted or unsubstituted isobenzothiophene. In certain embodiments, Ring A is substituted or unsubstituted benzofuran. In certain embodiments, Ring A is substituted or unsubstituted benzoisofuran. In certain embodiments, Ring A is substituted or unsubstituted benzimidazole. In certain embodiments, Ring A is substituted or unsubstituted benzoxazole. In certain embodiments, Ring A is substituted or unsubstituted benzisoxazole.
  • Ring A is substituted or unsubstituted benzothiazole. In certain embodiments, Ring A is substituted or unsubstituted benzisothiazole. In certain embodiments, Ring A is substituted or unsubstituted benzotriazole. In certain embodiments, Ring A is substituted or unsubstituted benzoxadiazole. In certain embodiments, Ring A is substituted or unsubstituted quinoline. In certain embodiments, Ring A is substituted or unsubstituted isoquinoline. In certain embodiments, Ring A is substituted or unsubstituted cinnoline. In certain embodiments, Ring A is substituted or unsubstituted quinoxaline. In certain embodiments, Ring A is substituted or unsubstituted phthalazine. In certain embodiments, Ring A is substituted or unsubstituted quinazoline.
  • Compounds of Formula (I) or (A) may include one or more substituent R A .
  • at least one instance of R A is H.
  • at least one instance of R A is halogen.
  • at least one instance of R A is F.
  • at least one instance of R A is CI.
  • at least one instance of R A is Br.
  • at least one instance of R A is I (iodine).
  • at least one instance of R A is substituted acyl.
  • at least one instance of R A is unsubstituted acyl.
  • at least one instance of R A is substituted alkyl.
  • At least one instance of R A is unsubstituted alkyl. In certain embodiments, at least one instance of R A is C 1-12 alkyl. In certain embodiments, at least one instance of R A is substituted Ci_6 alkyl. In certain embodiments, at least one instance of R A is unsubstituted C 1-6 alkyl. In certain embodiments, at least one instance of R A is substituted methyl. In certain embodiments, at least one instance of R A is -CH 2 F. In certain embodiments, at least one instance of R A is -CHF 2 . In certain embodiments, at least one instance of R A is -CF 3 . In certain embodiments, at least one instance of R A is Bn.
  • At least one instance of R A is unsubstituted methyl. In certain embodiments, at least one instance of R A is ethyl. In certain embodiments, at least one instance of R A is propyl. In certain embodiments, at least one instance of R A is butyl. In certain embodiments, at least one instance of R A is pentyl. In certain embodiments, at least one instance of R A is hexyl. In certain embodiments, at least one instance of R A is substituted alkenyl. In certain embodiments, at least one instance of R A is unsubstituted alkenyl. In certain embodiments, at least one instance of R A is substituted or unsubstituted C 1-6 alkenyl.
  • At least one instance of R A is vinyl. In certain embodiments, at least one instance of R A is substituted alkynyl. In certain embodiments, at least one instance of R is unsubstituted alkynyl. In certain embodiments, at least one instance of R A is ethynyl. In certain
  • At least one instance of R A is substituted carbocyclyl. In certain embodiments, at least one instance of R A is unsubstituted carbocyclyl. In certain embodiments, at least one instance of R A is saturated carbocyclyl. In certain embodiments, at least one instance of R A is unsaturated carbocyclyl. In certain embodiments, at least one instance of R A is carbocyclyl including zero, one, two, or three double bonds in the carbocyclic ring system. In certain embodiments, at least one instance of R A is monocyclic carbocyclyl. In certain embodiments, at least one instance of R A is 3- to 7-membered, monocyclic carbocyclyl.
  • At least one instance of R A is cylcopropyl. In certain embodiments, at least one instance of R A is cyclobutyl. In certain embodiments, at least one instance of R A is cyclopentyl. In certain embodiments, at least one instance of R A is cyclohexyl. In certain embodiments, at least one instance of R A is cycloheptyl. In certain embodiments, at least one instance of R A is bicyclic carbocyclyl. In certain embodiments, at least one instance of R A is 5- to 13-membered, bicyclic carbocyclyl. In certain embodiments, at least one instance of R A is substituted heterocyclyl. In certain embodiments, at least one instance of R A is
  • At least one instance of R A is saturated heterocyclyl. In certain embodiments, at least one instance of R A is unsaturated heterocyclyl. In certain embodiments, at least one instance of R A is heterocyclyl including zero, one, two, or three double bonds in the heterocyclic ring system. In certain embodiments, at least one instance of R A is heterocyclyl, wherein one, two, or three atoms in the heterocyclic ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, at least one instance of R A is monocyclic heterocyclyl. In certain embodiments, at least one instance of R A is 3- to 7-membered, monocyclic heterocyclyl.
  • At least one instance of R A is bicyclic heterocyclyl. In certain embodiments, at least one instance of R A is 5- to 13-membered, bicyclic heterocyclyl. In certain embodiments, at least one instance of R A is substituted aryl. In certain embodiments, at least one instance of R A is unsubstituted aryl. In certain embodiments, at least one instance of R A is 6- to 14-membered aryl. In certain embodiments, at least one instance of R A is 6- to 10-membered aryl. In certain embodiments, at least one instance of R A is substituted phenyl. In certain embodiments, at least one instance of R A is unsubstituted phenyl.
  • At least one instance of R A is substituted naphthyl. In certain embodiments, at least one instance of R A is unsubstituted naphthyl. In certain embodiments, at least one instance of R A is substituted heteroaryl. In certain embodiments, at least one instance of R A is unsubstituted heteroaryl. In certain embodiments, at least one instance of R is heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, at least one instance of R A is monocyclic heteroaryl. In certain embodiments, at least one instance of R A is 5-membered, monocyclic heteroaryl.
  • At least one instance of R A is 6-membered, monocyclic heteroaryl. In certain embodiments, at least one instance of R A is substituted pyridyl. In certain embodiments, at least one instance of R A is unsubstituted 2-pyridyl, unsubstituted 3-pyridyl, or unsubstituted 4-pyridyl. In certain embodiments, at least one instance of R A is bicyclic heteroaryl, wherein the point of attachment may be on any atom of the bicyclic heteroaryl ring system, as valency permits. In certain embodiments, at least one instance of R A is 9-membered, bicyclic heteroaryl.
  • At least one instance of R A is 10-membered, bicyclic heteroaryl. In certain embodiments, at least one instance of R A is -OR A1 . In certain embodiments, at least one instance of R A is -OR A1 , wherein R A1 is substituted or unsubstituted alkyl. In certain embodiments, at least one instance of R A is -OMe. In certain embodiments, at least one instance of R A is -OEt. In certain embodiments, at least one instance of R A is -OPr. In certain embodiments, at least one instance of R A is -OBu. In certain embodiments, at least one instance of R A is -O(pentyl).
  • At least one instance of R A is - O(hexyl). In certain embodiments, at least one instance of R A is -OBn. certain embodiments, at least one instance of R A is -OPh. In certain embodiments, at least one instance of R A is - OH. In certain embodiments, at least one instance of R A is -SR A1 . In certain embodiments, at least one instance of R A is -SMe. In certain embodiments, at least one instance of R A is -SH. In certain embodiments, at least one instance of R A is -N(R A1 ) 2 . In certain embodiments, at least one instance of R A is -NMe 2 .
  • at least one instance of R A is -N0 2 .
  • two R A groups may be joined to form a substituted or unsubstituted carbocyclic ring.
  • two instances of R A are joined to form a saturated or unsaturated carbocyclic ring.
  • two instances of R A are joined to form a carbocyclic ring including zero, one, two, or three double bonds in the carbocyclic ring system.
  • two instances of R A are joined to form a 3- to 7-membered, monocyclic carbocyclic ring.
  • two instances of R A are joined to form a 3-membered carbocyclic ring.
  • two instances of R A are joined to form a 4-membered carbocyclic ring. In certain embodiments, two instances of R A are joined to form a 5-membered carbocyclic ring. In certain embodiments, two instances of R A are joined to form a 6-membered carbocyclic ring. In certain embodiments, two instances of R A are joined to form a 7-membered carbocyclic ring. In certain embodiments,
  • two instances of R A are joined to form a 5- to 13-membered, bicyclic carbocyclic ring. [0089] In certain embodiments, two instances of R are joined to form a substituted or unsubstituted heterocyclic ring. In certain embodiments, two instances of R A are joined to form a saturated or unsaturated heterocyclic ring. In certain embodiments, two instances of R A are joined to form a heterocyclic ring including zero, one, two, or three double bonds in the heterocyclic ring system. In certain embodiments, two instances of R A are joined to form a heterocyclic ring, wherein one, two, or three atoms in the heterocyclic ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • two instances of R A are joined to form a 3- to 7-membered, monocyclic heterocyclic ring. In certain embodiments, two instances of R A are joined to form a 5- to 13- membered, bicyclic heterocyclic ring.
  • two instances of R A are joined to form a substituted or unsubstituted aryl ring. In certain embodiments, two instances of R A are joined to form a 6- to 14-membered aryl ring. In certain embodiments, two instances of R A are joined to form a 6- to 10-membered aryl ring. In certain embodiments, two instances of R A are joined to form a monocyclic aryl ring. In certain embodiments, two instances of R A are joined to form an unsubstituted phenyl ring. In certain embodiments, two instances of R A are joined to form a substituted phenyl ring. In certain embodiments, two instances of R A are joined to form a bicyclic aryl ring. In certain embodiments, two instances of R A are joined to form a naphthyl ring.
  • two instances of R A are joined to form a substituted or unsubstituted heteroaryl ring.
  • two instances of R A are joined to form a 5- or 6-membered, monocyclic heteroaryl ring, wherein one, two, or three atoms in the heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • two instances of R A are joined to form a substituted or unsubstituted pyridyl ring.
  • two instances of R A are joined to form a 9- or 10-membered, bicyclic heteroaryl ring, wherein one, two, three, or four atoms in the heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • At least one instance of R A is halogen, substituted or unsubstituted alkyl, or -OR A1 . In certain embodiments, at least one instance of R A is halogen, substituted or unsubstituted C 1-6 alkyl, or -OR A1 , wherein R A1 is substituted or unsubstituted Ci-6 alkyl.
  • At least one instance of R A1 is H. In certain embodiments, at least one instance of R A1 is substituted acyl. In certain embodiments, at least one instance of R A1 is unsubstituted acyl. In certain embodiments, at least one instance of R A1 is acetyl. In certain embodiments, at least one instance of R A1 is substituted alkyl. In certain embodiments,
  • At least one instance of R A1 is unsubstituted alkyl. In certain embodiments, at least one instance of R A1 is C 1-12 alkyl. In certain embodiments, at least one instance of R A1 is Ci-6 alkyl. In certain embodiments, at least one instance of R A1 is methyl. In certain embodiments, at least one instance of R A1 is ethyl. In certain embodiments, at least one instance of R A1 is propyl. In certain embodiments, at least one instance of R A1 is butyl. In certain embodiments, at least one instance of R A1 is pentyl. In certain embodiments, at least one instance of R A1 is hexyl.
  • At least one instance of R A1 is substituted alkenyl. In certain embodiments, at least one instance of R A1 is unsubstituted alkenyl. In certain embodiments, at least one instance of R A1 is vinyl. In certain embodiments,
  • At least one instance of R A1 is substituted alkynyl. In certain embodiments, at least one instance of R A1 is unsubstituted alkynyl. In certain embodiments, at least one instance of R A1 is ethynyl. In certain embodiments, at least one instance of R A1 is substituted carbocyclyl. In certain embodiments, at least one instance of R A1 is unsubstituted carbocyclyl. In certain embodiments, at least one instance of R A1 is saturated carbocyclyl. In certain embodiments, at least one instance of R A1 is unsaturated carbocyclyl.
  • At least one instance of R A1 is carbocyclyl including zero, one, two, or three double bonds in the carbocyclic ring system. In certain embodiments, at least one instance of R A1 is 3- to 7- membered, monocyclic carbocyclyl. In certain embodiments, at least one instance of R A1 is cylcopropyl. In certain embodiments, at least one instance of R A1 is cyclobutyl. In certain embodiments, at least one instance of R A1 is cyclopentyl. In certain embodiments, at least one instance of R A1 is cyclohexyl. In certain embodiments, at least one instance of R A1 is cycloheptyl.
  • At least one instance of R A1 is 5- to 13-membered, bicyclic carbocyclyl. In certain embodiments, at least one instance of R A1 is substituted heterocyclyl. In certain embodiments, at least one instance of R A1 is unsubstituted
  • heterocyclyl In certain embodiments, at least one instance of R A1 is saturated heterocyclyl. In certain embodiments, at least one instance of R A1 is unsaturated heterocyclyl. In certain embodiments, at least one instance of R is heterocyclyl including zero, one, two, or three double bonds in the heterocyclic ring system. In certain embodiments, at least one instance of R A1 is heterocyclyl, wherein one, two, or three atoms in the heterocyclic ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, at least one instance of R A1 is 3- to 7-membered, monocyclic heterocyclyl. In certain embodiments, at least one instance of R A1 is 5- to 13-membered, bicyclic
  • R A1 is substituted or
  • At least one instance of R A1 is 6- to 14-membered aryl. In certain embodiments, at least one instance of R A1 is 6- to 10-membered aryl. In certain embodiments, at least one instance of R A1 is monocyclic aryl. In certain embodiments, at least one instance of R A1 is unsubstituted phenyl. In certain embodiments, at least one instance of R A1 is substituted phenyl. In certain embodiments, at least one instance of R A1 is bicyclic aryl. In certain embodiments, at least one instance of R A1 is naphthyl.
  • At least one instance of R A1 is substituted or unsubstituted heteroaryl.
  • at least one instance of R A1 is 5- or 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • at least one instance of R A1 is pyridyl.
  • at least one instance of R A1 is bicyclic heteroaryl, wherein the point of attachment may be on any atom of the bicyclic heteroaryl ring system, as valency permits.
  • At least one instance of R A1 is 9- or 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • at least one instance of R A1 is a nitrogen protecting group when attached to a nitrogen atom.
  • at least one instance of R A1 is Bn, Boc, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl, acetyl, or Ts when attached to a nitrogen atom.
  • R A1 is an oxygen protecting group when attached to an oxygen atom.
  • R A1 is silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, ⁇ -Bu, Bn, allyl, acetyl, pivaloyl, or benzoyl when attached to an oxygen atom.
  • R A1 is a sulfur protecting group when attached to a sulfur atom.
  • R A1 is acetamidomethyl, ⁇ -Bu, 3-nitro-2-pyridine sulfenyl, 2-pyridine-sulfenyl, or triphenylmethyl when attached to a sulfur atom.
  • two instances of R A1 are joined to form a substituted or unsubstituted heterocyclic ring. In certain embodiments, two instances of R A1 are joined to form a saturated or unsaturated heterocyclic ring. In certain embodiments, two instances of R are joined to form a heterocyclic ring including zero, one, two, or three double bonds in the heterocyclic ring system. In certain embodiments, two instances of R A1 are joined to form a heterocyclic ring, wherein one, two, or three atoms in the heterocyclic ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • two instances of R A1 are joined to form a 3- to 7-membered, monocyclic heterocyclic ring. In certain embodiments, two instances of R A1 are joined to form a 5- to 13- membered, bicyclic heterocyclic ring.
  • k is 0. In certain embodiments, k is 1. In certain embodiments, k is 2. In certain embodiments, k is 3. In certain embodiments, k is 4. In certain embodiments, k is 5.
  • k is 1; and R A is halogen, substituted or unsubstituted alkyl, or -OR A1 . In certain embodiments, k is 1; and R A is halogen, substituted or
  • R A1 is substituted or unsubstituted C 1-6 alkyl, or -OR A1 , wherein R A1 is substituted or unsubstituted C 1-6 alkyl.
  • k is 2; and each instance of R A is independently halogen, substituted or unsubstituted alkyl, or -OR A1 .
  • k is 2; and each instance of R A is independently halogen, substituted or unsubstituted C 1-6 alkyl, or -OR A1 , wherein each instance of R A1 is independently substituted or unsubstituted C 1-6 alkyl.
  • Exemplary compounds of Formula (A) include, but are not limited to, compounds of any one of the formulae:
  • the methods of the invention also involves an imidating agent, such as an N- fluorosulfonimide, e.g., a compound of Formula (B), or a salt thereof.
  • an imidating agent such as an N- fluorosulfonimide, e.g., a compound of Formula (B), or a salt thereof.
  • Formula (B) may include one or more substituents R .
  • at least one instance of R B is H.
  • at least one instance of R B is halogen.
  • at least one instance of R is F.
  • at least one instance of R B is CI.
  • at least one instance of R B is Br.
  • at least one instance of R B is I (iodine).
  • at least one instance of R B is substituted acyl.
  • at least one instance of R is unsubstituted acyl.
  • at least one instance of R is substituted alkyl.
  • At least one instance of R is unsubstituted alkyl.
  • at least one instance of R B is C 1-12 alkyl.
  • at least one instance of R B is substituted Ci-6 alkyl.
  • at least one instance of R is unsubstituted C 1-6 alkyl.
  • at least one instance of R is substituted methyl.
  • At least one instance of R is -CH 2 F. In certain embodiments, at least one instance of R B is -CHF 2 . In certain embodiments, at least one instance of R B is -CF 3 . In certain embodiments, at least one instance of R is Bn. In certain embodiments, at least one instance of R B is unsubstituted methyl. In certain embodiments, at least one instance of R B is ethyl. In certain embodiments, at least one instance of R is propyl. In certain embodiments, at least one instance of R B is butyl. In certain embodiments, at least one instance of R B is pentyl. In certain embodiments, at least one instance of R is hexyl.
  • At least one instance of R is substituted alkenyl. In certain embodiments, at least one instance of R B is unsubstituted alkenyl. In certain embodiments, at least one instance of R B is substituted or unsubstituted C 1-6 alkenyl. In certain embodiments, at least one instance of R is vinyl. In certain embodiments, at least one instance of R is substituted alkynyl. In certain embodiments, at least one instance of R is unsubstituted alkynyl. In certain embodiments, at least one instance of R B is ethynyl. In certain embodiments, at least one instance of R B is substituted carbocyclyl.
  • At least one instance of R is unsubstituted carbocyclyl. In certain embodiments, at least one instance of R is saturated carbocyclyl. In certain embodiments, at least one instance of R is unsaturated carbocyclyl. In certain embodiments, at least one instance of R is carbocyclyl including zero, one, two, or three double bonds in the carbocyclic ring system. In certain embodiments, at least one instance of
  • R B is monocyclic carbocyclyl. In certain embodiments, at least one instance of R B is 3- to 7- membered, monocyclic carbocyclyl. In certain embodiments, at least one instance of R is cylcopropyl. In certain embodiments, at least one instance of R is cyclobutyl. In certain embodiments, at least one instance of R is cyclopentyl. In certain embodiments, at least one instance of R B is cyclohexyl. In certain embodiments, at least one instance of R B is cycloheptyl. In certain embodiments, at least one instance of R is bicyclic carbocyclyl.
  • At least one instance of R is 5- to 13-membered, bicyclic carbocyclyl. In certain embodiments, at least one instance of R is substituted heterocyclyl. In certain embodiments, at least one instance of R is unsubstituted heterocyclyl. In certain
  • At least one instance of R is saturated heterocyclyl. In certain embodiments, at least one instance of R is unsaturated heterocyclyl. In certain embodiments, at least one instance of R is heterocyclyl including zero, one, two, or three double bonds in the heterocyclic ring system. In certain embodiments, at least one instance of R is heterocyclyl, wherein one, two, or three atoms in the heterocyclic ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, at least one instance of R is monocyclic heterocyclyl. In certain embodiments, at least one instance of R is 3- to 7-membered, monocyclic heterocyclyl.
  • At least one instance of R B is bicyclic heterocyclyl. In certain embodiments, at least one instance of R B is 5- to 13-membered, bicyclic heterocyclyl. In certain embodiments, at least one instance of R is substituted aryl. In certain embodiments, at least one instance of R is unsubstituted aryl. In certain embodiments, at least one instance of R is 6- to 14-membered aryl. In certain embodiments, at least one instance of R is 6- to 10-membered aryl. In certain embodiments, at least one instance of R is substituted phenyl. In certain embodiments, at least one instance of R B is unsubstituted phenyl.
  • At least one instance of R B is substituted naphthyl. In certain embodiments, at least one instance of R is unsubstituted naphthyl. In certain embodiments, at least one instance of R is substituted heteroaryl. In certain embodiments, at least one instance of R is unsubstituted heteroaryl. In certain embodiments, at least one instance of R is heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, at least one instance of R is monocyclic heteroaryl. In certain embodiments, at least one instance of R is 5-membered, monocyclic heteroaryl.
  • At least one instance of R is 6-membered, monocyclic heteroaryl. In certain embodiments, at least one instance of R is substituted pyridyl. In certain embodiments, at least one instance of R is unsubstituted 2-pyridyl, unsubstituted 3-pyridyl, or unsubstituted 4-pyridyl. In certain embodiments, at least one instance of R is bicyclic heteroaryl, wherein the point of attachment may be on any atom of the bicyclic heteroaryl ring system, as valency permits. In certain embodiments, at least one instance of R is 9-membered, bicyclic heteroaryl.
  • At least one instance of R is 10-membered, bicyclic heteroaryl.
  • at least one instance of R B is -OR B 1.
  • at least one instance of R B is -OR B 1 , wherein R B 1 is substituted or unsubstituted alkyl.
  • at least one instance of R B is -OMe.
  • at least one instance of R B is -OEt.
  • at least one instance of R is -OPr.
  • at least one instance of R B is -OBu.
  • at least one instance of R B is -O(pentyl).
  • At least one instance of R is -O(hexyl). In certain embodiments, at least one instance of R is -OBn. In certain embodiments, at least one instance of R is - OPh. In certain embodiments, at least one instance of R is -OH. In certain embodiments, at least one instance of R B is -SR B 1. In certain embodiments, at least one instance of R B is - SMe. In certain embodiments, at least one instance of R is -SH. In certain embodiments, at least one instance of R B is -N(R B 1 ) 2 . In certain embodiments, at least one instance of R B is - NMe 2 . In certain embodiments, at least one instance of R is -NH 2 .
  • at least one instance of R B is -N0 2 .
  • at least one instance of R B is
  • two R B groups may be joined to form a substituted or unsubstituted carbocyclic ring.
  • two instances of R are joined to form a saturated or unsaturated carbocyclic ring.
  • two instances of R are joined to form a carbocyclic ring including zero, one, two, or three double bonds in the carbocyclic ring system.
  • two instances of R are joined to form a 3- to 7-membered, monocyclic carbocyclic ring.
  • two instances of R are joined to form a 3-membered carbocyclic ring.
  • two instances of R are joined to form a 4-membered carbocyclic ring.
  • two instances of R are joined to form a 5-membered carbocyclic ring. In certain embodiments, two instances of R are joined to form a 6-membered carbocyclic ring. In certain embodiments, two instances of R are joined to form a 7-membered carbocyclic ring. In certain embodiments,
  • two instances of R are joined to form a 5- to 13-membered, bicyclic carbocyclic ring.
  • two instances of R B are joined to form a substituted or unsubstituted heterocyclic ring. In certain embodiments, two instances of R are joined to form a saturated or unsaturated heterocyclic ring. In certain embodiments, two instances of R are joined to form a heterocyclic ring including zero, one, two, or three double bonds in the heterocyclic ring system. In certain embodiments, two instances of R are joined to form a heterocyclic ring, wherein one, two, or three atoms in the heterocyclic ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, two instances of R are joined to form a 3- to 7-membered, monocyclic heterocyclic ring. In certain embodiments, two instances of R are joined to form a 5- to 13- membered, bicyclic heterocyclic ring.
  • two instances of R B are joined to form a substituted or unsubstituted aryl ring. In certain embodiments, two instances of R are joined to form a 6- to 14-membered aryl ring. In certain embodiments, two instances of R are joined to form a 6- to 10-membered aryl ring. In certain embodiments, two instances of R are joined to form a monocyclic aryl ring. In certain embodiments, two instances of R are joined to form an unsubstituted phenyl ring. In certain embodiments, two instances of R are joined to form a substituted phenyl ring. In certain embodiments, two instances of R are joined to form a bicyclic aryl ring. In certain embodiments, two instances of R are joined to form a naphthyl ring.
  • two instances of R B are joined to form a substituted or unsubstituted heteroaryl ring.
  • two instances of R are joined to form a 5- or 6-membered, monocyclic heteroaryl ring, wherein one, two, or three atoms in the heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • two instances of R are joined to form a substituted or unsubstituted pyridyl ring.
  • each instance of R is H.
  • at least one instance of R is halogen or substituted or unsubstituted alkyl.
  • at least one instance of R is halogen or substituted or unsubstituted C 1-6 alkyl.
  • At least one instance of R B1 is H. In certain embodiments, at least one instance of R B 1 is substituted acyl. In certain embodiments, at least one instance of R B 1 is unsubstituted acyl. In certain embodiments, at least one instance of R B 1 is acetyl. In certain embodiments, at least one instance of R B 1 is substituted alkyl. In certain embodiments, at least one instance of R B 1 is unsubstituted alkyl. In certain embodiments, at least one instance of R B 1 is C 1-12 alkyl. In certain embodiments, at least one instance of R B 1 is C 1-6 alkyl. In certain embodiments, at least one instance of R B 1 is methyl.
  • At least one instance of R B 1 is ethyl. In certain embodiments, at least one instance of R B 1 is propyl. In certain embodiments, at least one instance of R B 1 is butyl. In certain embodiments, at least one instance of R B 1 is pentyl. In certain embodiments, at least one instance of R B 1 is hexyl. In certain embodiments, at least one instance of R B 1 is substituted alkenyl. In certain embodiments, at least one instance of R B 1 is unsubstituted alkenyl. In certain embodiments, at least one instance of R B 1 is vinyl. In certain embodiments, at least one instance of R B 1 is substituted alkynyl. In certain embodiments, at least one instance of R B 1 is unsubstituted alkynyl. In certain embodiments, at least one instance of R B 1 is ethynyl. In certain
  • At least one instance of R B 1 is substituted carbocyclyl. In certain embodiments, at least one instance of R B 1 is unsubstituted carbocyclyl. In certain embodiments, at least one instance of R B 1 is saturated carbocyclyl. In certain embodiments, at least one instance of R B 1 is unsaturated carbocyclyl. In certain embodiments, at least one instance of R B 1 is carbocyclyl including zero, one, two, or three double bonds in the carbocyclic ring system. In certain embodiments, at least one instance of R B 1 is 3- to 7-membered, monocyclic carbocyclyl. In certain embodiments, at least one instance of R B 1 is cylcopropyl.
  • At least one instance of R B 1 is cyclobutyl. In certain embodiments, at least one instance of R B 1 is cyclopentyl. In certain embodiments, at least one instance of R B 1 is cyclohexyl. In certain embodiments, at least one instance of R B 1 is cycloheptyl. In certain embodiments, at least one instance of R B 1 is 5- to 13-membered, bicyclic carbocyclyl. In certain embodiments, at least one instance of R B 1 is substituted heterocyclyl. In certain embodiments, at least one instance of R B 1 is unsubstituted heterocyclyl. In certain embodiments, at least one instance of R B 1 is saturated heterocyclyl.
  • At least one instance of R B 1 is unsaturated heterocyclyl. In certain embodiments, at least one instance of R B 1 is heterocyclyl including zero, one, two, or three double bonds in the heterocyclic ring system. In certain embodiments, at least one instance of R is heterocyclyl, wherein one, two, or three atoms in the heterocyclic ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, at least one instance of R B 1 is 3- to 7-membered, monocyclic heterocyclyl. In certain embodiments, at least one instance of R B 1 is 5- to 13- membered, bicyclic heterocyclyl. In certain embodiments, at least one instance of R B 1 is substituted or unsubstituted aryl. In certain embodiments, at least one instance of R B 1 is 6- to
  • At least one instance of R B 1 is 6- to 10-membered aryl. In certain embodiments, at least one instance of R B 1 is monocyclic aryl. In certain embodiments, at least one instance of R B 1 is unsubstituted phenyl. In certain embodiments, at least one instance of R B 1 is substituted phenyl. In certain embodiments, at least one instance of R B 1 is bicyclic aryl. In certain embodiments, at least one instance of R B 1 is naphthyl. In certain embodiments, at least one instance of R B 1 is substituted or unsubstituted heteroaryl.
  • At least one instance of R B 1 is 5- or 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • at least one instance of R B 1 is pyridyl.
  • at least one instance of R B 1 is bicyclic heteroaryl, wherein the point of attachment may be on any atom of the bicyclic heteroaryl ring system, as valency permits.
  • At least one instance of R B 1 is 9- or 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • at least one instance of R B 1 is a nitrogen protecting group when attached to a nitrogen atom.
  • at least one instance of R B 1 is Bn, Boc, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl, acetyl, or Ts when attached to a nitrogen atom.
  • R B 1 is an oxygen protecting group when attached to an oxygen atom.
  • R B 1 is silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, ⁇ -Bu, Bn, allyl, acetyl, pivaloyl, or benzoyl when attached to an oxygen atom.
  • R B 1 is a sulfur protecting group when attached to a sulfur atom.
  • R B 1 is acetamidomethyl, ⁇ -Bu, 3-nitro-2-pyridine sulfenyl, 2-pyridine-sulfenyl, or triphenylmethyl when attached to a sulfur atom.
  • two instances of R B1 are joined to form a substituted or unsubstituted heterocyclic ring. In certain embodiments, two instances of R B 1 are joined to form a saturated or unsaturated heterocyclic ring. In certain embodiments, two instances of
  • R B 1 are joined to form a heterocyclic ring including zero, one, two, or three double bonds in the heterocyclic ring system.
  • two instances of R B 1 are joined to form a heterocyclic ring, wherein one, two, or three atoms in the heterocyclic ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • two instances of R B 1 are joined to form a 3- to 7-membered, monocyclic heterocyclic ring.
  • two instances of R B 1 are joined to form a 5- to 13- membered, bicyclic heterocyclic ring.
  • At least one instance of m is 0. In certain embodiments, at least one instance of m is 1. In certain embodiments, at least one instance of m is 2. In certain embodiments, at least one instance of m is 3. In certain embodiments, at least one instance of m is 4. In certain embodiments, at least one instance of m is 5. In certain embodiments, both instances of m are 0. In certain embodiments, both instances of m are 1. In certain embodiments,
  • both instances of m are 2. In certain embodiments, both instances of m are 3. In certain embodiments, both instances of m are 4. In certain embodiments, both instances of m are 5.
  • a compound of Formula (B) is commercially available.
  • An exemplary compound of Formula (B) is N-fluorobenzenesulfonimide (NFBS or NFSI).
  • the methods of the invention involve a catalyst.
  • the catalyst employed in the inventive methods includes a transition metal complex, such as a complex of any one of Formulae (CI) to (C25).
  • Complexes of any one of Formulae (CI) to (C25) include a transition metal ion M.
  • M is a transition metal cation.
  • M is a monovalent transition metal ion.
  • M is Ag + , Cu + , or Co + .
  • M is a divalent transition metal ion.
  • M is Pd 2+ , Ni 2+ , Cu 2+ , Ir 2+ , Zn 2+ , Mn 2+ , or Fe 2+ .
  • M is a trivalent transition metal ion.
  • M is Rh 3+ .
  • M is a tetravalent, pentavalent, or hexavalent transition metal ion.
  • Complexes of Formula (CI) include at least two instances of Ring B.
  • all instances of Ring B are independently substituted or unsubstituted heteroaryl.
  • at least one instance of Ring B is monocyclic, 5- membered heteroaryl, wherein one, two, or three atoms in the heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • At least one instance of Ring B is of the formula: . In certain In certain
  • At least one instance of Ring B is of the formula: e instance of Ring B is of the formula: , or embodiments, at least one instance of Ring B is of the formula: , 5 or In certain embodiments at least one instance of
  • Ring B is of the formula: embodiments, at least one instance of Ring B is of the formula:
  • Ring B is of the formula:
  • At least one instance of Ring B is of the
  • At least one instance of Ring B is of the formula: ,
  • At least one instance of Ring B is of the
  • Ring B is of the formula: . In certain embodiments,
  • At least one instance of Ring B is of the formula: . In certain embodiments, at least
  • Ring B is of the formula: .
  • at least one instance of Ring B is monocyclic, 6-membered heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • at least one instance of Ring B is of the
  • At least one instance of Ring B is of the
  • At least one instance of Ring B is of the formula: , (RC, ' , , or .
  • At least one instance of Ring B is of the formula:
  • each instance of Ring B is substituted or unsubstituted, monocyclic, 5- or 6-membered heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • at least one instance of Ring B is bicyclic, 9- or 10-membered heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • Complexes of Formula (CI) may include one or more substituents R c .
  • at least one instance of R is H.
  • at least one instance of R c is halogen.
  • at least one instance of R c is F.
  • at least one instance of R is CI.
  • at least one instance of R is Br.
  • at least one instance of R c is I (iodine).
  • at least one instance of R is substituted acyl.
  • at least one instance of R c is unsubstituted acyl.
  • at least one instance of R c is substituted alkyl.
  • at least one instance of R is unsubstituted alkyl.
  • At least one instance of R is C 1-12 alkyl. In certain embodiments, at least one instance of R is substituted C 1-6 alkyl. In certain embodiments, at least one instance of R c is unsubstituted C 1-6 alkyl. In certain embodiments, at least one instance of R c is substituted methyl. In certain embodiments, at least one instance of R is -CH 2 F. In certain embodiments, at least one instance of R is -CHF 2 . In certain embodiments, at least one instance of R c is -CF 3 . In certain embodiments, at least one instance of R c is Bn. In certain embodiments, at least one instance of R is unsubstituted methyl. In certain embodiments, at least one instance of R c is ethyl. In certain embodiments, at least one instance of R c is propyl.
  • At least one instance of R is butyl. In certain embodiments, at least one instance of R c is pentyl. In certain embodiments, at least one instance of R c is hexyl. In certain embodiments, at least one instance of R is substituted alkenyl. In certain embodiments,
  • At least one instance of R is unsubstituted alkenyl. In certain embodiments, at least one instance of R is substituted or unsubstituted C 1-6 alkenyl. In certain embodiments, at least one instance of R c is vinyl. In certain embodiments, at least one instance of R c is substituted alkynyl. In certain embodiments, at least one instance of R is unsubstituted alkynyl. In certain embodiments, at least one instance of R is ethynyl. In certain
  • At least one instance of R is substituted carbocyclyl. In certain embodiments, at least one instance of R is unsubstituted carbocyclyl. In certain embodiments, at least one instance of R c is saturated carbocyclyl. In certain embodiments, at least one instance of R c is unsaturated carbocyclyl. In certain embodiments, at least one instance of R is carbocyclyl including zero, one, two, or three double bonds in the carbocyclic ring system. In certain embodiments, at least one instance of R is monocyclic carbocyclyl. In certain embodiments, at least one instance of R is 3- to 7-membered, monocyclic carbocyclyl. In certain embodiments, at least one instance of R is cylcopropyl. In certain embodiments, at least one instance of R c is cyclobutyl. In certain embodiments, at least one instance of R c is
  • At least one instance of R is cyclohexyl. In certain embodiments, at least one instance of R is cycloheptyl. In certain embodiments, at least one instance of R c is bicyclic carbocyclyl. In certain embodiments, at least one instance of R c is bicyclic, 5- to 13-membered carbocyclyl. In certain embodiments, at least one instance of R is substituted heterocyclyl. In certain embodiments, at least one instance of R is
  • At least one instance of R is saturated heterocyclyl. In certain embodiments, at least one instance of R is unsaturated heterocyclyl.
  • At least one instance of R is heterocyclyl including zero, one, two, or three double bonds in the heterocyclic ring system. In certain embodiments, at least one instance of R is heterocyclyl, wherein one, two, or three atoms in the heterocyclic ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • At least one instance of R is monocyclic heterocyclyl. In certain embodiments, at least one instance of R is monocylic, 3- to 7-membered heterocyclyl. In certain embodiments, at least one instance of R is bicyclic heterocyclyl. In certain embodiments, at least one instance of R is bicyclic, 5- to 13-membered heterocyclyl. In certain embodiments, at least one instance of R is substituted aryl. In certain embodiments, at least one instance of R is unsubstituted aryl. In certain embodiments, at least one instance of R c is 6- to 14-membered aryl. In certain embodiments, at least one instance of R c is 6- to
  • At least one instance of R is substituted phenyl.
  • At least one instance of R is unsubstituted phenyl. In certain embodiments, at least one instance of R is substituted naphthyl. In certain embodiments, at least one instance of R is unsubstituted naphthyl. In certain embodiments, at least one instance of R c is substituted heteroaryl. In certain embodiments, at least one instance of R c is unsubstituted heteroaryl. In certain embodiments, at least one instance of R is heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, at least one instance of R is monocyclic heteroaryl.
  • At least one instance of R is monocyclic, 5-membered heteroaryl. In certain embodiments, at least one instance of R is monocyclic, 6-membered heteroaryl. In certain embodiments, at least one instance of R c is substituted pyridyl. In certain embodiments, at least one instance of R c is unsubstituted 2-pyridyl, unsubstituted 3-pyridyl, or unsubstituted 4-pyridyl. In certain embodiments, at least one instance of R is bicyclic heteroaryl, wherein the point of attachment may be on any atom of the bicyclic heteroaryl ring system, as valency permits.
  • At least one instance of R is bicyclic, 9-membered heteroaryl. In certain embodiments, at least one instance of R is bicyclic, 10-membered heteroaryl. In certain embodiments, at least one instance of R C is -OR CI . In certain embodiments, at least one instance of R C is -OR CI , wherein R CI is substituted or unsubstituted alkyl. In certain embodiments, at least one instance of R is -OMe. In certain embodiments, at least one instance of R c is -OEt. In certain embodiments, at least one instance of R c is -OPr. In certain embodiments, at least one instance of R is -OBu. In certain embodiments, at least one instance of R c is -O(pentyl). In certain embodiments, at least one instance of R c is -
  • At least one instance of R is -OBn.
  • At least one instance of R is -OPh. In certain embodiments, at least one instance of R C is -OH. In certain embodiments, at least one instance of R C is -SR CI . In certain embodiments, at least one instance of R is -SMe. In certain embodiments, at least one instance of R C is -SH. In certain embodiments, at least one instance of R C is -N(R CI ) 2 . In certain embodiments, at least one instance of R is -NMe 2 . In certain embodiments, at least one instance of R c is -NH 2 . In certain embodiments, at least one instance of R c is -CN. In certain embodiments, at least one instance of R is -SCN.
  • at least one instance of R c is -
  • at least one instance of R c is -N0 2 .
  • two R c groups may be joined to form a substituted or unsubstituted carbocyclic ring.
  • two instances of R are joined to form a saturated or unsaturated carbocyclic ring.
  • two instances of R are joined to form a carbocyclic ring including zero, one, two, or three double bonds in the carbocyclic ring system.
  • two instances of R are joined to form a 3- to 7-membered, monocyclic carbocyclic ring.
  • two instances of R are joined to form a 3-membered carbocyclic ring.
  • two instances of R are joined to form a 4-membered carbocyclic ring.
  • two instances of R are joined to form a 5-membered carbocyclic ring. In certain embodiments, two instances of R are joined to form a 6-membered carbocyclic ring. In certain embodiments, two instances of R are joined to form a 7-membered carbocyclic ring. In certain embodiments,
  • two instances of R are joined to form a 5- to 13-membered, bicyclic carbocyclic ring.
  • two instances of R c are joined to form a substituted or unsubstituted heterocyclic ring. In certain embodiments, two instances of R are joined to form a saturated or unsaturated heterocyclic ring. In certain embodiments, two instances of R are joined to form a heterocyclic ring including zero, one, two, or three double bonds in the heterocyclic ring system. In certain embodiments, two instances of R are joined to form a heterocyclic ring, wherein one, two, or three atoms in the heterocyclic ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, two instances of R are joined to form a 3- to 7-membered, monocyclic heterocyclic ring. In certain embodiments, two instances of R are joined to form a 5- to 13- membered, bicyclic heterocyclic ring.
  • two instances of R c are joined to form a substituted or unsubstituted aryl ring.
  • two instances of R are joined to form a 6- to 14-membered aryl ring.
  • two instances of R are joined to form a 6- to 10-membered aryl ring.
  • two instances of R are joined to form a monocyclic aryl ring.
  • two instances of R are joined to form an unsubstituted phenyl ring.
  • two instances of R are joined to form a substituted phenyl ring.
  • two instances of R are joined to form a bicyclic aryl ring.
  • two instances of R are joined to form a naphthyl ring.
  • two instances of R c are joined to form a substituted or unsubstituted heteroaryl ring.
  • two instances of R are joined to form a 5- or 6-membered, monocyclic heteroaryl ring, wherein one, two, or three atoms in the heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • two instances of R are joined to form a substituted or unsubstituted pyridyl ring.
  • two instances of R are joined to form a 9- or 10-membered, bicyclic heteroaryl ring, wherein one, two, three, or four atoms in the heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • each instance of R c is H.
  • at least one instance of R is halogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, or -OR CI .
  • at least one instance of R c is halogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted phenyl, or -OR CI , wherein R CI is substituted or unsubstituted C 1-6 alkyl.
  • At least one instance of R C 1 is H. In certain embodiments, at least one instance of R C 1 is substituted acyl. In certain embodiments, at least one instance of R CI is unsubstituted acyl. In certain embodiments, at least one instance of R CI is acetyl. In certain embodiments, at least one instance of R CI is substituted alkyl. In certain embodiments, at least one instance of R C 1 is unsubstituted alkyl. In certain embodiments, at least one instance of R CI is C 1-12 alkyl. In certain embodiments, at least one instance of R CI is C 1-6 alkyl. In certain embodiments, at least one instance of R CI is methyl.
  • At least one instance of R CI is ethyl. In certain embodiments, at least one instance of R CI is propyl. In certain embodiments, at least one instance of R C 1 is butyl. In certain embodiments, at least one instance of R CI is pentyl. In certain embodiments, at least one instance of R CI is hexyl. In certain embodiments, at least one instance of R C 1 is substituted alkenyl. In certain embodiments, at least one instance of R CI is unsubstituted alkenyl. In certain embodiments, at least one instance of R CI is vinyl. In certain embodiments, at least one instance of R CI is substituted alkynyl. In certain embodiments, at least one instance of R is unsubstituted alkynyl. In certain embodiments, at least one instance of R CI is ethynyl. In certain
  • At least one instance of R CI is substituted carbocyclyl. In certain embodiments, at least one instance of R C 1 is unsubstituted carbocyclyl. In certain embodiments, at least one instance of R CI is saturated carbocyclyl. In certain embodiments, at least one instance of R CI is unsaturated carbocyclyl. In certain embodiments, at least one instance of R C 1 is carbocyclyl including zero, one, two, or three double bonds in the carbocyclic ring system. In certain embodiments, at least one instance of R CI is 3- to 7-membered, monocyclic carbocyclyl. In certain embodiments, at least one instance of R CI is cylcopropyl.
  • At least one instance of R CI is cyclobutyl. In certain embodiments, at least one instance of R CI is cyclopentyl. In certain embodiments, at least one instance of R CI is cyclohexyl. In certain embodiments, at least one instance of R CI is cycloheptyl. In certain embodiments, at least one instance of R C 1 is bicyclic, 5- to 13-membered carbocyclyl. In certain embodiments, at least one instance of R CI is substituted heterocyclyl. In certain embodiments, at least one instance of R CI is unsubstituted heterocyclyl. In certain embodiments, at least one instance of R CI is saturated heterocyclyl.
  • At least one instance of R C 1 is unsaturated heterocyclyl. In certain embodiments, at least one instance of R CI is heterocyclyl including zero, one, two, or three double bonds in the heterocyclic ring system. In certain embodiments, at least one instance of R C 1 is heterocyclyl, wherein one, two, or three atoms in the heterocyclic ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, at least one instance of R C 1 is monocyclic, 3- to
  • At least one instance of R CI is bicyclic, 5- to 13-membered heterocyclyl. In certain embodiments, at least one instance of R C 1 is substituted or unsubstituted aryl. In certain embodiments, at least one instance of R CI is 6- to
  • At least one instance of R C 1 is 6- to 10-membered aryl. In certain embodiments, at least one instance of R C 1 is monocyclic aryl. In certain embodiments, at least one instance of R CI is unsubstituted phenyl. In certain embodiments, at least one instance of R CI is substituted phenyl. In certain embodiments, at least one instance of R CI is bicyclic aryl. In certain embodiments, at least one instance of R CI is naphthyl. In certain embodiments, at least one instance of R CI is substituted or unsubstituted heteroaryl. In certain embodiments, at least one instance of R CI is 5- or 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are
  • At least one instance of R CI is pyridyl.
  • at least one instance of R is bicyclic heteroaryl, wherein the point of attachment may be on any atom of the bicyclic heteroaryl ring system, as valency permits.
  • R is 9- or 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently selected from the group consisting of
  • At least one instance of R is a nitrogen protecting group when attached to a nitrogen atom. In certain embodiments, at least
  • R is Bn, Boc, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl, acetyl, or Ts
  • R is an oxygen protecting group
  • R is silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, ⁇ -Bu, Bn, allyl, acetyl, pivaloyl, or benzoyl when attached to
  • R is a sulfur protecting group when attached to a
  • R is acetamidomethyl, ⁇ -Bu, 3-nitro-2-pyridine sulfenyl, 2-pyridine-sulfenyl, or triphenylmethyl when attached to a sulfur atom.
  • two instances of R are joined to form a saturated or unsaturated heterocyclic ring. In certain embodiments, two instances of
  • R are joined to form a heterocyclic ring including zero, one, two, or three double bonds in
  • heterocyclic ring system two instances of R are joined to form a heterocyclic ring, wherein one, two, or three atoms in the heterocyclic ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • two instances of R are joined to form a 3- to 7-membered, monocyclic
  • heterocyclic ring In certain embodiments, two instances of R are joined to form a 5- to 13- membered, bicyclic heterocyclic ring.
  • At least one instance of r is 0. In certain embodiments, at least one instance of r is 1. In certain embodiments, at least one instance of r is 2. In certain embodiments, at least one instance of r is 3. In certain embodiments, at least one instance of r is 4. In certain embodiments, at least one instance of r is 5. In certain embodiments, each instance of r is 0. In certain embodiments, each instance of r is 1. In certain embodiments, each instance of r is 2. In certain embodiments, each instance of r is 3. In certain
  • each instance of r is 4. In certain embodiments, each instance of r is 5.
  • At least one instance of r is 1 ; and at least one instance of
  • R is halogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, or -OR .
  • at least one instance of r is 1 ; and at least one instance of R is halogen, substituted or unsubstituted C . alkyl, substituted or unsubstituted phenyl, or - OR CI , wherein R CI is substituted or unsubstituted C 1-6 alkyl.
  • each instance of r is 1; and each instance of R is halogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, or -OR C 1.
  • each instance of r is 1; and each instance of R is halogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted phenyl, or -OR CI , wherein R CI is substituted or unsubstituted C 1-6 alkyl.
  • Complexes of Formula (CI) or (C2) include more than one substituent R D .
  • R D is substituted acyl.
  • at least one instance of R D is unsubstituted acyl.
  • at least one instance of R D is substituted alkyl.
  • at least one instance of R D is unsubstituted alkyl.
  • at least one instance of R D is C 1-12 alkyl.
  • At least one instance of R D is substituted C 1-6 alkyl. In certain embodiments, at least one instance of R D is unsubstituted C 1-6 alkyl. In certain embodiments, at least one instance of R D is substituted methyl. In certain embodiments, at least one instance of R D is - CH 2 F. In certain embodiments, at least one instance of R D is -CHF 2 . In certain embodiments, at least one instance of R D is -CF 3 . In certain embodiments, at least one instance of R D is Bn. In certain embodiments, at least one instance of R D is unsubstituted methyl. In certain embodiments, at least one instance of R D is ethyl.
  • At least one instance of R D is propyl. In certain embodiments, at least one instance of R D is butyl. In certain embodiments, at least one instance of R D is pentyl. In certain embodiments, at least one instance of R D is hexyl. In certain embodiments, at least one instance of R D is substituted alkenyl. In certain embodiments, at least one instance of R D is unsubstituted alkenyl. In certain embodiments, at least one instance of R D is substituted or unsubstituted C 1-6 alkenyl. In certain embodiments, at least one instance of R D is vinyl. In certain embodiments, at least one instance of R D is substituted alkynyl.
  • At least one instance of R D is unsubstituted alkynyl. In certain embodiments, at least one instance of R D is ethynyl. In certain embodiments, at least one instance of R D is substituted carbocyclyl. In certain embodiments, at least one instance of R D is unsubstituted carbocyclyl. In certain embodiments,
  • At least one instance of R D is saturated carbocyclyl. In certain embodiments, at least one instance of R D is unsaturated carbocyclyl. In certain embodiments, at least one instance of R D is carbocyclyl including zero, one, two, or three double bonds in the carbocyclic ring system. In certain embodiments, at least one instance of R D is monocyclic carbocyclyl. In certain embodiments, at least one instance of R D is 3- to 7-membered, monocyclic carbocyclyl. In certain embodiments, at least one instance of R D is cylcopropyl. In certain embodiments, at least one instance of R D is cyclobutyl. In certain embodiments, at least one instance of R is cyclopentyl.
  • At least one instance of R is cyclohexyl. In certain embodiments, at least one instance of R D is cycloheptyl. In certain embodiments, at least one instance of R D is bicyclic carbocyclyl. In certain embodiments, at least one instance of R D is 5- to 13-membered, bicyclic carbocyclyl. In certain embodiments, at least one instance of R D is substituted heterocyclyl. In certain embodiments, at least one instance of R D is unsubstituted heterocyclyl. In certain embodiments, at least one instance of R D is saturated heterocyclyl. In certain embodiments, at least one instance of R D is unsaturated heterocyclyl.
  • At least one instance of R D is heterocyclyl including zero, one, two, or three double bonds in the heterocyclic ring system. In certain embodiments, at least one instance of R D is heterocyclyl, wherein one, two, or three atoms in the heterocyclic ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, at least one instance of R D is monocyclic heterocyclyl. In certain embodiments, at least one instance of R D is 3- to 7-membered, monocyclic heterocyclyl. In certain embodiments, at least one instance of R D is bicyclic heterocyclyl. In certain embodiments, at least one instance of R D is 5- to 13-membered, bicyclic heterocyclyl. In certain embodiments, at least one instance of R D is substituted aryl. In certain embodiments, at least one instance of R D is unsubstituted aryl. In certain embodiments,
  • At least one instance of R D is 6- to 14-membered aryl. In certain embodiments, at least one instance of R D is 6- to 10-membered aryl. In certain embodiments, at least one instance of R D is substituted phenyl. In certain embodiments, at least one instance of R D is unsubstituted phenyl. In certain embodiments, at least one instance of R D is substituted naphthyl. In certain embodiments, at least one instance of R D is unsubstituted naphthyl. In certain embodiments, at least one instance of R D is substituted heteroaryl. In certain embodiments, at least one instance of R D is unsubstituted heteroaryl.
  • At least one instance of R D is heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • at least one instance of R D is monocyclic heteroaryl.
  • at least one instance of R D is 5-membered, monocyclic heteroaryl.
  • at least one instance of R D is 6-membered, monocyclic heteroaryl.
  • at least one instance of R D is substituted pyridyl.
  • At least one instance of R D is unsubstituted 2-pyridyl, unsubstituted 3- pyridyl, or unsubstituted 4-pyridyl.
  • at least one instance of R D is bicyclic heteroaryl, wherein the point of attachment may be on any atom of the bicyclic heteroaryl ring system, as valency permits.
  • at least one instance of R is 9-membered, bicyclic heteroaryl.
  • at least one instance of R is 10-membered, bicyclic heteroaryl.
  • at least one instance of R D is a nitrogen protecting group.
  • at least one instance of R D is Bn, Boc, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl, acetyl, or Ts.
  • two instances of R D are joined to form a substituted or unsubstituted heterocyclic ring. In certain embodiments, two instances of R D are joined to form a saturated or unsaturated heterocyclic ring. In certain embodiments, two instances of R D are joined to form a heterocyclic ring including zero, one, two, or three double bonds in the heterocyclic ring system. In certain embodiments, two instances of R D are joined to form a heterocyclic ring, wherein one, two, or three atoms in the heterocyclic ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • two instances of R D are joined to form a 3- to 7-membered, monocyclic heterocyclic ring.
  • two instances of R D are joined to form a substituted or unsubstituted, 4- to 7-membered, monocyclic heterocyclic ring including zero, one, or two double bonds in the heterocyclic ring system, wherein one, two, or three atoms in the heterocyclic ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • two instances of R D are joined to form a
  • heterocyclic ring of 5 wherein the heterocyclic ring is substituted or unsubstituted.
  • two instances of R 1 are joined to form a 5- to 13-membered, bicyclic heterocyclic ring.
  • two instances of R D are joined to form a substituted or unsubstituted, 7- to 11-membered, bicyclic heterocyclic ring including zero, one, or two double bonds in the heterocyclic ring system, wherein one, two, or three atoms in the heterocyclic ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • heterocyclic ring of the formula: , wherein the heterocyclic ring is substituted or unsubstituted.
  • At least one instance of R D is H, substituted or
  • R D is H, substituted or unsubstituted C 1-6 alkyl, or two instances of R are joined to form a substituted or unsubstituted, 4- to 7-membered, monocyclic heterocyclic ring including zero, one, or two double bonds in the heterocyclic ring system, wherein one, two, or three atoms in the heterocyclic ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • each instance of R D is H, substituted or unsubstituted alkyl, or two instances of R D are joined to form a substituted or unsubstituted heterocyclic ring. In certain embodiments, each instance of R D is H, substituted or
  • At least one instance of R D1 is H. In certain embodiments, at least one instance of R D1 is substituted acyl. In certain embodiments, at least one instance of R D1 is unsubstituted acyl. In certain embodiments, at least one instance of R D1 is acetyl. In certain embodiments, at least one instance of R D1 is substituted alkyl. In certain
  • At least one instance of R D1 is unsubstituted alkyl. In certain embodiments, at least one instance of R D1 is C 1-12 alkyl. In certain embodiments, at least one instance of R D1 is Ci-6 alkyl. In certain embodiments, at least one instance of R D1 is methyl. In certain embodiments, at least one instance of R D1 is ethyl. In certain embodiments, at least one instance of R D1 is propyl. In certain embodiments, at least one instance of R D1 is butyl. In certain embodiments, at least one instance of R D1 is pentyl. In certain embodiments, at least one instance of R D1 is hexyl.
  • At least one instance of R D1 is substituted alkenyl. In certain embodiments, at least one instance of R D1 is unsubstituted alkenyl. In certain embodiments, at least one instance of R D1 is vinyl. In certain embodiments,
  • At least one instance of R D1 is substituted alkynyl. In certain embodiments, at least one instance of R D1 is unsubstituted alkynyl. In certain embodiments, at least one instance of R D1 is ethynyl. In certain embodiments, at least one instance of R D1 is substituted carbocyclyl. In certain embodiments, at least one instance of R D1 is unsubstituted carbocyclyl. In certain embodiments, at least one instance of R D1 is saturated carbocyclyl. In certain embodiments, at least one instance of R D1 is unsaturated carbocyclyl.
  • At least one instance of R D1 is carbocyclyl including zero, one, two, or three double bonds in the carbocyclic ring system. In certain embodiments, at least one instance of R D1 is 3- to 7- membered, monocyclic carbocyclyl. In certain embodiments, at least one instance of R D1 is cylcopropyl. In certain embodiments, at least one instance of R is cyclobutyl. In certain embodiments, at least one instance of R D1 is cyclopentyl. In certain embodiments, at least one instance of R D1 is cyclohexyl. In certain embodiments, at least one instance of R D1 is cycloheptyl.
  • At least one instance of R D1 is 5- to 13-membered, bicyclic carbocyclyl. In certain embodiments, at least one instance of R D1 is substituted heterocyclyl. In certain embodiments, at least one instance of R D1 is unsubstituted
  • heterocyclyl In certain embodiments, at least one instance of R D1 is saturated heterocyclyl. In certain embodiments, at least one instance of R D1 is unsaturated heterocyclyl. In certain embodiments, at least one instance of R D1 is heterocyclyl including zero, one, two, or three double bonds in the heterocyclic ring system. In certain embodiments, at least one instance of R D1 is heterocyclyl, wherein one, two, or three atoms in the heterocyclic ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, at least one instance of R D1 is 3- to 7-membered, monocyclic heterocyclyl. In certain embodiments, at least one instance of R D1 is 5- to 13-membered, bicyclic
  • R D1 is substituted or
  • At least one instance of R D1 is 6- to 14-membered aryl. In certain embodiments, at least one instance of R D1 is 6- to 10-membered aryl. In certain embodiments, at least one instance of R D1 is monocyclic aryl. In certain embodiments, at least one instance of R D1 is unsubstituted phenyl. In certain embodiments, at least one instance of R D1 is substituted phenyl. In certain embodiments, at least one instance of R D1 is bicyclic aryl. In certain embodiments, at least one instance of R D1 is naphthyl.
  • At least one instance of R D1 is substituted or unsubstituted heteroaryl.
  • at least one instance of R D1 is 5- or 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • at least one instance of R D1 is pyridyl.
  • at least one instance of R D1 is bicyclic heteroaryl, wherein the point of attachment may be on any atom of the bicyclic heteroaryl ring system, as valency permits.
  • At least one instance of R D1 is 9- or 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • at least one instance of R D1 is a nitrogen protecting group when attached to a nitrogen atom.
  • at least one instance of R D1 is Bn, Boc, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl, acetyl, or Ts when attached to a nitrogen atom.
  • R D1 is an oxygen protecting group when attached to an oxygen atom.
  • R is silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, i-Bu, Bn, allyl, acetyl, pivaloyl, or benzoyl when attached to an oxygen atom.
  • R D1 is a sulfur protecting group when attached to a sulfur atom.
  • R D1 is acetamidomethyl, ⁇ -Bu, 3-nitro-2-pyridine sulfenyl, 2-pyridine-sulfenyl, or triphenylmethyl when attached to a sulfur atom.
  • two instances of R D1 are joined to form a substituted or unsubstituted heterocyclic ring. In certain embodiments, two instances of R D1 are joined to form a saturated or unsaturated heterocyclic ring. In certain embodiments, two instances of R D1 are joined to form a heterocyclic ring including zero, one, two, or three double bonds in the heterocyclic ring system. In certain embodiments, two instances of R D1 are joined to form a heterocyclic ring, wherein one, two, or three atoms in the heterocyclic ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • two instances of R D1 are joined to form a 3- to 7-membered, monocyclic heterocyclic ring. In certain embodiments, two instances of R D1 are joined to form a 5- to 13- membered, bicyclic heterocyclic ring.
  • Complexes of Formula (CI) or (C2) may include one or more substituent R E .
  • At least one instance of R is absent. In certain embodiments, at least one instance of R E is H. In certain embodiments, at least one instance of R E is substituted p
  • acyl In certain embodiments, at least one instance of R is unsubstituted acyl. In certain embodiments,
  • At least one instance of R is substituted alkyl. In certain embodiments, at least one instance of R E is unsubstituted alkyl. In certain embodiments, at least one instance of R E p
  • R is C 1-12 alkyl. In certain embodiments, at least one instance of R is substituted C 1-6 alkyl. In p
  • At least one instance of R is unsubstituted C 1-6 alkyl.
  • At least one instance of R is substituted methyl. In certain embodiments, at least one instance of R E is -CH 2 F. In certain embodiments, at least one instance of R E is - p
  • At least one instance of R is -CF 3 . In certain embodiments, at least one instance of R E is Bn. In certain embodiments, at least one instance of R E is
  • At least one instance of R is ethyl.
  • At least one instance of R is propyl. In certain embodiments, at least one instance of R E is butyl. In certain embodiments, at least one instance of R E is pentyl. In
  • At least one instance of R is hexyl. In certain embodiments, at least one instance of R E is substituted alkenyl. In certain embodiments, at least one instance of R E p
  • R is unsubstituted alkenyl. In certain embodiments, at least one instance of R is substituted or p
  • At least one instance of R is substituted alkynyl. In certain embodiments, at least one instance of R is unsubstituted alkynyl. In certain embodiments, at least one instance of R is ethynyl. In certain embodiments, at least one instance of R is substituted carbocyclyl. In certain embodiments, at least one instance of
  • R is unsubstituted carbocyclyl. In certain embodiments, at least one instance of R is saturated carbocyclyl. In certain embodiments, at least one instance of R is unsaturated carbocyclyl. In certain embodiments, at least one instance of R is carbocyclyl including zero, one, two, or three double bonds in the carbocyclic ring system. In certain embodiments, at least one instance of R is monocyclic carbocyclyl. In certain embodiments, at least one instance of R is 3- to 7-membered, monocyclic carbocyclyl. In certain embodiments, at least one instance of R is cylcopropyl. In certain embodiments, at least one instance of R is cyclobutyl.
  • At least one instance of R is cyclopentyl. In certain embodiments, at least one instance of R is cyclohexyl. In certain embodiments, at least one instance of R is cycloheptyl. In certain embodiments, at least one instance of R is bicyclic carbocyclyl. In certain embodiments, at least one instance of R is 5- to 13-membered, bicyclic carbocyclyl. In certain embodiments, at least one instance of R is substituted heterocyclyl. In certain embodiments, at least one instance of R is unsubstituted
  • heterocyclyl In certain embodiments, at least one instance of R is saturated heterocyclyl. In certain embodiments, at least one instance of R is unsaturated heterocyclyl. In certain embodiments, at least one instance of R is heterocyclyl including zero, one, two, or three double bonds in the heterocyclic ring system. In certain embodiments, at least one instance of
  • R is heterocyclyl, wherein one, two, or three atoms in the heterocyclic ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • at least one instance of R is monocyclic heterocyclyl.
  • at least one instance of R is 3- to 7-membered, monocyclic heterocyclyl.
  • at least one instance of R is bicyclic heterocyclyl.
  • at least one instance of R is 5- to 13-membered, bicyclic heterocyclyl.
  • at least one instance of R is substituted aryl.
  • R is unsubstituted aryl. In certain embodiments, at least one instance of R is 6- to 14- membered aryl. In certain embodiments, at least one instance of R is 6- to 10-membered aryl. In certain embodiments, at least one instance of R is substituted phenyl. In certain embodiments, at least one instance of R is unsubstituted phenyl. In certain embodiments, at least one instance of R is substituted naphthyl. In certain embodiments, at least one instance of R is unsubstituted naphthyl. In certain embodiments, at least one instance of R is substituted heteroaryl. In certain embodiments, at least one instance of R is unsubstituted heteroaryl.
  • At least one instance of R is heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, at least one instance of R is monocyclic heteroaryl. In certain embodiments, at least one instance of R is
  • At least one instance of R is 6- membered, monocyclic heteroaryl. In certain embodiments, at least one instance of R is substituted pyridyl. In certain embodiments, at least one instance of R is unsubstituted 2- pyridyl, unsubstituted 3-pyridyl, or unsubstituted 4-pyridyl. In certain embodiments, at least one instance of R is bicyclic heteroaryl, wherein the point of attachment may be on any atom of the bicyclic heteroaryl ring system, as valency permits. In certain embodiments, at least one instance of R is 9-membered, bicyclic heteroaryl. In certain embodiments, at least one instance of R is 10-membered, bicyclic heteroaryl. In certain embodiments, at least one instance of R is a nitrogen protecting group. In certain embodiments, at least one instance of
  • R is Bn, Boc, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl, acetyl, or Ts.
  • two instances of R E are joined to form a substituted or unsubstituted heterocyclic ring. In certain embodiments, two instances of R are joined to form a saturated or unsaturated heterocyclic ring. In certain embodiments, two instances of
  • R are joined to form a heterocyclic ring including zero, one, two, or three double bonds in the heterocyclic ring system.
  • two instances of R are joined to form a heterocyclic ring, wherein one, two, or three atoms in the heterocyclic ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • two instances of R are joined to form a 3- to 7-membered, monocyclic heterocyclic ring.
  • two instances of R are joined to form a substituted or unsubstituted, 4- to 7-membered, monocyclic heterocyclic ring including zero, one, or two double bonds in the heterocyclic ring system, wherein one, two, or three atoms in the heterocyclic ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • two instances of R are joined to form a 5- to 13- membered, bicyclic heterocyclic ring.
  • two instances of R are joined to form a substituted or unsubstituted, 7- to 11 -membered, bicyclic heterocyclic ring including zero, one, or two double bonds in the heterocyclic ring system, wherein one, two, or three atoms in the heterocyclic ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • At least one instance of R E is H or substituted or unsubstituted alkyl. In certain embodiments, at least one instance of R is H or substituted or unsubstituted C 1-6 alkyl. In certain embodiments, each instance of R is H or substituted or unsubstituted alkyl. In certain embodiments, each instance of R is H or substituted or unsubstituted C 1-6 alkyl.
  • At least one instance of R E1 is H. In certain embodiments, at least one instance of R El is substituted acyl. In certain embodiments, at least one instance of R El is unsubstituted acyl. In certain embodiments, at least one instance of R El is acetyl. In certain embodiments, at least one instance of R El is substituted alkyl. In certain embodiments, at least one instance of R El is unsubstituted alkyl. In certain embodiments, at least one instance of R El is C 1-12 alkyl. In certain embodiments, at least one instance of R El is C 1-6 alkyl. In certain embodiments, at least one instance of R El is methyl.
  • At least one instance of R El is ethyl. In certain embodiments, at least one instance of R El is propyl. In certain embodiments, at least one instance of R El is butyl. In certain embodiments, at least one instance of R El is pentyl. In certain embodiments, at least one instance of R El is hexyl. In certain embodiments, at least one instance of R El is substituted alkenyl. In certain embodiments, at least one instance of R El is unsubstituted alkenyl. In certain embodiments, at least one instance of R El is vinyl. In certain embodiments, at least one instance of R El is substituted alkynyl. In certain embodiments, at least one instance of R El is unsubstituted alkynyl. In certain embodiments, at least one instance of R El is ethynyl. In certain
  • At least one instance of R El is substituted carbocyclyl. In certain embodiments, at least one instance of R El is unsubstituted carbocyclyl. In certain embodiments, at least one instance of R El is saturated carbocyclyl. In certain embodiments, at least one instance of R El is unsaturated carbocyclyl. In certain embodiments, at least one instance of R El is carbocyclyl including zero, one, two, or three double bonds in the carbocyclic ring system. In certain embodiments, at least one instance of R El is 3- to 7-membered, monocyclic carbocyclyl. In certain embodiments, at least one instance of R El is cylcopropyl.
  • At least one instance of R El is cyclobutyl. In certain embodiments, at least one instance of R El is cyclopentyl. In certain embodiments, at least one instance of R El is cyclohexyl. In certain embodiments, at least one instance of R El is cycloheptyl. In certain embodiments, at least one instance of R El is 5- to 13-membered, bicyclic carbocyclyl. In certain embodiments, at least one instance of R El is substituted heterocyclyl. In certain embodiments, at least one instance of R El is unsubstituted heterocyclyl. In certain embodiments, at least one instance of R El is saturated heterocyclyl.
  • At least one instance of R El is unsaturated heterocyclyl. In certain embodiments, at least one instance of R El is heterocyclyl including zero, one, two, or three double bonds in the heterocyclic ring system. In certain embodiments, at least one instance of R is heterocyclyl, wherein one, two, or three atoms in the heterocyclic ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur. In certain embodiments, at least one instance of R El is 3- to 7-membered, monocyclic heterocyclyl. In certain embodiments, at least one instance of R El is 5- to 13- membered, bicyclic heterocyclyl. In certain embodiments, at least one instance of R El is substituted or unsubstituted aryl. In certain embodiments, at least one instance of R El is 6- to
  • At least one instance of R El is 6- to 10-membered aryl. In certain embodiments, at least one instance of R El is monocyclic aryl. In certain embodiments, at least one instance of R El is unsubstituted phenyl. In certain embodiments, at least one instance of R El is substituted phenyl. In certain embodiments, at least one instance of R El is bicyclic aryl. In certain embodiments, at least one instance of R El is naphthyl. In certain embodiments, at least one instance of R El is substituted or unsubstituted heteroaryl.
  • At least one instance of R El is 5- or 6-membered, monocyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • at least one instance of R El is pyridyl.
  • at least one instance of R El is bicyclic heteroaryl, wherein the point of attachment may be on any atom of the bicyclic heteroaryl ring system, as valency permits.
  • At least one instance of R El is 9- or 10-membered, bicyclic heteroaryl, wherein one, two, three, or four atoms in the heteroaryl ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • at least one instance of R El is a nitrogen protecting group when attached to a nitrogen atom.
  • at least one instance of R El is Bn, Boc, Cbz, Fmoc, trifluoroacetyl, triphenylmethyl, acetyl, or Ts when attached to a nitrogen atom.
  • R El is an oxygen protecting group when attached to an oxygen atom.
  • R El is silyl, TBDPS, TBDMS, TIPS, TES, TMS, MOM, THP, ⁇ -Bu, Bn, allyl, acetyl, pivaloyl, or benzoyl when attached to an oxygen atom.
  • R El is a sulfur protecting group when attached to a sulfur atom.
  • R El is acetamidomethyl, ⁇ -Bu, 3-nitro-2-pyridine sulfenyl, 2-pyridine-sulfenyl, or triphenylmethyl when attached to a sulfur atom.
  • two instances of R E1 are joined to form a substituted or unsubstituted heterocyclic ring.
  • two instances of R El are joined to form a saturated or unsaturated heterocyclic ring.
  • R El are joined to form a heterocyclic ring including zero, one, two, or three double bonds in the heterocyclic ring system.
  • two instances of R El are joined to form a heterocyclic ring, wherein one, two, or three atoms in the heterocyclic ring system are independently selected from the group consisting of nitrogen, oxygen, and sulfur.
  • two instances of R El are joined to form a 3- to 7-membered, monocyclic heterocyclic ring.
  • two instances of R El are joined to form a 5- to 13- membered, bicyclic heterocyclic ring.
  • At least one instance of n is 0. In certain embodiments, at least one instance of n is 1. In certain embodiments, each instance of n is 0. In certain embodiments, each instance of n is 1.
  • p is 1. In certain embodiments, p is 2.
  • Complexes of any one of Formulae (CI) to (C25) are typically electrically neutral compounds and include one or more anionic counterions X.
  • each instance of X is a non-coordinating anionic counterion.
  • each instance of X is a monovalent anionic counterion.
  • each instance of X is C10 4
  • each instance of X is B[3,5-
  • each instance of X is a divalent anionic counterion. In certain embodiments, each instance of X is S0 4 " .
  • q is 1. In certain embodiments, q is 2. In certain embodiments, q is 3.
  • M is a monovalent transition metal ion; p is 1; X is a monovalent anionic counterion; and q is 1.
  • M is a divalent transition metal ion; p is 1; X is a monovalent anionic counterion; and q is 2.
  • M is a trivalent transition metal ion; p is 1; X is a monovalent anionic counterion; and q is 3.
  • the transition metal complex is of Formula (CI). In certain embodiments, the transition metal complex is of the formula:
  • lex is of the formula:
  • lex is of the formula:
  • each instance of X is a monovalent anionic counterion (e.g. , C10 4 , ⁇ , BF 4 , PF 4 PF 6 , or SbF 6 ).
  • the transition metal complex is of any one of the formulae:
  • each instance of X is a monovalent anionic counterion (e.g. , C10 4 , ⁇ , BF 4 , PF 4 , PF 6 , or SbF 6 ).
  • the transition metal complex is of Formula (C2).
  • the transition metal complex is of the formula: wherein each instance of X is a monovalent anionic counterion (e.g. , C10 4 , ⁇ , BF 4 , PF 4 , PF 6 , or SbF 6 -).
  • the transition metal complex is of Formula (C3).
  • the transition metal complex is of the formula: wherein each instance of X is a monovalent anionic counterion (e.g. , C10 4 , ⁇ , BF 4 , PF 4 , PF 6 , or SbF 6 ).
  • the transition metal complex is of the formula:
  • the transition metal complex is of Formula (C4). In certain embodiments the transition metal complex is of any one of the formulae:
  • each instance of X is a monovalent anionic counterion (e.g. , C10 4 , ⁇ , BF 4 , PF 4 , PF 6 , or SbF 6 ).
  • Exemplary complexes of Formula (C4) include, but are not limited to:
  • the transition metal complex is of any one of Formulae (C5) to (C25).
  • the methods of the invention may involve a single-electron reductant.
  • the single-electron reductant is an inorganic single-electron reductant.
  • the single-electron reductant is a single-electron reductive, transition metal salt.
  • the single-electron reductant is an Ag(I) salt.
  • the single-electron reductant is Ag(2,2'-bipyridine) 2 C10 4 (i.e. , Ag(bipy) 2 C10 4 ).
  • the single-electron reductant is a Ru(II) salt.
  • the single-electron reductant is Ru(2,2'-bipyridine)3(PF6) 2 (i.e. , Ru(bipy)3(PF6) 2 ).
  • the single-electron reductant is an lr(0) complex, Cu(I) salt, Sm(II) salt, Co(II) salt, Cr(II) salt, Fe(II) salt, Ni(III) salt, Nd(III) salt, Yb(III) salt, or Ti(III) salt.
  • the single-electron reductant is Cu(bipy) 2 PF 6 , Cu(bipy) 2 (OTf) 2 ,
  • the single- electron reductant is an organic single-electron reductant. In certain embodiments, the single- electron reductant is commercially available.
  • Complexes of Formula (CI) may be synthesized by contacting a ligand of Formula (Dl), or a salt thereof, with a transition metal salt of Formula (E) to provide the complexes of Formul
  • Ring B, R , R , R , r, n, M, X, p, and q are as described herein;
  • each instance of L is independently a ligand molecule
  • s 0, 1, 2, 3, or 4.
  • the transition metal salt of Formula (E) is N-(2-aminoethyl)-2-aminoethyl
  • Transition metal salts of Formula (E) may include one or more ligand molecules L.
  • at least one instance of L is a ligand molecule described herein.
  • each instance of L is a ligand molecule described herein.
  • at least one instance of L is a molecule of a suitable solvent described herein.
  • each instance of L is a molecule of a suitable solvent described herein.
  • at least one instance of L is acetonitrile (ACN).
  • each instance of L is acetonitrile.
  • at least one instance of L is an amide (e.g.
  • At least one instance of L is dimethyl sulfoxide (DMSO).
  • at least one instance of L is an ether (e.g. , tetrahydrofuran (THF), 2-methly-tetrahydrofuran, tetrahydropyran, dioxane, diethyl ether, methyl i-butyl ether (MTBE), dimethoxyethane (DME), or diglyme).
  • at least one instance of L is a ketone (e.g.
  • At least one instance of L is a chlorohydrocarbon (e.g. , dichloromethane (DCM), chloroform, carbon tetrachloride, or 1,2-dichloroethane (DCE)).
  • at least one instance of L is an ester (e.g. , propylene carbonate or ethyl acetate).
  • at least one instance of L is commercially available. In certain embodiments, each instance of L is commercially available.
  • s is 0. In certain embodiments, s is 1. In certain embodiments, s is 2. In certain embodiments, s is 3. In certain embodiments, s is 4.
  • the ligand of Formula (Dl) is commercially available.
  • the transition metal salt of Formula (E) is commercially available.
  • Complexes of Formula (C2) may be prepared by contacting a ligand of Formula (D2), or a salt thereof, with a transition metal salt of Formula (E) to provide the complexes of Formula (C2):
  • Complexes of any one of Formulae (C3) to (C25) may be synthesized by contacting a ligand of any one of Formulae (D3) to (D25), or a salt thereof, with a transition metal salt of Formula (E) to provide the complex of any one of Formulae (C3) to (C25), respectively:
  • the ligand of any one of Formulae (D3) to (D25), or the salt thereof is commercially available.
  • Complexes of any one of Formulae (CI) to (C25) may be isolated or may be generated in situ and reacted with a reagent or intermediate involved in a method of the invention.
  • N-aryl sulfonimides or N-heteroaryl sulfonimides obtained by methods of the invention may be partially deprotected to provide N-aryl sulfonamides or N-heteroaryl sulfonamides or fully deprotected to provide aryl amines or heteroaryl amines (e.g., compounds of Formula (II), and salts thereof).
  • the N-aryl sulfonimides or N-heteroaryl sulfonimides are partially or fully deprotected by reacting them with a reductant, a strong acid, or a nucleophile.
  • the reductant employed in the deprotection step is a mixture of an alkaline earth metal and an alcohol.
  • the reductant is a mixture of magnesium and an alcohol.
  • the reductant is a mixture of magnesium and an unsubstituted Ci_6 alkyl alcohol (e.g. , MeOH, EtOH, i-PrOH, or i-BuOH).
  • the reductant is a mixture of zinc and an acid.
  • the reductant is a mixture of zinc and an acid selected from the group consisting of HC1, HBr, HI, HC10 4 , HN0 3 , H 2 S0 4 , CH 3 S0 3 H, CF S0 3 H, CH C0 2 H, and CF C0 2 H.
  • the reductant is a mixture of an alkali metal and ammonia.
  • the reductant is a mixture of zinc and HC1.
  • the strong acid employed in the deprotection step may be a strong inorganic acid or strong organic acid.
  • the strong acid is an acid having a ⁇ ⁇ value of less than 3, less than 2, less than 1, or less than 0 at ambient temperature.
  • the strong acid is HC1, HBr, HI, HC10 4 , HN0 3 , H 2 S0 4 , CH 3 S0 3 H, CF 3 S0 3 H, or CF 3 C0 2 H.
  • the nucleophile useful in the deprotection step may be an alkyl lithium or phenyl lithium.
  • the nucleophile is an unsubstituted Ci_6 alkyl lithium (e.g. , MeLi, w-BuLi, sec-BuLi, or ⁇ -BuLi).
  • the nucleophile may also be a Grignard reagent.
  • the nucleophile is of Formula: YMgZ, wherein Y is unsubstituted Ci_6 alkyl, unsubstituted phenyl, or -Si(unsubstituted Ci_6 alkyl) ; and Z is halogen.
  • the nucleophile is MeMgCl, MeMgBr, or MeMgl. In certain embodiments, the nucleophile is EtMgCl, EtMgBr, or EtMgl. In certain embodiments, the nucleophile is PhMgCl, PhMgBr, or PhMgl. In certain embodiments, the nucleophile is TMSMgCl or TMSMgBr.
  • the various step(s) of the inventive methods for preparing the N-aryl or N- heteroaryl sulfonimides e.g., compounds of Formula (I), and salts thereof
  • aryl or heteroaryl amines e.g., compounds of Formula (II), and salts thereof
  • catalysts e.g. , complexes of any one of Formulae (CI) to (C25)
  • a suitable condition is a combination of physical and chemical parameters under which an intended product (e.g. , a compound of any one of Formulae (I), (II), and (CI) to (C25), or a salt thereof) may be formed using the inventive methods.
  • a suitable condition may include a suitable solvent.
  • the suitable solvent is a solvent described herein.
  • the suitable solvent is an aprotic solvent.
  • the suitable solvent is acetonitrile (ACN).
  • the suitable solvent is an amide solvent (e.g., N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMA), or N-methyl-2-pyrrolidone (NMP).
  • the suitable solvent is dimethyl sulfoxide (DMSO).
  • the suitable solvent is an ether solvent (e.g., tetrahydrofuran (THF), 2-methly-tetrahydrofuran, tetrahydropyran, dioxane, diethyl ether, methyl i-butyl ether (MTBE), dimethoxyethane (DME), or diglyme).
  • the suitable solvent is a ketone solvent (e.g. , acetone or butanone).
  • the suitable solvent is a chlorohydrocarbon solvent (e.g. , dichloromethane (DCM), chloroform, carbon tetrachloride, or 1,2-dichloroethane (DCE)).
  • the suitable solvent is an ester solvent (e.g. , propylene carbonate or ethyl acetate).
  • the suitable solvent is a pro tic solvent.
  • the suitable solvent is a mixture of two or more solvents described herein. In certain embodiments, the suitable solvent is commercially available.
  • a suitable condition may also include a suitable temperature under which a step of a method of preparing the compounds of the invention is performed.
  • the suitable temperature is at least about 0 °C, at least about 4 °C, at least about 10 °C, at least about 20 °C, at least about 23 °C, at least about 40 °C, at least about 50 °C, at least about 60 °C, at least about 80 °C, or at least about 100 °C.
  • the suitable temperature is at most about 100 °C, at most about 80 °C, at most about 60 °C, at most about 50 °C, at most about 40 °C, at most about 23 °C, at most about 20 °C, at most about 10 °C, at most about 4 °C, or at most about 0 °C. Combinations of the above-referenced ranges (e.g., at least about 0 °C and at most about 60 °C) are also within the scope of the invention.
  • a suitable temperature may be a variable temperature during a step of a method of preparing the compounds of the invention.
  • a suitable condition may also include a suitable pressure under which a step of a method of preparing the compounds of the invention is performed.
  • the suitable pressure is about 1 atmosphere.
  • a suitable condition may also include a suitable atmosphere under which a step of a method of preparing the compounds of the invention is performed.
  • the suitable atmosphere is air.
  • the suitable atmosphere is an inert atmosphere.
  • the suitable atmosphere is a nitrogen or argon atmosphere.
  • a suitable condition may also include a suitable time duration that a step of a method of preparing the compounds of the invention lasts.
  • the suitable time duration is in the order of minutes (e.g., about 10 minutes or about 30 minutes), hours (e.g. , about 1 hour, about 2 hours, about 4 hours, about 8 hours, or about 16 hours), or days (e.g., about 1 day).
  • a suitable condition may also include agitating (e.g., stirring, sonicating, and/or shaking) one or more reactants, reagents, solvents, and/or solid supports involved in a method of the invention, or a mixture thereof.
  • agitating e.g., stirring, sonicating, and/or shaking
  • One or more intermediates resulting from a step of a method of preparing the compounds of the invention may be isolated and/or purified, and the isolated and/or purified intermediate may be reacted in a next step of the method.
  • the isolated and/or purified intermediates may be substantially free of impurities or may contain one or more other components, such as reagents and solvents employed in the step yielding the intermediates, and byproducts.
  • the one or more intermediates may also be reacted in a next step without being isolated and/or purified.
  • the intermediates and/or intended products of the methods of preparing the N-aryl or N-heteroaryl sulfonimides (e.g., compounds of Formula (I), and salts thereof) and aryl or heteroaryl amines (e.g., compounds of Formula (II), and salts thereof) may be isolated and/or purified using methods known in the art, such as chromatography normal phase chromatography (e.g. , silica gel flash chromatography), reverse phase chromatography (e.g., high performance liquid chromatography (HPLC)), precipitation, decanting, filtration, centrifuge, trituration, crystallization, recrystallization, liquid-liquid phase separation, evaporation, and drying.
  • chromatography normal phase chromatography e.g. , silica gel flash chromatography
  • reverse phase chromatography e.g., high performance liquid chromatography (HPLC)
  • precipitation decanting, filtration, centrifuge, trituration, crystallization
  • the intended products described herein are substantially pure (e.g. , substantially free of impurities) (e.g., at least about 90%, at least about 95%, at least about 98%, at least about 99%, at least about 99.5%, at least about 99.9%, or more pure).
  • la (I) is of the formula:
  • Compounds of Formula (I) that may be prepared by the inventive methods include, but are not limited to, compounds of any one of the formulae:
  • the transition metal complexes of the invention include amine-N-oxide ligands, such as ligands of Formula (Dl) to (D25).
  • the inventive transition metal complexes are the transition metal complexes described herein
  • the inventive transition metal complexes are complexes of Formula (CI).
  • the inventive transition metal complexes are complexes of Formula (C2).
  • the inventive transition metal complexes are complexes of Formula (C3).
  • the inventive transition metal complexes are complexes of Formula (C4).
  • the inventive transition metal complexes are complexes of any one of Formulae (C5) to (C25).
  • the inventive transition metal complexes are electrically neutral.
  • the complexes of the invention may be prepared according to the methods described herein or by processes known in the art. For example, one can use synthetic chemistry transformations (including protecting group methodologies), e.g., those described in R. Larock,
  • kits e.g., packs.
  • the kits are useful for preparing the compounds described herein (e.g., N-aryl or N-heteroaryl sulfonimides and aryl or heteroaryl amines) from an arene or heteroarene (e.g., a compound of Formula (A), or a salt thereof).
  • the kits are useful for preparing the compounds of Formula (I), and salts thereof.
  • the kits are useful for preparing the compounds of Formula (II), and salts thereof.
  • a kit of the invention may include an N-fluorosulfonimide as an imidating agent; a catalyst; and a single-electron reductant.
  • a kit of the invention includes a compound of Formula (B), or a salt thereof; a transition metal complex of any one of Formulae (C1)-(C25); and a single-electron reductant.
  • a kit of the invention includes a compound of Formula (B), or a salt thereof; a transition metal complex of any one of Formulae (C1)-(C25); and a single-electron reductant.
  • a kit of the invention includes a compound of Formula (B), or a salt thereof; a transition metal complex of Formula (CI); and a single-electron reductant.
  • a kit of the invention includes a compound of Formula (B), or a salt thereof; a transition metal complex of Formula (C2); and a single-electron reductant.
  • a kit of the invention includes a compound of Formula (B), or a salt thereof; a transition metal complex of Formula (C3); and a single-electron reductant.
  • a kit of the invention includes a compound of Formula (B), or a salt thereof; a transition metal complex of Formula (C4); and a single-electron reductant.
  • a kit of the invention includes a compound of Formula (B), or a salt thereof; a transition metal complex of any one of Formulae (C5) to (C25); and a single-electron reductant.
  • a kit of the invention includes N-fluorobenzenesulfonimide (NFBS or NFSI); a transition metal complex of any one of Formulae (C1)-(C25); and a single-electron reductant.
  • a kit of the invention includes a compound of Formula (B), or a salt thereof; a transition metal complex of any one of Formulae (C1)-(C25); and an Ag(I) or Ru(II) salt.
  • kits may further include an arene or heteroarene.
  • a kit of the invention further includes a compound of Formula (A), or a salt thereof.
  • a kit of the invention may also include a deprotecting agent that is useful in deprotecting the N-aryl or N-heteroaryl sulfonimides prepared by the inventive methods to provide partially deprotected N-aryl or N-heteroaryl sulfonamides or fully deprotected aryl or heteroaryl amines (e.g., compounds of Formula (II), and salts thereof).
  • a deprotecting agent that is useful in deprotecting the N-aryl or N-heteroaryl sulfonimides prepared by the inventive methods to provide partially deprotected N-aryl or N-heteroaryl sulfonamides or fully deprotected aryl or heteroaryl amines (e.g., compounds of Formula (II), and salts thereof).
  • a kit of the invention further includes a reductant.
  • a kit of the invention further includes an alkaline earth metal (e.g. , magnesium) and an alcohol (e.g., an unsubstituted Ci_6 alkyl alcohol).
  • a kit of the invention further includes zinc and an acid (e.g. , HC1, HBr, HI, HC10 4 , HN0 3 , H 2 S0 4 , CH 3 S0 3 H, CF S0 3 H, CH C0 2 H, or CF C0 2 H).
  • a kit of the invention further includes a strong acid (e.g.
  • kits of the invention further includes a nucleophile.
  • a kit of the invention further includes alkyl lithium (e.g. , an
  • a kit of the invention further includes a Grignard reagent (e.g. , a compound of Formula: YMgZ, wherein Y and Z are as described herein).
  • a Grignard reagent e.g. , a compound of Formula: YMgZ, wherein Y and Z are as described herein.
  • kits provided may further include a container (e.g. , a vial, ampule, bottle, syringe, flask, tube, beaker, dish, microtiter plate, and/or dispenser package, or other suitable container), a solvent (e.g. , a suitable solvent described herein), or an organic or inorganic agent (e.g. , a phase-transfer agent, a solubilizing agent, a stabilizing agent, an anti- oxidative agent, protecting agent, deprotecting agent, and/or a preservative agent).
  • a container e.g. , a vial, ampule, bottle, syringe, flask, tube, beaker, dish, microtiter plate, and/or dispenser package, or other suitable container
  • a solvent e.g. , a suitable solvent described herein
  • an organic or inorganic agent e.g. , a phase-transfer agent, a solubilizing agent, a stabilizing
  • kits further include instructions for using the kits of the invention.
  • the kits and instructions provide for preparing the compounds described herein (e.g., N-aryl or N-heteroaryl sulfonimides, aryl or heteroaryl amines, and transition metal complexes).
  • the kits and instructions provide for preparing the compounds of Formula (I), and salts thereof.
  • the kits and instructions provide for preparing the compounds described herein (e.g., N-aryl or N-heteroaryl sulfonimides, aryl or heteroaryl amines, and transition metal complexes).
  • the kits and instructions provide for preparing the compounds of Formula (I), and salts thereof.
  • kits and instructions provide for preparing the compounds of Formula (II), and salts thereof.
  • the kits and instructions provide for preparing the complexes of any one of Formulae (C1)-(C25).
  • Example 1 Preparation of the Complexes of any one of Formulae (CI) to (C25), the N-Aryl or ⁇ -Heteroaryl Sulfonimides of Formula (I), and the Aryl or Heteroaryl Amines of Formula (I).
  • Complexes of any one of Formulae (CI) to (C25) may be prepared from ligands of Formula (Dl) to (D25), or salts thereof, with transition metal salts of Formula (E).
  • complex 1 a complex of Formula (CI), is synthesized by reacting N-(2- pyridylmethyl)pyrrolidine-N-oxide with a palladium(II) salt (e.g.,
  • the ligand N-(2-pyridylmethyl)pyrrolidine-N- oxide can be prepared in two steps from commercially available starting materials.
  • the complexes of the invention may also be s nthesized by methods known in the art.
  • N-fluorobenzenesulfonimide (NFBS or NFS I) is used as an imidating agent, complex 1 may act as a catalyst, and Ag(bipy) 2 C10 4 may work as a single- electron reductant. Both complex 1 and the Ag(bipy) 2 C10 4 are required in a reaction of Scheme 1 ; control experiments in which either complex 1 or the Ag(bipy) 2 C10 4 is omitted gave only trace amounts of imidated products. In another set of experiments, Ag(bipy) 2 C10 4 can be replaced with Ru(bipy) 3 (PF 6 ) 2 with similar results (Table 1, entry 2a). The reactions proceed similarly well in the presence or absence of light. Complex 1 involves an unusual pyridine-N- oxide ligand motif.
  • complex 1 is easily prepared and conveniently handled, it can be isolated, and the isolated complex 1 can be employed in the methods of the invention.
  • Complex 1 can also be generated in situ by reacting N-(2-pyridylmethyl)pyrrolidine-N-oxide with a palladium(II) salt (e.g., Pd(NCMe)4(OTf) 2 ), and the in situ generated complex 1 can be used in the inventive methods.
  • a palladium(II) salt e.g., Pd(NCMe)4(OTf) 2
  • a variety of substrates i.e., arenes and heteroarenes, can be efficiently imidated (e.g., Table 1).
  • Regio selectivity is substrate-intrinsic.
  • Resonance donors such as alkoxy and halogen groups, may direct imidation ortho/para, similar to the regio selectivity in an electrophilic aromatic substitution reaction.
  • inductive donors e.g., 2c and 2j
  • Arenes and heteroarenes more electron-poor than those shown in Table 1 may show diminished reactivity and give lower yields.
  • the sulfonyl protecting groups of the N-aryl or N-heteroaryl sulfonimides can be removed using methods of the invention to provide aryl or heteroaryl amines (e.g., compounds of Formula (II), and salts thereof).
  • aryl or heteroaryl amines e.g., compounds of Formula (II), and salts thereof.
  • treatment of compound 2b with magnesium in methanol under sonication produced aryl amine 3 in 85% yield (Scheme 2).
  • Triethylamine (5mL) was added and the reaction mixture was concentrated in vacuo. The residue was purified by chromatography on silica gel, eluting with (hexanes/EtOAc 5: 1 (v/v) with 1% triethylamine) to afford 11.5 g of the title compound (83% yield), which is spectroscopically identical to the compound prepared according to the standard procedure (vide supra).
  • the intermediate of Formula (G) formally transfers a sulfonimidyl radical to the bound arene substrate, which expels a delocalized radical intermediate and regenerates complex 1.
  • the delocalized radical intermediate is subsequently oxidized by the Ag(II) intermediate, then deprotonated to furnish the sulfonimidated product.
  • the rate of the non-productive catalytic reduction of NFBS is substantially identical to the rate of the productive imidation reaction (Scheme 3).
  • the rate law and the substantially identical rate for both reactions shown in Scheme 3 are consistent with a turnover-limiting oxidation of complex 1 by NFBS to yield a common, short-lived, high-valent palladium intermediate of Formula (F).
  • Oxidation of a transition metal complex of the invention typically requires strongly ⁇ -donating anionic ligands such as hydrocarbyl ligands, which are absent from complex l.
  • anionic ligands such as hydrocarbyl ligands, which are absent from complex l.
  • 8 DFT (density functional theory) calculations reveal that the highest occupied molecular orbital (HOMO) of complex 1 is an extended M-L ⁇ -antibonding orbital of d xz parentage from palladium, instead of the J z 2 -based orbital more typical of square-planar d complexes.
  • a single-electron reductant e.g. , an Ag(I) salt
  • G intermediate of Formula (G)
  • EPR electron paramagnetic resonance
  • KIE indicates a rehybridization of the C-H bond from sp 2 to sp 3 in the product-determining transition state, consistent with a C-N bond formation via inner-sphere addition of a dibenzenesulfonimidyl radical to the bound arene in an intermediate of Formula (G).
  • Electrophilic addition would also be consistent with the observed intramolecular isotope effect.
  • inverse secondary KIE values for electrophilic substitution are rare; 11 commonly, KIEs close to unity are observed for electrophilic processes due to the opposing effects of rehybridization and hyperconjugation on the zero-point vibrational energy of the affected C-H bond.
  • 12 Inner-sphere attack from an intermediate, such as an intermediate of Formula (G), to form the putative aryl radical is supported by an intermolecular competition KIE 1.03 + 0.02. The absence of a KIE in this case is consistent with irreversible substrate bindin prior to C-N bond formation. 9 ' 1013
  • Fluorobenzene was chosen as the substrate for the determination of the rate law of the catalytic imidation reaction because fluorobenzene is a competent substrate for the imidation reaction (81 yield), and the consumption of fluorobenzene and appearance of the products could be followed concurrently with the consumption of NFBS by 19 F NMR.
  • the data was acquired at 50 °C because this temperature was found to facilitate a more convenient rate of reaction for kinetic analysis. To justify the acquisition of kinetic data with fluorobenzene as a substrate at a reaction temperature of 50 °C, the catalytic imidation on fluorobenzene under these conditions has been performed , and no substantial diminution in yield has been found.

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Abstract

Cette invention concerne de nouveaux complexes de métaux de transition (par ex., complexes selon l'une quelconque des Formules (C1) à (C25)) qui contiennent un motif d'oxyde d'amine N. L'invention concerne également des procédés d'utilisation desdits complexes de métaux de transition pour préparer des N-aryl ou des N- hétéroaryl-sulfonimides (par ex., composés de Formule (I)) et des aryl- ou des hétéroaryl-amines (par ex., composés de Formule (II)). Les procédés selon l'invention impliquent l'imidation d'arènes et d'hétéroarènes (par ex., composés de Formule (A)) à l'aide d'un agent d'imidation (par ex., composé de Formule (B), tel qu'un N-fluorobenzène-sulfonimide (NFBS ou NFSI)) en présence d'un agent réducteur transférant un seul électron (par ex., sel d'Ag(I) ou de Ru(II)).
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