CN114031615A - Hydroxy-substituted pyridine oxazoline ligands and application thereof in hydrohalogenation reaction of olefin - Google Patents

Hydroxy-substituted pyridine oxazoline ligands and application thereof in hydrohalogenation reaction of olefin Download PDF

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CN114031615A
CN114031615A CN202111392445.5A CN202111392445A CN114031615A CN 114031615 A CN114031615 A CN 114031615A CN 202111392445 A CN202111392445 A CN 202111392445A CN 114031615 A CN114031615 A CN 114031615A
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CN114031615B (en
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刘国生
李响
金剑波
陈品红
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Shanghai Institute of Organic Chemistry of CAS
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Abstract

The invention discloses a hydroxyl-substituted pyridine oxazoline ligand and application thereof in an anti-Markov hydrohalogenation reaction of olefin. Specifically, the invention discloses a hydroxyl group shown as a formula IA substituted pyridine oxazoline ligand. The ligand of the invention can realize the anti-Ma's hydrochlorination and the hydrobromination of the olefin, including the terminal olefin and the internal olefin, and also can be mixed olefin, and the first-order alkyl halide is obtained singly. And the reaction condition is mild, the regioselectivity is high, and the substrate universality is wide.

Description

Hydroxy-substituted pyridine oxazoline ligands and application thereof in hydrohalogenation reaction of olefin
Technical Field
The invention relates to a hydroxy-substituted pyridine oxazoline ligand and an application thereof in a hydrohalogenation reaction of olefin.
Background
Alkyl halides are synthetic building blocks widely used in organic synthesis, and the segment also widely exists in natural products, drug molecules, pesticides and material molecules. Conventional methods for synthesizing such compounds typically involve functional group transformations, particularly from the hydrohalogenation of alcohols. The hydrohalogenation reaction of olefins is an important reaction in organic chemistry, and is the most direct and efficient method for synthesizing alkyl halides from inexpensive and readily available olefins as raw materials. The reaction often uses an acid as a catalyst and follows the mahalanobis rule of addition to give the predominantly branched alkyl halide. The mahalanobis hydrohalogenation reaction to obtain primary alkyl chlorides is extremely challenging. In patent US20120190879a1, Coleman et al have carried out the hydrochlorination of electron deficient terminal olefins to form primary alkyl chlorides using acetyl chloride as chlorinating agent, but the reaction is limited to electron deficient olefins such as acrylic acid, acrylonitrile, acrylamide, etc. Although primary alkyl bromides can be obtained by hydrobromination of terminal olefins by free radical processes (j.am. chem. soc.1933,55,2468), the reaction is limited to bromination and chlorination is difficult to achieve (j.am. chem. soc.1954,76,5392). Therefore, there is a need in the art for a method for synthesizing alkyl halides from olefins, including terminal olefins and internal olefins, with high efficiency, simplicity and mild conditions.
Pyridine oxazoline ligands are used as an important ligand, and a lot of reports exist, generally, a substituent on an oxazoline ring is chiral, the substituent is often substituted alkyl, aryl and the like, and pyridine oxazoline skeleton ligands introducing hydroxyl on the oxazoline ring are few. Hydroxy oxazoline ligands are reported in the chem. Ber.1989,122,499 literature
Figure BDA0003364682590000011
The catalyst is used for rhodium-catalyzed asymmetric reduction reaction of aryl ketone (22% yield and 10.4% enantioselectivity), but the reaction result is not good in the effect of corresponding methyl-substituted pyridine oxazoline (94% yield and 65.6% enantioselectivity). Recent studies have found that the introduction of a substituent at the 6-position of pyridine can increase the electrophilicity of palladium catalyst and promote nucleophilic palladium reaction of olefin while controlling the enantioselectivity of the reaction (J.Am.chem.Soc.2018,140, 7415; Angew.chem.int.Ed.2019,58,2392; Angew.chem.int.Ed.2020,59,2735). Based on the strategy of the pyridine oxazoline ligand with large steric hindrance, novel pyridine oxazoline ligands can be developed by combining hydroxyl as a weak coordination group, and a novel reaction of high-selectivity conversion among olefin molecules is realized.
In view of the above-mentioned current reaction situation, there is a need to develop a novel pyridine oxazoline ligand, which can realize the anti-mah hydrohalogenation reaction of olefins, including terminal olefins and internal olefins, and can synthesize primary alkyl halides with high efficiency and high selectivity.
Disclosure of Invention
The invention aims to provide a novel pyridine oxazoline ligand which can synthesize primary alkyl halide with high efficiency and high selectivity.
In a first aspect of the invention, a hydroxy-substituted pyridine oxazoline ligand shown in a formula I is provided,
Figure BDA0003364682590000021
wherein the content of the first and second substances,
R1is substituted or unsubstituted C1-C10Alkyl, substituted or unsubstituted C3-C6Cycloalkyl, substituted or unsubstituted C6-C20An aryl group;
R2is hydrogen, substituted or unsubstituted C1-C10Alkyl, substituted or unsubstituted C3-C6Cycloalkyl, substituted or unsubstituted C6-C30An aryl group;
R3is hydrogen, substituted or unsubstituted C1-C10Alkyl, substituted or unsubstituted C6-C30An aryl group; or, R2、R3Together with the carbon atom to which they are attached form C3-C7Cycloalkyl or C6-C30An aryl group;
R4is one or more substituents on the pyridine ring, and said R4The substituents are selected from the group consisting of: halogen, substituted or unsubstituted C1-C6Alkyl, C substituted by one or more halogens1-C6Alkyl radical, C1-C6Alkoxy or
Figure BDA0003364682590000022
Wherein R is4-1Is C1-C6An alkyl group;
or R1And R4Together form- (CH)2)n-, or R1And R4And the carbon atoms to which they are attached together form C6-C10Aryl of (a); wherein n is 2,3 or 4;
wherein said substitution means that one or more hydrogen atoms on the group are substituted with a substituent selected from the group consisting of: halogen, C1-C10Alkyl radical, C3-C6Cycloalkyl, phenyl of (a); and when the substituent is plural, each substituent is the same or different.
In another preferred embodiment, the ligand comprises:
R1is substituted or unsubstituted C1-C10Alkyl, substituted or unsubstituted C3-C6Cycloalkyl, substituted or unsubstituted C6-C10An aryl group;
R2is hydrogen, substituted or unsubstituted C1-C6Alkyl, substituted or unsubstituted C3-C6Cycloalkyl, benzyl of (a);
R3is hydrogen, substituted or unsubstituted C1-C10Alkyl, substituted or unsubstituted C6-C10An aryl group;
or R2And R3Together with the carbon atom to which they are attached form C3-C7Cycloalkyl groups of (a);
R4is one or more substituents on the pyridine ring, and said R4The substituents are selected from the group consisting of: halogen, substituted or unsubstituted C1-C6Alkyl, C substituted by one or more halogens1-C6An alkyl group;
or R1And R4Together form- (CH)2)n-, or R1And R4And the carbon atoms to which they are attached together form C6-C10Aryl of (a); wherein n is 2,3 or 4;
wherein said substitution means that one or more hydrogen atoms on the group are substituted with a substituent selected from the group consisting of: halogen, C1-C10Alkyl radical, C3-C6Cycloalkyl groups of (a); and when the substituent is plural, each substituent is the same or different.
In another preferred embodiment, the ligand comprises:
R1is substituted or unsubstituted C1-C10Alkyl, substituted or unsubstituted C3-C6Cycloalkyl, substituted or unsubstituted phenyl;
R2is hydrogen, substituted or unsubstituted C1-C4Alkyl, benzyl;
R3is hydrogen, substituted or unsubstituted phenyl;
R4is a substituent on the pyridine ring, and said R4The substituents are selected from the group consisting of: halogen, substituted or unsubstituted C1-C4Alkyl, C substituted by one or more halogens1-C4An alkyl group;
or R1And R4Together form- (CH)2)n-, or R1And R4And the carbon atoms to which they are attached together form C6An aryl group; wherein n is 2,3 or 4;
wherein said substitution refers to one or more of the groupsAnd each hydrogen atom is substituted with a substituent selected from the group consisting of: halogen, C1-C10Alkyl radical, C3-C6Cycloalkyl groups of (a); and when the substituent is plural, each substituent is the same or different.
In another preferred embodiment, the ligand is selected from the group consisting of:
Figure BDA0003364682590000031
in a second aspect of the invention there is provided the use of a ligand according to the first aspect of the invention as a ligand in the anti-mahalanobis halogenation of an olefin, wherein the halogenation is preferably a chlorination or bromination reaction.
In a third aspect of the present invention, there is provided a palladium-catalyzed anti-mahalanobis hydrochlorination process for an olefin, characterized in that the process comprises the steps of:
in a solvent, in the presence of a palladium catalyst and a ligand according to the first aspect of the invention, reacting an olefin shown as a formula II with a halogenating agent and hydrosilation to obtain a compound containing a primary alkyl halide shown as a formula III; wherein X is halogen;
Figure BDA0003364682590000032
wherein the content of the first and second substances,
R5selected from the group consisting of: substituted or unsubstituted C1-30Alkyl, substituted or unsubstituted C3-8A substituted or unsubstituted 5-to 12-membered heterocyclic group (saturated or partially unsaturated, which includes 1 to 3 heteroatoms selected from N, O or S), a substituted or unsubstituted C6-30An aryl group;
R6selected from the group consisting of: hydrogen, substituted or unsubstituted C1-30Alkyl (preferably, when R is6Is substituted C1-30Alkyl, the substituent not being terminal);
R7is hydrogen, or substituted or unsubstituted C1-30An alkyl group;
or R5And R6With adjacent carbon to form C5-8A cycloolefin of (a);
R8is a chemical bond, or substituted or unsubstituted C1-30An alkylene group;
wherein said substitution means that one or more hydrogen atoms on the group are substituted with a substituent selected from group a: halogen, hydroxy, NO2Benzyl, OBz, NBoc, N (Ts) Boc, C1-C10Alkyl radical, C2-C10Alkenyl radical, C2-C10Alkynyl, C1-C10Alkoxy radical, C3-C6Cycloalkyl of, C6-C30Aryl of (a), 5-30 membered heteroaryl, RC (O) O-, RC (O) NH-, RC (O) -; r is selected from the group consisting of: H. c1-C10Alkyl radical, C3-C6Cycloalkyl of, C2-C10Alkenyl radical, C6-C30Aryl of (a), 5-30 membered heteroaryl;
and each of the above substituents of group a may be further substituted with a substituent selected from group B: halogen, oxygen (═ O), hydroxy, NO2Benzyl, OBz, NBoc, N (Ts) Boc, C1-C10Alkyl radical, C1-C10Alkoxy radical, C3-C6Cycloalkyl of, C6-C10Aryl of (2), 5-12 membered heteroaryl.
In another preferred embodiment, the solvent is selected from the group consisting of: an alkane solvent, a nitrile solvent, a halogenated hydrocarbon solvent, an ether solvent, a ketone solvent, an ester solvent, an amide solvent, or a combination thereof.
In another preferred embodiment, the alkane solvent is preferably n-hexane.
In another preferred embodiment, the nitrile solvent is preferably acetonitrile.
In another preferred embodiment, the halogenated hydrocarbon solvent is preferably dichloromethane and chloroform.
In another preferred embodiment, the ether solvent is preferably one or more of tetrahydrofuran, diethyl ether, methyl tertiary butyl ether and 1, 4-dioxane.
In another preferred embodiment, the ketone solvent is preferably acetone.
In another preferred embodiment, the ester solvent is preferably ethyl acetate.
In another preferred embodiment, the amide solvent is preferably N, N-Dimethylformamide (DMF).
In another preferred example, the solvent is a nitrile solvent and/or a halogenated hydrocarbon solvent; more preferably, the solvent is a mixed solvent of acetonitrile and dichloromethane.
In another preferred embodiment, the solvent may be subjected to anhydrous treatment in the hydrohalogenation reaction (the operation and method of anhydrous treatment are conventional in the art).
In another preferred embodiment, the concentration of the olefin II in the solvent is 0.01 to 1.00mol/L, and more preferably 0.1 mol/L.
In another preferred embodiment, the palladium catalyst is selected from the group consisting of: palladium acetate, palladium trifluoroacetate, palladium pentanate, dichlorodiacetonitrile palladium, bis (benzonitrile) palladium chloride, palladium bromide, tetranitrile palladium tetrafluoroborate, palladium hexafluoroacetylacetonate, bis (acetylacetonato) palladium, tetranitrile palladium trifluoromethanesulfonate, palladium pivalate, (1E,4E) -bis (dibenzylideneacetone) palladium, bis (dibenzylideneacetone) dipalladium, and tris (dibenzylideneacetone) dipalladium.
In another preferred embodiment, when X is Cl, the palladium catalyst is palladium dichlorodiacetonitrile.
In another preferred embodiment, when X is Br, the palladium catalyst is palladium hexafluoroacetylacetonate.
In another preferred embodiment, in the hydrohalogenation reaction, the molar ratio of the palladium catalyst to the olefin II is (1 to 50): 100, respectively; preferably (1-10): 100.
in another preferred example, in the hydrohalogenation reaction, the molar ratio of the oxazoline ligand to the olefin II is (1 to 75): 100.
in another preferred embodiment, in the hydrohalogenation reaction, the molar ratio of the palladium catalyst to the oxazoline ligand may be a molar ratio conventional in the art for such reactions, preferably 1: (1-3).
In another preferred embodiment, the halogenating agent is selected from the group consisting of: n-chlorosuccinimide, N-bromo-N-methyl sodium isocyanurate (Na-NMBI).
In another preferred embodiment, in the hydrohalogenation reaction, the molar ratio of the halogenating agent to the olefin II is preferably (1.0-5.0): 1.
In another preferred embodiment, the silicon hydride is selected from the group consisting of: alkyl hydrosilicones, aryl hydrosilicones, polymethylhydrosiloxanes; wherein the alkyl is C1-C4Alkyl, said aryl being C6-C10And (4) an aryl group.
In another preferred example, in the hydrohalogenation reaction, the silicon hydride is triisopropyl silicon hydride or triphenyl silicon hydride.
In another preferred embodiment, in the hydrohalogenation reaction, the molar ratio of the silicon hydride to the olefin II is preferably (1.0-10): 1, and more preferably (2.5-10): 1.
In another preferred example, in the hydrohalogenation reaction, the temperature of the addition reaction is 20-30 ℃.
In another preferred embodiment, in the hydrohalogenation reaction, the addition reaction is carried out under a protective gas; preferably, the protective gas is nitrogen and/or argon.
In another preferred embodiment, when R is8When the bond is a chemical bond, the compound shown as the formula II is selected from any one of the following compounds:
Figure BDA0003364682590000051
in another preferred embodiment, the compound represented by formula III is selected from any one of the following compounds:
Figure BDA0003364682590000061
in another preferred embodiment, the compound represented by formula III is selected from any one of the following compounds:
Figure BDA0003364682590000062
in another preferred embodiment, when R is8When the compound is alkylene, the compound shown in the formula II is selected from any one of the following compounds:
Figure BDA0003364682590000071
in another preferred embodiment, when R is8When the compound is alkylene, the compound shown in the formula III is selected from any one of the following compounds:
Figure BDA0003364682590000072
in another preferred embodiment, the compound represented by formula III is selected from any one of the following compounds:
Figure BDA0003364682590000081
it is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. Not to be reiterated herein, but to the extent of space.
Detailed Description
The inventor of the invention has long and intensive research and preparation, and the technical problem to be solved by the invention is to overcome the defects that the prior art is mainly used for carrying out the mahalanobis addition on the hydrohalogenation reaction of olefin, and an anti-mahalanobis addition product and an alkyl halide are difficult to obtain. The method has the advantages of high yield, good regioselectivity, wide substrate universality, good functional group compatibility, mild reaction conditions and the like. Based on the above findings, the inventors have completed the present invention.
Term(s) for
In the invention, the term "room temperature" means 10 to 30 ℃.
In the present invention, the term "halogen" means fluorine, chlorine, bromine or iodine.
In the present invention, the term "alkyl" refers to a straight or branched chain saturated hydrocarbon group having the specified number of carbon atoms. Examples of alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, and the like.
In the present invention, the term "alkenyl" refers to a straight or branched hydrocarbon group having one or more carbon-carbon double bonds and no carbon-carbon triple bonds. The one or more carbon-carbon double bonds may be internal (e.g., in a 2-butenyl group) or terminal (e.g., in a 1-butenyl group).
In the present invention, the term "alkynyl" refers to a straight or branched hydrocarbon group having one or more carbon-carbon triple bonds and optionally one or more carbon-carbon double bonds.
In the present invention, the term "cycloalkyl" refers to a saturated monocyclic ring, or a carbocyclic substituent comprising a fused, bridged or spiro polycyclic ring system.
In the present invention, "heterocycloalkyl" refers to a "heterocycloalkyl" of a non-aromatic ring system. The heterocycloalkyl group can either be monocyclic ("monocyclic heterocyclyl") or a fused, bridged or spiro ring system (e.g., a bicyclic system ("bicyclic heterocyclyl")) and can be saturated or can be partially unsaturated.
In the present invention, "heterocycloalkenyl" means a "heterocyclic group" containing an ethylenic bond, an unsaturated non-aromatic ring system. The heterocycloalkenyl group can be either monocyclic ("monocyclic heterocycloalkenyl") or a fused, bridged or spiro ring system (e.g., a bicyclic ring system ("bicyclic heterocycloalkenyl")) and can be saturated or can be partially unsaturated. In some embodiments, heterocycloalkenyl refers to heterocycloalkenyl having 1-2, 5-6 members heteroatoms of one or more of N, O and S.
In the present invention, the term "alkoxy" denotes a cyclic or acyclic alkyl group linked via an oxygen bridge, the alkyl and cycloalkyl groups being as defined above.
As used herein, "aryl" refers to a group having 6-14 atoms and zero heteroatoms, a monocyclic or polycyclic (e.g., bicyclic or tricyclic) 4n +2 aromatic ring system (e.g., having 6,10, or 14 shared p electrons in a cyclic array) ("C6-C14 aryl").
In the present invention, "heteroaryl" refers to a group of a 5-10 membered monocyclic or bicyclic 4n +2 aromatic ring system (e.g., having 6 or 10 shared p electrons in a cyclic array) having carbon atoms and 1-4 heteroatoms provided in the aromatic ring system, wherein each heteroatom is independently selected from one or more of nitrogen, oxygen, and sulfur, and the number of heteroatoms is 1,2, 3, or 4 ("5-10 membered heteroaryl"). In heteroaryl groups containing one or more nitrogen atoms, the point of attachment may be a carbon or nitrogen atom, as valency permits.
On the basis of the common knowledge in the field, the above preferred conditions can be combined randomly to obtain the preferred embodiments of the invention.
The reagents and starting materials used in the present invention are commercially available.
Hydroxy-substituted pyridinooxazoline ligands
The invention provides a hydroxyl-substituted pyridine oxazoline ligand shown as a formula I:
Figure BDA0003364682590000091
wherein the content of the first and second substances,
R1is substituted or unsubstituted C1-C10Alkyl, substituted or unsubstituted C3-C6Cycloalkyl, substituted or unsubstituted C6-C30Aryl, or with R4And are connected to each otherTogether form C4-C6Cycloalkyl or C6-C30An aryl group;
R2is hydrogen, substituted or unsubstituted C1-C10Alkyl, substituted or unsubstituted C3-C6Cycloalkyl, substituted or unsubstituted C6-C30An aryl group; or, R2、R3Together with the carbon atom to which they are attached form C3-C7Cycloalkyl groups of (a);
R3is hydrogen, substituted or unsubstituted C1-C10Alkyl, substituted or unsubstituted C6-C30An aryl group; or, R2、R3Together with the carbon atom to which they are attached form C3-C6Cycloalkyl or C6-C30An aryl group;
R4is halogen, substituted or unsubstituted C1-C6Alkyl, C substituted by one or more halogens1-C6Alkyl radical, C1-C6Alkoxy or
Figure BDA0003364682590000092
Or with R1And the carbon atoms to which they are attached together form C4-C6Cycloalkyl or C6-C30And (4) an aryl group. R4-1Is C1-C6An alkyl group. Wherein, when the number of the substituents is plural, the substituents are the same or different.
Preferred hydroxy-substituted pyridinooxazoline ligands of formula I are selected from any of the following compounds:
Figure BDA0003364682590000101
use of hydroxy-substituted pyridinooxazoline ligands
The invention also provides the use of a hydroxy-substituted pyridinooxazoline ligand as hereinbefore described as a key ligand in the anti-mahalanobis halogenation reaction of an olefin. The halogenation reactions are preferably chlorination and bromination reactions.
The palladium-catalyzed anti-mahalanobis hydrochlorination of an olefin comprises the steps of: in a solvent, reacting olefin shown as a formula II with a chlorinating reagent and hydrosilicon under the conditions of a palladium catalyst and a ligand to obtain primary alkyl chloride shown as a formula III;
Figure BDA0003364682590000102
preferably, the palladium-catalyzed anti-mahalanobis hydrobromination of the olefin comprises the steps of: in a solvent, under the condition of a palladium catalyst and a ligand, the olefin shown as the formula II reacts with a bromination reagent and silicon hydride to react to obtain a primary alkyl bromide containing the compound shown as the formula IV;
Figure BDA0003364682590000103
wherein the content of the first and second substances,
R5each independently selected from substituted or unsubstituted C1-30Alkyl, substituted or unsubstituted C3-8Cycloalkyl, substituted or unsubstituted C6-30A substituent in an aryl group;
R6each independently selected from hydrogen, substituted or unsubstituted C1-30An alkyl group; when R is6Is substituted C1-30Alkyl, the substituent not being terminal;
R7each independently selected from hydrogen, substituted or unsubstituted C1-30An alkyl group;
or R5And R6With adjacent carbon to form C5-8A cycloolefin of (b).
In the hydrohalogenation reaction, the solvent can be a solvent which is conventional in the reaction in the field, and preferably, the solvent is one or more of alkane solvents, nitrile solvents, halogenated hydrocarbon solvents, ether solvents, ketone solvents, ester solvents and amide solvents. The alkane solvent is preferably n-hexane. The nitrile solvent is preferably acetonitrile. The halogenated hydrocarbon solvent is preferably dichloromethane and chloroform. The ether solvent is preferably one or more of tetrahydrofuran, diethyl ether, methyl tertiary butyl ether and 1, 4-dioxane. The ketone solvent is preferably acetone. The ester solvent is preferably ethyl acetate. The amide solvent is preferably N, N-Dimethylformamide (DMF). More preferably, the solvent is a nitrile solvent and/or a halogenated hydrocarbon solvent; further, the solvent is a mixed solvent of acetonitrile and dichloromethane.
In the hydrohalogenation reaction, the solvent may be subjected to anhydrous treatment (operation and method of anhydrous treatment are conventional in the art). Preferably, the concentration of the olefin II in the solvent can be a concentration conventional in the art, preferably 0.01 to 1.00mol/L, and more preferably 0.1 mol/L.
In the hydrohalogenation reaction, the palladium catalyst can be one or more of palladium acetate, palladium trifluoroacetate, palladium pentanate, dichlorodiacetonitrile palladium, bis (benzonitrile) palladium chloride, palladium bromide, tetranitrile palladium tetrafluoroborate, palladium hexafluoroacetylacetonate, bis (acetylacetone) palladium, tetranitrile palladium trifluoromethanesulfonate, palladium pivalate, (1E,4E) -bis (dibenzylidene acetone) palladium, bis (dibenzylidene acetone) dipalladium and tris (dibenzylidene acetone) dipalladium; more preferably, the palladium catalyst in the hydrochlorination reaction is dichlorodiacetonitrile palladium; the palladium catalyst in the hydrobromination reaction is palladium hexafluoroacetylacetonate.
The palladium catalyst may be used in the hydrohalogenation reaction in amounts conventional in the art for such reactions. Preferably, the molar ratio of the palladium catalyst to the olefin II is (1-50): 100, respectively; preferably (1-10): 100, respectively; for example, 5:100 or 10: 100.
In the halogenation reaction, the oxazoline ligand may be used in an amount conventional to such reactions in the art. The mol ratio of the oxazoline ligand to the olefin II is (1-75): 100, e.g. 7.5: 100 or 15: 100.
In the hydrohalogenation reaction, the molar ratio of the palladium catalyst to the oxazoline ligand may be a molar ratio conventional in the art for such reactions, and is preferably 1: (1-3), for example, 1: 1.5.
In the halogenation reaction, the chlorinating agent can be a chlorinating agent which is conventional in the reaction in the field, and preferably, the chlorinating agent is N-chlorosuccinimide.
In the hydrohalogenation reaction, the brominating reagent can be a brominating reagent which is conventional in the art for such reactions, and preferably, the brominating reagent is sodium N-bromo-N-methyl isocyanurate (Na-NMBI).
In the hydrohalogenation reaction, the molar ratio of the chlorinating agent or the brominating agent to the olefin II is preferably (1.0-5.0): 1, and more preferably 3: 1.
In the hydrohalogenation reaction, the silicon hydride can be one or more of alkyl silicon hydride, aryl silicon hydride and polymethylhydrosiloxane; preferably, the hydrosilane is triisopropylhydrosilane or triphenylhydrosilane.
In the hydrohalogenation reaction, the molar ratio of the silicon hydride to the olefin II is preferably (1.0-10): 1, more preferably (2.5-10): 1, for example, 3: 1.
In the halogenation reaction, the temperature of the addition reaction can be a temperature conventional in the field of such reactions, and preferably, the temperature of the addition reaction is 20-30 ℃, for example, room temperature.
In the halogenation reaction, the addition reaction can also be carried out under a protective gas. The protective gas can be nitrogen and/or argon.
Compared with the prior art, the invention has the positive improvement effects that:
the preparation method of the beta-acyloxy carboxylic ester compound has the advantages of high yield, wide substrate universality, good functional group compatibility, good corresponding selectivity control, mild reaction conditions and simple operation.
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental procedures, in which specific conditions are not noted in the following examples, are generally carried out under conventional conditions or conditions recommended by the manufacturers. Unless otherwise indicated, percentages and parts are by weight.
Example 1 preparation of hydroxy-substituted pyridine-oxazoline ligands
Figure BDA0003364682590000121
To be provided with
Figure BDA0003364682590000122
For example, the synthetic procedures for hydroxy-substituted pyridinooxazolines are described:
a500 mL reaction flask was charged with substituted pyridine S1(13.5g,100mmol,1.0equiv.) and dichloromethane (150mL), stirred with m-chloroperoxybenzoic acid (32.5g,150mmol,1.5equiv.) added in portions, reacted at room temperature, and monitored by TLC. After the reaction is finished, K is added2CO3(27.6g,200mmol,2.0equiv.), stirring at room temperature for 30min, vacuum filtering, spin-drying the filtrate to obtain pyridine nitrogen oxide S2, and directly putting into the next reaction.
S2, methylene chloride (150mL), and trimethylsilyl cyanide (14.4g,150mmol,1.5equiv.) were added to a 100mL egg-shaped flask, stirred at room temperature for 15 minutes, added with N, N-dimethylcarbamoyl chloride (15.6g,150mmol,1.5equiv.), and stirred at room temperature overnight. Adding Na2CO3The reaction was quenched with aqueous solution (80mL), stirred at room temperature for 10min, then separated, the aqueous phase extracted with DCM, the organic phases combined, dried over anhydrous magnesium sulphate, suction filtered and spin dried, and separated by column chromatography to give S3 as a yellow oil (10.1g, 63% over two steps).
S3(2.0g,10mmol,1.0equiv.) and MeOH (10mL) were added to a 50mL egg-shaped flask, sodium methoxide (270mg,5mmol,0.5equiv.) was added with stirring, heated to 40 ℃ for reaction, and the reaction was monitored by TLC. After the reaction was completed, most of the methanol was removed under reduced pressure, an appropriate amount of methylene chloride and aqueous solution were added to the residue, the organic phase was washed once with saturated brine, dried over anhydrous magnesium sulfate, and suction-filtered and spin-dried to obtain S4(1.61g, 84% yield) (the product had sufficient purity to be directly put into the next reaction).
S4(960.1mg,5.0mmol,1.0equiv.), 2-amino-2-methylpropane was added to a 25ml egg-shaped bottle1, 3-diol (577.5mg,5.5mmol,1.1equiv.), PhCl (15mL), and concentrated HCl (2 drops) was added after the mixture was stirred well. The reaction was heated to 80 ℃ under nitrogen and monitored by TLC. After the reaction is finished, chlorobenzene is removed under reduced pressure, and column chromatography separation is carried out (eluent: PE: EA: Et)3N-10: 1:1) to give a white solid (737.0mg, 67% yield).1H NMR(400MHz,CDCl3)δ7.87(d,J＝7.6Hz,1H),7.61(t,J＝8.0Hz,1H),7.17(d,J＝7.6Hz,1H),4.47(d,J＝8.4Hz,1H),4.09(d,J＝8.4Hz,1H),3.43(d,J＝9.6Hz,1H),3.40(d,J＝9.2Hz,1H),2.75(d,J＝7.2Hz,2H),2.10–2.07(m,1H),1.36(s,3H),0.88(d,J＝6.4Hz,6H).13C NMR(100MHz,CDCl3) Delta 162.8,161.8,146.3,136.2,125.3,121.6,79.5,67.6,47.3,28.9,28.3,22.2HRMS M/z (ESI) calculated value [ M + H]+249.1598, found 249.1595.
Following the above reaction procedure, starting with 6-substituted 2-cyanopyridine, the following ligands were prepared:
Figure BDA0003364682590000131
1H NMR(400MHz,CDCl3)δ7.72(d,J＝8.0Hz,1H),7.41(d,J＝7.6Hz,1H),4.54(d,J＝8.4Hz,1H),4.16(d,J＝8.4Hz,1H),3.79(d,J＝11.6Hz,1H),3.48(d,J＝11.6Hz,1H),3.00(t,J＝6.4Hz,1H),2.81(t,J＝6.4Hz,1H),2.44(br,1H),1.92–1.78(m,4H),1.35(s,3H).13C NMR(100MHz,CDCl3) Δ 163.7,158.0,143.3,137.2,135.4,121.4,75.3,72.2,68.2,32.6,28.9,23.6,22.9,22.4 HRMS M/z (ESI) calculated value [ M + H]+247.1442, found 247.1446.
Figure BDA0003364682590000132
1H NMR(400MHz,CDCl3)δ7.73(d,J＝7.6Hz,1H),7.42(d,J＝8.0Hz,1H),4.57(dd,J＝9.6,7.6Hz,1H),4.53–4.49(m,1H),4.40(t,J＝7.6Hz,1H),3.98(dd,J＝11.6,3.6Hz,1H),3.69(dd,J＝11.6,4.4Hz,1H),3.00(t,J＝6.4Hz,2H),2.82(t,J＝6.4Hz,2H),2.15(br,1H),1.93–1.80(m,4H).13C NMR(100MHz,CDCl3) Δ 164.7,158.0,143.3,137.2,135.3,121.3,69.8,68.3,64.1,32.6,28.9,22.8,22.4 HRMS M/z (ESI) calculated value [ M + H]+233.1284, found 233.1285.
Figure BDA0003364682590000133
1H NMR(400MHz,CDCl3)δ7.73(d,J＝8.0Hz,1H),7.58(t,J＝8.0Hz,1H),7.19(d,J＝8.0Hz,1H),4.54(d,J＝8.4Hz,1H),4.13(d,J＝8.4Hz,1H),3.81(d,J＝11.6Hz,1H),3.48(d,J＝11.6Hz,1H),2.58(s,3H),1.34(s,3H).
Figure BDA0003364682590000134
1H NMR(400MHz,CDCl3)δ7.74(d,J＝7.6Hz,1H),7.52(t,J＝8.0Hz,1H),7.10(d,J＝7.6Hz,1H),4.52(d,J＝8.4Hz,1H),4.16(d,J＝8.4Hz,1H),3.79(d,J＝11.6Hz,1H),3.50(d,J＝11.6Hz,1H),2.71(t,J＝7.6Hz,2H),1.64–1.58(m,2H),1.35(s,3H),0.83(t,J＝7.2Hz,3H).
Figure BDA0003364682590000135
1H NMR(400MHz,CDCl3)δ7.88(d,J＝8.0Hz,1H),7.68(t,J＝8.0Hz,1H),7.27(d,J＝8.8Hz,1H),4.49(d,J＝8.4Hz,1H),4.14(d,J＝8.4Hz,1H),3.78(d,J＝11.2Hz,1H),3.48(d,J＝11.2Hz,1H),2.93(q,J＝7.6Hz,1H),1.39(s,3H),1.31(t,J＝7.6Hz,1H).
Figure BDA0003364682590000141
1H-NMR(400MHz CDCl3)δ7.85(d,J＝7.6Hz,1H),7.64(t,J＝8.0Hz,1H),7.22(d,J＝7.6Hz,1H),4.51(d,J＝8.4Hz,1H),4.18(d,J＝8.4Hz,1H),3.79(d,J＝11.2Hz,1H),3.50(d,J＝11.2Hz,1H),2.79(t,J＝8.8Hz,1H),2.25(m,2H),1.30-1.57(m,19H).
Figure BDA0003364682590000142
1H-NMR(400MHz CDCl3)δ8.31(m,2H),8.11(d,J＝8.4Hz,1H),7.88(d,J＝8.4Hz,1H),7.77(d,J＝6.8Hz,1H),7.63(d,J＝7.2Hz,1H),4.55(d,J＝8.4Hz,1H),4.25(d,J＝8.4Hz,1H),3.84(d,J＝11.2Hz,1H),3.53(d,J＝11.2Hz,1H),1.35(s,3H).
Figure BDA0003364682590000143
1H-NMR(400MHz CDCl3)δ7.86(d,J＝7.6Hz,1H),7.67(t,J＝8.0Hz,1H),7.22(d,J＝7.6Hz,1H),4.53(d,J＝8.0Hz,1H),4.18(d,J＝8.4Hz,1H),3.73(d,J＝11.6Hz,1H),3.50(d,J＝11.2Hz,1H),2.92(m,1H),1.64(m,4H),1.35(s,3H),1.24(m,4H),0.84(t,J＝7.6Hz,6H).
Figure BDA0003364682590000144
1H-NMR(400MHz CDCl3)δ7.80(d,J＝8.0Hz,1H),7.64(t,J＝8.0Hz,1H),7.24(d,J＝8.0Hz,1H),4.54(dd,J＝9.6,7.6Hz,1H),4.50–4.46(m,1H),4.42(t,J＝7.6Hz,1H),4.02(dd,J＝11.6,3.6Hz,1H),3.72(dd,J＝11.6,4.4Hz,1H),2.60(s,3H).
Example 2 Palladium catalyzed Hydrochloridation of olefins
Figure BDA0003364682590000145
Pd (CH)3CN)2Cl2(6.5mg,0.025mmol,5 mol%), L1(9.2mg,0.0375mmol,7.5 mol%), and NCS (133.3mg,1.0mmol,2.0equiv.) were weighed into a sealed tube in this order and subjected to evacuation to place the system under a nitrogen atmosphere, and then a dry mixed solvent CH was added in this order3CN:CH2Cl2(2:8,5.0mL), olefin substrate (0.5mmol,1.0equiv), water (10.0. mu.L), triethylamine (25. mu.L, 1M in DCM,0.025mmol,5 mol%) and triisopropylhydrosilane (0.3mL,1.5mmol,3.0equiv) were reacted to completion with stirring at ambient temperature. After the reaction is finished, passing through a silica gel short column (300-400 mesh, CH)2Cl2Elution), solvent is dried by spinning, and the product is obtained by column chromatography separation (300-400 mesh, PE: EA elution).
Figure BDA0003364682590000151
A colorless liquid (111.7mg, 89% yield).1H NMR(400MHz,CDCl3)δ7.82–7.80(m,2H),7.71–7.68(m,2H),3.67(t,J＝7.6Hz,2H),3.50(t,J＝6.8Hz,2H),1.83–1.76(m,2H),1.72–1.65(m,2H),1.51–1.45(m,2H).13C NMR(100MHz,CDCl3)δ168.4,133.9,132.1,123.2,44.7,37.6,32.0,27.8,24.1.
Figure BDA0003364682590000152
A colorless liquid (131.4mg, 87% yield).1H NMR(400MHz,CDCl3)δ3.52(t,J＝6.8Hz,2H),1.80–1.73(m,2H),1.44–1.40(m,2H),1.32–1.26(m,28H),0.88(t,J＝6.4Hz,3H).13C NMR(100MHz,CDCl3)δ45.1,32.7,31.9,29.70,29.66,29.63,29.56,29.5,29.4,28.9,26.9,22.7,14.1.
Figure BDA0003364682590000153
A colorless liquid (86.7mg, 85% yield).1H NMR(400MHz,CDCl3)δ3.52(t,J＝6.8Hz,2H),1.80–1.73(m,2H),1.44–1.40(m,2H),1.32–1.26(m,16H),0.88(t,J＝6.4Hz,3H).13C NMR(400MHz,CDCl3)δ45.1 32.7,31.9,29.63,29.56,29.49,29.35,28.9,26.9,22.7,14.1.
Figure BDA0003364682590000154
A colorless liquid (79.8mg, 76% yield).1H NMR(400MHz,CDCl3)δ3.53(t,J＝6.8Hz,4H),1.80–1.73(m,4H),1.42–1.29(m,12H).13C NMR(100MHz,CDCl3)δ45.2,32.6,29.3,28.8,26.8.
Figure BDA0003364682590000155
A colorless liquid (82.6mg, 86% yield).1H NMR(400MHz,CDCl3)δ3.61(t,J＝6.8Hz,2H),3.51(t,J＝6.8Hz,2H),1.78–1.71(m,3H),1.57–1.50(m,2H),1.42–1.28(m,12H).13C NMR(100MHz,CDCl3)δ62.9,45.1,32.7,32.6,29.4,29.3,28.8,26.8,25.7.
Figure BDA0003364682590000161
A colorless liquid (93.5mg, 85% yield).1H NMR(400MHz,CDCl3)δ3.77–3.74(m,1H),3.50(t,J＝6.8Hz,2H),1.77–1.70(m,3H),1.48–1.26(m,16H),1.45(d,J＝6.4Hz,3H).13C NMR(100MHz,CDCl3) Δ 68.1,45.1,39.3,32.6,29.55,29.49,29.39,29.36,28.8,26.8,25.7,23.4 HRMS: M/z (EI) calculated [ M]+219.1510, found 219.1509.
Figure BDA0003364682590000162
A colorless liquid (81.2mg, 75% yield).1H NMR(400MHz,CDCl3)δ3.52(t,J＝6.8Hz,2H),2.40(t,J＝7.2Hz,2H),2.12(s,3H),1.79–1.72(m,2H),1.57–1.54(m,2H),1.42–1.37(m,2H).1.27(m,10H).13C NMR(100MHz,CDCl3)209.4,45.1,43.8,32.6,29.8,29.34,29.30,29.29,29.1,28.8,26.8,23.8 HRMS: M/z (FI) calculated [ M]+218.1432, found 218.1430.
Figure BDA0003364682590000163
A colorless liquid (64.2mg, 79% yield).1H NMR(400MHz,CDCl3)δ9.76(s,1H),3.52(t,J＝6.8Hz,2H),2.43(td,J＝7.2,1.2Hz,2H),1.78–1.72(m,2H),1.65–1.61(m,2H),1.45–1.32(m,6H).13C NMR(100MHz,CDCl3)δ202.6,44.9,43.7,32.4,28.8,28.5,26.5,21.8.
Figure BDA0003364682590000164
A colorless liquid (108.1mg, 89% yield).1H NMR(400MHz,CDCl3)δ8.19(d,J＝9.6Hz,2H),8.94(d,J＝9.2Hz,2H),4.06(t,J＝6.4Hz,2H),3.58(t,J＝6.4Hz,2H),1.90-1.83(m,4H),1.68–1.59(m,2H).13C NMR(100MHz,CDCl3)162.1,161.1,155.8,143.4,128.7,112.9,112.8,112.4,101.2,68.1,44.7,32.1,28.2,23.3 HRMS M/z (EI) calculated value [ M]+243.0657, found 243.0653.
Figure BDA0003364682590000165
White solid (109.2mg, 82% yield).1H NMR(400MHz,CDCl3)δ7.61(d,J＝9.6Hz,1H),7.34(d,J＝8.8Hz,1H),6.80(dd,J＝8.8,2.4Hz,1H),6.75(d,J＝2.0Hz,1H),6.21(d,J＝9.2Hz,1H),4.00(t,J＝6.0Hz,2H),3.55(t,J＝6.4Hz,2H),1.87–1.79(m,4H),1.66–1.58(m,2H).13C NMR(100MHz,CDCl3)162.1,161.1,155.8,143.4,128.7,112.9,112.8,112.4,101.2,68.1,44.7,32.1,28.2,23.3 HRMS M/z (EI) calculated value [ M]+266.0704, found 266.0709.
Figure BDA0003364682590000171
A colorless liquid (147.8mg, 96% yield).1H NMR(400MHz,CDCl3)δ8.08(d,J＝7.2Hz,2H),7.26(d,J＝8.4Hz,2H),4.33(t,J＝6.8Hz,2H),3.54(t,J＝6.4Hz,2H),1.82–1.77(m,4H),1.52–1.47(m,4H).19F NMR(376MHz,CDCl3)-63.1.13C NMR(100MHz,CDCl3) δ 165.4,152.5,131.5,128.8,120.3(q, J ═ 257.4Hz), calculated value [ M/z (fi): 120.2,65.1,44.9,32.4,28.5,26.5,25.3 HRMS: M/z: (fi)]+324.0735, found 324.0741.
Figure BDA0003364682590000172
A colorless liquid (97.3mg, 85% yield).1H NMR(400MHz,CDCl3)δ3.53(t,J＝6.8Hz,2H),1.78–1.75(m,2H),1.51–1.33(m,16H).13C NMR(100MHz,CDCl3) Δ 125.1,45.0,41.0,32.5,32.3,29.3,28.6,26.7,26.62,26.60,25.1 HRMS calculated for M/z (EI) [ M-H]+200.1201, found 200.1203.
Figure BDA0003364682590000173
White solid (151.6mg, 84% yield).1H NMR(400MHz,CDCl3)δ7.74(d,J＝8.4Hz,2H),7.27(d,J＝8.4Hz,2H),3.83(t,J＝6.4Hz,2H),3.56(t,J＝6.4Hz,2H),2.40(s,3H),1.88–1.82(m,4H),1.30(s,9H).13C NMR(100MHz,CDCl3) Δ 150.8,144.1,137.2,129.2,127.7,84.2,46.2,44.3,29.5,27.7,27.4,21.5 HRMS M/z (ESI) calculated [ M + Na ]]+384.1007, found 384.0999.
Figure BDA0003364682590000174
White solid (107.4mg, 87% yield).1H NMR(400MHz,CDCl3)δ4.06(br,2H),3.54(t,J＝6.4Hz,2H),2.66(t,J＝12.0Hz,2H),1.70–1.62(m,5H),1.42(s,9H),1.12–1.01(m,2H).13C NMR(400MHz,CDCl3)154.7,79.2,43.9,42.2,38.9,33.1,31.5,28.4 HRMS M/z (ESI) calcd for [ M + Na ]]+270.1231, found 270.1233.
Figure BDA0003364682590000175
A colorless liquid (124.1mg, 88% yield).1H NMR(400MHz CDCl3)δ8.59(d,J＝8.0Hz,1H),8.38(s,1H),7.87(d,J＝8.0Hz,1H),7.49(t,J＝7.2Hz,1H),7.41(t,J＝8.0Hz,1H),4.38(t,J＝6.8Hz,2H),3.58(t,J＝6.8Hz,2H),1.90–1.82(m,4H),1.68–1.60(m,2H).13C NMR(100MHz CDCl3) Delta 162.7,140.0,136.6,136.5,127.2,125.3,124.9,124.6,122.4,64.2, 44.732.1, 28.0,23.4 HRMS M/z (EI) calculated [ M]+282.0476, found 282.0478.
Figure BDA0003364682590000181
A colorless liquid (89.6mg, 83% yield).1H NMR(400MHz,CDCl3)δ7.40(d,J＝2.0Hz,1H),6.34–6.30(m,2H),4.43(s,2H),3.52(t,J＝6.8Hz,2H),3.46(t,J＝6.4Hz,2H),1.78–1.74(m,2H),1.63–1.56(m,2H),1.46–1.34(m,4H).13C NMR(100MHz,CDCl3) Delta 152.0,142.7,110.2,109.0,70.1,64.7,45.0,32.5,29.4,26.6,25.4 HRMS M/z (EI) calculated value [ M]+216.0912, found 216.0914.
Figure BDA0003364682590000182
A colorless liquid (105.6mg, 91% yield).1H NMR(400MHz,CDCl3)δ7.28(d,J＝4.8Hz,1H),7.00–7.96(m,2H),4.66(s,2H),3.53(t,J＝6.8Hz,2H),3.48(t,J＝6.8Hz,2H),1.79–1.74(m,2H),1.67–1.58(m,2H),1.47–1.37(m,4H).13C NMR(100MHz,CDCl3) Delta 141.4,126.5,126.1,125.5, 69.867.2, 44.9,32.5,29.4,26.6,25.4 HRMS M/z (EI) calculated value [ M]+232.0683, found 232.0688.
Figure BDA0003364682590000183
White solid (91.6mg, 73% yield).1H NMR(400MHz,CDCl3)δ7.85–7.83(m,2H),7.73–7.71(m,2H),3.74(t,J＝6.8Hz,2H),3.55–3.51(m,2H),1.92–1.86(m,2H),1.66–1.59(m,1H),1.10(d,J＝6.4Hz,3H).13C NMR(100MHz,CDCl3) Delta 168.2,133.9,132.0,123.1,50.5,35.7,32.9,32.5,17.4 HRMS M/z (EI) calculated [ M]+251.0708, found 251.0703.
Figure BDA0003364682590000184
A colorless liquid (82.4mg, 80% yield).1H NMR(400MHz,CDCl3)δ7.38-7.33(m,5H),5.17(s,2H),3.75(dd,J＝17.6,6.8Hz,1H),3.63(dd,J＝16.8,6.0Hz,1H),2.93–2.88(m,1H),1.30(d,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3) Delta 135.6,128.6,128.3,128.1,66.7,45.9,42.3,15.1 HRMS M/z (EI) calculated [ M]+212.0599, found 212.0601.
Figure BDA0003364682590000185
A colorless liquid (96.1mg, 85% yield, 99% e.e.).1H NMR(400MHz,CDCl3)δ8.03(d,J＝8.4Hz,2H),7.56(t,J＝7.2Hz,1H),7.44(t,J＝6.4Hz,2H),5.22–5.18(m,1H),3.58(t,J＝6.4Hz,2H),1.92–1.82(m,4H),1.37(d,J＝6.0Hz,3H).13C NMR(100MHz,CDCl3) Delta 166.1,132.9,130.6,129.5,128.3,70.8,44.7,33.3,28.6,20.1 HRMS M/z (EI) calculated [ M]+226.0755, found 226.0762.HPLC (IG,0.46 × 25cm,5 μm, n-hexane/isopropanol 97/3, flow rate 0.7mL/min, detection wavelength 214nm) retention time 8.16min (small amount), 9.11min (large amount).
Figure BDA0003364682590000191
A colorless liquid (160.9mg, 93% yield).1H NMR(400MHz,CDCl3)δ3.64(t,J＝8.0Hz,2H),2.01–1.92(m,2H),1.57–1.01(m,25H),0.87–0.83(m,12H).13C NMR(100MHz,CDCl3) δ 72.4,44.3,40.5,39.3,37.44,37.39,37.35,37.3,32.8,32.7,28.0,26.8,24.8,24.4,22.7,22.6,21.3,19.7,19.6 HRMS M/z (EI) calculated [ M-H2O]+314.2735, found 314.2740.
Figure BDA0003364682590000192
A colorless liquid (124.5mg, 85% yield).1H NMR(400MHz,CDCl3)δ7.83–7.81(m,2H),7.70–7.68(m,2H),3.66(t,J＝7.2Hz,2H),3.50(t,J＝6.8Hz,2H),1.75–1.64(m,4H),1.41–1.32(m,8H).13C NMR(100MHz,CDCl3) Δ 168.4,133.8,132.1,123.1,45.0,37.9,32.5,28.9,28.6,28.5,26.7,26.6 HRMS M/z (EI) calculation [ M]+293.1177, found 293.1177.
Figure BDA0003364682590000193
A colorless liquid (111.3mg, 84% yield).1H NMR(400MHz,CDCl3)δ7.82–7.80(m,2H),7.69–7.67(m,2H),3.65(t,J＝7.2Hz,2H),3.49(t,J＝6.4Hz,2H),1.75–1.63(m,4H),1.47–1.63(m,2H),1.38–1.32(m,2H).13C NMR(100MHz,CDCl3) Delta 168.3,133.8,132.1,123.1,44.8,37.7,32.3,28.3,26.3,26.0 HRMS M/z (EI) calculated value [ M]+265.0864, found 265.0868.
Figure BDA0003364682590000194
A colorless liquid (104.1mg, 83% yield).1H NMR(400MHz,CDCl3)δ7.82–7.80(m,2H),7.71–7.68(m,2H),3.67(t,J＝7.6Hz,2H),3.50(t,J＝6.8Hz,2H),1.83–1.76(m,2H),1.72–1.65(m,2H),1.51–1.45(m,2H).13C NMR(100MHz,CDCl3)δ168.4,133.9,132.1,123.2,44.7,37.6,32.0,27.8,24.1.
Figure BDA0003364682590000201
A colorless liquid (62.5mg, 71% yield).1H NMR(400MHz,CDCl3)δ3.53(t,J＝6.8Hz,2H),1.78–1.73(m,2H),1.44–1.40(m,2H),1.32–1.26(m,12H),0.88(t,J＝6.4Hz,3H).13C NMR(100MHz,CDCl3)δ45.2,32.6,31.9,29.5,29.47,29.3,28.9,26.9,22.7,14.1.
Figure BDA0003364682590000202
A colorless liquid (77.5mg, 76% yield).1H NMR(400MHz,CDCl3)δ3.52(t,J＝6.8Hz,2H),1.80–1.73(m,2H),1.44–1.40(m,2H),1.39–1.28(m,16H),0.88(t,J＝6.4Hz,3H).13C NMR(100MHz,CDCl3)δ45.1,32.7,31.9,29.63.29.56.29.49,29.35,28.9,26.8,22.7,14.1.
Figure BDA0003364682590000203
A colorless liquid (86.2mg, 74% yield).1H NMR(400MHz,CDCl3)δ3.53(t,J＝6.8Hz,2H),1.78–1.75(m,2H),1.44–1.40(m,2H),1.32–1.26(m,20H),0.88(t,J＝6.4Hz,3H).13C NMR(100MHz,CDCl3)δ45.2,32.7,31.9,29.7,29.65,29.6,29.5,29.47,29.4,28.9,26.9,22.7,14.1.
Figure BDA0003364682590000204
White solid (116.4mg, 65% yield).1H NMR(400MHz,CDCl3)δ3.53(t,J＝6.4Hz,2H),1.78–1.75(m,2H),1.42–1.25(m,40H),0.88(t,J＝6.4Hz,3H).13C NMR(100MHz,CDCl3) Δ 45.2,32.6,31.9,29.7,29.65,29.61,29.5,29.46,29.4,28.9,26.9,22.7,14.1 HRMS: M/z (FI) calculated [ M]+:358.3361，Measured value 358.3358.
Figure BDA0003364682590000205
White solid (84.8mg, 64% yield).1H NMR(400MHz,CDCl3)δ7.56(d,J＝8.8Hz,2H),6.92(d,J＝8.8Hz,2H),3.99(t,J＝6.4Hz,2H),3.53(t,J＝6.8Hz,2H),1.83–1.73(m,4H),1.49–1.34(m,8H).13C NMR(100MHz,CDCl3) Δ 162.4,133.9,119.3,115.1,103.6,68.3,45.1,32.5,29.1,28.9,28.7,26.7,25.8 HRMS M/z (FI) calculated value [ M]+265.1228, found 265.1231.
Figure BDA0003364682590000211
A colorless liquid (77.3mg, 75% yield).1H NMR(400MHz,CDCl3)δ4.05(t,J＝6.8Hz,2H),3.53(t,J＝6.8Hz,2H),2.04(s,3H),1.78–1.74(m,2H),1.63–1.60(m,2H),1.43–1.32(m,8H).13C NMR(100MHz,CDCl3)δ170.7,64.1,44.7,32.2,28.8,28.4,28.3,26.5,25.5,20.6.
Figure BDA0003364682590000212
A colorless liquid (113.4mg, 63% yield).1H NMR(400MHz,CDCl3)δ6.92(d,J＝9.2Hz,1H),4.07(t,J＝6.8Hz,2H),3.54(t,J＝6.8Hz,2H),2.15(t,J＝8.4Hz,1H),1.97(d,J＝8.4Hz,1H),1.80–1.75(m,2H),1.67–1.62(m,2H),1.50–1.44(m,2H),1.42–1.36(m,2H).1.29(d,J＝2.8Hz,6H).19F NMR(376MHz,CDCl3)δ-67.1.13C NMR(100MHz,CDCl3) δ 170.3,130.2(q, J ═ 4.4Hz),121.7,120.4(q, J ═ 269.5Hz), 64.544.9, 33.0,32.4,30.7,28.5,28.4,26.5,25.3,14.9 HRMS: M/z (fi) calculated value [ M/z (fi) ]]+360.0865, found 360.0871.
Figure BDA0003364682590000213
White solid (103.8mg, 60% yield).1H NMR(400MHz,CDCl3)δ4.12(q,J＝7.2Hz,2H),3.53(t,J＝6.8Hz,2H),2.28(t,J＝7.6Hz,2H),1.74–1.74(m,2H),1.63–1.59(m,2H),1.43–1.40(m,2H),1.28–1.23(m,27H).13C NMR(100MHz,CDCl3) δ 174.0,60.1,45.2,34.4,32.6,29.64,29.60,29.57,29.53,29.4,29.2,29.1,28.9,26.9,25.0,14.2 HRMS calculated as [ M/z (ei) ]]+346.2633, found 346.2640.
Figure BDA0003364682590000214
A colorless liquid (115.5mg, 70% yield).1H NMR(400MHz,CDCl3)δ7.59(t,J＝8.4Hz,4H),7.45(t,J＝7.2Hz,2H),7.36(t,J＝7.2Hz,1H),7.17(d,J＝8.4Hz,2H),3.56(t,J＝6.4Hz,2H),2.60(t,J＝7.2Hz,2H),1.83–1.78(m,4H),1.51–1.41(m,6H).13C NMR(100MHz,CDCl3) Δ 172.2,150.1,140.3,138.9,128.7,128.1,127.3,127.1,121.8,45.0,34.3,32.5,28.9,28.5,26.6,24.8 HRMS M/z (EI) calculated value [ M]+330.1381, found 330.1379.
Figure BDA0003364682590000221
A colorless liquid (185.3mg, 58% yield).1H NMR(400MHz,CDCl3)δ7.68(d,J＝16.0Hz,1H),7.53–7.51(m,2H),7.38–7.37(m,3H),6.44(d,J＝16.4Hz,1H),4.20(t,J＝6.4Hz,2H),3.53(t,J＝6.8Hz,2H),1.79–1.68(m,4H),1.45–1.35(m,8H).13C NMR(100MHz,CDCl3) Δ 167.0,144.5,134.4,130.2,128.8,128.0,118.2,64.6,45.1,32.5,29.0,28.7,28.6,26.7,25.8 HRMS M/z (FI) calculated value [ M]+294.1381, found 294.1385.
Figure BDA0003364682590000222
White solid (161.4)mg,83％yield).1H NMR(400MHz,CDCl3)δ7.75(d,J＝8.0Hz,2H),7.29(d,J＝8.4Hz,2H).3.80(t,J＝7.2Hz,2H),3.52(t,J＝6.8Hz,2H),2.42(s,3H),1.80–1.72(m,4H),1.50–1.45(m,2H),1.40–1.37(m,2H),1.31(s,9H).13C NMR(100MHz,CDCl3) Δ 150.9,144.0,137.5,129.2,127.7,84.0,46.5,44.9,32.4,29.9,27.8,26.4,25.9,21.5 HRMS M/z (ESI) calculated [ M + Na ]]+412.1320, found 412.1324.
Figure BDA0003364682590000223
A colorless liquid (69.4mg, 80% yield).1H NMR(400MHz,CDCl3)δ3.53(t,J＝6.8Hz,2H),2.34(t,J＝7.2Hz,2H),1.79–1.75(m,2H),1.68–1.64(m,2H),1.47–1.33(m,8H).13C NMR(100MHz,CDCl3)119.8,45.0,32.4,28.6,28.55,28.52,26.7,25.3,17.1.
Figure BDA0003364682590000224
Yellow liquid (74.3mg, 77% yield).1H NMR(400MHz,CDCl3)δ4.37(t,J＝6.8Hz,2H),3.52(t,J＝7.2Hz,2H),2.00–1.97(m,2H),1.79–1.71(m,2H),1.44–1.32(m,8H).13C NMR(100MHz,CDCl3)δ75.6,45.0,32.4,28.7,28.5,27.3,26.6,26.1.
Figure BDA0003364682590000225
A colorless liquid (90.6mg, 60% yield).1H NMR(400MHz,CDCl3)δ7.89(d,J＝7.2Hz,2H),7.65(t,J＝7.2Hz,1H),7.56(t,J＝8.0Hz,2H),3.50(t,J＝6.8Hz,2H),3.06(t,J＝7.6Hz,2H),1.74–1.67(m,4H),1.39–1.24(m,10H).13C NMR(100MHz,CDCl3) Δ 139.1,133.6,129.2,128.0,56.2,45.0,32.5,28.9,28.8,28.6,28.1,26.7,22.5 HRMS M/z (ESI) calculated value [ M + Na]+325.0999, found 325.0994.
Figure BDA0003364682590000231
A colorless liquid (109.5mg, 74% yield).1H NMR(400MHz,CDCl3)δ8.59(d,J＝8.4Hz,1H),8.38(s,1H),7.88(d,J＝8.0Hz,1H),7.49(t,J＝7.2Hz,1H),7.41(t,J＝8.0Hz,1H),4.38(t,J＝6.8Hz,2H),3.56(t,J＝6.4Hz,2H),1.85–1.80(m,4H),1.58–1.51(m,4H).13C NMR(100MHz,CDCl3) Delta 162.9,140.1,136.7,136.5,127.3,125.4,125.0,124.7,122.5,64.5,44.9,32.4,28.6,26.5,25.4 HRMS M/z (EI) calculated value [ M]+296.0632, found 296.0637.
Figure BDA0003364682590000232
A colorless liquid (102.7mg, 79% yield).1H NMR(400MHz,CDCl3)δ7.28(dd,J＝4.2,2.0Hz,1H),7.15(s,1H),7.04(d,J＝4.8Hz,1H),4.1(t,J＝6.8Hz,2H),3.65(s,2H),3.52(t,J＝6.8Hz,2H),1.80–1.72(m,2H),1.68–1.61(m,2H),1.50–1.42(m,2H),1.37–1.32(m,2H).13C NMR(100MHz,CDCl3) Δ 171.2,133.7,128.5,125.7,122.8,64.8,44.9,36.0,32.4,28.4,26.5,25.2 HRMS: M/z (EI) calculated value [ M]+260.0632, found 260.0634.
Figure BDA0003364682590000233
A colorless liquid (113.4mg, 81% yield).1H NMR(400MHz,CDCl3)δ7.68(d,J＝7.6Hz,1H),7.60(d,J＝7.6Hz,1H),7.52(s,1H),7.45(t,J＝7.2Hz,1H),7.31(t,J＝8.0Hz,1H),4.39(t,J＝6.8Hz,2H),3.55(t,J＝6.4Hz,2H),1.84–1.78(m,4H),1.54–1.48(m,4H).13C NMR(100MHz,CDCl3) Delta 159.7,155.7,145.6,127.6,126.9,123.8,122.8,113.8,112.4,65.3,44.9,32.4,28.5,26.5,25.3 HRMS M/z (EI) calculated value [ M]+280.0861, found 280.0863.
Figure BDA0003364682590000234
A colorless liquid (37.4mg, 42% yield).1H NMR(400MHz,CDCl3)δ3.64(s,3H),3.50(t,J＝6.4Hz,2H),2.30(t,J＝7.6Hz,2H),1.77–1.74(m,2H),1.64–1.61(m,2H),1.46–1.42(m,2H).13C NMR(100MHz,CDCl3)δ174.0,51.5,44.7,33.7,32.1,26.3,24.1.
Figure BDA0003364682590000235
A colorless liquid (96.3mg, 56% yield).1H NMR(400MHz,CDCl3)δ3.65(t,J＝7.6Hz,2H),1.95(t,J＝7.6Hz,2H),1.85–1.82(m,1H),1.66–1.51(m,6H),1.44–1.23(m,5H),1.19–1.13(m,8H),0.93–0.90(m,2H),0.86(s,3H),0.78(s,6H).13C NMR(100MHz,CDCl3) Δ 75.0,72.5,61.7,56.0,46.1,44.8,44.2,41.9,40.7,39.6,39.2,33.3,33.2,25.6,24.3,21.4,20.4,18.6,18.4,15.4 HRMS M/z (ESI) calculated [ M + Na: (M + Z)]+367.2374, found 367.2374.
Figure BDA0003364682590000241
Light yellow liquid (195.7mg, 91% yield).1H NMR(400MHz,CDCl3)δ7.84(d,J＝8.4Hz,1H),6.77(s,1H),6.51(d,J＝8.8Hz,1H),6.45(s,1H),5.24(t,J＝8.8Hz,1H),5.07(s,1H),4.93(s,2H),4.61(dd,J＝12.0,3.2Hz,1H),4.18(d,J＝12.0Hz,1H),3.84–3.76(m,8H),3.32(dd,J＝10.0,4.0Hz,1H),2.95(dd,J＝15.6,8.4Hz,1H),1.76(s,3H).13C NMR(100MHz,CDCl3) Delta 188.9,167.3,157.9,149.3,147.2,143.8,143.0,129.9,113.3,112.9,112.6,110.2,104.9,104.7,100.8,87.8,72.2,66.2,56.2,55.8,44.5,31.2,17.1 HRMS M/z (EI) calculated [ M + Na]+453.1075, found 453.1063.
Figure BDA0003364682590000242
A colorless liquid (93.6mg, 72% yield).1H NMR(400MHz,CDCl3)δ3.67(s,3H),3.49(t,J＝6.4Hz,2H),2.61–2.56(m,1H),2.35–2.04(m,5H),1.79–1.70(m,3H),1.56–1.39(m,6H),1.37–1.20(m,1H).13C NMR(100MHz,CDCl3) Δ 219.5,172.6,54.0,51.6,45.0,38.8,38.0,37.6,32.3,27.5,27.2,27.0,25.8 HRMS: M/z (FI) calculated [ M]+260.1174, found 260.1175.
Figure BDA0003364682590000243
A colorless liquid (130.2mg, 64% yield).1H NMR(400MHz,CDCl3)δ7.11(d,J＝7.6Hz,2H),6.80(d,J＝8.0Hz,2H),4.15(t,J＝6.4Hz,2H),3.48(t,J＝6.8Hz,2H),2.83(dd,J＝10.0,8.4Hz,1H),1.94(dd,J＝10.8,7.2Hz,1H),1.80–1.55(m,11H),1.41–1.35(m,2H),1.28–1.23(m,2H).13C NMR(100MHz,CDCl3) Δ 174.3,155.0,129.6127.9,118.2, 79.0,65.3,44.8,35.7,32.3,28.2,26.3,25.8,25.39,25.36,25.1 HRMS: M/z (FI) calculated [ M]+406.0864, found 406.0861.
Figure BDA0003364682590000244
Light yellow liquid (168.5mg, 67% yield).1H NMR(400MHz,CDCl3)δ7.65(d,J＝8.4Hz,2H),7.46(d,J＝8.4Hz,2H),6.96(s,1H),6.87(d,J＝8.8Hz,1H),6.67(d,J＝9.2Hz,1H),4.09(t,J＝6.8Hz,2H),3.83(s,3H),3.65(s,2H),3.51(t,J＝6.8Hz,2H),2.38(s,3H),1.77–1.70(m,2H),1.66–1.59(m,2H),1.40–1.37(m,2H),1.35–1.27(m,6H).13C NMR(100MHz,CDCl3) Δ 170.9,168.2,156.0,139.2,135.8,133.9,131.1,130.7,130.6,129.1,114.9,112.7,111.6,101.3,65.0,55.6,45.0,32.5,30.4,28.9,28.7,28.5,26.7,25.7,13.3 HRMS M/z (ESI) calculated [ M + Na: (M + Na)]+526.1522, found 526.1525.
Figure BDA0003364682590000251
A colorless liquid (83.6mg, 76% yield).1H NMR(400MHz,CDCl3)δ4.82–4.79(m,1H),3.52(t,J＝6.8Hz,2H),2.04(s,3H),1.79–1.72(m,2H),1.59–1.49(m,4H),1.44–1.41(m,2H),1.31–1.25(m,4H),0.88(t,J＝7.6Hz,3H).13C NMR(100MHz,CDCl3) Δ 171.0,75.4,45.0,33.5,32.5,28.7,26.9,26.7,25.1,21.2,9.6 HRMS M/z (EI) calculated value [ M]+220.1225, found 220.1228.
Figure BDA0003364682590000252
A colorless liquid (133.5mg, 87% yield).1H NMR(400MHz,CDCl3)δ7.83–7.81(m,2H),7.73–7.70(m,2H),4.13–4.08(m,1H),3.48(t,J＝6.8Hz,2H),2.09–2.01(m,2H),1.79–1.68(m,4H),1.37–1.24(m,6H),0.86(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3) Δ 168.8,133.8,131.8,123.1,53.8,45.0,32.4,32.0,28.5,26.7,26.5,25.5,11.1 HRMS M/z (ESI) calculated [ M + Na ]]330.1231, found 330.1237.
Figure BDA0003364682590000253
A colorless liquid (77.4mg, 79% yield).1H NMR(400MHz,CDCl3)δ3.86–3.82(m,1H),3.53(t,J＝6.4Hz,2H),1.83–1.67(m,6H),1.58–1.25(m,8H),1.02(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3) Delta 65.7,45.0,37.9,32.5,31.5,28.4,26.7,26.3,10.9 HRMS M/z (EI) calculated [ M-HCl ]]+160.1013, found 160.1016.
Figure BDA0003364682590000254
A colorless liquid (66.3mg, 65% yield).1H NMR(400MHz,CDCl3)δ3.59–3.53(m,2H),1.80–1.77(m,1H),1.65–1.50(m,2H),1.29–1.20(m,8H),1.15–1.08(m,3H),0.92–0.83(m,9H).13C NMR(100MHz,CDCl3) Δ 43.4,39.77,36.6,34.4,30.3,29.48,27.3,27.15,19.20,19.08,11.4.dr 43.4,39.75,36.6,34.4,30.3,29.45,27.2,27.14,19.19,19.07,11.4.HRMS: M/z (EI) calcd [ M.3532, 19.07,11.4.HRMS: M/z (EI) ]calcd]+204.1639, found 204.1636.
Figure BDA0003364682590000261
A colorless liquid (64.2mg, 73% yield).1H NMR(400MHz,CDCl3)δ3.54(t,J＝6.8Hz,2H),1.77–1.73(m,2H),1.44–1.09(m,11H),0.89(t,J＝6.8Hz,3H),0.85(d,J＝6.8Hz,3H).13C NMR(100MHz,CDCl3) Δ 45.2,36.6,36.2,33.0,32.6,29.3,24.4,23.0,19.6,14.1 HRMS M/z (FI) calculated value [ M]+176.1326, found 176.1329.
Figure BDA0003364682590000262
A colorless liquid (58.2mg, 64% yield).1H NMR(400MHz,CDCl3)δ7.51(d,J＝7.2Hz,2H),7.45(d,J＝8.0Hz,2H),7.36(t,J＝7.6Hz,2H),7.26(t,J＝7.2Hz,1H),7.20–7.18(m,2H),3.50(t,J＝6.0Hz,2H),2.62(t,J＝6.8Hz,2H),1.76(m,4H).13C NMR(100MHz,CDCl3)δ141.0,140.9,138.8,128.8,128.7,127.1,127.0,126.96,44.9,34.7,32.1,28.5.
Figure BDA0003364682590000263
A colorless liquid (58.2mg, 64% yield).1H NMR(400MHz,CDCl3)δ7.32–7.29(m,2H),7.21–7.19(m,3H),3.55(t,J＝6.8Hz,2H),2.65(t,J＝8.0Hz,2H),1.84–1.81(m,2H),1.69–1.66(m,2H),1.54–1.48(m,2H).13C NMR(100MHz,CDCl3)δ142.3,128.34,128.28,125.7,45.0,35.7,32.5,30.7,26.5.
Example 3 Palladium catalyzed hydrobromination of olefins
Figure BDA0003364682590000264
Pd (hfacac)2(26.0mg,0.05mmol,10mol％),L3(17.5mg,0.075mmol,15mol％),LiClO4(53.4mg,0.5mmol,1.0equiv) or HCl (50. mu.L, 40 mol%, 4.0M in dioxane), Na-NMBI (229.0mg,1.0mmol,2.0equiv) were weighed into a sealed tube in order and subjected to air-suction to make the system under nitrogen atmosphere, and then dried mixed solvent CH was added in order3CN:CH2Cl2(4:6,5.0mL), olefinic substrate (0.5mmol,1.0equiv), H2O(4.0μL for HCl,10μL for LiClO4) The resulting mixture was reacted with triisopropylhydrosilane (0.22mL,1.1mmol,2.2equiv) under stirring at room temperature. After 6 hours, Na-NMBI (114.5mg,0.5mmol,1.0equiv) and triisopropylhydrosilane (0.11mL,0.55mmol,1.1equiv) were added thereto, and the reaction was continued until completion. After the reaction is finished, passing through a silica gel short column (300-400 mesh, CH)2Cl2Elution), solvent is dried by spinning, and the product is obtained by column chromatography separation (300-400 mesh, PE: EA elution).
Figure BDA0003364682590000265
A colorless liquid (123.0mg, 73% yield).1H NMR(400MHz,CDCl3)δ7.85–7.83(m,2H),7.72–7.69(m,2H),3.68(t,J＝7.2Hz,2H),3.40(t,J＝6.8Hz,2H),1.86–1.82(m,2H),1.70–1.66(m,2H),1.43–1.25(m,8H).13C NMR(100MHz,CDCl3)δ168.5,133.9,132.1,123.2,37.9,34.0,32.7,28.9,28.6,28.5,28.0,26.7.
Figure BDA0003364682590000271
A colorless liquid (112.1mg, 77% yield).1H NMR(400MHz,CDCl3)δ7.82–7.80(m,2H),7.71–7.68(m,2H),3.67(t,J＝7.6Hz,2H),3.37(t,J＝6.8Hz,2H),1.83–1.76(m,2H),1.72–1.65(m,2H),1.51–1.45(m,2H).13C NMR(100MHz,CDCl3)δ168.3,133.9,132.1,123.2,37.5,33.4,32.1,27.6,25.3.
Figure BDA0003364682590000272
A colorless liquid (59.4mg, 54% yield).1H NMR(400MHz,CDCl3)δ3.40(t,J＝6.8Hz,2H),1.89–1.82(m,2H),1.44–1.27(m,14H),0.88(t,J＝6.0Hz,3H).13C NMR(100MHz,CDCl3)δ34.1,32.9,31.9,29.55,29.49,29.32,28.82,28.2,22.7,14.1.
Figure BDA0003364682590000273
A colorless liquid (76.9mg, 57% yield).1H NMR(400MHz,CDCl3)δ3.40(t,J＝6.8Hz,2H),1.87–1.82(m,2H),1.44–1.27(m,22H),0.88(t,J＝6.0Hz,3H).13C NMR(100MHz,CDCl3)δ34.1,32.8,31.9,29.7,29.65,29.63,29.5,29.4,28.8,28.2,22.7,14.1.
Figure BDA0003364682590000274
A colorless liquid (108.5mg, 54% yield).1H NMR(400MHz,CDCl3)δ3.41(t,J＝6.8Hz,2H),1.87–1,83(m,2H),1.44–1.25(m,40H),0.88(t,J＝6.4Hz,3H).13C NMR(100MHz,CDCl3) Δ 34.1,32.9,32.0,29.73,29.69,29.66,29.58,29.47,29.4,28.8,28.2,22.7,14.2 HRMS: M/z (FI) calculated [ M]+402.2856, found 402.2862.
Figure BDA0003364682590000275
A colorless liquid (128.1mg, 61% yield).1H NMR(400MHz,CDCl3)δ7.44(s,1H),7.29(s,2H),4.03(t,J＝6.4Hz,2H),3.42(t,J＝6.8Hz,2H),1.89–1.81(m,4H),1.48–1.38(m,8H).19F NMR(376MHz,CDCl3)δ-63.1.13C NMR(100MHz,CDCl3) δ 159.7,132.7(q, J ═ 32.9Hz),123.2(q, J ═ 271.1Hz),114.7(d, J ═ 2.3Hz),114.0(h, J ═ 3.9Hz),68.7,33.9,32.7,29.1,28.9,28.6,28.0,25.8 HRMS: M/z (ei) calculated value [ M, J: (ei) ]]+420.0518, found 420.0521.
Figure BDA0003364682590000281
A colorless liquid (66.6mg, 60% yield).1H NMR(400MHz,CDCl3)δ3.99(t,J＝6.8Hz,2H),3.34(t,J＝6.8Hz,2H),1.98(s,3H),1.82–1.78(m,2H),1.59–1.55(m,2H),1.40–1.31(m,4H).13C NMR(100MHz,CDCl3)δ170.9,64.1,33.6,32.4,28.2,27.6,24.9,20.8.
Figure BDA0003364682590000282
A colorless liquid (58.5mg, 60% yield).1H NMR(400MHz,CDCl3)δ4.35(t,J＝6.8Hz,2H),3.36(t,J＝6.4Hz,2H),2.01–1.94(m,2H),1.89–1.82(m,2H),1.53–1.47(m,2H).13C NMR(100MHz,CDCl3)δ75.1,32.9,31.6,26.2,24.6.
Figure BDA0003364682590000283
White solid (166.7mg, 77% yield).1H NMR(400MHz,CDCl3)δ7.74(d,J＝8.0Hz,2H),7.28(d,J＝8.0Hz,2H),3.79(t,J＝7.2Hz,2H),3.39(t,J＝6.8Hz,2H),2.41(s,3H),1.87–1.82(m,2H),1.77–1.71(m,2H),1.50–1.55(m,2H),1.40–1.30(m,11H).13C NMR(100MHz,CDCl3) Δ 150.9,144.1,137.5,129.2,127.7,84.1,47.0,33.8,32.6,29.9,27.8,27.7,25.8,21.6 HRMS M/z (ESI) calculated [ M + Na ]]+456.0815, found 456.0827.
Figure BDA0003364682590000284
A colorless liquid (102.1mg, 59% yield).1H NMR(400MHz,CDCl3)δ7.89(d,J＝7.2Hz,2H),7.66–7.62(m,1H),7.57–7.53(m,2H),3.37(t,J＝6.8Hz,2H),3.06(t,J＝7.6Hz,2H),1.84–1.77(m,2H),1.72–1.64(m,2H),1.37–1.23(m,10H).13C NMR(100MHz,CDCl3) Δ 139.1,133.6,129.2,128.0,56.2,34.0,32.7,29.0,28.8,28.5,28.2,28.0,22.6 HRMS M/z (FI) calculated value [ M]+346.0597, found 346.0595.
Figure BDA0003364682590000285
A colorless liquid (117.3mg, 69% yield).1H NMR(400MHz,CDCl3)δ8.58(d,J＝8.4Hz,1H),8.38(s,1H),7.87(d,J＝8.0Hz,1H),7.47(t,J＝7.6Hz,1H),7.41(t,J＝7.6Hz,1H),4.37(t,J＝6.4Hz,2H),3.43(t,J＝6.4Hz,2H),1.90–1.82(m,4H),1.60–1.53(m,4H).13C NMR(100MHz,CDCl3) Delta 162.9,140.1,136.7,136.5,127.3,125.4,125.0,124.7,122.5,64.5,33.7,32.6,28.6,27.8,25.3 HRMS M/z (EI) calculated value [ M]+340.0127, found 340.0137.
Figure BDA0003364682590000291
A colorless liquid (106.4mg, 70% yield).1H NMR(400MHz,CDCl3)δ7.30–7.28(m,1H),7.15(s,1H),7.04(d,J＝5.2Hz,1H),4.10(t,J＝6.4Hz,2H),3.65(s,2H),3.39(t,J＝6.8Hz,2H),1.86–1.81(m,2H),1.66–1.63(m,2H),1.47–1.41(m,2H),1.38–1.32(m,2H).13C NMR(100MHz,CDCl3)δ171.2,133.7,128.5,125.7,122.8,64.8,36.0,33.7,32.6,28.4,27.7,25.1.
Figure BDA0003364682590000292
A colorless liquid (111.1mg, 55% yield).1H NMR(400MHz,CDCl3)δ6.92(d,J＝9.6Hz,1H),4.06(t,J＝7.2Hz,2H),3.40(t,J＝6.8Hz,2H),2.14(t,J＝8.8Hz,1H),1.966(d,J＝8.4Hz,1H),1.88-1.84(m,2H),1.66-1.61(m,2H),1.49-1.29(m,10H).19F NMR(396MHz,CDCl3)δ-68.7.13C NMR(100MHz,CDCl3) δ 170.3,130.2(q, J ═ 4.6Hz),121.4(q, J ═ 36.8Hz),120.4(q, J ═ 293.4Hz),64.5,33.6,33.0,32.5,30.7,28.45,28.40,28.3,27.7,25.1 HRMS: M/z (fi) calculated value [ M, J ═ 293.4Hz ], M/z (fi) ]]+404.0360, found 404.0358.
Figure BDA0003364682590000293
A colorless liquid (81.4mg, 69% yield).1H NMR(400MHz,CDCl3)δ4.11(q,J＝6.8Hz,2H),3.39(t,J＝6.4Hz,2H),2.30(t,J＝7.6Hz,2H),1.88–1.83(m,2H),1.66–1.60(m,2H),1.50–1.44(m,2H),1.24(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ173.4,60.3,34.1,33.5,32.4,27.6,24.1,14.2.
Figure BDA0003364682590000294
A colorless liquid (115.1mg, 78% yield).1H NMR(400MHz,CDCl3)δ7.82–7.80(m,2H),7.71–7.68(m,2H),3.67(t,J＝7.6Hz,2H),3.37(t,J＝6.8Hz,2H),1.83–1.76(m,2H),1.72–1.65(m,2H),1.51–1.45(m,2H).13C NMR(100MHz,CDCl3)δ168.3,133.9,132.1,123.2,37.5,33.4,32.1,27.6,25.3.
Figure BDA0003364682590000301
A colorless liquid (6.9mg, 62% yield).1H NMR(400MHz,CDCl3)δ3.40(t,J＝6.8Hz,2H),1.89–1.82(m,2H),1.44–1.40(m,2H),1.32–1.26(m,16H),0.88(t,J＝6.8Hz,3H).13C NMR(400MHz,CDCl3)δ34.0,32.8,31.9,29.6,29.5,29.4,29.3,28.8,28.2,22.7.
Figure BDA0003364682590000302
A colorless liquid (106.2mg, 74% yield).1H NMR(400MHz,CDCl3)δ8.20(d,J＝9.2Hz,2H),6.94(d,J＝9.2Hz,2H),4.06(t,J＝6.0Hz,2H),3.45(t.J＝6.4Hz,2H),1.97–1.87(m,4H),1.67–1.63(m,2H).13C NMR(100MHz,CDCl3)δ164.2,141.5,125.9,114.4,68.5,33.4,32.3,28.2,24.7.
Figure BDA0003364682590000303
A colorless liquid (146.1mg, 83% yield).1H NMR(400MHz,CDCl3)δ8.15(d,J＝8.0Hz,2H),7.70(d,J＝8.0Hz,2H),4.36(t,J＝6.4Hz,2H),3.42(t,J＝6.8Hz,2H),1.93–1.86(m,2H),1.84–1.77(m,2H),1.55–1.46(m,4H).19F NMR(376MHz,CDCl3)δ-63.1.13C NMR(100MHz,CDCl3) δ 165.4,134.2,133.6,129.9,125.4(q, J ═ 38.0Hz),123.6(q, J ═ 271.0Hz),65.4,33.6,32.5,28.5,27.8,25.2 HRMS: M/z (fi) calculated value [ M + Na: (M + Na): M/z (fi): calculated value]+352.0280, found 352.0287.
Figure BDA0003364682590000304
A colorless liquid (73.3mg, 66% yield).1H NMR(4 00MHz,CDCl3)δ3.99(t,J＝6.8Hz,2H),3.34(t,J＝6.8Hz,2H),1.98(s,3H),1.82–1.78(m,2H),1.59–1.55(m,2H),1.40–1.31(m,4H).13C NMR(100MHz,CDCl3)δ170.9,64.1,33.6,32.4,28.2,27.6,24.9,20.8.
Figure BDA0003364682590000305
White solid (136.9mg, 70% yield).1H NMR(400MHz,CDCl3)δ7.77(d,J＝7.6Hz,2H),7.31(d,J＝8.0Hz,2H),3.96(t,J＝6.8Hz,2H),3.45(t,J＝6.4Hz,2H),2.44(s,3H),2.34–2.31(m,2H),1.35(s,9H).13C NMR(100MHz,CDCl3)δ150.8,144.3,137.0,129.3,127.8,84.5,46.0,33.1,30.0,27.8,21.6 HRMS M/z (ESI) calculated [ M + Na]+414.0345, found 414,0342.
Figure BDA0003364682590000306
A colorless liquid (72.8mg, 75% yield).1H NMR(400MHz,CDCl3)δ4.35(t,J＝6.8Hz,2H),3.36(t,J＝6.4Hz,2H),2.01–1.94(m,2H),1.89–1.82(m,2H),1.53–1.47(m,2H).13C NMR(100MHz,CDCl3)δ75.1,32.9,31.6,26.2,24.6.
Figure BDA0003364682590000311
A colorless liquid (104.7mg, 71% yield).1H NMR(400MHz,CDCl3)δ7.85–7.83(m,2H),7.72–7.70(m,2H),3.72(t,J＝6.8Hz,2H),3.48–3.39(m,2H),1.90–1.80(m,2H),1.63–1.58(m,1H),1.10(d,J＝6.4Hz,3H).13C NMR(100MHz,CDCl3) Δ 168.3,134.0,132.0,123.2,40.7,35.7,33.4,32.5,18.5 HRMS calculated M/z (dart) [ M + H ]]+296.0281, found 296.0275.
Figure BDA0003364682590000312
A colorless liquid (102.4mg, 80% yield).1H NMR(400MHz,CDCl3)δ7.36–7.34(m,5H),5.17(s,2H),3.66(dd,J＝10.0,6.8Hz,1H),3.49(dd,J＝10.0,6.0Hz,1H),2.98–2.93(m,1H),1.31(d,J＝6.8Hz,3H).13C NMR(100MHz,CDCl3)δ173.3,135.7,128.7,128.5,128.3,66.9,42.3,34.2,16.4.
Figure BDA0003364682590000313
A colorless liquid (128.3mg, 78% yield).1H NMR(400MHz,CDCl3)δ8.15(d,J＝7.6Hz,2H),7.51(td,J＝8.0,1.2Hz,2H),7.43(d,J＝8.0Hz,2H),7.28(td,J＝7.6,0.8Hz,2H),4.34(t,J＝7.2Hz,2H),3.39(t,J＝6.8Hz,2H),1.96–1.81(m,4H),1.53–1.41(m,4H).13C NMR(100MHz,CDCl3)δ140.4,125.6,122.8,120.3,118.8,108.6,42.8,33.7,32.6,28.8,27.9,26.4.
Figure BDA0003364682590000314
A colorless liquid (85.2mg, 67% yield).1H NMR(400MHz,CDCl3)δ7.59(s,1H),7.18(d,J＝2.8Hz,1H),6.52(dd,J＝3.6,2.0Hz,1H),4.34(t,J＝6.0Hz,2H),3.48(t,J＝6.4Hz,2H),2.03–1.91(m,4H).13C NMR(100MHz,CDCl3)δ158.7,146.4,144.7,117.0,111.9,63.9,33.0,29.3,27.4.
Figure BDA0003364682590000315
A colorless liquid (100.8mg, 65% yield).1H NMR(400MHz,CDCl3)δ8.59(d,J＝8.0Hz,1H),8.38(s,1H),7.88(d,J＝8.0Hz,1H),7.49(t,J＝8.4Hz,1H),7.41(t,J＝8.0Hz,1H),4.37(t,J＝6.8Hz,2H),1.92–1.82(m,4H),1.58–1.49(m,4H).13C NMR(100MHz,CDCl3) Delta 162.8,140.1,136.7,136.5,127.3,125.4,125.0,124.7,122.5,64.5,33.7,32.6,28.6,27.8,25.3 HRMS M/z (EI) calculated value [ M]+310.0199, found 310.0197.
Figure BDA0003364682590000321
White solid (97.6mg, 63% yield).1H NMR(400MHz,CDCl3)δ7.62(d,J＝9.6Hz,1H),7.36(d,J＝8.8Hz,1H),6.84–6.78(m,2H),6.23(d,J＝9.6Hz,1H),4.02(t,J＝6.0Hz,2H),3.44(t,J＝6.4Hz,2H),1.98–1.90(m,2H),1.86–1.81(m,2H),1.68–1.62(m,2H).13C NMR(100MHz,CDCl3)δ162.2,161.2,155.9,143.4,128.7,113.0,112.9,112.4,101.3,68.2,33.4,32.3,28.1,24.7.
Figure BDA0003364682590000322
A colorless liquid (109.2mg, 74% yield, 99% e.e.).1H NMR(400MHz,CDCl3)δ7.83–7.81(m,2H),7.72–7.70(m,2H),4.40–4.34(m,1H),3.40(t,J＝6.4Hz,2H),2.25–2.19(m,1H),1.94–1.78(m,3H),1.49(d,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3) Delta 168.4,133.9,131.9,123.1,46.5,32.8,32.2,29.9,18.7 HRMS M/z (EI) calculated [ M]+295.0202, found 295.0202.HPLC (IF3,0.46 × 25cm,5 μm, hexane/isoproanol 98/2, flow 0.7mL/min, detection at 214nm) coverage time 24.13min (minor) and 28.59min (major).
Figure BDA0003364682590000323
A colorless liquid (108.2mg, 82% yield).1H NMR(400MHz,CDCl3)δ4.81-4.78(m,1H),3.39(t,J＝6.8Hz,2H),2.04(s,3H),1.88–1.80(m,2H),1.62–1.25(m,10H),0.87(t,J＝7.6Hz,3H).13C NMR(100MHz,CDCl3)171.1,75.4,33.9,33.5,32.7,28.6,28.0,26.9,25.1,21.2,9.6 HRMS M/z (FI) Calculations [ M + H]+265.0798, found 265.0802.
Figure BDA0003364682590000324
Colorless liquid (122.8, 70% yield).1H NMR(400MHz,CDCl3)δ7.83–7.82(m,2H),7.72–7.70(m,2H),4.12–4.09(m,1H),3.36(t,J＝6.4Hz,2H),2.09–1.82(m,2H),1.80–1.68(m,4H),1.38–1.22(m,6H),0.86(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)168.9,133.9,131.8,123.1,53.8,33.9,32.6,32.1,29.7,28.4,28.0,26.5,25.6,11.1 HRMS calculated as [ M + H ] (dart)]+352.0907, found 352.0900.
Figure BDA0003364682590000325
A colorless liquid (76.8mg, 64% yield).1H NMR(400MHz,CDCl3)δ3.87-3.80(m,1H),3.41(t,J＝6.8Hz,2H),1.91–1.66(m,6H),1.58–1.30(m,6H),1.02(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3) Δ 65.8,38.0,34.0,32.7,31.6,28.3,28.0,26.4,11.0.HRMS M/z (FI) calculated value [ M]+240.0275, found 240.0278.
EXAMPLE 4 hydrochlorination of Mixed olefins
Figure BDA0003364682590000331
Pd (CH)3CN)2Cl2(6.5mg,0.025mmol,5 mol%), L1(9.2mg,0.0375mmol,7.5 mol%), and NCS (133.3mg,1.0mmol,2.0equiv.) were weighed into a sealed tube in this order and subjected to evacuation to place the system under a nitrogen atmosphere, and then a dry mixed solvent CH was added in this order3CN:CH2Cl2(2:8,5.0mL), octene substrate (0.5mmol,1.0equiv), water (10.0. mu.L), triethylamine (25. mu.L, 1M in DCM,0.025mmol,5 mol%) and triisopropylhydrosilane (0.3mL,1.5mmol,3.0equiv) were mixed and the reaction was stirred at ambient temperature to completion. After the reaction is finished, passing through a silica gel short column (300-400 mesh, CH)2Cl2Elution), solvent spin-drying, column chromatography separation (300-400 mesh, PE: EA elution) to obtain 55.6mg of the product 11a with a yield of 75%.1H NMR(400MHz,CDCl3)δ3.53(t,J＝6.8Hz,2H),1.80–1.73(m,2H),1.44–1.40(m,2H),1.32–1.26(m,10H),0.88(t,J＝6.4Hz,3H).13C NMR(100MHz,CDCl3)δ45.2,32.6,31.7,29.1,28.8,26.9,22.6,14.1.
EXAMPLE 5 hydrobromination of Mixed olefins
Figure BDA0003364682590000332
Pd (hfacac)2(26.0mg,0.05mmol,10mol％),L3(17.5mg,0.075mmol,15mol％),LiClO4(53.4mg,0.5mmol,1.0equiv) or HCl (50. mu.L, 40 mol%, 4.0M in dioxane), Na-NMBI (229.0mg,1.0mmol,2.0equiv) are weighed into a sealed tube in sequence and subjected to air-suction to make the system under nitrogen atmosphere, and then the dry mixed solvent CH is added in sequence3CN:CH2Cl2(4:6,5.0mL), Mixed octene substrate (0.5mmol,1.0equiv), H2O(4.0μL for HCl,10μL for LiClO4) The resulting mixture was reacted with triisopropylhydrosilane (0.22mL,1.1mmol,2.2equiv) under stirring at room temperature. After 6 hours, Na-NMBI (114.5mg,0.5mmol,1.0equiv) and triisopropylhydrosilane (0.11mL,0.55mmol,1.1equiv) were added thereto, and the reaction was continued until completion. After the reaction is finished, passing through a silica gel short column (300-400 mesh, CH)2Cl2Elution), solvent spin-drying, column chromatography separation (300-400 mesh, PE: EA elution) to obtain 11b 53mg of product with 53% yield1H NMR(400MHz,CDCl3)δ3.40(t,J＝6.8Hz,2H),1.89–1.81(m,2H),1.44–1.28(m,10H),0.88(t,J＝6.8Hz,3H).13C NMR(100MHz,CDCl3)δ34.1,32.8,31.7,29.1,28.7,28.2,22.6,14.1.
EXAMPLE 6 Effect of different ligands on hydrochlorination
Following the procedure of example 2, the following ligands were used and the results are shown below.
Figure BDA0003364682590000341
(yield in1H NMR determination with CF3DMA as internal standard)
EXAMPLE 7 Effect of different ligands on hydrobromination
Following the procedure of example 3, the following ligands were used and the results are shown below.
Figure BDA0003364682590000342
(yield in1H NMR determination with CF3DMA as internal standard)
EXAMPLE 8 Effect of hydrosilation on hydrochlorination
The procedure of example 2 was followed using the following hydrosilation reagents and the results are shown below.
Figure BDA0003364682590000351
(yield in1H NMR determination with CF3DMA as internal standard)
Example 9 Effect of Palladium catalyst on hydrobromination
The procedure of example 3 was followed using the following palladium catalyst, and the reaction results are shown below.
Figure BDA0003364682590000352
(yield in1H NMR determination with CF3DMA as internal standard)
All documents referred to herein are incorporated by reference into this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications of the present invention can be made by those skilled in the art after reading the above teachings of the present invention, and these equivalents also fall within the scope of the present invention as defined by the appended claims.

Claims (10)

1. A hydroxyl-substituted pyridine oxazoline ligand shown in a formula I,
Figure FDA0003364682580000011
wherein the content of the first and second substances,
R1is substituted or unsubstituted C1-C10Alkyl, substituted or unsubstituted C3-C6Cycloalkyl, substituted or unsubstituted C6-C20An aryl group;
R2is hydrogen, substituted or unsubstituted C1-C10Alkyl, substituted or unsubstituted C3-C6Cycloalkyl, substituted or unsubstituted C6-C30An aryl group;
R3is hydrogen, substituted or unsubstituted C1-C10Alkyl, substituted or unsubstituted C6-C30An aryl group; or, R2、R3Together with the carbon atom to which they are attached form C3-C7Cycloalkyl or C6-C30An aryl group;
R4is one or more substituents on the pyridine ring, and said R4The substituents are selected from the group consisting of: halogen, substituted or unsubstituted C1-C6Alkyl, C substituted by one or more halogens1-C6Alkyl radical, C1-C6Alkoxy or
Figure FDA0003364682580000012
Wherein R is4-1Is C1-C6An alkyl group;
or R1And R4Together form- (CH)2)n-, or R1And R4And the carbon atoms to which they are attached together form C6-C10Aryl of (a); wherein n is 2,3 or 4;
wherein said substitution means that one or more hydrogen atoms on the group are substituted with a substituent selected from the group consisting of: halogen, C1-C10Alkyl radical, C3-C6Cycloalkyl, phenyl of (a); and when the substituent is plural, each substituent is the same or different.
2. The ligand of claim 1, wherein said ligand comprises:
R1is substituted or unsubstituted C1-C10Alkyl, substituted or unsubstituted C3-C6Cycloalkyl, substituted or unsubstituted C6-C10An aryl group;
R2is hydrogen, substituted or unsubstituted C1-C6Alkyl, substituted or unsubstituted C3-C6Ring ofAlkyl, benzyl;
R3is hydrogen, substituted or unsubstituted C1-C10Alkyl, substituted or unsubstituted C6-C10An aryl group;
or R2And R3Together with the carbon atom to which they are attached form C3-C7Cycloalkyl groups of (a);
R4is one or more substituents on the pyridine ring, and said R4The substituents are selected from the group consisting of: halogen, substituted or unsubstituted C1-C6Alkyl, C substituted by one or more halogens1-C6An alkyl group;
or R1And R4Together form- (CH)2)n-, or R1And R4And the carbon atoms to which they are attached together form C6-C10Aryl of (a); wherein n is 2,3 or 4;
wherein said substitution means that one or more hydrogen atoms on the group are substituted with a substituent selected from the group consisting of: halogen, C1-C10Alkyl radical, C3-C6Cycloalkyl groups of (a); and when the substituent is plural, each substituent is the same or different.
3. The ligand of claim 1, wherein said ligand comprises:
R1is substituted or unsubstituted C1-C10Alkyl, substituted or unsubstituted C3-C6Cycloalkyl, substituted or unsubstituted phenyl;
R2is hydrogen, substituted or unsubstituted C1-C4Alkyl, benzyl;
R3is hydrogen, substituted or unsubstituted phenyl;
R4is a substituent on the pyridine ring, and said R4The substituents are selected from the group consisting of: halogen, substituted or unsubstituted C1-C4Alkyl, C substituted by one or more halogens1-C4An alkyl group;
or R1And R4Together form- (CH)2)n-, or R1And R4And the carbon atoms to which they are attached together form C6An aryl group; wherein n is 2,3 or 4;
wherein said substitution means that one or more hydrogen atoms on the group are substituted with a substituent selected from the group consisting of: halogen, C1-C10Alkyl radical, C3-C6Cycloalkyl groups of (a); and when the substituent is plural, each substituent is the same or different.
4. The ligand of claim 1, wherein said ligand is selected from the group consisting of:
Figure FDA0003364682580000021
5. use of a ligand according to any one of claims 1 to 4 as a ligand in the anti-Markov hydrohalogenation of an olefin, wherein the halogenation is preferably a chlorination and bromination reaction.
6. A process for palladium-catalyzed anti-mah hydrochlorination of an olefin, the process comprising the steps of:
reacting an olefin as shown in formula II with a halogenating agent and hydrosilation in a solvent in the presence of a palladium catalyst and a ligand as described in any one of claims 1 to 4 to obtain a compound containing a primary alkyl halide as shown in formula III; wherein X is halogen;
Figure FDA0003364682580000022
wherein the content of the first and second substances,
R5selected from the group consisting of: substituted or unsubstituted C1-30Alkyl, substituted or unsubstituted C3-8A substituted or unsubstituted 5-to 12-membered heterocyclic group (saturated or partially unsaturated, which includes1-3 heteroatoms selected from N, O or S), substituted or unsubstituted C6-30An aryl group;
R6selected from the group consisting of: hydrogen, substituted or unsubstituted C1-30Alkyl (preferably, when R is6Is substituted C1-30Alkyl, the substituent not being terminal);
R7is hydrogen, or substituted or unsubstituted C1-30An alkyl group;
or R5And R6With adjacent carbon to form C5-8A cycloolefin of (a);
R8is a chemical bond, or substituted or unsubstituted C1-30An alkylene group;
wherein said substitution means that one or more hydrogen atoms on the group are substituted with a substituent selected from group a: halogen, hydroxy, NO2Benzyl, OBz, NBoc, N (Ts) Boc, C1-C10Alkyl radical, C2-C10Alkenyl radical, C2-C10Alkynyl, C1-C10Alkoxy radical, C3-C6Cycloalkyl of, C6-C30Aryl of (a), 5-30 membered heteroaryl, RC (O) O-, RC (O) NH-, RC (O) -; r is selected from the group consisting of: H. c1-C10Alkyl radical, C3-C6Cycloalkyl of, C2-C10Alkenyl radical, C6-C30Aryl of (a), 5-30 membered heteroaryl;
and each of the above substituents of group a may be further substituted with a substituent selected from group B: halogen, oxygen (═ O), hydroxy, NO2Benzyl, OBz, NBoc, N (Ts) Boc, C1-C10Alkyl radical, C1-C10Alkoxy radical, C3-C6Cycloalkyl of, C6-C10Aryl of (2), 5-12 membered heteroaryl.
7. The method of claim 6, wherein the solvent is selected from the group consisting of: an alkane solvent, a nitrile solvent, a halogenated hydrocarbon solvent, an ether solvent, a ketone solvent, an ester solvent, an amide solvent, or a combination thereof.
8. The method of claim 6, wherein the palladium catalyst is selected from the group consisting of: palladium acetate, palladium trifluoroacetate, palladium pentanate, dichlorodiacetonitrile palladium, bis (benzonitrile) palladium chloride, palladium bromide, tetranitrile palladium tetrafluoroborate, palladium hexafluoroacetylacetonate, bis (acetylacetonato) palladium, tetranitrile palladium trifluoromethanesulfonate, palladium pivalate, (1E,4E) -bis (dibenzylideneacetone) palladium, bis (dibenzylideneacetone) dipalladium, and tris (dibenzylideneacetone) dipalladium.
9. The method of claim 6, wherein the halogenating agent is selected from the group consisting of: n-chlorosuccinimide, N-bromo-N-methyl sodium isocyanurate (Na-NMBI).
10. The method of claim 6, wherein the hydrosilation is selected from the group consisting of: alkyl hydrosilicones, aryl hydrosilicones, polymethylhydrosiloxanes; wherein the alkyl is C1-C4Alkyl, said aryl being C6-C10And (4) an aryl group.
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