Axial chiral cyano biaryl compound as well as preparation method and application thereof

Abstract

The invention discloses an axially chiral cyano biaryl compound as well as a preparation method and application thereof. The axially chiral cyano biaryl compound is a compound 3, and the preparation method of the axially chiral cyano biaryl compound comprises the following step: in an organic solvent, in the presence of a rhodium catalyst, silver salt and alkali, carrying out a cyanation reaction as shown in the specification on a compound as shown in a formula I and a compound as shown in a formula II. The preparation method provided by the invention has the advantages of easily available raw materials, good substrate universality and high enantioselectivity. The compound prepared by the invention can be used as a catalyst to be applied to asymmetric allylation reaction, and corresponding allylation products can be prepared with higher yield and enantioselectivity. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to an axially chiral cyanobiaryl compound, a preparation method and application thereof. Background Art

[0002] Aromatic nitrile compounds are widely found in natural products and have a wide range of applications in dyes, agrochemicals, materials, and pharmaceuticals, such as febuxostat, lodoxamide, enzalutamide, and rilpivirine. Nitriles are amenable to diverse transformations, converting them into other important functional groups such as carboxylic acids, amines, amidines, tetrazoles, aldehydes, and amides. Classical methods for synthesizing aromatic nitriles include amide dehydration, the Sandmeyer reaction, the Rosemund-Von Braun reaction, and aryl halide cyanation. In recent years, with the development of C-H activation reactions, an increasing number of transition-metal-catalyzed C-H cyanation reactions have been realized. For example, in 2014, the Ackermann group reported a ruthenium(II)-catalyzed C-H cyanation reaction using NCTS as the cyanide source, yielding the cyanide product in yields up to 92% (Chem. Commun. 2014, 50, 1878). In 2014, the Glorius group achieved a cobalt(III)-catalyzed C-H cyanation reaction using NCTS as a cyanide source (yields up to 96%). This reaction can tolerate pyrimidine, pyridine, and pyrazole directing groups (J.Am.Chem.Soc.2014,136,17722). In 2013, the Fu Yao group first achieved a rhodium(II)-catalyzed C-H cyanation reaction using NCTS as a cyanide source. They used an oxime ether as a directing group and [Cp*Rh(MeCN)3](SbF6)2 as a catalyst, achieving yields of up to 94% for the cyanated product. This reaction can tolerate a variety of directing groups (J.Am.Chem.Soc.2013,135,10630). Although transition metal-catalyzed C-H cyanation reactions have been developed, the strong coordination of the cyanide group to the metal affects the binding of the metal to the ligand, making asymmetric control of the C-H cyanation reaction difficult to achieve. Axially chiral molecules are widely present in biologically active natural products, and they can also be widely used as ligands or catalysts in the field of asymmetric catalysis.

[0003] Currently, there is a lack of methods to construct axially chiral cyano compounds via asymmetric CH activation.

[0004] Furthermore, phenyl homoallyl alcohol is a core building block for the synthesis of a variety of bioactive molecules and drugs. For example, it is a key intermediate in the synthesis of drugs such as the natural anticancer drug paclitaxel (which contains an allyl alcohol structural unit) and vitamin E. The allyl alcohol unit in its structure can be further transformed with functional groups (such as epoxidation and reduction) to efficiently construct complex drug molecular backbones. As a pharmaceutical intermediate, phenyl homoallyl alcohol is indispensable in the synthesis of high-value-added products such as glycerol, pesticides, and fragrances. Summary of the Invention

[0005] The present invention aims to overcome the lack of effective synthesis methods for axially chiral cyano compounds by providing an axially chiral cyanobiaryl compound, a preparation method thereof, and its application. The preparation method of the present invention utilizes readily available raw materials, exhibits good substrate universality, and exhibits high enantioselectivity. The resulting compound can be used as a catalyst in asymmetric allylation reactions to produce the corresponding allylated product with high yield and enantioselectivity.

[0006] The present invention provides a method for preparing compound 3, comprising the following steps: in an organic solvent, in the presence of a rhodium catalyst, a silver salt and a base, subjecting a compound represented by formula I and a compound represented by formula II to a cyanation reaction as shown below to obtain compound 3;

[0007] The rhodium catalyst is one or both of a cyclopentadiene rhodium (III) complex derived from a binaphthyl skeleton and a cyclopentadiene rhodium (III) complex derived from a spirocyclic skeleton;

[0008]

[0009] Among them, R 1 is hydrogen, halogen, C1-C8 alkyl, -O-C1-C8 alkyl, C6-C 12 The aryl group or one or more R 1-1 Substituted C6-C 12 aryl groups;

[0010] R 1-1 is halogen, C1-C8 alkyl or -O-C1-C8 alkyl;

[0011] R 2 is hydrogen, halogen, C1-C8 alkyl or -O-C1-C8 alkyl;

[0012] R 3 is halogen, C1-C8 alkyl substituted by hydroxy, aldehyde, acetyl, cyano, C1-C8 alkyl, -O-C1-C8 alkyl, C2-C8 oxaalkyl or

[0013] R3-1 is hydrogen or a C1-C8 alkyl group;

[0014] Or, "R 1 and R 2 ” or “R 2 and R 3 "Together with the carbon atoms to which it is connected, it independently forms a C6-C 12 The aryl group, one or more R 2-1 Substituted C 6-12 aryl, 5-12 membered heteroaryl, or one or more R 2-2 substituted 5-12 membered heteroaryl; said 5-12 membered heteroaryl and one or more R 2-2 The heteroatoms in the substituted 5-12 membered heteroaryl group are independently selected from one, two or three of N, O and S, and the number of heteroatoms is independently 1-4;

[0015] R 2-1 and R 2-2 Each is independently halogen, C1-C8 alkyl or -O-C1-C8 alkyl;

[0016] Or, R 1 、R 2 and R 3 Together with the carbon atoms to which it is attached, Ring A is C6-C 12 Ring B is C6-C 12 aryl or C3-C7 cycloalkenyl, wherein It means that a ring structure is formed with the benzene ring in the parent body through this bond;

[0017] R 4 is aldehyde, cyano, carboxyl, C1-C8 alkyl substituted by one or more halogens, C1-C8 alkyl, -O-C1-C8 alkyl or

[0018] R 4-1 is hydrogen or a C1-C8 alkyl group;

[0019] R 5 is hydrogen, halogen, C1-C8 alkyl or -O-C1-C8 alkyl;

[0020] Or, R 4 and R 5 Together with the carbon atom it is connected to, it independently forms a C6-C 12 The aryl group, one or more R 5-1 Substituted C 6-12 aryl, 5-12 membered heteroaryl, or one or more R 5-2substituted 5-12 membered heteroaryl; said 5-12 membered heteroaryl and one or more R 5-2 The heteroatoms in the substituted 5-12 membered heteroaryl group are independently selected from one, two or three of N, O and S, and the number of heteroatoms is independently 1-4;

[0021] R 5-1 and R 5-2 Each is independently halogen, C1-C8 alkyl or -O-C1-C8 alkyl;

[0022] R 6 is hydrogen, halogen, C1-C8 alkyl, -O-C1-C8 alkyl, C6-C 12 The aryl group or one or more R 6-1 Substituted C6-C 12 aryl groups;

[0023] R 6-1 is halogen, C1-C8 alkyl or -O-C1-C8 alkyl;

[0024] R 7 for

[0025] R 7a 、R 7b and R 7c Each is independently halogen, C1-C8 alkyl or -O-C1-C8 alkyl;

[0026] n1, n2 and n3 are each independently 0, 1, 2 or 3.

[0027] In certain preferred embodiments of the present invention, certain groups in the compound 3 are defined as follows (unmentioned groups are the same as those described in a certain embodiment of the present application).

[0028] In one scenario, R 1 、R 1-1 、R 2 、R 3 、R 2-1 、R 2-2 、R 5 、R 5-1 、R 5-2 、R 6 、R 6-1 、R 7a 、R 7b and R 7c wherein the halogen is fluorine, chlorine, bromine or iodine; for example, fluorine, chlorine or bromine.

[0029] In one scenario, R 1 、R 1-1 、R 2、R 3 、R 2-1 、R 2-2 、R 4 、R 5 、R 5-1 、R 5-2 、R 6 、R 6-1 、R 7a 、R 7b and R 7c In the above, the C1-C8 alkyl group and the C1-C8 alkyl group in the -O-C1-C8 alkyl group are independently C1-C6 alkyl groups; preferably methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl, such as methyl or ethyl.

[0030] In one scenario, R 1 In the C6-C 12 The aryl group and the one or more R 1-1 Substituted C6-C 12 The C6-C 12 The aryl groups of are independently phenyl or naphthyl; for example, phenyl.

[0031] In one scenario, R 3 In the C1-C8 alkyl group substituted by hydroxy, the C1-C8 alkyl group is a C1-C6 alkyl group; for example, a methyl group, an ethyl group, a propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group, an isobutyl group or a tert-butyl group.

[0032] In one scenario, R 3 wherein the C2-C8 oxaalkyl group is C 2-4 Oxaalkyl, such as -CH2-O-CH3.

[0033] In one scenario, R 3-1 and R 4-1 In the embodiment, the C1-C8 alkyl group is a C1-C6 alkyl group; preferably, it is a methyl group, an ethyl group, a propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group, an isobutyl group or a tert-butyl group.

[0034] In a certain scheme, when “R 1 and R 2 ” or “R 2 and R 3 "Together with the carbon atoms to which it is connected, it independently forms a C6-C 12 aryl, or one or more R 2-1 Substituted C 6-12 When the aryl group is C6-C 12 The aryl group is phenyl or naphthyl.

[0035] In a certain scheme, when “R 1 and R 2 ” or “R 2 and R 3 "Together with the carbon atoms to which it is attached, independently form a 5-12 membered heteroaryl group, or be replaced by one or more R 2-2 When the 5- to 12-membered heteroaryl group is substituted, the 5- to 12-membered heteroaryl group is a 5- to 10-membered heteroaryl group.

[0036] In a certain scheme, when “R 1 and R 2 ” or “R 2 and R 3 "Together with the carbon atoms to which it is attached, independently form a 5-12 membered heteroaryl group, or be replaced by one or more R 2-2 In the case of a substituted 5-12 membered heteroaryl, the heteroatoms in the 5-12 membered heteroaryl are independently selected from one or two of O and S; for example, O; the number of heteroatoms is preferably 1, 2 or 3; for example

[0037] In one embodiment, in ring A and ring B, the C6-C 12 The aryl group is phenyl, naphthyl or

[0038] In one embodiment, in ring B, the C3-C7 cycloalkenyl group is a C5-C6 cycloalkenyl group; for example

[0039] In one scenario, R 4 In the C1-C8 alkyl group substituted by one or more halogens, the C1-C8 alkyl group is a C1-C6 alkyl group; for example, a methyl group, an ethyl group, a propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group, an isobutyl group or a tert-butyl group.

[0040] In one scenario, R 4 wherein the halogen in the C1-C8 alkyl group substituted by one or more halogens is fluorine, chlorine, bromine or iodine.

[0041] In a certain scheme, when R 4 and R 5 Together with the carbon atom it is connected to, it independently forms a C6-C 12 aryl, or one or more R 2-1 Substituted C 6-12 When the aryl group is C6-C 12 The aryl group of is phenyl or naphthyl; for example in This indicates that a cyclic structure is formed with the pyridine ring in the parent compound through this bond.

[0042] In a certain scheme, when R 4 and R 5 Together with the carbon atoms to which it is connected, it independently forms a 5-12 membered heteroaryl group, or is replaced by one or more R 2-2 When the 5- to 12-membered heteroaryl group is substituted, the 5- to 12-membered heteroaryl group is a 5- to 10-membered heteroaryl group.

[0043] In a certain scheme, when R 4 and R 5 Together with the carbon atoms to which it is connected, it independently forms a 5-12 membered heteroaryl group, or is replaced by one or more R 2-2 In the case of a substituted 5-12 membered heteroaryl group, the heteroatoms in the 5-12 membered heteroaryl group are independently selected from one or two of O and S; the number of heteroatoms is preferably 1, 2 or 3.

[0044] In one scenario, R 6 In the C6-C 12 The aryl group and the one or more R 6-1 Substituted C6-C 12 The C6-C 12 The aryl groups of are independently phenyl or naphthyl.

[0045] In one scenario, R 1 is hydrogen, halogen, C1-C8 alkyl, -O-C1-C8 alkyl or C6-C 12 of aromatic groups.

[0046] In one scenario, R 2 It is hydrogen or C1-C8 alkyl.

[0047] In one scenario, R 3 is halogen, C1-C8 alkyl or C2-C8 oxaalkyl.

[0048] In one scenario, R 2 and R 3 Together with the carbon atom it is connected to, it independently forms a C6-C 12 aryl or 5-12 membered heteroaryl.

[0049] In one scenario, R 4 and R 5 Together with the carbon atom it is connected to, it forms C6-C 12 of aromatic groups.

[0050] In one scenario, R 7a and R 7c Each is independently a C1-C8 alkyl group.

[0051] In one scenario, R 1is H, -CH3, -OCH3, phenyl, F, Cl or Br.

[0052] In one scenario, R 2 It is H or -CH3.

[0053] In one scenario, R 3 It is -CH3, Cl, -CH2CH3 or -CH2OCH3.

[0054] In one scenario, R 2 and R 3 Together with the carbon atoms to which it is attached,

[0055] In one scenario, R 1 、R 2 and R 3 Together with the carbon atoms to which it is attached,

[0056] In one scenario, R 4 and R 5 Together with the carbon atoms in between,

[0057] In one scenario, R 6 For H.

[0058] In one plan, for

[0059] In one plan, for

[0060] In one scenario, R 7 for

[0061] In one embodiment, the compound represented by formula I is any of the following compounds:

[0062]

[0063]

[0064] In a certain embodiment, the compound 3 is any one of the following compounds, its enantiomers or the racemates of the two:

[0065]

[0066]

[0067] In one embodiment, the reaction is carried out under a protective gas atmosphere, wherein the protective gas is one or more of helium, neon, nitrogen and argon, more preferably argon.

[0068] The organic solvent is a conventional organic solvent used in cyanation reactions in the art.

[0069] In one embodiment, the organic solvent is one or more of an alcohol solvent (for example, one or more of methanol, hexafluoroisopropanol and tert-amyl alcohol), a halogenated hydrocarbon solvent (for example, dichloromethane and / or dichloroethane), an ether solvent (for example, 1,4-dioxane and / or tetrahydrofuran), a benzene solvent (for example, toluene), a nitrile solvent (for example, acetonitrile) and an amide solvent (for example, N,N-dimethylformamide); preferably, the organic solvent is a halogenated hydrocarbon solvent (for example, dichloroethane).

[0070] In one embodiment, the compound 3 is a compound represented by formula III and / or a compound represented by formula III';

[0071]

[0072] Among them, R 1 、R 2 、R 3 、R 4 、R 5 and R 6 The definition of is as described in the previous scheme.

[0073] In a certain embodiment, the rhodium catalyst is one or both of a chiral cyclopentadiene rhodium (III) complex derived from a binaphthyl skeleton and a chiral cyclopentadiene rhodium (III) complex derived from a spirocyclic skeleton.

[0074] In a certain embodiment, when the rhodium catalyst is one or both of a cyclopentadiene rhodium (III) complex derived from an S-binaphthyl skeleton and a cyclopentadiene rhodium (III) complex derived from an S-spiro skeleton, among the compound 3, the compound shown in formula III is the dominant configuration.

[0075] In one embodiment, when the rhodium catalyst is one or both of a cyclopentadiene rhodium (III) complex derived from an R-binaphthyl skeleton and a cyclopentadiene rhodium (III) complex derived from an R-spirocyclic skeleton, the compound 3 has the dominant configuration as shown in formula III'.

[0076] In one embodiment, the rhodium catalyst is or its enantiomers, or its enantiomers, or its enantiomers; wherein R 8 and R 8’Each independently represents H, C1-C8 alkyl or -O-C1-C8 alkyl; R 9 and R 9’ Each independently represents H, C1-C8 alkyl or -O-C1-C8 alkyl; R 10 and R 10’ Each independently represents H, C1-C8 alkyl or -O-C1-C8 alkyl; X 1 and X 2 Each is independently -CH2- or -O-.

[0077] In one embodiment, the rhodium catalyst is or its enantiomers, or its enantiomers, or its enantiomers, or its enantiomers, or its enantiomers, or its enantiomers, or an enantiomer thereof.

[0078] In one embodiment, the rhodium catalyst is or an enantiomer thereof.

[0079] In a certain embodiment, when the rhodium catalyst is When, among the compounds 3, the compound shown in formula III is the dominant configuration.

[0080] In a certain embodiment, when the rhodium catalyst is When, among the compounds 3, the compound represented by formula III' is the dominant configuration.

[0081] The silver salt is a conventional silver salt used in cyanation reaction in the art. In one embodiment, the silver salt is AgSbF6, AgF, AgNTf2, AgOTf, AgOAc, Ag2CO3, AgBF4, AgNO3 and i One or more of PrCOOAg, further preferably one or more of AgSbF6, AgF, AgNTf2, AgOTf, AgBF4 and AgNO3; further preferably AgSbF6.

[0082] The base is a conventional base used in cyanation reactions in the art. In one embodiment, the base is one, two, or three of an alkali metal carbonate, an alkali metal bicarbonate, and an alkali metal acetate; for example, one or more of potassium carbonate, sodium carbonate, lithium carbonate, cesium carbonate, potassium phosphate, potassium bicarbonate, sodium bicarbonate, potassium acetate, and sodium acetate; preferably, potassium acetate.

[0083] In one embodiment, the reaction is carried out in the presence of molecular sieves, for example, 4A molecular sieves.

[0084] In one embodiment, the molar volume ratio of the compound of Formula I to the organic solvent is (0.5-1.2) mol / L; for example, (0.6-1) mol / L; for example, 0.8 mol / L.

[0085] In one embodiment, the molar ratio of the compound represented by Formula II to the compound represented by Formula I is (0.5-4):1; preferably (1.5-3):1; for example, 2:1.

[0086] In one embodiment, the molar ratio of the rhodium catalyst to the compound of formula I is (0.01-0.2):1, more preferably (0.02-0.1):1; for example, 0.05:1.

[0087] In one embodiment, the molar ratio of the silver salt to the compound of formula I is (0.02-0.8):1, more preferably (0.04-0.4):1; for example, 0.4:1.

[0088] In one embodiment, the molar ratio of the base to the compound of formula I is (0.5-5):1, more preferably (0.8-3):1; for example, 1:1.

[0089] In one embodiment, the molar ratio of the mass of the molecular sieve to the compound of formula I is (200-700) g / mol; preferably (400-600) g / mol; for example, 500 g / mol.

[0090] In one embodiment, the temperature of the cyanation reaction is 0-100°C, preferably 25-90°C, such as 60-90°C, and another such as 80°C.

[0091] In one embodiment, the preparation method of the compound 3 comprises the following steps: in an organic solvent, in the presence of a rhodium catalyst, a silver salt, a base and a molecular sieve, subjecting the compound represented by formula I to a cyanation reaction with the compound represented by formula II;

[0092] The organic solvent is a halogenated hydrocarbon solvent;

[0093] The rhodium catalyst is or an enantiomer thereof;

[0094] The silver salt is AgSbF6;

[0095] The alkali is potassium acetate.

[0096] The progress of the cyanation reaction can be monitored using conventional assays in the art (e.g., TLC, HPLC, GC, or NMR), with the reaction endpoint generally being the point at which the compound of Formula I ceases to react. The cyanation reaction time is 0.5-72 hours, preferably 1-60 hours, and more preferably 2-48 hours.

[0097] In one embodiment, after the cyanation reaction is completed, it may further include a post-treatment operation. The post-treatment operation and method may be conventional operations and methods for post-treatment of this type of reaction in the art.

[0098] Preferably, the method comprises the following steps: quenching, extraction, and separation and purification. The quenching solvent is preferably water; the extraction solvent is preferably dichloromethane; and the separation and purification is preferably column chromatography, wherein the developing solvent system of the column chromatography separation is an alkane solvent: an ester solvent (e.g., petroleum ether: ethyl acetate), more preferably an alkane solvent: ester solvent ratio of 5:1.

[0099] The present invention also provides a compound 3,

[0100]

[0101] Among them, R 1 、R 2 、R 3 、R 4 、R 5 and R 6 The definition of is as described in the previous scheme.

[0102] The compound 3 is preferably a compound represented by formula III and / or a compound represented by formula III':

[0103]

[0104] In a certain embodiment, the compound 3 is any one of the following compounds, its enantiomers or the racemates of the two:

[0105]

[0106]

[0107] The present invention also provides a compound 4,

[0108]

[0109] Among them, R 1 、R 2 、R 3 、R 4 、R 5 and R6 The definition of is as described in the previous scheme.

[0110] The compound 4 is preferably a compound represented by formula III-O and / or a compound represented by formula III'-O:

[0111]

[0112] In a certain embodiment, the compound 4 is any one of the following compounds, its enantiomers or the racemates of the two:

[0113]

[0114] The present invention also provides a use of the aforementioned compound 4 as a catalyst in an asymmetric allylation reaction, wherein the asymmetric allylation reaction site is the allylic position.

[0115] In one embodiment, the reaction comprises the following steps:

[0116] In a solvent, in the presence of compound 4 and an organic base, a compound containing an aldehyde group and allyl chlorosilane are reacted as shown below to generate a compound shown in formula IV;

[0117]

[0118] Preferably, the compound containing an aldehyde group is benzaldehyde.

[0119] The conditions and operations of the asymmetric propylation reaction are conventional conditions and operations of asymmetric propylation reactions in the art.

[0120] In one embodiment, the compound represented by formula IV is a compound represented by formula IV-1 and / or a compound represented by formula IV-2;

[0121]

[0122] In a certain embodiment, when compound 4 is a compound as shown in formula III-O; among the compounds as shown in formula IV, the compound as shown in formula IV-1 is the dominant configuration.

[0123] In a certain embodiment, when compound 4 is a compound represented by formula III'-O, among the compounds represented by formula IV, the compound represented by formula IV-2 is the dominant configuration.

[0124] Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain preferred embodiments of the present invention.

[0125] The reagents and raw materials used in the present invention are commercially available.

[0126] The positive progress of the present invention is as follows: (1) the preparation method of the present invention has a wide substrate adaptability, a high yield of up to 94%, and a high enantioselectivity of up to 91%.

[0127] (2) The prepared compound can be used as a catalyst in an asymmetric allylation reaction to obtain the corresponding allylation product with a high yield of up to 90% and a high enantioselectivity of up to 80%.

[0128] the term

[0129] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0130] The term "one or more" means 1, 2 or 3.

[0131] The term "halogen" is F, Cl, Br or I, for example F.

[0132] The term "alkyl" refers to a group having a specified number of carbon atoms (e.g., C1-C6, C1-C8, or C1-C 20 ) is a straight or branched chain alkyl group. The alkyl group includes, but is not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, n-pentyl, n-hexyl, n-heptyl, n-octyl, etc.

[0133] The term "oxaalkyl" refers to an alkyl group in which one carbon is replaced by another oxygen, wherein the number of carbons replaced by oxygen is not less than one.

[0134] The term "aryl" refers to a group having a specified number of carbon atoms (e.g., C6 to C 12 ), a cyclic aromatic group consisting only of carbon atoms, which is monocyclic or polycyclic (for example, when it is bicyclic or tricyclic, at least one ring satisfies Huckel's rule). Examples of aryl include, but are not limited to, monocyclic aryl such as C6 aryl (phenyl), bicyclic aryl such as naphthyl or

[0135] The term "heteroaryl" refers to a cyclic aromatic group containing heteroatoms, which may be monocyclic or polycyclic (for example, when bicyclic or tricyclic, at least one ring satisfies Huckel's rule). Preferably, the heteroaryl group is a 5-12-membered or 5-10-membered group containing 1-4 heteroaryls independently selected from one or more of N, O, and S. Examples thereof include, but are not limited to, benzofuranyl or benzo[b][1,4]thiothiopyrimidine.

[0136] The term "cycloalkenyl" refers to an unsaturated non-aromatic cyclic group containing a double bond. In some embodiments, it is preferably a (C3-C7 or C5-C6) non-aromatic cyclic group containing a double bond; for example BRIEF DESCRIPTION OF THE DRAWINGS

[0137] Figure 1 This is the thermal ellipsoid diagram of compound III-11 measured by single crystal X-ray diffraction. DETAILED DESCRIPTION

[0138] The present invention is further described below by way of examples, but the present invention is not limited to the scope of the examples.

[0139] Example 1: Optimization of reaction conditions

[0140]

[0141] Except for the conditions specifically indicated in Table 1 below, the remaining conditions and operations are the same as those in condition a.

[0142] Table 1

[0143]

[0144] Note: a: The reaction conditions are 1a (0.05 mmol), 2a (0.1 mmol), [Rh] (10 mol%), AgSbF6 (40 mol%) and KOAc (0.05 mmol) in DCE (0.5 mL) at 80 °C.

[0145] b: Use the reaction mixture 1 H NMR (with CH2Br2 as internal standard) spectroscopy was performed.

[0146] c: HPLC analysis using a chiral stationary phase.

[0147] d: represents the separation yield.

[0148] e: Reaction conditions were 2a (0.25 mmol).

[0149] f: Use MS (100 mg).

[0150] g: 10 mol% (R)-Rh7 and 60 mol% AgSbF6.

[0151] h: Reaction conditions were the same as 1a (0.2 mmol).

[0152] The results of using different cyanation reagents are shown in Table 2 below. The reaction conditions are the same as those in No. 1 in Table 1 above.

[0153]

[0154] Table 2

[0155]

[0156] Example 2: Rhodium-catalyzed asymmetric C—H cyanation

[0157]

[0158] The general operation steps of the reaction were as follows: KOAc (19.6 mg, 0.2 mmol) and AgSbF6 (20.0 mg, 0.08 mmol) were added to the glove box. Under argon protection, 1-arylisoquinoline derivatives I (0.2 mmol), II (0.4 mmol), (R)-Rh7 (14.9 mg, 5 mol%) and Molecular sieves (100 mg) and 1,2-dichloroethane (0.25 mL) were added. The mixture was then sealed with a polytetrafluoroethylene stopper and reacted at 80°C for 48 h. After completion of the reaction as monitored by TLC, the reaction mixture was cooled to room temperature and quenched with water (5 mL). The mixture was extracted with dichloromethane (3 × 15 mL). The combined organic phases were washed twice with water and dried over anhydrous sodium sulfate. Filtered, the solvent was removed under reduced pressure, and purified by silica gel column chromatography to obtain the target product III (PE / EA = 5 / 1).

[0159] The compounds of the following Examples 3 to 20 were prepared with reference to Example 2.

[0160] Example 3:

[0161]

[0162] III-1, 54.7 mg, 83% yield, white solid, melting point = 159.6-161.5°C. 1 H NMR (400MHz, CDCl3) δ8.88(d,J=5.2Hz,1H),8.08(d,J=8.8Hz,1H),7.98(t,J=7.6Hz,2H),7.88(d,J=5.2Hz,1H),7.85(dd, J=7.6,1.2Hz,1H),7.79(t,J=8.8Hz,2H),7.64-7.56(m,1H),7.46-7.32(m,3H),7.19(d,J=8.4Hz,1H),7.07-6.96(m,1H). 13C NMR (100 MHz, CDCl3) δ 153.6, 147.8, 144.3, 138.4, 135.4, 133.5, 132.9, 131.0, 129.5, 129.4, 129.2, 128.64, 128.58, 128.4, 127.4, 127.34, 127.25, 126.8, 125.81, 125.78, 125.7, 122.6, 118.0, 109.5. IR (thin film): ν max (cm -1 )=3051,2921,2222,2114,1957,1915,1764,1697,1608,1584,1553,1504,1464,1423,1395,1365,1331,1301,1268,1237,1199,1146,1121,1101,1050,1025,988,961,938,906,852,816,745,688,647,619; HRMS (ESI): calculated value C 24 H 15 N2[M+H] + :331.1230, measured value 331.1229. [Chiralpak IA column, n-hexane / isopropanol, 90 / 10 v / v, flow rate 1 mL / min, detection wavelength = 254 nm, 25°C). R (minor)=17.23min,t R (major)=20.14min,ee=88%. (c=0.2, chloroform).

[0163] Embodiment 4:

[0164]

[0165] III-2, 50.6 mg, 74% yield, white solid, melting point = 180.4-182.4°C. 1 H NMR (400MHz, CDCl3) δ8.87(d,J=5.2Hz,1H),8.14(d,J=8.4Hz,1H),7.97(d,J=8.8Hz,1H),7.88(d,J=5.2Hz,1H),7.85(dd,J=8.0,1.6Hz,1 H),7.81(d,J=8.8Hz,1H),7.68-7.59(m,2H),7.47-7.38(m,2H),7.38-7.32(m,1H),7.27(d,J=8.4Hz,1H),7.07-6.99(m,1H),2.84(s,3H).13 CNMR (100 MHz, CDCl3) δ 153.9, 146.2, 144.3, 138.4, 136.5, 134.9, 133.5, 132.8, 131.1, 129.4, 129.1, 128.8, 127.9, 127.53, 127.50, 127.4, 127.2, 125.91, 125.86, 125.8, 124.8, 122.5, 118.2, 109.1, 19.7. IR (thin film): ν max (cm -1 )=3047,2921,2851,2222,2120,1924,1712,1585,1552,1507,1447,1424,1403,1365,1303,1272,1234,1187,1165,1145,1124,1102,1031,990,903,867,804,753,694,661,620; HRMS (ESI): calculated value C 25 H 17 N2[M+H] + :345.1386, measured value 345.1385. [Chiralpak AD-H column, n-hexane / isopropanol, 90 / 10 v / v, flow rate 1 mL / min, detection wavelength = 254 nm, 25°C). R (minor)=13.23min,t R (major)=14.08min,ee=85%. (c=0.2, chloroform).

[0166] Example 5:

[0167]

[0168] III-3, 60.7 mg, 84% yield, white solid, melting point = 207.6-209.7°C. 1 H NMR (400MHz, CDCl3) δ8.87(d,J=5.2Hz,1H),8.42(d,J=8.4Hz,1H),7.97(d,J=8.8Hz,1H),7.91-7.83(m,2H),7 .80(d,J=8.8Hz,1H),7.64-7.56(m,1H),7.47-7.41m,1H),7.39-7.29(m,3H),7.11-7.00(m,2H),4.12(s,3H). 13C NMR (100 MHz, CDCl3) δ 156.0, 153.8, 144.4, 140.6, 138.4, 133.5, 132.8, 132.0, 129.4, 128.9, 128.7, 128.6, 128.0, 127.4, 127.2, 126.7, 126.1, 125.9, 125.7, 122.7, 122.4, 118.3, 109.4, 104.9, 56.2. IR (thin film): ν max (cm -1 )=3053,3009,2931,2849,2224,2089,1924,1715,1671,1586,1553,1508,1460,1415,1386,1364,1343,1303,1272,1232,1186,1164,1146,1109,1032,984,906,855,835,805,768,728,697,649,623; HRMS (ESI): calculated value C 25 H 17 ON2[M+H] + :361.1335, measured value 361.1333. [Chiralpak IA column, n-hexane / isopropanol, 80 / 20 v / v, flow rate 1 mL / min, detection wavelength = 254 nm, 25°C). R (minor)=9.33min,t R (major)=10.60min,ee=83%. (c=0.2, chloroform).

[0169] Example 6:

[0170]

[0171] III-4, 69.6 mg, 86% yield, yellow solid, melting point = 198.2-200.2°C. 1 H NMR (400MHz, CDCl3) δ8.90(d,J=5.2Hz,1H),8.05(d,J=8.8Hz,1H),7.99(d,J=8.8Hz,1H),7.91-7.85(m,2H),7.82(d,J= 8.8Hz,1H),7.75(s,1H),7.65-7.50(m,6H),7.49-7.45(m,2H),7.44-7.39(m,1H),7.39-7.32(m,1H),7.15-7.06(m,1H). 13C NMR (100 MHz, CDCl3) δ 153.8, 147.0, 144.4, 142.1, 138.8, 138.4, 134.0, 133.5, 132.9, 131.5, 130.1, 129.5, 129.4, 129.29, 129.26, 128.8, 128.7, 128.3, 128.1, 127.9, 127.5, 127.3, 127.2, 126.9, 125.9, 125.83, 125.75, 122.6, 117.9, 109.2. IR (thin film): ν max (cm -1 )=3052,2923,2853,2225,2119,2104,1917,1704,1582,1552,1488,1447,1422,1405,1360,1301,1266,1225,1165,1120,1082,1025,995,970,957,917,887,875,852,808,770,751,698,650,618; HRMS (ESI): calculated value C 30 H 19 N2[M+H] + :407.1543, measured value 407.1540. [Chiralpak IA column, n-hexane / isopropanol, 80 / 20 v / v, flow rate 1 mL / min, detection wavelength = 254 nm, 25°C). R (minor)=8.05min,t R (major)=12.26min,ee=78%. (c=0.2, chloroform).

[0172] Example 7:

[0173]

[0174] III-5, 32.1 mg, 46% yield, yellow solid, melting point = 153.5-155.6°C. 1 H NMR (400MHz, CDCl3) δ8.89(d,J=5.2Hz,1H),8.28(d,J=8.4Hz,1H),8.00(d,J=8.8Hz,1H),7.91(d,J=5.2H z,1H),7.90-7.80(m,2H),7.74-7.67(m,1H),7.56-7.38(m,4H),7.20(d,J=8.4Hz,1H),7.13-7.03(m,1H). 13C NMR (100MHz, CDCl3) δ158.6 (d, J = 254.8Hz), 152.9, 144.4, 144.3 (d, J = 4.9Hz), 138 .5,133.6,133.0,132.7(d,J=5.6Hz),129.7(d,J=2.1Hz),129.5,129.4,128.6,12 7.5,127.4,127.0(d,J=2.8Hz),126.3(d,J=16.2Hz),126.0,125.8,125.7,122.7, 121.3(d,J=5.1Hz), 117.1(d,J=2.9Hz), 111.2(d,J=24.0Hz), 109.3(d,J=10.0Hz). 19 F NMR (376MHz, CDCl3) δ-119.10 (d, J = 9.8Hz). IR (thin film): ν max (cm -1 )=3067,3051,2955,2923,2853,2229,1711,1599,1584,1554,1506,1461,1417,1386,1363,1301,1271,1234,1212,1193,1168,1146,1122,1066,1029,988,905,852,762,743,697,669,617,571,542,508,482,438,420; HRMS (ESI): calculated value C 24 H 14 N2F[M+H] + :349.1136, measured value 349.1131. [Chiralpak IA column, n-hexane / isopropanol, 90 / 10 v / v, flow rate 1 mL / min, detection wavelength = 254 nm, 25°C). R (minor)=11.30min,t R (major)=12.30min,ee=73%. (c=0.2, chloroform).

[0175] Example 8:

[0176]

[0177] III-6, 55.2 mg, 76% yield, yellow oil. 1H NMR (400MHz, CDCl3) δ8.88(d,J=5.2Hz,1H),8.45(d,J=8.4Hz,1H),7.99(d,J=9.2Hz,1H),7.94-7.85(m, 3H),7.82(d,J=8.8Hz,1H),7.77-7.70(m,1H),7.50-7.41(m,3H),7.24-7.21(m,1H),7.12-7.04(m,1H). 13 C NMR (100MHz, CDCl3) δ152.8,147.1,144.4,138.4,133.5,133.4,133.04,133.01,132.1,130.4,129.5,1 29.1,128.5,127.6,127.5,127.4,127.1,125.9,125.72,125.68,125.3,122.8,116.9,109.7.IR(thin film):ν max (cm -1 )=3049,2922,2852,2226,1922,1712,1609,1581,1554,1503,1420,1360,1301,1267,1238,1178,1145,1121,1102,1035,991,957,910,856,805,726,695,648,621,595,564,538,511,484,454; HRMS (ESI): calculated value C 24 H 14 N2Cl[M+H] + :365.0840, measured value 365.0833. [Chiralpak OJ-H column, n-hexane / isopropanol, 70 / 30 v / v, flow rate 1 mL / min, detection wavelength = 254 nm, 25°C). R (minor)=8.54min,t R (major)=16.75min,ee=85%. (c=0.2, chloroform).

[0178] Example 9:

[0179]

[0180] III-7, 74.4 mg, 91% yield, oil. 1H NMR (400MHz, CDCl3) δ8.92(d,J=5.2Hz,1H),8.46(d,J=8.8Hz,1H),8.14(s,1H),8.03(d,J=8.8Hz,1H),7.96-7. 89(m,2H),7.85(d,J=8.8Hz,1H),7.76(m,1H),7.53-7.44(m,3H),7.29(d,J=8.4Hz,1H),7.12(t,J=8.0Hz,1H). 13 C NMR (100MHz, CDCl3) δ152.8,147.7,144.4,138.4,134.2,133.5,133.0,132.0,130.69,130.65,129.53, 129.49,129.3,129.1,128.4,128.0,127.6,127.4,125.7,125.6,123.8,122.7,116.7,110.1.IR(thin film):ν max (cm -1 )=3257,3051,2923,2228,1922,1707,1584,1555,1494,1450,1419,1405,1358,1301,1265,1239,1159,1122,1090,1026,992,949,910,871,856,835,811,734,694,657,620; HRMS (ESI): calculated value C 24 H 14 N2Br[M+H] + :409.0335, measured value 409.0334. [Chiralpak IG column, n-hexane / isopropanol, 80 / 20 v / v, flow rate 1 mL / min, detection wavelength = 254 nm, 25°C). R (major)=12.54min,t R (minor)=14.06min,ee=85%. (c=0.2, chloroform).

[0181] Embodiment 10:

[0182]

[0183] III-8, 59.1 mg, 83% yield, yellow oil. 1H NMR (400MHz, CDCl3) δ8.86(d,J=5.2Hz,1H),7.96(d,J=8.8Hz,1H),7.87-7.82(m,2H),7.79(d,J=8. 8Hz,1H),7.57(s,1H),7.45-7.37(m,3H),7.35-7.29(m,1H),7.10-7.00(m,2H),3.60-3.44(m,4H). 13 C NMR (100 MHz, CDCl3) δ 153.5, 147.7, 146.4, 144.3, 143.8, 141.3, 138.3, 133.5, 132.7, 130.1, 129.3, 129.2, 129.0, 127.2, 127.1, 125.9, 125.8, 125.7, 122.9, 122.3, 121.8, 121.2, 118.9, 110.7, 30.6, 30.4. IR (thin film): ν max (cm -1 )=3050,2921,2850,2222,1930,1715,1606,1583,1552,1506,1444,1418,1395,1365,1301,1279,1235,1171,1142,1102,1087,990,907,861,805,779,726,640,605,586,564,542,512,451,420; HRMS (ESI): calculated value C 26 H 17 N2[M+H] + :357.1386, measured value 357.1382. [Chiralpak IA column, n-hexane / isopropanol, 90 / 10 v / v, flow rate 1 mL / min, detection wavelength = 254 nm, 25°C). R (major)=14.78min,t R (minor)=17.80min,ee=84%. (c=0.2, chloroform).

[0184] Example 11:

[0185]

[0186] III-9, 62.4 mg, 77% yield, yellow solid, melting point = 109.8-111.9°C. 1H NMR (400MHz, CDCl3) δ9.00-8.85(m,1H),8.28-8.16(m,1H),8.04-7.75(m,7H),7.53-7.38(m,4H),7.37-7.27(m,2H),7.04-6.93(m,1H). 13 C NMR (100MHz, CDCl3) δ152.8,147.5,144.2,139.8,138.3,138.2,138.0,137.6,134.5,133.5,132.9,130.3,129.4,129 .1,128.8,128.5,128.1,127.31,127.28,126.2,126.1,125.6,123.1,122.5,122.11,122.06,118.5,111.3.IR(thin film):ν max (cm -1 )=3048,2922,2851,2224,1936,1712,1606,1582,1552,1506,1447,1413,1364,1298,1235,1171,1144,1107,990,906,855,806,777,751,726,646,614,571,546,508,449,428; HRMS (ESI): calculated value C 30 H 17 N2[M+H] + :405.1386, measured value 405.1383. [Chiralpak IA column, n-hexane / isopropanol, 80 / 20 v / v, flow rate 1 mL / min, detection wavelength = 254 nm, 25°C). R (major)=11.99min,t R (minor)=14.87min,ee=85%. (c=0.2, chloroform).

[0187] Example 12:

[0188]

[0189] III-10, 74.9 mg, 93% yield, yellow solid, melting point = 192.2-194.2°C. 1H NMR (400MHz, CDCl3) δ8.94(d,J=5.2Hz,1H),8.59(s,1H),8.25(d,J=7.6Hz,1H),8.21(d,J=8.8Hz,1H),8.14(d,J=9.6Hz,2H),8.05(t,J=7.6Hz,1H), 7.97(d,J=8.8Hz,1H),7.93-7.87(m,2H),7.86-7.79(m,2H),7.59(d,J=9. 2Hz,1H),7.33(t,J=7.2Hz,1H),7.08(d,J=8.4Hz,1H),6.86-6.75(m,1H). 13 C NMR (100MHz, CDCl3) δ154.2,144.4,141.4,138.4,133.6,132.9,131.9,131.5,131.2,129.9,129.6,129.5,129.4,128. 9,128.8,127.8,127.3,127.2,127.0,126.8,126.6,126.4,126.2,125.8,124.7,124.2,122.5,118.4,109.8.IR(thin film):ν max (cm -1 )=3044,2922,2848,2221,2109,2085,1921,1767,1711,1583,1551,1506,1449,1412,1392,1369,1300,1266,1236,1180,1146,1103,1084,1061,1040,988,967,929,876,859,835,806,750,734,686,658; HRMS (ESI): calculated value C 30 H 17 N2[M+H] + :405.1386, measured value 405.1385. [Chiralpak IA column, n-hexane / isopropanol, 80 / 20 v / v, flow rate 1 mL / min, detection wavelength = 254 nm, 25°C). R (major)=13.40min,t R (minor)=15.83min,ee=85%. (c=0.2, chloroform).

[0190] Example 13:

[0191]

[0192] III-11, 66.4 mg, 90% yield, white solid, melting point = 251.2-253.3°C. 1 H NMR (400MHz, CDCl3) δ8.90(d,J=5.2Hz,1H),7.99(d,J=8.8Hz,1H),7.96-7.90(m,2H),7.88-7.82(m,2H),7.80(d,J=8.4Hz,1 H),7.55(d,J=8.0Hz,1H),7.51-7.41(m,2H),7.39-7.31(m,1H),7.15-7.05(m,1H),6.95-6.86(m,1H),6.46(d,J=7.6Hz,1H). 13 C NMR (100 MHz, CDCl3) δ 158.6, 157.1, 152.4, 144.6, 142.9, 138.5, 133.5, 133.0, 132.3, 129.4, 128.9, 128.7, 127.53, 127.50, 125.6, 125.4, 125.1, 123.74, 123.65, 122.9, 122.4, 122.2, 117.7, 112.6, 111.9, 106.7. IR (thin film): ν max (cm -1 )=3057,3034,2922,2852,2221,2096,1938,1903,1708,1581,1547,1476,1446,1419,1367,1348,1315,1294,1264,1236,1192,1169,1112,1087,1060,1041,1016,993,930,897,851,829,808,770,742,694,664,614; HRMS (ESI): calculated value C 26 H 15 ON2[M+H] + :371.1179, measured value 371.1178. [Chiralpak IA column, n-hexane / isopropanol, 90 / 10 v / v, flow rate 1 mL / min, detection wavelength = 254 nm, 25°C). R (minor)=16.18min,t R (major)=17.45min,ee=80%. (c=0.2, chloroform).

[0193] Single crystal growth method: III-11 (5 mg) was dissolved in 1 mL of isopropanol solution, and single crystals were grown using volatile solvents. The absolute configuration was determined to be S by X-ray single crystal diffraction. a The relevant data are shown in Table 3. The thermal ellipsoid diagram is shown in Figure 1 shown.

[0194] Table 3 Crystallographic data and structure refinement

[0195]

[0196]

[0197] Example 14:

[0198]

[0199] III-12, 75.4 mg, 94% yield, white solid, melting point = 187.6-189.6°C. 1 H NMR (400MHz, CDCl3) δ8.85(d,J=5.2Hz,1H),7.95(d,J=8.8Hz,1H),7.85(d,J=8.0Hz,1H),7.82(d,J=5.2Hz,1H),7.77(d,J=8.8Hz,2H),7.56(d,J=8.4H z,1H),7.42(t,J=8.0Hz,1H),7.33(d,J=8.4Hz,1H),7.21-7.11(m,1H),7.0 2-6.90(m,1H),6.89-6.78(m,1H),6.74-6.62(m,1H),5.62(d,J=8.4Hz,1H). 13 C NMR (100 MHz, CDCl3) δ 150.9, 150.4, 149.8, 144.2, 137.9, 136.6, 133.3, 132.3, 129.7, 129.2, 129.1, 128.9, 128.1, 127.5, 127.4, 127.2, 126.4, 125.64, 125.61, 125.2, 125.0, 122.4, 118.3, 117.5, 117.2, 111.7. IR (thin film): ν max (cm -1)=3054,2922,2852,2229,1922,1708,1578,1551,1499,1468,1423,1400,1381,1311,1282,1265,1238,1210,1169,1121,1100,1073,1026,988,945,910,852,834,809,749,687,656,636,613; HRMS (ESI): calculated value C 26 H 15 ON2S[M+H] + :403.0900, measured value 403.0898. [Chiralpak IA column, n-hexane / isopropanol, 80 / 20 v / v, flow rate 1 mL / min, detection wavelength = 254 nm, 25°C). R (major)=12.47min,t R (minor)=19.88min,ee=45%. (c=0.2, chloroform).

[0200] Example 15:

[0201]

[0202] III-13, 42.3 mg, 72% yield, white solid, melting point = 159.7-161.7°C. 1 H NMR (400MHz, CDCl3) δ8.83(d,J=5.2Hz,1H),7.95(d,J=8.8Hz,1H),7.89(d,J=8.0Hz,1H),7.81(d,J=5.2Hz,1H),7.76(d,J=8.8 Hz,1H),7.72(d,J=7.6Hz,1H),7.61(d,J=7.6Hz,1H),7.58-7.49(m,2H),7.45(d,J=8.8Hz,1H),7.29-7.23(m,1H),1.99(s,3H). 13 C NMR (100MHz, CDCl3) δ154.5,147.2,144.3,138.3,137.5,135.3,133.5,132.7,131.4,129 .5,129.2,128.8,127.6,127.3,125.8,124.9,124.8,122.3,117.8,112.5,19.7.IR(thin film):ν max (cm -1)=3051,2920,2852,2226,1939,1713,1607,1584,1552,1506,1459,1440,1413,1378,1308,1278,1233,1202,1165,1144,1101,1067,1038,989,929,912,854,804,785,752,650; HRMS (ESI): calculated value C 21 H 15 N2[M+H] + :295.1230, measured value 295.1229. [Chiralpak OJ-H column, n-hexane / isopropanol, 80 / 20 v / v, flow rate 1 mL / min, detection wavelength = 254 nm, 25°C). R (minor)=10.92min,t R (major)=15.08min,ee=84%. (c=0.2, chloroform).

[0203] Example 16:

[0204]

[0205] III-14, 55.4 mg, 90% yield, white solid, melting point = 138.5-140.5°C. 1 H NMR (400MHz, CDCl3) δ8.81(d,J=5.2Hz,1H),7.94(d,J=8.8Hz,1H),7.88(d,J=7.6Hz,1H),7.80(d,J=5.2Hz,1H),7.75(d,J=8.8Hz,1H) ,7.61(d,J=8.0Hz,1H),7.57-7.50(m,1H),7.47(d,J=8.8Hz,1H),7.41(d,J=8.0Hz,1H),7.30-7.22(m,1H),2.42(s,3H),1.90(s,3H). 13 C NMR (100MHz, CDCl3) δ155.2,147.1,144.2,143.8,138.2,136.0,133.5,132.6,131.0,130.3, 129.4,129.2,127.6,127.2,125.8,125.1,124.9,122.2,118.1,110.0,21.1,16.5.IR(thin film):ν max (cm -1)=3050,2978,2921,2854,2223,1954,1921,1898,1813,1710,1607,1584,1553,1509,1448,1423,1374,1309,1275,1234,1203,1171,1146,1102,1053,1010,989,964,919,851,819,799,745,647; HRMS (ESI): calculated value C 22 H 17 N2[M+H] + :309.1386, measured value 309.1385. [Chiralpak AD-H column, n-hexane / isopropanol, 95 / 5 v / v, flow rate 1 mL / min, detection wavelength = 254 nm, 25°C). R (minor)=18.01min,t R (major)=19.07min,ee=80%. (c=0.2, chloroform).

[0206] Example 17:

[0207]

[0208] III-15, 56.8 mg, 90% yield, white solid, melting point = 119.4-121.5°C. 1 H NMR (400MHz, CDCl3) δ8.82(d,J=5.2Hz,1H),7.95(d,J=8.8Hz,1H),7.90(d,J=8.0Hz,1H),7.81(d,J=5. 2Hz,1H),7.76(d,J=8.8Hz,1H),7.60-7.51(m,1H),7.49-7.40(m,2H),7.39-7.27(m,2H),1.98(s,3H). 13 C NMR (100MHz, CDCl3) δ161.67(d,J=248.9Hz),153.50,144.35,143.72(d,J=3 .6Hz),140.53(d,J=8.0Hz),138.35,133.49,132.74,129.62,129.00,127.7 0,127.46,125.81,125.01,124.70,122.63(d,J=20.8Hz),122.46,118.02(d ,J=24.3Hz), 116.62(d,J=3.3Hz), 113.88(d,J=9.8Hz), 20.00(d,J=1.6Hz).19 F NMR (376 MHz, CDCl3) δ-111.41 (t, J = 8.6 Hz, 1F). IR (thin film): ν max (cm -1 )=3051,2923,2853,2228,1920,1710,1584,1551,1509,1472,1442,1412,1378,1308,1235,1206,1169,1128,1106,1026,986,854,802,752,696,661; HRMS (ESI): calculated value C 21 H 14 N2F[M+H] + :313.1136, measured value 313.1133. [Chiralpak AD-H column, n-hexane / isopropanol, 95 / 5 v / v, flow rate 1 mL / min, detection wavelength = 254 nm, 25°C). R (major)=15.57min,t R (minor)=16.77min,ee=83%. (c=0.2, chloroform).

[0209] Example 18:

[0210]

[0211] III-16, 24.5 mg, 39% yield, white solid, melting point = 176.6-178.7°C. 1 H NMR (400MHz, CDCl3) δ8.84(d,J=5.2Hz,1H),7.98(d,J=8.8Hz,1H),7.92(d,J=8.0Hz,1H),7.85(d,J=5.2Hz,1 H),7.81(d,J=8.0Hz,2H),7.78(d,J=8.8Hz,1H),7.64-7.54(m,2H),7.48(d,J=8.4Hz,1H),7.36-7.27(m,1H). 13 C NMR (100MHz, CDCl3) δ152.3,146.3,144.3,138.3,134.7,134.5,133.5,132.8,132.3,1 30.0,129.6,128.9,127.7,127.5,125.8,125.1,124.8,122.9,116.6,114.7.IR(thin film):ν max (cm -1)=3058,2921,2851,2227,1950,1923,1887,1702,1607,1583,1556,1509,1445,1407,1378,1309,1269,1234,1204,1171,1144,1099,1057,988,931,911,866,841,790,745,698,647; HRMS (ESI): calculated value C 20 H 12 N2Cl[M+H] + :315.0684, found 315.0683. [Chiralpak OJ-H column, n-hexane / isopropanol, 80 / 20 v / v, flow rate 1 mL / min, detection wavelength = 254 nm, 25°C). R (minor)=16.28min,t R (major)=19.90min,ee=91%. (c=0.2, chloroform).

[0212] Example 19:

[0213]

[0214] III-17, 26.9 mg, 44% yield, white solid, melting point = 136.6-138.8°C. 1 H NMR (400MHz, CDCl3) δ8.83(d,J=5.2Hz,1H),7.96(d,J=8.8Hz,1H),7.90(d,J=8.0Hz,1H),7.82(d,J=5.2Hz,1H),7.77(d,J=8.8Hz,1H),7.75- 7.66(m,2H),7.59(t,J=7.6Hz,1H),7.56-7.50(m,1H),7.43(d,J=8.4Hz,1H),7.30-7.21(m,1H),2.34(q,J=7.6Hz,2H),0.94(t,J=7.6Hz,3H). 13 C NMR (100MHz, CDCl3) δ154.5,146.8,144.2,143.1,138.3,133.7,133.5,132.7,131.4,129.5, 129.2,129.1,127.5,127.3,125.9,125.4,125.0,122.3,117.8,112.6,26.2,14.0.IR(thin film):ν max (cm -1)=3054,2965,2924,2853,2226,1950,1826,1711,1607,1583,1552,1506,1459,1411,1378,1308,1289,1232,1200,1164,1144,1103,1077,1064,1042,988,928,911,855,803,754,719,651; HRMS (ESI): calculated value C 22 H 17 N2[M+H] + :309.1386, measured value 309.1385. [Chiralpak AD-H column, n-hexane / isopropanol, 95 / 5 v / v, flow rate 1 mL / min, detection wavelength = 254 nm, 25°C). R (minor)=11.30min,t R (major)=12.02min,ee=83%. (c=0.2, chloroform).

[0215] Example 20:

[0216]

[0217] III-18, 40.4 mg, 62% yield, white solid, melting point = 94.2-96.3°C. 1 H NMR (400MHz, CDCl3) δ8.81(d,J=5.2Hz,1H),8.02-7.94(m,2H),7.90(d,J=8.0Hz,1H),7.82(d,J=5.2Hz,1H),7.80-7.74(m,2H),7.65(t,J =7.8Hz,1H),7.54(t,J=8.0Hz,1H),7.42(d,J=8.4Hz,1H),7.30-7.21(m,1H),4.25(d,J=13.6Hz,1H),4.10(d,J=13.6Hz,1H),3.08(s,3H). 13 C NMR (100 MHz, CDCl3) δ 153.4, 145.6, 144.2, 138.3, 133.5, 132.8, 132.6, 132.3, 129.5, 129.03, 128.99, 127.6, 127.4, 125.7, 125.3, 125.0, 122.4, 117.4, 112.6, 71.4, 58.7. IR (thin film): ν max (cm -1)=3051,2986,2926,2891,2822,2228,1929,1691,1605,1584,1552,1506,1449,1413,1377,1310,1281,1236,1193,1167,1108,989,957,910,855,796,751,728,650,631; HRMS (ESI): calculated value C 22 H 17 ON2[M+H] + :325.1335, measured value 325.1334. [Chiralpak AD-H column, n-hexane / isopropanol, 90 / 10 v / v, flow rate 1 mL / min, detection wavelength = 254 nm, 25°C). R (minor)=9.63min,t R (major)=10.89min,ee=91%. (c=0.2, chloroform).

[0218] Application Example 1:

[0219]

[0220] Under argon protection, III-1 (33.0 mg, 0.1 mmol), m-m-chloroperbenzoic acid (86.3 mg, 0.5 mmol) and tetrahydrofuran (0.5 mL) were added to a reaction tube with a magnetic stirrer. The resulting mixture was stirred at room temperature. After the reaction was completed (monitored by thin layer chromatography), the mixture was cooled to room temperature and quenched with water (5 mL). The aqueous phase was extracted with dichloromethane (3×15 mL). The combined organic layers were then washed with water and brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The residue was then purified by silica gel column chromatography (ethyl acetate) to obtain the desired product IV.

[0221]

[0222] IV, 27.3 mg, 79% yield, yellow oil. 1H NMR (400MHz, CDCl3) δ8.62(d,J=6.4Hz,1H),8.17(d,J=8.4Hz,1H),8.04(d,J=8.0Hz,1H),7.94(d,J=5.6Hz,1H),7.89(d,J=8.8Hz,1 H),7.84(t,J=7.2Hz,2H),7.76(d,J=8.8Hz,1H),7.66(t,J=7.2Hz,1H),7.55-7.39(m,3H),7.01-6.93(m,1H),6.90(d,J=8.4Hz,1H). 13 C NMR (100 MHz, CDCl3) δ 140.0, 137.8, 135.3, 134.3, 132.7, 131.4, 130.9, 130.8, 130.2, 129.7, 129.6, 129.11, 129.05, 128.2, 128.1, 127.7, 127.6, 127.1, 125.8, 125.6, 125.5, 125.1, 117.3, 110.6. IR (thin film): ν max (cm -1 )=3058,2921,2851,2226,1702,1573,1501,1430,1393,1286,1252,1210,1176,1085,1031,995,916,868,841,820,733,704,677,646,624,519,469,424; HRMS (ESI): calculated value C 24 H 15 N2O[M+H] + :347.1179, measured value 347.1174. [Chiralpak IG column, n-hexane / isopropanol, 40 / 60 v / v, flow rate 1 mL / min, detection wavelength = 254 nm, 25°C). R (minor)=15.24min,t R (major)=22.26min,ee=87%. (c=0.2, chloroform).

[0223]

[0224] To a dry Schlenk tube, under argon, catalyst (Sa)-IV (13.9 mg, 0.04 mmol, 10 mol%), N-ethyldiisopropylamine (64.6 mg, 0.5 mmol, 1.25 equiv.), benzaldehyde (42.4 mg, 0.4 mmol, 1.0 equiv.), and dichloromethane (2 mL) were added. The mixture was cooled to -40°C, and allylsilyl chloride (69.5 μL, 0.48 mmol, 1.2 equiv.) was added. After reacting at -40°C for 48 hours, the reaction was quenched by addition of saturated aqueous sodium bicarbonate (5 mL) and extracted with dichloromethane. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and the solvent removed under reduced pressure. The resulting crude product was purified by column chromatography (petroleum ether / ethyl acetate = 9 / 1, v / v) to afford a colorless oil (53 mg, 90% yield, 80% ee).

[0225] Although specific embodiments of the present invention have been described above, those skilled in the art will appreciate that these are merely illustrative and that the scope of the present invention is defined by the appended claims. Those skilled in the art may make various changes or modifications to these embodiments without departing from the principles and essence of the present invention, and such changes and modifications are intended to fall within the scope of the present invention.

Claims

1. A method for preparing compound 3, characterized in that: It includes the following steps: In an organic solvent, in the presence of a rhodium catalyst, a silver salt and a base, the compound represented by Formula I and the compound represented by Formula II are subjected to a cyanation reaction as shown below to obtain Compound 3; The rhodium catalyst is one or both of a cyclopentadiene rhodium (III) complex derived from a binaphthyl skeleton and a cyclopentadiene rhodium (III) complex derived from a spirocyclic skeleton; Among them, R 1 is hydrogen, halogen, C1-C8 alkyl, -O-C1-C8 alkyl, C6-C 12 The aryl group or one or more R 1-1 Substituted C6-C 12 aryl groups; R 1-1 is halogen, C1-C8 alkyl or -O-C1-C8 alkyl; R 2 is hydrogen, halogen, C1-C8 alkyl or -O-C1-C8 alkyl; R 3 is halogen, C1-C8 alkyl substituted by hydroxy, aldehyde, acetyl, cyano, C1-C8 alkyl, -O-C1-C8 alkyl, C2-C8 oxaalkyl or R 3-1 is hydrogen or a C1-C8 alkyl group; Or, "R 1 and R 2 ” or "R 2 and R 3 "Together with the carbon atoms to which it is connected, it independently forms a C6-C 12 The aryl group, one or more R 2-1 Substituted C 6-12 aryl, 5-12 membered heteroaryl, or one or more R 2-2 substituted 5-12 membered heteroaryl; said 5-12 membered heteroaryl and one or more R 2-2 The heteroatoms in the substituted 5-12 membered heteroaryl group are independently selected from one, two or three of N, O and S, and the number of heteroatoms is independently 1-4; R 2-1 and R 2-2 Each is independently halogen, C1-C8 alkyl or -O-C1-C8 alkyl; Or, R 1 、R 2 and R 3 Together with the carbon atoms to which it is attached, Ring A is C6-C 12 Ring B is C6-C 12 aryl or C3-C7 cycloalkenyl; R 4 is aldehyde, cyano, carboxyl, C1-C8 alkyl substituted by one or more halogens, C1-C8 alkyl, -O-C1-C8 alkyl or R 4-1 is hydrogen or a C1-C8 alkyl group; R 5 is hydrogen, halogen, C1-C8 alkyl or -O-C1-C8 alkyl; Or, R 4 and R 5 Together with the carbon atom it is connected to, it independently forms a C6-C 12 The aryl group, one or more R 5-1 Substituted C 6-12 aryl, 5-12 membered heteroaryl, or one or more R 5-2 substituted 5-12 membered heteroaryl; said 5-12 membered heteroaryl and one or more R 5-2 The heteroatoms in the substituted 5-12 membered heteroaryl group are independently selected from one, two or three of N, O and S, and the number of heteroatoms is independently 1-4; R 5-1 and R 5-2 Each is independently halogen, C1-C8 alkyl or -O-C1-C8 alkyl; R 6 is hydrogen, halogen, C1-C8 alkyl, -O-C1-C8 alkyl, C6-C 12 The aryl group or one or more R 6-1 Substituted C6-C 12 aryl groups; R 6-1 is halogen, C1-C8 alkyl or -O-C1-C8 alkyl; R 7 for R 7a 、R 7b and R 7c Each is independently halogen, C1-C8 alkyl or -O-C1-C8 alkyl; n1, n2 and n3 are each independently 0, 1, 2 or 3.

2. The method for preparing compound 3 according to claim 1, wherein It meets one or more of the following conditions: (1)R 1 、R 1-1 、R 2 、R 3 、R 2-1 、R 2-2 、R 5 、R 5-1 、R 5-2 、R 6 、R 6-1 、R 7a 、R 7b and R 7c wherein the halogen is fluorine, chlorine, bromine or iodine; for example, fluorine, chlorine or bromine; (2)R 1 、R 1-1 、R 2 、R 3 、R 2-1 、R 2-2 、R 4 、R 5 、R 5-1 、R 5-2 、R 6 、R 6-1 、R 7a 、R 7b and R 7c wherein the C1-C8 alkyl group and the C1-C8 alkyl group in the -O-C1-C8 alkyl group are independently C1-C6 alkyl groups; preferably methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl, such as methyl or ethyl; (3)R 1 In the C6-C 12 The aryl group and the one or more R 1-1 Substituted C6-C 12 The C6-C 12 The aryl groups of are independently phenyl or naphthyl; for example, phenyl; (4)R 3 wherein the C1-C8 alkyl group in the C1-C8 alkyl group substituted by a hydroxyl group is a C1-C6 alkyl group; for example, a methyl group, an ethyl group, a propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group, an isobutyl group or a tert-butyl group; (5)R 3 wherein the C2-C8 oxaalkyl group is C 2-4 Oxaalkyl, such as -CH2-O-CH3; (6)R 3-1 and R 4-1 wherein the C1-C8 alkyl group is a C1-C6 alkyl group; preferably a methyl group, an ethyl group, a propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group, an isobutyl group or a tert-butyl group; (7) When "R 1 and R 2 ” or "R 2 and R 3 "Together with the carbon atoms to which it is connected, it independently forms a C6-C 12 When the aryl group is 12 The aryl group is phenyl or naphthyl; (8) When "R 1 and R 2 ” or "R 2 and R 3 "Together with the carbon atoms to which it is attached, independently forms a 2-1 Substituted C 6-12 When the aryl group is one or more R 2-1 Substituted C 6-12 The C6-C 12 The aryl group is phenyl or naphthyl; (9) When "R 1 and R 2 ” or "R 2 and R 3 "When the carbon atom to which it is attached independently forms a 5-12-membered heteroaryl group, the 5-12-membered heteroaryl group is a 5-10-membered heteroaryl group; (10) When "R 1 and R 2 ” or "R 2 and R 3 "When the carbon atoms to which it is connected independently form a 5-12 membered heteroaryl group, the heteroatoms in the 5-12 membered heteroaryl group are independently selected from one or two of O and S; for example, O; the number of heteroatoms is preferably 1, 2 or 3; (11) When "R 1 and R 2 ” or "R 2 and R 3 "When the carbon atom to which it is connected independently forms a 5-12 membered heteroaryl group, the 5-12 membered heteroaryl group is (12) When "R 1 and R 2 ” or "R 2 and R 3 "Together with the carbon atoms to which it is attached, independently forms a 2-2 When the 5-12 membered heteroaryl is substituted, the 2-2 The 5-12-membered heteroaryl in the substituted 5-12-membered heteroaryl is a 5-10-membered heteroaryl; (13) When "R 1 and R 2 ” or "R 2 and R 3 "Together with the carbon atoms to which it is attached, independently forms a 2-2 When the 5-12 membered heteroaryl is substituted, the 2-2 The heteroatoms of the 5-12-membered heteroaryl in the substituted 5-12-membered heteroaryl are independently selected from one or two of O and S; for example, O; the number of heteroatoms is preferably 1, 2 or 3; (14) When "R 1 and R 2 ” or "R 2 and R 3 "Together with the carbon atoms to which it is attached, independently forms a 2-2 When the 5-12 membered heteroaryl is substituted, the 2-2 The substituted 5-12 membered heteroaryl is (15) In ring A and ring B, the C6-C 12 The aryl group is phenyl, naphthyl or (16) In ring B, the C3-C7 cycloalkenyl group is a C5-C6 cycloalkenyl group; for example (17)R 4 wherein the C1-C8 alkyl group substituted by one or more halogens is a C1-C6 alkyl group; for example, a methyl group, an ethyl group, a propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group, an isobutyl group or a tert-butyl group; (18)R 4 wherein the halogen in the C1-C8 alkyl group substituted by one or more halogens is fluorine, chlorine, bromine or iodine; (19) When R 4 and R 5 Together with the carbon atom it is connected to, it forms C6-C 12 When the aryl group is 12 The aryl group of is phenyl or naphthyl; for example (20) When R 4 and R 5 Together with the carbon atom to which it is attached, it forms a 2-1 Substituted C 6-12 When the aryl group is one or more R 2-1 Substituted C 6-12 The aryl group of is phenyl or naphthyl; for example (21) When R 4 and R 5 When the carbon atom to which it is connected forms a 5-12-membered heteroaryl group, the 5-12-membered heteroaryl group is a 5-10-membered heteroaryl group; (22) When R 4 and R 5 When the carbon atoms to which it is connected form a 5-12 membered heteroaryl group, the heteroatoms in the 5-12 membered heteroaryl group are independently selected from one or two of O and S; the number of heteroatoms is preferably 1, 2 or 3; (23) When R 4 and R 5 Together with the carbon atom to which it is attached, it forms a 2-2 When the 5-12 membered heteroaryl is substituted, the 2-2 The substituted 5-12 membered heteroaryl is a 5-10 membered heteroaryl; (24) When R 4 and R 5 Together with the carbon atom to which it is attached, it forms a 2-2 When the 5-12 membered heteroaryl is substituted, the 2-2 The heteroatoms of the 5-12-membered heteroaryl in the substituted 5-12-membered heteroaryl are independently selected from one or two of O and S; the number of heteroatoms is preferably 1, 2 or 3; (25)R 6 In the C6-C 12 The aryl group and the one or more R 6-1 Substituted C6-C 12 The C6-C 12 The aryl groups of are independently phenyl or naphthyl; (26) The compound 3 is a compound represented by formula III and / or a compound represented by formula III'; (27) The reaction is carried out under a protective gas atmosphere, wherein the protective gas is preferably one or more of helium, neon, nitrogen and argon, more preferably argon; (28) The organic solvent is one or more of an alcohol solvent, a halogenated hydrocarbon solvent, an ether solvent, a benzene solvent, a nitrile solvent, and an amide solvent; preferably, a halogenated hydrocarbon solvent; The alcohol solvent is preferably one or more of methanol, hexafluoroisopropanol and tert-amyl alcohol; the halogenated hydrocarbon solvent is preferably dichloromethane and / or dichloroethane, such as dichloroethane; the ether solvent is preferably 1,4-dioxane and / or tetrahydrofuran; the benzene solvent is preferably toluene; the nitrile solvent is preferably acetonitrile; and the amide solvent is preferably N,N-dimethylformamide. (29) The rhodium catalyst is one or both of a chiral cyclopentadiene rhodium (III) complex derived from a binaphthyl skeleton and a chiral cyclopentadiene rhodium (III) complex derived from a spirocyclic skeleton; (30) The silver salt is AgSbF6, AgF, AgNTf2, AgOTf, AgOAc, Ag2CO3, AgBF4, AgNO3 and i One or more of PrCOOAg, more preferably one or more of AgSbF6, AgF, AgNTf2, AgOTf, AgBF4 and AgNO3; further preferably AgSbF6; (31) The base is one, two or three of alkali metal carbonates, alkali metal bicarbonates and alkali metal acetates; for example, one or more of potassium carbonate, sodium carbonate, lithium carbonate, cesium carbonate, potassium phosphate, potassium bicarbonate, sodium bicarbonate, potassium acetate and sodium acetate; preferably potassium acetate; (32) The reaction is also carried out in the presence of molecular sieves, for example, in the presence of 4A molecular sieves; (33) The molar volume ratio of the compound of formula I to the organic solvent is (0.5-1.2) mol / L; for example, (0.6-1) mol / L; for example, 0.8 mol / L; (34) The molar ratio of the compound represented by Formula II to the compound represented by Formula I is (0.5-4):1; preferably (1.5-3):1; for example, 2:1; (35) The molar ratio of the rhodium catalyst to the compound of formula I is (0.01-0.2):1, more preferably (0.02-0.1):1; for example, 0.05:1; (36) The molar ratio of the silver salt to the compound of formula I is (0.02-0.8):1, more preferably (0.04-0.4):1; for example, 0.4:1; (37) The molar ratio of the base to the compound of formula I is (0.5-5):1, more preferably (0.8-3):1; for example, 1:1; (38) The temperature of the cyanation reaction is 0-100°C; preferably 25-90°C; for example 60-90°C; and for example 80°C.

3. The method for preparing compound 3 according to claim 1, wherein It meets one or more of the following conditions: (1)R 1 is hydrogen, halogen, C1-C8 alkyl, -O-C1-C8 alkyl or C6-C 12 aryl groups; (2)R 2 is hydrogen or a C1-C8 alkyl group; (3)R 3 is halogen, C1-C8 alkyl or C2-C8 oxaalkyl; (4)R 2 and R 3 Together with the carbon atom it is connected to, it independently forms a C6-C 12 aryl or 5-12 membered heteroaryl; (5)R 4 and R 5 Together with the carbon atom it is connected to, it forms C6-C 12 aryl groups; (6)R 7a and R 7c Each is independently a C1-C8 alkyl group; (7) When the reaction is carried out in the presence of a molecular sieve, the molar ratio of the mass of the molecular sieve to the compound of Formula I is (200-700) g / mol; preferably (400-600) g / mol; for example, 500 g / mol.

4. The method for preparing compound 3 according to claim 1, wherein It meets one or more of the following conditions: (1)R 1 is H, -CH3, -OCH3, phenyl, F, Cl or Br; (2)R 2 is H or -CH3; (3)R 3 is -CH3, Cl, -CH2CH3 or -CH2OCH3; (4)R 2 and R 3 Together with the carbon atoms to which it is attached, (5)R 1 、R 2 and R 3 Together with the carbon atoms to which it is attached, (6)R 4 and R 5 Together with the carbon atoms in between, (7)R 6 For H.

5. The method for preparing compound 3 according to claim 1, wherein It meets one or more of the following conditions: (1) for (2) for (3)R 7 for 6. The method for preparing compound 3 according to claim 1, wherein It meets one or both of the following conditions: (1) The compound represented by formula I is any of the following compounds: (2) Compound 3 is any of the following compounds, its enantiomers, or the racemates of the two:

7. The method for preparing compound 3 according to claim 1, wherein The rhodium catalyst is or its enantiomers, or its enantiomers, or its enantiomers; wherein R 8 and R 8’ Each independently represents H, C1-C8 alkyl or -O-C1-C8 alkyl; R 9 and R 9’ Each independently represents H, C1-C8 alkyl or -O-C1-C8 alkyl; R 10 and R 10’ Each independently represents H, C1-C8 alkyl or -O-C1-C8 alkyl; X 1 and X 2 Each independently represents -CH2- or -O-; Preferably, the rhodium catalyst is or its enantiomers, or its enantiomers, or its enantiomers, or its enantiomers, or its enantiomers, or its enantiomers, or its enantiomers; e.g. or an enantiomer thereof.

8. The method for preparing compound 3 according to claim 1, wherein The preparation method of the compound 3 comprises the following steps: in an organic solvent, in the presence of a rhodium catalyst, a silver salt, a base and a molecular sieve, subjecting the compound represented by formula I to a cyanation reaction with the compound represented by formula II to obtain compound 3; The organic solvent is a halogenated hydrocarbon solvent; The rhodium catalyst is or an enantiomer thereof; The silver salt is AgSbF6; The alkali is potassium acetate.

9. A compound 3, in, R 1 、R 2 、R 3 、R 4 、R 5 and R 6 The definition as set forth in any one of claims 1 to 6; Preferably, the compound 3 is a compound represented by formula III and / or a compound represented by formula III': Preferably, the compound 3 is any one of the following compounds, its enantiomers or the racemates of the two:

10. A compound 4, in, R 1 、R 2 、R 3 、R 4 、R 5 and R 6 The definition as set forth in any one of claims 1 to 6; Preferably, the compound 4 is a compound represented by formula III-O and / or a compound represented by formula III'-O: Preferably, the compound 4 is any one of the following compounds, its enantiomers or the racemates thereof:

11. Use of the compound 4 according to claim 10 as a catalyst in an asymmetric allylation reaction, wherein the asymmetric allylation reaction site is an allylic position; Preferably, the reaction comprises the steps of: In a solvent, in the presence of compound 4 and an organic base, a compound containing an aldehyde group and allyl chlorosilane are reacted as shown below to generate a compound represented by formula IV;

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