Preparation method and use of azo compounds

Abstract

The present invention discloses a method for preparing a class of azo compounds and their uses. The method for preparing the compound represented by Formula I is simple, efficient, has high substrate universality, and high selectivity. #imgabs0#

Description

Technical Field

[0001] The present invention relates to a preparation method and application of azo compounds. Background Art

[0002] Alkylarylazo compounds:

[0003]

[0004] Among them, R 1 , R 2 , R 4 is a variety of (hetero)aryl substituents; R 3 are various alkyl substituents.

[0005] Currently, there are not many methods reported in the literature for the synthesis of this type of alkylarylazo compounds. Most of the synthetic methods are based on the addition reaction of diazonium salts to unsaturated bonds [(a) Blank, O.; Heinrich, M.R.Eur. J. Org. Chem. 2006, 4331–4334; (b) Heinrich, M.R.; Blank, O.; Wofel, S. Org. Lett. 2006, 8, 3323–3325; Blank, O.; (c) Raschke, N.; Heinrich, M.R. Tetrahedron Lett. 2010, 51, 1758–1760; (d) Blank, O.; Wetzel, A.; Ullrich, D.; Heinrich, M.R.Eur. J. Org.Chem.2008,3179–3189; (e) Liu, C.; Lv, J.; Luo, S.; Cheng, J.-P.Org.Lett.2014, 16, 5458-5461. (f) Zhang, Y.; Huang, C.; Lin, X.; Hu, Q.; Hu, B.; Zhou, Y.; Zhu, G. Org.Le tt.2019, 21, 2261-2264. (g) Nelson, HM; Patel, JS; Shunatona, HP; Toste, FDChem. Sci. 2015, 6, 170–173. (h) Stephens, DE; Larionov, OVEur. However, these synthetic methods have their insurmountable limitations: narrow substrate range, low raw material utilization, and cumbersome processes.

[0006] This alkylarylazo compound can be further converted into an α-quaternary carbon amine, thus providing a method for the synthesis of natural products or active pharmaceutical molecules. The azo functional group in this alkylarylazo compound can also be used as a luminescent group in photochemical research [(a) Movassaghi, M.; Ahmad, OK; Lathrop, SP J Am. Chem. Soc. 2011, 133, 13002–13005. (b) Lindovska, P.; Movassaghi, M J Am. Chem. Soc. 2017, 139, 17590–17596.]. Summary of the Invention

[0007] The technical problem to be solved by the present invention is to overcome the shortcomings of existing methods for preparing azo compounds, such as a narrow substrate range, low raw material utilization, and cumbersome processes. The present invention provides a method for preparing azo compounds and its use, which is simple, efficient, has high substrate universality, and high selectivity.

[0008] The present invention provides a compound as shown in Formula I;

[0009]

[0010] in:

[0011] R 1 is a 6-10 membered aromatic group, supported by one or more R 11 a substituted 6-10 membered aryl group, or a "5-6 membered heteroaryl group having 1, 2 or 3 heteroatoms independently selected from N, O and S"; when there are multiple substituents, the substituents may be the same or different;

[0012] R 2 is a C1-C6 alkyl group;

[0013] R 3 is a 6-10 membered aromatic group, supported by one or more R 31 a substituted 6-10 membered aryl group, or a "5-6 membered heteroaryl group having 1, 2 or 3 heteroatoms independently selected from N, O and S"; when there are multiple substituents, the substituents may be the same or different;

[0014] R 4 is a 6-10 membered aromatic group, supported by one or more R 41 a substituted 6-10 membered aryl group, or a "5-6 membered heteroaryl group having 1, 2 or 3 heteroatoms independently selected from N, O and S"; when there are multiple substituents, the substituents may be the same or different;

[0015] R 11 are independently halogen, C1-C6 alkyl, C1-C6 alkoxy, -COOR111 or cyano;

[0016] R 31 are independently halogen, C1-C6 alkyl, C1-C6 alkoxy, -COOR 311 or cyano;

[0017] R 41 are independently halogen, C1-C6 alkyl, C1-C6 alkoxy, -COOR 411 or cyano;

[0018] R 111 is a C1-C6 alkyl group;

[0019] R 311 is a C1-C6 alkyl group;

[0020] R 411 is a C1-C6 alkyl group;

[0021] The carbon atom with "*" indicates that when it is a chiral carbon atom, the carbon atom with "*" is in S configuration, R configuration or a mixture thereof;

[0022] or, R 2 With R 3 Together with the atoms to which they are attached, they form a 5-7 membered cycloalkyl group;

[0023] Or, when the R 11 When there are multiple R 11 Together with the atoms to which they are attached, they form a 5-6 membered heterocycloalkenyl group having 1, 2 or 3 heteroatoms independently selected from N, O and S;

[0024] Or, when the R 31 When there are multiple R 31 Together with the atoms to which they are attached, they form a 5-6 membered heterocycloalkenyl group having 1, 2 or 3 heteroatoms independently selected from N, O and S;

[0025] Or, when the R 41 When there are multiple R 41 Together with the atoms to which they are attached, they form a 5-6 membered heterocycloalkenyl group with 1, 2 or 3 heteroatoms independently selected from N, O and S.

[0026] In a certain embodiment, in the compound of Formula I, the definitions of certain groups may be as follows, and the definitions of the remaining groups are as described in any of the above embodiments: (For this expression, it is hereinafter referred to as "in a certain embodiment")

[0027] When R 1When it is a 6-10 membered aryl group, the 6-10 membered aryl group is a phenyl group or a naphthyl group, for example

[0028] In a certain scheme: when R 1 For one or more R 11 In the case of a substituted 6-10 membered aryl group, the 6-10 membered aryl group is a phenyl group or a naphthyl group.

[0029] In a certain scheme: when R 1 For one or more R 11 When the substituted 6-10 membered aryl group or the 6-10 membered aryl group is a phenyl group, the R 11 Independently located at the ortho, para or meta position of the connecting chain connected to the 2 carbon atom.

[0030] In a certain scheme: when R 1 To be multiple R 11 In the case of a substituted 6-10 membered aryl group, the plurality is two or three.

[0031] In a certain scheme: when R 11 When it is halogen, the halogen is fluorine, chlorine, bromine or iodine, for example fluorine or chlorine.

[0032] In a certain scheme: when R 11 When it is a C1-C6 alkyl group, the C1-C6 alkyl group is a C1-C3 alkyl group, such as methyl.

[0033] In a certain scheme: when R 11 When it is a C1-C6 alkoxy group, the C1-C6 alkoxy group is a C1-C3 alkoxy group, such as a methoxy group.

[0034] In a certain scheme: when R 111 When it is a C1-C6 alkyl group, the C1-C6 alkyl group is a C1-C3 alkyl group, such as methyl.

[0035] In a certain scheme: when R 1 To be an R 11 When the 6-10 membered aryl group is substituted, the substituted aryl group is replaced by an R 11 The substituted 6-10 membered aryl group is

[0036] In a certain scheme: when R 1 "a 5-6 membered heteroaryl group having 1, 2 or 3 heteroatoms independently selected from N, O and S" is a furyl group, for example

[0037] In a certain scheme: when R 2When it is a C1-C6 alkyl group, the C1-C6 alkyl group is a C1-C3 alkyl group, such as methyl or ethyl.

[0038] In a certain scheme: when R 3 When it is a 6-10 membered aryl group, the 6-10 membered aryl group is a phenyl group or a naphthyl group, for example

[0039] In a certain scheme: when R 3 For one or more R 31 In the case of a substituted 6-10 membered aryl group, the 6-10 membered aryl group is a phenyl group or a naphthyl group.

[0040] In a certain scheme: when R 3 For one or more R 31 When the substituted 6-10 membered aryl group or the 6-10 membered aryl group is a phenyl group, the R 31 Independently located at the ortho, para or meta position of the connecting chain connected to the carbon atom 1.

[0041] In a certain scheme: when R 3 To be multiple R 31 In the case of a substituted 6-10 membered aryl group, the plurality is two or three.

[0042] In a certain scheme: when R 31 When it is halogen, the halogen is fluorine, chlorine, bromine or iodine, for example fluorine or chlorine.

[0043] In a certain scheme: when R 31 When it is a C1-C6 alkyl group, the C1-C6 alkyl group is a C1-C3 alkyl group, such as methyl.

[0044] In a certain scheme: when R 31 When it is a C1-C6 alkoxy group, the C1-C6 alkoxy group is a C1-C3 alkoxy group, such as a methoxy group.

[0045] In a certain scheme: when R 311 When it is a C1-C6 alkyl group, the C1-C6 alkyl group is a C1-C3 alkyl group, such as methyl.

[0046] In a certain scheme: when R 3 To be an R 31 When the 6-10 membered aryl group is substituted, the substituted aryl group is replaced by an R 31 The substituted 6-10 membered aryl group is

[0047] In a certain scheme: when R 3"a 5-6 membered heteroaryl group having 1, 2 or 3 heteroatoms independently selected from N, O and S" is a furyl group, for example

[0048] In a certain scheme: when R 4 When it is a 6-10 membered aryl group, the 6-10 membered aryl group is a phenyl group or a naphthyl group.

[0049] In one embodiment, the compound shown in Formula I is any of the following structures:

[0050] Preferred

[0051] In a certain scheme: when R 2 With R 3 When together with the atoms to which they are attached form a 5-7 membered cycloalkyl group, the 5-7 membered cycloalkyl group is a cyclohexyl group.

[0052] In one embodiment: when the R 11 For multiple, any two adjacent R 11 When the number of heteroatoms formed together with the atoms to which they are attached is 1, 2 or 3, and the heteroatoms are independently selected from N, O and S, the 5-6 membered heterocycloalkenyl is 1,3-dioxolane, for example

[0053] In one embodiment: when the R 31 For multiple, any two adjacent R 31 When the number of heteroatoms formed together with the atoms to which they are attached is 1, 2 or 3, and the heteroatoms are independently selected from N, O and S, the 5-6 membered heterocycloalkenyl is 1,3-dioxolane, for example

[0054] In one embodiment: when the R 41 For multiple, any two adjacent R 41 When the number of heteroatoms formed together with the atoms to which they are attached is 1, 2 or 3, and the heteroatoms are independently selected from N, O and S, the 5-6 membered heterocycloalkenyl is 1,3-dioxolane, for example

[0055] In one scenario: R 4 is a 6-10 membered aryl group, for example, phenyl.

[0056] In one scenario: R 11 are independently halogen, C1-C6 alkyl or C1-C6 alkoxy.

[0057] In a certain scheme: when R 1 is a 6-10 membered aromatic group or is replaced by one or more R 11 In the case of a substituted 6-10 membered aryl group, the 6-10 membered aryl group is a phenyl group.

[0058] In a certain scheme: when R 1 For one or more R 11 When the substituted 6-10 membered aryl group or the 6-10 membered aryl group is a phenyl group, the R 11 Independently located at the para or meta position of the connecting chain connected to the 2 carbon atom, preferably the para position.

[0059] In one scenario: R 2 It is a methyl group.

[0060] In one scenario: R 3 is a 6-10 membered aromatic group or is replaced by one or more R 31 Substituted 6-10 membered aryl.

[0061] In a certain scheme: when R 3 is a 6-10 membered aromatic group or is replaced by one or more R 31 In the case of a substituted 6-10 membered aryl group, the 6-10 membered aryl group is a phenyl group.

[0062] In one scenario: R 31 is halogen, C1-C6 alkyl or C1-C6 alkoxy.

[0063] In a certain scheme: when R 3 For one or more R 31 When the substituted 6-10 membered aryl group or the 6-10 membered aryl group is a phenyl group, the R 31 Independently located at the para or meta position of the connecting chain connected to the carbon atom of 1, preferably the para position.

[0064] In a certain embodiment, the compound as shown in Formula I is any of the following embodiments:

[0065] Option 1:

[0066] R 4 is a 6-10 membered aryl group, such as a phenyl group;

[0067] R 11 are independently halogen, C1-C6 alkyl or C1-C6 alkoxy;

[0068] Option 2:

[0069] R 2 is methyl;

[0070] R 4 is a 6-10 membered aryl group, such as a phenyl group;

[0071] R 11 are independently halogen, C1-C6 alkyl or C1-C6 alkoxy;

[0072] When R 1 is a 6-10 membered aromatic group or is replaced by one or more R 11 When the substituted 6-10 membered aryl group is a phenyl group;

[0073] When R 1 When it is a “5-6 membered heteroaryl group having 1, 2 or 3 heteroatoms, which are independently selected from N, O and S”, the 5-6 membered heteroaryl group is furyl;

[0074] Option 3:

[0075] R 2 is methyl;

[0076] R 4 is a 6-10 membered aryl group, such as a phenyl group;

[0077] R 11 are independently halogen, C1-C6 alkyl or C1-C6 alkoxy;

[0078] When R 1 is a 6-10 membered aromatic group or is replaced by one or more R 11 When the substituted 6-10 membered aryl group is a phenyl group;

[0079] When R 1 When it is a “5-6 membered heteroaryl group having 1, 2 or 3 heteroatoms, which are independently selected from N, O and S”, the 5-6 membered heteroaryl group is furyl;

[0080] When R 1 For one or more R 11 When the substituted 6-10 membered aryl group or the 6-10 membered aryl group is a phenyl group, the R 11 Independently located at the para or meta position of the connecting chain connected to the 2-carbon atom, preferably the para position;

[0081] When R 3 For one or more R 31 When the substituted 6-10 membered aryl group or the 6-10 membered aryl group is a phenyl group, the R 31 Independently located at the para or meta position of the connecting chain connected to the carbon atom 1, preferably the para position;

[0082] Option 4:

[0083] R 2 is methyl;

[0084] R4 is a 6-10 membered aryl group, such as a phenyl group;

[0085] R 11 are independently halogen, C1-C6 alkyl or C1-C6 alkoxy;

[0086] When R 1 is a 6-10 membered aromatic group or is replaced by one or more R 11 When the substituted 6-10 membered aryl group is a phenyl group;

[0087] When R 1 When it is a “5-6 membered heteroaryl group having 1, 2 or 3 heteroatoms, which are independently selected from N, O and S”, the 5-6 membered heteroaryl group is furyl;

[0088] When R 1 For one or more R 11 When the substituted 6-10 membered aryl group or the 6-10 membered aryl group is a phenyl group, the R 11 Independently located at the para or meta position of the connecting chain connected to the 2-carbon atom, preferably the para position;

[0089] R 3 is a 6-10 membered aromatic group or is replaced by one or more R 31 substituted 6-10 membered aryl;

[0090] R 31 is halogen, C1-C6 alkyl or C1-C6 alkoxy;

[0091] When R 3 For one or more R 31 When the substituted 6-10 membered aryl group or the 6-10 membered aryl group is a phenyl group, the R 31 Independently located at the para or meta position of the connecting chain connected to the carbon atom of 1, preferably the para position.

[0092] In a certain embodiment, the compound as shown in formula I is selected from the following group or its enantiomers:

[0093]

[0094] The present invention also provides a method for preparing the compound shown in Formula I, comprising the following steps:

[0095] Step 1: In a solvent, a compound represented by Formula III is subjected to a hydrogen extraction reaction with a strong base to obtain a mixture A;

[0096] Step 2: In the presence of a base, a catalyst, and a ligand, catalyze a reaction between the mixture A and the compound of Formula II to obtain the compound of Formula I;

[0097]

[0098] Among them, R 1 、R 2 、R 3 、R 4 and “carbon atom marked with “*”” are defined as above;

[0099] The strong base is LiHMDS, LDA and n One or more of BuLi;

[0100] The base is t BuOK;

[0101] The ligand is any of the following compounds:

[0102] R A and R A’ are independently "phenyl substituted by one or more C1-C6 alkyl groups" or

[0103]

[0104] R B and R B’ are each independently "a 6-10 membered aryl group substituted by one or more C1-C6 alkyl groups" or a 6-10 membered aryl group;

[0105]

[0106] X - Cl - 、OTf - or BF4 - .

[0107] In one embodiment, in the compound 1, the definitions of certain groups may be as follows, and the definitions of the remaining groups are as described in any of the above schemes:

[0108] When R A and R A’ When they are independently "phenyl substituted by one or more C1-C6 alkyl groups", the C1-C6 alkyl group is a C1-C3 alkyl group, such as methyl or isopropyl.

[0109] In one embodiment, in the compound 1, the definitions of certain groups may be as follows, and the definitions of the remaining groups are as described in any of the above schemes:

[0110] When R A and R A’When each is independently a "phenyl group substituted by a plurality of C1-C6 alkyl groups", the plurality is two or three.

[0111] In one embodiment, in the compound 1, the definitions of certain groups may be as follows, and the definitions of the remaining groups are as described in any of the above schemes:

[0112] When R A and R A’ When each of the above is independently a "phenyl group substituted by multiple C1-C6 alkyl groups", the "phenyl group substituted by multiple C1-C6 alkyl groups" is

[0113] In one embodiment, in the compound 3, the definitions of certain groups may be as follows, and the definitions of the remaining groups are as described in any of the above schemes:

[0114] When R B and R B’ When they are independently "a 6-10 membered aryl group substituted by one or more C1-C6 alkyl groups", the C1-C6 alkyl group is a C1-C3 alkyl group, such as methyl.

[0115] In one embodiment, in the compound 3, the definitions of certain groups may be as follows, and the definitions of the remaining groups are as described in any of the above schemes:

[0116] When R B and R B’ When each of the above groups is independently a “6-10 membered aryl group substituted by one or more C1-C6 alkyl groups”, the 6-10 membered aryl group is a phenyl group or a naphthyl group.

[0117] In one embodiment, in the compound 3, the definitions of certain groups may be as follows, and the definitions of the remaining groups are as described in any of the above schemes:

[0118] When R B and R B’ When each independently represents a "6-10 membered aryl group substituted by a plurality of C1-C6 alkyl groups", the plurality is two or three.

[0119] In one embodiment, in the compound 3, the definitions of certain groups may be as follows, and the definitions of the remaining groups are as described in any of the above schemes:

[0120] When R B and R B’ When they are independently 6-10 membered aryl groups, the 6-10 membered aryl groups are phenyl or naphthyl, for example

[0121] In one embodiment, in the compound 3, the definitions of certain groups may be as follows, and the definitions of the remaining groups are as described in any of the above schemes:

[0122] When R B and R B’ When each of them is independently a "6-10 membered aryl group substituted by a C1-C6 alkyl group", the "6-10 membered aryl group substituted by a C1-C6 alkyl group" is

[0123] In the catalytic reaction, the catalyst may be any of the following structures: Preferred

[0124] In the catalytic reaction, the solvent may be one or more of an aromatic hydrocarbon solvent (such as toluene, xylene or mesitylene), an alkane solvent (such as n-hexane), a nitrile solvent (such as acetonitrile) and an ether solvent (such as 1,4-dioxane, tetrahydrofuran or diethyl ether).

[0125] In the catalytic reaction, the reaction temperature may be a conventional temperature for such catalytic reactions in the art, such as 0°C-30°C.

[0126] In the catalytic reaction, the molar ratio of the strong base to the compound represented by Formula III may be 1:1 to 2:1.

[0127] In the catalytic reaction, the molar ratio of the base to the compound represented by Formula III may be 0.01:1 to 0.1:1, for example, 0.0625:1.

[0128] In the catalytic reaction, the molar ratio of the compound represented by Formula III to the compound represented by Formula II may be 1:1 to 2:1.

[0129] In the catalytic reaction, the molar ratio of the ligand to the compound represented by Formula III may be 0.005:1 to 0.25:1, for example, 0.025:1.

[0130] In the catalytic reaction, the molar ratio of the catalyst to the compound represented by Formula III may be 0.005:1 to 0.25:1, for example, 0.0125:1.

[0131] In the catalytic reaction, the concentration of the compound represented by Formula III in the solvent may be a conventional concentration for such catalytic reactions in the art, such as 0.05 mol / L to 0.5 mol / L, for example 0.09 mol / L or 0.17 mol / L.

[0132] In the catalytic reaction, the catalyst may be a Pd(II) catalyst, such as [Pd(C3H5)Cl]2 and / or [Pd(cinnammyl)Cl]2.

[0133] In the catalytic reaction, the reaction time may be the conventional reaction time for this type of catalytic reaction in the art, with the disappearance of the compound shown in Formula II being the reaction endpoint. The reaction time may be, for example, 1 hour to 14 hours.

[0134] The preparation method of the compound represented by Formula I may further comprise post-treatment, and the post-treatment preferably comprises the following steps: quenching the reaction (e.g., adding water), and separation and purification (e.g., thin layer chromatography and / or column chromatography) to obtain the compound represented by Formula I.

[0135] A compound as shown in formula IV:

[0136]

[0137] Among them, R 1 、R 2 、R 3 and “carbon atom marked with “*”” are as defined above.

[0138] The compound shown in Formula IV may be any of the following structures:

[0139]

[0140] The present invention also provides a use of a compound represented by Formula I in the preparation of a tertiary amine, wherein the preparation comprises the following steps: in a solvent, in the presence of hydrogen and a catalyst, subjecting the compound represented by Formula I to a reduction reaction as shown below to obtain a compound represented by Formula IV;

[0141]

[0142] Among them, R 1 、R 2 、R 3 and “carbon atom marked with “*”” are as defined above.

[0143] In the reduction reaction, the solvent may be a conventional solvent for this type of reduction reaction in the art, such as an alcohol solvent, and another example is methanol.

[0144] In the reduction reaction, the catalyst may be a conventional catalyst for this type of reduction reaction in the art, such as palladium-carbon.

[0145] In the reduction reaction, the mass ratio of the catalyst to the compound represented by Formula I can be a conventional ratio for this type of reduction reaction in the art, such as 0.2:1 to 0.5:1, and another example is 0.26:1.

[0146] In the reduction reaction, the concentration of the compound of Formula I in the solvent can be a conventional concentration for such reactions in the art, such as 0.01 mol / L to 0.1 mol / L, for example 0.02 mol / L.

[0147] The reduction reaction may further include post-treatment, and the post-treatment preferably includes the following steps: after the reduction reaction is completed, filtering, concentrating, and separating on a plate to obtain the compound as shown in Formula IV.

[0148] The use of the compound shown in Formula I in the preparation of a tertiary amine may further include a method for preparing the compound shown in Formula I, which comprises the following steps:

[0149] Step 1: In a solvent, the compound represented by Formula III undergoes a hydrogen extraction reaction with a strong base to obtain a mixture A;

[0150] Step 2: In the presence of a base, a catalyst, and a ligand, the mixture A is subjected to a catalytic reaction with the compound shown in Formula II to obtain the compound shown in Formula I;

[0151]

[0152] Among them, R 1 、R 2 、R 3 、R 4 and “carbon atom marked with “*”” are defined as above;

[0153] The conditions for the preparation method of the compound shown in Formula I are as described above.

[0154] Unless otherwise specified, the terms used in this invention have the following meanings:

[0155] The term "plurality" refers to 2, 3, 4 or 5.

[0156] The term "halogen" refers to fluorine, chlorine, bromine or iodine.

[0157] The term "alkyl" refers to a straight or branched chain alkyl 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.

[0158] The term "alkoxy" refers to the group -OR C , where R C is an alkyl group as defined above.

[0159] The term "cycloalkyl" includes any stable cyclic alkyl group comprising a monocyclic ring system. Examples of these cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and the like.

[0160] Unless otherwise specified, "heterocycloalkenyl" includes any cyclic monocyclic alkenyl group preferably containing 1, 2, or 3 ring heteroatoms independently selected from N, O, and S, and containing one or more unsaturated carbon-carbon double bonds at any position in the group, but any ring of the system is non-aromatic. In some embodiments, the heterocycloalkenyl group is a 5-6 membered alkenyl group. Examples of such heterocycloalkenyl groups include, but are not limited to, 1,3-dioxolanyl and the like.

[0161] On the basis of conforming to the common sense in this field, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

[0162] The reagents and raw materials used in the present invention are commercially available.

[0163] The positive progress of the present invention is that it provides an azo compound, a preparation method, and uses thereof. The method for preparing the compound represented by Formula I is simple, efficient, highly substrate universal, and highly selective. The compound represented by Formula I can be used to prepare the compound represented by Formula IV conveniently, efficiently, with high stereoselectivity, and high substrate universality, providing a new approach for preparing such tertiary amine compounds (i.e., such α-quaternary carbon amine compounds). BRIEF DESCRIPTION OF THE DRAWINGS

[0164] Figure 1 This is the single crystal X-ray diffraction structure of compound T1. DETAILED DESCRIPTION

[0165] The present invention is further illustrated by way of examples below, but the present invention is not limited to the scope of the examples. Experimental methods in the following examples where specific conditions are not specified were performed according to conventional methods and conditions, or selected according to the product specifications.

[0166] Example 1: Palladium-catalyzed asymmetric allylic substitution of hydrazones

[0167]

[0168] Hydrazone (acetophenone phenylhydrazone) (0.4 mmol, 84.1 mg) and toluene (2.0 mL) were added to a 10 mL dry reaction tube. LiHMDS (1.0 M in THF, 0.4 mL, 0.4 mmol) was added under ice bath. After the addition was complete, the mixture was stirred at room temperature for 30 min. [Pd(η 3 -C3H5)Cl]2 (1.83 mg, 0.005 mmol), L (5.5 mg, 0.01 mmol) and toluene (1.0 mL) were added under ice bath or room temperature. t-BuOK (1.0 M in THF, 25 uL, 0.025 mmol) was added. After the addition was completed, the mixture was stirred at room temperature for 30 min and then added to the above 10 mL reaction tube. Cinnamyl pivalate (0.2 mmol) and toluene (1.0 mL) were added and the reaction was continued at room temperature or 10 ° C overnight. After the reaction was completed, water (0.5 mL) was added to quench the reaction. The mixture was passed through a short silica gel column, washed with ethyl acetate (50 mL), concentrated, and mesitylene was added as an internal standard. The regioselectivity and diastereoselectivity of the reaction were 1 The crude H NMR spectrum was confirmed, and the product was obtained by preparative plate separation (petroleum ether / ethyl acetate 50 / 1). (For the preparation of acetophenone phenylhydrazone compounds, see: a) Hu, J.; Xu, H.; Nie, P.; Xie, X.; Nie, Z.; Rao, Y. Synthesis of indazoles and azaindazoles by intramolecular aerobic oxidative CN coupling under transition-metal-free conditions. Chem. Eur. J. 2014, 20, 3932-3938; b) Yang, X.-L.; Peng, X.-X.; Chen, F.; Han, B. TEMPO-Mediated Aza-Diels–Alder Reaction: Synthesis of Tetrahydropyridazines Using Ketohydrazones and Olefins. Org. Lett. 2016, 18, 2070-2073.)

[0169] The following compounds were prepared by selecting corresponding raw materials:

[0170]

[0171] Bright yellow liquid; 40.5 mg; Yield: 62%; 3aa / 4aa / 5aa: 92 / 2 / 6; dr (i.e., the ratio of the SS- and RR-configured products of compound 3 to the SR- and RS-configured products of compound 3): >20 / 1; ee (i.e., the ratio of the RR-configured product of compound 3 to the SS-configured product of compound 3): 91%; [α] D 29 =-55.8 (c 1.0, CHCl3); 1 H NMR(400MHz, CDCl3)δ7.61(s,2H),7.34(dd,J=21.9,7.8Hz,5H),7.20(s,2H),7.12(s,1H),7.05(s,3H ),6.93(s,2H),6.10–5.89(m,1H),4.91(dd,J=22.2,13.6Hz,2H),4.17(d,J=9.1Hz,1H),1.48(s,3H); 13 C NMR (101MHz, CDCl3) δ152.12,143.94,140.61,137.19,130.40,130.05,128.98,127.88,127.68,127.56,126.71,126.43,122.36,117.58 ,77.29,61.28,21.56; IR(film):ν3059,3027,2980,1684,1598,1492,1448,1370,1302,1216,1148,1068,1027,993,917,754,690; ESI-MS m / z(rel):327.0(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 23 H 23 N2(M+H) + :327.1856; Found:327.1863; HPLC (PC-3 (Phenomenex Cellulose-3), 250*4.60mm, CH3CN:H2O=80:20, 0.7mL / min, 214nm, Column Temperature: 25℃): t minor =6.85min,t major =7.94min.

[0172]

[0173] Bright yellow liquid; 51.0 mg; Yield: 73%; 3ba / 4ba / 5ba: 82 / 4 / 14; dr: >20 / 1; ee: 94%; [α] D 31 =-52.8 (c 1.0, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.83–7.69(m,2H),7.51(dt,J=6.8,4.7Hz,3H),7.41(dd,J=8.8,5.4Hz,2H),7.25–7.16(m,3H),7 .03(t,J=8.7Hz,4H),6.13(dt,J=16.9,9.7Hz,1H),5.06(dd,J=27.0,13.6Hz,2H),4.24(d,J=9.2Hz,1H),1.62(s,3H); 13 C NMR (101MHz, CDCl3) δ161.65 (d, J = 245.5Hz), 152.06, 140.41, 139.68, 139.65, 136.97, 130.55, 130.0 0,129.56(d,J=7.8Hz),127.66,126.56,122.36,117.77,114.43(d,J=21.0Hz),76.86,61.44,21.79; 19 F NMR(376MHz, CDCl3)δ-116.12; IR(film): ν3058,3026,1596,1489,1446,1361,1296,1225,1156,1028,963,835,748,690; ESI-MS m / z(rel):345.0(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 23 H 22 FN2(M+H) + :345.1762; Found:345.1764; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=80:20, 0.7mL / min, 214nm, Column Temperature: 20℃): t minor =7.04min,t major =7.92min.

[0174]

[0175] Bright yellow liquid; 48.0 mg; Yield: 66%; 3ca / 4ca / 5ca: 88 / 4 / 8; Dr: >20 / 1; ee: 94%; [α] D 31 =-62.9 (c 1.0, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.81–7.65(m,2H),7.56–7.45(m,3H),7.37(d,J=8.6Hz,2H),7.30(d,J=8.6Hz,2H),7.21(d,J=6.9Hz ,3H),7.08–6.97(m,2H),6.10(dt,J=16.9,9.7Hz,1H),5.05(dd,J=26.9,13.6Hz,2H),4.23(d,J=9.2Hz,1H),1.59(s,3H); 13 C NMR (101MHz, CDCl3) δ152.01,142.46,140.26,136.82,132.59,130.60,129.97,129.37,129.03,127.77,127.69,126.60,122.35 ,117.88,76.89,61.27,21.68; IR(film):ν3058,3025,1594,1487,1447,1360,1296,1154,1091,1028,912,828,748,689; ESI-MS m / z(rel):361.0(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 23 H 22 ClN2(M+H) + :361.1466; Found:361.1468; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=80:20, 0.7mL / min, 214nm, Column Temperature: 20℃): t minor =7.96min,t major =10.1min.

[0176]

[0177] Bright yellow liquid; 50.0 mg; Yield: 71%; 3da / 4da / 5da: 86 / 4 / 10; Dr: >20 / 1; ee: 93%; [α] D 30 =-29.3 (c 1.0, CHCl3);1 H NMR (400MHz, CDCl3) δ7.60(d,J=7.1Hz,2H),7.43–7.28(m,3H),7.24(d,J=8.8Hz,2H),7.07(d,J=7.1Hz,3H),6.97–6.84(m,2H),6. 75(d,J=8.8Hz,2H),6.00(dt,J=17.1,9.7Hz,1H),4.91(dd,J=24.6,13.6Hz,2H),4.15(d,J=9.1Hz,1H),3.70(s,3H),1.45(s,3H); 13 C NMR (101MHz, CDCl3) δ158.19,152.14,140.68,137.34,135.87,130.31,130.05,129.06,128.94,127.56,126.40,122.30,117.47,112. 96,76.88,61.16,55.20,21.54; IR(film):ν3059,2980,2933,1598,1492,1415,1370,1303,1131,1067,1027,993,916,759,690; ESI-MS m / z(rel):357.0(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 24 H 25 N2O(M+H) + :357.1961; Found:357.1962; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=80:20, 0.7mL / min, 214nm, Column Temperature: 20℃): t minor =7.42min,t major =10.6min.

[0178]

[0179] Bright yellow liquid; 53.3 mg; Yield: 78%; 3ea / 4ea / 5ea: 84 / 4 / 12; DR: >20 / 1; ee: 94%; [α] D 26 =-46.6 (c 1.0, CHCl3); 1H NMR (400MHz, CDCl3) δ7.79–7.67(m,2H),7.47(ddd,J=7.8,7.1,5.2Hz,3H),7.33(dd,J=8.0,1.3Hz,2H),7.17(ddd,J=21.1,10.7,4.6Hz,5H ),7.10–7.02(m,2H),6.13(ddd,J=18.7,10.4,1.5Hz,1H),5.03(dd,J=23.1,13.6Hz,2H),4.31(d,J=9.0Hz,1H),2.36(s,3H),1.59(s,3H); 13 C NMR (101MHz, CDCl3) δ152.16,140.81,140.72,137.37,136.20,130.28,130.09,128.92,128.39,127.80,127.54,126.37,122.31,117.45, 77.14,61.04,21.49,21.08; IR(film):ν3059,3026,2978,1597,1511,1450,1369,1301,1260,1188,1068,1018,916,808,758,688; ESI-MS m / z(rel):.3410(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 24 H 25 N2(M+H) + :341.2012; Found:341.2016; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=80:20, 0.7mL / min, 214nm, Column Temperature: 20℃): t minor =11.34min,t major =19.11min.

[0180]

[0181] Bright yellow liquid; 30.4 mg; Yield: 40%; 3fa / 4fa / 5fa: 87 / 5 / 8; dr: >20 / 1; ee: 93%; [α] D 29 =-42.5 (c 1.0, CHCl3); 1H NMR (400MHz, CDCl3) δ7.99(d,J=8.4Hz,2H),7.76(d,J=8.0Hz,2H),7.56–7.42(m,5H),7.18(d,J=6.0Hz,3H),7.03(d,J=7 .5Hz,2H),6.08(dt,J=17.0,9.7Hz,1H),5.04(dd,J=23.0,13.5Hz,2H),4.25(d,J=9.3Hz,1H),3.93(s,3H),1.62(s,3H); 13 C NMR (101MHz, CDCl3) δ167.09,151.97,149.37,140.14,136.67,130.66,129.92,129.05,128.91,128.40,127.90,127.69,126.61,122.38,1 17.95,77.34,61.38,52.08,21.72; IR(film):ν3060,2980,2320,1714,1605,1490,1433,1406,1275,1184,1106,995,921,762,688; ESI-MS m / z(rel):385.0(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 25 H 25 N2O2(M+H) + :385.1911; Found:385.1915; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=80:20, 0.7mL / min, 214nm, Column Temperature: 25℃): t minor =7.03min,t major =7.63min.

[0182]

[0183] Bright yellow liquid; 35.0mg; Yiled:50%; 3ga / 4ga / 5ga:54 / 5 / 41; dr:>20 / 1; ee:86%; [α] D 29 =-25.7 (c 1.0, CHCl3); 1H NMR (400MHz, CDCl3) δ7.77–7.68(m,2H),7.57(d,J=8.5Hz,2H),7.54–7.40(m,5H),7.17(dd,J=7.0,3.7Hz,3H),6.97(d d,J=6.5,2.9Hz,2H),6.03(dt,J=16.9,9.8Hz,1H),5.03(dd,J=28.0,13.6Hz,2H),4.15(d,J=9.3Hz,1H),1.59(s,3H); 13 C NMR (101MHz, CDCl3) δ151.80,149.60,139.74,136.21,131.40,130.89,129.79,129.09,128.61,127.78,126.78,122.38,119.00,118 .29,110.46,77.13,61.46,21.68; IR(film):ν3061,2980,2226,1729,1691,1603,1497,1451,1370,1152,1018,920,757,689; ESI-MS m / z(rel):352.0(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 24 H 22 N3(M+H) + :352.1808; Found:352.181; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=65:35, 0.7mL / min, 214nm, Column Temperature: 25℃): t minor =12.26min,t major =13.09min.

[0184]

[0185] Bright yellow liquid; 41.0 mg; Yield: 60%; 3ha / 4ha / 5ha: 90 / 5 / 5; Dr: >20 / 1; ee: 94%; [α] D 25 =-18.1 (c 1.0, CHCl3); 1H NMR(400MHz, CDCl3)δ7.75(d,J=7.1Hz,2H),7.56–7.44(m,3H),7.28–7.15(m,6H),7.08(t,J=7.2Hz,3 H),6.29–5.97(m,1H),5.05(dd,J=22.6,13.6Hz,2H),4.32(d,J=9.1Hz,1H),2.36(s,3H),1.61(s,3H); 13 C NMR (101MHz, CDCl3) δ152.18,143.81,140.70,137.31,137.05,130.31,130.11,128.94,128.62,127.52,127.49,127.41,126.39,124.99,12 2.33,117.47,77.28,61.14,21.76,21.51; IR(film):ν3060,3026,2979,1600,1489,1450,1369,1303,1262,1097,1019,915,758,688; ESI-MS m / z(rel):341.0(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 24 H 25 N2(M+H) + :341.2012; Found:341.202; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=80:20, 0.7mL / min, 214nm, Column Temperature: 25℃): t minor =14.34min,t major =15.15min.

[0186]

[0187] Bright yellow liquid; 57.0 mg; Yield: 79%; 3ia / 4ia / 5ia: 85 / 4 / 11; dr: >20 / 1; ee: 87%; [α] D 29 =-50.1 (c 1.0, CHCl3); 1H NMR(400MHz, CDCl3)δ7.79(dd,J=7.1,1.3Hz,2H),7.59–7.44(m,3H),7.32–7.18(m,4H),7.18–6.98(m,4H),6.95 –6.78(m,1H),6.27–6.04(m,1H),5.09(dd,J=20.5,13.8Hz,2H),4.31(d,J=9.1Hz,1H),3.79(s,3H),1.65(s,3H); 13 C NMR (101MHz, CDCl3) δ159.00,152.14,145.66,140.66,137.20,130.44,1 30.09,129.00,128.59,127.59,126.47,122.39,120.34,117.59,114.41, 111.74,77.25,61.36,55.21,21.63;IR(film):ν3060,2980,2832,1600, 1581,1487,1451,1430,1314,1290,1068,1044,917,876,735,689; ESI-MS m / z(rel):357.0(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 24 H 25 N2O(M+H) + :357.1961; Found:357.1964; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=70:30, 0.7mL / min, 214nm, Column Temperature: 25℃): t minor =9.35min,t major =10.56min.

[0188]

[0189] Bright yellow liquid; 25.0 mg; Yield: 36%; 3ja / 4ja / 5ja: 91 / 4 / 5; dr: >20 / 1; ee: 89%; [α] D 27 =-105.2 (c 1.0, CHCl3); 1H NMR (400MHz, CDCl3) δ7.80(d,J=7.0Hz,2H),7.57–7.44(m,3H),7.27(d,J=7.5Hz,2H),7.16(dt,J=22.8,7.1Hz,4H),7.03(ddd,J=1 9.8,10.1,4.8Hz,2H),6.93(t,J=7.6Hz,1H),6.11–5.92(m,1H),5.08(dd,J=16.8,13.6Hz,2H),4.54(d,J=9.3Hz,1H),1.68(s,3H); 13 C NMR (101MHz, CDCl3) δ160.10 (d, J = 247.4Hz), 151.94, 141.19, 137.21, 131.97 (d, J = 11.6Hz), 130.61, 129.75, 129.04, 128.90 (d, J = 5.2H z),128.47(d,J=8.9Hz),127.54,126.26,123.40(d,J=3.1Hz),122.51,117.62,116.13(d,J=24.1Hz),76.75,58.89(d,J=3.7Hz),21.81; 19 F NMR (376MHz, CDCl3) δ-107.88; IR (film): ν3062,1578,1486,1447,1370,1274,1210,1064,1035,993,918,754,688; ESI-MSm / z(rel):345.0(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 23 H 22 FN2(M+H) + :345.1762; Found:345.1766; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=80:20, 0.7mL / min, 214nm, Column Temperature: 25℃): t minor =6.44min,t major =8.93min.

[0190]

[0191] Bright yellow liquid; 29.0 mg; Yield: 41%; 3ka / 4ka / 5ka: 91 / 4 / 5; DR: >20 / 1; ee: 89%; [α] D 29=-121.5 (c 1.0, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.80(d,J=7.3Hz,2H),7.50(dt,J=21.9,7.1Hz,3H),7.33(d,J=7.4Hz,2H),7.20–7.07(m,4H),6.92(d,J=7.7Hz,1 H),6.83(d,J=8.2Hz,1H),6.74(t,J=7.5Hz,1H),6.02–5.87(m,1H),5.07–4.96(m,2H),4.80(d,J=9.2Hz,1H),3.84(s,3H),1.67(s,3H); 13 C NMR (101MHz, CDCl3) δ156.46,152.19,142.23,138.25,133.40,130.25,1 29.86,129.00,128.25,127.81,127.32,125.89,122.46,120.02,116.80, 111.32,77.44,57.55,55.14,21.44;IR(film):ν3061,3027,2935,2834,1 725,1597,1581,1489,1452,1365,1240,1153,1025,915,750,697; ESI-MS m / z(rel):357.0(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 24 H 25 N2O(M+H) + :357.1961; Found:357.1963; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=80:20, 0.7mL / min, 214nm, Column Temperature: 25℃): t minor =5.96min,t major =6.90min.

[0192]

[0193] Bright yellow liquid; 44.5 mg; Yield: 59%; 3la / 4la / 5la: 87 / 5 / 8; Dr: >20 / 1; ee: 96%; [α] D 29 =-57.6 (c 1.0, CHCl3); 1H NMR (400MHz, CDCl3) δ7.74–7.61(m,6H),7.54(d,J=8.8Hz,1H),7.43–7.31(m,5H),7.05(d,J=5.0Hz,3H),7 .00–6.91(m,2H),6.03(dt,J=17.0,9.7Hz,1H),4.91(t,J=12.2Hz,2H),4.32(d,J=9.1Hz,1H),1.58(s,3H); 13 C NMR (101MHz, CDCl3) δ152.13,141.44,140.55,137.13,132.91,132.23,130.4 3,130.07,128.99,128.30,127.60,127.42,127.05,126.63,126.47,126.39,1 25.80,125.77,122.36,117.68,77.52,60.94,21.60; IR(film):ν3057,3025,2 979,2933,1597,1493,1450,1371,1261,1129,1068,917,815,744,687; ESI-MS m / z(rel):377.0(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 27 H 25 N2(M+H) + :377.2012; Found:377.2017; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=80:20, 0.7mL / min, 214nm, Column Temperature: 25℃): t minor =8.56min,t major =15.51min.

[0194]

[0195] Bright yellow liquid; 47.5 mg; Yield: 64%; 3mA / 4mA / 5mA: 88 / 5 / 7; Dr: >20 / 1; ee: 96%; [α] D 29 =-18.6 (c 1.0, CHCl3); 1H NMR (400MHz, CDCl3) δ7.67(d,J=6.9Hz,2H),7.43(t,J=8.2Hz,3H),7.14(d,J=6.9Hz,3H),7.08–6.92(m,3H),6.80(d,J=7.9Hz, 1H),6.71(d,J=8.1Hz,1H),6.15–5.98(m,1H),5.92(s,2H),4.98(dd,J=26.5,13.5Hz,2H),4.18(d,J=9.0Hz,1H),1.49(s,3H). 13 C NMR (101MHz, CDCl3) δ152.14,147.21,146.17,140.62,137.93,137.21,130 .49,130.10,129.04,127.66,126.55,122.42,121.22,117.68,108.93,107 .50,100.99,77.13,61.34,21.67.IR(film):ν3060,2979,2887,1724,1677 ,1598,1502,1484,1432,1235,1149,1104,1036,933,807,760,688.ESI-MS m / z(rel):371.0(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 24 H 23 N2O2(M+H) + :371.1754; Found:371.175; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=80:20, 0.7mL / min, 214nm, Column Temperature: 25℃): t minor =7.04min,t major =7.41min.

[0196]

[0197] Bright yellow liquid; 21.0 mg; Yield: 33%; 3Na / 4Na / 5Na: 87 / 9 / 4; Dr: >20 / 1; ee: 94%; [α] D 31 =-26.8 (c 1.0, CHCl3); 1H NMR(400MHz, CDCl3)δ7.70–7.58(m,2H),7.44(dd,J=14.8,7.4Hz,4H),7.25–7.16(m,3H),7.05(d,J=6.6Hz ,2H),6.36–6.24(m,2H),6.17(d,J=3.2Hz,1H),5.08(t,J=12.3Hz,2H),4.47(d,J=8.9Hz,1H),1.55(s,3H); 13 C NMR (101MHz, CDCl3) δ155.89,151.96,141.88,140.13,137.26,130.44,129.71,128.87,127.73,126.58,122.30,117.43,110. 00,108.52,75.73,58.95,19.79; IR(film):ν3061,2982,1678,1598,1494,1451,1367,1302,1155,1013,918,759,688; ESI-MS m / z(rel):317.0(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 21 H 21 N2O(M+H) + :317.1648; Found:317.1651; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=80:20, 0.7mL / min, 214nm, Column Temperature: 25℃): t major =6.67min,t minor =7.30min.

[0198]

[0199] Bright yellow liquid; 19.1 mg; Yield: 28%; 3oa / 4oa / 5oa: 60 / 3 / 37; dr: >20 / 1; ee: 78%; [α] D 25 =1.8.(c 1.0,CHCl3); 1H NMR (400MHz, CDCl3) δ7.80 (dd, J=8.2, 1.2Hz, 2H), 7.50 (tdd, J=6.9, 4.5, 2.1Hz, 3H) ,7.38–7.29(m,4H),7.28–7.24(m,1H),7.12(dd,J=6.4,3.8Hz,3H),6.81(dd,J=6.6 ,3.0Hz,2H),5.89(dt,J=16.9,9.8Hz,1H),5.02–4.83(m,2H),3.99(d,J=9.5Hz,1H) ,2.38(dd,J=14.2,7.2Hz,1H),1.95(dd,J=14.3,7.3Hz,1H),0.55(t,J=7.3Hz,3H); 13 C NMR (101MHz, CDCl3) δ152.22,140.89,140.46,137.30,130.47,129.97,129.08,129.02,127.45,127.40,126.46,126.30,122.26,11 6.90,79.57,61.73,29.70,8.18; IR(film):ν3058,3025,2971,2934,1597,1491,1446,1305,1150,1070,1020,915,758,689; ESI-MS m / z(rel):341.0(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 24 H 25 N2(M+H) + :341.2012; Found:341.2015; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=70:30, 0.7mL / min, 254nm, Column Temperature: 25℃): t minor =11.02min,t major =14.47min.

[0200]

[0201] Bright yellow liquid; 42.6 mg; Yield: 70%; 3pa / 4pa / 5pa: 85 / 6 / 9; ee: 92%; [α] D 24 =-130.3 (c 1.0, CHCl3); 1H NMR (400MHz, CDCl3) δ7.70 (d, J=7.2Hz, 2H), 7.49 (dt, J=20.5, 7.0Hz, 3H), 7.2 1(ddd,J=21.3,14.0,6.8Hz,5H),6.35(dt,J=16.8,9.9Hz,1H),5.13(dd,J=13. 6,8.0Hz,2H),3.74(d,J=9.7Hz,1H),2.23(d,J=8.3Hz,1H),2.16–2.04(m,1H) ,1.80–1.69(m,1H),1.62(d,J=2.7Hz,3H),1.50(s,1H),1.38(d,J=4.4Hz,3H); 13 C NMR (101MHz, CDCl3) δ152.28,140.95,137.90,130.06,129.68,128.95,127.84,126.33,121.99,116.85,73.80,59.29,33.03,32. 43,25.75,22.28,22.14; IR(film):ν3062,3027,2928,2856,1635,1598,1490,1450,1297,1263,1141,1068,913,761,687; ESI-MS m / z(rel):305.0(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 21 H 25 N2(M+H) + :305.2012; Found:305.201; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=80:20, 0.7mL / min, 214nm, Column Temperature: 25℃): t minor =8.61min,t major =10.16min.

[0202]

[0203] Bright yellow liquid; 44 mg; Yield: 64%; 3ab / 4ab / 5ab: 89 / 4 / 7; Dr: >20 / 1; ee: 95%; [α] D 29 =-42.0 (c 1.0, CHCl3); 1H NMR(400MHz, CDCl3)δ7.83–7.65(m,2H),7.48(ddd,J=8.9,7.2,3.9Hz,3H),7.44–7.37(m,2H),7.29(dt,J=23.0,6.7Hz,3H),7.06–6.95 (m,2H),6.87(dd,J=12.3,5.0Hz,2H),6.07(dt,J=17.2,9.7Hz,1H),5.04(dd,J=28.2,13.6Hz,2H),4.27(d,J=9.0Hz,1H),1.61(s,3H); 13 C NMR(101MHz, CDCl3) δ161.50(d,J=244.4Hz),152.04,143.89,137.04,136.36(d,J=3.2Hz,10H),,131.39(d,J= 7.8Hz),130.51,129.02,127.75,127.71,126.77,122.33,117.72,114.33(d,J=21.0Hz),77.16,60.53,21.64; 19 FNMR(376MHz, CDCl3)δ-116.63; IR(film): ν3058,3033,1596,1505,1489,1444,1362,1294,1224,1156,994,840,752,690; ESI-MS m / z(rel):345.0(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 23 H 22 FN2(M+H) + :345.1762; Found:345.1764; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=75:25, 0.7mL / min, 254nm, Column Temperature: 25℃): t minor =7.71min,t major =8.63min.

[0204]

[0205] Bright yellow liquid; 27.0 mg; Yield: 37%; 3ac / 4ac / 5ac: 88 / 4 / 8; DR: >20 / 1; ee: 96%; [α] D 29 =-55.7 (c 1.0, CHCl3); 1H NMR (400MHz, CDCl3) δ7.73(d,J=6.9Hz,2H),7.54–7.44(m,3H),7.37(d,J=7.4Hz,2H),7.32–7.24(m,3H),7.13(d,J=8.4Hz, 2H), 6.95 (d, J = 8.4Hz, 2H), 6.03 (dt, J = 17.2, 9.7Hz, 1H), 5.02 (dd, J = 27.4, 13.6Hz, 2H), 4.23 (d, J = 9.1Hz, 1H), 1.58 (s, 3H); 13 C NMR (101MHz, CDCl3) δ151.97,143.75,139.20,136.75,132.13,131.30,130.54,129.00,127.76,127.64,126.79,122.33,117 .89,77.02,60.62,21.72; IR(film):ν3059,2979,2925,1683,1595,1490,1446,1370,1260,1090,1014,919,760,691; ESI-MS m / z(rel):360.9(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 23 H 22 ClN2(M+H) + :361.1466; Found:361.1465; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=80:20, 0.7mL / min, 214nm, Column Temperature: 25℃): t minor =7.07min,t major =8.43min.

[0206]

[0207] Bright yellow liquid; 55.0 mg; Yield: 76%; 3ad / 4ad / 5ad: 85 / 4 / 11; Dr: >20 / 1; ee: 85%; [α] D 25 =-39.8 (c 1.0, CHCl3); 1H NMR (400MHz, CDCl3) δ7.71(d,J=7.8Hz,2H),7.52–7.42(m,3H),7.40(d,J=7.9Hz,2H),7.30(t,J=7.5Hz,2H),7.24(d,J=7.2Hz,1H),6.92(d,J=8 .6Hz,2H),6.71(d,J=8.7Hz,2H),6.05(dt,J=17.1,9.7Hz,1H),4.98(dd,J=24.7,13.6Hz,2H),4.21(d,J=9.1Hz,1H),3.75(s,3H),1.56(s,3H); 13 C NMR (101MHz, CDCl3) δ158.02,152.12,143.94,137.40,132.69,130.90,130.30,128.91,127.87,127.60,126.60,122.29,117.17,112. 89,77.33,60.34,55.10,21.48; IR(film):ν3058,2932,2834,1682,1601,1509,1444,1359,1244,1174,1030,966,833,756,690; ESI-MS m / z(rel):357.2(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 24 H 25 N2O(M+H) + :357.1961; Found:357.1962; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=80:20, 0.7mL / min, 214nm, Column Temperature: 25℃): t minor =6.85min,t major =7.95min.

[0208]

[0209] Bright yellow liquid; 39.3 mg; Yield: 58%; 3ae / 4ae / 5ae: 89 / 4 / 7; DR: >20 / 1; ee: 89%; [α] D 23 =-40.3 (c 1.0, CHCl3); 1H NMR (400MHz, CDCl3) δ7.76(d,J=7.4Hz,2H),7.58–7.41(m,5H),7.30(dt,J=25.5,7.3Hz,3H),7.01(d,J=7.6Hz,2H),6. 94(d,J=7.6Hz,2H),6.25–5.98(m,1H),5.02(dd,J=20.7,13.6Hz,2H),4.28(d,J=9.1Hz,1H),2.30(s,3H),1.60(s,3H); 13 C NMR (101MHz, CDCl3) δ152.17,143.97,137.57,137.42,135.86,130.31,129.88,128.93,128.28,127.93,127.62,126.64,122.34,11 7.27,77.31,60.80,21.54,21.04; IR(film):ν3057,3021,2979,1597,1511,1492,1446,1370,1263,1111,1024,916,759,690; ESI-MS m / z(rel):341.0(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 24 H 25 N2(M+H) + :341.2012; Found:341.2015; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=80:20, 0.7mL / min, 214nm, Column Temperature: 25℃): t minor =6.86min,t major =7.74min.

[0210]

[0211] Bright yellow liquid; 47.0 mg; Yield: 46%; 3af / 4af / 5af: 90 / 3 / 7; Dr: >20 / 1; ee: 96%; [α] D 29 =-40.5 (c 1.0, CHCl3); 1H NMR (400MHz, CDCl3) δ7.84–7.70(m,2H),7.55–7.43(m,3H),7.42–7.37(m,2H),7.35–7.28(m,2H),7.25(ddd,J=7.4,3.6,1.3Hz,1H),7 .12(dt,J=14.1,3.9Hz,1H),6.90–6.76(m,3H),6.19–5.93(m,1H),5.05(dd,J=24.7,13.6Hz,2H),4.28(d,J=9.0Hz,1H),1.62(s,3H); 13 C NMR (101MHz, CDCl3) δ162.19 (d, J = 244.4Hz), 152.00, 143.26 (d, J = 7.1Hz), 143.23, 136.65, 130.56, 129.03, 128.82 (d, J = 8.2Hz), 127.78, 127.64, 126.83, 125.76 (d, J = 2.7Hz), 122.35, 118.02, 116.83 (d, J = 21.7Hz), 113.25 (d, J = 21.0Hz), 77.13, 61.01, 21.72; 19 F NMR (376MHz, CDCl3) δ-114.11 (dd, J=15.6, 8.5Hz); IR (film): ν3060,3025,2981,1611,1585,1487,1444,1371,1261,1144,1068,918,760,688; ESI-MS m / z(rel):345.0(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 23 H 22 FN2(M+H) + :345.1762; Found:345.1765; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=80:20, 0.7mL / min, 214nm, Column Temperature: 25℃): t minor =6.24min,t major =6.94min.

[0212]

[0213] Bright yellow liquid; 47.2 mg; Yield: 66%; 3ag / 4ag / 5ag: 88 / 4 / 8; Dr: >20 / 1; ee: 91%; [α] D29 =-49.2 (c 1.0, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.83–7.68(m,2H),7.48(ddd,J=10.7,8.5,6.0Hz,5H),7.33(t,J=7.3Hz,2H),7.27(dd,J=7.8,5.4Hz,1H),7.11(t,J=7.9Hz, 1H),6.79–6.60(m,2H),6.56(s,1H),6.10(dt,J=17.0,9.7Hz,1H),5.04( dd,J=19.9,13.6Hz,2H),4.27(d,J=9.2Hz,1H),3.65(s,3H),1.61(s,3H); 13 C NMR (101MHz, CDCl3) δ158.77,152.13,143.89,142.15,137.08,130.41,128.96,128.43,127.93,127.66,126.72,122.49,122.35,117.58, 115.37,112.34,77.28,61.26,54.98,21.60; IR(film):ν3058,2934,2832,1682,1596,1489,1449,1262,1155,1043,917,759,689; ESI-MS m / z(rel):357.0(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 24 H 25 N2O(M+H) + :357.1961; Found:357.196; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=80:20, 0.7mL / min, 214nm, Column Temperature: 25℃): t minor =6.44min,t major =8.93min.

[0214]

[0215] Bright yellow liquid; 33.2 mg; Yield: 48%; 3ah / 4ah / 5ah: 88 / 4 / 8; Dr: >20 / 1; ee: 94%; [α] D 29 =-57.3 (c 1.0, CHCl3); 1H NMR (400MHz, CDCl3) δ7.76(d,J=7.0Hz,2H),7.48(dt,J=7.0,4.6Hz,3H),7.41(d,J=7.2Hz,2H),7.33–7.19(m,3H),7.13(dd,J= 13.2, 6.2Hz, 2H), 6.95 (dt, J = 18.6, 8.1Hz, 2H), 6.18–5.94 (m, 1H), 5.05 (t, J = 13.7Hz, 2H), 4.72 (d, J = 9.0Hz, 1H), 1.66 (s, 3H); 13 C NMR(101MHz, CDCl3) δ160.66(d,J=245.1Hz),152.09,143.97,136.33,131.22(d,J=3.9Hz)130.45,128.96,127.95, 127.87,127.66,127.63,126.73,123.18(d,J=3.5Hz),122.40,118.05,115.04(d,J=24.0Hz),77.50,52.39,21.69; 19 F NMR(376MHz, CDCl3)δ-115.59; IR(film): ν3061,2981,1598,1487,1448,1370,1226,1068,919,754,689; ESI-MS m / z(rel):345.0(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 23 H 22 FN2(M+H) + :345.1762; Found:345.1765; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=80:20, 0.7mL / min, 214nm, Column Temperature: 25℃): t minor =6.48min,t major =7.40min.

[0216]

[0217] Bright yellow liquid; 37 mg; Yield: 51%; 3ai / 4ai / 5ai: 85 / 4 / 11; DR: >20 / 1; ee: 79%; [α] D 29 =-88.6 (c 1.0, CHCl3); 1H NMR (400MHz, CDCl3) δ7.74(d,J=7.4Hz,2H),7.46(dt,J=19.2,6.9Hz,3H),7.37(d,J=7.3Hz,2H),7.29–7.16(m,4H),7.11(dd,J=18.9,7.9Hz,2H),6 .81(t,J=7.5Hz,1H),6.70(d,J=8.2Hz,1H),6.13–5.98(m,1H),5.03(s,1H ),4.99(d,J=7.6Hz,1H),4.83(d,J=9.2Hz,1H),3.60(s,3H),1.61(s,3H); 13 C NMR (101MHz, CDCl3) δ156.98,152.21,144.52,137.63,130.52,130.22,129.19,128.87,127.82,127.27,127.26,126.37,122.38,119.66,11 7.14,110.27,77.77,55.28,51.72,22.05; IR(film):ν3060,3029,2935,2834,1685,1597,1489,1460,1337,1241,1028,917,752,692; ESI-MS m / z(rel):357.0(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 24 H 25 N2O(M+H) + :357.1961; Found:357.1963; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=80:20, 0.7mL / min, 214nm, Column Temperature: 25℃): t minor =6.38min,t major =6.75min.

[0218]

[0219] Bright yellow liquid; 30.8 mg; Yield: 41%; 3aj / 4aj / 5aj: 85 / 8 / 7; Dr: >20 / 1; ee: 92%; [α] D 29 =-71.3 (c 1.0, CHCl3); 1H NMR(400MHz, CDCl3)δ7.78(dd,J=8.1,5.6Hz,3H),7.74–7.62(m,2H),7.55–7.40(m,8H),7.36–7.24(m,3H),7.2 1–7.14(m,1H),6.23(dt,J=17.1,9.7Hz,1H),5.08(dd,J=21.0,13.6Hz,2H),4.48(d,J=9.0Hz,1H),1.65(s,3H); 13 C NMR (101MHz, CDCl3) δ152.13,143.83,138.27,137.20,133.03,132.24,130. 42,128.98,128.89,128.49,127.95,127.79,127.70,127.44,126.81,126.78 ,125.67,125.43,122.37,117.73,77.43,61.23,21.76; IR(film):ν3055,30 21,2976,1597,1492,1445,1369,1261,1068,1018,917,817,760,689; ESI-MS m / z(rel):377.0(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 27 H 25 N2(M+H) + :377.2012; Found:377.2012; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=80:20, 0.7mL / min, 214nm, Column Temperature: 25℃): t minor =9.11min,t major =12.30min.

[0220]

[0221] Bright yellow liquid; 43 mg; Yield: 58%; 3ak / 4ak / 5ak: 79 / 5 / 16; DR: >20 / 1; ee: 88%; [α] D 29 =-33.9 (c 1.0, CHCl3); 1H NMR(400MHz, CDCl3)δ7.72(d,J=7.2Hz,2H),7.55–7.42(m,3H),7.39(d,J=7.8 Hz,2H),7.30(t,J=7.5Hz,2H),7.24(d,J=8.4Hz,1H),6.61(d,J=8.0Hz,1H),6 .55(s,1H),6.48(d,J=8.1Hz,1H),5.99(dt,J=21.2,10.3Hz,1H),5.87(d,J=9 .2Hz, 2H), 4.99 (dd, J=23.5, 13.5Hz, 2H), 4.18 (d, J=9.2Hz, 1H), 1.57 (s, 3H). 13 C NMR (101MHz, CDCl3) δ152.09,146.86,145.93,143.92,137.33,134.48,130.44,129.00,127.81,127.71,126.72,123.34,122.34,117.42,110.2 8,107.47,100.75,77.35,60.91,21.70; IR(film):ν3059,2979,2887,1598,1501,1486,1441,1368,1302,1233,1037,920,811,760,689; ESI-MS m / z(rel):371.0(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 24 H 23 N2O2(M+H) + :371.1754; Found:371.1756; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=80:20, 0.7mL / min, 214nm, Column Temperature: 25℃): t minor =6.73min,t major =7.50min.

[0222]

[0223] Bright yellow liquid; Yield: 79%; 3al / 4al / 5al: 84 / 4 / 12; DR: >20 / 1; EE: 94%; [α] D 29 =-30.5 (c 1.0, CHCl3); 1H NMR (400MHz, CDCl3) δ7.76–7.65(m,2H),7.53–7.43(m,5H),7.35(t,J=7.5Hz,2H),7.28(t,J=5.9Hz,2H),6.25(dd,J=3.0,1.9Hz,1 H),5.99(d,J=3.1Hz,1H),5.89(ddd,J=17.1,10.2,8.9Hz,1H),5.01(dd,J=35.2,13.6Hz,2H),4.58(d,J=8.8Hz,1H),1.65(s,3H); 13 C NMR (101MHz, CDCl3) δ154.05,152.17,143.45,140.95,134.46,130.32,128.92,127.84,127.53,126.83,122.27,118.24,110.07 ,108.07,77.38,53.79,20.37; IR(film):ν3059,3025,2981,1597,1493,1446,1371,1264,1148,1101,1013,920,731,689; ESI-MS m / z(rel):317.0(M+H) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 21 H 21 N2O(M+H) + :317.1648; Found:317.1649; HPLC (PC-3 (Phenomenex Cellulose-3), CH3CN:H2O=80:20, 0.7mL / min, 214nm, Column Temperature: 25℃): t minor =6.31min,t major =7.30min.

[0224] Example 2: Synthesis of α-quaternary carbon amine T1

[0225]

[0226] To a 50 mL reaction tube, P1 (0.116 mmol, 38 mg) and methanol (5.0 mL) were added, followed by palladium on carbon (10 mg). The hydrogen was exchanged three times, and the mixture was heated to 50 ° C. for 36 h. The mixture was filtered, concentrated, and separated on a preparative plate (petroleum ether / ethyl acetate = 10 / 1) to give a light yellow solid T1 (23.0 mg, 83%).

[0227]

[0228] Pale yellow solid; 89% ee; [α] D 28 =34.8(1.0,CHCl3);mp:72.6-73.5℃; 1 H NMR (400MHz, CDCl3) δ7.42(d,J=7.6Hz,2H),7.29(t,J=7.6Hz,2H),7.26–7.14(m,4H),7.08(d,J= 7.0Hz,2H),2.78(dd,J=10.9,4.2Hz,1H),1.67–1.56(m,3H),1.49(s,3H),0.60(t,J=7.3Hz,3H); 13 C NMR (101MHz, CDCl3) δ148.26,140.31,130.13,127.71,127.64,126.39,126.31,126.24,60.20,57.63,26.69,22.20,12. 85; IR (film): ν3360,3054,3021,2967,2884,1598,1575,1490,1447,1379,1299,1207,1107,1059,939,776,698; ESI-MS m / z(rel):223.2(M-NH2) + ; HRMS (ESI) high resolution mass spectrometry calculated value: C 17 H 19 (M-NH2) + :223.1481; Found:223.1482.HPLC (OD-H, HEX:IPA=90:10, 0.7mL / min, 225nm):t major =5.13min,t minor =7.08min.

[0229] Compound T1 (11.0 mg) (HPLC retention time is the above t major =5.13min)(dissolved in 0.5mL chloroform, evaporated slowly at room temperature, crystallized to obtain crystals, and the crystals were subjected to X-ray diffraction detection. Figure 1 The structure of compound T1 was determined to be as follows configuration.

[0230]

[0231]

[0232] Example 3:

[0233]

[0234] 1a (0.4 mmol, 84.1 mg) and toluene (2.0 mL) were added to a 10 mL dry reaction tube. LiHMDS (1.0 M in THF, 0.4 mL, 0.4 mmol) was added under ice bath. After the addition, the mixture was stirred at room temperature for 30 min. [Pd(η 3 -C3H5)Cl]2 (1.83 mg, 0.005 mmol), Ligand (0.01 mmol) and toluene (1.0 mL) were added under ice bath, t-BuOK (1.0 M in THF, 25 uL, 0.025 mmol) was added, and after the addition was completed, the mixture was stirred at room temperature for 30 min and then added to the above 10 mL reaction tube, and then 2a (0.2 mmol, 43.7 mg) and toluene (1.0 mL) were added and reacted at room temperature overnight. After the reaction was completed, water (0.5 mL) was added to quench the reaction, and the mixture was passed through a short silica gel column, rinsed with ethyl acetate (50 mL), concentrated, and mesitylene was added as an internal standard. The yield, regioselectivity and diastereoselectivity of the reaction were determined by 1 The crude H NMR spectrum was confirmed, and the product ee value was determined by HPLC. (The structures of Compounds 4 and 5 in Example 1 refer to Compounds 4aa and 5aa)

[0235] by As the ligand, the yield of branched product 3aa was 48%, 3aa / 4aa / 5aa=47 / 6 / 47, ant / syn=2 / 1;

[0236] by As the ligand, the yield of branched product 3aa was 11%, 3aa / 4aa / 5aa=18 / 45 / 47, ant / syn=2 / 1;

[0237] by As the ligand, the yield of branched product 3aa was 71%, 3aa / 4aa / 5aa=72 / 11 / 17, ant / syn=5 / 1;

[0238] by The ligand was used as the ligand, and the yield of the branched product 3aa was 18%, with 3aa / 4aa / 5aa = 15 / 4 / 81, ant / syn > 20 / 1, and ee = 5%. (For the preparation of the ligand, see: Wang, W.-Y.; Wu, J.-Y.; Liu, Q.-R.; Liu, X.-Y.; Ding, C.-H.; Hou, X.-L. Org. Lett. 2018, 20, 4773.)

[0239] by As the ligand, trace amounts of branched product 3aa were observed;

[0240] by For the ligand, no branched products were observed, 3aa / 4aa / 5aa=0 / 8 / 92;

[0241] by The ligand was used, and the yield of the branched product 3aa was 19%, 3aa / 4aa / 5aa = 90 / 5 / 5, ant / syn > 20 / 1, and ee = 63%; (For the preparation of the ligand, see: Katayev, D.; Jia, YX; Sharma, AK; Banerjee, D.; Besnard, C.; Sunoj, RB; Kundig, EP Chem. Eur. J. 2013, 19, 119-16.)

[0242] by The ligand was used as the branched product 3aa in a 15% yield, with 3aa / 4aa / 5aa = 63 / 16 / 21, ant / syn > 20 / 1, and ee = 53%. (For the preparation of the ligand, see: Katayev, D.; Jia, YX; Sharma, AK; Banerjee, D.; Besnard, C.; Sunoj, RB; Kundig, EP Chem. Eur. J. 2013, 19, 119-16.)

[0243] by The ligand was used as the branched product 3aa in a 64% yield, with 3aa / 4aa / 5aa ratios of 92 / 2 / 6, ant / syn ratios >20 / 1, and ee of 91%. (For the preparation of the ligand, see: Katayev, D.; Jia, YX; Sharma, AK; Banerjee, D.; Besnard, C.; Sunoj, RB; Kundig, EP Chem. Eur. J. 2013, 19, 119-16.)

[0244] by The ligand was a trace amount of branched product 3aa was observed; (For the preparation of the ligand, see: Urban, S.; Ortega, N.; Glorius, F. Angew. Chem. Int. Ed. 2011, 50, 3803.)

[0245] by The ligand was a branched product, and no branched product was observed. 3aa / 4aa / 5aa = 0 / 0 / 100. (For the preparation of the ligand, see: Rodeschini, V.; Simpkins, NS; Zhang, F. Organic Syntheses. 2007, 84, 306.)

[0246] by The ligand was used, and the yield of the branched product 3aa was 13%, with 3aa / 4aa / 5aa = 40 / 34 / 26, and ant / syn > 20 / 1. (For the preparation of the ligand, see: Steinbeck, M.; Frey, GD; Schoeller, WW; Herrmann, WAJ Organomet. Chem. 2011, 696, 3945.)

[0247] by As a ligand, trace amounts of branched products were observed; (purchased from J&K Technology Co., Ltd.)

[0248] With (R)-BINAP as the ligand, no branched products were observed, 3aa / 4aa / 5aa = 0 / 0 / 100;

[0249] With PPh3 as the ligand, no branched products were observed, 3aa / 4aa / 5aa=0 / 0 / 100.

[0250]

[0251] 1a (0.4 mmol, 84.1 mg) and solvent (2.0 mL) were added to a 10 mL dry reaction tube. Base (1.0 M in THF, 0.4 mL, 0.4 mmol) was added under ice bath. After the addition, the mixture was stirred at room temperature for 30 min. [Pd(η 3 -C3H5)Cl]2 (1.83 mg, 0.005 mmol), L9 (0.01 mmol, 5.5 mg) and solvent (1.0 mL) were added under ice bath, t-BuOK (1.0 M in THF, 25 uL, 0.025 mmol) was added, and after the addition was completed, the mixture was stirred at room temperature for 30 min and then added to the above 10 mL reaction tube, and then 2a (0.2 mmol, 43.7 mg) and solvent (1.0 mL) were added and reacted at room temperature overnight. After the reaction was completed, water (0.5 mL) was added to quench the reaction, and the mixture was passed through a short silica gel column, rinsed with ethyl acetate (50 mL), concentrated, and mesitylene was added as an internal standard. The yield, regioselectivity and diastereoselectivity of the reaction were obtained by 1 The crude product was confirmed by H NMR spectrum and the ee value was determined by HPLC.

[0252] Using LiHMDS as base and toluene as solvent, the yield was 54%, 3aa / 4aa / 5aa=92 / 2 / 6, ant / syn>20 / 1, ee=91%;

[0253] Using KHMDS as base and toluene as solvent, no branched products were observed, 3aa / 4aa / 5aa = 0 / 0 / 100;

[0254] Using NaHMDS as base and toluene as solvent, no branched products were observed, 3aa / 4aa / 5aa = 0 / 0 / 100;

[0255] by t BuOK was used as the base and toluene as the solvent. No branched products were observed. 3aa / 4 / 5 = 0 / 0 / 100.

[0256] by t BuOLi is a base and toluene is a solvent, so the reaction cannot proceed;

[0257] Using LDA as base and toluene as solvent, the yield was 34%, 3aa / 4aa / 5aa=75 / 4 / 21, ant / syn>20 / 1, ee=92%;

[0258] by n BuLi was used as the base and toluene was used as the solvent. The yield was 70%, 3aa / 4aa / 5aa=86 / 4 / 10, ant / syn>20 / 1, and ee=91%;

[0259] Using LiHMDS as base and tetrahydrofuran as solvent, the yield was 34%, 3aa / 4aa / 5aa=58 / 9 / 33, ant / syn>20 / 1, ee=90%;

[0260] Using LiHMDS as base and 1,4-dioxane as solvent, the yield was 10%, 3aa / 4aa / 5aa=46 / 21 / 33, ant / syn>20 / 1, ee=84%;

[0261] The reaction could not proceed using LiHMDS as base and dichloromethane as solvent;

[0262] Using LiHMDS as base and n-hexane as solvent, the yield was 41%, 3aa / 4aa / 5aa=83 / 1 / 16, ant / syn>20 / 1, and ee=85%.

[0263] Example 4

[0264]

[0265] 1a (0.4 mmol, 84.1 mg) and toluene (2.0 mL) were added to a 10 mL dry reaction tube. LiHMDS (1.0 M in THF, 0.4 mL, 0.4 mmol) was added under ice bath. After the addition, the mixture was stirred at room temperature for 30 min. [Pd(η 3-C3H5)Cl]2 (1.83 mg, 0.005 mmol), L9 (0.01 mmol, 5.5 mg) and toluene (1.0 mL) were added to the mixture under ice bath. t-BuOK (1.0 M in THF, 25 uL, 0.025 mmol) was added. After the addition was completed, the mixture was stirred at room temperature for 30 min and then added to the above 10 mL reaction tube. Allyl reagent 2 (0.2 mmol) and toluene (1.0 mL) were added and the reaction was allowed to proceed overnight at the corresponding temperature. After the reaction was completed, water (0.5 mL) was added to quench the reaction. The mixture was passed through a short silica gel column, rinsed with ethyl acetate (50 mL), concentrated, and mesitylene was added as an internal standard. The yield, regioselectivity and diastereoselectivity of the reaction were obtained by 1 The crude product was confirmed by H NMR spectrum and the ee value was determined by HPLC.

[0266] With OPiv as the leaving group (i.e., when X is Opiv), the reaction was carried out at room temperature with a yield of 64%, 3aa / 4aa / 5aa = 92 / 2 / 6, ant / syn > 20 / 1, and ee = 91%;

[0267] With OCO2Me as the leaving group (i.e., when X is OCO2Me), the reaction was carried out at room temperature, and a trace amount of product 3aa was detected;

[0268] With OCOCO2Me as the leaving group (i.e., when X is OCOCO2Me), the reaction was carried out at room temperature, and a trace amount of product 3aa was detected;

[0269] When OAc was used as the leaving group (i.e., when X was OAc), the reaction did not occur at room temperature.

[0270] The ligand synthesis method refers to: Katayev, D.; Jia, YX; Sharma, AK; Banerjee, D.; Besnard, C.; Sunoj, RB; Kundig, EPChem.Eur.J.2013,19,11916.

Claims

1. A method for preparing a compound as shown in Formula I, comprising the following steps: Step 1: In a solvent, a compound represented by Formula III is subjected to a hydrogen extraction reaction with a strong base to obtain a mixture A; Step 2: In the presence of a base, a catalyst, and a ligand, catalyze a reaction between the mixture A and the compound of Formula II to obtain the compound of Formula I; The strong base is LiHMDS, LDA and n One or more of BuLi; The base is t BuOK; The solvent is one or more of an aromatic hydrocarbon solvent, an alkane solvent and an ether solvent; The catalyst is [Pd(η 3 -C3H5)Cl]2; The ligand is any of the following compounds: R A and R A’ are independently "phenyl substituted by one or more C1-C6 alkyl groups" or R B and R B’ are each independently "a 6-10 membered aryl group substituted by one or more C1-C6 alkyl groups" or a 6-10 membered aryl group; X - Cl - 、OTf - or BF4 - ; R 1 is a 6-10 membered aromatic group, supported by one or more R 11 a substituted 6-10 membered aryl group, or a 5-6 membered heteroaryl group having 1, 2 or 3 heteroatoms independently selected from N, O and S; when there are multiple substituents, the substituents may be the same or different; R 2 is a C1-C6 alkyl group; R 3 is a 6-10 membered aromatic group, supported by one or more R 31 a substituted 6-10 membered aryl group, or a 5-6 membered heteroaryl group having 1, 2 or 3 heteroatoms independently selected from N, O and S; when there are multiple substituents, the substituents may be the same or different; R 4 is a 6-10 membered aromatic group; R 11 are independently halogen, C1-C6 alkyl, C1-C6 alkoxy, -COOR 111 or cyano; R 31 are independently halogen, C1-C6 alkyl, C1-C6 alkoxy, -COOR 311 or cyano; R 111 is a C1-C6 alkyl group; R 311 is a C1-C6 alkyl group; or, R 2 With R 3 Together with the atoms to which they are attached, they form a 5-7 membered cycloalkyl group; Or, when the R 11 When there are multiple R 11 Together with the atoms to which they are attached, they form a 5-6 membered heterocycloalkenyl group having 1, 2 or 3 heteroatoms independently selected from N, O and S; Or, when the R 31 When there are multiple R 31 Together with the atoms to which they are attached, they form a 5-6 membered heterocycloalkenyl group with 1, 2 or 3 heteroatoms independently selected from N, O and S.

2. The method for preparing the compound of formula I according to claim 1, wherein: When R 1 When it is a 6-10 membered aryl group, the 6-10 membered aryl group is a phenyl group or a naphthyl group; and / or, when R 1 For one or more R 11 When the substituted 6-10 membered aryl group is a phenyl group or a naphthyl group; and / or, when R 11 When it is a halogen, the halogen is fluorine, chlorine, bromine or iodine; and / or, when R 11 When it is a C1-C6 alkyl group, the C1-C6 alkyl group is a C1-C3 alkyl group; and / or, when R 11 When it is a C1-C6 alkoxy group, the C1-C6 alkoxy group is a C1-C3 alkoxy group; and / or, when R 111 When it is a C1-C6 alkyl group, the C1-C6 alkyl group is a C1-C3 alkyl group; and / or, when R 1 "a 5-6 membered heteroaryl group having 1, 2 or 3 heteroatoms independently selected from N, O and S", wherein the 5-6 membered heteroaryl group is furyl; and / or, when R 2 When it is a C1-C6 alkyl group, the C1-C6 alkyl group is a C1-C3 alkyl group; and / or, when R 3 When it is a 6-10 membered aryl group, the 6-10 membered aryl group is a phenyl group or a naphthyl group; and / or, when R 3 For one or more R 31 When the substituted 6-10 membered aryl group is a phenyl group or a naphthyl group; and / or, when R 31 When it is a halogen, the halogen is fluorine, chlorine, bromine or iodine; and / or, when R 31 When it is a C1-C6 alkyl group, the C1-C6 alkyl group is a C1-C3 alkyl group; and / or, when R 31 When it is a C1-C6 alkoxy group, the C1-C6 alkoxy group is a C1-C3 alkoxy group; and / or, when R 311 When it is a C1-C6 alkyl group, the C1-C6 alkyl group is a C1-C3 alkyl group; and / or, when R 3 "a 5-6 membered heteroaryl group having 1, 2 or 3 heteroatoms independently selected from N, O and S", wherein the 5-6 membered heteroaryl group is furyl; and / or, when R 4 When it is a 6-10 membered aryl group, the 6-10 membered aryl group is a phenyl group or a naphthyl group; and / or, when R 2 With R 3 When together with the atoms to which they are attached form a 5-7 membered cycloalkyl group, the 5-7 membered cycloalkyl group is a cyclohexyl group; and / or, when the R 11 For multiple, any two adjacent R 11 When the number of heteroatoms formed by the 5- to 6-membered heterocycloalkenyl radicals together with the atoms to which they are attached is 1, 2 or 3 and the heteroatoms are independently selected from N, O and S, the 5- to 6-membered heterocycloalkenyl radicals are and / or, when the R 31 For multiple, any two adjacent R 31 When the number of heteroatoms formed by the 5- to 6-membered heterocycloalkenyl radicals together with the atoms to which they are attached is 1, 2 or 3 and the heteroatoms are independently selected from N, O and S, the 5- to 6-membered heterocycloalkenyl radicals are 3. The method for preparing the compound of formula I according to claim 2, wherein: When R 1 When it is a 6-10 membered aryl group, the 6-10 membered aryl group is and / or, when R 11 When halogen, the halogen is fluorine or chlorine; and / or, when R 11 When it is a C1-C6 alkyl group, the C1-C6 alkyl group is a methyl group; and / or, when R 11 When it is a C1-C6 alkoxy group, the C1-C6 alkoxy group is a methoxy group; and / or, when R 111 When it is a C1-C6 alkyl group, the C1-C6 alkyl group is a methyl group; and / or, when R 1 "a 5-6 membered heteroaryl group having 1, 2 or 3 heteroatoms independently selected from N, O and S", wherein the 5-6 membered heteroaryl group is and / or, when R 2 When it is a C1-C6 alkyl group, the C1-C6 alkyl group is a methyl group or an ethyl group; and / or, when R 3 When it is a 6-10 membered aryl group, the 6-10 membered aryl group is and / or, when R 31 When halogen, the halogen is fluorine or chlorine; and / or, when R 31 When it is a C1-C6 alkyl group, the C1-C6 alkyl group is a methyl group; and / or, when R 31 When it is a C1-C6 alkoxy group, the C1-C6 alkoxy group is a methoxy group; and / or, when R 311 When it is a C1-C6 alkyl group, the C1-C6 alkyl group is a methyl group; and / or, when R 3 "a 5-6 membered heteroaryl group having 1, 2 or 3 heteroatoms independently selected from N, O and S", wherein the 5-6 membered heteroaryl group is 4. The method for preparing the compound of formula I according to claim 2, wherein: When R 1 For one or more R 11 When the substituted 6-10 membered aryl group or the 6-10 membered aryl group is a phenyl group, the R 11 Independently located at the ortho, para or meta position of the connecting chain connected to the 2-carbon atom; and / or, when R 1 To be multiple R 11 In the case of a substituted 6-10 membered aryl group, the plurality is two or three; and / or, when R 1 To be an R 11 When the 6-10 membered aryl group is substituted, the substituted aryl group is replaced by an R 11 The substituted 6-10 membered aryl group is and / or, when R 3 For one or more R 31 When the substituted 6-10 membered aryl group or the 6-10 membered aryl group is a phenyl group, the R 31 independently located at the ortho, para or meta position of the connecting chain connected to the carbon atom of 1; and / or, when R 3 To be multiple R 31 In the case of a substituted 6-10 membered aryl group, the plurality is two or three; and / or, when R 3 To be an R 31 When the 6-10 membered aryl group is substituted, the substituted aryl group is replaced by an R 31 The substituted 6-10 membered aryl group is 5. The method for preparing the compound of formula I according to claim 2, wherein: R 4 is a 6-10 membered aromatic group; and / or, R 11 are independently halogen, C1-C6 alkyl or C1-C6 alkoxy; and / or, R 1 is a 6-10 membered aromatic group or is replaced by one or more R 11 substituted 6-10 membered aryl; and / or, when R 1 is a 6-10 membered aromatic group or is replaced by one or more R 11 When the substituted 6-10 membered aryl group is a phenyl group; and / or, R 3 is a 6-10 membered aromatic group or is replaced by one or more R 31 substituted 6-10 membered aryl; and / or, R 31 is halogen, C1-C6 alkyl or C1-C6 alkoxy; and / or, when R 3 is a 6-10 membered aromatic group or is replaced by one or more R 31 In the case of a substituted 6-10 membered aryl group, the 6-10 membered aryl group is a phenyl group.

6. The method for preparing the compound of formula I according to claim 5, wherein R 4 is phenyl; and / or, when R 1 For one or more R 11 When the substituted 6-10 membered aryl group is a phenyl group, the R 11 Independently located at the para or meta position of the connecting chain connected to the 2-carbon atom; and / or, when R 3 For one or more R 31 When the substituted 6-10 membered aryl group is a phenyl group, the R 31 Independently located at the para or meta position of the connecting chain connected to the carbon atom 1.

7. The method for preparing the compound of formula I according to claim 6, wherein: When R 1 For one or more R 11 When the substituted 6-10 membered aryl group is a phenyl group, the R 11 independently located in the para position of the connecting chain connected to the 2-carbon atom; and / or, when R 3 For one or more R 31 When the substituted 6-10 membered aryl group is a phenyl group, the R 31 Independently located in the para position of the connecting chain connected to the carbon atom of 1.

8. The method for preparing the compound of formula I according to any one of claims 1 to 7, wherein: The compound shown in Formula I is any of the following: Option 1: R 4 is a 6-10 membered aromatic group; R 11 are independently halogen, C1-C6 alkyl or C1-C6 alkoxy; Option 2: R 2 is methyl; R 4 is a 6-10 membered aromatic group; R 11 are independently halogen, C1-C6 alkyl or C1-C6 alkoxy; When R 1 is a 6-10 membered aromatic group or is replaced by one or more R 11 When the substituted 6-10 membered aryl group is a phenyl group; When R 1 When it is a "5-6 membered heteroaryl group having 1, 2 or 3 heteroatoms independently selected from N, O and S", the 5-6 membered heteroaryl group is furyl; Option 3: R 2 is methyl; R 4 is a 6-10 membered aromatic group; R 11 are independently halogen, C1-C6 alkyl or C1-C6 alkoxy; When R 1 is a 6-10 membered aromatic group or is replaced by one or more R 11 When the substituted 6-10 membered aryl group is a phenyl group; When R 1 When it is a "5-6 membered heteroaryl group having 1, 2 or 3 heteroatoms independently selected from N, O and S", the 5-6 membered heteroaryl group is furyl; When R 1 For one or more R 11 When the substituted 6-10 membered aryl group or the 6-10 membered aryl group is a phenyl group, the R 11 Independently located at the para or meta position of the connecting chain connected to the 2-carbon atom; When R 3 For one or more R 31 When the substituted 6-10 membered aryl group or the 6-10 membered aryl group is a phenyl group, the R 31 Independently located at the para or meta position of the connecting chain connected to the carbon atom of 1; Option 4: R 2 is methyl; R 4 is a 6-10 membered aromatic group; R 11 are independently halogen, C1-C6 alkyl or C1-C6 alkoxy; When R 1 is a 6-10 membered aromatic group or is replaced by one or more R 11 When the substituted 6-10 membered aryl group is a phenyl group; When R 1 When it is a "5-6 membered heteroaryl group having 1, 2 or 3 heteroatoms independently selected from N, O and S", the 5-6 membered heteroaryl group is furyl; When R 1 For one or more R 11 When the substituted 6-10 membered aryl group or the 6-10 membered aryl group is a phenyl group, the R 11 Independently located at the para or meta position of the connecting chain connected to the 2-carbon atom; R 3 is a 6-10 membered aromatic group or is replaced by one or more R 31 substituted 6-10 membered aryl; R 31 is halogen, C1-C6 alkyl or C1-C6 alkoxy; When R 3 For one or more R 31 When the substituted 6-10 membered aryl group or the 6-10 membered aryl group is a phenyl group, the R 31 Independently located at the para or meta position of the connecting chain connected to the carbon atom 1.

9. The method for preparing the compound of formula I according to claim 8, wherein: The compound shown in Formula I is any of the following: Option 1: R 4 is phenyl; R 11 are independently halogen, C1-C6 alkyl or C1-C6 alkoxy; Option 2: R 2 is methyl; R 4 is phenyl; R 11 are independently halogen, C1-C6 alkyl or C1-C6 alkoxy; When R 1 is a 6-10 membered aromatic group or is replaced by one or more R 11 When the substituted 6-10 membered aryl group is a phenyl group; When R 1 When it is a "5-6 membered heteroaryl group having 1, 2 or 3 heteroatoms independently selected from N, O and S", the 5-6 membered heteroaryl group is furyl; Option 3: R 2 is methyl; R 4 is phenyl; R 11 are independently halogen, C1-C6 alkyl or C1-C6 alkoxy; When R 1 is a 6-10 membered aromatic group or is replaced by one or more R 11 When the substituted 6-10 membered aryl group is a phenyl group; When R 1 When it is a "5-6 membered heteroaryl group having 1, 2 or 3 heteroatoms independently selected from N, O and S", the 5-6 membered heteroaryl group is furyl; When R 1 For one or more R 11 When the substituted 6-10 membered aryl group or the 6-10 membered aryl group is a phenyl group, the R 11 independently located in the para position of the connecting chain connected to the 2-carbon atom; When R 3 For one or more R 31 When the substituted 6-10 membered aryl group or the 6-10 membered aryl group is a phenyl group, the R 31 independently located in the para position of the connecting chain connected to the carbon atom of 1; Option 4: R 2 is methyl; R 4 is phenyl; R 11 are independently halogen, C1-C6 alkyl or C1-C6 alkoxy; When R 1 is a 6-10 membered aromatic group or is replaced by one or more R 11 When the substituted 6-10 membered aryl group is a phenyl group; When R 1 When it is a "5-6 membered heteroaryl group having 1, 2 or 3 heteroatoms independently selected from N, O and S", the 5-6 membered heteroaryl group is furyl; When R 1 For one or more R 11 When the substituted 6-10 membered aryl group or the 6-10 membered aryl group is a phenyl group, the R 11 independently located in the para position of the connecting chain connected to the 2-carbon atom; R 3 is a 6-10 membered aromatic group or is replaced by one or more R 31 substituted 6-10 membered aryl; R 31 is halogen, C1-C6 alkyl or C1-C6 alkoxy; When R 3 For one or more R 31 When the substituted 6-10 membered aryl group or the 6-10 membered aryl group is a phenyl group, the R 31 Independently located in the para position of the connecting chain connected to the carbon atom of 1.

10. The method for preparing the compound of formula I according to claim 1, wherein: The compound as shown in formula I is selected from the following group or its enantiomers:

11. The method for preparing the compound of formula I according to claim 1, wherein: When R A and R A’ When they are each independently "phenyl substituted by one or more C1-C6 alkyl groups", the C1-C6 alkyl group is a C1-C3 alkyl group; and / or, when R A and R A’ When each of the above is independently a "phenyl group substituted by a plurality of C1-C6 alkyl groups", the plurality is two or three; and / or, when R B and R B’ When they are independently "a 6-10 membered aryl group substituted by one or more C1-C6 alkyl groups", the C1-C6 alkyl group is a C1-C3 alkyl group; and / or, when R B and R B’ When each of the above is independently a "6-10 membered aryl group substituted by one or more C1-C6 alkyl groups", the 6-10 membered aryl group is a phenyl group or a naphthyl group; and / or, when R B and R B’ When each of the groups is independently a "6-10 membered aryl group substituted by a plurality of C1-C6 alkyl groups", the plurality is two or three; and / or, when R B and R B’ When they are independently 6-10 membered aryl groups, the 6-10 membered aryl groups are phenyl or naphthyl; And / or, in the catalytic reaction, the reaction temperature is 0°C-30°C; And / or, in the catalytic reaction, the molar ratio of the strong base to the compound represented by Formula III is 1:1 to 2:1; And / or, in the catalytic reaction, the molar ratio of the base to the compound represented by Formula III is 0.01:1 to 0.1:1; And / or, in the catalytic reaction, the molar ratio of the compound represented by Formula III to the compound represented by Formula II is 1:1 to 2:1; And / or, in the catalytic reaction, the molar ratio of the ligand to the compound represented by Formula III is 0.005:1 to 0.25:1; And / or, in the catalytic reaction, the molar ratio of the catalyst to the compound represented by Formula III is 0.005:1 to 0.25:1; And / or, in the catalytic reaction, the concentration of the compound represented by Formula III in the solvent is 0.05 mol / L to 0.5 mol / L; And / or, in the catalytic reaction, the reaction time is 1 hour to 14 hours; And / or, the preparation method of the compound as shown in Formula I further comprises post-treatment, and the post-treatment comprises the following steps: quenching the reaction, and isolating and purifying to obtain the compound as shown in Formula I.

12. The method for preparing the compound of formula I according to claim 11, wherein: When R A and R A’ When they are each independently "phenyl substituted by one or more C1-C6 alkyl groups", the C1-C6 alkyl group is methyl or isopropyl; and / or, when R A and R A’ When each of them is independently "phenyl substituted by multiple C1-C6 alkyl groups", the "phenyl substituted by multiple C1-C6 alkyl groups" is and / or, when R B and R B’ When they are each independently "a 6-10 membered aryl group substituted by one or more C1-C6 alkyl groups", the C1-C6 alkyl group is a methyl group; and / or, when R B and R B’ When each of them is independently a "6-10 membered aryl group substituted by a C1-C6 alkyl group", the "6-10 membered aryl group substituted by a C1-C6 alkyl group" is and / or, when R B and R B’ When they are independently 6-10 membered aryl groups, the 6-10 membered aryl groups are And / or, in the catalytic reaction, the solvent is one or more of an aromatic hydrocarbon solvent, an alkane solvent, and an ether solvent; the aromatic hydrocarbon solvent is toluene, xylene, or mesitylene, the alkane solvent is n-hexane, and the ether solvent is 1,4-dioxane, tetrahydrofuran, or diethyl ether; And / or, in the catalytic reaction, the molar ratio of the base to the compound represented by Formula III is 0.0625:1; And / or, in the catalytic reaction, the molar ratio of the ligand to the compound represented by Formula III is 0.025:1; And / or, in the catalytic reaction, the molar ratio of the catalyst to the compound represented by Formula III is 0.0125:1; And / or, in the catalytic reaction, the concentration of the compound represented by Formula III in the solvent is 0.09 mol / L or 0.17 mol / L.

13. The method for preparing the compound of formula I according to claim 12, wherein: The ligand is any of the following structures:

14. The method for preparing the compound of formula I according to claim 13, wherein: The ligand is any of the following structures:

15. Use of the method for preparing a compound of formula I according to any one of claims 1 to 14 in the preparation of a tertiary amine, the method comprising the following steps: subjecting the compound of formula I to a reduction reaction as shown below in a solvent in the presence of hydrogen and a catalyst to obtain a compound of formula IV; The application of the method for preparing the compound as shown in Formula I in the preparation of a tertiary amine further comprises a method for preparing the compound as shown in Formula I, comprising the following steps: Step 1: In a solvent, the compound represented by Formula III undergoes a hydrogen extraction reaction with a strong base to obtain a mixture A; Step 2: In the presence of a base, a catalyst, and a ligand, the mixture A is subjected to a catalytic reaction with the compound shown in Formula II to obtain the compound shown in Formula I; in, R 1 、R 2 、R 3 and R 4 The definition as set forth in any one of claims 1 to 10; The conditions of the preparation method of the compound shown in Formula I are as described in any one of claims 1 or 11 to 14.

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