Method for preparing chiral amine through asymmetric hydrogenation of aromatic imine

Abstract

The invention provides a method for preparing chiral amine by catalyzing asymmetric hydrogenation of high-steric-hindrance aromatic imine through iridium / chiral bidentate phosphoramidite ester ligands. According to the method, iridium precursors and ligands are easy to obtain, reaction conditions are mild, operation is easy, target chiral amine compounds can be obtained with high yield and high stereoselectivity, and continuous large-scale preparation can be achieved. The catalyst system is high in activity, the molar ratio of imine to the catalyst can reach 1000000: 1, and the catalyst has a very good industrial application prospect.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and specifically relates to an asymmetric hydrogenation method of highly hindered imines catalyzed by iridium / chiral bidentate phosphinamide ester ligands. The method can be used to obtain a series of highly hindered chiral aromatic amines with high efficiency, high yield and high stereoselectivity. Background Art

[0002] Asymmetric catalytic hydrogenation is the most direct and economical method for synthesizing chiral compounds. Among them, chiral amine compounds are very important organic intermediates that can be used to synthesize chiral drugs and natural compounds. In particular, highly hindered chiral aromatic amines are key precursors of chiral pesticides (S)-s-isopropylamine and (S)-metalaxyl. Asymmetric hydrogenation of imines is undoubtedly the simplest and most efficient method for synthesizing chiral amines. Therefore, this method has made great progress in recent years [(a) Nan, L.–F.; Chen, X.–S.; Hu, X.-P. Org. Biomol. Chem., 2022, 20, 8420–8424; (b) A. Cabré, X. Verdaguer and A. Riera, Chem. Rev., 2022, 122, 269; (c) Amelia K. Gilio, Thomas W.

[0003] Thorpe, Nicholas Turner and Gideon Grogan. Chem. Sci., 2022, 13, 4697–4713; (d) Y. Tian, ​​L. Hu, YZ Wang, X. Zhang and Q. Yin, Org. Chem. Front., 2021, 8, 2328; (e) Qing-Li, Chuan-Jin Hou, Xiao-Ning Liu, De-Zhi Huang, Yan-Jun Liu, Rui-Feng Yang, Xiang-Ping Hu. RSC Adv. 2015, 5, 13702-13708]. These catalytic systems have problems such as harsh reaction conditions, low catalyst activity and large dosage, and narrow substrate application range. Therefore, it is of great significance to develop asymmetric hydrogenation methods for highly hindered imines with high activity, high stereoselectivity, and wide substrate application range. Especially now that people have higher and higher requirements for environmental protection, it is urgent to explore and develop new methods for synthesizing green pesticides. Summary of the invention

[0004] The purpose of the present invention is to provide an iridium / chiral bidentate phosphinamide ester ligand-catalyzed asymmetric hydrogenation method for highly hindered imines, and to efficiently synthesize a series of chiral aromatic amines. The method is clean and environmentally friendly, the catalyst is easy to prepare, and has high stereoselectivity and activity.

[0005] The present invention provides an iridium / chiral bidentate phosphinamide ester ligand-catalyzed imine asymmetric hydrogenation synthesis method, which utilizes metal iridium salt and chiral bidentate phosphinamide ester ligand to generate iridium catalyst in situ, and under the action of additives, the substrate highly hindered aromatic imine undergoes asymmetric hydrogenation reaction to obtain chiral aromatic amine with high yield and high stereoselectivity. The specific steps are as follows:

[0006] In a glove box, iridium and chiral bidentate phosphinamide ester ligands are dissolved in a solvent, stirred at room temperature for 30-60 minutes, added to the solvent of the substrate imine, added additives, placed in a high-pressure reactor, and taken out of the glove box. The autoclave is replaced with hydrogen three times, and then hydrogen is introduced to 20-100 bar, reacted at 20-100 ° C for 1-24 hours, hydrogen is slowly released, and the solvent is removed by column chromatography to obtain the product. The general formula is as follows:

[0007]

[0008] The imine (I) and chiral amine compound (II) have the following structures:

[0009]

[0010] Wherein: R1 is Cl~C40 alkyl such as CH3, CH3CH2, etc., C3~C12 cycloalkyl such as cyclopentyl, cyclohexyl, etc., or Cl~C10 alkyl containing one or more functional groups of N, S, O, P such as methoxymethyl, ethoxymethyl, etc., or C3~C10 cycloalkyl containing one or more functional groups of N, S, O, P such as 2-tetrahydrofuranyl, 4-tetrahydrofuranyl, etc.; or aryl such as C6~C30 containing or not containing N, S, O, P, etc. Aromatic groups with functional groups such as phenyl, 4-methoxyphenyl, etc.; or ester groups such as COOCH3, COOCH2CH3, etc.; R2 is H, alkyl or aryl within Cl~C40; Ar is 2,6-disubstituted, 2,4,6-trisubstituted aryl, etc., aromatic groups with or without N, S, O, P functional groups within C6~C30, such as 2,6-dimethylphenyl, 2,4,6-trimethylphenyl, 2-methyl-6-ethylphenyl, 2,4-dimethyl-3-thienyl, etc. .

[0011] The chiral bidentate phosphinamide ester ligand L has the following structure:

[0012]

[0013] In the formula, Ar is one of phenyl and substituted phenyl, naphthyl and substituted naphthyl, and the substituents on the phenyl and naphthyl are selected from one or more of C1-C40 alkoxy, C1-C40 alkyl, nitro, cyano, halogen (F, Cl, Br, I), and the number of substituents is 1-5.

[0014] R1 is one of hydrogen, C1-C40 alkyl, phenyl and substituted phenyl, and the substituent on the phenyl is one or more of C1-C40 alkoxy, C1-C40 alkyl, nitro, cyano, halogen (F, Cl, Br, I), and the number of substituents is 1-5.

[0015] R2 is one of hydrogen, C1~C40 alkyl, phenyl and substituted phenyl, and the substituent on the phenyl is one or more of C1~C40 alkoxy, C1~C40 alkyl, nitro, cyano, halogen (F, Cl, Br, I), and the number of substituents is 1-5.

[0016] The X group is a chiral or achiral alkyl group. The C1 in the figure below is connected to the O in L. The specific structure is as follows

[0017]

[0018] wherein n is an integer of 0-10, Ar is phenyl and substituted phenyl, naphthyl and substituted naphthyl, a five-membered or six-membered heterocyclic aromatic group containing one or more oxygen, sulfur or nitrogen atoms, and the substituent on the phenyl or the substituent on the naphthyl is a C1-C40 alkyl, a C1-C40 alkoxy, a halogen, a nitro, an ester group, or a cyano group;

[0019] The X group is also 1,2-phenyl and substituted 1,2-phenyl, chiral or achiral 1,1-biphenyl and substituted 1,1-biphenyl, chiral or achiral 1,1-binaphthyl and substituted 1,1-binaphthyl, chiral or achiral 1,1-tetrahydronaphthyl and substituted 1,1-tetrahydronaphthyl, and C1 in the figure below is connected to O in L, respectively. The specific structure is as follows:

[0020]

[0021] R3 and R4 are respectively the same or different groups, and are one or more of hydrogen, C1-C40 alkoxy, C1-C40 alkyl, phenyl and substituted phenyl, naphthyl and substituted naphthyl, halogen (F, Cl, Br, I), etc.; the substituents on phenyl and naphthyl are respectively selected from one or more of C1-C40 alkoxy, C1-C40 alkyl, nitro, cyano, halogen (F, Cl, Br, I), and the number of substituents is 1-5.

[0022] The iridium is one of [Ir(COD)Cl]2, Ir(COD)2BARF or Ir(COD)2BF4. Preferably, it is [Ir(COD)Cl]2. The iridium concentration in the reaction solution is 0.0001-0.01 mol / L

[0023] The reaction medium is at least one of toluene, benzene, methanol, ethanol, isopropanol, dichloromethane, dichloroethane, carbon tetrachloride, ethyl acetate, ether, tetrahydrofuran, dimethyl sulfoxide or N,N-dimethylformamide, preferably dichloromethane or 1,2-dichloroethane.

[0024] The additive is one or more of various iodides such as iodine, potassium iodide, sodium iodide, zinc iodide, tetrabutylammonium iodide, phenyltributylammonium iodide, dioctyldimethylammonium iodide, hexadecyltrimethylammonium iodide, N-iodosuccinimide, iodobenzene, and various acids such as camphorsulfonic acid, tartaric acid, trifluoroacetic acid, etc.; the molar ratio of the substrate imine to the additive is between 100-100000:1, preferably 500-5000:1.

[0025] The molar ratio of iridium to the chiral bidentate phosphinamide ester ligand is 1:1-5, preferably 1:1-1:2.5.

[0026] The molar ratio of the substrate imine to iridium is between 100-1,000,000:1, preferably 100,000-500,000:1.

[0027] The catalytic reaction conditions are:

[0028] Temperature: room temperature - 120°C, preferably 100°C;

[0029] Pressure: 10-100 bar, preferably 50 bar;

[0030] Time: 1-24 hours, preferably 12 hours.

[0031] The iridium precursor and ligand of this method are easily available, the reaction conditions are mild, the operation is simple, and the target chiral amine compound can be obtained with high yield and high stereoselectivity, and can be prepared continuously on a large scale. The catalyst system is highly active, and the molar ratio of imine to catalyst can reach 1000000:1, which has very good industrial application prospects.

[0032] The present invention has the following advantages:

[0033] 1. Raw materials are easily available

[0034] 2. High reaction activity, mild reaction conditions, high stereoselectivity and high yield.

[0035] 3. The ligand preparation is simple and the catalyst dosage is small. The whole process is suitable for industrial production. DETAILED DESCRIPTION

[0036] The following examples will further illustrate the present invention, but are not intended to limit the present invention. Nuclear magnetic resonance was measured by a Bruker 400 nuclear magnetic resonance instrument, gas chromatography (GC) was measured by an Agilent 7820 chromatograph, and high performance liquid chromatography (HPLC) was measured by an Agilent 1100 series high performance liquid chromatograph.

[0037] Example 1

[0038] The structural formulas of L-1, I-1, and II-1 are as follows:

[0039]

[0040] In a glove box filled with nitrogen protection, [Ir(COD)Cl]2 (0.0025 mmol, 0.5 mol% relative to the reaction substrate) and chiral bidentate phosphinamide ester ligand L-1) (0.0055 mmol, 1.1 mol% relative to the reaction substrate) were dissolved in dichloromethane (1.0 mL), stirred at room temperature for 30 minutes, added to a solvent of dichloromethane (1.0 mL) containing substrate (E)-2,6-dimethyl-N-(1-phenylethylidene)aniline I-1 (0.5 mmol), added additive KI (0.001 mol, 0.2 mol% relative to the reaction substrate), placed in a high-pressure reactor, and taken out of the glove box. The autoclave was replaced with hydrogen three times, and then hydrogen was introduced to 20 bar. The reaction was carried out at 50°C for 10 hours, and hydrogen was slowly released. The solvent was removed and the product 2,6-dimethyl-N-(l-phenylethyl)aniline II-1 was obtained by column chromatography with a yield of 90%, a slightly yellow liquid, and 90% ee by HPLC analysis. 1 H NMR (400MHz, CDCl3): δ7.43–7.23(m,5H),7.00(d,J=7.4Hz,2H),6.89–6.78(m,1H), 4.37(qd,J=6.7,2.2Hz,1H),3.00(s,1H),2.22(d,J=1.8Hz,6H),1.61–1.49(m,3H);

[0041] Example 2

[0042] The structural formula of L-2 is as follows:

[0043]

[0044] The chiral bidentate phosphinamide ester ligand L-1 in Example 1 was replaced with an equimolar amount of L-2, and the other conditions and processes remained unchanged. Finally, the product 2,6-dimethyl-N-(l-phenylethyl)aniline II-1 was obtained by column chromatography with a yield of 91% and an ee of 96% by HPLC analysis.

[0045] Example 3

[0046] The structural formula of L-3 is as follows:

[0047]

[0048] The chiral bidentate phosphinamide ester ligand L-1 in Example 1 was replaced with an equimolar amount of L-3, and the other conditions and processes remained unchanged. Finally, the product 2,6-dimethyl-N-(l-phenylethyl)aniline II-1 was obtained by column chromatography with a yield of 95% and an ee of 90% by HPLC analysis.

[0049] Example 4

[0050] The structural formula of L-4 is as follows:

[0051]

[0052] The chiral bidentate phosphinamide ester ligand L-1 in Example 1 was replaced with an equimolar amount of L-4, and the other conditions and processes remained unchanged. Finally, the product 2,6-dimethyl-N-(l-phenylethyl)aniline II-1 was obtained by column chromatography with a yield of 93% and an HPLC analysis of 89% ee.

[0053] Example 5

[0054] The structural formula of L-5 is as follows:

[0055]

[0056] The chiral bidentate phosphinamide ester ligand L-1 in Example 1 was replaced with an equimolar amount of L-5, and the other conditions and processes remained unchanged. Finally, the product 2,6-dimethyl-N-(l-phenylethyl)aniline II-1 was obtained by column chromatography with a yield of 96% and an HPLC analysis of 97% ee.

[0057] Example 6

[0058] The structural formula of L-6 is as follows:

[0059]

[0060] The chiral bidentate phosphinamide ester ligand L-1 in Example 1 was replaced with an equimolar amount of L-6, while the conditions and process remained unchanged. Finally, the product 2,6-dimethyl N-(l-phenylethyl)aniline II-1 was obtained by column chromatography with a yield of 96% and an HPLC analysis of 94% ee.

[0061] Example 7

[0062] The KI in Example 6 was replaced by I2 (0.001 mol, 0.2 mol% relative to the reaction substrate), and the rest (process and conditions) were the same as Example 6. Finally, column chromatography gave the product 2,6-dimethyl-N-(l-phenylethyl)aniline II-1 with a yield of 95% and an HPLC analysis of 97% ee.

[0063] Example 8

[0064] The dichloromethane in Example 6 was replaced by an equal volume of dichloroethane, and the rest (process and conditions) were the same as Example 6. Finally, column chromatography gave the product 2,6-dimethyl-N-(l-phenylethyl)aniline II-1 with a yield of 95% and an HPLC analysis of 96% ee.

[0065] Example 9

[0066] The hydrogen pressure of 20 bar in Example 6 was changed to 50 bar, and the rest (process and conditions) were the same as Example 6. Finally, column chromatography gave the product 2,6-dimethyl-N-(l-phenylethyl)aniline II-1 with a yield of 98% and an HPLC analysis of 98% ee.

[0067] Example 10

[0068] The ratio of the substrate (unchanged amount) and iridium (i.e., [Ir(COD)Cl]2 was adjusted to (0.0000025 mmol, 0.0005 mol% relative to the reaction substrate), the chiral bidentate phosphinamide ester ligand L-6 was 0.0000055 mmol, 0.0011 mol% relative to the reaction substrate) in Example 9 was changed to 100000 / 1, and the rest (process and conditions) were the same as Example 9. Finally, the product 2,6-dimethyl-N-(l-phenylethyl)aniline II-1 was obtained by column chromatography with a yield of 98% and an ee of 98% by HPLC analysis.

[0069] Embodiment 11

[0070]

[0071] The substrate in Example 10 was replaced with an equimolar amount of N-(2,6-dimethylphenyl)-3-methylbutan-2-imine I-2, and the rest (process and conditions) were the same as Example 10. Finally, column chromatography was performed to obtain the product N-(3-methylbutan-2-yl)-2,6-dimethylaniline II-2 with a yield of 92% and a colorless oily liquid. GC analysis showed 74% ee. 1H NMR (400MHz, CDCl3): δ6.89 (d, J=7.5Hz, 2H), 6.69 (t, J=7.4Hz, 1H), 3.10 (m, J=6 .5,4.8Hz,1H),2.42(s,1H),2.18(s,6H),1.81–1.59(m,1H),1.01–0.81(m,9H);

[0072] Example 12

[0073]

[0074] The substrate in Example 10 was replaced with an equal molar amount of 2-ethyl-N-(1-methoxy-2-propyl)-6-methylaniline I-3, and the rest of the process and conditions were the same as Example 10. Finally, column chromatography was performed to obtain the product 2-ethyl-N-(1-methoxy-2-propyl)-6-methylaniline II-3, with a yield of 99%, a colorless oily liquid, and an HPLC analysis of 86% ee. ). 1 H NMR (400MHz, CDCl3): δ7.11–6.97(m,2H),6.88(t,J=7.5Hz,1H),3.36(m,7H),2.67(q,J=7.5Hz,2H),2.30(s,3H),1.33–1.10(m,6H);

[0075] Example 13

[0076]

[0077] The substrate in Example 10 was replaced with an equal mole of methyl 2-(2,6-dimethylphenylimino)propionate I-4, and the rest of the process and conditions were the same as in Example 10. Finally, column chromatography was performed to obtain the product methyl 2-(2,6-dimethylphenylimino)propionate II-4, with a yield of 97%, a slightly yellow oily liquid, and 91% ee by HPLC analysis. ). 1 H NMR (400MHz, CDCl3): δ6.96 (d, J=7.5Hz, 2H), 6.80 (t, J=7.5Hz, 1H), 4.06–3.92 (m,1H),3.76(d,J=5.0Hz,1H),3.66(s,3H),2.30(s,6H),1.38(d,J=7.0Hz,3H);

[0078] Embodiment 14

[0079]

[0080] The substrate in Example 9 was replaced with an equimolar amount of (E)-N-(2,6-dimethylphenyl)-1-(3-nitrophenyl)ethane-1-imine I-5, and the rest of the process and conditions were the same as in Example 9. Finally, column chromatography was performed to obtain the product N-[1-(3-nitrophenyl)ethyl]-2,6-dimethylaniline II-5 with a yield of 99%, a yellow liquid, and 99% ee by HPLC analysis. ). 1 H NMR (400MHz, CDCl3): δ8.23(t,J=1.9Hz,1H),8.08(ddd,J=8.2,2.2,1.0Hz,1H),7.62(t,J=9.8Hz,1H),7.44(t,J=7.9Hz ,1H),6.95(d,J=7.5Hz,2H),6.85–6.76(m,1H),4.41(q,J=6.7Hz,1H),3.22(s,1H),2.17(s,6H),1.56(d,J=6.8Hz,3H);

[0081] Embodiment 15

[0082]

[0083] The substrate in Example 9 was replaced with an equimolar amount of (E)-N-(2-ethyl-6-methylphenyl)-1-phenylethane-1-imine I-6, and the rest of the process and conditions were the same as in Example 9. Finally, column chromatography was performed to obtain the product N-(1-phenylethyl)-2-ethyl-6-methylaniline II-6, with a yield of 99%, a colorless oily liquid, and an HPLC analysis of 97% ee. ). 1 H NMR (400MHz, CDCl3): δ7.45–7.21(m,5H),7.03(dd,J=14.1,7.4Hz,2H),6.90(t,J=7.5Hz,1H),4.33(q,J= 6.7Hz,1H),3.24(s,1H),2.57(q,J=7.5Hz,2H),2.24(s,3H),1.55(d,J=6.8Hz,3H),1.22(t,J=7.6Hz,3H);

[0084] Example 16

[0085]

[0086] In Example 9, the substrate was changed to an equimolar amount of 1-(4-chlorophenyl)-N-(2,6-dimethylphenyl)ethane-1-imine I-7, and the rest of the process and conditions were the same as in Example 9. Finally, column chromatography was performed to obtain the product N-(1-(4-chlorophenyl)ethyl)-2,6-dimethylaniline II-7, with a yield of 99%, a slightly yellow liquid, and HPLC analysis showed 99% ee. ). 1H NMR (400MHz, CDCl3): δ7.31–7.13(m,4H),6.94(d,J=7.5Hz,2H),6.83–6.73(m ,1H),4.27(q,J=6.7Hz,1H),3.07(s,1H),2.15(s,6H),1.48(d,J=6.8Hz,3H);

[0087] The above-mentioned implementation cases only express the implementation methods of the present invention, but they cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that for those skilled in the art, several modifications and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention.

Claims

1. A method for preparing chiral amines by asymmetric hydrogenation of aromatic imines, characterized in that : With aromatic imine as substrate, in the presence of hydrogen in a reaction solvent, under the action of iridium / chiral bidentate phosphinamide ester ligand catalyst, aromatic imine (Ⅰ) undergoes asymmetric hydrogenation to obtain chiral amine compound (Ⅱ); The imine (I) and chiral amine compound (II) have the following structures: In the formula: R1 is a Cl~C40 alkyl group (such as one or more of CH3, CH3CH2, etc.), a C3~C12 cycloalkyl group (such as one or more of cyclopentyl, cyclohexyl, etc.), or a Cl~C10 alkyl group containing one or more of N, S, O, P functional groups (such as one or more of methoxymethyl, ethoxymethyl, etc.), or a C3~C10 cycloalkyl group containing one or more of N, S, O, P functional groups (such as one or more of 2-tetrahydrofuranyl, 4-tetrahydrofuranyl, etc.); or a C6~C30 aryl group, such as an aromatic group in C6~C30 that may or may not contain one or more of N, S, O, P, etc. (such as one or more of phenyl, 4-methoxyphenyl, etc.), or a C2~C20 ester group (such as one or more of COOCH3, COOCH2CH3, etc.); R2 is H, one or more of a Cl-C40 alkyl group or a C6-C40 aryl group; Ar is one or more of 2,6-disubstituted or 2,4,6-trisubstituted C6-C30 aromatic groups, and other aromatic groups in C6-C30 that may or may not contain one or more functional groups of N, S, O, P, etc. (e.g., one or more of 2,6-dimethylphenyl, 2,4,6-trimethylphenyl, 2-methyl-6-ethylphenyl, 2,4-dimethyl-3-thienyl, etc.).

2. The method according to claim 1, characterized in that: The specific steps are as follows: under nitrogen protection, iridium and chiral bidentate phosphinamide ester ligands are dissolved in a solvent, stirred at room temperature for 30-60 minutes, added to a solvent containing substrate imine, an additive is added, and the mixture is placed in a high-pressure reactor; the atmosphere in the autoclave is replaced with hydrogen, and then hydrogen is introduced to 20-100 bar, reacted at 20-100° C. for 1-24 hours, hydrogen is released, the solvent is removed, and the product is separated; the specific reaction formula is as follows:

3. The method according to claim 2, characterized in that: The chiral bidentate phosphinamidate ligand has one or more of the following structures: Wherein Ar is one or more of phenyl and substituted phenyl, naphthyl and substituted naphthyl, and the substituents on phenyl and naphthyl are selected from one or more of C1-C40 alkoxy, C1-C40 alkyl, nitro, cyano, halogen (F, Cl, Br, I), and the number of substituents is 1-5; R1 is one of hydrogen, C1-C40 alkyl, phenyl and substituted phenyl, and the substituent on the phenyl is one or more of C1-C40 alkoxy, C1-C40 alkyl, nitro, cyano, halogen (F, Cl, Br, I), and the number of substituents is 1-5; R2 is one of hydrogen, C1-C40 alkyl, phenyl and substituted phenyl, and the substituent on the phenyl is one or more of C1-C40 alkoxy, C1-C40 alkyl, nitro, cyano, halogen (F, Cl, Br, I), and the number of substituents is 1-5; The X group is one or more of the following groups: Chiral or achiral alkyl, C1 in the figure below is connected to O in L, and the specific structure is one or more of the following: wherein n is an integer of 0-10, Ar is phenyl and substituted phenyl, naphthyl and substituted naphthyl, a five-membered or six-membered heterocyclic aromatic group containing one or more of one or two of oxygen, sulfur and nitrogen atoms, and the substituent on the phenyl or the substituent on the naphthyl is one or more of C1-C40 alkyl, C1-C40 alkoxy, halogen, nitro, ester or cyano; Alternatively, the X group may be one or more of 1,2-phenyl and substituted 1,2-phenyl, chiral or achiral 1,1-biphenyl and substituted 1,1-biphenyl, chiral or achiral 1,1-binaphthyl and substituted 1,1-binaphthyl, chiral or achiral 1,1-tetrahydronaphthyl and substituted 1,1-tetrahydronaphthyl, and C1 in the figure below is connected to O in L, respectively. The specific structure is as follows: R3 and R4 are the same or different groups, and are independently one or more of hydrogen, C1-C40 alkoxy, C1-C40 alkyl, phenyl and substituted phenyl, naphthyl and substituted naphthyl, halogen (F, Cl, Br, I), etc.; the substituents on the phenyl and naphthyl groups are selected from one or more of C1-C40 alkoxy, C1-C40 alkyl, nitro, cyano, halogen (F, Cl, Br, I), and the number of substituents is 1-5.

4. The method according to claim 2 or 3, characterized in that: The iridium is one or more of [Ir(COD)Cl]2, Ir(COD)2BARF or Ir(COD)2BF4.

5. The method according to claim 2, characterized in that: The additive is one or more of various iodides such as iodine, potassium iodide, sodium iodide, zinc iodide, tetrabutylammonium iodide, phenyltributylammonium iodide, dioctyldimethylammonium iodide, hexadecyltrimethylammonium iodide, N-iodosuccinimide, iodobenzene, and various acids such as camphorsulfonic acid, tartaric acid, trifluoroacetic acid, etc.; The molar ratio of the substrate imine to the additive is between 100-100000:1, preferably 100-50000:1, and more preferably 100-10000:

1.

6. The method according to claim 2, characterized in that: The solvent is one or more of toluene, benzene, methanol, ethanol, isopropanol, dichloromethane, dichloroethane, carbon tetrachloride, ethyl acetate, ether, tetrahydrofuran, dimethyl sulfoxide or N,N-dimethylformamide.

7. The method according to any one of claims 2 to 6, characterized in that: The iridium concentration in the reaction solution is 0.0001-0.01 mol / L, preferably 0.0002-0.01 mol / L, more preferably 0.0005-0.01 mol / L; The molar ratio of the chiral bidentate phosphinamide ester ligand to iridium is 1-5:1, preferably 1-4:1, more preferably 1.05-3:1; The molar ratio of the imine substrate to iridium is 100-1000000:1, preferably 100-8000000:1, and more preferably 100-600000:

1.

8. The method according to claim 2, characterized in that : The reaction conditions are controlled as follows: the hydrogen pressure is 20-100 bar, preferably 20-90 bar, more preferably 20-80 bar; The reaction temperature is 20-120°C, preferably 25-110°C, more preferably 25-100°C; The reaction time is 1-24 hours, preferably 2-20 hours, more preferably 2.5-20 hours.

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