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 an iridium / chiral bidentate phosphoramidite ester ligand. According to the method, the bidentate phosphoramidite ester ligand based on an achiral phosphine-amine skeleton is applied to asymmetric hydrogenation of iridium-catalyzed imine for the first time. The iridium precursor and ligand are easy to obtain, the reaction condition is mild, the operation is simple, the target chiral amine compound can be obtained with high yield and high stereoselectivity, and continuous large-scale preparation can be realized. The catalyst system is high in activity, the molar ratio of imine to the catalyst can reach 600000: 1, and the catalyst has a very good industrial application prospect.

Description

Technical Field

[0001] The present invention belongs to the field of organic synthesis, and particularly relates to a method for asymmetric hydrogenation of highly hindered imines catalyzed by iridium / chiral bidentate phosphonamidite ligands. The chiral bidentate phosphonamidite ligands have an achiral phosphine-amine backbone. A series of highly hindered chiral aromatic amines can be obtained with high efficiency, high yield and high stereoselectivity by using this method. Background Art

[0002] Asymmetric catalytic hydrogenation is one of the most direct and economical methods for synthesizing chiral compounds. Among them, chiral amine compounds are very important organic intermediates, which can be used to synthesize chiral drugs and natural compounds. In particular, highly hindered chiral aromatic amines are the key precursors of chiral pesticides (S)-S-metolachlor and (S)-metalaxyl. Asymmetric hydrogenation of imines is undoubtedly the simplest and most efficient method for synthesizing chiral amines. Our recent research has shown that iridium / chiral bidentate phosphonamidite catalysts exhibit excellent catalytic activity and selectivity in the asymmetric hydrogenation of imines [(a) Long-Fei Nan, Xiu-Shuai Chen, Hao Chen, Xin-Hu Hu, Xin-Hong Wang and Xiang-Ping Hu. Org. Biomol. Chem. 2022, 20, 8420-8424; (b) Chuan-Jin Hou, Ya-Hui Wang, Zhuo Zheng, Jie Xu, Xiang-Ping Hu. Org. Lett. 2012, 14, 3554-3557]. However, these chiral ligands are all based on chiral phosphine-amine backbones, which are difficult to synthesize and have high usage costs. Therefore, the present invention aims to report a method for asymmetric hydrogenation of imines catalyzed by iridium / chiral bidentate phosphonamidite ligands, which have an achiral phosphine-amine backbone, are simple to synthesize and have low costs. Summary of the Invention

[0003] The object of the present invention is to provide a method for asymmetric hydrogenation of imines catalyzed by iridium / chiral bidentate phosphonamidite ligands to efficiently synthesize a series of chiral aromatic amines. This method is clean and environmentally friendly. The chiral bidentate phosphonamidite ligands have an achiral phosphine-amine backbone, the catalyst is easy to prepare, and has high stereoselectivity and activity.

[0004] The present invention provides a method for synthesizing asymmetric hydrogenation of imines catalyzed by iridium / chiral bidentate phosphonamidite ligands. An iridium catalyst is in-situ generated by using a metal iridium salt and a chiral bidentate phosphonamidite ligand. Under the action of an additive, the substrate aromatic imine undergoes an asymmetric hydrogenation reaction to obtain chiral aromatic amines with high yield and high stereoselectivity. The specific steps are as follows:

[0005] In the glove box, dissolve iridium and the chiral bidentate phosphonamidite ligand in a solvent, stir at room temperature for 30 - 60 minutes, add it to the solvent of the substrate imine, add an additive, place it in a high-pressure reactor, and take it out of the glove box. Replace the high-pressure reactor with hydrogen 3 times, then introduce hydrogen to 20 - 100 bar, react at 20 - 100 °C for 1 - 24 hours, slowly release hydrogen, remove the solvent, and obtain the product by column chromatography. The general formula is as follows:

[0006]

[0007] The imine (Ⅰ) and the chiral amine compound (Ⅱ) have the following structures:

[0008]

[0009] In the formula: R 1 is a Cl - C40 alkyl group such as CH 3 , CH 3 CH 2 etc., a C3 - C12 cycloalkyl group such as cyclopentyl, cyclohexyl, etc., or a Cl - C10 alkyl group containing one or more functional groups of N, S, O, P such as methoxymethyl, ethoxymethyl, etc., or a C3 - C10 cycloalkyl group containing one or more functional groups of N, S, O, P such as 2 - tetrahydrofuranyl, 4 - tetrahydrofuranyl, etc.; or an aryl group, an aromatic group containing or not containing functional groups such as N, S, O, P within C6 - C30 such as phenyl, 4 - methoxyphenyl, etc.; or an ester group such as COOCH 3 , COOCH 2 CH 3 etc.; R 2 is H, an alkyl group or an aryl group within Cl - C40; Ar is a 2,6 - disubstituted, 2,4,6 - trisubstituted aryl group, etc., an aromatic group containing or not containing functional groups such as N, S, O, P within C6 - C30 such as 2,6 - dimethylphenyl, 2,4,6 - trimethylphenyl, 2 - methyl - 6 - ethylphenyl, 2,4 - dimethyl - 3 - thienyl, etc..

[0010] The chiral bidentate phosphonamidite ligand L has the following structure:

[0011]

[0012] R is one of hydrogen, a C1 - C40 alkyl group, phenyl and substituted phenyl, etc., and the substituents on the phenyl are one or more of a C1 - C40 alkoxy group, a C1 - C40 alkyl group, a nitro group, a cyano group, a halogen (F, Cl, Br, I), and the number of substituents is 1 - 5.

[0013] The X group is: a chiral or achiral alkyl group, C in the following formula 1Are respectively connected to the O in L, and the specific structure is as follows

[0014]

[0015] In the formula, n is an integer from 0 to 10, Ar is phenyl and substituted phenyl, naphthyl and substituted naphthyl, a five- or six-membered heteroaromatic group containing one or more oxygen, sulfur, or nitrogen atoms, and the substituents on the phenyl or naphthyl are respectively C1-C40 alkyl, C1-C40 alkoxy, halogen, nitro, ester group, or cyano;

[0016] 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-bitetrahydronaphthyl and substituted 1,1-bitetrahydronaphthyl, and C in the following formula 1 Are respectively connected to the O in L, and the specific structure is as follows:

[0017]

[0018] R 3 、R 4 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 the 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.

[0019] The iridium is [Ir(COD)Cl] 2 、Ir(COD) 2 BARF or Ir(COD) 2 BF 4 One of them. Preferably [Ir(COD)Cl] 2 , and the iridium concentration in the reaction solution is 0.0001-0.01 mol / L

[0020] 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. Preferably tetrahydrofuran and dichloromethane.

[0021] The additives described above are one or more of various iodides such as iodine, sodium iodide, potassium iodide, zinc iodide, tetrabutylammonium iodide, N-iodosuccinimide, dioctyldimethylammonium iodide, phenyltributylammonium iodide, cetyltrimethylammonium iodide, iodobenzene, etc., and various acids such as tartaric acid, camphorsulfonic acid, trifluoroacetic acid, etc.; the molar ratio of the substrate imine to the additive is between 100 - 100000:1, preferably 10 - 40000:1, more preferably 500 - 10000:1.

[0022] The molar ratio of the iridium to the chiral bidentate phosphinoamidite ligand is 1:1 - 5, preferably the molar ratio is 1:1 - 1:2.5.

[0023] The molar ratio of the substrate imine to the iridium is between 100 - 600000:1. Preferably, it is 100000 - 500000:1.

[0024] The catalytic reaction conditions are as follows:

[0025] Temperature: room temperature - 120 °C, preferably 80 °C;

[0026] Pressure: 10 - 100 bar, preferably 60 bar;

[0027] Time: 1 - 24 hours, preferably 10 hours.

[0028] This method first uses a bidentate phosphinoamidite ligand based on an achiral phosphine - amine backbone in the iridium - catalyzed asymmetric hydrogenation of imines. In this method, the iridium precursor and the ligand are easily available, the reaction conditions are mild, the operation is simple, the target chiral amine compound can be obtained in high yield and high stereoselectivity, and it can be continuously prepared on a large scale. The catalyst system has high activity, and the molar ratio of the imine to the catalyst can reach 600000:1, having very good industrial application prospects.

[0029] The present invention has the following advantages:

[0030] 1. The ligand used is applied in the iridium - catalyzed asymmetric hydrogenation of imines for the first time.

[0031] 2. The raw materials are easily available, the reaction activity is high, the reaction conditions are mild, the stereoselectivity is high, and the yield is high.

[0032] 3. The catalyst preparation is simple, the synthesis cost is low, and the catalyst dosage is small. The whole process is suitable for industrial production. Detailed implementation manners

[0033] The following examples will further illustrate the present invention, but do not limit the present invention thereby. Nuclear magnetic resonance was measured by a Bruker 400 nuclear magnetic resonance spectrometer, 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.

[0034] Example 1

[0035] The structural formulas of L-1, I-1, and II-1 are as follows:

[0036]

[0037] In a glove box filled with nitrogen protection, [Ir(COD)Cl] 2 (0.0025 mmol, 0.5 mol% relative to the reaction substrate) and the chiral bidentate phosphonamide ester ligand L-1) (0.0055 mmol, 1.1 mol% relative to the reaction substrate) were dissolved in tetrahydrofuran (1.0 mL), stirred at room temperature for 30 minutes, and added to a solvent of tetrahydrofuran (1.0 mL) containing the substrate (E)-2,6-dimethyl-N-(1-phenylethylidene)aniline I-1 (0.5 mmol). Additive NaI (0.001 mol, 0.2 mol% relative to the reaction substrate) was added, and it was placed in a high-pressure reactor and taken out of the glove box. The high-pressure reactor was purged with hydrogen 3 times, and then hydrogen was introduced to 30 bar, and the reaction was carried out at 80 °C for 8 hours. The hydrogen was released, the solvent was removed, and column chromatography (petroleum ether:ethyl acetate = 20 / 1) was used to obtain the product 2,6-dimethyl-N-(1-phenylethyl)aniline II-1 with a yield of 93%, a slightly yellow liquid, and 92% ee (optical purity (e.e. value)) by HPLC analysis. 1 1H NMR (400 MHz, CDCl 3 ): δ 7.43–7.23 (m, 5H), 7.00 (d, J = 7.4 Hz, 2H), 6.89–6.78 (m, 1H), 4.37 (qd, J = 6.7, 2.2 Hz, 1H), 3.00 (s, 1H), 2.22 (d, J = 1.8 Hz, 6H), 1.61–1.49 (m, 3H);

[0038] Example 2

[0039] The structural formula of L-2 is as follows:

[0040]

[0041] The procedure and conditions were the same as those in Example 1, except that the chiral bidentate phosphonamidite ligand L-1 in Example 1 was replaced with an equimolar amount of L-2, and the remaining conditions and procedures remained unchanged. Finally, the product 2,6-dimethyl-N-(1-phenylethyl)aniline II-1 was obtained by column chromatography in a 95% yield and with 93% ee as analyzed by HPLC.

[0042] Example 3

[0043] The structural formula of L-3 is as follows:

[0044]

[0045] The procedure and conditions were the same as those in Example 1, except that the chiral bidentate phosphonamidite ligand L-1 in Example 1 was replaced with an equimolar amount of L-3, and the remaining conditions and procedures remained unchanged. Finally, the product 2,6-dimethyl-N-(1-phenylethyl)aniline II-1 was obtained by column chromatography in a 95% yield and with 95% ee as analyzed by HPLC.

[0046] Example 4

[0047] The structural formula of L-4 is as follows:

[0048]

[0049] The procedure and conditions were the same as those in Example 1, except that the chiral bidentate phosphonamidite ligand L-1 in Example 1 was replaced with an equimolar amount of L-4, and the remaining conditions and procedures remained unchanged. Finally, the product 2,6-dimethyl-N-(1-phenylethyl)aniline II-1 was obtained by column chromatography in a 95% yield and with 94% ee as analyzed by HPLC.

[0050] Example 5

[0051] The structural formula of L-5 is as follows:

[0052]

[0053] The procedure and conditions were the same as those in Example 1, except that the chiral bidentate phosphonamidite ligand L-1 in Example 1 was replaced with an equimolar amount of L-5, and the remaining conditions and procedures remained unchanged. Finally, the product 2,6-dimethyl-N-(1-phenylethyl)aniline II-1 was obtained by column chromatography in a 93% yield and with 75% ee as analyzed by HPLC.

[0054] Example 6

[0055] The structural formula of L-6 is as follows:

[0056]

[0057] The procedure and conditions were the same as in Example 1, except that the chiral bidentate phosphonamidite ligand L-1 in Example 1 was replaced with an equimolar amount of L-6, and the remaining conditions and procedures remained unchanged. Finally, the product 2,6-dimethyl-N-(1-phenylethyl)aniline II-1 was obtained by column chromatography in 96% yield and 95% ee by HPLC analysis.

[0058] Example 7

[0059] The structural formula of L-7 is as follows:

[0060]

[0061] The procedure and conditions were the same as in Example 1, except that the chiral bidentate phosphonamidite ligand L-1 in Example 1 was replaced with an equimolar amount of L-7, and the remaining conditions and procedures remained unchanged. Finally, the product 2,6-dimethyl-N-(1-phenylethyl)aniline II-1 was obtained by column chromatography in 97% yield and 97% ee by HPLC analysis.

[0062] Example 8

[0063] The procedure and conditions were the same as in Example 7, except that NaI in Example 7 was replaced with KI (0.001 mol, 0.2 mol% relative to the reaction substrate), and the rest was the same as (the procedure and conditions) in Example 7. Finally, the product 2,6-dimethyl-N-(1-phenylethyl)aniline II-1 was obtained by column chromatography in 93% yield and 97% ee by HPLC analysis.

[0064] Example 9

[0065] The procedure and conditions were the same as in Example 7, except that NaI in Example 7 was replaced with I 2 (0.001 mol, 0.2 mol% relative to the reaction substrate), and the rest was the same as (the procedure and conditions) in Example 7. Finally, the product 2,6-dimethyl-N-(1-phenylethyl)aniline II-1 was obtained by column chromatography in 98% yield and 98% ee by HPLC analysis.

[0066] Example 10

[0067] The procedure and conditions were the same as in Example 7, except that NaI in Example 7 was replaced with tartaric acid (0.001 mol, 0.2 mol% relative to the reaction substrate), and the rest was the same as (the procedure and conditions) in Example 7. Finally, the product 2,6-dimethyl-N-(1-phenylethyl)aniline II-1 was obtained by column chromatography in 91% yield and 82% ee by HPLC analysis.

[0068] Example 11

[0069] The procedure and conditions were the same as in Example 9, except that the tetrahydrofuran in Example 9 was replaced with an equal volume of dichloroethane, and the rest was the same as (the procedure and conditions of) Example 9. Finally, the product 2,6-dimethyl-N-(1-phenylethyl)aniline II-1 was obtained by column chromatography with a 96% yield and 95% ee by HPLC analysis.

[0070] Example 12

[0071] The procedure and conditions were the same as in Example 9, except that the tetrahydrofuran in Example 9 was replaced with an equal volume of dichloromethane, and the rest was the same as (the procedure and conditions of) Example 9. Finally, the product 2,6-dimethyl-N-(1-phenylethyl)aniline II-1 was obtained by column chromatography with a 97% yield and 96% ee by HPLC analysis.

[0072] Example 13

[0073] The procedure and conditions were the same as in Example 9, except that the hydrogen pressure in Example 9 was changed from 20 bar to 60 bar, and the rest was the same as (the procedure and conditions of) Example 9. Finally, the product 2,6-dimethyl-N-(1-phenylethyl)aniline II-1 was obtained by column chromatography with a 98% yield and 99% ee by HPLC analysis.

[0074] Example 14

[0075] The procedure and conditions were the same as in Example 13, except that the reaction temperature in Example 13 was changed from 80 °C to 100 °C, and the rest was the same as (the procedure and conditions of) Example 13. Finally, the product 2,6-dimethyl-N-(1-phenylethyl)aniline II-1 was obtained by column chromatography with a 98% yield and 96% ee by HPLC analysis.

[0076] Example 15

[0077] The procedure and conditions were the same as in Example 13, except that the substrate in Example 13 (with the same amount) and iridium (i.e., adjusting [Ir(COD)Cl] 2 to (0.0000025 mmol, 0.0005 mol% relative to the reaction substrate), and the chiral bidentate phosphonamide ester ligand L-6 was 0.0000055 mmol, 0.0011 mol% relative to the reaction substrate) ratio was changed to 100000 / 1, and the rest was the same as (the procedure and conditions of) Example 13. Finally, the product 2,6-dimethyl-N-(1-phenylethyl)aniline II-1 was obtained by column chromatography with a 97% yield and 98% ee by HPLC analysis.

[0078] Example 16

[0079]

[0080] The procedure and conditions were the same as in Example 13, except that the substrate in Example 13 was changed to an equimolar amount of N-(2,6-dimethylphenyl)-3-methylbut-2-imine I-2. The rest was the same as in (the procedure and conditions of) Example 13. Finally, column chromatography (petroleum ether:ethyl acetate = 20 / 1) gave the product N-(3-methylbutan-2-yl)-2,6-dimethylaniline II-2 in 95% yield as a colorless oily liquid, and the GC analysis showed 81% ee. 1 H NMR(400MHz,CDCl 3 ):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);

[0081] Example 17

[0082]

[0083] The procedure and conditions were the same as in Example 13, except that the substrate in Example 15 was changed to an equimolar amount of 2-ethyl-N-(1-methoxypropan-2-ylidene)-6-methylaniline I-3. The rest was the same as in (the procedure and conditions of) Example 15. Finally, column chromatography (petroleum ether:ethyl acetate = 20 / 1) gave the product 2-ethyl-N-(1-methoxypropyl)-6-methylaniline II-3 in 99% yield as a colorless oily liquid, and the HPLC analysis showed 88% ee.). 1 H NMR(400MHz,CDCl 3 ):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);

[0084] Example 18

[0085]

[0086] The procedure and conditions were the same as in Example 13, except that the substrate in Example 15 was changed to an equimolar amount of methyl 2-(2,6-dimethylphenylimino)propionate I-4. The rest was the same as in (the procedure and conditions of) Example 15. Finally, column chromatography (petroleum ether:ethyl acetate = 20 / 1) gave the product methyl 2-(2,6-dimethylphenylamino)propionate II-4 in 97% yield as a slightly yellow oily liquid, and the HPLC analysis showed 98% ee.). 1 H NMR(400MHz,CDCl 3): δ 6.96 (d, J = 7.5 Hz, 2H), 6.80 (t, J = 7.5 Hz, 1H), 4.06–3.92 (m, 1H), 3.76 (d, J = 5.0 Hz, 1H), 3.66 (s, 3H), 2.30 (s, 6H), 1.38 (d, J = 7.0 Hz, 3H); Example 19

[0087]

[0088] The process and conditions were the same as those in Example 13, except that the substrate in Example 13 was changed to an equimolar amount of (E)-N-(2,6-dimethylphenyl)-1-(3-nitrophenyl)ethan-1-imine I-5, and the rest was the same as (the process and conditions) in Example 13. Finally, column chromatography (petroleum ether:ethyl acetate = 10 / 1) gave the product N-[1-(3-nitrophenyl)ethyl]-2,6-dimethylaniline II-5 in 99% yield, as a yellow liquid, and 99% ee by HPLC analysis.). 1 H NMR (400 MHz, CDCl 3 ): δ 8.23 (t, J = 1.9 Hz, 1H), 8.08 (ddd, J = 8.2, 2.2, 1.0 Hz, 1H), 7.62 (t, J = 9.8 Hz, 1H), 7.44 (t, J = 7.9 Hz, 1H), 6.95 (d, J = 7.5 Hz, 2H), 6.85–6.76 (m, 1H), 4.41 (q, J = 6.7 Hz, 1H), 3.22 (s, 1H), 2.17 (s, 6H), 1.56 (d, J = 6.8 Hz, 3H);

[0089] Example 20

[0090]

[0091] The process and conditions were the same as those in Example 13, except that the substrate in Example 13 was changed to an equimolar amount of (E)-N-(2-ethyl-6-methylphenyl)-1-phenylethan-1-imine I-6, and the rest was the same as (the process and conditions) in Example 13. Finally, column chromatography (petroleum ether:ethyl acetate = 20 / 1) gave the product N-(1-phenylethyl)-2-ethyl-6-methylaniline II-6 in 99% yield, as a colorless oily liquid, and 98% ee by HPLC analysis.). 1 H NMR (400 MHz, CDCl 3): δ 7.45–7.21 (m, 5H), 7.03 (dd, J = 14.1, 7.4 Hz, 2H), 6.90 (t, J = 7.5 Hz, 1H), 4.33 (q, J = 6.7 Hz, 1H), 3.24 (s, 1H), 2.57 (q, J = 7.5 Hz, 2H), 2.24 (s, 3H), 1.55 (d, J = 6.8 Hz, 3H), 1.22 (t, J = 7.6 Hz, 3H);

[0092] Example 21

[0093]

[0094] The procedure and conditions were the same as in Example 13, except that in Example 13, the substrate was changed to equimolar 1-(4-chlorophenyl)-N-(2,6-dimethylphenyl)ethan-1-imine I-7, and the rest was the same as (the procedure and conditions) in Example 13. Finally, column chromatography (petroleum ether:ethyl acetate = 20 / 1) gave the product N-(1-(4-chlorophenyl)ethyl)-2,6-dimethylaniline II-7 in 98% yield as a slightly yellow liquid, with 98% ee by HPLC analysis.). 1 H NMR (400 MHz, CDCl 3 ): δ 7.31–7.13 (m, 4H), 6.94 (d, J = 7.5 Hz, 2H), 6.83–6.73 (m, 1H), 4.27 (q, J = 6.7 Hz, 1H), 3.07 (s, 1H), 2.15 (s, 6H), 1.48 (d, J = 6.8 Hz, 3H);

[0095] The above-described embodiments only represent the implementation modes of the present invention, but should not be construed as limiting the scope of the present invention patent. It should be noted that for those skilled in the art, without departing from the concept of the present invention, several modifications and improvements can still be made, and these 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: Wherein: R1 is Cl~C40 alkyl (preferably Cl~C10 alkyl, such as CH3, CH3CH2, (CH3)2CH 、 (CH3)3C, etc.), C3-C12 cycloalkyl (preferably C3-C6 cycloalkyl, such as cyclopentyl, cyclohexyl, etc.), or Cl-C10 alkyl containing one or more functional groups of N, S, O, P (preferably Cl-C6 alkyl, such as methoxymethyl, ethoxymethyl, etc.), or C3-C10 cycloalkyl containing one or more functional groups of N, S, O, P (preferably C3-C6 cycloalkyl, such as 2 -tetrahydrofuranyl, 4-tetrahydrofuranyl, etc.); or C6-C30 aryl, etc. or aromatic groups containing or not containing one or more functional groups of N, S, O, P, etc. in C6-C30 (preferably C6-C12 aryl, such as phenyl, 4-methoxyphenyl, etc., one or more), or C2-C20 ester group (preferably C2-C12 ester group, such as COOCH3, COOCH2CH3, etc., one or more); R2 is H, one or more of a Cl-C40 alkyl group (preferably a Cl-C10 alkyl group) or a C6-C40 aryl group (preferably a C6-C18 aryl group); Ar is one or more of 2,6-disubstituted, 2,4,6-trisubstituted C6-C30 aromatic groups or aromatic groups in C6-C30 that may or may not contain one or more functional groups such as N, S, O, P, etc. (preferably C6-C18 aromatic groups, such as 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 the protection of an inert atmosphere (such as nitrogen), iridium and a chiral bidentate phosphinamide ester ligand are dissolved in a solvent, stirred at room temperature for 30-60 minutes, added to a solvent containing a 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.

3. The method according to claim 1, characterized in that: The specific reaction formula is as follows:

4. The method according to claim 1 or 2, characterized in that: The chiral bidentate phosphinamidate ligand has an achiral phosphine-amine skeleton and has one or more of the following structures: R is one or more of hydrogen, C1-C40 alkyl (preferably C1-C18 alkyl), phenyl and substituted phenyl; the substituent on the phenyl in the substituted phenyl is one or more of C1-C40 alkoxy (preferably C1-C18 alkoxy), C1-C40 alkyl (preferably C1-C18 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, the two carbons C1 in the following formula are respectively connected to one O of the above structural formula L, and the specific structure is one or more of the following, wherein n is an integer of 0-10, Ar is one or more of phenyl and substituted phenyl, naphthyl and substituted naphthyl, and a five-membered or six-membered heterocyclic aromatic group containing one or more of one or more of two or more of oxygen, sulfur, and nitrogen atoms, and the substituent on the substituted phenyl or the substituent on the substituted naphthyl is one or more of C1-C40 alkyl (preferably C1-C18 alkyl), C1-C40 alkoxy (preferably C1-C18 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-bi-tetrahydronaphthyl and substituted 1,1-bi-tetrahydronaphthyl, and the two carbons C1 in the following formula are respectively connected to one O in the above structural formula L, and 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 (preferably C1-C12 alkoxy), C1-C40 alkyl (preferably C1-C12 alkyl), phenyl and substituted phenyl, naphthyl and substituted naphthyl, halogen (F, Cl, Br, I), etc.; the substituents on the substituted phenyl and substituted naphthyl are selected from one or more of C1-C40 alkoxy (preferably C1-C12 alkoxy), C1-C40 alkyl (preferably C1-C12 alkyl), nitro, cyano, halogen (F, Cl, Br, I), and the number of substituents is 1-5.

5. The method according to claim 1, 2 or 3, characterized in that: The iridium is one or more of [Ir(COD)Cl]2, Ir(COD)2BARF or Ir(COD)2BF4.

6. The method according to claim 1 or 2, characterized in that: The additive is one or more of various iodides, such as iodine, sodium iodide, potassium iodide, zinc iodide, tetrabutylammonium iodide, N-iodosuccinimide, dioctaalkyldimethylammonium iodide, phenyltributylammonium iodide, hexadecyltrimethylammonium iodide, iodobenzene, and various acids such as tartaric acid, camphorsulfonic acid, trifluoroacetic acid, etc.; The molar ratio of the substrate imine to the additive is between 10-100000:1, preferably 100-40000:1, and more preferably 500-10000:

1.

7. The method according to claim 1 or 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; preferably one or more of tetrahydrofuran and dichloromethane.

8. The method according to any one of claims 1 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 1-3:1, more preferably 1.01-2.5:1; The molar ratio of the imine substrate to iridium is 100-600000:1, preferably 100-500000:1, and more preferably 100-300000:

1.

9. The method according to claim 1 or 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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