Multi-component composite chiral catalyst system as well as preparation and application thereof

Abstract

The invention provides a novel multi-component composite chiral catalyst system and application of the novel multi-component composite chiral catalyst system in catalysis of asymmetric hydrogenation. Specifically, the chiral hydrogenation catalyst system is prepared by compounding an Ir-metal precursor, chlorinated phosphite, a chiral phosphinamine compound, a halide and alkali in proportion. The multi-component composite chiral hydrogenation catalyst system prepared by the invention can obtain enantioselectivity as high as 99% ee through asymmetric hydrogenation reaction of double bonds such as C = O, C = C and C = N; and the catalyst has high activity, and TON (Total Organic Nitrogen) reaches The novel multi-component composite chiral hydrogenation catalyst system provided by the invention is simple and convenient to prepare and stable in property, and has the characteristics of excellent activity, enantioselectivity and the like in catalytic asymmetric hydrogenation reactions of ketone, olefin, imine and the like.

Description

Technical Field

[0001] The present invention relates to a novel multi-component composite chiral catalyst system and a preparation method thereof, and also relates to the application of the catalyst system in the catalytic asymmetric hydrogenation reaction of olefins, imines and carbonyls. Background Art

[0002] Asymmetric catalysis is a highly efficient and easily controllable chiral value-added method. Among them, asymmetric hydrogenation reaction has become one of the most effective methods for synthesizing chiral compounds due to its high atom economy, high reaction efficiency and simple post-processing. In the development of asymmetric catalytic hydrogenation, the development of chiral catalysts occupies a very important position. In recent years, the inventor's research group has been committed to the development and application of iridium-asymmetric hybrid chiral phosphine-phosphoramidate ligand catalytic system [(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) Hong-Quan Du, Xiang-Ping Hu.Org.Lett.2021,23,7678-7682; (c) Chao Dong, Dao-Sheng Liu, Lei Zhang, Xiang-Ping Hu.Tetrahedron Lett.2021,65,152763; (d) Xin-Hu Hu, Xiang-Ping Hu.Org.Lett.2019,21,10003-10006. (e) Xiu-Shuai Chen, Chuan-Jin Hou, Xiang-Ping Hu. Synth. Commun. 2016, 46, 917-941.; (f) Hou Chuanjin, Liu Xiaoning, Xia Ying, Hu Xiangping, Application progress of asymmetric hybrid chiral phosphine-phosphoramidate ligands in asymmetric catalytic reactions, <<Organic Chemistry>>, 2012, 32, 2239.]. The chiral phosphine-phosphoramidate ligands used in these catalytic systems are all pre-synthesized, and then in situ complexes are formed with metal precursors for use in catalytic reactions. This method of preparing catalysts not only has the disadvantages of difficult preparation and purification of ligands and metal complexes, but also metal complex catalysts are usually unstable and need to be prepared and used immediately, which is inconvenient to store. The present invention aims to develop a new type of multi-component composite catalyst system, which is simple to prepare, does not require pre-preparation, separation and purification of ligands, is stable and easy to store, is easy to use, and has excellent activity and stereoselectivity in asymmetric catalytic hydrogenation reactions. Summary of the invention

[0003] The present invention relates to a novel multi-component composite chiral catalyst system and a preparation method thereof, and also relates to the application of the catalyst system in the catalytic asymmetric hydrogenation reaction of ketones, olefins and imines.

[0004] A novel multi-component composite chiral catalyst system is prepared by mixing Ir-metal precursor (I), chlorophosphite (II), chiral phosphine amine compound (III), halide (IV) and base (V) in proportion.

[0005] The Ir-metal precursor (I) is selected from one or more of IrCl3, [Ir(COD)Cl]2, Ir(COD)2BARF or Ir(COD)2BF4.

[0006] The chlorophosphite (II) has the following structure

[0007]

[0008] The group is one or more of the following groups:

[0009] Chiral or achiral alkyl, C1 in the following structural formula is connected to O in chlorophosphite (II), and the specific structure is one or more of the following:

[0010]

[0011] 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;

[0012] 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 the C1 in the following structural formula is connected to the O in the chlorophosphite (II) respectively, and the specific structure is as follows:

[0013]

[0014] 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.

[0015] The chiral phosphine amine compound (III) has the following structure:

[0016]

[0017] Wherein Ar is one 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

[0018] R1 and R2 are the same or different groups, and are one of hydrogen, C1-C40 alkyl, phenyl and substituted phenyl. 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.

[0019] The halide (IV) is selected from fluoride, chloride, bromide, iodide, including but not limited to potassium fluoride, tetrabutylammonium fluoride, potassium chloride, zinc chloride, tetrabutylammonium chloride, potassium bromide, tetrabutylammonium bromide, benzyltriylammonium bromide, iodine, potassium iodide, sodium iodide, zinc iodide, tetrabutylammonium iodide, phenyltributylammonium iodide, bromobenzene, iodobenzene, etc., one or more.

[0020] Base (V) is selected from KOH, NaOH, Na2CO3, K2CO3, NaHCO3, i Pr2NEt, i PrNMe2, NEt3, t BuOK, t BuONa, t One or more of BuOLi, MeONa, MeOK or K3PO4.

[0021] The present invention also provides a molar ratio of each component of Ir-metal precursor (I): chlorophosphite (II): chiral phosphine amine compound (III): halide (IV): base (V): 1:1-5:1-5:1-1000:1-100

[0022] The preparation method of the multi-component composite chiral catalyst system of the present invention is as follows: the five components of the Ir-metal precursor (I), chlorophosphite (II), chiral phosphine amine compound (III), halide (IV) and base (V) are dissolved in a solvent according to a molar ratio, reacted at 0-100° C. for 0.5-12 h under a nitrogen atmosphere, and then the solvent is evaporated under reduced pressure to obtain a novel catalyst system.

[0023] The solvent used in the preparation method of the multi-component composite chiral catalyst system is selected from at least one of toluene, benzene, methanol, ethanol, isopropanol, dichloromethane, dichloroethane, carbon tetrachloride, ethyl acetate, ether, tetrahydrofuran, 2-methyltetrahydrofuran, dimethyl sulfoxide or N,N-dimethylformamide.

[0024] The application of the multi-component composite chiral catalyst system in the asymmetric hydrogenation reaction of ketones, olefins, and imines can hydrogenate the potential chiral compound to obtain the target chiral compound, with a catalytic activity TON of up to 1000000 and an enantioselectivity of up to 99% ee. The asymmetric hydrogenation reaction is a catalytic asymmetric hydrogenation reaction of the following types of substrates:

[0025] (1) Asymmetric hydrogenation of compounds containing C=O double bonds, including cyclic and acyclic ketones, β-diketones, α-ketoesters, β-ketoesters, etc.

[0026] (2) Asymmetric hydrogenation of compounds containing C=C double bonds, including: α-dehydroamino acids and their esters, β-dehydroamino acids and their esters, itaconates and β-substituted itaconates, α-acyclic and cyclic enamides, α-acyclic and cyclic enol esters and non-functionalized olefins, etc.;

[0027] (3) Asymmetric hydrogenation of compounds containing C=N double bonds, including non-cyclic imine compounds and nitrogen-containing heterocyclic compounds.

[0028] The novel multi-component composite chiral hydrogenation catalyst system provided by the present invention is easy to prepare, stable in nature, and has the characteristics of excellent activity and enantioselectivity in catalytic asymmetric hydrogenation reactions of ketones, olefins, imines, etc.

[0029] Beneficial effects of the present invention:

[0030] The invention provides a novel multi-component composite chiral catalyst system, which has the characteristics of wide raw material sources, simple synthesis, stable properties, good tolerance to air and humidity, easy storage, adjustable spatial structure and electronic properties of the adopted chlorophosphite (II) and chiral phosphine amine compound (III), excellent activity and enantioselectivity in catalytic asymmetric hydrogenation reaction, etc.; the asymmetric hydrogenation reaction conditions in which the catalyst participates are mild, the reaction can be carried out at room temperature, and the hydrogen pressure has a wide applicable range, and the activity and stereoselectivity of the catalyst are not affected from normal pressure to high pressure. DETAILED DESCRIPTION

[0031] The present invention is described in detail below by way of examples, but the present invention is not limited to the following examples. Nuclear magnetic resonance was measured by a Bruker nuclear magnetic resonance instrument, and high performance liquid chromatography (HPLC) was measured by an Agilent 1100 series high performance liquid chromatograph. Gas chromatography (GC) was measured by an Agilent 7890 series.

[0032] 1. Preparation of new multi-component composite chiral catalysts

[0033] Example 1

[0034] The chlorophosphite (II-1) and the chiral phosphine amine compound (III-1) have the following structures respectively:

[0035]

[0036] Under nitrogen protection, [Ir(COD)Cl]2(I-1): chlorophosphite (II-1): chiral phosphine compound (III-1): iodine (IV-1): sodium hydroxide (V-1) were dissolved in 3 mL of dichloromethane in a molar ratio of 1:2:2:5:3 (i.e., [Ir(COD)Cl]2(I-1) 0.001 mmol, chlorophosphite (II-1) 0.002 mmol, chiral phosphine compound (III-1) 0.002 mmol, iodine (IV-1) 0.005 mmol, sodium hydroxide (V-1) 0.003 mmol), and then reacted at 25°C for 60 min, and then the dichloromethane was removed by rotary evaporation under reduced pressure to obtain a solid mixture, named Cat-1.

[0037] Example 2

[0038] The chlorophosphite (II-2) and the chiral phosphine amine compound (III-1) have the following structures respectively:

[0039]

[0040] Under nitrogen protection, [Ir(COD)Cl]2(I-1): chlorophosphite (II-2): chiral phosphine compound (III-1): iodine (IV-1): sodium hydroxide (V-1) were dissolved in 3 mL of dichloromethane in a molar ratio of 1:2:2:5:3, i.e., [Ir(COD)Cl]2(I-1) 0.001 mmol, chlorophosphite (II-2) 0.002 mmol, chiral phosphine compound (III-1) 0.002 mmol, iodine (IV-1) 0.005 mmol, sodium hydroxide (V-1) 0.003 mmol, and then reacted at 25°C for 60 min, and then the light components were removed by rotary evaporation under reduced pressure to obtain a solid mixture, named Cat-2.

[0041] Example 3

[0042] The chlorophosphite (II-1) and the chiral phosphine amine compound (III-2) have the following structures respectively:

[0043]

[0044] Under nitrogen protection, [Ir(COD)Cl]2(I-1): chlorophosphite (II-1): chiral phosphine compound (III-2): iodine (IV-1): sodium hydroxide (V-1) were dissolved in 3 mL of dichloromethane in a molar ratio of 1:2:2:5:3, i.e., [Ir(COD)Cl]2(I-1) 0.001 mmol, chlorophosphite (II-1) 0.002 mmol, chiral phosphine compound (III-2) 0.002 mmol, iodine (IV-1) 0.005 mmol, sodium hydroxide (V-1) 0.003 mmol. The mixture was reacted at 25°C for 60 min, and then the dichloromethane was removed by rotary evaporation under reduced pressure to obtain a solid mixture, named Cat-3.

[0045] Example 4

[0046] The chlorophosphite (II-2) and the chiral phosphine amine compound (III-2) have the following structures respectively:

[0047]

[0048] Under nitrogen protection, [Ir(COD)Cl]2(I-1): chlorophosphite (II-2): chiral phosphine compound (III-2): iodine (IV-1): sodium hydroxide (V-1) were dissolved in 3 mL of dichloromethane in a molar ratio of 1:2:2:5:3, i.e., [Ir(COD)Cl]2(I-1) 0.001 mmol, chlorophosphite (II-2) 0.002 mmol, chiral phosphine compound (III-2) 0.002 mmol, iodine (IV-1) 0.005 mmol, sodium hydroxide (V-1) 0.003 mmol, and then reacted at 25°C for 60 min, and then the light components were removed by rotary evaporation under reduced pressure to obtain a solid mixture, named Cat-4.

[0049] Example 5

[0050] The chlorophosphite (II-3) and the chiral phosphine amine compound (III-2) have the following structures respectively:

[0051]

[0052] Under nitrogen protection, [Ir(COD)Cl]2(I-1): chlorophosphite (II-3): chiral phosphine compound (III-2): iodine (IV-1): sodium hydroxide (V-1) were dissolved in 3 mL of dichloromethane in a molar ratio of 1:2:2:5:3, i.e., [Ir(COD)Cl]2(I-1) 0.001 mmol, chlorophosphite (II-3) 0.002 mmol, chiral phosphine compound (III-2) 0.002 mmol, iodine (IV-1) 0.005 mmol, sodium hydroxide (V-1) 0.003 mmol, and then reacted at 25°C for 60 min, and then the light components were removed by rotary evaporation under reduced pressure to obtain a solid mixture, named Cat-5.

[0053] Example 6

[0054] The chlorophosphite (II-4) and the chiral phosphine amine compound (III-2) have the following structures respectively:

[0055]

[0056] Under nitrogen protection, [Ir(COD)Cl]2(I-1): chlorophosphite (II-4): chiral phosphine compound (III-2): iodine (IV-1): sodium hydroxide (V-1) were dissolved in 3 mL of dichloromethane in a molar ratio of 1:2:2:5:3, i.e., [Ir(COD)Cl]2(I-1) 0.001 mmol, chlorophosphite (II-4) 0.002 mmol, chiral phosphine compound (III-2) 0.002 mmol, iodine (IV-1) 0.005 mmol, sodium hydroxide (V-1) 0.003 mmol, and then reacted at 25°C for 60 min, and then the light components were removed by rotary evaporation under reduced pressure to obtain a solid mixture, named Cat-6.

[0057] Example 7

[0058] The chlorophosphite (II-5) and the chiral phosphine amine compound (III-2) have the following structures respectively:

[0059]

[0060] Under nitrogen protection, [Ir(COD)Cl]2(I-1): chlorophosphite (II-5): chiral phosphine compound (III-2): iodine (IV-1): sodium hydroxide (V-1) were dissolved in 3 mL of dichloromethane in a molar ratio of 1:2:2:5:3, i.e., [Ir(COD)Cl]2(I-1) 0.001 mmol, chlorophosphite (II-5) 0.002 mmol, chiral phosphine compound (III-2) 0.002 mmol, iodine (IV-1) 0.005 mmol, sodium hydroxide (V-1) 0.003 mmol, and then reacted at 25°C for 60 min, and then the light components were removed by rotary evaporation under reduced pressure to obtain a solid mixture, named Cat-7.

[0061] Example 8

[0062] The chlorophosphite (II-6) and the chiral phosphine amine compound (III-2) have the following structures respectively:

[0063]

[0064] Under nitrogen protection, [Ir(COD)Cl]2(I-1): chlorophosphite (II-6): chiral phosphine compound (III-2): iodine (IV-1): sodium hydroxide (V-1) were dissolved in 3 mL of dichloromethane in a molar ratio of 1:2:2:5:3, i.e., [Ir(COD)Cl]2(I-1) 0.001 mmol, chlorophosphite (II-6) 0.002 mmol, chiral phosphine compound (III-2) 0.002 mmol, iodine (IV-1) 0.005 mmol, sodium hydroxide (V-1) 0.003 mmol. The mixture was reacted at 25°C for 60 min, and then the light components were removed by rotary evaporation under reduced pressure to obtain a solid mixture, named Cat-8.

[0065] Example 9

[0066] The iodine (IV-1) in Example 1 was replaced by an equimolar amount of potassium iodide (IV-2), and the remaining processes and regulations were the same as in Example 1 to obtain catalyst Cat-9.

[0067] Example 10

[0068] The iodine (IV-1) in Example 1 was replaced with an equimolar amount of sodium iodide (IV-3), and the remaining processes and regulations were the same as those in Example 1 to obtain catalyst Cat-10.

[0069] Embodiment 11

[0070] The sodium hydroxide (V-1) in Example 2 was replaced by an equimolar amount of triethylamine (V-2), and the remaining processes and regulations were the same as those in Example 2 to obtain catalyst Cat-11.

[0071] Example 12

[0072] The sodium hydroxide (V-1) in Example 2 was replaced by an equimolar i Pr2NEt(V-3), the rest of the process and regulations are the same as Example 2, to obtain catalyst Cat-12.

[0073] Example 13

[0074] The dichloromethane in Example 2 was replaced with an equal volume of dichloroethane, and the remaining processes and regulations were the same as Example 2 to obtain catalyst Cat-13.

[0075] Embodiment 14

[0076] The dichloromethane in Example 2 was replaced with an equal volume of toluene, and the remaining processes and regulations were the same as Example 2 to obtain catalyst Cat-14.

[0077] Embodiment 15

[0078] The 0.001mmol [Ir(COD)Cl]2 in Example 2 was replaced with 0.002mmol Ir(COD)2BF4, and the rest was the same as Example 2 to obtain catalyst Cat-15.

[0079] 2. Asymmetric hydrogenation reaction

[0080] Example 16

[0081] In a glove box, Cat-1 was added to the substrate acetophenone (1 mmol, substrate / iridium molar ratio of 500 / 1), 3 mL of ethanol was added, and the mixture was placed in a high pressure reactor, hydrogen was replaced 3 times, and then hydrogen was introduced to 30 atmospheres, and the reaction was carried out at room temperature for 12 hours. The hydrogen was slowly released, and the product (S)-1-phenylethanol was separated by a silica gel column after removing the solvent, as a colorless oil with a yield of 97% and an ee of 94% by HPLC analysis. 1 H NMR (400MHz, CDCl3) δ7.54-7.13(m,5H),4.86(q,J=6.4Hz,1H),2.07(s,1H),1.47(d,J=6.4Hz,3H).

[0082] Embodiment 17

[0083] The Cat-1 in Example 16 was changed to Cat-2, and the other conditions and processes were the same as Example 16, and finally the product (S)-3-hydroxy-3-phenylpropionic acid methyl ester was obtained with a yield of 97% and an HPLC analysis of 97% ee.

[0084] Embodiment 18

[0085] The Cat-1 in Example 16 was changed to Cat-9, and the other conditions and processes were the same as Example 16, and finally the product (S)-3-hydroxy-3-phenylpropionic acid methyl ester was obtained with a yield of 97% and an HPLC analysis of 92% ee.

[0086] Embodiment 19

[0087] In a glove box, Cat-2 was added to the substrate ethyl benzoyl acetate (1 mmol, substrate / iridium molar ratio of 500 / 1), 3 mL of methanol was added, and the mixture was placed in a high pressure reactor, replaced with hydrogen 3 times, and then hydrogen was introduced to 20 atmospheres, and the reaction was carried out at room temperature for 12 hours. The hydrogen was slowly released, and the product (S)-3-hydroxy-3-phenylpropionic acid methyl ester was obtained by separation with a silica gel column after removing the solvent, as a colorless oil with a yield of 97%, and 97% ee by HPLC analysis. 1 H NMR (400MHz, CDCl3)7.44–7.27(m,5H),5.14(dd,1H),3.72(s,3H),2.97–2.67(m,3H).

[0088] Embodiment 20

[0089] The Cat-2 in Example 19 was changed to Cat-3, and the other conditions and processes were the same as Example 19, and finally the product (S)-3-hydroxy-3-phenylpropionic acid methyl ester was obtained with a yield of 97% and an HPLC analysis of 95% ee.

[0090] Embodiment 21

[0091] The Cat-2 in Example 19 was changed to Cat-4, and the other conditions and processes were the same as Example 19, and finally the product (S)-3-hydroxy-3-phenylpropionic acid methyl ester was obtained with a yield of 95% and an HPLC analysis of 91% ee.

[0092] Embodiment 22

[0093] The Cat-2 in Example 19 was changed to Cat-10, and the other conditions and processes were the same as Example 19, and finally the product (S)-3-hydroxy-3-phenylpropionic acid methyl ester was obtained with a yield of 95% and an HPLC analysis of 92% ee.

[0094] Embodiment 23

[0095] In a glove box, Cat-4 was added to the substrate α-acetamidostyrene (1 mmol, substrate / iridium molar ratio of 500 / 1), 3 mL of toluene was added, and the mixture was placed in a high pressure reactor, replaced with hydrogen 3 times, and then hydrogen was introduced to 10 atmospheres, and the reaction was carried out at room temperature for 24 hours. The hydrogen was slowly released, and the product (S)-N-acetyl α-phenylethylamine was obtained by separation with a silica gel column after removing the solvent, as a white solid with a yield of 98% and 97% ee by GC analysis. 1 H NMR(CDCl3): δ1.49(d,3H),1.98(s,3H),5.04-5.19(m,1H),5.68(br s,1H),7.22-7.39(m,5H).

[0096] Embodiment 24

[0097] In a glove box, Cat-4 was added to the substrate dimethyl itaconate (1 mmol, substrate / iridium molar ratio of 500 / 1), 3 mL of tetrahydrofuran was added, and it was placed in a high-pressure reactor, hydrogen was replaced 3 times, and then hydrogen was introduced to 10 atmospheres, and the reaction was carried out at room temperature for 24 hours. The hydrogen was slowly released, and the product (R)-2-methylsuccinic acid dimethyl ester was separated by a silica gel column after removing the solvent, as a colorless oil, with a yield of 98%, and 99% ee by GC analysis. 1H NMR(CDCl3): δ1.22(d,3H),2.41(dd,1H),2.75(dd,1H),2.87-2.99(m,1H),3.68(s,3H),3.70(s,3H).

[0098] Embodiment 25

[0099] The Cat-4 in Example 24 was changed to Cat-5, and the other conditions and processes were the same as Example 24, and finally the product (S)-2-methylsuccinic acid dimethyl ester was obtained with a yield of 75% and 61% ee according to HPLC analysis.

[0100] Embodiment 26

[0101] The Cat-4 in Example 24 was changed to Cat-13, and the remaining conditions and processes were the same as Example 24, and finally the product (S)-2-methylsuccinic acid dimethyl ester was obtained with a yield of 75% and an HPLC analysis of 99% ee.

[0102] Embodiment 27

[0103] The Cat-4 in Example 24 was changed to Cat-14, and the remaining conditions and processes were the same as Example 24, and finally the product (S)-2-methylsuccinic acid dimethyl ester was obtained with a yield of 75% and an HPLC analysis of 99% ee.

[0104] Embodiment 28

[0105] In a glove box, Cat-4 was added to the substrate (E)-2,6-dimethyl-N-(1-phenylethylidene)aniline (1mmol, substrate / iridium molar ratio of 500 / 1), 3mL of dichloromethane was added, and it was placed in a high-pressure reactor, replaced with hydrogen 3 times, and then hydrogen was introduced to 50 atmospheres, and the reaction was carried out at room temperature for 12 hours. Hydrogen was slowly released, and the product 2,6-dimethyl-N-(l-phenylethyl)aniline was obtained by column chromatography, with a yield of 99%, a slightly yellow liquid, and 95% 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).

[0106] Embodiment 29

[0107] The molar amount of the substrate in Example 28 was changed from 1 mmol to 200 mmol, that is, the substrate / iridium molar ratio was 100000 / 1, and the dichloromethane was changed to 50 mL. The rest was the same as Example 28, and the product 2,6-dimethyl-N-(l-phenylethyl)aniline was obtained with a yield of 97% and an HPLC analysis of 98% ee.

[0108] Embodiment 30

[0109] The substrate / iridium molar ratio in Example 29 was changed to 500000 / 1, and the rest was the same as Example 29 to obtain the product 2,6-dimethyl-N-(l-phenylethyl)aniline with a yield of 94% and an HPLC analysis of 96% ee.

[0110] Embodiment 31

[0111] The substrate / iridium molar ratio in Example 29 was changed to 1000000 / 1, and the rest was the same as Example 29 to obtain the product 2,6-dimethyl-N-(l-phenylethyl)aniline with a yield of 91% and an HPLC analysis of 92% ee.

[0112] Embodiment 32

[0113] The Cat-4 in Example 28 was changed to Cat-15, and the other conditions and processes were the same as Example 28, and finally the product 2,6-dimethyl-N-(l-phenylethyl)aniline was obtained with a yield of 95% and an HPLC analysis of 94% ee.

[0114] Embodiment 33

[0115] The substrate in Example 30 was changed to 2-ethyl-N-(1-methoxy-2-propyl)-6-methylaniline, and the rest was the same as in Example 30. Finally, the product was obtained by column chromatography. The product 2-ethyl-N-(1-methoxy-2-propyl)-6-methylaniline was obtained with a yield of 99% and was a colorless oily liquid. HPLC analysis showed 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).

[0116] Embodiment 34

[0117] The substrate in Example 29 was changed to methyl 2-(2,6-dimethylphenylimino)propionate, and the rest was the same as Example 29. Finally, column chromatography was performed to obtain the product methyl 2-(2,6-dimethylphenylimino)propionate, a slightly yellow oily liquid, with 91% ee according to HPLC analysis. 1H 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).

[0118] Embodiment 35

[0119] In a glove box, add Cat-5 to the substrate 3-methyl-2-phenylquinoline (1mmol substrate / iridium molar ratio is 500 / 1), add 5mL 1,4-dioxane, place it in a high-pressure reactor, replace it with hydrogen 3 times, then introduce hydrogen to 50 atmospheres, heat to 100℃ and react for 24 hours. Slowly release hydrogen, remove the solvent and separate with a silica gel column to obtain (2S,3R)-3-methyl-2-phenyl-1,2,3,4-tetrahydroquinoline, a yellow solid, 97% yield, 94% ee by HPLC analysis. 1 HNMR (400MHz, CDCl3) δ7.30–7.14(m,5H),6.93(dd,J=14.5,7.4Hz,2H),6.57(t,J=7.4Hz,1H),6.46(d,J=7.9Hz,1H),4.42(d,J=3.5H z,1H),4.02(bs,1H),2.88(dd,J=16.1,4.9Hz,1H),2.42(dd,J=16.1,6.7Hz,1H),2.22(dt,J=10.9,5.8Hz,1H),0.74(d,J=6.9Hz,3H).

[0120] Embodiment 36

[0121] The Cat-5 in Example 35 was changed to Cat-6, and the other conditions and processes were the same as Example 35, and finally the product (2S, 3R)-3-methyl-2-phenyl-1,2,3,4-tetrahydroquinoline was obtained as a yellow solid with a yield of 97% and an HPLC analysis of 92% ee.

[0122] Embodiment 37

[0123] The Cat-5 in Example 35 was changed to Cat-7, and the other conditions and processes were the same as those in Example 35. Finally, the product (2S, 3R)-3-methyl-2-phenyl-1,2,3,4-tetrahydroquinoline was obtained as a yellow solid with a yield of 97% and an ee of 90% by HPLC analysis.

[0124] Embodiment 38

[0125] The Cat-5 in Example 35 was changed to Cat-8, and the other conditions and processes were the same as those in Example 35. Finally, the product (2S, 3R)-3-methyl-2-phenyl-1,2,3,4-tetrahydroquinoline was obtained as a yellow solid with a yield of 97% and an HPLC analysis of 92% ee.

[0126] 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 multi-component composite chiral catalyst system, characterized in that: The catalyst system is prepared by mixing an Ir-metal precursor (I), a chlorophosphite (II), a chiral phosphine amine compound (III), a halide (IV) and a base (V) in a certain proportion. The molar ratio of Ir-metal precursor (I): chlorophosphite (II): chiral phosphine compound (III): halide (IV): base (V) is: 1:1-5:1-5:1-1000:1-100; preferably 1:1-3:1-3:1-500:1-50; more preferably 1:1-2:1-2:1-400:1-40.

2. The multi-component composite chiral catalyst system according to claim 1, characterized in that: The Ir-metal precursor (I) is selected from one or more of IrCl3, [Ir(COD)Cl]2, Ir(COD)2BARF or Ir(COD)2BF4.

3. The multi-component composite chiral catalyst system according to claim 1, characterized in that: The chlorophosphite (II) has the following structure The X group is one or more of the following groups: Chiral or achiral C1-C40 alkyl and C1-C100 groups containing aromatic substitution, wherein the C1 position in the following formula is connected to the O in the chlorophosphite (II), and the specific structure is one or more of the following: wherein n is an integer of 0-10; Ar is independently 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 oxygen, sulfur, and nitrogen atoms; the substituent on the phenyl or the substituent on the naphthyl is independently one or more of C1-C40 alkyl, C1-C40 alkoxy, halogen (one or more of fluorine, chlorine, bromine, or iodine), nitro, C1-C40 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 as shown in the following formula; the C1 position in the following formula is connected to O in the chlorophosphite (II), 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, 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, preferably 1-2.

4. The multi-component composite chiral catalyst system according to claim 1, characterized in that: The chiral phosphine amine compound (III) has the following structure: (R)-III and (S)-III are enantiomers of each other 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, preferably 1-2; R1 and R2 are respectively the same or different groups, and are one or more of hydrogen, C1-C40 alkyl, phenyl and substituted phenyl. 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, preferably 1-2.

5. The multi-component composite chiral catalyst system according to claim 1, characterized in that: The halide (IV) is selected from fluoride, chloride, bromide, iodide, including but not limited to potassium fluoride, tetrabutylammonium fluoride, potassium chloride, zinc chloride, tetrabutylammonium chloride, potassium bromide, tetrabutylammonium bromide, benzyltriylammonium bromide, iodine, potassium iodide, sodium iodide, zinc iodide, tetrabutylammonium iodide, phenyltributylammonium iodide, bromobenzene, iodobenzene, etc., one or more thereof; preferably iodide.

6. The multi-component composite chiral catalyst system according to claim 1, characterized in that: Base (V) is selected from KOH, NaOH, Na2CO3, K2CO3, NaHCO3, i Pr2NEt, i PrNMe2, NEt3, t BuOK, t BuONa, t One or more of BuOLi, MeONa, MeOK or K3PO4.

7. A method for preparing the multi-component composite chiral catalyst system according to any one of claims 1 to 6, characterized in that: The process is as follows: the five components of the Ir-metal precursor (I), chlorophosphite (II), chiral phosphine amine compound (III), halide (IV) and base (V) are dissolved in an organic solvent according to the required molar ratio, reacted at 0-100° C. (preferably 0-80° C.) for 0.5-12 h (preferably 0.5-8 h) under a nitrogen atmosphere, and then the solvent is removed to obtain the multi-component composite chiral catalyst system.

8. The method for preparing a multi-component composite chiral catalyst system according to claim 7 is characterized in that: The organic solvent is selected from at least one or more of toluene, benzene, methanol, ethanol, isopropanol, dichloromethane, dichloroethane, carbon tetrachloride, ethyl acetate, ether, tetrahydrofuran, 2-methyltetrahydrofuran, dimethyl sulfoxide or N,N-dimethylformamide; preferably at least one or more of toluene, dichloromethane, dichloroethane and tetrahydrofuran.

9. An application of the multi-component composite chiral catalyst system according to any one of claims 1 to 6, characterized in that: The catalytic system can hydrogenate a potential chiral compound (a compound containing one or more than two of carbonyl, olefin or imine) in an asymmetric hydrogenation reaction of one or more than two of carbonyl, olefin or imine to obtain a target chiral compound.

10. The use of the multi-component composite chiral catalyst system as claimed in claim 9, characterized in that: Asymmetric hydrogenation is a catalytic asymmetric hydrogenation reaction of one or more of the following types of substrates: (1) Asymmetric hydrogenation of compounds containing C=O double bonds, including one or more of cyclic and acyclic ketones, β-diketones, α-ketoesters, β-ketoesters, etc.; (2) Asymmetric hydrogenation of compounds containing C=C double bonds, including one or more of α-dehydroamino acids and their esters, β-dehydroamino acids and their esters, itaconates and β-substituted itaconates, α-acyclic and cyclic enamides, α-acyclic and cyclic enol esters and non-functionalized olefins; (3) Asymmetric hydrogenation of compounds containing C=N double bonds, including one or more of acyclic imine compounds and nitrogen-containing heterocyclic compounds.

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