Asymmetric catalytic hydrogenation method of cyclohexene derivative

Abstract

The invention discloses an asymmetric catalytic hydrogenation method of a cyclohexene derivative, which comprises the following step: in a hydrogen atmosphere, carrying out asymmetric hydrogenation reduction reaction on the cyclohexene derivative in the presence of a catalyst, acid and a solvent. In the asymmetric catalytic hydrogenation method provided by the invention, aiming at a cyclohexene derivative substrate, high conversion rate and excellent selectivity are realized, the ee value of the obtained reduction product is high and can reach 99%, and the asymmetric catalytic hydrogenation method is suitable for industrial large-scale production, can effectively improve the production efficiency and the product purity, and meets the requirements of large-scale production.

Description

Technical Field

[0001] The invention relates to the technical field of hydrogenation of organic compounds, and in particular to a method for asymmetric catalytic hydrogenation of cyclohexene derivatives. Background Art

[0002] In the field of compound synthesis, especially in the synthesis of drug intermediates, asymmetric hydrogenation reduction of double bonds is a crucial reaction step. This step aims to convert a substrate containing double bonds into a compound with a specific configuration through a specific catalytic process. At present, the most commonly used method for asymmetric catalytic hydrogenation reduction of double bonds is to use metals or metal complexes as catalysts. However, this method faces a series of challenges in practical applications. First, metal or metal complex catalysts often have poor selectivity when catalytically reducing substrates, which means that the catalytic reduction reaction may produce a variety of reduction products, and the compound of the target configuration is only one of them. Therefore, in order to obtain a pure target configuration compound, a cumbersome splitting step is usually required later, which not only increases the production cost but also reduces the production efficiency. Secondly, the substrate conversion efficiency is also a key factor affecting the application effect of asymmetric catalytic hydrogenation reduction of double bonds. In particular, when the structural difference between the substrate and the reduction product is small, the separation of the two becomes particularly difficult, resulting in a significant reduction in the substrate conversion efficiency. In this case, even if the catalyst itself has a certain activity, it is difficult to achieve efficient catalytic conversion. In addition, the choice of catalyst is crucial for the substrate to be reduced. An ideal catalyst should have high conversion rate and high selectivity, that is, it can almost completely convert the substrate to be reduced into a compound of the target configuration (for example, the conversion rate reaches 99% or more), and the generated reduction product has a high enantioselectivity (for example, the ee value reaches 99% or more). However, existing metal or metal complex catalysts often find it difficult to meet these requirements.

[0003] In order to solve the above problems, researchers have tried to use methods such as separation / resolution technology based on solubility differences or enzymatic resolution to separate diastereomers or prepare individual stereoisomers. However, the application range of these methods is limited and they are only applicable to compounds with special structures. In addition, the enzymatic resolution of corresponding isomers usually requires more stringent reaction conditions, such as temperature, pH value, etc., which limits its subsequent application to a certain extent. Chinese patent CN117362142A uses metal iridium catalysts for catalysis. Although it has achieved certain results, the expensive price of metal iridium limits its wide application.

[0004] Therefore, there is an urgent need to develop a new asymmetric catalytic hydrogenation reduction method for double bonds, which should be able to use cheaper and more readily available catalysts while achieving high conversion and high selectivity. Summary of the invention

[0005] In order to solve the above technical problems, the present invention provides a method for asymmetric catalytic hydrogenation of cyclohexene derivatives.

[0006] The present invention is achieved through the following technical solutions:

[0007] The present invention provides a method for asymmetric catalytic hydrogenation of a cyclohexene derivative, comprising the following steps:

[0008] In a hydrogen atmosphere, the compound represented by Formula I (i.e., a cyclohexene derivative) is subjected to an asymmetric hydrogenation reduction reaction in the presence of a catalyst, an acid, and a solvent to form a compound represented by Formula II. The reaction formula is shown below:

[0009]

[0010] wherein Ar is selected from aryl or heteroaryl, and the aryl or heteroaryl is optionally substituted with one or more substituents selected from alkyl, alkoxy, cycloalkyl, aryl, halogen, nitro, acyl-containing group, sulfonyl-containing group or heteroaryl;

[0011] R is selected from alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein the alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with one or more substituents selected from halogen, nitro, cyano, amino, alkyl, alkoxy, cycloalkyl, heterocyclyl, acyl-containing group, sulfonyl-containing group, aryl or heteroaryl;

[0012] The catalyst is obtained by reacting a ligand and a ruthenium salt, and the ligand is selected from the compound shown in the following formula:

[0013]

[0014] In Formula III, R 1 , R 2 , R 3 and R 4 Each is independently selected from hydrogen, halogen, alkyl, alkoxy, cycloalkyl or aryl, wherein the alkyl, alkoxy, cycloalkyl, aryl is optionally substituted with one or more substituents selected from halogen, nitro, cyano, alkyl, alkoxy, cycloalkyl, acyl-containing group, sulfonyl-containing group or aryl;

[0015] In formula IV and V, R 5 independently selected from hydrogen, alkyl, alkoxy, cycloalkyl or aryl, wherein the alkyl, alkoxy, cycloalkyl or aryl is optionally substituted with one or more substituents selected from halogen, nitro, alkyl, alkoxy, cycloalkyl, an acyl-containing group, a sulfonyl-containing group or an aryl group;

[0016] In Formula VI, R 6 and R 7are each independently selected from hydrogen, halogen, alkyl, alkoxy, cycloalkyl or aryl, or R 6 and R 7 Together with the carbon to which it is attached, it forms a 5- to 6-membered ring, or R on two benzene rings 7 Together with the carbon to which it is attached, it forms a 7 to 12 membered ring, wherein the alkyl, alkoxy, cycloalkyl, aryl, 5 to 6 membered ring, 7 to 12 membered ring is optionally substituted with one or more substituents selected from halogen, nitro, cyano, alkyl, alkoxy, cycloalkyl, acyl-containing group, sulfonyl-containing group or aryl; R 8 is aryl, wherein the aryl is optionally substituted with one or more substituents selected from halogen, nitro, cyano, alkyl, alkoxy, cycloalkyl, acyl-containing group, sulfonyl-containing group or aryl;

[0017] The ruthenium salt is selected from one or more of p-cymene diiodide ruthenium (II) dimer, dichlorobis (4-methylisopropylphenyl) ruthenium (II) dimer, dicarbonylcyclopentadienyl diruthenium (II) dimer, dichloro (pentamethylcyclopentadienyl) ruthenium (II) dimer, dichlorophenyl ruthenium (II) dimer, (hexamethylbenzene) dichlororuthenium (II) dimer, (1,5-cyclooctadiene) dichlororuthenium (II) and tricarbonyl dichlororuthenium dimer;

[0018] The acid is selected from one or more of hydrochloric acid, formic acid, sulfuric acid, acetic acid, trifluoroacetic acid, trifluoromethanesulfonic acid, benzoic acid and citric acid.

[0019] Preferably, in Formula I and Formula II, Ar is a benzene ring, wherein the benzene ring is substituted by one or more substituents selected from halogen, alkyl, and alkoxy.

[0020] Preferably, in Formula I and Formula II, R is a benzene ring, wherein the benzene ring is substituted by one or more substituents selected from halogen, nitro, cyano, amino, alkyl, and alkoxy.

[0021] Preferably, in Formula III, R 1 , R 2 , R 3 and R 4 Each is independently selected from hydrogen, alkyl, cycloalkyl or phenyl, wherein the alkyl, cycloalkyl, phenyl is optionally substituted by one or more substituents selected from alkyl, alkyl, cycloalkyl, phenyl.

[0022] Preferably, in formula IV and V, R 5 Independently selected from hydrogen, alkyl, cycloalkyl or phenyl, wherein the alkyl, cycloalkyl or phenyl is optionally substituted with one or more substituents selected from alkyl, cycloalkyl, phenyl.

[0023] Preferably, in Formula VI, R 6 and R 7are each independently selected from hydrogen, alkyl, cycloalkyl or phenyl, or R 6 and R 7 Together with the carbon to which it is attached, a 5- to 6-membered ring is formed, wherein the alkyl, cycloalkyl or phenyl is optionally substituted by one or more substituents selected from alkyl, alkyl, cycloalkyl, phenyl, and the 5- to 6-membered ring is substituted by a benzene ring and shares two carbon atoms with the substituted benzene ring.

[0024] Furthermore, the solvent is selected from one or more of methanol, ethanol, isopropanol, propanol, methyl chloride, acetonitrile, toluene, xylene, tert-butyl alcohol, butanol, isobutanol, acetone, 1,4-dioxane, tetrahydrofuran, methyl tert-butyl ether, ethyl acetate and methyl acetate.

[0025] Furthermore, the usage ratio of the compound represented by Formula I to the solvent is (5-40) mg:1 mL, preferably (10-20) mg:1 mL.

[0026] Furthermore, the structure of the compound represented by Formula I is shown in the following Formula I-1:

[0027]

[0028] Among them, R 9 is hydrogen or a hydroxyl protecting group;

[0029] R 10 and R 11 Each is independently selected from hydrogen, alkyl or an acyl-containing group, wherein the alkyl is optionally substituted with one or more substituents selected from halogen, nitro, cyano, amino, alkyl, alkoxy, cycloalkyl, phenyl, acyl-containing substituents;

[0030] R 12 is selected from hydrogen, alkyl or cycloalkyl, wherein the alkyl or cycloalkyl is optionally substituted by one or more substituents selected from halogen, nitro, cyano, amino, alkyl, alkoxy, and phenyl.

[0031] Preferably, the hydroxyl protecting group is selected from TMS (trimethylsilyl), TIPS (triisopropylsilyl), TBS (tert-butyldimethyl), Me (methyl), Et (ethyl), Pr (propyl), Bn (benzyl), CH3CO (acetyl), CH3CH2CO (propionyl), PhCO (benzoyl), CH3SO2 (methylsulfonyl) or PhSO2 (phenylsulfonyl).

[0032] Furthermore, the compound represented by formula I-1 is selected from one of the following structures:

[0033]

[0034] Furthermore, the temperature of the asymmetric hydrogenation reduction reaction is 0-130°C, preferably 50-100°C, and more preferably 60-90°C.

[0035] Furthermore, the asymmetric hydrogenation reduction reaction is carried out under a hydrogen pressure of 1-100 bar, preferably 50-80 bar.

[0036] Furthermore, the molar ratio of the compound represented by formula I to the catalyst is (100-10000):1, preferably (200-3000):1.

[0037] Furthermore, the preparation method of the catalyst comprises the following steps: the ligand and the ruthenium salt react to form a complex, thereby obtaining the catalyst.

[0038] Furthermore, the molar ratio of the ligand to the ruthenium salt is 1:(0.8-1.2).

[0039] Furthermore, the catalyst is selected from the compounds shown in the following structures:

[0040]

[0041]

[0042] The present invention also protects the use of the catalyst in asymmetric catalytic reduction of double bonds.

[0043] In a specific embodiment, the present invention provides a method for asymmetric catalytic hydrogenation of a compound represented by formula I-1, comprising the following steps:

[0044] Under a hydrogen atmosphere, the compound represented by Formula I-1 is subjected to an asymmetric hydrogenation reduction reaction in the presence of a catalyst, an acid and a solvent to form a compound represented by Formula II-1. The reaction formula is as follows:

[0045]

[0046] Among them, R 9 is selected from H, Bn, Cbz or Ac, and the catalyst is selected from the compounds shown in the following structure:

[0047]

[0048]

[0049] Beneficial effects of the present invention:

[0050] 1. In the asymmetric catalytic hydrogenation method of cyclohexene derivatives provided by the present invention, high conversion rate and excellent selectivity are achieved for cyclohexene derivative substrates, and the enantiomeric excess (ee) value of the obtained reduction product is high, which can reach 99%, is suitable for industrial scale-up production, can effectively improve production efficiency and product purity, and meet the needs of large-scale production.

[0051] 2. Compared with the chiral separation method commonly used in the prior art, the present invention uses a catalyst to carry out asymmetric catalytic hydrogenation of cyclohexene derivatives, which has lower cost. At the same time, the present invention uses a ruthenium catalyst to replace the iridium catalyst in the prior art for asymmetric catalytic hydrogenation. Since ruthenium is cheaper and more readily available than iridium, the production cost is further reduced. DETAILED DESCRIPTION

[0052] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art of the present invention. The terms used herein in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention. The term "and / or" used herein includes any and all combinations of one or more related listed items.

[0053] The present invention will be further described below in conjunction with the accompanying drawings and specific examples so that those skilled in the art can better understand the present invention and implement it, but the examples cited are not intended to limit the present invention. Unless otherwise specified, the percentages and parts used herein are weight percentages and weight parts.

[0054] Unless otherwise specified, the experimental methods used in the following examples are all conventional methods, and the materials, reagents, etc. used are all available from commercial sources unless otherwise specified.

[0055] The present invention provides a method for asymmetric catalytic hydrogenation of a cyclohexene derivative, comprising the following steps:

[0056] In a hydrogen atmosphere, the compound represented by Formula I (i.e., a cyclohexene derivative) is subjected to an asymmetric hydrogenation reduction reaction in the presence of a catalyst, an acid, and a solvent to form a compound represented by Formula II. The reaction formula is shown below:

[0057]

[0058] wherein Ar is selected from aryl or heteroaryl, and the aryl or heteroaryl is optionally substituted with one or more substituents selected from alkyl, alkoxy, cycloalkyl, aryl, halogen, nitro, acyl-containing group, sulfonyl-containing group or heteroaryl;

[0059] R is selected from alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein the alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with one or more substituents selected from halogen, nitro, amino, alkyl, alkoxy, cycloalkyl, heterocyclyl, acyl-containing group, sulfonyl-containing group, aryl or heteroaryl;

[0060] The ruthenium salt is selected from one or more of p-cymene diiodide ruthenium (II) dimer, dichlorobis (4-methylisopropylphenyl) ruthenium (II) dimer, dicarbonylcyclopentadienyl diruthenium (II) dimer, dichloro (pentamethylcyclopentadienyl) ruthenium (II) dimer, dichlorophenyl ruthenium (II) dimer, (hexamethylbenzene) dichlororuthenium (II) dimer, (1,5-cyclooctadiene) dichlororuthenium (II) and tricarbonyl dichlororuthenium dimer;

[0061] The acid is selected from one or more of hydrochloric acid, formic acid, sulfuric acid, acetic acid, trifluoroacetic acid, trifluoromethanesulfonic acid, benzoic acid and citric acid.

[0062] In a specific embodiment, the solvent is selected from one or more of methanol, ethanol, isopropanol, propanol, methyl chloride, acetonitrile, toluene, xylene, tert-butyl alcohol, butanol, isobutyl alcohol, acetone, 1,4-dioxane, tetrahydrofuran, methyl tert-butyl ether, ethyl acetate and methyl acetate. The amount of the solvent is a conventional amount so that the reactants can be completely dissolved therein.

[0063] In a specific embodiment, the ratio of the compound represented by formula I to the solvent is (5-40) mg:1 mL, preferably (10-20) mg:1 mL.

[0064] In a specific embodiment, the temperature of the asymmetric hydrogenation reduction reaction is 0-130°C, preferably 50-100°C, and more preferably 60-90°C.

[0065] In a specific embodiment, the asymmetric hydrogenation reduction reaction is carried out under a hydrogen pressure of 1-100 bar, preferably 50-80 bar.

[0066] In a specific embodiment, the molar ratio of the compound represented by formula I to the catalyst is (100-10000):1, preferably (200-3000):1.

[0067] With respect to the asymmetric catalytic hydrogenation method of the compound represented by Formula I in the prior art, the inventors of the present application have conducted extensive and in-depth research and developed a series of new catalysts formed by ruthenium salts and ligands. The catalysts are used for the asymmetric catalytic hydrogenation of the compound represented by Formula I, so that the conversion rate of the compound represented by Formula I is high and the reduction selectivity is good.

[0068] In a specific embodiment, the ligand is selected from the compounds represented by the following formulae:

[0069]

[0070] In a specific embodiment, the method for preparing the catalyst comprises the following steps:

[0071] Under nitrogen atmosphere, 10 mmol of the above ligand 1-40 and 10 mmol of dichlorobis(4-methylisopropylphenyl)ruthenium(II) were dissolved in 25 mL of methanol and heated under reflux for 2 h. Cooled to 25°C, the solvent was evaporated and separated by column chromatography (petroleum ether: ethyl acetate = 10:1) to obtain catalyst 1-40, the structural formula of which is shown below:

[0072]

[0073]

[0074] Example 1

[0075] A method for preparing a (R)-2-{2-[6-(benzyloxy)-(1,2,3,4-tetrahydronaphthalene)]yl)-5-methoxyphenyl)acetamide compound comprises the following steps:

[0076]

[0077] The compound shown in formula I-1-1 (200 mg, 0.500 mmol) and catalyst 40 (4 mg, 0.004 mmol) were added to a 30 mL reactor equipped with a magnetic stirrer. The nitrogen was replaced by vacuum, and 9 mL of anhydrous tert-butyl alcohol and 1 mL of benzoic acid were added. The gas in the reactor was replaced by hydrogen three times, and then hydrogen was added to a pressure of 80 bar. After stirring at 85°C for 80 hours, the temperature began to drop to room temperature and then the hydrogen was slowly released. The solvent was removed by evaporation under reduced pressure, and 5 mL of water was added to dilute it and extracted three times with 10 mL of ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, and the solvent was evaporated to obtain (R)-2-{2-[6-(benzyloxy)-(1,2,3,4-tetrahydronaphthalene)]yl)-5-methoxyphenyl)acetamide compound (compound shown in formula II-1-1), and the raw material conversion rate was above 97%, and the ee value was 99%.

[0078] The hydrogen nuclear magnetic resonance spectrum of catalyst 40 is as follows: 1H NMR(400MHz,Chloroform-d)δ7.77(ddd,J=7.1,4.1,1.4Hz,1H),7.60-7.54(m,4H),7.39-7.29(m,3H),7.3 3-7.22(m,5H),6.99(s,1H),δ6.91(dq,J=5.0,0.9Hz,2H),6.79–6.74(m,2H),4.20(dd,J=12.5,3.3Hz,1H), 4.12(dd,J=12.4,5.0Hz,1H),3.52(tdd,J=8.6,5.1,3.3Hz,1H),2.89–2.77(m,1H),2.22(d,J=2.0Hz,1H)1 .78(dd,J=12.3,8.6Hz,1H),1.55(dd,J=12.3,8.6Hz,1H),0.94(s,2H),0.88(d,J=6.6Hz,6H),0.85(s,7H).

[0079] The hydrogen nuclear magnetic resonance spectrum of the compound represented by formula II-1-1 is as follows: 1 H NMR (400MHz, DMSO-d6) δ9.34 (s, 1H), 7.47-7.34 (m, 4H), 7.32 (td, J = 7.2, 6.7, 3 .0Hz,1H),7.21(d,J=8.7Hz,1H),7.00-6.91(m,2H),6.81-6.72(m,3H),5.06(s, 2H),3.71(s,3H),3.07(ddt,J=14.5,7.9,4.0Hz,1H),2.91-2.72(m,3H),2.64( dd,J=16.0,11.6Hz,1H),2.01(s,3H),1.88-1.68(m,2H),1.24(d,J=5.9Hz,2H).

[0080] The method for preparing (R)-2-{2-[6-(benzyloxy)-(1,2,3,4-tetrahydronaphthalene)]yl)-5-methoxyphenyl)acetamide compound in Example 2-40 is basically the same as that in Example 1, except that catalyst 40 is replaced by the above-mentioned catalyst 1-39.

[0081] The method for preparing (R)-2-{2-[6-(benzyloxy)-(1,2,3,4-tetrahydronaphthalene)]yl)-5-methoxyphenyl)acetamide compound in Examples 41-46 is basically the same as that in Example 1, except that different acids are used for the reaction.

[0082] The method for preparing (R)-2-{2-[6-(benzyloxy)-(1,2,3,4-tetrahydronaphthalene)]yl)-5-methoxyphenyl)acetamide compound in Examples 47-52 is basically the same as that in Example 3, except that different acids are used for the reaction.

[0083] Examples 1-52 used different catalysts to carry out asymmetric catalytic hydrogenation reduction reactions. The catalytic evaluation results of the catalysts are shown in Table 1:

[0084] Table 1

[0085]

[0086]

[0087]

[0088] It can be seen from the above Examples 41-52 that, under the same hydrogen pressure and temperature conditions, the catalyst affects the catalytic yield and ee value under different acid conditions, and the best condition is to use benzoic acid for catalytic hydrogenation.

[0089] Obviously, the above embodiments of the present invention are only examples for clearly illustrating the present invention, and are not intended to limit the embodiments of the present invention. Those skilled in the art should understand that other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to list all the embodiments here. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the claims of the present invention.

Claims

1. A method for asymmetric catalytic hydrogenation of cyclohexene derivatives, characterized in that: The following steps are involved: Under a hydrogen atmosphere, the compound represented by Formula I is subjected to an asymmetric hydrogenation reduction reaction in the presence of a catalyst, an acid and a solvent to form a compound represented by Formula II. The reaction formula is shown below: wherein Ar is selected from aryl or heteroaryl, and the aryl or heteroaryl is optionally substituted with one or more substituents selected from alkyl, alkoxy, cycloalkyl, aryl, halogen, nitro, acyl-containing group, sulfonyl-containing group or heteroaryl; R is selected from alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein the alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with one or more substituents selected from halogen, nitro, amino, alkyl, alkoxy, cycloalkyl, heterocyclyl, acyl-containing group, sulfonyl-containing group, aryl or heteroaryl; The catalyst is obtained by reacting a ligand and a ruthenium salt, and the ligand is selected from the compound shown in the following formula: In Formula III, R 1 , R 2 , R 3 and R 4 Each is independently selected from hydrogen, halogen, alkyl, alkoxy, cycloalkyl or aryl, wherein the alkyl, alkoxy, cycloalkyl, aryl is optionally substituted with one or more substituents selected from halogen, nitro, cyano, alkyl, alkoxy, cycloalkyl, acyl-containing group, sulfonyl-containing group or aryl; In formula IV and V, R 5 independently selected from hydrogen, alkyl, alkoxy, cycloalkyl or aryl, wherein the alkyl, alkoxy, cycloalkyl or aryl is optionally substituted with one or more substituents selected from halogen, nitro, alkyl, alkoxy, cycloalkyl, an acyl-containing group, a sulfonyl-containing group or an aryl group; In Formula VI, R 6 and R 7 are each independently selected from hydrogen, halogen, alkyl, alkoxy, cycloalkyl or aryl, or R 6 and R 7 Together with the carbon to which it is attached, it forms a 5- to 6-membered ring, or R on two benzene rings 7 Together with the carbon to which it is attached, it forms a 7 to 12 membered ring, wherein the alkyl, alkoxy, cycloalkyl, aryl, 5 to 6 membered ring, 7 to 12 membered ring is optionally substituted with one or more substituents selected from halogen, nitro, cyano, alkyl, alkoxy, cycloalkyl, acyl-containing group, sulfonyl-containing group or aryl; R 8 is aryl, wherein the aryl is optionally substituted with one or more substituents selected from halogen, nitro, cyano, alkyl, alkoxy, cycloalkyl, acyl-containing group, sulfonyl-containing group or aryl; The ruthenium salt is selected from one or more of p-cymene diiodide ruthenium (II) dimer, dichlorobis (4-methylisopropylphenyl) ruthenium (II) dimer, dicarbonylcyclopentadienyl diruthenium (II) dimer, dichloro (pentamethylcyclopentadienyl) ruthenium (II) dimer, dichlorophenyl ruthenium (II) dimer, (hexamethylbenzene) dichlororuthenium (II) dimer, (1,5-cyclooctadiene) dichlororuthenium (II) and tricarbonyl dichlororuthenium dimer; The acid is selected from one or more of hydrochloric acid, formic acid, sulfuric acid, acetic acid, trifluoroacetic acid, trifluoromethanesulfonic acid, benzoic acid and citric acid.

2. The asymmetric catalytic hydrogenation method according to claim 1, characterized in that The structure of the compound represented by formula I is shown in the following formula I-1: Among them, R 9 is hydrogen or a hydroxyl protecting group; R 10 and R 11 Each is independently selected from hydrogen, alkyl or an acyl-containing group, wherein the alkyl is optionally substituted with one or more substituents selected from halogen, nitro, cyano, amino, alkyl, alkoxy, cycloalkyl, phenyl, acyl-containing substituents; R 12 is selected from hydrogen, alkyl or cycloalkyl, wherein the alkyl or cycloalkyl is optionally substituted by one or more substituents selected from halogen, nitro, cyano, amino, alkyl, alkoxy, and phenyl.

3. The asymmetric catalytic hydrogenation method according to claim 2, characterized in that: The hydroxy protecting group is selected from trimethylsilyl, triisopropylsilyl, tert-butyldimethyl, methyl, ethyl, propyl, benzyl, acetyl, propionyl, benzoyl, methylsulfonylbenzenesulfonyl.

4. The asymmetric catalytic hydrogenation method according to claim 1, characterized in that The compound represented by formula I-1 is selected from one of the following structures:

5. The asymmetric catalytic hydrogenation method according to claim 1, characterized in that: The temperature of the asymmetric hydrogenation reduction reaction is 0-130°C.

6. The asymmetric catalytic hydrogenation method according to claim 1, characterized in that The asymmetric hydrogenation reduction reaction is carried out under a hydrogen pressure of 1-100 bar.

7. The asymmetric catalytic hydrogenation method according to claim 1, characterized in that: The molar ratio of the compound represented by formula I to the catalyst is (100-10000):

1.

8. The asymmetric catalytic hydrogenation method according to any one of claims 1 to 7, characterized in that: The catalyst is selected from the compounds shown in the following structures:

9. A catalyst, characterized in that The catalyst is selected from the compounds shown in the following structures:

10. Use of the catalyst according to claim 9 in asymmetric catalytic reduction of double bonds.

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