Asymmetric catalytic hydrogenation method for cyclohexene derivative
By using inexpensive and readily available ruthenium salts and ligand catalysts for the asymmetric hydrogenation reduction of cyclohexene derivatives, the problems of low catalyst selectivity and conversion efficiency in existing technologies are solved, and efficient and low-cost compound synthesis is achieved.
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- ANHUI CAT-LAB TECHNOLOGY CO LTD
- Filing Date
- 2025-05-06
- Publication Date
- 2026-07-02
AI Technical Summary
In existing asymmetric catalytic hydrogenation reduction of double bonds, the catalyst selectivity and conversion efficiency are low, resulting in high production costs and low efficiency. Furthermore, the high price of existing metal catalysts limits their widespread application.
Using a catalyst formed from inexpensive and readily available ruthenium salts and ligands, an asymmetric hydrogenation reduction reaction is carried out with cyclohexene derivatives and acids in a solvent under a hydrogen atmosphere to form compounds with specific configurations.
It achieves high conversion rate and high selectivity, and the generated reduction product has a high enantiomeric excess value, which reduces production costs and is suitable for industrial production.
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Figure PCTCN2025092779-FTAPPB-I100001 
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Figure PCTCN2025092779-FTAPPB-I100003
Abstract
Description
An asymmetric catalytic hydrogenation method for cyclohexene derivatives Technical Field
[0001] This invention relates to the technical field of hydrogenation of organic compounds, specifically to an asymmetric catalytic hydrogenation method for cyclohexene derivatives. Background Technology
[0002] In the field of compound synthesis, particularly in the synthesis of pharmaceutical intermediates, asymmetric hydrogenation-reduction of double bonds is a crucial reaction step. This step aims to convert a substrate containing a double bond into a compound with a specific configuration through a specific catalytic process. Currently, the most common 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 exhibit poor selectivity when catalytically reducing the substrate, meaning that the catalytic reduction reaction may produce multiple reduction products, with the target configuration being only one of them. Therefore, to obtain a pure target configuration compound, subsequent cumbersome resolution steps are usually required, which not only increases production costs but also reduces production efficiency. Second, substrate conversion efficiency is also a key factor affecting the effectiveness of asymmetric catalytic hydrogenation-reduction of double bonds, especially when the structure of the substrate and the reduction product is very similar, making separation particularly difficult and leading to a significant decrease in substrate conversion efficiency. In such cases, even if the catalyst itself has a certain level of activity, it is difficult to achieve efficient catalytic conversion. Furthermore, the choice of catalyst is crucial for the substrate to be reduced. An ideal catalyst should possess high conversion and high selectivity, meaning it can convert the substrate to be reduced almost completely into a compound of the target configuration (e.g., conversion of 99% or higher), and the resulting reduction product should exhibit high enantioselectivity (e.g., ee value of 99% or higher). However, existing metal or metal complex catalysts often fall short of meeting these requirements.
[0003] To address these issues, researchers have attempted to separate diastereomers or prepare individual stereoisomers using methods such as solubility-based separation / resolution techniques or enzymatic resolution. However, these methods have limited applicability, only applicable to compounds with specific structures, and enzymatic resolution of corresponding isomers typically requires stringent reaction conditions, such as temperature and pH, which restricts their further application. Chinese patent CN117362142A uses iridium-based catalysts, achieving some success, but the high cost of iridium limits its widespread use.
[0004] Therefore, there is an urgent need to develop a novel asymmetric catalytic hydrogenation reduction method for double bonds that can use cheaper and more readily available catalysts while achieving high conversion and high selectivity. Summary of the Invention
[0005] To address the aforementioned technical problems, this invention provides an asymmetric catalytic hydrogenation method for cyclohexene derivatives.
[0006] This invention is achieved through the following technical solution:
[0007] This invention provides an asymmetric catalytic hydrogenation method for cyclohexene derivatives, comprising the following steps:
[0008] In a hydrogen atmosphere, the compound represented by Formula I (i.e., the cyclohexene derivative) undergoes an asymmetric hydrogenation-reduction reaction in the presence of a catalyst, acid, and solvent to form the compound represented by Formula II, as shown in the following reaction formula:
[0009] Wherein, Ar is selected from aryl or heteroaryl, and the aryl or heteroaryl is optionally replaced by one or more substituents selected from alkyl, alkoxy, cycloalkyl, aryl, halogen, nitro, acyl-containing group, sulfonyl-containing group or heteroaryl;
[0010] R is selected from alkyl, alkoxy, cycloalkyl, heterocyclic, aryl, or heteroaryl, wherein the alkyl, alkoxy, cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally substituted by one or more substituents selected from halogen, nitro, cyano, amino, alkyl, alkoxy, cycloalkyl, heterocyclic, acyl-containing group, sulfonyl-containing group, aryl, or heteroaryl group.
[0011] The catalyst is obtained by reacting a ligand with a ruthenium salt, wherein the ligand is selected from compounds represented by the following formula:
[0012] 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, or aryl group is optionally substituted by one or more substituents selected from halogen, nitro, cyano, alkyl, alkoxy, cycloalkyl, acyl-containing group, sulfonyl-containing group, or aryl group;
[0013] In equations IV and V, R 5 The group is independently selected from hydrogen, alkyl, alkoxy, cycloalkyl, or aryl, wherein the alkyl, alkoxy, cycloalkyl, or aryl group is optionally substituted by one or more substituents selected from halogen, nitro, alkyl, alkoxy, cycloalkyl, acyl-containing group, sulfonyl-containing group, or aryl group;
[0014] In Equation VI, R 6 and R 7Each is independently selected from hydrogen, halogen, alkyl, alkoxy, cycloalkyl, or aryl, or R 6 and R 7 Together with the carbon atoms attached to it, it forms a 5- or 6-membered ring, or R on the two benzene rings. 7 Together with the carbon atom connected thereto, a 7- to 12-membered ring is formed, wherein the alkyl, alkoxy, cycloalkyl, aryl, 5- to 6-membered ring, or 7- to 12-membered ring is optionally substituted by one or more substituents selected from halogen, nitro, cyano, alkyl, alkoxy, cycloalkyl, acyl-containing group, sulfonyl-containing group, or aryl; R 8 The aryl group is optionally substituted by one or more substituents selected from halogen, nitro, cyano, alkyl, alkoxy, cycloalkyl, acyl-containing group, sulfonyl-containing group or aryl group;
[0015] The ruthenium salt is selected from one or more of the following: p-cymene ruthenium(II) diiodide dimer, dichlorobis(4-methylisopropylphenyl)ruthenium(II) dimer, dicarbonylcyclopentadienyl diruthenium(II) dimer, dichloro(pentamethylcyclopentadienyl)ruthenium(II) dimer, dichlorophenylruthenium(II) dimer, (hexamethylphenyl) ruthenium(II) dichloride dimer, (1,5-cyclooctadiene)ruthenium(II) dichloride, and tricarbonyl dichlororuthenium dimer;
[0016] 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.
[0017] 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 halogens, alkyl groups, and alkoxy groups.
[0018] 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.
[0019] 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, or phenyl group is optionally substituted by one or more substituents selected from alkyl, alkyl, cycloalkyl, or phenyl.
[0020] Preferably, in formulas IV and V, R 5 The group is independently selected from hydrogen, alkyl, cycloalkyl, or phenyl, wherein the alkyl, cycloalkyl, or phenyl group is optionally substituted by one or more substituents selected from alkyl, cycloalkyl, or phenyl.
[0021] Preferably, in formula VI, R 6 and R 7Each is independently selected from hydrogen, alkyl, cycloalkyl, or phenyl, or R 6 and R 7 Together with the carbon atom to which it is attached, it forms a 5- or 6-membered ring, wherein the alkyl, cycloalkyl, or phenyl group is optionally substituted by one or more substituents selected from alkyl, alkyl, cycloalkyl, or phenyl, and the 5- or 6-membered ring is substituted with a benzene ring and shares two carbon atoms with the substituted benzene ring.
[0022] Furthermore, the solvent is selected from one or more of methanol, ethanol, isopropanol, propanol, chloromethane, acetonitrile, toluene, xylene, tert-butanol, butanol, isobutanol, acetone, 1,4-dioxane, tetrahydrofuran, methyl tert-butyl ether, ethyl acetate, and methyl acetate.
[0023] Furthermore, the ratio of the compound represented by Formula I to the solvent is (5-40) mg:1 mL, preferably (10-20) mg:1 mL.
[0024] Furthermore, the structure of the compound represented by Formula I is shown in Formula I-1 below:
[0025] Among them, R 9 It is a hydrogen or hydroxyl protecting group;
[0026] R 10 and R 11 Each group is independently selected from hydrogen, alkyl, or acyl groups, wherein the alkyl group is optionally substituted by one or more substituents selected from halogen, nitro, cyano, amino, alkyl, alkoxy, cycloalkyl, phenyl, or acyl groups;
[0027] R 12 The group is selected from hydrogen, alkyl, or cycloalkyl, wherein the alkyl or cycloalkyl group is optionally substituted by one or more substituents selected from halogen, nitro, cyano, amino, alkyl, alkoxy, or phenyl.
[0028] 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 (methanesulfonyl), or PhSO2 (benzenesulfonyl).
[0029] Furthermore, the compound represented by Formula I-1 is selected from one of the following structures:
[0030] Furthermore, the temperature of the asymmetric hydrogenation reduction reaction is 0-130°C, preferably 50-100°C, and more preferably 60-90°C.
[0031] Furthermore, the asymmetric hydrogenation reduction reaction is carried out under a hydrogen pressure of 1-100 bar, preferably 50-80 bar.
[0032] Furthermore, the molar ratio of the compound represented by Formula I to the catalyst is (100-10000):1, preferably (200-3000):1.
[0033] Furthermore, the preparation method of the catalyst includes the following steps: the ligand and the ruthenium salt react to form a complex, thereby obtaining the catalyst.
[0034] Furthermore, the molar ratio of the ligand to the ruthenium salt is 1:(0.8-1.2).
[0035] Furthermore, the catalyst is selected from compounds with the following structures:
[0036] This invention also protects the use of the above-mentioned catalyst in the asymmetric catalytic reduction of double bonds.
[0037] In a specific embodiment, the present invention provides an asymmetric catalytic hydrogenation method for the compound represented by Formula I-1, comprising the following steps:
[0038] In a hydrogen atmosphere, the compound shown in Formula I-1 undergoes an asymmetric hydrogenation-reduction reaction in the presence of a catalyst, acid, and solvent to form the compound shown in Formula II-1, as shown in the following reaction formula:
[0039] Among them, R 9 Selected from H, Bn, Cbz, or Ac.
[0040] The catalyst is selected from compounds with the following structures:
[0041] The beneficial effects of this invention are:
[0042] 1. The asymmetric catalytic hydrogenation method for cyclohexene derivatives provided by this invention achieves high conversion rate and excellent selectivity for cyclohexene derivative substrates. The enantiomeric excess (ee) value of the obtained reduction product is high, reaching 99%, which is suitable for industrial-scale production. It can effectively improve production efficiency and product purity, and meet the needs of large-scale production.
[0043] 2. Compared to the chiral resolution methods commonly used in the prior art, this invention employs a catalyst for asymmetric catalytic hydrogenation of cyclohexene derivatives, which is less costly. Furthermore, this invention uses a ruthenium catalyst instead of the iridium catalyst in the prior art for asymmetric catalytic hydrogenation. Since ruthenium is cheaper and more readily available than iridium, this further reduces production costs. Detailed Implementation
[0044] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used herein in the description of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.
[0045] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, so that those skilled in the art can better understand and implement the present invention. However, the embodiments described are not intended to limit the present invention. Unless otherwise stated, percentages and parts as used herein are weight percentages and parts by weight.
[0046] Unless otherwise specified, the experimental methods used in the following examples are conventional methods, and the materials and reagents used are commercially available.
[0047] This invention provides an asymmetric catalytic hydrogenation method for cyclohexene derivatives, comprising the following steps:
[0048] In a hydrogen atmosphere, the compound represented by Formula I (i.e., the cyclohexene derivative) undergoes an asymmetric hydrogenation-reduction reaction in the presence of a catalyst, acid, and solvent to form the compound represented by Formula II, as shown in the following reaction formula:
[0049] Wherein, Ar is selected from aryl or heteroaryl, and the aryl or heteroaryl is optionally replaced by one or more substituents selected from alkyl, alkoxy, cycloalkyl, aryl, halogen, nitro, acyl-containing group, sulfonyl-containing group or heteroaryl;
[0050] R is selected from alkyl, alkoxy, cycloalkyl, heterocyclic, aryl, or heteroaryl, wherein the alkyl, alkoxy, cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally substituted by one or more substituents selected from halogen, nitro, amino, alkyl, alkoxy, cycloalkyl, heterocyclic, acyl-containing group, sulfonyl-containing group, aryl, or heteroaryl group;
[0051] The ruthenium salt is selected from one or more of the following: p-cymene ruthenium(II) diiodide dimer, dichlorobis(4-methylisopropylphenyl)ruthenium(II) dimer, dicarbonylcyclopentadienyl diruthenium(II) dimer, dichloro(pentamethylcyclopentadienyl)ruthenium(II) dimer, dichlorophenylruthenium(II) dimer, (hexamethylphenyl) ruthenium(II) dichloride dimer, (1,5-cyclooctadiene)ruthenium(II) dichloride, and tricarbonyl dichlororuthenium dimer;
[0052] 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.
[0053] In a specific embodiment, the solvent is selected from one or more of methanol, ethanol, isopropanol, propanol, chloromethane, acetonitrile, toluene, xylene, tert-butanol, butanol, isobutanol, acetone, 1,4-dioxane, tetrahydrofuran, methyl tert-butyl ether, ethyl acetate, and methyl acetate. The amount of solvent used is conventional, ensuring complete dissolution of the reactants.
[0054] 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.
[0055] 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.
[0056] In a specific embodiment, the asymmetric hydrogenation reduction reaction is carried out under a hydrogen pressure of 1-100 bar, preferably 50-80 bar.
[0057] 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.
[0058] In response to the existing asymmetric catalytic hydrogenation method for the compound represented by Formula I, the inventors of this application have conducted extensive and in-depth research and developed a series of new catalysts formed by ruthenium salts and ligands. These catalysts are used for the asymmetric catalytic hydrogenation of the compound represented by Formula I, resulting in high conversion rate and good reduction selectivity for the compound represented by Formula I.
[0059] In a specific embodiment, the ligand is selected from compounds represented by the following formulas: ligand 1-ligand 40
[0060] In a specific embodiment, the catalyst preparation method includes the following steps:
[0061] Under a 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 the mixture was heated under reflux for 2 h. After cooling to 25 °C, the solvent was evaporated, and the mixture was separated by column chromatography (petroleum ether: ethyl acetate = 10:1) to obtain catalyst 1-40, the structural formula of which is shown below:
[0062] Example 1
[0063] A method for preparing (R)-2-{2-[6-(benzyloxy)-(1,2,3,4-tetrahydronaphthalene)]yl)-5-methoxyphenyl)acetamide compound, comprising the following steps:
[0064] The compound shown in Formula I-1-1 (200 mg, 0.500 mmol) and catalyst 40 (4 mg, 0.004 mmol) were sequentially added to a 30 mL reactor equipped with a magnetic stirrer. The reactor was evacuated to purge with nitrogen, and 9 mL of anhydrous tert-butanol and 1 mL of benzoic acid were added. After purging the reactor with hydrogen three times, hydrogen was added until the pressure reached 80 bar. The reactor was stirred at 85 °C for 80 h, then cooled to room temperature and hydrogen was slowly released. The solvent was removed by vacuum evaporation, diluted with 5 mL of water, 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 (the compound shown in Formula II-1-1). The conversion rate of the starting material was over 97%, and the ee value was 99%.
[0065] The 1H NMR 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).
[0066] The proton NMR 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).
[0067] The method for preparing (R)-2-{2-[6-(benzyloxy)-(1,2,3,4-tetrahydronaphthalene)]yl)-5-methoxyphenyl)acetamide compounds in Examples 2-40 is basically the same as that in Example 1, except that catalyst 40 is replaced with catalysts 1-39 as described above.
[0068] The methods for preparing (R)-2-{2-[6-(benzyloxy)-(1,2,3,4-tetrahydronaphthalene)]yl)-5-methoxyphenyl)acetamide compounds in Examples 41-46 are basically the same as those in Example 1, except that different acids are used for the reaction.
[0069] The method for preparing (R)-2-{2-[6-(benzyloxy)-(1,2,3,4-tetrahydronaphthalene)]yl)-5-methoxyphenyl)acetamide compounds in Examples 47-52 is basically the same as that in Example 3, except that different acids are used for the reaction.
[0070] Examples 1-52 employed different catalysts for asymmetric catalytic hydrogenation-reduction reactions. The catalytic evaluation results of the catalysts are shown in Table 1.
[0071] Table 1
[0072] As can be seen from Examples 41-52 above, under the same hydrogen pressure and temperature conditions, the catalyst affects the catalytic yield and ee value under different acid conditions, and the optimal condition is to use benzoic acid for catalytic hydrogenation.
[0073] Obviously, the above embodiments of the present invention are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation of the present invention. Those skilled in the art should understand that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively describe all embodiments here. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the scope of protection of the claims of the present invention.
Claims
1. An asymmetric catalytic hydrogenation method for cyclohexene derivatives, characterized in that, Includes the following steps: Under a hydrogen atmosphere, the compound represented by Formula I undergoes an asymmetric hydrogenation-reduction reaction in the presence of a catalyst, acid, and solvent to form the compound represented by Formula II, as shown in the following reaction formula: Wherein, Ar is selected from aryl or heteroaryl, and the aryl or heteroaryl is optionally replaced by 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, heterocyclic, aryl, or heteroaryl, wherein the alkyl, alkoxy, cycloalkyl, heterocyclic, aryl, or heteroaryl group is optionally substituted by one or more substituents selected from halogen, nitro, amino, alkyl, alkoxy, cycloalkyl, heterocyclic, acyl-containing group, sulfonyl-containing group, aryl, or heteroaryl group; The catalyst is obtained by reacting a ligand with a ruthenium salt, wherein the ligand is selected from compounds represented by 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, or aryl group is optionally substituted by one or more substituents selected from halogen, nitro, cyano, alkyl, alkoxy, cycloalkyl, acyl-containing group, sulfonyl-containing group, or aryl group; In equations IV and V, R 5 The group is independently selected from hydrogen, alkyl, alkoxy, cycloalkyl, or aryl, wherein the alkyl, alkoxy, cycloalkyl, or aryl group is optionally substituted by one or more substituents selected from halogen, nitro, alkyl, alkoxy, cycloalkyl, acyl-containing group, sulfonyl-containing group, or aryl group; In Equation VI, R 6 and R 7 Each is independently selected from hydrogen, halogen, alkyl, alkoxy, cycloalkyl, or aryl, or R 6 and R 7 Together with the carbon atoms attached to it, it forms a 5- or 6-membered ring, or R on the two benzene rings. 7 Together with the carbon atom connected thereto, a 7- to 12-membered ring is formed, wherein the alkyl, alkoxy, cycloalkyl, aryl, 5- to 6-membered ring, or 7- to 12-membered ring is optionally substituted by one or more substituents selected from halogen, nitro, cyano, alkyl, alkoxy, cycloalkyl, acyl-containing group, sulfonyl-containing group, or aryl; R 8 The aryl group is optionally substituted by one or more substituents selected from halogen, nitro, cyano, alkyl, alkoxy, cycloalkyl, acyl-containing group, sulfonyl-containing group or aryl group; The ruthenium salt is selected from one or more of the following: p-cymene ruthenium(II) diiodide dimer, dichlorobis(4-methylisopropylphenyl)ruthenium(II) dimer, dicarbonylcyclopentadienyl diruthenium(II) dimer, dichloro(pentamethylcyclopentadienyl)ruthenium(II) dimer, dichlorophenylruthenium(II) dimer, (hexamethylphenyl) ruthenium(II) dichloride dimer, (1,5-cyclooctadiene)ruthenium(II) dichloride, 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 Formula I-1 below: Among them, R 9 It is a hydrogen or hydroxyl protecting group; R 10 and R 11 Each group is independently selected from hydrogen, alkyl, or acyl groups, wherein the alkyl group is optionally substituted by one or more substituents selected from halogen, nitro, cyano, amino, alkyl, alkoxy, cycloalkyl, phenyl, or acyl groups; R 12 The group is selected from hydrogen, alkyl, or cycloalkyl, wherein the alkyl or cycloalkyl group is optionally substituted by one or more substituents selected from halogen, nitro, cyano, amino, alkyl, alkoxy, or phenyl.
3. The asymmetric catalytic hydrogenation method according to claim 2, characterized in that, The hydroxyl protecting group is selected from trimethylsilyl, triisopropylsilyl, tert-butyldimethyl, methyl, ethyl, propyl, benzyl, acetyl, propionyl, benzoyl, methanesulfonylbenzenesulfonyl.
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℃.
6. The asymmetric catalytic hydrogenation method according to claim 1, characterized in that, The asymmetric hydrogenation-reduction reaction is carried out under 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 1-7, characterized in that, The catalyst is selected from compounds with the following structures:
9. A catalyst, characterized in that, The catalyst is selected from compounds with the following structures:
10. The application of the catalyst according to claim 9 in the asymmetric catalytic reduction of double bonds.