CN1309728C - Chiral organic, inorganic polymer assembled catalyst, synthesis method and use - Google Patents

Abstract

The invention relates to a novel ligand, a chiral catalyst and a loading method and application of the chiral catalyst. Phosphorus-containing chiral ligands and transition metal ions are used to form organic-inorganic polymer assemblies through coordination. The catalyst can be used for asymmetric catalytic hydrogenation of α-dehydroamino acid and its derivatives, various enamines, itaconic acid and its derivatives and other compounds. The asymmetric catalytic hydrogenation of the above compounds can be used in the synthesis of compounds such as α-amino acids and their derivatives, chiral amines and their derivatives, and 2-alkyl-1,4-butanedioic acid and its derivatives. The structural formula of the self-supporting catalyst provided by the present invention is as follows.

Description

A class of chiral organic-inorganic polymer assembly catalyst, synthesis method and use

technical field

The invention relates to a novel ligand, a chiral catalyst and a loading method and application of the chiral catalyst. Using phosphorus-containing chiral ligands and transition metal ions to form organic-inorganic polymer assemblies through coordination, the metal ions in the assemblies provide catalytic centers, and the ligands provide chiral environments. The advantage is that these assemblies are insoluble in common Organic solvents, thus providing a new way for heterogeneous asymmetric catalysis, because this type of heterogeneous chiral catalyst does not use any other organic or inorganic support, so it is called self-supporting chiral catalyst. The catalyst can be used for asymmetric catalytic hydrogenation of α-dehydroamino acid and its derivatives, various enamines, itaconic acid and its derivatives and other compounds. The asymmetric catalytic hydrogenation of the above compounds can be used in the synthesis of compounds such as α-amino acids and their derivatives, chiral amines and their derivatives, and 2-alkyl-1,4-butanedioic acid and its derivatives.

Background technique

Asymmetric catalytic hydrogenation is one of the important methods in asymmetric synthesis and is widely used in chemical industrial processes [Ohkuma, T.; Kitamura, M.; Noryori, R. (1999) Asymmetric Hydrogenation. In: Ojiama, I. (ed) Catalytic Asymmetric Synthesis. (2nd Ed.). Wily-VCH: NewYork (Englinsh) 2000]. The key to asymmetric catalytic hydrogenation is to design and develop highly active and selective ligands and their catalytic systems. The continuous emergence of highly efficient chiral phosphorus ligands facilitates asymmetric catalytic hydrogenation

Figure 1 Development of representative chiral bidentate phosphine ligands. [Osborn, J.A.; Jardine, F.H.; Young, J.F.; Willinson, G.J. Chem. Soc. A1966, 1711], [Knowles, W.S.; Sabacky, M.J.J. J.D.; Burnett, R.E.; Anguiar, A.M.; Morrow, C.J.; Phillip, C.J. Am. Chem. Soc.1971, 93, 1301], [Yasuda, A.; ; Ito, T.; Souchi, T.; Noyo, R.J.Am.Chem.Soc.1980, 198O, 7392], [Nugent, W.A.; Rajababu, T.V.; M. J. Acc. Chem. Res. 2000, 33, 363]. So far, most of the more than 2000 chiral phosphorus ligands that have appeared are bidentate phosphorus ligands (as shown in Figure 1). Although chiral monodentate phosphorus ligands were the first class of ligands used in asymmetric catalytic hydrogenation reactions, and such ligands have also been widely used in other asymmetric reactions, but since Kagan et al. in 1971 synthesized the first A Chiral Bidentate Phosphorus Ligand The application of chiral monodentate phosphorus ligands in asymmetric catalytic hydrogenation has been neglected since. [Dang, T.P.; Kagan, H.B.J. Chem.Soc.Chem.Commun.1971, 481], [Lagasse, F.; Kagan, H.B.Chem.Pharm.Bull.2000, 48, 315], [Hayashi, T.J.Organomet.Chem .1999, 576, 195], [Hayashi, T. Acc. Chem. Res. 2000, 33, 354]. It was not until 2000 that the application of monodentate phosphorus ligands in asymmetric catalytic hydrogenation aroused people's attention again. With Feringa's reported phosphoramidite (MonoPhos, a) [van dern Berg, M.; Minnaard, A.J.; de Vries, A.H.M.; de Vries, J.G; Feringa, B.L.J.Am.Chem.Soc.2000, 122, 1539], [Pena, D.; Minnaard, A.J.; de Vries, J.G.; , 124, 14552], [van den Berg, M.; Minnaard, A.J.; de Vries, J.G.; Feringa, B.L. (DSM N.V.), World Patent WO 02/04466, 2002], [van den Berg, M.; Minnaard , A.J.; Haak, R.M.; Leeman, M.; Schudde, E.P; Meetsma, A.; Feringa, B.L.; De Vries, A.H.M.; Maljaars, C.E.P.; Willans, C.E.; Hyett, D.J.; der Vries, J.G.Adv.Synth.Catal.2003, 345, 308], Reetz reported monodentate phosphite ligand b [Reetz, M.T.; Sell, T.Tetrahedron Lett.2000, 41, 6333], [Reetz , M.T.; Mehler, G.Angew.Chem.Int.Ed.2000, 39, 3889], [Claver, C.; Fernandez, E.; Gillon, A.; Heslop, K.; Hyett, D.J.; Martovell, A. .; Orpen, A.G.; Pringli, P.G.Chem.Commun.2000, 961], [Reetz, M.T.; Sell, T.; Meiswinkel, A.; Mehler, G.Angew.Chem.Int.Ed. ] and the spirocyclic ligand SiPHOS(c) reported by Zhou Qilin et al., [Hu, A.-G.; Fu, Y.; Xie, J.-H.; Zhou, H.; Wang, L.-X. ; Zhou, Q.-L.Angew.Chem.Int.Ed.2002, 41, 2348] is the most representative.

Figure 2 Representative chiral monodentate phosphorus ligands

Although homogeneous asymmetric catalysis has the characteristics of high stereoselectivity, high reaction efficiency, and mild conditions, the amount of catalyst used is mostly between 1-10 mol%, and the catalyst is generally expensive and difficult to recover and recycle. [R. Noyori, Asymmetric Catalysis in Organic Synthesis, Wiley-Interscience, New York, 1994]; [Catalysis Asymmetric Synthesis 2nd ed. (Ed.: I.Ojima), Wiley-VCH, New York, 2000], [Comprehensive Asymmetric Catalysis , (Eds.: E.N.Jacobsen, A.Pfaltz, H.Yamamoto), Springer, Berlin, 1999, Vol.I-III]], [Lewis Acids in Organic Synthesis, (Ed.H.Yamamoto), Wiley-VCH, New York, 2001] In the homogeneous catalytic reaction, trace heavy metal pollutants in the product that are difficult to separate are a fatal problem in the production of chiral drugs. Due to the above reasons, most homogeneous catalysts are difficult to realize industrialization. [Chirality in industry: The Commercial Manufacture and Applications of Optically Active Compounds (Eds.: A.N. Collins, G.N. Sheldrake, J. Crosby), Wiley, Chichester, 1992]; [Chirality in Industry II: Developments in the Commercial Manufacture and Applications of Optically Active Compounds Active Compounds (Eds.: A.N.Collins, G.N.Sheldrake, J.Crosby), Wiley, Chichester, 1997]; [R.A.Sheldon, Chirotechnology: Industrial Synthesis of Optically Active Compounds, Dekker, New York, 1993] heterogeneous catalysis to solve the above The problem provides a good technical platform. Through the loading of homogeneous catalysts, it can not only solve the problem of recycling, but also reduce the metal pollutants from the catalyst and avoid complicated separation processes. [Chiral Catalyst Immobilization and Recycling, D.E.De Vos, I.F.J. Vankelccom, P.A. Jacobs, Eds., Wiley-VCH: Weinheim, 2000], [Chem. Rev. 2002, 102, issue 10].

At present, various strategies have been used to support homogeneous catalysts, such as using inorganic materials, organic polymers, dendrimers, membranes as supports, or using ionic phase and two-phase system strategies. Among them, organic polymer loading is a frequently used strategy, which can be summarized into the following three modes.

(1). Suspension type - chiral ligand or catalytic active unit is suspended on the organic polymer chain;

(2). Chimeric formula - chiral ligands are embedded in the polymer chain;

(3). Self-supporting type - chiral ligands and transition metal coordination, self-polymerization into polymer chains;

In the first loading mode, the ligands or active units are randomly loaded on the disordered polymer support, resulting in a lower loading of catalytically active species, while the stereoselectivity and catalytic efficiency of the catalyst are comparable to those of unsupported Corresponding homogeneous systems will have different degrees of reduction; [[de Vos, D.E.; Vankelecom, I.F.J.; Jacobs, P.A., Eds.In Chiral Catalyst Immobilization and Recycling; Wiley-VCH: Weinheim, 2000.] The second mode It makes up for the shortcomings of the first mode and improves the loading capacity, catalytic activity and selectivity of the catalyst. There have been some successful reports in recent years, but relatively speaking, the synthesis of polymer ligands in this mode is cumbersome. [Pu, L.; Chem.Eur.J.1999, 5, 2227], [Fan, Q.H.; Ren, C.Y.; Yeung, C.H.; Hu, W.H.; ], [ter Halle, R.; Colasson, B.; Schulz, E.; Spagnol, M.; Lemaire, M. Tetrahedron Lett.2000, 41, 643], [Arai, T.; K.; Takizawa, S.; Sasai, H. Angew Chem. Int. Ed.2003, 42, 2144], [Hu, A.; Ngo, H.L.; Lin, W. J. Am. Chem. Soc.2003, 125, 11490] , [Hu, A.; Ngo, H.L.; Lin, W. Anew.Chem.Int.Ed.2003, 115, 6182; Anew.Chem.Int.Ed.2003, 42, 6000]

In order to solve the problems existing in the above two load modes, we propose a third load mode - self-load mode, [Guo, H.; Wang, W.; Ding, K. Tetrahedron Lett.2004, 45.2009]; [ Takizawa, S.; Somei, H.; Jayaprakash, D.; Sasai, H.Angew.Chem.2003, 115, 5889; Angew.Chem.Int.Ed.2003, 42, 5711]; The ligand of the functional group and the metal ion are coordinated to form a polymer assembly as a catalyst. The chiral bridging ligands in the assembly participate in the formation of the chiral environment, and the metal ions serve as the catalytic active centers, so that the catalyst has a high-density catalytic active unit, and the catalyst has high catalytic activity and enantioselectivity. The catalyst is insoluble in general organic solvents, can perform heterogeneous catalysis, and is easy to recycle for many times. Based on this loading mode, the present invention provides catalysts for the formation of double-bridged monophosphorus ligands and Rh(I), synthesis methods, applications in heterogeneous asymmetric catalytic hydrogenation, recovery methods and recycling.

Contents of the invention

The purpose of the present invention is to provide a novel chiral catalyst and a new ligand. Another object of the present invention is to provide a synthesis method of the above-mentioned catalyst. The object of the present invention is also to provide the application of the above self-supporting catalyst, that is, it can be used to prepare a catalyst for asymmetric catalytic hydrogenation, and can be recycled for many times. In particular, the above-mentioned catalyst is applied to the asymmetric catalytic hydrogenation and multiple recycling of compounds such as α-dehydroamino acid and its derivatives, various enamines and their derivatives, and etoconic acid and its derivatives.

The structural formula of the new ligand provided by the invention can be:

Where: linker is a substituent such as a single bond, C _1-8 hydrocarbon group, 1,4-divinylphenyl, 1,4-diethynylphenyl, biphenyl or 9,10-anthracenyl. The C _1-8 hydrocarbon groups include p-phenyl, m-phenyl, o-phenyl, 1,4-methylenephenyl and the like.

或O-R^w，所述的烃基推荐为C_1～12的烃基，可以是甲基、乙基、正丙基、异丙基、正丁基、叔丁基、环戊基、环己基、环庚基、苯基、1-萘基、2-萘基等，进一步推荐为C_1～4的烃基；其中R^z、R^z和R^w可以分别为氢、C_1～12的烃基、C_1～12的烷氧基或卤素等，例如甲基、甲氧基、乙基、乙氧基、正丙基、异丙基、正丁基、叔丁基、环戊基、环己基、环庚基、苯基、苄基、1-苯基)乙基、1-萘基或2-萘基等，进一步推荐为C_1～4的烃基，C_1～4的烷氧基。R是C_mH_2m(m＝0-8)，O，N等。R can be hydrocarbyl, ethoxy,

Or OR ^w , the hydrocarbon group is recommended to be a C _1-12 hydrocarbon group, which can be methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, cyclopentyl, cyclohexyl, cycloheptyl phenyl, 1-naphthyl, 2-naphthyl, etc., which are further recommended as C _1-4 hydrocarbon groups; wherein R ^z , R ^z and R ^w can be hydrogen, C _1-12 hydrocarbon groups, C _{1-4 12} alkoxy or halogen, etc., such as methyl, methoxy, ethyl, ethoxy, n-propyl, isopropyl, n-butyl, tert-butyl, cyclopentyl, cyclohexyl, cycloheptyl , phenyl, benzyl, 1-phenyl)ethyl, 1-naphthyl or 2-naphthyl, etc., and further recommended are C _1-4 hydrocarbon groups, C _1-4 alkoxy groups. R is C _m H _2m (m=0-8), O, N and the like.

The ligand can be a compound of (R, R,) or (S, S,) configuration, and its structural formula is as follows:

In the formula, R, R' and linker are as described above.

The present invention also provides a synthetic method for the above-mentioned ligand, which may be the following 1) or 2):

在Pd(PPh₃)₄和碱的催化下发生Suzuki偶联反应得化合物6，有机溶剂中，酸作用下脱除MOM保护基得化合物7；7和PR₃在有机溶剂中回流反应并经后处理得8，1) Compound 5 and (linker)[B(OH) ₂ ] ₂ or

Under the catalysis of Pd(PPh ₃ ) ₄ and base, Suzuki coupling reaction occurred to obtain compound 6. In an organic solvent, the MOM protecting group was removed under the action of acid to obtain compound 7; 7 and PR ₃ were refluxed in an organic solvent and subjected to Handled 8,

In the formula, linker is a single bond, C═C, C≡C or C _1-8 hydrocarbon group, R is as mentioned above, MOM is methoxymethyl, and Pb is phenyl.

或其对映体和二酚或二醇、二胺类化合物用结构通式表示为HR’-linker-R’H，其中：linker为对苯基、间苯基、邻苯基、1，4-二乙烯基苯基、1，4-二乙炔基苯基、1，4-亚甲基苯基、联苯基或9，10-蒽基，R’如前所述。2) Under an inert gas atmosphere, the following compound 10

Or its enantiomers and diphenols or diols, diamine compounds are expressed as HR'-linker-R'H with a general structural formula, wherein: linker is p-phenyl, m-phenyl, o-phenyl, 1,4 - divinylphenyl, 1,4-diethynylphenyl, 1,4-methylenephenyl, biphenyl or 9,10-anthracenyl, R' is as described above.

The preparation process of the above-mentioned ligands is taken as an example with (S, S)-p-phenyl substituted double-bridged monophosphorus ligands, which can be simply represented by the following reaction formula:

In the formula, tBu stands for n-butyl, Bromine stands for bromine, Toluene stands for toluene, MOM stands for methoxymethyl, THF stands for tetrahydrofuran, DME stands for N,N-dimethylacetamide, aq. stands for aqueous solution, and reflux stands for reflux.

The specific reaction conditions recommended for the synthetic method in the above reaction process are as follows:

Optically pure (S)-BINOL and pivaloyl chloride (such as 1.1 molar ratio), add bases (such as triethylamine and pyridine), organic solvents such as THF, react from 0 ° C to room temperature, add water to quench after a few hours To quench the reaction, adjust the pH value of the system to 1 with an acid such as HCl, extract with a solvent such as toluene, combine the organic phases, evaporate the solvent under reduced pressure, recrystallize with a solvent such as n-hexane, and obtain 2 after the above post-treatment.

At 0°C, compound 2 was dissolved in a mixed solvent (such as acetonitrile and toluene), and Br ₂ was added dropwise, and the reaction was detected by HPLC until the raw materials disappeared. Add NaHSO ₃ aqueous solution to remove excess bromine, extract with ethyl acetate, combine the organic phases, evaporate the solvent under reduced pressure, separate by column chromatography, and obtain 3 after the above post-treatment.

Dissolve compound 3 in methanol, add NaOH aqueous solution dropwise, after completing the reaction (the reaction time is recommended to be 1 hour), adjust the pH value of the system to 1, extract with a solvent such as toluene, combine the organic phases, and evaporate under reduced pressure solvent, separated by column chromatography, and obtained 4 after the above-mentioned post-treatment.

At room temperature, an organic solvent solution of compound 4 such as a THF solution is added dropwise to an organic solvent suspension of NaH such as a THF suspension, after stirring, an organic solvent solution of MOMCl such as a THF solution is added dropwise, and the reaction takes 2 hours, for example, to Quench the reaction with methanol and water, extract with ether, combine the organic phases, wash with water, saturated NaHCO ₃ and NaCl aqueous solution successively, dry with anhydrous Na ₂ SO ₄ , evaporate the solvent, dichloromethane-n-hexane recrystallization, after Compound 5 was obtained by the above post-treatment.

Compound 5 and terephthalic acid undergo a Suzuki coupling reaction under the catalysis of Pd(PPh ₃ ) ₄ and a base such as aq.NaHCO ₃ to obtain compound 6b, which is removed in an organic solvent such as a mixture of chloroform and methanol and under the action of an acid such as hydrochloric acid Compound 7b was obtained from the MOM protecting group; 7b and P[N(CH ₃ ) ₂ ] ₃ were refluxed in an organic solvent such as toluene for 12 hours, stopped heating and cooled to room temperature, evaporated the solvent under reduced pressure, and separated by column chromatography , a white foamy solid was obtained, which was recrystallized from diethyl ether, and 8b was obtained after the above-mentioned post-treatment.

Compound 5 and m-phthalic diboronic acid undergo Suzuki coupling reaction under the catalysis of Pd(PPh ₃ ) ₄ and a base such as aq.NaHCO ₃ to obtain compound 6c, which is removed in an organic solvent such as a mixture of chloroform and methanol and under the action of an acid such as hydrochloric acid Compound 7c was obtained from the MOM protecting group; 7c and P[N(CH ₃ ) ₂ ] ₃ were refluxed in an organic solvent such as toluene for 12 hours, stopped heating and cooled to room temperature, evaporated the solvent under reduced pressure, and separated by column chromatography to obtain a white The foamy solid was recrystallized from ether and worked up as above to give 8c.

在Pd(PPh₃)₄和碱如aq.NaHCO₃的催化下发生Suzuki偶联反应得化合物6a，有机溶剂如氯仿和甲醇混合液中，盐酸作用下脱除MOM保护基得化合物7a；7a和P[N(CH₃)₂]₃在有机溶剂如甲苯溶液回流9小时，停止加热并冷却至室温，减压下蒸除溶剂，柱层析分离，得白色泡沫状固体，经乙醚重结晶，，经过上述后处理得8a。Compound 5 and

Under the catalysis of Pd(PPh ₃ ) ₄ and a base such as aq.NaHCO ₃ , a Suzuki coupling reaction occurs to obtain compound 6a. In an organic solvent such as a mixture of chloroform and methanol, the MOM protecting group is removed under the action of hydrochloric acid to obtain compound 7a; 7a and P[N(CH ₃ ) ₂ ] ₃ was refluxed in an organic solvent such as toluene for 9 hours, stopped heating and cooled to room temperature, evaporated the solvent under reduced pressure, and separated by column chromatography to obtain a white foamy solid, which was recrystallized from ether. , 8a is obtained after the above post-processing.

或其对映体和二酚、二醇或二胺类化合物在有机溶剂如甲苯溶液中回流，停止加热并冷却至室温后，减压下蒸除溶剂，柱层析分离，或经乙醚重结晶等后处理得到。The preparation process of the above ligand can also be: under an inert gas such as argon atmosphere, the following compound 10

Or its enantiomer and diphenol, diol or diamine compound are refluxed in an organic solvent such as toluene solution, stop heating and cool to room temperature, evaporate the solvent under reduced pressure, separate by column chromatography, or recrystallize through ether Wait for it to be processed later.

The preparation process of the above-mentioned ligands takes the reaction of compound 10 and a diphenol or diol compound to prepare double-bridged monophosphorus ligands 11 and 13 as an example, which can be simply represented by the following reaction formula:

The specific reaction conditions recommended for the synthetic method in the above reaction process are as follows:

Under argon protection, compound 1 was stirred in PCl ₃ and heated to reflux, stopped heating and cooled to room temperature, evaporated excess PCl ₃ under reduced pressure, repeatedly added dry organic solvents such as toluene three times, and evaporated under reduced pressure each time. To remove traces of _PCl3 , compound 10 was obtained as a white solid.

Dissolve hydroquinone in an organic solvent such as THF, cool the system down to -78°C, add n-BuLi dropwise, stir for 30 minutes, add the THF solution of compound 10, and gradually raise the reaction solution to room temperature, continue stirring for 2 hours , the reaction solution was filtered, the solvent was removed under reduced pressure, and compound 11 was obtained by column chromatography.

At room temperature, compound 10 was dissolved in an organic solvent such as THF, and Et ₃ N solution was added. After 15 minutes, the THF solution of compound 12 was slowly added dropwise, stirred at room temperature for 3 hours, the precipitate was filtered, and the solvent was removed under reduced pressure. Compound 13 was separated by column chromatography.

The present invention provides a class of novel self-supporting chiral catalysts, whose structural formula is as follows:

Among them, M is a transition metal, and it is recommended to be Rh, Ru, Pd, Ir, Cu, Zn, Ag, Au, Ti, Ni, Mo, Mn, etc.;

The linker is a single bond, C _1-8 hydrocarbon group, 1,4-divinylphenyl, 1,4-diethynylphenyl, biphenyl, 9,10-anthracenyl and other substituents. The C _1-8 hydrocarbon group is, for example, p-phenyl, m-phenyl, ortho-phenyl, etc.

R can be a hydrocarbon group, Or OR ^w , the hydrocarbon group is recommended to be a C _1-12 hydrocarbon group, which can be methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, cyclopentyl, cyclohexyl, cycloheptyl phenyl, 1-naphthyl, 2-naphthyl, etc., which are further recommended as C _1-4 hydrocarbon groups; where R ^z , R ^z′ and R ^w can be hydrogen, C _1-12 hydrocarbon groups, C _{1 ~12} alkoxy or halogen, etc., such as methyl, methoxy, ethyl, ethoxy, n-propyl, isopropyl, n-butyl, tert-butyl, cyclopentyl, cyclohexyl, cycloheptyl radical, phenyl, benzyl, (1-phenyl)ethyl, 1-naphthyl, 2-naphthyl or halogen, etc., further recommended are C _1-4 hydrocarbon groups, C _1-4 alkoxy groups. In the formula, n=a natural number greater than or equal to 2, preferably 10-100; k=0, 1, 2, 3 or 4.

Each structural unit of this self-supporting catalyst can be (R, R,) or (S, S,) configuration, and its structure is respectively as follows:

In the formula, linker, M, and n are as mentioned above.

The preparation method of described catalyst can be exemplified as following 1) or 2) by reaction formula:

The following reaction formula is recommended:

Reactant 8 is the ligand as mentioned above, M is the transition metal as mentioned above, X is halogen, ClO ₄ ^- , BF ₄ ^- , SbF ₆ ^- , PF ₆ ^- , OTf, etc., the ligand and transition metal The recommended molar ratio is 1:1 to 4:1, and further recommended to be 1:1 to 2:1. The recommended organic solvents are dichloromethane, chloroform, benzene, toluene, tetrahydrofuran, ethyl acetate, hexane, ether, acetone, Acetonitrile, dimethylformamide, dimethyl sulfoxide, etc. or mixed solvents between them, the recommended reaction temperature is 0-100°C, further recommended 0-25°C, the recommended reaction time is 1 hour, k is 0,1 , 2, 3 or 4; or MX _k is Rh(COD) ₂ BF ₄ , (wherein COD is cycloocta-1,5-diene).

Reactant 8 is the ligand as mentioned above, M is the transition metal as mentioned above, X is halogen, ClO ₄ ^- , BF ₄ ^- , SbF ₆ ^- , PF ₆ ^- , OTf, etc., the ligand and transition metal The recommended molar ratio is 1:1 to 4:1, and further recommended to be 1:1 to 2:1. The recommended organic solvents are dichloromethane, chloroform, benzene, toluene, tetrahydrofuran, ethyl acetate, hexane, ether, acetone, Acetonitrile, dimethylformamide, dimethyl sulfoxide, etc. or mixed solvents between them, the recommended reaction temperature is 0-100°C, further recommended 0-25°C, the recommended reaction time is 1 hour, k is 0,1 , 2, 3 or 4; or MX _k is Rh(COD) ₂ BF ₄ .

In the method of the present invention, the preparation process of the _above -mentioned self-supporting catalyst is to prepare the _self -supporting catalyst 9a, 9b, 9c, 11a, 13a as an example, it can be simply represented by the following reaction formula:

The specific reaction conditions recommended for the synthetic method in the above reaction process are as follows:

The dichloromethane solution of Rh(COD) ₂ BF ₄ was added dropwise to the toluene solution of 8b, and an orange-red precipitate was precipitated. The system was stirred at room temperature for 30 min, and the solvent was evaporated under reduced pressure. The residue was washed with anhydrous toluene, and the obtained orange-red solid was dried under vacuum for 2 hours, and used for the hydrogenation reaction of olefin derivatives.

The dichloromethane solution of Rh(COD)BF ₄ was added dropwise to the solution of 11 toluene, and an orange-red precipitate was precipitated. The system was stirred at room temperature for 30 min, and the solvent was evaporated under reduced pressure. The residue was washed with anhydrous toluene, and the obtained orange-red solid was dried under vacuum for 2 hours, and obtained from the supported chiral catalyst 11a for hydrogenation of olefin derivatives.

The dichloromethane solution of Rh(COD)BF ₄ was added dropwise to the solution of 13 toluene, and an orange-red precipitate was precipitated. The system was stirred at room temperature for 30 minutes, and the solvent was evaporated under reduced pressure. The residue was washed with anhydrous toluene, and the obtained orange-red solid was dried under vacuum for 2 hours, and obtained from the supported chiral catalyst 13a, which was used for the hydrogenation of olefin derivatives.

The hydrogenation reaction of self-supported catalysts to olefin derivatives and the method of catalyst recycling are recommended as follows: under the protection of argon, with toluene as solvent, add the self-supported catalyst prepared above and α-dehydroamino acid or enamine substrate In the hydrogenation bottle, the hydrogenation bottle was moved into the autoclave in an anhydrous and oxygen-free operation box, and after the gas in the autoclave was repeatedly replaced with hydrogen for 5-6 times, a hydrogen pressure of 40 atm was added and stirred at room temperature for 10 hours to complete the reaction. After the release of hydrogen pressure, under the protection of argon, filter the reaction solution through the filter membrane, wash the catalyst with toluene, add α-dehydroamino acid or enamine substrate again, and continue the second reaction according to the above operation. Repeat the reaction ten times. The conversion of the obtained product was determined by ¹ H NMR, and the enantiomeric excess was determined by HPLC or GC.

In the above-mentioned method of the present invention, the organic solvent of use recommends benzene, toluene, xylene, mesitylene, acetonitrile, ether, tetrahydrofuran (THF), ethylene glycol dimethylamine, chloroform, methylene dichloride, methyl alcohol, ethanol, Virahol, N,N-dimethylformamide, N,N-dimethylacetamide, dimethylsulfoxide, N-methylpyrrolidone, etc. The recommended alkali used is sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydride, potassium hydride, calcium hydride, triethylamine, diisopropylethylamine, Tetramethylethylenediamine, N,N-dimethylaniline, N,N-diethylaniline, 1,4-diazabicyclo[2,2,2]octane (DABCO), diaza Dicyclododecane (DBU), 1,4-dimethylpiperazine, 1-methylpiperidine, 1-methylpyrrole, quinoline, or pyridine, etc. Sulfuric acid, hydrochloric acid, phosphoric acid, hydrobromic acid, hydroiodic acid, acetic acid, trifluoroacetic acid, trichloroacetic acid, benzenesulfonic acid, p-toluenesulfonic acid, methanesulfonic acid or trifluoromethanesulfonic acid are recommended as the acid used.

The above-mentioned ligands provided by the invention can be used to prepare catalysts for asymmetric catalytic hydrogenation. The catalyst can be used for asymmetric catalytic hydrogenation of α-dehydroamino acid and its derivatives, various enamines, itaconic acid and its derivatives and other compounds. The asymmetric catalytic hydrogenation of the above compounds can be used for α-amino acids and their derivatives, β-amino acids and their derivatives, chiral amines and their derivatives, and 2-alkyl-1,4-butanedioic acid and its derivatives, etc. Synthesis of compounds.

Specific implementation method

The following examples help to further understand the present invention, but do not limit the content of the invention.

Preparation method of the present invention can be further embodied as follows with the preparation process of representative compound:

Example 1: In a dry 25mL standard Schlenk bottle, under argon protection, compound 7a (0.57g), hexamethylphosphinetriamine (0.46mL), anhydrous toluene (5mL) were added, stirred and heated to reflux for 9h, Heating was stopped and cooled to room temperature, the solvent was evaporated under reduced pressure, and column chromatography (n-hexane: ethyl acetate = 10:1) gave a white foamy solid, which was recrystallized from ether to give compound 8a (0.6 g). 83.5% yield.[α] _D ²⁰ =650.1°(c 1.0, CHCl3).IR(KBr): 3055, 2800, 1621, 1588, 1504, 1462, 1330, 1293, 1232, 1207, 1189, 1076, 983, 944, 821, 780, 749, 692, 678 cm-1.1H NMR (300MHz, CDCl3): δ8.24-8.26 (m, 2H), 7.94-8.08 (m, 6H), 7.64-7.71 (m, 2H) , 7.39-7.58 (m, 10H), 7.29-7.37 (m, 2H), 2.58-2.62 (m, 12H).31P NMR (121MHz, CDCl3) δ149.87 ppm. MS (ESI): (M+H) , 717.35; HRMS (MALDI): calcd.forC44H35N2O4P2: 717.2072; Found: 717.2053.

Example 2: In a dry 25mL standard Schlenk bottle, under argon protection, compound 7b (0.65g), hexamethylphosphinetriamine (0.46mL) and anhydrous toluene (5mL) were added, stirred and heated to reflux for 12h, Heating was stopped and cooled to room temperature, the solvent was evaporated under reduced pressure, and column chromatography (n-hexane: ethyl acetate = 10:1) gave a white foamy solid, which was recrystallized from ether to give compound 8b (0.62 g). 78.5% yield.[α] _D ²⁰ =500.6°(c 1.0, CHCl ₃ ).IR(KBr): 3054, 2799, 1590, 1494, 1464, 1333, 1292, 1232, 1208, 1047, 984, 945, 819 , 790, 749, 693cm _-1.1 H NMR (300MHz, CDCl ₃ ): δ8.18(s, 2H), 7.91-8.06(m, 6H), 7.82(s, 4H), 7.26-7.62(m, 14H) , 2.55-2.59 (m, 12H). ₃₁ P NMR (121MHz, CDCl ₃ ) δ149.87ppm. MS (ESI): (M+H), 793.55; HRMS (MALDI): calcd.for C ₅₀ H ₃₉ N ₂ O ₄ P ₂ : 793.2385; Found: 793.2379.

Example 3: In a dry 25mL standard Schlenk bottle, under argon protection, compound 7c (0.65g), hexamethylphosphinetriamine (0.46mL), anhydrous toluene (5mL) were added, stirred and heated to reflux for 12h, Heating was stopped and cooled to room temperature, the solvent was evaporated under reduced pressure, and column chromatography (n-hexane:ethyl acetate=10:1) gave a white foamy solid, which was recrystallized from ether to give compound 8c (0.67g). 85.0% yield.[α] _D ²⁰ =485.0°(c 1.0, CHCl ₃ ).IR(KBr): 3054, 2799, 1621, 1588, 1505, 1463, 1332, 1292, 1232, 1207, 1188, 1155, 1075 , 984, 945, 884, 820, 796, 749, 693cm _-1.1 HNMR (300MHz, CDCl ₃ ): 8.18-8.19 (m, 2H), 7.91-8.05 (m, 7H), 7.69-7.71 (m, 2H) , 7.41-7.65 (m, 13H), 7.29-7.34 (m, 2H), 2.55-2.59 (m, 12H). ₃₁ P NMR (121MHz, CDCl ₃ ) δ149.48 ppm. MS (ESI): (M+ H), 793.35; HRMS (MALDI): calcd.for C ₅₀ H ₃₉ N ₂ O ₄ P ₂ : 793.2385; Found: 793.2379.

Example 4: Under the protection of argon, 3.5g of compound 1 (12mmol) was stirred in 25g of PCl ₃ (0.18mol) and heated to reflux for 12h, the heating was stopped and cooled to room temperature, the excess PCl ₃ was distilled off under reduced pressure, and repeated addition of Dried toluene was evaporated under reduced pressure three times each time to remove traces of PCl ₃ to obtain white solid compound ^10.31 P NMR (121MHz, CDCl3) δ179.46ppm.

Example 5: 0.055g of hydroquinone (0.5mmol) was dissolved in 5mL of THF, the system was cooled to -78°C, 0.4mL of 2.5M n-BuLi was added dropwise, and after stirring for 30min, 0.35g of compound 10 (1mmol) 5mL of THF solution was added, the reaction solution was gradually raised to room temperature, continued to stir for 2 hours, the reaction solution was filtered, the solvent was removed under reduced pressure, and column chromatography separated compound 11 0.33g. 90% yield. ¹ H NMR (300MHz, CDCl ₃ ): 7.91-8.03 (m, 8H), 7.58 (d, 2H), 7.37-7.49 (m, 10H), 7.26-732 (m, 4H), 7.15 (s, 4H). ³¹ P NMR (121MHz, CDCl ₃ )δ 145.19ppm. MS (ESI): (M+H), 739.30.

Example 6: At room temperature, 0.35g of compound 10 (1mmol) was dissolved in 30mL of THF, 0.278mL of Et ₃ N (2mmol) was added, and after 15min, 0.115g of compound 12 (0.5mmol) in 10mL of THF was slowly dropped Added, stirred at room temperature for 3 hours, the precipitate was filtered, the solvent was removed under reduced pressure, and the compound 13 was separated by column chromatography 0.18g. 45% yield. ¹ H NMR (300MHz, CDCl ₃ ): 7.87-8.02 (m, 8H), 7.27-7.58 (m, 20H), 4.98 (q, 2H), 4.73 (q, 2H). ³¹ P NMR (121MHz, CDCl ₃ ) δ140.28 ppm. MS (ESI): (M+H), 797.42

Example 7: 6.0mg Rh(COD) ₂ BF ₄ (0.0148mmol) was dissolved in 0.5mL of dry dichloromethane, added dropwise to 1.0mL of dry toluene solution of 11.1mg 8b (0.0155mmol), and precipitated An orange-red precipitate was formed, and the system was stirred at room temperature for 30 min, and the solvent was distilled off under reduced pressure. The residue was washed with anhydrous toluene and dried under vacuum for 2 hours to obtain an orange solid (16 mg). 95% yield IR (KBr): 3060, 3018, 2975, 2888, 1621, 1588, 1505, 1463, 1326, 1226, 1075, 986, 946, 826, 695, 597cm _-1 .Anal.Calcd for [(1a) _1.05 Rh(COD)BF ₄ CH ₂ Cl ₂ ] _n : C, 58.41; H, 4.38; N, 2.59. Found: C, 59.39; H, 5.05; N, 3.08.

Example 8: Under argon protection, using 7.3 mL of toluene as a solvent, add the self-supported catalyst (0.01477 mmol) and α-dehydroamino acid or enamine substrate (1.477 mmol) prepared above into a hydrogenation bottle, and hydrogenate The bottle was moved into the autoclave in an anhydrous and oxygen-free operation box, and the gas in the autoclave was repeatedly replaced with hydrogen for 5-6 times, then a hydrogen pressure of 40 atm was added, and the reaction was completed by stirring at room temperature for 10 hours. After the hydrogen pressure is released, under the protection of argon, filter the reaction solution through the filter membrane, wash the catalyst with toluene, add α-dehydroamino acid or enamine substrate again, and continue the second reaction according to the above operation, and then cycle the reaction for ten years. Second-rate. The conversion of the obtained product was determined by ¹ H NMR, and the enantiomeric excess was determined by HPLC or GC.

Example 9: Asymmetric hydrogenation of methyl α-acetamido-β-phenylacrylate (I)

Under the protection of argon, the self-supporting catalyst 9a (0.01477mmol) and α-acetamido-β-phenylacrylate methyl ester (1.477mmol) prepared above were added to the hydrogenation bottle, and 7.3mL of toluene (0.2M) was used as The solvent and the hydrogenation bottle were moved into the autoclave in an anhydrous and oxygen-free operation box, and the gas in the autoclave was repeatedly replaced with hydrogen for 5-6 times, then a hydrogen pressure of 20 atm was added, and the reaction was completed by stirring at room temperature for 10 hours. The hydrogen in the autoclave was released, and the reaction solution was added to an 8 cm long silica gel column, and the developer (ethyl acetate: petroleum ether 1:

1) Wash down product α-acetamido-β-phenylpropionic acid methyl ester, nuclear magnetic resonance shows conversion rate 100%, HPLC shows ee 93.6% (Chiralpak Japan Dacheng company AD chiral column, λ=230nm; Flow rate: 1.0 mL/min, n-hexane:isopropanol=85:15; t(R)=7.29min; t(S)=10.04min; [α] _D ²⁰ =-96.7°(c=1, CHCl ₃ ); ¹ H NMR (300MHz, CDCl ₃ ) δ7.24-7.29(m, 3H), 7.06-7.09(m, 2H), 5.96(d, J=7.8Hz, 1H), 4.86-4.89(m, 1H), 3.72 (s, 3H), 3.09-3.13 (m, 2H), 1.97 (s, 3H), ¹³ C NMR (75MHz, CDCl ₃ ) δ172.06, 169.62, 135.71, 129.17, 128.54, 127.10, 53.01, 52.33, 37.71 , 23.11. The main enantiomer of the product is R configuration.

Example 10: Asymmetric hydrogenation of methyl α-acetamido-β-phenylacrylate (II)

Under the protection of argon, the self-supporting catalyst 9b (0.01477mmol) prepared above and methyl α-acetamido-β-phenylacrylate (1.477mmol) were added into the hydrogenation bottle, and 7.3mL of toluene (0.2M) was used as The solvent and the hydrogenation bottle were moved into the autoclave in an anhydrous and oxygen-free operation box, and the gas in the autoclave was repeatedly replaced with hydrogen for 5-6 times, then a hydrogen pressure of 20 atm was added, and the reaction was completed by stirring at room temperature for 10 hours. The hydrogen in the autoclave is released, and the reaction solution is added to a 8cm long silica gel column, and the product α-acetamido-β-phenylpropionic acid methyl ester is washed down with a developing solvent (ethyl acetate:petroleum ether 1:1), NMR shows conversion rate 100%, HPLC shows ee 92.7% (Chiralpak Japan Dacheng company AD chiral column, λ=230nm; Flow rate: 1.0mL/min, normal hexane: Virahol=85: 15; t(R)= 7.29min; t(S)=10.04min; [α] _D ²⁰ =-95.8°(c=1, CHCl ₃ ); ¹ H NMR (300MHz, CDCl ₃ ) δ7.24-7.29(m, 3H), 7.06 -7.09(m, 2H), 5.96(d, J=7.8Hz, 1H), 4.86-4.89(m, 1H), 3.72(s, 3H), 3.09-3.13(m, 2H), 1.97(s, 3H ), ¹³ C NMR (75MHz, CDCl ₃ ) δ172.06, 169.62, 135.71, 129.17, 128.54, 127.10, 53.01, 52.33, 37.71, 23.11. The main enantiomer of the product is R configuration.

Example 11: Asymmetric hydrogenation of methyl α-acetamido-β-phenylacrylate (III)

Under the protection of argon, the self-supporting catalyst 9c (0.01477mmol) and α-acetamido-β-phenylacrylate methyl ester (1.477mmol) prepared above were added to the hydrogenation bottle, and 7.3mL of toluene (0.2M) was used as The solvent and the hydrogenation bottle were moved into the autoclave in an anhydrous and oxygen-free operation box, and the gas in the autoclave was repeatedly replaced with hydrogen for 5-6 times, then a hydrogen pressure of 20 atm was added, and the reaction was completed by stirring at room temperature for 10 hours. The hydrogen in the autoclave is released, and the reaction solution is added to a 8cm long silica gel column, and the product α-acetamido-β-phenylpropionic acid methyl ester is washed down with a developing solvent (ethyl acetate:petroleum ether 1:1), NMR shows conversion rate 100%, HPLC shows ee 92.2% (Chiralpak Japan Dacheng company AD chiral column, λ=230nm; Flow rate: 1.0mL/min, normal hexane: Virahol=85: 15; t(R)= 7.29min; t(S)=10.04min; [α] _D ²⁰ =-96.4°(c=1, CHCl ₃ ); ¹ H NMR (300MHz, CDCl ₃ ) δ7.24-7.29(m, 3H), 7.06 -7.09(m, 2H), 5.96(d, J=7.8Hz, 1H), 4.86-4.89(m, 1H), 3.72(s, 3H), 3.09-3.13(m, 2H), 1.97(s, 3H ), ¹³ C NMR (75MHz, CDCl ₃ ) δ172.06, 169.62, 135.71, 129.17, 128.54, 127.10, 53.01, 52.33, 37.71, 23.11. The main enantiomer of the product is R configuration.

Example 12: Asymmetric hydrogenation of methyl α-acetamido-β-phenylacrylate (IV)

Under the protection of argon, the self-supporting catalyst 9a (0.01477mmol) and α-acetamido-β-phenylacrylate methyl ester (1.477mmol) prepared above were added to the hydrogenation bottle, and 7.3mL of toluene (0.2M) was used as The solvent and the hydrogenation bottle were moved into the autoclave in an anhydrous and oxygen-free operation box, and the gas in the autoclave was repeatedly replaced with hydrogen for 5-6 times, then a hydrogen pressure of 40 atm was added, and the reaction was completed by stirring at room temperature for 10 hours. The hydrogen in the autoclave is released, and the reaction solution is added to a 8cm long silica gel column, and the product α-acetamido-β-phenylpropionic acid methyl ester is washed down with a developing solvent (ethyl acetate:petroleum ether 1:1), NMR shows conversion rate 100%, HPLC shows ee 96.6% (Chiralpak Japan Dacheng company AD chiral column, λ=230nm; Flow rate: 1.0mL/min, n-hexane: Virahol=90: 10; t(R)= 10.8min; t(S)=14.0min; [α] _D ²⁰ =-98.3°(c=1, CHCl ₃ ); ¹ H NMR (300MHz, CDCl ₃ ) δ7.24-7.29(m, 3H), 7.06 -7.09(m, 2H), 5.96(d, J=7.8Hz, 1H), 4.86-4.89(m, 1H), 3.72(s, 3H), 3.09-3.13(m, 2H), 1.97(s, 3H ), ¹³ C NMR (75MHz, CDCl ₃ ) δ172.06, 169.62, 135.71, 129.17, 128.54, 127.10, 53.01, 52.33, 37.71, 23.11. The main enantiomer of the product is R configuration.

Example 13: Asymmetric hydrogenation of methyl α-acetamido-β-phenylacrylate (V)

Under the protection of argon, the self-supporting catalyst 9b (0.01477mmol) prepared above and methyl α-acetamido-β-phenylacrylate (1.477mmol) were added into the hydrogenation bottle, and 7.3mL of toluene (0.2M) was used as The solvent and the hydrogenation bottle were moved into the autoclave in an anhydrous and oxygen-free operation box, and the gas in the autoclave was repeatedly replaced with hydrogen for 5-6 times, then a hydrogen pressure of 40 atm was added, and the reaction was completed by stirring at room temperature for 10 hours. The hydrogen in the autoclave is released, and the reaction solution is added to a 8cm long silica gel column, and the product α-acetamido-β-phenylpropionic acid methyl ester is washed down with a developing solvent (ethyl acetate:petroleum ether 1:1), NMR shows conversion rate 100%, HPLC shows ee 94.7% (Chiralpak Japan Dacheng company AD chiral column, λ=230nm; Flow rate: 1.0mL/min, n-hexane: Virahol=90: 10; t(R)= 10.8min; t(S)=14.0min); [α] _D ²⁰ =-96.5° (c=1, CHCl ₃ ); ¹ H NMR (300MHz, CDCl ₃ ) δ7.24-7.29 (m, 3H), 7.06-7.09(m, 2H), 5.96(d, J=7.8Hz, 1H), 4.86-4.89(m, 1H), 3.72(s, 3H), 3.09-3.13(m, 2H), 1.97(s, 3H), ¹³ C NMR (75 MHz, CDCl ₃ ) δ 172.06, 169.62, 135.71, 129.17, 128.54, 127.10, 53.01, 52.33, 37.71, 23.11. The main enantiomer of the product is the R configuration.

Example 14: Asymmetric hydrogenation of methyl α-acetamido-β-phenylacrylate (VI)

Under the protection of argon, the self-supporting catalyst 9c (0.01477mmol) and α-acetamido-β-phenylacrylate methyl ester (1.477mmol) prepared above were added to the hydrogenation bottle, and 7.3mL of toluene (0.2M) was used as The solvent and the hydrogenation bottle were moved into the autoclave in an anhydrous and oxygen-free operation box, and the gas in the autoclave was repeatedly replaced with hydrogen for 5-6 times, then a hydrogen pressure of 40 atm was added, and the reaction was completed by stirring at room temperature for 10 hours. The hydrogen in the autoclave is released, and the reaction solution is added to a 8cm long silica gel column, and the product α-acetamido-β-phenylpropionic acid methyl ester is washed down with a developing solvent (ethyl acetate:petroleum ether 1:1), NMR shows conversion rate 100%, HPLC shows ee 96.2% (Chiralpak Japan Dacheng company AD chiral column, λ=230nm; Flow rate: 1.0mL/min, normal hexane: Virahol=90: 10; t(R)= 10.8min; t(S)=14.0min); [α] _D ²⁰ =-98.0° (c=1, CHCl ₃ ); ¹ H NMR (300MHz, CDCl ₃ ) δ7.24-7.29 (m, 3H), 7.06-7.09(m, 2H), 5.96(d, J=7.8Hz, 1H), 4.86-4.89(m, 1H), 3.72(s, 3H), 3.09-3.13(m, 2H), 1.97(s, 3H), ¹³ C NMR (75 MHz, CDCl ₃ ) δ 172.06, 169.62, 135.71, 129.17, 128.54, 127.10, 53.01, 52.33, 37.71, 23.11. The main enantiomer of the product is the R configuration.

Example 15: Recovery experiment (VII) of asymmetric hydrogenation of methyl α-acetamido-β-phenylacrylate

Under the protection of argon, the self-supporting catalyst 9a (0.01477mmol) and α-acetamido-β-phenylacrylate methyl ester (1.477mmol) prepared above were added to the hydrogenation bottle, and 7.3mL of toluene (0.2M) was used as The solvent and the hydrogenation bottle were moved into the autoclave in an anhydrous and oxygen-free operation box, and the gas in the autoclave was repeatedly replaced with hydrogen for 5-6 times, then a hydrogen pressure of 40 atm was added, and the reaction was completed by stirring at room temperature for 10 hours. Filter the reaction solution through a filter membrane under argon protection, wash the catalyst with toluene, re-add 7.3mL of toluene and α-acetamido-β-methyl phenylacrylate (1.477mmol) into the hydrogenation bottle, and continue as above The second reaction, such a circular reaction nine times. Add each reaction solution to an 8 cm long silica gel column, wash down the product α-acetamido-β-phenylpropionic acid methyl ester with a developing solvent (ethyl acetate:petroleum ether 1:1), and nuclear magnetic resonance shows that the conversion The rate is 100%, and HPLC shows that ee is respectively 94.0%, 88.7%, 88.5%, 89.1%, 89.0%, 88.3%, 87.7%, 86.5%, 82.9% (Chiralpak Japan Dacheng Company AD chiral column, λ=230nm ; Flow rate: 1.0mL/min, n-hexane:isopropanol=90:10; t(R)=10.8min; t(S)=14.0min); the first [α] _D ²⁰ =-96.6.0 °(c=1, CHCl ₃ ); ¹ H NMR (300MHz, CDCl ₃ ) δ7.24-7.29(m, 3H), 7.06-7.09(m, 2H), 5.96(d, J=7.8Hz, 1H) , 4.86-4.89 (m, 1H), 3.72 (s, 3H), 3.09-3.13 (m, 2H), 1.97 (s, 3H), ¹³ C NMR (75MHz, CDCl ₃ ) δ172.06, 169.62, 135.71, 129.17, 128.54, 127.10, 53.01, 52.33, 37.71, 23.11. The main enantiomer of the product is the R configuration.

Example 16: Asymmetric hydrogenation of methyl α-acetamido-β-methacrylate (I)

Under the protection of argon, the self-supporting catalyst 9a (0.01477mmol) and α-acetamido-β-methyl methacrylate (1.477mmol) prepared above were added to the hydrogenation bottle, and 7.3mL of toluene (0.2M) was used as The solvent and the hydrogenation bottle were moved into the autoclave in an anhydrous and oxygen-free operation box, and the gas in the autoclave was repeatedly replaced with hydrogen for 5-6 times, then a hydrogen pressure of 40 atm was added, and the reaction was completed by stirring at room temperature for 10 hours. The hydrogen in the autoclave is released, and the reaction solution is added to a 8cm long silica gel column, and the product α-acetamido-β-methyl propionate is washed down with a developing solvent (ethyl acetate:petroleum ether 1:2), NMR showed 100% conversion, GC showed ee 95.7% (Supelco GAMMA-DEX 225 chiral column, constant temperature: 130°C, flow rate: 1mL/min, t(R)=19.3min; t(S)=20.9min) ; [α] _D ²⁰ =-19.4° (c=1, CHCl ₃ ); ¹ H NMR (300 MHz, CDCl ₃ ) δ6.35 (s, 1H), 4.55-4.62 (m, 1H), 3.76 (s, 3H), 2.04(s, 3H), 1.68-1.94(m, 2H), 0.92(t, J=7.8Hz, 3H). ¹³ C NMR (75 MHz, CDCl ₃ ) δ 173.02, 169.86, 53.13, 52.19, 25.45, 22.98, 9.41. The main enantiomer of the product is the R configuration.

Example 17: Asymmetric hydrogenation of methyl α-acetamido-β-methacrylate (II)

Under the protection of argon, the self-supporting catalyst 9b (0.01477mmol) and α-acetamido-β-methyl methacrylate (1.477mmol) prepared above were added to the hydrogenation bottle, and 7.3mL of toluene (0.2M) was used as The solvent and the hydrogenation bottle were moved into the autoclave in an anhydrous and oxygen-free operation box, and the gas in the autoclave was repeatedly replaced with hydrogen for 5-6 times, then a hydrogen pressure of 40 atm was added, and the reaction was completed by stirring at room temperature for 10 hours. The hydrogen in the autoclave is released, and the reaction solution is added to a 8cm long silica gel column, and the product α-acetamido-β-methyl propionate is washed down with a developing solvent (ethyl acetate:petroleum ether 1:2), NMR showed 100% conversion, GC showed ee 94.9% (Supelco GAMMA-DEX 225 chiral column, constant temperature: 130°C, flow rate: 1mL/min, t(R)=19.3min; t(S)20.9min); [α] _D ²⁰ =-18.9° (c=1, CHCl ₃ ); ¹ H NMR (300 MHz, CDCl ₃ ) δ6.35 (s, 1H), 4.55-4.62 (m, 1H), 3.76 (s, 3H ), 2.04(s, 3H), 1.68-1.94(m, 2H), 0.92(t, J=7.8Hz, 3H). ¹³ C NMR (75 MHz, CDCl ₃ ) δ 173.02, 169.86, 53.13, 52.19, 25.45, 22.98, 9.41. The main enantiomer of the product is the R configuration.

Example 18: Asymmetric hydrogenation of methyl α-acetamido-β-methacrylate (III)

Under argon protection, the self-supporting catalyst 9c (0.01477mmol) and α-acetamido-β-methyl methacrylate (1.477mmol) prepared above were added into a hydrogenation bottle, and 7.3mL of toluene (0.2M) was used as The solvent and the hydrogenation bottle were moved into the autoclave in an anhydrous and oxygen-free operation box, and the gas in the autoclave was repeatedly replaced with hydrogen for 5-6 times, then a hydrogen pressure of 40 atm was added, and the reaction was completed by stirring at room temperature for 10 hours. The hydrogen in the autoclave is released, and the reaction solution is added to a 8cm long silica gel column, and the product α-acetamido-β-methyl propionate is washed down with a developing solvent (ethyl acetate:petroleum ether 1:2), NMR showed 100% conversion, GC showed ee 95.9% (Supelco GAMMA-DEX 225 chiral column, constant temperature: 130°C, flow rate: 1mL/min, t(R)=19.3min; t(S)=20.9min) ; [α] _D ²⁰ =-19.8° (c=1, CHCl ₃ ); ¹ H NMR (300 MHz, CDCl ₃ ) δ6.35 (s, 1H), 4.55-4.62 (m, 1H), 3.76 (s, 3H), 2.04(s, 3H), 1.68-1.94(m, 2H), 0.92(t, J=7.8Hz, 3H). ¹³ C NMR (75 MHz, CDCl ₃ ) δ 173.02, 169.86, 53.13, 52.19, 25.45, 22.98, 9.41. The main enantiomer of the product is the R configuration.

Example 19: Asymmetric hydrogenation of methyl α-acetamidoacrylate (I)

Under argon protection, the self-supporting catalyst 9a (0.01477mmol) and methyl α-acetamidoacrylate (1.477mmol) prepared above were added to the hydrogenation bottle, 7.3mL of toluene (0.2M) was used as the solvent, and the hydrogenation bottle was Move it into the autoclave in an anhydrous and oxygen-free operation box, replace the gas in the autoclave with hydrogen repeatedly for 5-6 times, add a hydrogen pressure of 40 atm, and stir at room temperature for 10 hours to complete the reaction. The hydrogen in the autoclave is released, the reaction solution is added to an 8cm long silica gel column, and the product α-acetamidopropionate methyl ester is washed down with a developing solvent (ethyl acetate:petroleum ether 1:2), and the conversion rate is shown by nuclear magnetic resonance. 100%, GC showed ee 95.8% (Supelco BETA-DEX 120 chiral column, constant temperature: 110°C, flow rate: 1mL/min, t(S)=14.3min; t(R)=14.8min); [α] _D ²⁰ = -7.8° (c = 1.0, CHCl ₃ ); ¹ H NMR (300 MHz, CDCl ₃ ) δ6.57 (s, 1H), 4.54-4.63 (m, 1H), 3.76 (s, 3H), 2.02 ( s, 3H), 1.40 (d, J=7.2Hz, 3H); ¹³ C NMR (75MHz, CDCl ₃ ) δ 173.91, 170.12, 52.60, 48.19, 23.16, 18.43. The main enantiomer of the product is the R configuration.

Example 20: Asymmetric hydrogenation of methyl α-acetamidoacrylate (II)

Under the protection of argon, the self-supporting catalyst 9b (0.01477mmol) and methyl α-acetamidoacrylate (1.477mmol) prepared above were added into the hydrogenation bottle, 7.3mL of toluene (0.2M) was used as the solvent, and the hydrogenation bottle was Move it into the autoclave in an anhydrous and oxygen-free operation box, replace the gas in the autoclave with hydrogen repeatedly for 5-6 times, add a hydrogen pressure of 40 atm, and stir at room temperature for 10 hours to complete the reaction. The hydrogen in the autoclave is released, the reaction solution is added to an 8cm long silica gel column, and the product α-acetamidopropionate methyl ester is washed down with a developing solvent (ethyl acetate:petroleum ether 1:2), and the conversion rate is shown by nuclear magnetic resonance. 100%, GC showed ee 94.3% (Supelco BETA-DEX 120 chiral column, constant temperature: 110°C, flow rate: 1mL/min, t(S)=14.3min; t(R)=14.8min); [α] _D ²⁰ = -7.5° (c = 1.0, CHCl ₃ ); ¹ H NMR (300 MHz, CDCl ₃ ) δ6.57 (s, 1H), 4.54-4.63 (m, 1H), 3.76 (s, 3H), 2.02 ( s, 3H), 1.40 (d, J=7.2Hz, 3H); ¹³ C NMR (75MHz, CDCl ₃ ) δ 173.91, 170.12, 52.60, 48.19, 23.16, 18.43. The main enantiomer of the product is the R configuration.

Example 21: Asymmetric hydrogenation of methyl α-acetamidoacrylate (III)

Under the protection of argon, the self-supporting catalyst 9c (0.01477mmol) and methyl α-acetamidoacrylate (1.477mmol) prepared above were added into the hydrogenation bottle, 7.3mL of toluene (0.2M) was used as the solvent, and the hydrogenation bottle was Move it into the autoclave in an anhydrous and oxygen-free operation box, replace the gas in the autoclave with hydrogen repeatedly for 5-6 times, add a hydrogen pressure of 40 atm, and stir at room temperature for 10 hours to complete the reaction. The hydrogen in the autoclave is released, the reaction solution is added to an 8cm long silica gel column, and the product α-acetamidopropionate methyl ester is washed down with a developing solvent (ethyl acetate:petroleum ether 1:2), and the conversion rate is shown by nuclear magnetic resonance. 100%, GC showed ee 95.0% (Supelco BETA-DEX 120 chiral column, constant temperature: 110°C, flow rate: 1mL/min, t(S)=14.3min; t(R)=14.8min); [α] _D ²⁰ = -7.7° (c = 1.0, CHCl ₃ ); ¹ H NMR (300 MHz, CDCl ₃ ) δ6.57 (s, 1H), 4.54-4.63 (m, 1H), 3.76 (s, 3H), 2.02 ( s, 3H), 1.40 (d, J=7.2Hz, 3H); ¹³ C NMR (75MHz, CDCl ₃ ) δ 173.91, 170.12, 52.60, 48.19, 23.16, 18.43. The main enantiomer of the product is the R configuration.

Example 22: Asymmetric hydrogenation of methyl α-acetamidoacrylate (IV)

Under argon protection, the self-supporting catalyst 11a (0.01477mmol) and methyl α-acetamidoacrylate (1.477mmol) prepared above were added to the hydrogenation bottle, 7.3mL of toluene (0.2M) was used as the solvent, and the hydrogenation bottle was Move it into the autoclave in an anhydrous and oxygen-free operation box, replace the gas in the autoclave with hydrogen repeatedly for 5-6 times, add a hydrogen pressure of 40 atm, and stir at room temperature for 10 hours to complete the reaction. The hydrogen in the autoclave is released, the reaction solution is added to an 8cm long silica gel column, and the product α-acetamidopropionate methyl ester is washed down with a developing solvent (ethyl acetate:petroleum ether 1:2), and the conversion rate is shown by nuclear magnetic resonance. 100%, GC showed ee 85.7% (Supelco BETA-DEX 120 chiral column, constant temperature: 110°C, flow rate: 1mL/min, t(S)=14.3min; t(R)=14.8min); [α] _D ²⁰ = -5.3° (c = 1.0, CHCl ₃ ); ¹ H NMR (300 MHz, CDCl ₃ ) δ6.57 (s, 1H), 4.54-4.63 (m, 1H), 3.76 (s, 3H), 2.02 ( s, 3H), 1.40 (d, J=7.2Hz, 3H); ¹³ C NMR (75MHz, CDCl ₃ ) δ 173.91, 170.12, 52.60, 48.19, 23.16, 18.43. The main enantiomer of the product is the R configuration.

Example 23: Asymmetric hydrogenation of methyl α-acetamidoacrylate (V)

Under the protection of argon, the self-supporting catalyst 13a (0.01477mmol) and methyl α-acetamidoacrylate (1.477mmol) prepared above were added into the hydrogenation bottle, 7.3mL of toluene (0.2M) was used as the solvent, and the hydrogenation bottle was Move it into the autoclave in an anhydrous and oxygen-free operation box, replace the gas in the autoclave with hydrogen repeatedly for 5-6 times, add a hydrogen pressure of 40 atm, and stir at room temperature for 10 hours to complete the reaction. The hydrogen in the autoclave is released, the reaction solution is added to an 8cm long silica gel column, and the product α-acetamidopropionate methyl ester is washed down with a developing solvent (ethyl acetate:petroleum ether 1:2), and the conversion rate is shown by nuclear magnetic resonance. 100%, GC showed ee 91.6% (Supelco BETA-DEX 120 chiral column, constant temperature: 110°C, flow rate: 1mL/min, t(S)=14.3min; t(R)=14.8min); [α] _D ²⁰ = -6.2° (c=1.0, CHCl ₃ ); ¹ H NMR (300 MHz, CDCl ₃ ) δ6.57 (s, 1H), 4.54-4.63 (m, 1H), 3.76 (s, 3H), 2.02 ( s, 3H), 1.40 (d, J=7.2Hz, 3H); ¹³ C NMR (75MHz, CDCl ₃ ) δ 173.91, 170.12, 52.60, 48.19, 23.16, 18.43. The main enantiomer of the product is the R configuration.

Example 24: Recovery experiment (VI) of asymmetric hydrogenation of methyl α-acetamidoacrylate

Under the protection of argon, the self-supporting catalyst 9c (0.01477mmol) and methyl α-acetamidoacrylate (1.477mmol) prepared above were added into the hydrogenation bottle, 7.3mL of toluene (0.2M) was used as the solvent, and the hydrogenation bottle was Move it into the autoclave in an anhydrous and oxygen-free operation box, replace the gas in the autoclave with hydrogen repeatedly for 5-6 times, add a hydrogen pressure of 40 atm, and stir at room temperature for 10 hours to complete the reaction. Under the protection of argon, the reaction solution was filtered out through a filter membrane, the catalyst was washed with toluene, and 7.3 mL of toluene and methyl α-acetamidoacrylate (1.477 mmol) were added to the hydrogenation bottle again, and the second reaction was continued as above. Repeat the reaction ten times. Add each reaction solution to an 8cm long silica gel column, wash down the product α-acetamidopropionate methyl ester with a developing solvent (ethyl acetate: petroleum ether 1: 1), and the nuclear magnetic resonance shows that the conversion rate is 100%. , HPLC shows that ee is respectively 95.0%, 93.5%, 90.2%, 90.9%, 90.5%, 90.0%, 89.5%, 87.7%, 87.3%, 87.3% ((Supelco BETA-DEX 120 chiral column, constant temperature: 110 ℃ , flow rate: 1 mL/min, t(S)=14.3min; t(R)=14.8min); [α] _D ²⁰ =-7.7°(c=1.0, CHCl ₃ ); ¹ HNMR (300MHz, CDCl ₃ ) δ6.57(s, 1H), 4.54-4.63(m, 1H), 3.76(s, 3H), 2.02(s, 3H), 1.40(d, J=7.2Hz, 3H); ¹³ C NMR (75MHz, CDCl ₃ ) δ173.91, 170.12, 52.60, 48.19, 23.16, 18.43. The main enantiomer of the product is R configuration.

Example 25: Asymmetric hydrogenation of N-acetyl-1-phenylethenylamine (I)

Under argon protection, the self-supporting catalyst 9a (0.01477mmol) and N-acetyl-1-phenylethyleneamine (1.477mmol) prepared above were added into a hydrogenation bottle, and 7.3mL of toluene (0.2M) was used as a solvent. The hydrogenation bottle was moved into the autoclave in an anhydrous and oxygen-free operation box, and the gas in the autoclave was repeatedly replaced with hydrogen for 5-6 times, then a hydrogen pressure of 40 atm was added, and the reaction was completed by stirring at room temperature for 10 hours. The hydrogen in the autoclave was released, the reaction solution was added to an 8cm long silica gel column, and the product N-acetyl-1-phenylethylamine was washed down with a developing solvent (ethyl acetate:petroleum ether 1:2), and nuclear magnetic resonance showed The conversion rate is 100%, and HPLC shows ee97.3% (Chiralpak Japan Dacheng Company AD chiral column, λ=230nm; Flow velocity: 1.0mL/min, n-hexane: Virahol=95:5; t(R)=11.0min ; t(S)=14.3min); [α] _D ²⁰ =+131.8°(c=1, CHCl ₃ ); ¹ H NMR (300MHz, CDCl ₃ ) δ7.25-7.38(m, 5H), 5.79( s, 1H), 5.11-5.16 (m, 1H), 1.99 (s, 3H), 1.50 (d, J=6.9Hz, 3H); ¹³ C NMR (75MHz, CDCl ₃ ) δ169.22, 143.25, 128.45, 127.12, 126.06, 48.63, 23.15, 21.68. The main enantiomer of the product is the R configuration.

Example 26: Asymmetric hydrogenation of N-acetyl-1-phenylethenylamine (II)

Under the protection of argon, the self-supporting catalyst 9b (0.01477mmol) and N-acetyl-1-phenylethyleneamine (1.477mmol) prepared above were added to the hydrogenation bottle, and 7.3mL of toluene (0.2M) was used as the solvent. The hydrogenation bottle was moved into the autoclave in an anhydrous and oxygen-free operation box, and the gas in the autoclave was repeatedly replaced with hydrogen for 5-6 times, then a hydrogen pressure of 40 atm was added, and the reaction was completed by stirring at room temperature for 10 hours. The hydrogen in the autoclave was released, the reaction solution was added to an 8cm long silica gel column, and the product N-acetyl-1-phenylethylamine was washed down with a developing solvent (ethyl acetate:petroleum ether 1:2), and nuclear magnetic resonance showed The conversion rate is 100%, and HPLC shows ee 96.8% (Chiralpak Japan Dacheng Company AD chiral column, λ=230nm; flow rate: 1.0mL/min, n-hexane:isopropanol=95:5; t(R)=11.0min; t(S)=14.3min); [α] _D ²⁰ =+129.5° (c=1, CHCl ₃ ); ¹ H NMR (300 MHz, CDCl ₃ ) δ7.25-7.38 (m, 5H), 5.79 ( s, 1H), 5.11-5.16 (m, 1H), 1.99 (s, 3H), 1.50 (d, J=6.9Hz, 3H); ¹³ C NMR (75MHz, CDCl ₃ ) δ169.22, 143.25, 128.45, 127.12, 126.06, 48.63, 23.15, 21.68. The main enantiomer of the product is the R configuration.

Example 27: Asymmetric hydrogenation of N-acetyl-1-phenylethenylamine (III)

Under the protection of argon, the self-supporting catalyst 9c (0.01477mmol) and N-acetyl-1-phenylethyleneamine (1.477mmol) prepared above were added into a hydrogenation bottle, and 7.3mL of toluene (0.2M) was used as a solvent. The hydrogenation bottle was moved into the autoclave in an anhydrous and oxygen-free operation box, and the gas in the autoclave was repeatedly replaced with hydrogen for 5-6 times, then a hydrogen pressure of 40 atm was added, and the reaction was completed by stirring at room temperature for 10 hours. The hydrogen in the autoclave was released, the reaction solution was added to an 8cm long silica gel column, and the product N-acetyl-1-phenylethylamine was washed down with a developing solvent (ethyl acetate:petroleum ether 1:2), and nuclear magnetic resonance showed The conversion rate is 100%, and HPLC shows ee95.9% (Chiralpak Japan Dacheng Company AD chiral column, λ=230nm; Flow velocity: 1.0mL/min, n-hexane: Virahol=95:5; t(R)=11.0min ; t(S)=14.3min); [α] _D ²⁰ =+128.6° (c=1, CHCl ₃ ); ¹ H NMR (300MHz, CDCl ₃ ) δ7.25-7.38 (m, 5H), 5.79( s, 1H), 5.11-5.16 (m, 1H), 1.99 (s, 3H), 1.50 (d, J=6.9Hz, 3H); ¹³ C NMR (75MHz, CDCl ₃ ) δ169.22, 143.25, 128.45, 127.12, 126.06, 48.63, 23.15, 21.68. The main enantiomer of the product is the R configuration.

Example 28: Recovery Experiment (IV) of Asymmetric Hydrogenation of N-Acetyl-1-Phenylethyleneamine

Under argon protection, the self-supporting catalyst 9a (0.01477mmol) and N-acetyl-1-phenylethyleneamine (1.477mmol) prepared above were added into a hydrogenation bottle, and 7.3mL of toluene (0.2M) was used as a solvent. The hydrogenation bottle was moved into the autoclave in an anhydrous and oxygen-free operation box, and the gas in the autoclave was repeatedly replaced with hydrogen for 5-6 times, then a hydrogen pressure of 40 atm was added, and the reaction was completed by stirring at room temperature for 10 hours. Under the protection of argon, the reaction solution was filtered out through a filter membrane, the catalyst was washed with toluene, and 7.3 mL of toluene and methyl α-acetamidoacrylate (1.477 mmol) were added to the hydrogenation bottle again, and the second reaction was continued as above. Repeat the reaction ten times. Add each reaction solution to a 8cm-long silica gel column, wash down the product N-acetyl-1-phenylethylamine with a developing solvent (ethyl acetate:petroleum ether 1:1), and the nuclear magnetic resonance shows that the conversion rate is 100%, HPLC shows that ee values are respectively 95.9%, 95.5%, 94.1%, 95.4%, 94.2%, 93.8%, 92.7%, 91.5%, 89.5%, 86.3%, 83.4% (Chiralpak Japan Dacheng Company AD chiral column , λ=230nm; flow rate: 1.0mL/min, n-hexane:isopropanol=95:5; t(R)=11.0min; t(S)=14.3min); the first [α] _D ²⁰ = +128.6° (c=1, CHCl ₃ ); ¹ H NMR (300 MHz, CDCl ₃ ) δ7.25-7.38 (m, 5H), 5.79 (s, 1H), 5.11-5.16 (m, 1H), 1.99 ( s, 3H), 1.50 (d, J=6.9Hz, 3H); ¹³ C NMR (75MHz, CDCl ₃ ) δ 169.22, 143.25, 128.45, 127.12, 126.06, 48.63, 23.15, 21.68. The main enantiomer of the product is the R configuration.

Example 29: Asymmetric hydrogenation of N-acetyl-1-(4-methylphenyl)vinylamine (I)

Under argon protection, the self-supporting catalyst 9a (0.01477mmol) and N-acetyl-1-(4-methylphenyl)vinylamine (1.477mmol) prepared above were added to the hydrogenation bottle, and 7.3mL of toluene ( 0.2M) as a solvent, the hydrogenation bottle was moved into the autoclave in an anhydrous and oxygen-free operation box, and the gas in the autoclave was repeatedly replaced with hydrogen for 5-6 times, then a hydrogen pressure of 40 atm was added, and the reaction was completed by stirring at room temperature for 10 hours. Release the hydrogen in the autoclave, add the reaction solution to an 8cm long silica gel column, wash down the product N-acetyl-1-(4-methylbenzene) with a developing solvent (ethyl acetate:petroleum ether 1:2) Base) ethylamine, nuclear magnetic resonance shows that the conversion rate is 100%, and HPLC shows that ee is 94.0% (Chiralpak Japan Dacheng Company AD chiral column, λ=230nm; Flow rate: 1.0mL/min, n-hexane: isopropanol=95:5; t(R)=14.1min; t(S)=18.7min); [α] _D ²⁰ ＝+163.4°(c=0.5, CHCl ₃ ); ¹ H NMR (300MHz, CDCl ₃ ) δ7.17(d, J=7.8Hz, 2H), 7.12(d, J=7.8Hz, 2H), 6.26(br s, 1H), 5.05-5.14(m, 1H), 2.31(s, 3H), 1.97(s, 3H) , 1.47 (d, J=7.2Hz, 3H); ¹³ C NMR (75MHz, CDCl ₃ ) δ 169.95, 169.11, 140.45, 140.22, 136.77, 129.12, 126.00, 48.35, 23.20, 21.64, 20.90. The main enantiomer of the product is the R configuration.

Example 30: Asymmetric hydrogenation of N-acetyl-1-(4-methylphenyl)vinylamine (II)

Under the protection of argon, the self-supporting catalyst 9b (0.01477mmol) and N-acetyl-1-(4-methylphenyl)vinylamine (1.477mmol) prepared above were added to the hydrogenation bottle, and 7.3mL of toluene ( 0.2M) as a solvent, the hydrogenation bottle was moved into the autoclave in an anhydrous and oxygen-free operation box, and the gas in the autoclave was repeatedly replaced with hydrogen for 5-6 times, then a hydrogen pressure of 40 atm was added, and the reaction was completed by stirring at room temperature for 10 hours. The hydrogen in the autoclave is released, the reaction solution is added to an 8cm long silica gel column, and the product N-acetyl-1-(4-methylphenyl) is washed down with a developing solvent (ethyl acetate:petroleum ether 1:2). Ethylamine, nuclear magnetic resonance shows conversion rate 100%, HPLC shows ee 95.9% (Chiralpak Japan Dacheng company AD chiral column, λ=230nm; Flow rate: 1.0mL/min, n-hexane: Virahol=95: 5; t( R) = 14.1min; t(S) = 18.7min); [α] _D ²⁰ = +165.7° (c = 0.5, CHCl ₃ ); ¹ H NMR (300MHz, CDCl ₃ ) δ7.17 (d, J = 7.8Hz, 2H), 7.12(d, J=7.8Hz, 2H), 6.26(br s, 1H), 5.05-5.14(m, 1H), 2.31(s, 3H), 1.97(s, 3H), 1.47 (d, J=7.2Hz, 3H); ¹³ C NMR (75MHz, CDCl ₃ ) δ169.95, 169.11, 140.45, 140.22, 136.77, 129.12, 126.00, 48.35, 23.20, 21.64, 20.90. The main enantiomer of the product is the R configuration.

Example 31: Asymmetric hydrogenation of N-acetyl-1-(4-methylphenyl)vinylamine (III)

Under argon protection, the self-supporting catalyst 9a (0.01477mmol) and N-acetyl-1-(4-methylphenyl)vinylamine (1.477mmol) prepared above were added to the hydrogenation bottle, and 7.3mL of toluene ( 0.2M) as a solvent, the hydrogenation bottle was moved into the autoclave in an anhydrous and oxygen-free operation box, and the gas in the autoclave was repeatedly replaced with hydrogen for 5-6 times, then a hydrogen pressure of 40 atm was added, and the reaction was completed by stirring at room temperature for 10 hours. The hydrogen in the autoclave is released, the reaction solution is added to an 8cm long silica gel column, and the product N-acetyl-1-(4-methylphenyl) is washed down with a developing solvent (ethyl acetate:petroleum ether 1:2). Ethylamine, nuclear magnetic resonance shows conversion rate 100%, HPLC shows ee 95.5% (Chiralpak Japan Dacheng company AD chiral column, λ=230nm; Flow rate: 1.0mL/min, n-hexane: Virahol=95: 5; t( R) = 14.1min; t(S) = 18.7min); [α] _D ²⁰ = +165.3° (c = 0.5, CHCl ₃ ); ¹ H NMR (300MHz, CDCl ₃ ) δ7.17 (d, J = 7.8Hz, 2H), 7.12(d, J=7.8Hz, 2H), 6.26(br s, 1H), 5.05-5.14(m, 1H), 2.31(s, 3H), 1.97(s, 3H), 1.47 (d, J=7.2Hz, 3H); ¹³ C NMR (75MHz, CDCl ₃ ) δ169.95, 169.11, 140.45, 140.22, 136.77, 129.12, 126.00, 48.35, 23.20, 21.64, 20.90. The main enantiomer of the product is the R configuration.

Example 32: Asymmetric hydrogenation of N-acetyl-1-(4-methoxyphenyl)vinylamine (I)

Under argon protection, the self-supporting catalyst 9a (0.01477mmol) and N-acetyl-1-(4-methoxyphenyl)ethyleneamine (1.477mmol) prepared above were added to the hydrogenation bottle, and 7.3mL of toluene (0.2M) as a solvent, the hydrogenation bottle was moved into the autoclave in an anhydrous and oxygen-free operation box, and the gas in the autoclave was repeatedly replaced with hydrogen for 5-6 times, then a hydrogen pressure of 40 atm was added, and the reaction was completed by stirring at room temperature for 10 hours . The hydrogen in the autoclave is released, the reaction solution is added to a 8cm long silica gel column, and the product N-acetyl-1-(4-methoxyphenyl ) Ethylamine, nuclear magnetic resonance shows that the conversion rate is 100%, and HPLC shows ee 96.3% (Chiralpak Japan Dacheng Company AD chiral column, λ=230nm; Flow rate: 1.0mL/min, n-hexane: Virahol=95: 5; t (R)=24.09min; t(S)=30.74min); [α] _D ²⁰ ＝+134.3°(c=1, CHCl ₃ ); ¹ H NMR (300MHz, CDCl ₃ ) δ7.23(d, J =8.1Hz, 2H), 6.85(d, J=8.1Hz, 2H), 6.40(br s, 1H), 5.03-5.13(m, 1H), 3.77(s, 3H), 1.92(s, 3H), 1.43 (d, J = 6.9 Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 169.11, 158.53, 135.37, 127.23, 113.72, 55.10, 47.97, 23.13, 21.57. The main enantiomer of the product is the R configuration.

Example 33: Asymmetric hydrogenation of N-acetyl-1-(4-methoxyphenyl)vinylamine (II)

Under the protection of argon, the self-supporting catalyst 9b (0.01477mmol) and N-acetyl-1-(4-methylphenyl)vinylamine (1.477mmol) prepared above were added to the hydrogenation bottle, and 7.3mL of toluene ( 0.2M) as a solvent, the hydrogenation bottle was moved into the autoclave in an anhydrous and oxygen-free operation box, and the gas in the autoclave was repeatedly replaced with hydrogen for 5-6 times, then a hydrogen pressure of 40 atm was added, and the reaction was completed by stirring at room temperature for 10 hours. The hydrogen in the autoclave is released, the reaction solution is added to a 8cm long silica gel column, and the product N-acetyl-1-(4-methoxyphenyl ) Ethylamine, nuclear magnetic resonance shows that the conversion rate is 100%, and HPLC shows ee 94.8% (Chiralpak Japan Dacheng Company AD chiral column, λ=230nm; Flow rate: 1.0mL/min, n-hexane: Virahol=95: 5; t (R)=24.09min; t(S)=30.74min); [α] _D ²⁰ ＝+130.2°(c=1, CHCl ₃ ); ¹ H NMR (300MHz, CDCl ₃ ) δ7.23(d, J =8.1Hz, 2H), 6.85(d, J=8.1Hz, 2H), 6.40(br s, 1H), 5.03-5.13(m, 1H), 3.77(s, 3H), 1.92(s, 3H), 1.43 (d, J = 6.9 Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 169.11, 158.53, 135.37, 127.23, 113.72, 55.10, 47.97, 23.13, 21.57. The main enantiomer of the product is the R configuration.

Example 34: Asymmetric hydrogenation of N-acetyl-1-(4-methoxyphenyl)vinylamine (III)

Under argon protection, the self-supporting catalyst 9c (0.01477mmol) and N-acetyl-1-(4-methoxyphenyl)ethyleneamine (1.477mmol) prepared above were added to the hydrogenation bottle, and 7.3mL of toluene (0.2M) as a solvent, the hydrogenation bottle was moved into the autoclave in an anhydrous and oxygen-free operation box, and the gas in the autoclave was repeatedly replaced with hydrogen for 5-6 times, then a hydrogen pressure of 40 atm was added, and the reaction was completed by stirring at room temperature for 10 hours . The hydrogen in the autoclave is released, the reaction solution is added to a 8cm long silica gel column, and the product N-acetyl-1-(4-methoxyphenyl ) Ethylamine, nuclear magnetic resonance shows that the conversion rate is 100%, and HPLC shows ee 90.4% (Chiralpak Japan Dacheng Company AD chiral column, λ=230nm; Flow rate: 1.0mL/min, n-hexane: Virahol=95: 5; t (R)=24.09min; t(S)=30.74min); [α] _D ²⁰ ＝+124.9°(c=1, CHCl ₃ ); ¹ H NMR (300MHz, CDCl ₃ ) δ7.23(d, J =8.1Hz, 2H), 6.85(d, J=8.1Hz, 2H), 6.40(br s, 1H), 5.03-5.13(m, 1H), 3.77(s, 3H), 1.92(s, 3H), 1.43 (d, J = 6.9 Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ) δ 169.11, 158.53, 135.37, 127.23, 113.72, 55.10, 47.97, 23.13, 21.57. The main enantiomer of the product is the R configuration.

Example 35: Asymmetric hydrogenation of N-acetyl-1-(4-fluorophenyl)vinylamine (I)

Under argon protection, the self-supporting catalyst 9a (0.01477mmol) and N-acetyl-1-(4-fluorophenyl)vinylamine (1.477mmol) prepared above were added into a hydrogenation bottle, and 7.3mL of toluene (0.2 M) as a solvent, the hydrogenation bottle is moved into the autoclave in an anhydrous and oxygen-free operation box, after replacing the gas in the autoclave repeatedly with hydrogen for 5-6 times, add a hydrogen pressure of 40 atm, and stir at room temperature for 10 hours to complete the reaction. The hydrogen in the autoclave was released, and the reaction solution was added to an 8cm-long silica gel column, and the product N-acetyl-1-(4-fluorophenyl) ethyl was washed down with a developing solvent (ethyl acetate:petroleum ether 1:2). Amine, nuclear magnetic resonance shows conversion rate 100%, HPLC shows ee 93.5% (Chiralpak Japan Dacheng company AD chiral column, λ=230nm; Flow rate: 1.0mL/min, n-hexane: Virahol=95: 5; t(R )=13.21 min; t(S)=16.93 min). [α] _D ²⁰ =+124.4° (c=1, CHCl ₃ ); ¹ H NMR (300 MHz, CDCl ₃ ) δ7.22-7.27 (m, 2H), 6.94-7.00 (m, 2H), 6.66 (br s, 1H), 4.98-5.08 (m, 1H), 1.89 (s, 3H), 1.42 (d, J=6.6Hz, 3H). The main enantiomer of the product is the R configuration.

Example 36: Asymmetric hydrogenation of N-acetyl-1-(4-fluorophenyl)vinylamine (II)

Under the protection of argon, the self-supporting catalyst 9b (0.01477mmol) and N-acetyl-1-(4-fluorophenyl)vinylamine (1.477mmol) prepared above were added to the hydrogenation bottle, and 7.3mL of toluene (0.2 M) as a solvent, the hydrogenation bottle is moved into the autoclave in an anhydrous and oxygen-free operation box, after replacing the gas in the autoclave repeatedly with hydrogen for 5-6 times, add a hydrogen pressure of 40 atm, and stir at room temperature for 10 hours to complete the reaction. The hydrogen in the autoclave was released, and the reaction solution was added to an 8cm-long silica gel column, and the product N-acetyl-1-(4-fluorophenyl) ethyl was washed down with a developing solvent (ethyl acetate:petroleum ether 1:2). Amine, nuclear magnetic resonance shows conversion rate 100%, HPLC shows ee 95.2% (Chiralpak Japan Dacheng company AD chiral column, λ=230nm; Flow rate: 1.0mL/min, n-hexane: Virahol=95: 5; t(R )=13.21 min; t(S)=16.93 min). [α] _D ²⁰ =+126.7° (c=1, CHCl ₃ ); ¹ H NMR (300 MHz, CDCl ₃ ) δ7.22-7.27 (m, 2H), 6.94-7.00 (m, 2H), 6.66 (br s, 1H), 4.98-5.08 (m, 1H), 1.89 (s, 3H), 1.42 (d, J=6.6Hz, 3H); ¹³ C NMR (75MHz, CDCl ₃ ) δ169.33, 163.32, 160.07, 139.19, 127.68, 127.58, 115.27, 114.98, 47.98, 23.03, 21.74. The main enantiomer of the product is the R configuration.

Example 37: Asymmetric hydrogenation of N-acetyl-1-(4-fluorophenyl)vinylamine (III)

Under argon protection, the self-supporting catalyst 9c (0.01477mmol) and N-acetyl-1-(4-fluorophenyl)vinylamine (1.477mmol) prepared above were added to a hydrogenation bottle, and 7.3mL of toluene (0.2 M) as a solvent, the hydrogenation bottle is moved into the autoclave in an anhydrous and oxygen-free operation box, after replacing the gas in the autoclave repeatedly with hydrogen for 5-6 times, add a hydrogen pressure of 40 atm, and stir at room temperature for 10 hours to complete the reaction. The hydrogen in the autoclave was released, and the reaction solution was added to an 8cm-long silica gel column, and the product N-acetyl-1-(4-fluorophenyl) ethyl was washed down with a developing solvent (ethyl acetate:petroleum ether 1:2). Amine, nuclear magnetic resonance shows conversion rate 100%, HPLC shows ee 95.5% (Chiralpak Japan Dacheng company AD chiral column, λ=230nm; Flow rate: 1.0mL/min, n-hexane: Virahol=95: 5; t(R )=13.21 min; t(S)=16.93 min). [α] _D ²⁰ =+126.9° (c=1, CHCl ₃ ); ¹ H NMR (300 MHz, CDCl ₃ ) δ7.22-7.27 (m, 2H), 6.94-7.00 (m, 2H), 6.66 (br s, 1H), 4.98-5.08 (m, 1H), 1.89 (s, 3H), 1.42 (d, J=6.6Hz, 3H); ¹³ C NMR (75MHz, CDCl ₃ ) δ169.33, 163.32, 160.07, 139.19, 127.68, 127.58, 115.27, 114.98, 47.98, 23.03, 21.74. The main enantiomer of the product is the R configuration.

Example 38: Asymmetric hydrogenation of N-acetyl-1-(4-bromophenyl)vinylamine (I)

Under argon protection, the self-supporting catalyst 9a (0.01477mmol) and N-acetyl-1-(4-bromophenyl)vinylamine (1.477mmol) prepared above were added to the hydrogenation bottle, and 7.3mL of toluene (0.2 M) as a solvent, the hydrogenation bottle is moved into the autoclave in an anhydrous and oxygen-free operation box, after replacing the gas in the autoclave repeatedly with hydrogen for 5-6 times, add a hydrogen pressure of 40 atm, and stir at room temperature for 10 hours to complete the reaction. The hydrogen in the autoclave was released, and the reaction solution was added to an 8cm-long silica gel column, and the product N-acetyl-1-(4-bromophenyl)ethane was washed down with a developing solvent (ethyl acetate:petroleum ether 1:2). Amine, nuclear magnetic resonance shows conversion rate 100%, HPLC shows ee 96.7% (Chiralpak Japan Dacheng company AD chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=95: 5; t(R )=18.30min; t(S)=23.74min). [α] _D ²⁰ = +104.9° (c = 1, CHCl ₃ ); ¹ H NMR (300 MHz, CDCl ₃ ) δ7.42 (d, J = 8.1 Hz, 2H), 7.16 (d, J = 8.1 Hz, 2H), 6.27(br s, 1H), 4.99-5.04(m, 1H), 1.95(s, 3H), 1.42(d, J=6.9Hz, 3H); ¹³ C NMR (75MHz, CDCl ₃ ) δ169. 29, 142.39, 131.55, 127.84, 120.91, 48.18, 23.16, 21.62. The main enantiomer of the product is the R configuration.

Example 39: Asymmetric hydrogenation of N-acetyl-1-(4-bromophenyl)vinylamine (II)

Under argon protection, the self-supporting catalyst 9c (0.01477mmol) and N-acetyl-1-(4-bromophenyl)vinylamine (1.477mmol) prepared above were added to the hydrogenation bottle, and 7.3mL of toluene (0.2 M) as a solvent, the hydrogenation bottle is moved into the autoclave in an anhydrous and oxygen-free operation box, after replacing the gas in the autoclave repeatedly with hydrogen for 5-6 times, add a hydrogen pressure of 40 atm, and stir at room temperature for 10 hours to complete the reaction. The hydrogen in the autoclave was released, and the reaction solution was added to an 8cm-long silica gel column, and the product N-acetyl-1-(4-bromophenyl)ethane was washed down with a developing solvent (ethyl acetate:petroleum ether 1:2). Amine, nuclear magnetic resonance shows conversion rate 100%, HPLC shows ee 93.4% (Chiralpak Japan Dacheng company AD chiral column, λ=230nm; Flow rate: 1.0mL/min, normal hexane: Virahol=95: 5; t(R )=18.30min; t(S)=23.74min). [α] _D ²⁰ = +98.5° (c = 1, CHCl ₃ ); ¹ H NMR (300 MHz, CDCl ₃ ) δ7.42 (d, J = 8.1 Hz, 2H), 7.16 (d, J = 8.1 Hz, 2H), 6.27(br s, 1H), 4.99-5.04(m, 1H), 1.95(s, 3H), 1.42(d, J=6.9Hz, 3H); ¹³ C NMR (75MHz, CDCl ₃ ) δ169. 29, 142.39, 131.55, 127.84, 120.91, 48.18, 23.16, 21.62. The main enantiomer of the product is the R configuration.

Example 40: Asymmetric hydrogenation of N-acetyl-1-(3-bromophenyl)vinylamine (I)

Under argon protection, the self-supporting catalyst 9c (0.01477mmol) and N-acetyl-1-(3-bromophenyl)vinylamine (1.477mmol) prepared above were added into a hydrogenation bottle, and 7.3mL of toluene (0.2 M) as a solvent, the hydrogenation bottle is moved into the autoclave in an anhydrous and oxygen-free operation box, after replacing the gas in the autoclave repeatedly with hydrogen for 5-6 times, add a hydrogen pressure of 40 atm, and stir at room temperature for 10 hours to complete the reaction. The hydrogen in the autoclave was released, and the reaction solution was added to an 8cm long silica gel column, and the product N-acetyl-1-(3-bromophenyl)ethane was washed down with a developing solvent (ethyl acetate:petroleum ether 1:2). Amine, nuclear magnetic resonance shows conversion rate 100%, HPLC shows ee 92.6% (Chiralpak Japan Dacheng company AD chiral column, λ=230nm; Flow rate: 1.0mL/min, n-hexane: Virahol=95: 5; t(R )=13.29min; t(S)=16.69min). [α] _D ²⁰ =+92.9° (c=1.0, CHCl ₃ ); ¹ H NMR (300 MHz, CDCl ₃ ) δ7.32-7.41 (m, 2H), 7.12-7.21 (m, 2H), 6.48 (br s, 1H), 4.95-5.05 (m, 1H), 1.88 (s, 3H), 1.40 (d, J=7.5Hz, 3H); ¹³ C NMR (75MHz, CDCl ₃ ) δ169.40, 145.81, 130.17, , 130.08, 129.03, 124.87, 122.55, 48.28, 23.11, 21.74. The main enantiomer of the product is the R configuration.

Example 41: Asymmetric hydrogenation of N-acetyl-1-(2-naphthyl)vinylamine (I)

Under argon protection, the self-supporting catalyst 9a (0.01477mmol) and N-acetyl-1-(2-naphthyl)vinylamine (1.477mmol) prepared above were added to the hydrogenation bottle, and 7.3mL of toluene (0.2M ) as a solvent, the hydrogenation bottle was moved into the autoclave in an anhydrous and oxygen-free operation box, and after replacing the gas in the autoclave repeatedly with hydrogen for 5-6 times, a hydrogen pressure of 40 atm was added, and the reaction was completed by stirring at room temperature for 10 hours. The hydrogen in the autoclave is released, the reaction solution is added to a 8cm long silica gel column, and the product N-acetyl-1-(2-naphthyl)ethylamine is washed down with a developing solvent (ethyl acetate:petroleum ether 1:2) , NMR shows conversion rate 100%, HPLC shows ee 92.4% (Chiralpak Japan Dacheng company AD chiral column, λ=230nm; Flow rate: 1.0mL/min, n-hexane: Virahol=95: 5; t(R) = 17.17 min; t(S) = 25.26 min). [α] _D ²⁰ =+182.4° (c=1, CHCl ₃ ); ¹ H NMR (300 MHz, CDCl ₃ ) δ7.74-7.76 (m, 3H), 7.69 (d, J=0.6Hz, 1H), 7.37-7.42(m, 3H), 6.46(br s, 1H), 5.19-5.23(m, 1H), 1.88(s, 3H), 1.48(d, J=6.6Hz, 3H); ¹³ C NMR (75MHz , CDCl ₃ ) δ169.29, 140.59, 133.16, 132.51, 128.26, 127.71, 127.46, 126.05, 125.69, 124.64, 124.36, 48.66, 23.18, 21.54. The main enantiomer of the product is the R configuration.

Example 42: Asymmetric hydrogenation of N-acetyl-1-(2-naphthyl)vinylamine (II)

Under argon protection, the self-supporting catalyst 9b (0.01477mmol) and N-acetyl-1-(2-naphthyl)vinylamine (1.477mmol) prepared above were added to the hydrogenation bottle, and 7.3mL of toluene (0.2M ) as a solvent, the hydrogenation bottle was moved into the autoclave in an anhydrous and oxygen-free operation box, and after replacing the gas in the autoclave repeatedly with hydrogen for 5-6 times, a hydrogen pressure of 40 atm was added, and the reaction was completed by stirring at room temperature for 10 hours. The hydrogen in the autoclave is released, the reaction solution is added to a 8cm long silica gel column, and the product N-acetyl-1-(2-naphthyl)ethylamine is washed down with a developing solvent (ethyl acetate:petroleum ether 1:2) , NMR shows conversion rate 100%, HPLC shows ee 90.5% (Chiralpak Japan Dacheng company AD chiral column, λ=230nm; Flow rate: 1.0mL/min, n-hexane: Virahol=95: 5; t(R) = 17.17 min; t(S) = 25.26 min). [α] _D ²⁰ =+178.2° (c=1, CHCl ₃ ); ¹ H NMR (300 MHz, CDCl ₃ ) δ7.74-7.76 (m, 3H), 7.69 (d, J=0.6Hz, 1H), 7.37-7.42(m, 3H), 6.46(br s, 1H), 5.19-5.23(m, 1H), 1.88(s, 3H), 1.48(d, J=6.6Hz, 3H); ¹³ C NMR (75MHz , CDCl ₃ ) δ169.29, 140.59, 133.16, 132.51, 128.26, 127.71, 127.46, 126.05, 125.69, 124.64, 124.36, 48.66, 23.18, 21.54. The main enantiomer of the product is the R configuration.

Example 43: Asymmetric hydrogenation of N-acetyl-1-(2-naphthyl)vinylamine (III)

Under the protection of argon, the self-supporting catalyst 9c (0.01477mmol) and N-acetyl-1-(2-naphthyl)vinylamine (1.477mmol) prepared above were added to the hydrogenation bottle, and 7.3mL of toluene (0.2M ) as a solvent, the hydrogenation bottle was moved into the autoclave in an anhydrous and oxygen-free operation box, and after replacing the gas in the autoclave repeatedly with hydrogen for 5-6 times, a hydrogen pressure of 40 atm was added, and the reaction was completed by stirring at room temperature for 10 hours. The hydrogen in the autoclave is released, the reaction solution is added to a 8cm long silica gel column, and the product N-acetyl-1-(2-naphthyl)ethylamine is washed down with a developing solvent (ethyl acetate:petroleum ether 1:2) , NMR shows conversion rate 100%, HPLC shows ee 90.8% (Chiralpak Japan Dacheng company AD chiral column, λ=230nm; Flow velocity: 1.0mL/min, n-hexane: Virahol=95: 5; t(R) = 17.17 min; t(S) = 25.26 min). [α] _D ²⁰ =+178.5° (c=1, CHCl ₃ ); ¹ H NMR (300 MHz, CDCl ₃ ) δ7.74-7.76 (m, 3H), 7.69 (d, J=0.6Hz, 1H), 7.37-7.42(m, 3H), 6.46(br s, 1H), 5.19-5.23(m, 1H), 1.88(s, 3H), 1.48(d, J=6.6Hz, 3H); ¹³ C NMR (75MHz , CDCl ₃ ) δ169.29, 140.59, 133.16, 132.51, 128.26, 127.71, 127.46, 126.05, 125.69, 124.64, 124.36, 48.66, 23.18, 21.54. The main enantiomer of the product is the R configuration.

Example 44: Asymmetric hydrogenation of methyl itaconate (I)

Under argon protection, the self-supporting catalyst 9a (0.01477mmol) and methyl itaconate (1.477mmol) prepared above were added into a hydrogenation bottle, 7.3mL of toluene (0.2M) was used as a solvent, and the hydrogenation bottle was Move it into the autoclave in the oxygen operation box, replace the gas in the autoclave with hydrogen repeatedly for 5-6 times, add a hydrogen pressure of 40 atm, and stir at room temperature for 10 hours to complete the reaction. The hydrogen in the autoclave was released, and the reaction solution was added to a 8 cm long silica gel column, and the product 2-methyl-1,4-butanedioic acid methyl ester was washed down with a developing solvent (ethyl acetate:petroleum ether 1:5), NMR showed 100% conversion, GC showed ee 69, 2% (SupelcoGAMMA-DEX 225 chiral column, constant temperature: 130°C, flow rate: 1mL/min, t(R)=13.69min; t(S)=14.22min ). [α] _D ²⁰ =+78.5° (c=0.5, CHCl ₃ ); ¹ H NMR (300 MHz, CDCl ₃ ) δ 3.70 (d, J=2.1 Hz, 6H), 2.90-2.95 (m, 1H), 2.71-2.79 (m, 1H), 2.38-2.45 (m, 1H), 1.23 (d, J=7.2Hz, 3H). The main enantiomer of the product is the R configuration.

Example 45: Asymmetric hydrogenation of methyl itaconate (II)

Under argon protection, the self-supporting catalyst 9b (0.01477mmol) and methyl itaconate (1.477mmol) prepared above were added into a hydrogenation bottle, 7.3mL of toluene (0.2M) was used as a solvent, and the hydrogenation bottle was Move it into the autoclave in the oxygen operation box, replace the gas in the autoclave with hydrogen repeatedly for 5-6 times, add a hydrogen pressure of 40 atm, and stir at room temperature for 10 hours to complete the reaction. The hydrogen in the autoclave was released, and the reaction solution was added to a 8 cm long silica gel column, and the product 2-methyl-1,4-butanedioic acid methyl ester was washed down with a developing solvent (ethyl acetate:petroleum ether 1:5), NMR showed that the conversion rate was 100%, and GC showed that ee was 46.0% (SupelcoGAMMA-DEX 225 chiral column, constant temperature: 130°C, flow rate: 1mL/min, t(R)=13.69min; t(S)=14.22min). [α] _D ²⁰ =+47.8° (c=0.5, CHCl ₃ ); ¹ H NMR (300 MHz, CDCl ₃ ) δ 3.70 (d, J=2.1 Hz, 6H), 2.90-2.95 (m, 1H), 2.71-2.79 (m, 1H), 2.38-2.45 (m, 1H), 1.23 (d, J=7.2Hz, 3H). The main enantiomer of the product is the R configuration.

Example 46: Asymmetric hydrogenation of methyl itaconate (III)

Under argon protection, the self-supporting catalyst 9c (0.01477mmol) and methyl itaconate (1.477mmol) prepared above were added into a hydrogenation bottle, 7.3mL of toluene (0.2M) was used as a solvent, and the hydrogenation bottle was Move it into the autoclave in the oxygen operation box, replace the gas in the autoclave with hydrogen repeatedly for 5-6 times, add a hydrogen pressure of 40 atm, and stir at room temperature for 10 hours to complete the reaction. The hydrogen in the autoclave was released, and the reaction solution was added to a 8 cm long silica gel column, and the product 2-methyl-1,4-butanedioic acid methyl ester was washed down with a developing solvent (ethyl acetate:petroleum ether 1:5), NMR showed 100% conversion, GC showed ee 58.4% (SupelcoGAMMA-DEX 225 chiral column, constant temperature: 130°C, flow rate: 1mL/min, t(R)=13.69min; t(S)=14.22min). [α] _D ²⁰ =+65.3° (c=0.5, CHCl ₃ ); ¹ H NMR (300 MHz, CDCl ₃ ) δ 3.70 (d, J=2.1 Hz, 6H), 2.90-2.95 (m, 1H), 2.71-2.79 (m, 1H), 2.38-2.45 (m, 1H), 1.23 (d, J=7.2Hz, 3H). The main enantiomer of the product is the R configuration.

Example 47: Asymmetric hydrogenation of methyl itaconate (IV)

Under argon protection, the self-supporting catalyst 11a (0.01477mmol) and methyl itaconate (1.477mmol) prepared above were added into a hydrogenation bottle, 7.3mL of toluene (0.2M) was used as a solvent, and the hydrogenation bottle was Move it into the autoclave in the oxygen operation box, replace the gas in the autoclave with hydrogen repeatedly for 5-6 times, add a hydrogen pressure of 40 atm, and stir at room temperature for 10 hours to complete the reaction. The hydrogen in the autoclave was released, and the reaction solution was added to a 8 cm long silica gel column, and the product 2-methyl-1,4-butanedioic acid methyl ester was washed down with a developing solvent (ethyl acetate:petroleum ether 1:5), NMR showed 100% conversion, GC showed ee 65.5% (SupelcoGAMMA-DEX 225 chiral column, constant temperature: 130°C, flow rate: 1mL/min, t(R)=13.69min; t(S)=14.22min). [α] _D ²⁰ =+76.2° (c=0.5, CHCl ₃ ); ¹ H NMR (300 MHz, CDCl ₃ ) δ 3.70 (d, J=2.1 Hz, 6H), 2.90-2.95 (m, 1H), 2.71-2.79 (m, 1H), 2.38-2.45 (m, 1H), 1.23 (d, J=7.2Hz, 3H). The main enantiomer of the product is the R configuration.

Example 48: Asymmetric hydrogenation of methyl itaconate (V)

Under argon protection, the self-supporting catalyst 11a (0.01477mmol) and methyl itaconate (1.477mmol) prepared above were added into a hydrogenation bottle, 7.3mL of DCM (0.2M) was used as a solvent, and the hydrogenation bottle was Move it into the autoclave in the oxygen operation box, replace the gas in the autoclave with hydrogen repeatedly for 5-6 times, add a hydrogen pressure of 40 atm, and stir at room temperature for 10 hours to complete the reaction. The hydrogen in the autoclave was released, and the reaction solution was added to a 8 cm long silica gel column, and the product 2-methyl-1,4-butanedioic acid methyl ester was washed down with a developing solvent (ethyl acetate:petroleum ether 1:5), NMR showed 100% conversion, GC showed ee 93.5% (SupelcoGAMMA-DEX 225 chiral column, constant temperature: 130°C, flow rate: 1mL/min, t(R)=13.69min; t(S)=14.22min). [α] _D ²⁰ =+117.5° (c=0.5, CHCl ₃ ); ¹ H NMR (300 MHz, CDCl ₃ ) δ 3.70 (d, J=2.1 Hz, 6H), 2.90-2.95 (m, 1H), 2.71-2.79 (m, 1H), 2.38-2.45 (m, 1H), 1.23 (d, J=7.2Hz, 3H). The main enantiomer of the product is the R configuration.

Example 549: Asymmetric hydrogenation of methyl itaconate (VI)

Under argon protection, the self-supporting catalyst 13a (0.01477mmol) and methyl itaconate (1.477mmol) prepared above were added into a hydrogenation bottle, 7.3mL of toluene (0.2M) was used as a solvent, and the hydrogenation bottle was Move it into the autoclave in the oxygen operation box, replace the gas in the autoclave with hydrogen repeatedly for 5-6 times, add a hydrogen pressure of 40 atm, and stir at room temperature for 10 hours to complete the reaction. The hydrogen in the autoclave was released, and the reaction solution was added to a 8 cm long silica gel column, and the product 2-methyl-1,4-butanedioic acid methyl ester was washed down with a developing solvent (ethyl acetate:petroleum ether 1:5), NMR showed 100% conversion, GC showed ee 90.6% (SupelcoGAMMA-DEX 225 chiral column, constant temperature: 130°C, flow rate: 1mL/min, t(R)=13.69min; t(S)=14.22min). [α] _D ²⁰ = +108.9° (c = 0.5, CHCl ₃ ); ¹ H NMR (300 MHz, CDCl ₃ ) δ 3.70 (d, J = 2.1 Hz, 6H), 2.90-2.95 (m, 1H), 2.71-2.79 (m, 1H), 2.38-2.45 (m, 1H), 1.23 (d, J=7.2Hz, 3H). The main enantiomer of the product is the R configuration.

Claims (10)

1. part, its structural formula is:

Wherein: linker is singly-bound, C _1-8Alkyl, 1,4-divinyl phenyl, 1,4-diacetylene phenyl, xenyl or 9,10-anthryl;

R is C _1～12Alkyl, oxyethyl group,

Or O-R ^wR wherein ^z, R ^{Z '}And R ^wBe respectively hydrogen, C _1～12Alkyl, C _1～12Alkoxy or halogen.

2. part as claimed in claim 1 is characterized in that described part is the compound of (R, R) or (S, S) configuration, and its structural formula is as follows respectively:

Linker, R are according to claim 1 in the formula.

3. part as claimed in claim 1 or 2 is characterized in that described C _1～12Alkyl be methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, the tertiary butyl, cyclopentyl, cyclohexyl, suberyl, phenyl, benzyl, (1-phenyl) ethyl, 1-naphthyl or 2-naphthyl.

4. the synthetic method of claim 1 or 2 described parts, its feature is as follows: compound 5 and (linker) [B (OH) ₂] ₂Or

At Pd (PPh ₃) ₄Get compound 6 with the following Suzuki linked reaction that takes place of the catalysis of alkali, in the organic solvent, remove the MOM protecting group under the acid effect and get compound 7; Compound 7 and PR ₃Back flow reaction and get compound 8 in organic solvent through aftertreatment,

Linker is singly-bound, C in the formula _1-8Alkyl, R according to claim 1, described MOM represents methoxyl methyl, Ph represents phenyl.

5. one kind from the loaded chiral catalyzer, and its structural formula is as follows:

Wherein: M is a transition metal;

Linker is singly-bound, C _1-8Alkyl, 1,4-divinyl phenyl, 1,4-diacetylene phenyl, xenyl or 9,10-anthryl;

R is C _1～12Alkyl, oxyethyl group, Or O-R ^wR wherein ^z, R ^{Z '}And R ^wBe respectively hydrogen, C _1～12Alkyl, C _1～12Alkoxy or halogen;

The natural number of n=2 in the formula～100.

6. catalyzer as claimed in claim 5 is characterized in that described each structural unit can be (R, R) or (S, S) configuration, and its structure is as follows respectively:

Linker, M in the formula, n are as described in the claim 5.

7. as claim 5 or 6 described catalyzer, it is characterized in that described transition metal is Rh, Ru, Pd, Ir, Cu, Au or Ni; Described C _1～12Alkyl be methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, the tertiary butyl, cyclopentyl, cyclohexyl, suberyl, phenyl, 1-naphthyl or 2-naphthyl; Described n is 10～100 natural number.

8. as claim 5 or 6 described Preparation of catalysts methods, it is characterized in that being expressed as follows with reaction formula:

Reactant 8 is claim 1 or 2 described parts, and M is the described transition metal of claim 7, and X is halogen, ClO ₄ ^-, BF ₄ ^-, SbF ₆ ^-, PF ₆ ^-Or OTf ^-, k is 0,1,2,3 or 4, perhaps MX _kBe Rh (COD) ₂BF ₄N is 2～100 natural number.

9. the purposes of claim 5 or 6 described catalyzer is characterized in that being used for asymmetric catalytic hydrogenation.

10. purposes as claimed in claim 9 is characterized in that being used for a-amino acid and derivative thereof, beta-amino acids and derivative thereof, Chiral Amine and derivative thereof and 2-alkyl-1,4-Succinic Acid and derivative thereof synthetic.