CN100482671C - Chiral monophosphorous ligand, synthetic method and its use - Google Patents

Chiral monophosphorous ligand, synthetic method and its use Download PDF

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CN100482671C
CN100482671C CNB2004100668921A CN200410066892A CN100482671C CN 100482671 C CN100482671 C CN 100482671C CN B2004100668921 A CNB2004100668921 A CN B2004100668921A CN 200410066892 A CN200410066892 A CN 200410066892A CN 100482671 C CN100482671 C CN 100482671C
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CN1616470A (en
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丁奎岭
赵宝国
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Shanghai Institute of Organic Chemistry of CAS
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Abstract

The present invention relates to a new kind of chiral monophosphoprous ligand and its synthesis process and use. The ligand may be (1R, 2R, 3S, 4S) configuration compound or (1S, 2S, 3R, 4R) configuration compound. The ligand may be used in preparing catalyst for asymmetric catalytic hydrogenation of alpha-dehydrogenated amino acid and its derivative, beta-dehydrogenated amino acid and its derivative, various enamines, itaconic acid and its derivative and other compounds, to synthesize alpha-amino acid and its derivative, beta-amino acid and its derivative, chiral amine and its derivative, 2-alkyl-1, 4-succinic acid and its derivative, and other compounds.

Description

Chiral monophosphorous ligand, preparation method and use
Technical field
The present invention relates to the preparation method and use of a class novel chiral monophosphorous ligand and such part.Such part can be used for preparing the catalyzer of asymmetric catalytic hydrogenation.This catalyzer can be used for the asymmetric catalytic hydrogenation of α-dehydroamino acid and derivative, β-dehydroamino acid and derivative thereof, various enamine and compounds such as methylene-succinic acid and derivative thereof.The asymmetric catalytic hydrogenation of above-claimed cpd can be used for a-amino acid and derivative, beta-amino acids and derivative thereof, Chiral Amine and derivative thereof and 2-alkyl-1, compounds such as 4-Succinic Acid and derivative thereof synthetic.
Background technology
The asymmetric catalytic hydrogenation reaction is one of important method in the asymmetric synthesis, is widely used in chemical industry process [Ohkuma, T.; Kitamura, M.; Noryori, R. (1999) Asymmetric Hydrogenation.In:Ojiama, I. (ed) Catalytic Asymmetric Synthesis. (2nd Ed.) .Wily-VCH:NewYork (Englinsh) 2000].And the part of design and exploitation high reactivity and highly selective and catalyst system thereof are the keys of asymmetric catalytic hydrogenation reaction.Chiral phosphine ligand continues to bring out the development that has promoted asymmetric catalytic hydrogenation efficiently.[Osborn，J.A.；Jardine，F.H.；Young，J.F.；Willinson，G.J.Chem.Soc.A1966，1711]，[Knowles，W.S.；Sabacky，M.J.J.Chem.Soc.，Chem.Commun.1968，1445]，[Morrison，J.D.；Burnett，R.E.；Anguiar，A.M.；Morrow，C.J.；Phillip，C.J.Am.Chem.Soc.1971，93，1301]，[Yasuda，A.；Takaya，H.；Miyashita，A.；Toriumi，K，；Ito，T.；Souchi，T.；Noyori，R.J.Am.Chem.Soc.1980，102，7392]，[Nugent，W.A.；RajaBabu，T.V.；Burk，M.J.Science?1993，259，479]，[Burk，M.J.Acc.Chem.Res.2000，33，363]。Up to the present, more than 2000 kind of chiral phosphine ligand great majority that occurred are bidentate phosphine ligandses.Although being the first kind, chiral monodentate phosphorus part is used for the part that asymmetric catalytic hydrogenation reacts, and this class part has also obtained using widely in other asymmetric reactions, but since Kagan in 1971 etc. had synthesized first chirality bidentate phosphine ligands, the application of chiral monodentate phosphorus part in asymmetric catalytic hydrogenation just ignored by people always.[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]。Up to 2000, the application of monodentate phosphorus ligand in asymmetric catalytic hydrogenation just caused people's attention again, with the amino phosphorous acid ester of reports such as Feringa
Figure C200410066892D00061
(MonoPhos) allow people see the huge applications prospect of this class part in asymmetric catalytic hydrogenation again for several chiral monodentate phosphorus parts of representative.The catalytic activity and the enantioselectivity of chiral monodentate phosphorus part can compare favourably with bidentate phosphine ligands, and have advantages such as synthesizing conveniently, be easy to combination simultaneously.[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.TetrahedronLett.2000，41，6333]，[Reetz，M.T.；Mehler，G.Angew.Chem.Int.Ed.2000，39，3889]，[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.；deVries，J.G.；Feringa，B.L.J.Am.Chem.Soc.2002，124，14552]，[M.van?den?Berg，A.J.Minnaard，J.G.de?Vries，B.L.Feringa(DSM?N.V.)，World?Patent?WO?02/04466，2002]，[M.van?den?Berg，A.J.Minnaard，R.M.Haak，M.Leeman，E.P?Schudde，A.Meetsma，B.L.Feringa，A.H.M.De?Vries，C.E.PMaljaars，C.E.Willans，D.J.Hyett，J.A.F.Boogers，H.J.W.Henderickx，J.G.der?Vries，Adv.Synth.Catal.2003，345，308][Hu，A.-G.；Fu，Y.；Xie，J.-H.；Zhou，H.；Wang，L.-X.；Zhou，Q.-L.Angew.Chem.Int.Ed.2002，41，2348]。
Summary of the invention
The problem that will solve of the present invention provides the novel chiral monodentate phosphorus part of a class.
The problem that also will solve of the present invention provides a kind of synthetic method of above-mentioned part and the purposes of above-mentioned part.
The structural formula of part provided by the invention is as follows:
Figure C200410066892D00071
The natural number of n=4-8, R 1And R 1 'Can be respectively hydrogen or C 1-12Alkyl,
R 2Can be respectively hydrogen or C 1-12Alkyl,
R 3And R 3 'Can be respectively hydrogen, C 1-12Alkyl,
Figure C200410066892D00072
O-R wOr halogen, R y, R Y ', R Y ", R z, R Z 'And R wCan be respectively hydrogen, C 1-8Alkyl, C 5～C 7Cycloalkyl, phenyl, benzyl, (1-phenyl) ethyl, 1-naphthyl or 2-naphthyl, be recommended as hydrogen, methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, the tertiary butyl, cyclopentyl, cyclohexyl, suberyl, phenyl, benzyl, (1-phenyl) ethyl, 1-naphthyl, 2-naphthyl or halogen etc.;
R 4Can be C 1-12Alkyl,
Figure C200410066892D00073
Or O-R w, R wherein z, R Z 'And R wAs previously mentioned.
Above-mentioned C 1-12Alkyl unless otherwise indicated, recommend methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, the tertiary butyl, cyclopentyl, cyclohexyl, suberyl, 1-naphthyl, 2-naphthyl etc.
This part can be (1R, 2R, 3S, 4S) or (1S, 2S, 3R, 4R) (wherein 1,2,3 and 4 is numberings of carbon in the ligand structure formula to the compound of configuration, when judging the configuration of C1, C2, R 1The group of being used as priority ranking minimum in four groups that link to each other with C1 is R 1 'The group of being used as priority ranking minimum in four groups that link to each other with C2).Its structural formula is as follows respectively:
Figure C200410066892D00081
The present invention also provides the synthetic method of above-mentioned part, be exactly with trans 1,2-cyclohexanediamine (1 ') is a raw material, obtain (1R by splitting with tartrate, 2R) or (1S, the cyclohexanediamine tartrate (2 ') of configuration 2S), (1R, 2R) or (1S, the cyclohexanediamine tartrate (2 ') of configuration 2S) with
Figure C200410066892D00082
Condensation make (1R, 2R) or (1S, the Salen (3 ') of configuration 2S), Salen (3 ') close ring obtain (1R, 2R, 3S, 4S) or (1S, 2S, 3R, the 4R) compound 4 ' of configuration, compound 4 ' with Or
Figure C200410066892D00084
Reaction obtain (1R, 2R, 3S, 4S) or (1S, 2S, 3R, the 4R) compound 5 ' of configuration, compound 5 ' and PR 4(being recommended as hexamethyl phosphine triamine) reaction obtains target ligand, and promptly (1R, 2R, 3S, 4S) or (1S, 2S, 3R, 4R) compound 6 ' of configuration.(wherein 1,2,3,4 is the numbering of carbon in the structural formula of respective compound, when judging the configuration of C1, C2, R 1The group of being used as priority ranking minimum in four groups that link to each other with C1 is R 1 'The group of being used as priority ranking minimum in four groups that link to each other with C2)
Described compound 1 '～6 ' structural formula as follows:
Figure C200410066892D00091
R in the formula 1, R 1 ', R 2, R 3, R 3,, n, R 4As previously mentioned.In the inventive method compound 5 ', 6 ' can be (1R, 2R, 3S, 4S) configuration, its structure is as follows:
Figure C200410066892D00092
Also can be (1S, 2S, 3R, 4R) configuration, its structure is as follows:
Figure C200410066892D00093
R in the said structure 1, R 1 ', R 2, R 3, R 3 ', R 4With n as previously mentioned.
In the inventive method, the preparation process of above-claimed cpd with (1R, 2R, 3S, 4S) configuration of compound is an example, can represent with following reaction process simply:
Figure C200410066892D00101
The reaction conditions that synthetic method in the above-mentioned reaction process is recommended can specify as follows:
Trans 1 from racemization, 2-cyclohexanediamine (1) split and obtain (1R, 2R) or (1S, 2S) configuration is trans 1,2-cyclohexanediamine tartrate (2):
In water, racemization trans 1, the tartrate effect of 2-cyclohexanediamine (1) and L or D configuration, can split respectively and obtain (1R, 2R) or (1S, 2S) compound 2 of configuration.Wherein compound 1 with tartaric mol ratio is: 1:1-5, and temperature of reaction: 0 ℃-100 ℃, the reaction times: 1-20h.
From (1R, 2R) or (1S, the 2S) compound 2 of configuration preparation (1R, 2R) or (1S, 2S) compound 3 of configuration:
In organic solvent, (1R, 2R) or (1S, 2S) compound 2 of configuration under the effect of alkali, with
Figure C200410066892D00111
Reaction can make respectively (1R, 2R) or (1S, 2S) compound 3 of configuration.Wherein compound 2, alkali and
Figure C200410066892D00112
Mol ratio be: 1:1-5:2-10, temperature of reaction: 0 ℃-100 ℃, the reaction times: 1-20h.
From (1R, 2R) or (1S, the 2S) compound 3 of configuration preparation (1R, 2R, 3S, 4S) or (1S, 2S, 3R, 4R) compound 4 of configuration:
In organic solvent, (1R, 2R) or (1S, 2S) compound 3 of configuration and metal and acid effect, intramolecular cyclization can make respectively (1R, 2R, 3S, 4S) or (1S, 2S, 3R, 4R) compound 4 of configuration.Wherein the mol ratio of compound 3, metal and acid is: 1:1-5:1-10, and temperature of reaction :-78 ℃-100 ℃, the reaction times: 1-20h.
From (1R, 2R, 3S, 4S) or (1S, 2S, 3R, the 4R) compound 4 of configuration preparation (1R, 2R, 3S, 4S) or (1S, 2S, 3R, 4R) compound 5 of configuration:
In organic solvent, (1R, 2R, 3S, 4S) or (1S, 2S, 3R, 4R) compound 4 of configuration under the effect of alkali, with
Figure C200410066892D00113
Or
Figure C200410066892D00114
Reaction can make respectively (1R, 2R, 3S, 4S) or (1S, 2S, 3R, 4R) compound 5 of configuration.Wherein compound 4, alkali and
Figure C200410066892D00115
Or
Figure C200410066892D00116
Mol ratio be: 1:1-5:2-10, temperature of reaction: 0 ℃-150 ℃, the reaction times: 1-20h.
From (1R, 2R, 3S, 4S) or (1S, 2S, 3R, the 4R) compound 5 of configuration preparation (1R, 2R, 3S, 4S) or (1S, 2S, 3R, 4R) compound 6 of configuration:
In organic solvent, (1R, 2R, 3S, 4S) or (1S, 2S, 3R, 4R) compound 5 of configuration can make respectively with hexamethyl phosphine triamine (1R, 2R, 3S, 4S) or (1S, 2S, 3R, 4R) compound 6 of configuration.Wherein compound 5 with the mol ratio of hexamethyl phosphine triamine is: 1:1-5, and temperature of reaction: 0 ℃-150 ℃, the reaction times: 1-20h.
The organic solvent that uses in aforesaid method of the present invention can be benzene,toluene,xylene, trimethylbenzene, acetonitrile, ether, tetrahydrofuran (THF), glycol dimethyl ether, chloroform, methylene dichloride, methyl alcohol, ethanol, Virahol, N, dinethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide (DMSO), N-Methyl pyrrolidone etc.
The alkali that uses in aforesaid method of the present invention can be sodium hydroxide, potassium hydroxide, yellow soda ash, salt of wormwood, cesium carbonate, sodium bicarbonate, saleratus, sodium hydride, potassium hydride KH, hydrolith, triethylamine, diisopropyl ethyl amine, Tetramethyl Ethylene Diamine, N, accelerine, N, N-Diethyl Aniline, 1,4-diazabicylo [2.2.2] octane (DABCO), diazabicylo dodecane (DBU), 1,4-lupetazin, 1-methyl piperidine, 1-methylpyrrole, quinoline or pyridine etc.
The acid of using in aforesaid method of the present invention can be sulfuric acid, hydrochloric acid, phosphoric acid, Hydrogen bromide, hydroiodic acid HI, acetic acid, trifluoroacetic acid, trichoroacetic acid(TCA), Phenylsulfonic acid, tosic acid, methylsulfonic acid or trifluoromethanesulfonic acid etc.
The metal that uses in aforesaid method of the present invention can be lithium, sodium, potassium, magnesium, calcium, strontium, titanium, iron, manganese, nickel, copper, zinc, aluminium, tin or lead etc.
Above-mentioned part provided by the invention can be used for catalyzer, is the catalyzer of preparation asymmetric catalytic hydrogenation specifically.This catalyzer is applicable to the asymmetric catalytic hydrogenation of α-dehydroamino acid and derivative, β-dehydroamino acid and derivative thereof, various enamine and compounds such as methylene-succinic acid and derivative thereof and is used for a-amino acid and derivative, beta-amino acids and derivative thereof, Chiral Amine and derivative thereof and 2-alkyl-1, compounds such as 4-Succinic Acid and derivative thereof synthetic.
Specific implementation method
Help further to understand the present invention by following embodiment, but do not limit the content of invention.
Preparation method of the present invention can be further as follows with the preparation process embodiment of representational compound:
Embodiment 1: from 1 of racemization, 2-cyclohexanediamine 1 splits and obtains that (1R, 2R) configuration is trans 1,2-cyclohexanediamine tartrate 2
The there-necked flask of-500ml adds 80g L-(+) tartrate and 220ml water in bottle, be stirred to tartrate and dissolve fully.Slowly drip 1, and the 2-cyclohexanediamine (trans: cis=70:30) (128ml), the liquid temperature is not above 70 ℃; After cyclohexanediamine dropwises, drip Glacial acetic acid (53ml) in reaction system, the liquid temperature does not surpass 90 ℃, has a large amount of white solids to separate out.Naturally cooling also stirred 2 hours; Stop to stir, place reaction flask ice bath to cool off 2h, filter, filter cake elder generation washs with 5 ℃ water (50ml), use again methanol wash (5 * 80ml), drain, vacuum-drying obtains white solid, promptly (1R, 2R) configuration is trans 1,2-cyclohexanediamine tartrate 2 (94g, yield: 99%). 1HNMR(300MHz，D 2O)δ?1.30-1.37(m，2H)，1.45-1.52(m，2H)，1.79-1.82(m，2H)，2.12-2.16(m，2H)，3.34-3.37(m，2H)，4.32(s，2H)。
Embodiment 2: from (1R, the 2R) compound 2 of configuration preparation (1R, 2R) compound 3 of configuration (R wherein 3, R 3 '=H)
The there-necked flask of-250ml, in bottle, add (1R, 2R) configuration is trans 1,2-cyclohexanediamine tartrate (2) (10.5g), salt of wormwood (11.4g) and distilled water (50ml), be stirred to solid and dissolve fully.Add dehydrated alcohol (150ml) and be heated to 80 ℃, under this temperature, drip ethanol (20mL) solution of salicylic aldehyde (10.2g) in the 2h, dropwise backflow 4h.Stopped reaction is sloughed solvent under the decompression.With dichloromethane extraction (3100mL), organic layer merges, and washing is (50mL) once, and anhydrous sodium sulfate drying filters, and concentrates, drains and obtain yellow oil (12.75g), be i.e. (1R, 2R) the compound 3 (yield: 99%) of configuration. 1H?NMR(300MHz，CDCl 3)δ?1.49-1.99(m，8H)，3.32-3.35(m，2H)，6.78-6.91(m，4H)，7.15-7.28(m，4H)，8.26(s，2H)，13.33(s，2H)。
Embodiment 3: from (1R, the 2R) compound 3 of configuration preparation (1R, 2R, 3S, 4S) compound 4 of configuration (R wherein 3, R 3 '=H)
The there-necked flask of-1L, in bottle, add (1R, 2R) compound 3 (30g) of configuration, manganese powder (10.2g), dry toluene (90mL) and anhydrous acetonitrile (850mL), vigorous stirring, slowly drip trifluoroacetic acid (30mL) under the room temperature, dropwise stirring at room 24h.Stopped reaction filters, and filter cake places 200mL water, uses saturated NaHCO 3Solution is neutralized to pH=8-9, (3 * 500mL), organic layer merges, washing (200mL) with ethyl acetate extraction, anhydrous sodium sulfate drying, filter, concentrate, crystallization (ethyl acetate: normal hexane=1:1) white needle-like crystals, i.e. (1R, 2R, 3S, 4S) compound 4 of configuration (25.5g, yield: 84.5%).M.p.226-227 ℃, [α] 20 D-5.5 (c1.00, CHCl 3); 1H NMR (300MHz, CDCl 3) δ 1.41-1.46 (m, 4H), 1.76-1.82 (m, 4H), 2.41 (s, 2H), 2.67-2.70 (m, 2H), 4.15 (s, 2H), 6.12 (dd, 2H, J=1.8,7.5Hz), 6.42 (dt, 2H, J=1.2,7.5Hz), 6.84 (dd, 2H, J=1.2,8.1Hz), 7.07 (dt, 2H, J=1.8,7.8Hz), 10.86 (s, 2H); 13C NMR (75MHz, CDCl 3) δ 154.67,130.0,12.8.8,123.1,118.4,116.4,63.2,59.5,31.4,24.2; MS (EI, 70eV) m/z (relative abundance %) 324 (M +, 11), 203 (43), 122 (100).
Embodiment 4: from (1R, 2R, 3S, the 4S) compound 4 of configuration preparation (1R, 2R, 3S, 4S) the compound 5a of configuration (R wherein 1, R 1 '=H, R 2=phenyl, R 3, R 3 '=H, n=4)
The there-necked flask of-500mL adds (1R, 2R in bottle, 3S, 4S) compound 4 (8g) of configuration, diisopropyl ethyl amine (19.3mL), dry toluene (150mL) stir and are heated to 80 ℃, slowly drip trimethyl silicane chlorine (6.3mL) under this temperature, dropwise backflow 1h.Stop the heating and be cooled to 0 ℃, in reaction flask, add methylene dichloride (30mL) after, slowly drip Benzoyl chloride (6.3mL), stirred overnight at room temperature.Stopped reaction adds entry (50mL), the tetrahydrofuran solution (1M of tetrabutyl ammonium fluoride, 55mL), continue to stir 2h, stop to stir, tell organic layer, (3 * 200mL), organic layer merges water layer with ethyl acetate extraction, washing is (200mL) once, and anhydrous sodium sulfate drying filters, concentrate, column chromatography for separation (ethyl acetate: normal hexane=1:3) white solid, i.e. (1R, 2R, 3S, 4S) the compound 5a of configuration (9.8g, yield: 71%).M.p.197-198 ℃, [α] 20 D+ 15.6 (c1.00, CH 3OH); 1H NMR (300MHz, CDCl 3) δ 1.56-1.79 (m, 8H), 2.77 (s, 2H), 4.12 (m, 2H), 6.60 (d, 2H, J=8.1Hz), 6.87 (d, 2H, J=7.2Hz), 7.02-7.09 (m, 6H), 7.16-7.24 (m, 4H), 7.63 (d, 2H, J=7.5Hz); 13C NMR (75MHz, DMSO) δ 173.1,154.0, and 136.6,129.9,128.6,128.1,127.9,126.5,118.8,115.2,60.6,55.1,31.1,24.9; MS (EI, 70eV) m/z (relative abundance %) 532 (M +, 2.7), 427 (11.5), 306 (5.5), 105 (100); IR (KBr) cm -13236,2934,1625,1602,1579,1485,1388,1337,1239,1110,905,755,701.
Embodiment 5: from (1R, 2R, 3S, the 4S) compound 4 of configuration preparation (1R, 2R, 3S, 4S) the compound 5b of configuration (R wherein 1, R 1 '=H, R 2=methyl, R 3, R 3 '=H, n=4)
The there-necked flask of-250mL adds (1R, 2R in bottle, 3S, 4S) compound 4 (5g) of configuration, diisopropyl ethyl amine (12.1mL), dry toluene (100mL) stir and are heated to 80 ℃, slowly drip trimethyl silicane chlorine (3.9mL) under this temperature, dropwise backflow 1h.Stop heating and be cooled to 0 ℃, in reaction flask, add methylene dichloride (20mL) after, slow dripping acetyl chloride (2.45g), stirred overnight at room temperature.Stopped reaction adds entry (50mL), the tetrahydrofuran solution (1M of tetrabutyl ammonium fluoride, 35mL), continue to stir 2h, stop to stir, tell organic layer, (3 * 200mL), organic layer merges water layer with ethyl acetate extraction, washing is (150mL) once, and anhydrous sodium sulfate drying filters, concentrate, column chromatography for separation (ethyl acetate: normal hexane=1:3) white solid, i.e. (1R, 2R, 3S, 4S) the compound 5b of configuration (5.7g, yield: 90.5%).M.p.294-295 ℃, [α] 20 D-5.0 (c1.00, CH 3OH); 1H NMR (300MHz, CD 3OD) δ 1.29-1.46 (m, 4H), 1.71 (m, 2H), 1.92 (s, 6H), 2.90 (m, 2H), 3.60 (m 2H), 6.43 (s, 2H), 6.85-6.93 (m, 4H), 7.19 (dt, 2H, J=1.5,7.5Hz), 7.39 (d, 2H, J=6.3Hz); 13C NMR (75MHz, DMSO) δ 171.4,154.0, and 128.6,127.5,125.7,119.1,115.5,57.8,56.0,31.0,24.8,22.0; MS (EI, 70eV) m/z (relative abundance %) 408 (M +, 37), 365 (22), 323 (45), 202 (33), 122 (100); IR (KBr) cm -13240,2943,1633,1591,1455,1415,1371,1290,1236,1037,967,765,752.
Embodiment 6: from (1R, 2R, 3S, the 4S) compound 4 of configuration preparation (1R, 2R, 3S, 4S) the compound 5c of configuration (R wherein 1, R 1 '=H, R 2=3,5-3,5-dimethylphenyl, R 3, R 3 '=H, n=4)
The there-necked flask of-250mL adds (1R, 2R in bottle, 3S, 4S) compound 4 (3g) of configuration, diisopropyl ethyl amine (7.25mL), dry toluene (50mL) stir and are heated to 80 ℃, slowly drip trimethyl silicane chlorine (2.36mL) under this temperature, dropwise reflux 1h.Stop the heating and be cooled to 0 ℃, in reaction flask, add methylene dichloride (20mL) after, slowly drip 3, the toluene solution (10mL) of 5-dimethyl benzoyl chloride (3.2g), stirred overnight at room temperature.Stopped reaction adds entry (30mL), the tetrahydrofuran solution (1M of tetrabutyl ammonium fluoride, 20mL), continue to stir 2h, stop to stir, tell organic layer, (3 * 100mL), organic layer merges water layer with ethyl acetate extraction, washing is (100mL) once, and anhydrous sodium sulfate drying filters, concentrate, column chromatography for separation (ethyl acetate: normal hexane=1:3) white solid, i.e. (1R, 2R, 3S, 4S) the compound 5c of configuration (5.3g, yield: 97%).m.p.197-198℃，[α] 20 D-35.5(c?1.00，CH 3OH)； 1H?NMR(300MHz，DMSO)δ?1.39-1.54(m，4H)，1.70-1.80(m，2H)，2.04(s，12H)，2.60-2.70(m，2H)，3.86(m2H)，5.84(s，2H)，6.53(s，4H)，6.73(d，2H，J＝7.5Hz)，6.92(s，2H)，7.00(m，2H)，7.21(t，2H，J＝7.5Hz)，7.64(s，2H)，9.05(s，2H)；IR(KBr)cm -1?3198，2933，1654，1625，1597，1458，1388，1339，1260，1242，1181，860，812，754。
Embodiment 7: from (1R, 2R, 3S, the 4S) compound 4 of configuration preparation (1R, 2R, 3S, 4S) the compound 5d of configuration (R wherein 1, R 1 '=H, R 2=2-naphthyl, R 3, R 3 '=H, n=4)
The there-necked flask of-250mL adds (1R, 2R in bottle, 3S, 4S) compound 4 (3g) of configuration, diisopropyl ethyl amine (7.25mL), dry toluene (50mL) stir and are heated to 80 ℃, slowly drip trimethyl silicane chlorine (2.36mL) under this temperature, dropwise reflux 1h.Stop heating and be cooled to 0 ℃, in reaction flask, add methylene dichloride (20mL) after, slowly drip the toluene solution (10mL) of 2-naphthoyl chloride (3.6g), stirred overnight at room temperature.Stopped reaction adds entry (30mL), the tetrahydrofuran solution (1M of tetrabutyl ammonium fluoride, 20mL), continue to stir 2h, stop to stir, tell organic layer, (3 * 100mL), organic layer merges water layer with ethyl acetate extraction, washing is (100mL) once, and anhydrous sodium sulfate drying filters, concentrated, column chromatography for separation (ethyl acetate: normal hexane=1: 3) get white solid, i.e. (1R, 2R, 3S, 4S) the compound 5d of configuration (5.55g, yield: 97%).M.p.316 ℃ of decomposition, [α] 20 D-168.1 (c 0.50, CH 3OH); 1H NMR (300MHz, DMSO) δ 1.46 (m, 2H), 1.64 (m, 2H), 1.78 (m, 2H), 2.76 (m, 2H), 4.00 (m, 2H), 6.00 (s, 2H), 6.74 (d, 2H, J=7.8Hz), 7.08 (d, 4H, J=7.8Hz), 7.26 (m, 2H), 7.38-7.50 (m, 8H), 7.74 (d, 2H, J=8.8Hz), 7.84 (d, 4H, J=7.8Hz), 8.97 (s, 2H); IR (KBr) cm -13226,2933,1621,1457,1390,1330,1239,1105,819,755.
Embodiment 8: from (1R, 2R, 3S, 4S) the compound 5a of configuration preparation (1R, 2R, 3S, 4S) the compound 6a of configuration (R wherein 1, R 1 '=H, R 2=phenyl, R 3, R 3 '=H, R 4=dimethylin, n=4)
The single port bottle of-25mL; in bottle, add (1R; 2R; 3S; 4S) the compound 5a (1.5g) of configuration; hexamethyl phosphine triamine (0.67mL); dry toluene (20mL) under the argon shield, stirs and reflux 20h; the solid of adularescent is separated out; stop the heating and be cooled to 0 ℃, leave standstill 3h under this temperature, filter white powder solid (0.95g); the mother liquor column chromatography for separation (normal hexane: ethyl acetate: triethylamine=1:0.15:0.06) white powder solid (0.65g); promptly obtain (1R, 2R, 3S altogether; 4S) the compound 6a of configuration (1.6g, yield: 94%).M.p.278-279 ℃, [α] 20 D-151.4 (c1.00, CHCl 3); 1HNMR (300MHz, CDCl 3) δ 1.50-1.95 (m, 6H), 2.30 (d, 6H, J=12Hz), 2.80 (m, 1H), 3.12 (m, 1H), 4.05 (m, 1H), 4.44 (m, 1H), 5.31 (d, 1H, J=15.6Hz), 5.84 (s1H), 6.52 (d, 2H, J=9.3Hz), 6.74-7.30 (m, 14H), 7.56-7.63 (m, 2H); 13C NMR (75MHz, CDCl 3) δ 176.9,175.2,151.13,151.06,150.98,150.92,136.27,135.73,135.32,129.76,129.67,129.00,128.49,128.09,127.73,126.74,126.42,125.77,125.64,124.05,123.96,122.01,121.97,121.80,66.17,65.91,58.09,57.92,56.04,34.07,33.82,32.61,32.38,25.26,25.01; 31P NMR (121MHz, CDCl 3) δ 140.47; MS (EI, 70eV) m/z (relative abundance %) 605 (M +, 0.8), 561 (1.3), 405 (6.6), 285 (5.5), 105 (100); IR (KBr) cm -13059,2931,1650,1602,1579,1478,1457,1421,1328,1238,1109,969,883,863,763,697,658; Ultimate analysis (EA): theoretical value C 36H 36N 3O 4P:C:71.39%, H:5.99%, N:6.94%, measured value: C:71.13%, H:5.94%, N:6.79%.
Embodiment 9: from (1R, 2R, 3S, 4S) the compound 5a of configuration preparation (1R, 2R, 3S, 4S) the compound 6b of configuration (R wherein 1, R 1 '=H, R 2=phenyl, R 3, R 3 '=H, R 4=diethylin, n=4)
The single port bottle of-25mL; in bottle, add (1R; 2R; 3S; 4S) the compound 5a (0.5g) of configuration; Hexaethyl phosphine triamine (0.27mL); anhydrous dimethyl benzene (5mL) under the argon shield, stirs and reflux 20h; the solid of adularescent is separated out; stop the heating and be cooled to 0 ℃, leave standstill 3h under this temperature, filter white powder solid (0.35g); the mother liquor column chromatography for separation (normal hexane: ethyl acetate: triethylamine=1:0.15:0.06) white solid (0.1g); promptly obtain (1R, 2R, 3S altogether; 4S) the compound 6b of configuration (0.45g, yield: 75%).M.p.241-242 ℃, [α] 20 D-160.8 (c 1.00, CHCl 3); 1HNMR (300MHz, CDCl 3) δ 0.95 (t, 6H, J=8.7Hz), 1.50-1.94 (m, 6H), 2.74 (m, 4H), 2.80 (m, 1H), 3.14 (m, 1H), 4.03 (m, 5H), 4.43 (m, 1H), 5.33 (d, 1H, J=16.5Hz), 5.88 (s1H), 6.48 (dd, 2H, J=1.26.9Hz), 6.71-6.77 (m, 2H), 6.88-7.30 (m, 12H), 7.60 (m, 2H); 13C NMR (75MHz, CDCl 3) δ 177.07,175.30,151.40,15133,151.22,136.38,135.79,135.43,129.77,129.60,128.99,128.45,128.11,127.76,126.80,126.56,125.80,125.69,123.92,123.84,122.12,121.77,66.31,66.04,58.01,56.03,38.35,38.08,32.68,32.48,25.30,25.09,14.94,14.87; 31P NMR (121MHz, CDCl 3) δ 142.17; MS (EI, 70eV) m/z (relative abundance %) 633 (M +, 1.9), 561 (4.1), 433 (20), 313 (19), 105 (100); IR (KBr) cm -13062,2950,1650,1601,1578,1457,1380,1329,1205,1108,1025,958,880,863,765,700,669; Ultimate analysis (EA): theoretical value C 38H 40N 3O 4P:C:72.02%, H:6.36%, N:6.63%, measured value: C:71.77%, H:6.33%, N:6.48%.
Embodiment 10: from (1R, 2R, 3S, 4S) the compound 5b of configuration preparation (1R, 2R, 3S, 4S) the compound 6c of configuration (R wherein 1, R 1 '=H, R 2=methyl, R 3, R 3 '=H, R 4=dimethylin, n=4)
The single port bottle of-25mL adds (1R, 2R in bottle; 3S, 4S) the compound 5b (0.847g) of configuration, hexamethyl phosphine triamine (0.432mL), dry toluene (10mL) are under the argon shield; stir and reflux 20h; stop heating and be cooled to room temperature, (normal hexane: ethyl acetate: triethylamine=1:0.15:0.06) get white foam shape solid promptly obtains (1R to column chromatography for separation; 2R; 3S, 4S) the compound 6c of configuration (0.5g, yield: 49%). 1H NMR (300MHz, CDCl 3) δ 1.20-1.32 (m, 2H), 1.57 (s, 3H), 1.58-1.85 (m, 4H), 1.86 (s, 3H), 2.84 (d, 6H, J=11.4Hz), 3.00 (m, 1H), 3.38 (m, 1H), 3.70 (m, 1H), 4.10 (m, 1H), 5.67 (d, 1H, J=16.8Hz), 6.23 (s1H), 7.01 (d, 1H, J=8.1Hz), 7.08 (d, 1H, J=8.1Hz), 7.14-7.32 (m, 4H), 7.40 (d, 2H, J=5.7Hz); MS (EI, 70eV) m/z (relative abundance %) 481 (M +, 3.0), 437 (14), 351 (5), 256 (6), 119 (100).
Embodiment 11: from (1R, 2R, 3S, 4S) the compound 5b of configuration preparation (1R, 2R, 3S, 4S) the compound 6d of configuration (R wherein 1, R 1 '=H, R 2=methyl, R 3, R 3 '=H, R 4=diethylin, n=4)
The single port bottle of-25mL adds (1R, 2R in bottle; 3S, 4S) the compound 5b (0.5g) of configuration, Hexaethyl phosphine triamine (0.352mL), anhydrous dimethyl benzene (6mL) are under the argon shield; stir and reflux 40h; stop heating and be cooled to room temperature, (normal hexane: ethyl acetate: triethylamine=1:0.15:0.06) get white foam shape solid promptly obtains (1R to column chromatography for separation; 2R; 3S, 4S) the compound 6d of configuration (0.12g, yield: 19%).m.p.162-163℃，[α] 20 D-127.6(c0.50，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?1.27(t，7H，J＝7.2Hz)，1.34-1.34(m，1H)，1.42-1.60(m，5H)，1.64-1.87(m，5H)，3.00(m，1H)，3.36(m，5H)，3.70(m，1H)，4.07(m，1H)，5.68(d，1H，J＝17.1Hz)，5.27(s1H)，6.99(d，1H，J＝7.8Hz)，7.06-7.20(m，3H)，7.25-7.31(m，2H)，7.40(dd，2H，J＝1.5，7.5Hz)； 31P?NMR(121MHz，CDCl 3)δ?141.30。
Embodiment 12: from (1R, 2R, 3S, 4S) the compound 5c of configuration preparation (1R, 2R, 3S, 4S) the compound 6e of configuration (R wherein 1, R 1 '=H, R 2=3,5-3,5-dimethylphenyl, R 3, R 3 '=H, R 4=dimethylin, n=4)
The single port bottle of-25mL adds (1R, 2R in bottle; 3S, 4S) the compound 5c (1.0g) of configuration, hexamethyl phosphine triamine (0.343mL), dry toluene (10mL) are under the argon shield; stir and reflux 40h; stop heating and be cooled to room temperature, (normal hexane: ethyl acetate: triethylamine=1:0.15:0.06) get white foam shape solid promptly obtains (1R to column chromatography for separation; 2R; 3S, 4S) the compound 6e of configuration (0.91g, yield: 81%).m.p.88-89℃，[α] 20 D-170.4(c1.00，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?1.50-1.91(m，4H)，1.93(s，6H)，1.99(s，6H)，2.08-2.13(m，2H)，2.34(d，6H，J＝12.0Hz)，2.96(m，1H)，3.17(m，1H)，4.00(m，1H)，4.39(m，1H)，5.05-5.29(m，1H)，5.74(s1H)，6.03(d，2H，J＝6.3Hz)，6.49(d，2H，J＝6.3Hz)，6.71-6.84(m，4H)，7.19-7.34(m，4H)，7.54-7.61(m，2H)。
Embodiment 13: from (1R, 2R, 3S, 4S) the compound 5d of configuration preparation (1R, 2R, 3S, 4S) the compound 6f of configuration (R wherein 1, R 1 '=H, R 2=2-naphthyl, R 3, R 3 '=H, R 4=dimethylin, n=4)
The single port bottle of-25mL adds (1R, 2R in bottle; 3S, 4S) the compound 5d (0.8g) of configuration, hexamethyl phosphine triamine (0.255mL), dry toluene (10mL) are under the argon shield; stir and reflux 20h; stop heating and be cooled to room temperature, (normal hexane: ethyl acetate: triethylamine=1:0.15:0.06) get white foam shape solid promptly obtains (1R to column chromatography for separation; 2R; 3S, 4S) the compound 6f of configuration (0.51g, yield: 57%).m.p.121-122℃，[α] 20 D-211.5(c?1.00，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?1.61(d，6H，J＝12.0Hz)，1.63-2.05(m，6H)，3.02(m，1H)，3.24(m，1H)，4.14(m，1H)，4.52(m，1H)，5.32(d，1H，J＝16.2Hz)，5.81(s1H)，6.59-6.70(m，2H)，6.89(s，1H)，7.00(dd，1H，J＝1.5，8.4Hz)，7.26-7.44(m，12H)，7.53-7.74(m，6H)； 31P?NMR(121MHz，CDCl 3)δ?140.31。
Embodiment 14: the asymmetric hydrogenation (I) of α-acetamido-beta-phenyl methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1R; 2R; 3S; 4S) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido-beta-phenyl methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 99.5% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=95:5; T (R)=19.4min; T (S)=26.7min).[α] D 20＝-126.0°(c＝0.5，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ7.24-7.31(m，3H)，7.09-7.12(m，2H)，6.22(d，J＝7.8Hz，1H)，4.85-4.91(m，1H)，3.72(s，3H)，3.04-3.14(m，2H)，1.97(s，3H)。The main enantiomer of product is the R configuration.
Embodiment 15: the asymmetric hydrogenation (II) of α-acetamido-beta-phenyl methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1S; 2S; 3R; 4R) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido-beta-phenyl methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 99.5% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=95:5; T (R)=19.4min; T (S)=26.7min).[α] D 20＝+126.5°(c＝0.5，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.24-7.31(m，3H)，7.09-7.12(m，2H)，6.22(d，J＝7.8Hz，1H)，4.85-4.91(m，1H)，3.72(s，3H)，3.04-3.14(m，2H)，1.97(s，3H)。The main enantiomer of product is the S configuration.
Embodiment 16: the asymmetric hydrogenation (III) of α-acetamido-beta-phenyl methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1R; 2R; 3S; 4S) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (12mL) solution of α-acetamido-beta-phenyl methyl acrylate (7.4mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 4cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC HPLC shows ee 98.2% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=95:5; T (R)=19.4min; T (S)=26.7min).[α] D 20＝-125.2°(c＝0.5，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.24-7.31(m，3H)，7.09-7.12(m，2H)，6.22(d，J＝7.8Hz，1H)，4.85-4.91(m，1H)，3.72(s，3H)，3.04-3.14(m，2H)，1.97(s，3H)。The main enantiomer of product is the R configuration.
Embodiment 17: the asymmetric hydrogenation (IV) of α-acetamido-beta-phenyl methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1S; 2S; 3R; 4R) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (12mL) solution of α-acetamido-beta-phenyl methyl acrylate (7.4mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 4cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC HPLC shows ee 98.2% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=95:5; T (R)=19.4min; T (S)=26.7min).[α] D 20＝+125.0°(c＝0.5，CHCl3)； 1H?NMR(300MHz，CDCl 3)δ?7.24-7.31(m，3H)，7.09-7.12(m，2H)，6.22(d，J＝7.8Hz，1H)，4.85-4.91(m，1H)，3.72(s，3H)，3.04-3.14(m，2H)，1.97(s，3H)。The main enantiomer of product is the S configuration.
Embodiment 18: the asymmetric hydrogenation (I) of α-acetamido-β-(4-chloro-phenyl-) methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1R; 2R; 3S; 4S) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido-β-(4-chloro-phenyl-) methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 99.9% (the Chiralcel Japan OJ of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=90:10; T (R)=10.33min; T (S)=13.95min).[α] D 20＝-89.0°(c＝0.25，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.14(dd，J＝8.7，71.4Hz，4H)，5.95(d，J＝6.9Hz，1H)，4.84-4.90(m，1H)，3.73(s，3H)，3.04-3.17(m，2H)，2.05(s，3H)。The main enantiomer of product is the R configuration.
Embodiment 19: the asymmetric hydrogenation (II) of α-acetamido-β-(4-chloro-phenyl-) methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1S; 2S; 3R; 4R) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido-β-(4-chloro-phenyl-) methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 99.9% (the Chiralcel Japan OJ of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=90:10; T (R)=10.33min; T (S)=13.95min).[α] D 20＝+89.4°(c＝0.25，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.14(dd，J＝8.7，71.4Hz，4H)，5.95(d，J＝6.9Hz，1H)，4.84-4.90(m，1H)，3.73(s，3H)，3.04-3.17(m，2H)，2.05(s，3H)。The main enantiomer of product is the S configuration.
Embodiment 20: the asymmetric hydrogenation (I) of α-acetamido-β-(3-chloro-phenyl-) methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1R; 2R; 3S; 4S) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido-β-(3-chloro-phenyl-) methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 99.4% (the Chiralcel Japan OJ of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=90:10; T (R)=9.20min; T (S)=13.03min).[α] D 20＝-97.9°(c＝0.5，CHCl3)； 1H?NMR(300MHz，CDCl 3)δ?7.20-7.24(m，2H)，7.09(s，1H)，6.97-7.00(m，1H)，5.96(d，J＝7.5Hz，1H)，4.85-4.91(m，1H)，3.75(s，3H)，3.03-3.18(m，2H)，2.01(s，3H)。The main enantiomer of product is the R configuration.
Embodiment 21: the asymmetric hydrogenation (II) of α-acetamido-β-(3-chloro-phenyl-) methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1S; 2S; 3R; 4R) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido-β-(3-chloro-phenyl-) methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 99.6% (the Chiralcel Japan OJ of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=90:10; T (R)=9.20min; T (S)=13.03min).[α] D 20＝+98.1°(c＝0.5，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.20-7.24(m，2H)，7.09(s，1H)，6.97-7.00(m，1H)，5.96(d，J＝7.5Hz，1H)，4.85-4.91(m，1H)，3.75(s，3H)，3.03-3.18(m，2H)，2.01(s，3H)。The main enantiomer of product is the S configuration.
Embodiment 22: the asymmetric hydrogenation (I) of α-acetamido-β-(2-chloro-phenyl-) methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1R; 2R; 3S; 4S) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido-β-(2-chloro-phenyl-) methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 97.7% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=90:10; T (R)=9.50min; T (S)=12.60min).[α] D 20＝-47.2°(c＝0.25，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.35-7.37(m，1H)，7.21(d，J＝2.7Hz，3H)，6.28(d，J＝7.5Hz，1H)，4.91-4.93(m，1H)，3.73(s，3H)，3.17-3.34(m，2H)，1.97(s，3H)。The main enantiomer of product is the R configuration.
Embodiment 23: the asymmetric hydrogenation (II) of α-acetamido-β-(2-chloro-phenyl-) methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1S; 2S; 3R; 4R) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido-β-(2-chloro-phenyl-) methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 97.7% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=90:10; T (R)=9.50min; T (S)=12.60min).[α] D 20＝+47.2°(c＝0.25，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.35-7.37(m，1H)，7.21(d，J＝2.7Hz，3H)，6.28(d，J＝7.5Hz，1H)，4.91-4.93(m，1H)，3.73(s，3H)，3.17-3.34(m，2H)，1.97(s，3H)。The main enantiomer of product is the S configuration.
Embodiment 24: the asymmetric hydrogenation (I) of α-acetamido-β-(4-bromophenyl) methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1R; 2R; 3S; 4S) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido-β-(4-bromophenyl) methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 99.3% (the Chiralcel Japan OJ of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=90:10; T (R)=13.04min; T (S)=16.03min).[α] D 20＝-87.9°(c＝0.5，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.40-7.43(m，2H)，6.97(dd，J＝2.4，6.6Hz，2H)，5.99(d，J＝6.0Hz，1H)，4.84-4.91(m，1H)，3.74(s，3H)，3.01-3.16(m，2H)，2.01(s，3H)。The main enantiomer of product is the R configuration.
Embodiment 25: the asymmetric hydrogenation (II) of α-acetamido-β-(4-bromophenyl) methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1S; 2S; 3R; 4R) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido-β-(4-bromophenyl) methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 99.3% (the Chiralcel Japan OJ of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=90:10; T (R)=13.04min; T (S)=16.03min).[α] D 20＝+87.5°(c＝0.5，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.40-7.43(m，2H)，6.97(dd，J＝2.4，6.6Hz，2H)，5.99(d，J＝6.0Hz，1H)，4.84-4.91(m，1H)，3.74(s，3H)，3.01-3.16(m，2H)，2.01(s，3H)。The main enantiomer of product is the S configuration.
Embodiment 26: the asymmetric hydrogenation (I) of α-acetamido-β-(3-bromophenyl) methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1R; 2R; 3S; 4S) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido-β-(3-bromophenyl) methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 99.6% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=90:10; T (R)=9.55min; T (S)=11.03min).[α] D 20＝-74.0°(c＝0.25，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.38-7.42(m，1H)，7.26-7.28(m，1H)，7.18(t，J＝7.8Hz，1H)，7.04(d，J＝7.8Hz，1H)，5.99(d，J＝8.4Hz，1H)，4.85-4.90(m，1H)，3.76(s，3H)，3.05-3.14(m，2H)，2.02(s，3H)。The main enantiomer of product is the R configuration.
Embodiment 27: the asymmetric hydrogenation (II) of α-acetamido-β-(3-bromophenyl) methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1S; 2S; 3R; 4R) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido-β-(3-bromophenyl) methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 99.6% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=90:10; T (R)=9.55min; T (S)=11.03min).[α] D 20＝+74.3°(c＝0.25，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.38-7.42(m，1H)，7.26-7.28(m，1H)，7.18(t，J＝7.8Hz，1H)，7.04(d，J＝7.8Hz，1H)，5.99(d，J＝8.4Hz，1H)，4.85-4.90(m，1H)，3.76(s，3H)，3.05-3.14(m，2H)，2.02(s，3H)。The main enantiomer of product is the S configuration.
Embodiment 28: the asymmetric hydrogenation (I) of α-acetamido-β-(2-bromophenyl) methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1R; 2R; 3S; 4S) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido-β-(2-bromophenyl) methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 98.7% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=90:10; T (R)=10.71min; T (S)=14.12min).[α] D 20＝-39.6°(c＝1.0，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.55(dd，J＝1.5，8.1Hz，1H)，7.08-7.26(m，3H)，6.00(d，J＝9.3Hz，1H)，4.88-4.95(m，1H)，3.72(s，3H)，3.15-3.36(m，2H)，2.04(s，3H)。The main enantiomer of product is the R configuration.
Embodiment 29: the asymmetric hydrogenation (II) of α-acetamido-β-(2-bromophenyl) methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1S; 2S; 3R; 4R) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido-β-(2-bromophenyl) methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 98.7% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=90:10; T (R)=10.71min; T (S)=14.12min).[α] D 20＝+39.3°(c＝1.0，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.55(dd，J＝1.5，8.1Hz，1H)，7.08-7.26(m，3H)，6.00(d，J＝9.3Hz，1H)，4.88-4.95(m，1H)，3.72(s，3H)，3.15-3.36(m，2H)，2.04(s，3H)。The main enantiomer of product is the S configuration.
Embodiment 30: the asymmetric hydrogenation (I) of α-acetamido-β-(3-fluorophenyl) methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1R; 2R; 3S; 4S) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido-β-(3-fluorophenyl) methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 99.2% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=90:10; T (R)=9.77min; T (S)=11.48min).[α] D 20＝-117.5°(c＝0.5，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.23-7.30(m，1H)，6.78-6.99(m，3H)，5.94(d，J＝6.6Hz，1H)，4.86-4.92(m，1H)，3.75(s，3H)，3.06-3.20(m，2H)，2.05(s，3H)。The main enantiomer of product is the R configuration.
Embodiment 31: the asymmetric hydrogenation (II) of α-acetamido-β-(3-fluorophenyl) methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1S; 2S; 3R; 4R) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido-β-(3-fluorophenyl) methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 99.2% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=90:10; T (R)=9.77min; T (S)=11.48min).[α] D 20＝+117.8°(c＝0.5，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.23-7.30(m，1H)，6.78-6.99(m，3H)，5.94(d，J＝6.6Hz，1H)，4.86-4.92(m，1H)，3.75(s，3H)，3.06-3.20(m，2H)，2.05(s，3H)。The main enantiomer of product is the S configuration.
Embodiment 32: the asymmetric hydrogenation (I) of α-acetamido-β-(4-p-methoxy-phenyl) methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1R; 2R; 3S; 4S) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido-β-(4-p-methoxy-phenyl) methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 95.0% (the Chiralcel Japan OJ of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=90:10; T (R)=18.61min; T (S)=35.65min).[α] D 20＝-78.0°(c＝0.5，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.02(d，J＝8.4Hz，2H)，6.80-6.85(m，2H)，6.08(d，J＝7.8Hz，1H)，4.81-4.88(m，1H)，3.79(s，3H)，3.73(s，3H)，3.00-3.13(m，2H)，1.99(s，3H)。The main enantiomer of product is the R configuration.
Embodiment 33: the asymmetric hydrogenation (II) of α-acetamido-β-(4-p-methoxy-phenyl) methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1S; 2S; 3R; 4R) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido-β-(4-p-methoxy-phenyl) methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee95.0% (the Chiralcel Japan OJ of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=90:10; T (R)=18.61min; T (S)=35.65min).[α] D 20＝+77.8°(c＝0.5，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.02(d，J＝8.4Hz，2H)，6.80-6.85(m，2H)，6.08(d，J＝7.8Hz，1H)，4.81-4.88(m，1H)，3.79(s，3H)，3.73(s，3H)，3.00-3.13(m，2H)，1.99(s，3H)。The main enantiomer of product is the S configuration.
Embodiment 34: the asymmetric hydrogenation (I) of α-acetamido-β-(3-p-methoxy-phenyl) methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1R; 2R; 3S; 4S) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido-β-(3-p-methoxy-phenyl) methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 90.0% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=90:10; T (R)=12.32min; T (S)=13.39min).[α] D 20＝-89.3°(c＝2.0，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.20(t，J＝8.1Hz，1H)，6.78-6.81(m，1H)，6.64-6.69(m，2H)，5.90(d，J＝7.5Hz，1H)，4.85-4.91(m，1H)，3.77(s，3H)，3.73(s，3H)，3.07-3.11(m，2H)，1.99(s，3H)。The main enantiomer of product is the R configuration.
Embodiment 35: the asymmetric hydrogenation (II) of α-acetamido-β-(3-p-methoxy-phenyl) methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1S; 2S; 3R; 4R) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido-β-(3-p-methoxy-phenyl) methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 90.0% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=90:10; T (R)=12.32min; T (S)=13.39min).[α] D 20＝+89.6°(c＝2.0，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.20(t，J＝8.1Hz，1H)，6.78-6.81(m，1H)，6.64-6.69(m，2H)，5.90(d，J＝7.5Hz，1H)，4.85-4.91(m，1H)，3.77(s，3H)，3.73(s，3H)，3.07-3.11(m，2H)，1.99(s，3H)。The main enantiomer of product is the S configuration.
Embodiment 36: the asymmetric hydrogenation (I) of α-acetamido-β-(3, the 4-Dimethoxyphenyl) methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1R; 2R; 3S; 4S) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then, stirred 10 minutes, add α-acetamido-β-(3 again with syringe; the 4-Dimethoxyphenyl) anhydrous methylene dichloride (1.7mL) solution of methyl acrylate (0.74mmol); continue to stir 10 minutes, the hydrogenation bottle be transferred in the autoclave, with hydrogen with the careful displacement of the nitrogen in the autoclave three times after; add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 98.8% (the Chiralcel Japan OJ of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=90:10; T (R)=26.96min; T (S)=40.03min).[α] D 20＝-79.5°(c＝0.5，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?6.79(d，J＝7.8Hz，1H)，6.63-6.66(m，2H)，6.09(d，J＝7.5Hz，1H)，4.84-4.86(m，1H)，3.86(s，3H)，3.85(s，3H)，3.73(s，3H)，3.05-3.08(m，2H)，2.00(s，3H)。The main enantiomer of product is the R configuration.
Embodiment 37: the asymmetric hydrogenation (II) of α-acetamido-β-(3, the 4-Dimethoxyphenyl) methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1S; 2S; 3R; 4R) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then, stirred 10 minutes, add α-acetamido-β-(3 again with syringe; the 4-Dimethoxyphenyl) anhydrous methylene dichloride (1.7mL) solution of methyl acrylate (0.74mmol); continue to stir 10 minutes, the hydrogenation bottle be transferred in the autoclave, with hydrogen with the careful displacement of the nitrogen in the autoclave three times after; add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee98.8% (the Chiralcel Japan OJ of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=90:10; T (R)=26.96min; T (S)=40.03min).[α] D 20＝+79.1°(c＝0.5，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?6.79(d，J＝7.8Hz，1H)，6.63-6.66(m，2H)，6.09(d，J＝7.5Hz，1H)，4.84-4.86(m，1H)，3.86(s，3H)，3.85(s，3H)，3.73(s，3H)，3.05-3.08(m，2H)，2.00(s，3H)。The main enantiomer of product is the S configuration.
Embodiment 38: the asymmetric hydrogenation (I) of α-acetamido-β-(3-methoxyl group-4-acetoxyl group phenyl) methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1R; 2R; 3S; 4S) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido-β-(3-methoxyl group-4-acetoxyl group phenyl) methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 98.8% (the Chiralcel Japan OJ of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=90:10; T (R)=20.23min; T (S)=22.99min).[α] D 20＝-86.0°(c＝0.5，CHCl3)； 1H?NMR(300MHz，CDCl 3)δ?6.95(d，J＝8.1Hz，1H)，6.71(d，J＝1.8Hz，1H)，6.66(dd，J＝1.8，8.1Hz，1H)，6.00(d，J＝8.1Hz，1H)，4.85-4.92(m，1H)，3.80(s，3H)，3.73(s，3H)，3.12(d，J＝5.7Hz，2H)，2.30(s，3H)，2.00(s，3H)。The main enantiomer of product is the R configuration.
Embodiment 39: the asymmetric hydrogenation (II) of α-acetamido-β-(3-methoxyl group-4-acetoxyl group phenyl) methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1S; 2S; 3R; 4R) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido-β-(3-methoxyl group-4-acetoxyl group phenyl) methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 98.8% (the Chiralcel Japan OJ of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=90:10; T (R)=20.23min; T (S)=22.99min).[α] D 20＝+86.2°(c＝0.5，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?6.95(d，J＝8.1Hz，1H)，6.71(d，J＝1.8Hz，1H)，6.66(dd，J＝1.8，8.1Hz，1H)，6.00(d，J＝8.1Hz，1H)，4.85-4.92(m，1H)，3.80(s，3H)，3.73(s，3H)，3.12(d，J＝5.7Hz，2H)，2.30(s，3H)，2.00(s，3H)。The main enantiomer of product is the S configuration.
Embodiment 40: the asymmetric hydrogenation (I) of α-acetamido-Beta-methyl methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1R; 2R; 3S; 4S) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido-Beta-methyl methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 99.3% (the Chiralcel Japan OD of DaCheng Co., Ltd chiral column, λ=220nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=95:5; T (R)=12.23min; T (S)=16.22min).[α] D 20＝-4.9°(c＝1.75，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?6.03(s，1H)，4.57-4.64(m，1H)，3.77(s，3H)，2.05(s，3H)，1.66-1.95(m，2H)，0.92(t，J＝7.8Hz，3H)。The main enantiomer of product is the R configuration.
Embodiment 41: the asymmetric hydrogenation (II) of α-acetamido-Beta-methyl methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1S; 2S; 3R; 4R) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido-Beta-methyl methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 99.3% (the Chiralcel Japan OD of DaCheng Co., Ltd chiral column, λ=220nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=95:5; T (R)=12.23min; T (S)=16.22min).[α]D 20＝+4.8°(c＝1.75，CHCl3)； 1H?NMR(300MHz，CDCl 3)δ?6.03(s，1H)，4.57-4.64(m，1H)，3.77(s，3H)，2.05(s，3H)，1.66-1.95(m，2H)，0.92(t，J＝7.8Hz，3H)。The main enantiomer of product is the S configuration.
Embodiment 42: the asymmetric hydrogenation (I) of α-acetamido methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1R; 2R; 3S; 4S) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 98.5% (the Chiralcel Japan OD of DaCheng Co., Ltd chiral column, λ=220nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=98.5:1.5; T (R)=45.09min; T (S)=51.21min).[α] D 20＝-9.5°(c＝2.0，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ6.46(s，1H)，4.57-4.62(m，1H)，3.76(s，3H)，2.03(s，3H)，1.40(d，J＝7.2Hz，3H)。The main enantiomer of product is the R configuration.
Embodiment 43: the asymmetric hydrogenation (II) of α-acetamido methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1S; 2S; 3R; 4R) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of α-acetamido methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 2 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 98.5% (the Chiralcel Japan OD of DaCheng Co., Ltd chiral column, λ=220nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=98.5:1.5; T (R)=45.09min; T (S)=51.21min).[α] D 20＝+9.7°(c＝2.0，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ6.46(s，1H)，4.57-4.62(m，1H)，3.76(s，3H)，2.03(s，3H)，1.40(d，J＝7.2Hz，3H)。The main enantiomer of product is the S configuration.
The asymmetric hydrogenation (I) of embodiment 44:N-ethanoyl-1-phenyl vinyl-amine
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1R; 2R; 3S; 4S) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of N-ethanoyl-1-phenyl vinyl-amine (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 10 atmospheric hydrogen, stirred 20 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 98.0% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=95:5; T (R)=12.03min; T (S)=14.72min).[α] D 20＝+154.0°(c＝0.25，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ7.24-7.38(m，5H)，6.01(s，1H)，5.10-5.15(m，1H)，1.98(s，3H)，1.49(d，J＝6.9Hz，3H)。The main enantiomer of product is the R configuration.
The asymmetric hydrogenation (II) of embodiment 45:N-ethanoyl-1-phenyl vinyl-amine
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1S; 2S; 3R; 4R) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of N-ethanoyl-1-phenyl vinyl-amine (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 10 atmospheric hydrogen, stirred 20 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 98.0% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=95:5; T (R)=12.03min; T (S)=14.72min).[α] D 20＝-154.4°(c＝0.25，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.24-7.38(m，5H)，6.01(s，1H)，5.10-5.15(m，1H)，1.98(s，3H)，1.49(d，J＝6.9Hz，3H)。The main enantiomer of product is the S configuration.
The asymmetric hydrogenation (I) of embodiment 46:N-ethanoyl-1-(4-chloro-phenyl-) vinyl-amine
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1R; 2R; 3S; 4S) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of N-ethanoyl-1-(4-chloro-phenyl-) vinyl-amine (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 10 atmospheric hydrogen, stirred 20 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 96.7% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=95:5; T (R)=16.21min; T (S)=21.08min).[α] D 20＝+133.6°(c＝1.0，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.22-7.32(m，4H)，5.72(br?s，1H)，5.04-5.13(m，1H)，1.98(s，3H)，1.45(d，J＝6.6Hz，3H)。The main enantiomer of product is the R configuration.
The asymmetric hydrogenation (II) of embodiment 47:N-ethanoyl-1-(4-chloro-phenyl-) vinyl-amine
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1S; 2S; 3R; 4R) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of N-ethanoyl-1-(4-chloro-phenyl-) vinyl-amine (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 10 atmospheric hydrogen, stirred 20 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 96.7% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=95:5; T (R)=16.21min; T (S)=21.08min).[α] D 20＝-133.8°(c＝1.0，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.22-7.32(m，4H)，5.72(br?s，1H)，5.04-5.13(m，1H)，1.98(s，3H)，1.45(d，J＝6.6Hz，3H)。The main enantiomer of product is the S configuration.
The asymmetric hydrogenation (I) of embodiment 48:N-ethanoyl-1-(4-bromophenyl) vinyl-amine
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1R; 2R; 3S; 4S) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of N-ethanoyl-1-(4-bromophenyl) vinyl-amine (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 10 atmospheric hydrogen, stirred 20 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 93.6% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=95:5; T (R)=16.87min; T (S)=22.82min).[α] D 20＝+113.9°(c＝0.5，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.45(d，J＝8.1Hz，2H)，7.18(d，J＝8.1Hz，2H)，5.87(br?s，1H)，5.03-5.08(m，1H)，1.98(s，3H)，1.45(d，J＝6.9Hz，3H)。The main enantiomer of product is the R configuration.
The asymmetric hydrogenation (II) of embodiment 49:N-ethanoyl-1-(4-bromophenyl) vinyl-amine
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1S; 2S; 3R; 4R) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of N-ethanoyl-1-(4-bromophenyl) vinyl-amine (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 10 atmospheric hydrogen, stirred 20 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 93.6% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=95:5; T (R)=16.87min; T (S)=22.82min).[α] D 20＝-113.8°(c＝0.5，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.45(d，J＝8.1Hz，2H)，7.18(d，J＝8.1Hz，2H)，5.87(br?s，1H)，5.03-5.08(m，1H)，1.98(s，3H)，1.45(d，J＝6.9Hz，3H)。The main enantiomer of product is the S configuration.
The asymmetric hydrogenation (I) of embodiment 50:N-ethanoyl-1-(3-bromophenyl) vinyl-amine
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1R; 2R; 3S; 4S) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of N-ethanoyl-1-(3-bromophenyl) vinyl-amine (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 10 atmospheric hydrogen, stirred 20 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 90.9% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=95:5; T (R)=12.89min; T (S)=16.44min).[α] D 20＝+91.6°(c＝1.0，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.34-7.44(m，2H)，7.17-7.26(m，2H)，5.96(br?s，1H)，5.02-5.11(m，1H)，1.99(s，3H)，1.45(d，J＝7.5Hz，3H)。The main enantiomer of product is the R configuration.
The asymmetric hydrogenation (II) of embodiment 51:N-ethanoyl-1-(3-bromophenyl) vinyl-amine
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1S; 2S; 3R; 4R) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of N-ethanoyl-1-(3-bromophenyl) vinyl-amine (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 10 atmospheric hydrogen, stirred 20 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 90.9% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=95:5; T (R)=12.89min; T (S)=16.44min).[α] D 20＝-92.0°(c＝1.0，CHCl 3)； 1HNMR(300MHz，CDCl 3)δ?7.34-7.44(m，2H)，7.17-7.26(m，2H)，5.96(br?s，1H)，5.02-5.11(m，1H)，1.99(s，3H)，1.45(d，J＝7.5Hz，3H)。The main enantiomer of product is the S configuration.
The asymmetric hydrogenation (I) of embodiment 52:N-ethanoyl-1-(4-fluorophenyl) vinyl-amine
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1R; 2R; 3S; 4S) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of N-ethanoyl-1-(4-fluorophenyl) vinyl-amine (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 10 atmospheric hydrogen, stirred 20 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 91.6% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=95:5; T (R)=14.56min; T (S)=18.20min).[α] D 20＝+109.4°(c＝0.5，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.25-7.31(m，2H)，6.98-7.06(m，2H)，5.74(br?s，1H)，5.05-5.15(m，1H)，1.98(s，3H)，1.47(d，J＝6.6Hz，3H)。The main enantiomer of product is the R configuration.
The asymmetric hydrogenation (II) of embodiment 53:N-ethanoyl-1-(4-fluorophenyl) vinyl-amine
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1S; 2S; 3R; 4R) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of N-ethanoyl-1-(4-fluorophenyl) vinyl-amine (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 10 atmospheric hydrogen, stirred 20 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 91.6% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=95:5; T (R)=14.56min; T (S)=18.20min).[α] D 20＝-109.0°(c＝0.5，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.25-7.31(m，2H)，6.98-7.06(m，2H)，5.74(br?s，1H)，5.05-5.15(m，1H)，1.98(s，3H)，1.47(d，J＝6.6Hz，3H)。The main enantiomer of product is the S configuration.
The asymmetric hydrogenation (I) of embodiment 54:N-ethanoyl-1-(4-aminomethyl phenyl) vinyl-amine
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1R; 2R; 3S; 4S) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of N-ethanoyl-1-(4-aminomethyl phenyl) vinyl-amine (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 10 atmospheric hydrogen, stirred 20 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 97.4% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=95:5; T (R)=13.98min; T (S)=17.98min).[α] D 20＝+139.8°(c＝0.5，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.22(d，J＝7.8Hz，2H)，7.16(d，J＝7.8Hz，2H)，5.67(br?s，1H)，5.05-5.14(m，1H)，2.33(s，3H)，1.97(s，3H)，1.47(d，J＝7.2Hz，3H)。The main enantiomer of product is the R configuration.
The asymmetric hydrogenation (II) of embodiment 55:N-ethanoyl-1-(4-aminomethyl phenyl) vinyl-amine
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1S; 2S; 3R; 4R) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of N-ethanoyl-1-(4-aminomethyl phenyl) vinyl-amine (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 10 atmospheric hydrogen, stirred 20 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee97.4% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=95:5; T (R)=13.98min; T (S)=17.98min).[α] D 20＝-140.0°(c＝0.5，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.22(d，J＝7.8Hz，2H)，7.16(d，J＝7.8Hz，2H)，5.67(br?s，1H)，5.05-5.14(m，1H)，2.33(s，3H)，1.97(s，3H)，1.47(d，J＝7.2Hz，3H)。The main enantiomer of product is the S configuration.
The asymmetric hydrogenation (I) of embodiment 56:N-ethanoyl-1-(4-p-methoxy-phenyl) vinyl-amine
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1R; 2R; 3S; 4S) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of N-ethanoyl-1-(4-p-methoxy-phenyl) vinyl-amine (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 10 atmospheric hydrogen, stirred 20 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 94.1% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=95:5; T (R)=22.12min; T (S)=28.23min).[α] D 20＝+140.6°(c＝0.5，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.25(d，J＝8.1Hz，2H)，6.88(d，J＝8.1Hz，2H)，5.66(br?s，1H)，5.05-5.13(m，1H)，3.80(s，3H)，1.97(s，3H)，1.47(d，J＝6.9Hz，3H)。The main enantiomer of product is the R configuration.
The asymmetric hydrogenation (II) of embodiment 57:N-ethanoyl-1-(4-p-methoxy-phenyl) vinyl-amine
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1S; 2S; 3R; 4R) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of N-ethanoyl-1-(4-p-methoxy-phenyl) vinyl-amine (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 10 atmospheric hydrogen, stirred 20 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 94.1% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=95:5; T (R)=22.12min; T (S)=28.23min).[α] D 20＝-140.3°(c＝0.5，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.25(d，J＝8.1Hz，2H)，6.88(d，J＝8.1Hz，2H)，5.66(br?s，1H)，5.05-5.13(m，1H)，3.80(s，3H)，1.97(s，3H)，1.47(d，J＝6.9Hz，3H)。The main enantiomer of product is the S configuration.
The asymmetric hydrogenation (I) of embodiment 58:N-ethanoyl-1-(2-naphthyl) vinyl-amine
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1R; 2R; 3S; 4S) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of N-ethanoyl-1-(2-naphthyl) vinyl-amine (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 10 atmospheric hydrogen, stirred 20 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 96.8% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=95:5; T (R)=20.40min; T (S)=29.48min).[α] D 20＝+178.0°(c＝0.5，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.79-7.86(m，3H)，7.74(d，J＝0.6Hz，1H)，7.41-7.51(m，3H)，5.90(br?s，1H)，5.24-5.33(m，1H)，2.04(s，3H)，1.56(d，J＝6.6Hz，3H)。The main enantiomer of product is the R configuration.
The asymmetric hydrogenation (II) of embodiment 59:N-ethanoyl-1-(2-naphthyl) vinyl-amine
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1S; 2S; 3R; 4R) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of N-ethanoyl-1-(2-naphthyl) vinyl-amine (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 10 atmospheric hydrogen, stirred 20 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 96.8% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=95:5; T (R)=20.40min; T (S)=29.48min).[α] D 20＝-178.3°(c＝0.5，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.79-7.86(m，3H)，7.74(d，J＝0.6Hz，1H)，7.41-7.51(m，3H)，5.90(br?s，1H)，5.24-5.33(m，1H)，2.04(s，3H)，1.56(d，J＝6.6Hz，3H)。The main enantiomer of product is the S configuration.
Embodiment 60: the asymmetric hydrogenation of methylene-succinic acid methyl esters (I)
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1R; 2R; 3S; 4S) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of methylene-succinic acid methyl esters (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 24 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:5) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 64% (the Chiralcel Japan OD of DaCheng Co., Ltd chiral column, λ=220nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=90:10; T (S)=5.28min; T (R)=7.44min).[α] D 20＝+74.1°(c＝0.5，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?3.70(d，J＝2.1Hz，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 product is the R configuration.
Embodiment 61: the asymmetric hydrogenation of methylene-succinic acid methyl esters (II)
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1S; 2S; 3R; 4R) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 1mL then with syringe; stirred 10 minutes, and added anhydrous methylene dichloride (1.7mL) solution of methylene-succinic acid methyl esters (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 20 atmospheric hydrogen, stirred 24 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:5) sweep away product, nucleus magnetic resonance shows transformation efficiency 100% with developping agent, HPLC shows ee 64% (the Chiralcel Japan OD of DaCheng Co., Ltd chiral column, λ=220nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=90:10; T (S)=5.28min; T (R)=7.44min).[α] D 20＝-75.0°(c＝0.5，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?3.70(d，J＝2.1Hz，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 product is the S configuration.
Embodiment 62: the asymmetric hydrogenation (I) of β-acetamido-beta-phenyl methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1R; 2R; 3S; 4S) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 0.6mL then with syringe; stirred 10 minutes, and added anhydrous tetrahydrofuran (THF) (1.8mL) solution of α-acetamido-beta-phenyl methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 60 atmospheric hydrogen, stirred 24 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 71% with developping agent, HPLC shows ee 75% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=97:3; T (S)=51.98min; T (R)=56.81min).[α] D 20＝-13.6°(c＝1.0，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.27-7.37(m，5H)，6.67(d，J＝7.2Hz，1H)，5.40-5.47(m，1H)，3.62(s，3H)，2.80-2.98(m，2H)，2.02(s，3H)。The main enantiomer of product is the R configuration.
Embodiment 63: the asymmetric hydrogenation (II) of β-acetamido-beta-phenyl methyl acrylate
Under the Ar protection, with Rh (COD) 2BF 4(3mg) with (1S; 2S; 3R; 4R) the compound 6a (9.4mg) of configuration adds in the hydrogenation bottle; cover soft rubber ball; gas argon replaces three times in the bottle; under argon shield, add anhydrous methylene dichloride 0.6mL then with syringe; stirred 10 minutes, and added anhydrous tetrahydrofuran (THF) (1.8mL) solution of α-acetamido-beta-phenyl methyl acrylate (0.74mmol) again, continue to stir 10 minutes; the hydrogenation bottle is transferred in the autoclave; with hydrogen with the careful displacement of the nitrogen in the autoclave three times after, add 60 atmospheric hydrogen, stirred 24 hours under the room temperature.Hydrogen in the autoclave is bled off, reaction solution is added on the long silicagel column of 3cm, and (ethyl acetate: sherwood oil 1:1) sweep away product, nucleus magnetic resonance shows transformation efficiency 71% with developping agent, HPLC shows ee 75% (the Chiralpak Japan AD of DaCheng Co., Ltd chiral column, λ=230nm; Flow velocity: 1.0mL/min, normal hexane: Virahol=97:3; T (S)=51.98min; T (R)=56.81min).[α] D 20＝+13.2°(c＝1.0，CHCl 3)； 1H?NMR(300MHz，CDCl 3)δ?7.27-7.37(m，5H)，6.67(d，J＝7.2Hz，1H)，5.40-5.47(m，1H)，3.62(s，3H)，2.80-2.98(m，2H)，2.02(s，3H)。The main enantiomer of product is the S configuration.

Claims (6)

1. compound, its structural formula is as follows:
Figure C200410066892C00021
Wherein: the natural number of n=4-8; R 1And R 1 'Be respectively hydrogen or C 1-12Alkyl;
R 2Be hydrogen or C 1-12Alkyl;
R 3And R 3 'Be respectively hydrogen, C 1-12Alkyl,
Figure C200410066892C00022
O-R wOr halogen, wherein R y, R Y ', R Y ", R z, R Z 'And R wBe respectively hydrogen, C 1-8Alkyl, C 5～C 7Cycloalkyl, phenyl, benzyl, (1-phenyl) ethyl, 1-naphthyl or 2-naphthyl;
R 4Be C 1-12Alkyl,
Figure C200410066892C00023
Or O-R w, R wherein z, R Z 'And R wAs defined above.
2. compound as claimed in claim 1 is characterized in that described C 1-12Alkyl be methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, the tertiary butyl, cyclopentyl, cyclohexyl, suberyl, 1-naphthyl or 2-naphthyl.
3. compound as claimed in claim 1, it is characterized in that described compound be (1R, 2R, 3S, 4S) or (1S, 2S, 3R, the 4R) compound of configuration, its structural formula is as follows respectively:
Figure C200410066892C00024
Wherein n, R 1, R 1 ', R 2, R 3, R 3 'And R 4According to claim 1.
4. the synthetic method of claim 1 or 3 compound, it is characterized in that with trans 1,2-cyclohexanediamine 1 ' be raw material, obtain (1R by splitting with tartrate, 2R) or (1S, the cyclohexanediamine tartrate 2 of configuration 2S) ', (1R, 2R) or (1S, the cyclohexanediamine tartrate 2 of configuration 2S) ' with
Figure C200410066892C00031
Condensation make (1R, 2R) or (1S, 3 of configuration 2S) ', 3 ' close ring obtain (1R, 2R, 3S, 4S) or (1S, 2S, 3R, 4R) compound 4 of configuration ', compound 4 ' with Or
Figure C200410066892C00033
The reaction obtain (1R, 2R, 3S, 4S) or (1S, 2S, 3R, 4R) compound 5 of configuration ', compound 5 ' obtain target product with hexamethyl phosphine triamine, promptly (1R, 2R, 3S, 4S) or (1S, 2S, 3R, 4R) compound 6 of configuration ';
Described compound 1 '～6 ' structural formula as follows:
Figure C200410066892C00034
Wherein n, R 1, R 1 ', R 2, R 3, R 3 'And R 4According to claim 1.
5. the purposes of claim 1 or 3 compound is characterized in that being used to prepare the catalyzer of asymmetric catalytic hydrogenation.
6. purposes as claimed in claim 5 is characterized in that being used to preparing the catalyzer of the asymmetric catalytic hydrogenation of α-dehydroamino acid and derivative, β-dehydroamino acid and derivative thereof, enamine and methylene-succinic acid and derivative thereof.
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5543536A (en) * 1994-04-26 1996-08-06 E. I. Du Pont De Nemours And Company Monodentate phosphite and nickel catalyst composition for monoolefin hydrocyanation
CN1440416A (en) * 2000-07-07 2003-09-03 Dsm有限公司 Catalyst for asymmetric (transfer) hydrogenation

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5543536A (en) * 1994-04-26 1996-08-06 E. I. Du Pont De Nemours And Company Monodentate phosphite and nickel catalyst composition for monoolefin hydrocyanation
CN1440416A (en) * 2000-07-07 2003-09-03 Dsm有限公司 Catalyst for asymmetric (transfer) hydrogenation

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