METAL COMPLEX, INTERMEDIATE, AND PREPARATION METHOD AND APPLICATION THEREOF

Abstract

Provided is a metal complex as represented by formula I. The metal complex may be used as a catalyst for asymmetric catalytic hydrogenation, is capable of efficiently catalyzing and synthesizing a series of chiral p-aryl amides having high optical purity, and is especially capable of asymmetrically catalyzing and hydrogenating a tetra-substituted enamide compound, chiral amides having high optical purity are synthesized, and the carrying amount of ligand may reach 100,000.

##STR00001##

Claims

1. A metal complex according to Formula I: ##STR00090## wherein, R.sup.1 and R.sup.2 are each independently hydrogen, C.sub.1-C.sub.10 alkyl, C.sub.1-C.sub.4 alkoxy, C.sub.3-C.sub.3o cycloalkyl, halogen or C.sub.6-C.sub.30 aryl; M.sup.n+ is a transition metal ion; n is 1, 2 or 3, which corresponds to the ion valence of the transition metal M; the carbons atoms marked with * are all S configuration chiral carbons or all R configuration chiral carbons; the P marked with * are all S configuration chiral P or all R configuration chiral P.

2. The metal complex according to Formula I of claim 1, wherein when R.sup.1 or R.sup.2 are each independently C.sub.1-C.sub.10 alkyl, the C.sub.1-C.sub.10 alkyl is C.sub.1-6 alkyl; and/or, when R.sup.1 or R.sup.2 are each independently C.sub.1-C.sub.4 alkoxy, the C.sub.1-C.sub.4 alkoxy is methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, sec-butoxy, iso-butoxy or tert-butoxy; and/or, when R.sup.1 or R.sup.2 are each independently C.sub.3-C.sub.30 cycloalkyl, the C.sub.3-C.sub.30 cycloalkyl is C.sub.3-C.sub.8 cycloalkyl; and/or, when R.sup.1 or R.sup.2 are each independently C.sub.6-C.sub.30 aryl, the C.sub.6-C.sub.30 aryl is C.sub.6-C.sub.14 aryl; and/or, when R.sup.1 or R.sup.2 are each independently halogen, the halogen is fluorine, chlorine, bromine or iodine; and/or, the transition metal ion M.sup.n+ is Rh.sup.+, Ru.sup.2+, Ni.sup.2+, Ir.sup.2+, Pd.sup.2+, Cu.sup.2+, Pt.sup.2+, Co.sup.2+ or Au.sup.3+; and/or, the anion R.sup.1 is BF.sub.4.sup.−, SbF.sub.6.sup.−, TfO.sup.−, B(C.sub.6H.sub.5).sub.4.sup.−, B[3,5-(CF.sub.3).sub.2C.sub.6H.sub.3].sub.4.sup.− or PF.sub.6.sup.−.

3. The metal complex according to Formula I of claim 2, wherein when R.sup.1 or R.sup.2 are each independently C.sub.1-C.sub.6 alkyl, the C.sub.1-6 alkyl is methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tent-butyl, n-pentyl, iso-pentyl, neo-pentyl, or hexyl; and/or, when R.sup.1 or R.sup.2 are each independently C.sub.3-C.sub.8 cycloalkyl, the C.sub.3-C.sub.8 cycloalkyl is cyclopropanyl, cyclobutanyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; and/or, when R.sup.1 or R.sup.2 are each independently C.sub.6-C.sub.14 aryl, the C.sub.6-C.sub.14 aryl is phenyl or naphthyl; and/or, the transition metal ion M.sup.n+ is Ru.sup.2+ or Rh.sup.+; and/or, the anion R.sup.− is BF.sub.4.sup.− or PF.sub.6.sup.−; and/or, R.sup.1 is the same as R.sup.2; and/or, the metal complex according to Formula I is ##STR00091##

4. The metal complex according to Formula I of claim 1, wherein the metal complex according to Formula I is any one of the following compounds: ##STR00092##

5. A method for preparing the metal complex according to Formula I of claim 1, comprising the following steps: in an inert gas atmosphere, in the first organic solvent, the transition metal precursor according to Formula III and the ligand compound according to Formula II are subjected to the complexation reaction shown below to afford the metal complex according to Formula I; ##STR00093## wherein, the definitions of R.sup.1, R.sup.2, n and * are as described in claim 1.

6. A metal complex according to Formula I of claim 1 in use of asymmetric catalytic hydrogenation, comprising the following steps: in the organic solvent, in a hydrogen atmosphere and the presence of the metal complex according to Formula I, the compound A containing the structure of ##STR00094## is subjected to asymmetric catalytic hydrogenation reduction reaction to obtain the corresponding compound B; wherein, when the metal complex according to Formula I is ##STR00095## the predominant configuration of compound B contains the structure of ##STR00096## when the metal complex according to Formula I is ##STR00097## the predominant configuration of compound B contains the structure of ##STR00098## wherein, the definitions of R.sup.1, R.sup.2 and n are as described in claim 1.

7. The application of claim 6, wherein the compound A containing the structure of ##STR00099## is of Formula A-1: ##STR00100## wherein, the dotted line represents no or ring formation; R.sup.a, R.sup.b and R.sup.c are each independently H, —COOH, —OH, —CN, optionally substituted alkyl-oxy, optionally substituted alkyl-oxy-carbonyl, optionally substituted alkyl-carbonyl-oxy, optionally substituted alkyl or cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl or optionally substituted heteroaryl; or, R.sup.a, R.sup.b, together with the carbon atom to which they are connected, form optionally substituted cycloalkene or optionally substituted heterocycloalkene; R.sup.d is independently optionally substituted alkyl or cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl or optionally substituted heteroaryl; the “optionally substituted” is unsubstituted or substituted by the following groups: halogen, haloalkyl, —OH, —CN, alkyl-oxy, alkyl-S-, carboxyl, ester group, carbonyl, amido, optionally substituted aminosulfonyl or optionally substituted phenyl; the number of “substitution” is not limited; when being optionally substituted cycloalkenyl or optionally substituted heterocycloalkenyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl or optionally substituted heteroaryl, the “substituted” refers to forming fused ring with the cycloalkene and heterocycloalkene, cycloalkyl, heterocycloalkyl, aryl or heteroaryl.

8. The application of claim 7, wherein, when R.sup.a, R.sup.b or R.sup.c are optionally substituted alkyl, the optionally substituted alkyl is C.sub.1-C.sub.10 alkyl; and/or, when R.sup.a, R.sup.b or R.sup.c are optionally substituted alkyl-oxy-carbonyl, the optionally substituted alkyl-oxy-carbonyl is C.sub.1-C.sub.6 alkyl-oxy-carbonyl; and/or, when R.sup.a, R.sup.b or R.sup.c are optionally substituted aryl, the optionally substituted aryl is phenyl or halogen-substituted phenyl; and/or, when “R.sup.a, R.sup.b, together with the carbon atom to which they are connected, form optionally substituted cycloalkene”, the “optionally substituted cycloalkene” is benzocyclohexene or cyclohexene; and/or, when Rd is optionally substituted alkyl, the optionally substituted alkyl is C.sub.1-C.sub.6 alkyl.

9. The application of claim 8, wherein the compound A and the corresponding compound B-1 are selected from the following compounds: ##STR00101## the compound A and the corresponding compound B-2 are selected from the following: ##STR00102##

10. A compound II, which has any of the following structures: ##STR00103##

Description

DESCRIPTION OF THE DRAWINGS

[0226] FIG. 1 is the single crystal X-ray diffraction of compound h-1;

[0227] FIG. 2 is the single crystal X-ray diffraction of compound h-3.

EMBODIMENTS FOR CARRYING OUT THE INVENTION

[0228] The present invention will be further explained by examples below, but the present invention is not limited to the scope of the described examples. In the following examples, the experimental methods without specific conditions are selected according to conventional methods and conditions, or according to the manual of product.

EXAMPLE 1

[0229] The example uses the preparation of (2R, 2′R, 3S, 3′S)-3,3′-di-t-butyl-2,2′-bis([1,3]oxaphospholanyl) (1) and its metal complex {(norbornadiene) [(2R,2′R,3 S,3′S)-3,3′-di-tert-butyl-2,2′-bis([1,3]oxaphospholanyl)]} rhodium tetrafluoroborate, i.e, Rh(nbd)(1)BF.sub.4 (the reaction route is shown below) as an example to illustrate in detail the preparation method of the chiral bisphosphine ligand and its metal rhodium complex of the present invention, the reaction route is as follows:

##STR00064##

[0230] 1. Preparation of Tert-Butyl (Hydroxymethyl) (Vinyl) Phosphine Oxide (a)

##STR00065##

[0231] A 1000 mL four-necked flask was dried with baking gun and protected at nitrogen atmosphere. Thermowell and a low-temperature thermometer were inserted into one neck of the flask, a mechanical stirring device was inserted into another neck, and constant pressure dropping funnel was installed into the rest neck of the flask. The system was replaced with nitrogen for 3-5 times. 10 mL of PCl.sub.3 was carefully drawed with syringe and dropped into pear-shaped bottle until the analytical balance showed 20 g (145.6 mmol, 1 equivalent), then the syringe was taken out. Under the protection of nitrogen, 40 mL of THF refluxed for three hours with sodium wire was added to dissolve, and the mixture was poured into the four-necked flask. 15 mL of tetrahydrofuran was added for rinsing the pear-shaped flask and transferred to the four-necked flask for 3 times.

[0232] The device was placed in an ice bath at −50° C., 176.9 mL (176.9 mmol, 1 equivalent) of tert-butylmagnesium chloride was drawed with syringe, injected into constant pressure dropping funnel to slowly add dropwise. The ice bath device was removed after dripping and warmed to the room temperature. After the temperature was stabilized, the mixture was reacted for 2 h. .sup.31P-NMR was used to detect the reaction. When the reaction was completed, the product was proceed directly to the next step without separation.

[0233] The device was placed in an ice bath at −50° C., 154.9 mL (154.9 mmol, 1.1 equivalents) of vinylmagnesium bromide was drawed with syringe, injected into constant pressure dropping funnel to slowly add dropwise. The ice bath device was removed after dripping and warmed to the room temperature. After the temperature was stabilized, the mixture was reacted for 2 h. .sup.31P-NMR was used to detect the reaction. When the reaction was completed, the product was proceed directly to the next step without separation.

[0234] A certain amount of deionized water was added into the container and sealed. Nitrogen was injected into the container to remove trace oxygen dissolved in the water. 20 mL of oxygen-free deionized water was drawed with syringe and injected into constant pressure dropping funnel, and slowly added dropwise. The device was put in an oil bath at 45° C. for 3 h (or 20 h at room temperature) after dripping. .sup.31P-NMR was used to detect the reaction. When the reaction was completed, the product was proceed directly to the next step without separation.

[0235] Saturated sodium hydroxide solution containing 29 g of NaOH (725 mmol, 5 equivalents) which was configured with oxygen-free deionized water and blown with part of nitrogen was added into container. Under nitrogen atmosphere, 100 mL of formaldehyde solution (1233 mmol, 10 equivalents) and newly prepared NaOH solution were drawed using syringe, injected into constant pressure dropping funnel, and slowly dropped in an ice bath at −20° C. After addition, the device was warmed to room temperature, and then was put in an 50° C. oil bath for 3 h. TLC (developing solvent: ethyl acetate and methanol with volume ratio of 10:1, potassium permanganate as color developer) was used to detect the reaction. Post-treatment was performed after the reaction was completed.

[0236] The device was cooled to room temperature, and the reaction system pH was adjusted to 1 with 2 mol/L HCl solution. The reaction mixture was extracted several times with ethyl acetate and water, and the organic phase was concentrated, dried over saturated brine and anhydrous sodium sulfate, and spin-dried. Silica gel powder (200-300 mesh) was added to the organic phase to mix. The column was packed with pure ethyl acetate, and sample was dry-loaded. The column chromatography was performed with the eluent (ethyl acetate: methanol was 20:1 v/v) to afford the product as a yellow viscous liquid (5.502 g, yield 27.5%).

[0237] a: .sup.1H NMR (500 MHz, Chloroform-d) δ 6.46-6.15 (m, 3H), 4.15-4.10 (d, J=14.4 Hz, 1H), 4.01-3.96 (d, J=14.4 Hz, 1H), 1.19 (d, J=14.5 Hz, 9H); .sup.13C NMR (126 MHz, Chloroform-d) δ 136.99, 125.79, 57.71, 31.53, 24.35 ; .sup.31P NMR (162 MHz, Chloroform-d) δ 45.59; ESI-MS: m/z 163.00 [M+H]+.

[0238] 2. Preparation of 3-(Tert-Butyl)-2-Hydro-1,3-Oxophosphoryl-3-Oxy(b)

##STR00066##

[0239] Under the protection of nitrogen, 10 g (25 mmol, 1 equivalent) of tert-butyl (hydroxymethyl) (vinyl) phosphine oxide was added into the dried Schlenk line, and 8 g (2.7 mL) of liquid bromine (50 mmol, 2 equivalents) and 50 mL of carbon tetrachloride were added. At an external temperature of 0° C., the mixture was magnetic stirred for about 0.5 h, then warmed to room temperature to react for 3 h. TLC (eluent: ethyl acetate: methanol=20:1 v/v, potassium permanganate as color developer) was used to detect the reaction. Post-treatment was performed after the reaction was completed. After the reaction was completed, the stirring bar was taken out and saturated sodium sulfite solution was gradually added dropwise until the orange-red color disappeared. Then the liquid was separated, the organic phase was taken and dried over anhydrous sodium sulfate, spin-dried to use in the next step.

[0240] 4.8 g of sodium tert-butoxide (50 mmol, 2 equivalents) was added and reacted with 50 mL of tetrahydrofuran for 40 min TLC (eluent: ethyl acetate: methanol=20:1 v/v, potassium permanganate as color developer) was used to detect the reaction. Post-treatment was performed after the reaction was completed. After the reaction was completed, the stirring bar was taken out. Appropriate amount of silica gel powder was added and sample was dry-loaded. The column was packed with ethyl acetate. The column chromatography was performed by using eluent (ethyl acetate: methanol=80:1 v/v). The product was collected, concentrated and spin-dried to afford yellow oily liquid product (7.5 g, yield of 75%).

[0241] b: .sup.1H NMR (500 MHz, Chloroform-d) δ 7.24-7.19 (dd, J=25.4, 4.7 Hz, 1H), 5.34-5.31 (dd, J=16.75, 4.7 Hz, 1H), 4.25 (dd, J=14.4, 3.9 Hz, 1H), 4.16 (dd, J=14.4, 10.2 Hz, 1H), 1.16 (d, fJ=16.0 Hz, 9H); .sup.13C NMR (126 MHz, Chloroform-d) δ 163.89 (d, J=10.4 Hz), 91.75 , 91.05 , 64.39 , 63.93, 32.25 (d, J=75.4 Hz), 24.37; .sup.31P NMR (162 MHz, Chloroform-d) δ 72.56 . ESI-MS: m/z 161.0 [M+H]+.

[0242] 3. Preparation of 3 -(Tert-Butyl)-2-Hydro-1,3-Oxaphospholanyl-3-Oxy(c)

##STR00067##

[0243] 1 g (6.2473 mmol, 1 equivalent) of 3-(tert-butyl)-2-hydro-1,3-oxaphospholanyl-3-oxy was put into the Schlenk line, 5 mL of ethyl acetate and 0.1 g of palladium carbon (10%) were added. After replaced with hydrogen under 1 atmosphere for three times, the reaction mixture was magnetic stirred at an external temperature of 40° C. for about 6 h, and cooled to room temperature after that. TLC (eluent: ethyl acetate: methanol=20:1 v/v, potassium permanganate as color developer) was used to detect the reaction. Post-treatment was performed after the reaction was completed. After the reaction was complete, the stirring bar was taken out. Appropriate amount of silica gel powder was added and sample was dry-loaded. The column was packed with ethyl acetate. The column chromatography was performed with the eluent (ethyl acetate: methanol=20:1 v/v), then the product was collected, concentrated and spin-dried to afford the product as a yellow oily liquid, 0.8904 g, yield 89%.

[0244] c: .sup.1H NMR (500 MHz, Chloroform-d) δ 7.27 (s, OH), 4.19 (ddd, J=19.2, 9.5, 6.8 Hz, 1H), 4.12 (dd, J=13.2, 2.6 Hz, 1H), 4.04 (tt, J=10.0, 6.5 Hz, 1H), 3.59 (dd, J=13.2, 6.7 Hz, 1H), 1.23 (d, J=15.1 Hz, 9H); .sup.13C NMR (126 MHz, Chloroform-d) δ 68.11 , 64.19 , 63.71 , 31.79 , 31.28 , 24.27 ; .sup.31P NMR (162 MHz, Chloroform-d) δ 48.63, 48.35, 48.01, 47.73. ESI-MS: m/z 163.05 [M+H].sup.+.

[0245] 4. Preparation of 3 -(Tert-Butyl)-2-Hydro-1,3 -Oxaphospholanyl-3 -Sulfur (d)

##STR00068##

[0246] Under the protection of nitrogen, 10 g (62.473 mmol, 1 equivalent) of 3-(tert-butyl)-2-hydro-1,3-oxaphospholanyl-3-oxy was put into the Schlenk line, 100 mL of tetrahydrofuran, 60.8 mL of polymethylhydrogensiloxane, and 25.2 mL of tetraisopropyl titanate (87.462 mmol, 1.4 equivalents) were added. The mixture was reacted at an external temperature of 70° C. for 4 h. TLC (eluent: ethyl acetate: methanol=10:1 v/v, potassium permanganate as color developer) was used to detect the reaction. Next step was performed after the reaction was completed. After the reaction was completed, the reaction system was cooled to 0° C., 3 g of sulfur powder (93.7 mmol, 1.5 equivalents) was slowly added dropwise, and the mixture was reacted at an external temperature of 0° C. for 1 h. TLC (eluent: ethyl acetate: methanol=2:1 v/v, potassium permanganate as color developer) was used to detect the reaction. Water was added to quench after the reaction was completed. The reaction solution was extracted with dichloromethane and water and separated, and the organic phase was dried.

[0247] Appropriate amount of silica gel powder was added and sample was dry-loaded. The column was packed with petroleum ether. The column chromatography was performed with the eluent (petroleum ether: ethyl acetate=20:1 v/v), then the product was collected, concentrated and spin-dried to afford the product as a white solid, 9.4 g, yield 86%.

[0248] d: .sup.1H NMR (500 MHz, Chloroform-d) δ 4.47 (d, J=12.4 Hz, 1H), 4.37-4.25 (m, 1H), 4.01-3.94 (m, 1H), 3.63 (dd, J=12.4, 1.0 Hz, 1H), 2.43 (d, J=10.3 Hz, 1H), 2.05 (d, J=6.1 Hz, 1H), 1.28 (d, J=16.7 Hz, 9H); .sup.13C NMR (126 MHz, Chloroform-d) δ 77.27, 77.02, 76.76, 70.80, 70.44, 69.02, 33.54, 33.19, 30.12, 29.70, 24.98, 24.96; .sup.31P NMR (162 MHz, Chloroform-d) δ 76.17. ESI-MS: m/z 179.04 [M+H].sup.+.

[0249] 5. Preparation of R-3-(Tert-Butyl)-2-Hydro-1,3-Oxaphospholanyl-3-Sulfur (e-1)

##STR00069##

[0250] The compound was obtained by separating with chiral preparative column AD-H column. Specifically, the method comprises:

[0251] Preparing column model: CHIRALPAK AD-H, Particle Size=5 μm; Dimensions=4 6 mm*250 mm;

[0252] Mobile phase: isopropanol/n-hexane=5/95, Flow rate: 1 ml per minute; Detection wavelength: 210 nm. Retention time: t.sub.1=7.1 min (S configuration), t2=12.3 min (R configuration).

[0253] 6. Preparation of R-3 -(Tert-Butyl)-2 -Hydro-1,3 -Oxaphospholanyl-3 -Oxy (f-1)

##STR00070##

[0254] 1 g (5.6 mmol, 1 equivalent) of R-3-(tert-butyl)-2-hydro-1,3-oxaphospholanyl-3-sulfur was put into the Schlenk line, 5 mL of methanol and 0.3 mL of hydrogen peroxide (30%) were added. The mixture was magnetic stirred at an external temperature of 30° C. for about 6 h. TLC (eluent: ethyl acetate: methanol=20:1 v/v, potassium permanganate as color developer) was used to detect the reaction. Post-treatment was performed after the reaction was completed. After the reaction was completed, the stirring bar was taken out. Appropriate amount of silica gel powder was added and the sample was dry-loaded. The column was packed with ethyl acetate. The column chromatography was performed with the eluent (petroleum ether: ethyl acetate=20:1 v/v). Then the product was collected, concentrated and spin-dried to afford the product as a yellow oily liquid, 0.86 g, yield 95%.

[0255] f-1: .sup.1H NMR (500 MHz, Chloroform-d) δ 4.24-4.10 (m, 2H), 4.12 (dd, J=13.2, 2.6 Hz, 1H), 4.08-4.01 (m, 1H), 3.59-3.57 (dd, J=13.2, 6.7 Hz, 1H), 2.10-1.86 (m, 2H), 1.24-1.21 (d, J=15.1 Hz, 9H); .sup.13C NMR (126 MHz, Chloroform-d) δ 68.11 , 64.19 , 63.71 , 31.79 , 31.28 , 24.27; .sup.31P NMR (162 MHz, Chloroform-d) δ 48.63, 48.35, 48.01, 47.73. ESI-MS: m/z 163.05 [M+H].sup.+.

[0256] 7. Preparation of S-3-(Tert-Butyl)-2-Hydro-1,3-Oxaphospholanyl-3-Borane (g)

##STR00071##

[0257] Under the protection of nitrogen, 5 g (30.8 mmol, 1 equivalent) of S-3-(tert-butyl)-2-hydro-1,3-oxaphospholanyl-3-oxy was added, and 50 mL of THF, 10 mL of polymethylhydrogensiloxane, and 11.6 mL of tetraisopropyl titanate (40 mmol, 1.3 equivalents) were added. The mixture was reacted at an external temperature of 70° C. for 4 h. TLC (eluent: ethyl acetate: methanol=10:1 v/v, potassium permanganate as color developer) was used to detect the reaction.

[0258] Next step was performed after the reaction was completed. After the reaction was completed, the reaction system was cooled to 0° C., and 36.9 mL of 1M borane tetrahydrofuran solution (36.9 mmol, 1.2 equivalents) was slowly added dropwise. The mixture was reacted at an external temperature of 0° C. for 1 h. TLC (eluent: petroleum ether: ethyl acetate=6:1 v/v, potassium permanganate as color developer) was used to detect the reaction. Saturated sodium hydroxide aqueous solution was immediately added to quench the reaction after the reaction was completed. The reaction solution was extracted with dichloromethane, separated, and the organic phase was dried. Appropriate amount of silica gel powder was added to the organic phase and sample was dry-loaded. The column was packed with petroleum ether. The column chromatography was performed with the eluent (petroleum ether: ethyl acetate=50:1 v/v), then the product was collected, concentrated and spin-dried to afford product as a white solid, 4.5 g, yield 90%.

[0259] g-1: .sup.1H NMR (500 MHz, Chloroform-d) δ 4.43 (dd, J=12.3, 3.2 Hz, 1H), 4.27-4.19 (m, 1H), 3.73-3.66 (m, 2H), 2.10-2.01 (m, 2H), 1.21-1.18 (d, J=15), 0.9-0.21 (m, 3H); .sup.13C NMR (126 MHz, Chloroform-d) δ 69.32, 69.29, 65.55, 65.34, 27.39, 27.18, 25.55, 25.53, 22.65, 22.38; .sup.31P NMR (162 MHz, Chloroform-d) δ 48.18 (dd, J=100.6, 45.4 Hz). ESI-MS: m/z 163.1 [M+H].sup.+.

[0260] 8. Preparation of (2R,2′R,3 S,3′S)-3,3′-Di-Tert-Butyl-2,2′-bis(1,3-Oxaphospholanyl)-3,3′-Diborane (h-1)

##STR00072##

[0261] Under the protection of nitrogen, 2 g (12.3 mmol, 1 equivalent) of S-3-(tert-butyl)-2-hydro-1,3-oxaphospholanyl-3-borane was put into the Schlenk line, 10 mL of THF and 1.4 mL of TMEDA (18.5 mmol, 1.5 equivalents) were added. At an external temperature of -78° C., 10.9 mL of 1.7M tert-butyllithium (18.5 mmol, 1.5 equivalents) was added dropwise to the mixture at a rate of 2 drops/s and the resulting mixture was magnetic stirred for about 15 min. After that, 4.1 g of copper chloride (30.8 mmol, 2.5 equivalents) was added while the system was maintained at the external temperature of −78° C. The reaction mixture was warmed to room temperature to react for 45 min after addition. TLC (eluent: petroleum ether: ethyl acetate=6:1 v/v, potassium permanganate as color developer) was used to detect the reaction. Post-treatment was performed after the reaction was completed. After the reaction was completed, the reaction solution was extracted with ethyl acetate and 10% sodium hydroxide aqueous solution, separated, and the organic phase was dried. Appropriate amount of silica gel powder was added to the organic phase, and sample was dry-loaded.

[0262] The column was packed with petroleum ether. The column chromatography was performed with the eluent (petroleum ether: ethyl acetate=100:1 v/v), then the product was collected, concentrated and spin-dried to afford product as a white solid, 0.6 g, yield 30.6%.

[0263] h-1: .sup.1H NMR (500 MHz, Chloroform-d) δ 4.39-4.37 (dd, 2H), 4.27-4.24 (m, 2H), 3.74 (m, 2H), 2.21-2.20 (m, 2H), 2.08-2.07 (m, 2H), 1.25 (d, J=13.9 Hz, 18H), 0.81-0.25(m, 6H); .sup.13C NMR (101 MHz, Chloroform-d) δ 73.67, 70.12, 28.34, 28.08, 25.71, 22.58, 22.26.; .sup.31P NMR (162 MHz, Chloroform-d) δ 59.04 . ESI-MS: m/z 321.21 [M+H].sup.+.

[0264] Single crystal X-ray diffraction: space group: P 21 21 2, unit cell parameters: a=10.2841(4) Å, b=11.1975(5) Å, c=8.5616(3) Å, α=90°, β=90°, γ=90°, unit cell volume: 985.92(7) Å.sup.3.

[0265] The product h-3 was (2R, 2′S, 3S, 3′S)-3,3′-di-tert-butyl-2,2′-bis(1,3-oxaphospholanyl)-3,3′-diborane: .sup.1H NMR (500 MHz, Chloroform-d) δ 4.39-4.37 (dd, 1H), 4.34-4.31 (m, 1H), 4.23-4.17 (m, 2H), 4.02-3.95 (m, 1H), 3.74-3.68 (m, 1H), 2.24-2.06 (m, 4H), 1.29-1.23 (dd, 18H), 0.90-0.21(m, 6H); .sup.31P NMR (162 MHz, Chloroform-d) δ 60.78, 50.14. ESI-MS: m/z 321.21 [M+H]+.

[0266] Its single crystal X-ray diffraction: space group: P 21, unit cell parameters: a=7.4199(7) Å, b=24.550(3) Å, c=11.3537(12) Å, α=90°, β=107.131(3)°, γ=90°, unit cell volume: 1976.4(4) Å.sup.3.

[0267] 9. Preparation of (2R, 2′R, 3S, 3′S)-3,3′-Di-Tert-Butyl-2,2′-Bis(1,3-Oxaphospholanyl) (1)

##STR00073##

[0268] Under the protection of nitrogen, 100 mg (0.31 mmol, 1 equivalent) of (2R, 2′R, 3S, 3′S)-3,3′-di-tert-butyl-2,2′-bis(1,3-oxaphospholanyl)-3,3′-diborane was placed in Schlenk line. 6 mL of toluene and 105 mg of 1,4-diazabicyclo [2.2.2]octane (0.94 mmol, 3 equivalent) were added. The mixture was magnetic stirred for about 2h at an external temperature of 60° C. Most of the toluene solvent was removed by the vacuum pump under reduced pressure. Degassed water (5 mL) was carefully added to the residue. At room temperature, degassed ether (5 mL) was added to the mixture, stirred at 60° C. for 0.5 hours, then separated to afford organic phase. The organic phase was dried over sodium sulfate, concentrated, and column chromatography purified on anhydrous oxygen-free neutral alumina (petroleum ether/ether=3:1) to afford a colorless oily target ligand (2R, 2′R, 3S, 3′S)-3,3′-di-tert-butyl-2,2′-bis(1,3-oxaphospholanyl) (68 mg, 75%).

[0269] 1: .sup.1H NMR (500 MHz, Chloroform-d) δ 4.79-4.77 (d, J=3.72, 2H), 4.20-4.17 (m, 4H), 2.16(m, 4H), 1.24-1.19 (d, J=15); .sup.31P NMR (162 MHz, Chloroform-d) δ 2.51. ESI-MS: m/z 291.21 [M+H].sup.+.

[0270] 10. Preparation of Metal Complex {(Norbornadiene)[(2R,2′R,3S,3′S)-3,3′-Di-Tert-Butyl-2,2′-Bis(1,3-Oxaphospholany 1)]}Rhodium Tetrafluoroborate, Namely Rh(nbd)(1)BF.sub.4

##STR00074##

[0271] Under the protection of nitrogen, bis(norbornadiene)rhodium(I) tetrafluoroborate (18.7 mg, 0.05 mmol, 1 equivalent) was dissolved in tetrahydrofuran (0.5 mL). The tetrahydrofuran (0.5 mL) solution of ligand (2R, 2′R, 3S, 3′S)-3,3′-di-tert-butyl-2,2′-bis(1,3-oxaphospholanyl) (1, 16 mg, 0.055 mmol, 1.1 equivalent) was added with stirring system at 0° C. After the reaction system was stirred at room temperature for 0.5 hours, the vacuum pump was used for concentrating under reduced pressure to remove most of solvent. Degassed ether (10 mL) was added and stirred for 10 minutes, the mixture was filtered under nitrogen protection to afford the target compound {(norbornadiene)[(2R,2′R,3S,3′S)-3,3′-di-tert-butyl-2,2′-bis(1,3-oxaphospholany 1)]} rhodium tetrafluoroborate, namely Rh(nbd)(1)BF.sub.4 (43.4 mg, 0.0425 mmol, 85%).

[0272] Rh(nbd)(1)BF.sub.4: .sup.1H NMR (400 MHz, Chloroform-d) δ 6.98 (br s, 2H), 5.26 (s, 2H), 4.58-4.50 (m, 2H), 4.40-4.38 (d, J=10 Hz, 2H), 2.35 (br s, 2H), 2.17 (br s, 2H), 1.23-1.21 (d, J=10 Hz, 18H); .sup.31P NMR (162 MHz, CDCl.sub.3) δ 92.3-91.3, (d, 2J RhP=160 Hz).

EXAMPLE 2

[0273] Preparation of (2S,2S,3R,3′R)-3,3′-di-tert-butyl-2,2′-bis(1,3-oxaphospholanyl) (2) and its metal complex 1(norbornadiene)[(2S,25,3R,3′R)-3,3′-di-tert-butyl -2,2′-bis(1,3-oxaphospholanyl)])rhodium tetrafluoroborate, namely

[0274] Rh(nbd)(2)BF.sub.4 (the reaction route was shown below)

##STR00075##

[0275] The compound e-2 preparation separated by the chiral column in step (5) of Example 1 was prepared according to the operation and conditions in Example 1. Preparation of S-3-(tert-butyl)-2-hydro-1,3-oxaphospholanyl-3-oxy 1 g (5 6 mmol, 1 equivalent) of S-3-(tert-butyl)-2-hydro-1,3-oxaphospholanyl -3-sulfur was put into Schlenk line. 5 mL of methanol and 0.3 mL of hydrogen peroxide (30%) were added. The mixture was magnetic stirred at an external temperature of 30° C. for about 6 h. TLC (eluent: ethyl acetate: methanol=20:1 v/v, potassium permanganate as color developer) was used to detect the reaction.

[0276] Post-treatment was performed after the reaction was completed. After the reaction was completed, the stirring bar was taken out. Appropriate amount of silica gel powder was added, and sample was dry-loaded. The column was packed with ethyl acetate. The column chromatography was performed with the eluent (ethyl acetate: methanol=20:1 v/v), then the product was collected, concentrated and spin-dried to afford product as a yellow oily liquid, 0.86 g, yield 95%.

[0277] f-2: .sup.1H NMR (500 MHz, Chloroform-d) δ 4.24-4.10 (m, 2H), 4.12 (dd, J=13.2, 2.6 Hz, 1H), 4.08-4.01 (m, 1H), 3.59-3.57 (dd, J=13.2, 6.7 Hz, 1H), 2.10-1.86 (m, 2H), 1.24-1.21 (d, J=15.1 Hz, 9H); .sup.13C NMR (126 MHz, Chloroform-d) δ 68.11 , 64.19 , 63.71 , 31.79 , 31.28 , 24.27; .sup.31P NMR (162 MHz, Chloroform-d) δ 48.63, 48.35, 48.01, 47.73. ESI-MS: m/z 163.05 [M+H].sup.+.

[0278] Preparation of R-3 -(Tert-Butyl)-2-Hydro-1,3 -Oxaphospholanyl-3 -Borane

[0279] Under the protection of nitrogen, 5 g (30.8 mmol, 1 equivalent) of S-3-(tert-butyl)-2-hydro-1,3-oxaphospholanyl-3-oxy was added. 50 mL of THF, 10 mL of polymethylhydrogensiloxane, and 11.6 mL of tetraisopropyl titanate (40 mmol, 1.3 equivalents) were added. The mixture was reacted at an external temperature of 70° C. for 4 h. TLC (eluent: ethyl acetate: methanol=10:1 v/v, potassium permanganate as color developer) was used to detect the reaction. Next step was performed after the reaction was completed. After the reaction was completed, the reaction system was cooled to 0° C., and 36.9 mL of 1M borane tetrahydrofuran solution (36.9 mmol, 1.2 equivalents) was slowly added dropwise. The mixture was reacted at an external temperature of 0° C. for 1 h. TLC (eluent: petroleum ether: ethyl acetate=6:1 v/v, potassium permanganate as color developer) was used to detect the reaction. When the reaction was completed, saturated sodium hydroxide aqueous solution was immediately added to quench the reaction. The reaction solution was extracted with dichloromethane, separated, and the organic phase was dried. Appropriate amount of silica gel powder was added to the organic phase, and sample was dry-loaded. The column was packed with petroleum ether. The column chromatography was performed with the eluent (petroleum ether: ethyl acetate=50:1 v/v), then the product was collected, concentrated and spin-dried to afford product as a white solid, 4.5 g, yield 90%.

[0280] g-2: .sup.1H NMR (500 MHz, Chloroform-d) δ 4.43 (dd, J=12.3, 3.2 Hz, 1H), 4.27-4.19 (m, 1H), 3.73-3.66 (m, 2H), 2.10-2.01 (m, 2H), 1.21-1.18 (d, J=15), 0.9-0.21 (m, 3H); .sup.13C NMR (126 MHz, Chloroform-d) δ 69.32, 69.29, 65.55, 65.34, 27.39, 27.18, 25.55, 25.53, 22.65, 22.38; .sup.31P NMR (162 MHz, Chloroform-d) δ 48.18 (dd, J=100.6, 45.4 Hz). ESI-MS: m/z 163.1 [M+H].sup.+.

[0281] Preparation of (2S,2′S,3R,3′R)-3,3′-Di-Tert-Butyl-2,2′-Bis(1,3-Oxaphospholanyl)-3,3′-Diborane

[0282] Under the protection of nitrogen, 2 g (12.3 mmol, 1 equivalent) of R-3-(tert-butyl)-2-hydro-1,3-oxaphospholanyl-3-borane was put into the Schlenk line. 10 mL of THF and 1.4 mL of TMEDA (18.5 mmol, 1.5 equivalents) were added. At an external temperature of −78° C., 10.9 mL of 1.7M tert-butyllithium (18.5 mmol, 1.5 equivalents) was added dropwise at a rate of 2 drops/s. The resulting mixture was magnetic stirred for about 15 min After that, 4.1 g of copper chloride (30.8 mmol, 2.5 equivalents) was added while the system was maintained at the external temperature of −78° C. Then the reaction mixture was warmed to room temperature to react for 45 min. TLC (eluent: petroleum ether: ethyl acetate=6:1 v/v, potassium permanganate as color developer) was used to detect the reaction. Post-treatment was performed after the reaction was completed. After the reaction was completed, the reaction solution was extracted with ethyl acetate and 10% sodium hydroxide aqueous solution, separated, and the organic phase was dried. Appropriate amount of silica gel powder was added to the organic phase, and sample was dry-loaded. The column was packed with petroleum ether. The column chromatography was performed with the eluent (petroleum ether: ethyl acetate=100:1 v/v), then the product was collected, concentrated and spin-dried. The product was obtained as a white solid, 0.6 g, yield 30.6%.

[0283] h-2: .sup.1H NMR (500 MHz, Chloroform-d) δ 4.39-4.37 (dd, 2H), 4.27-4.24 (m, 2H), 3.74 (m, 2H), 2.21-2.20 (m, 2H), 2.08-2.07 (m, 2H), 1.25 (d, J=13.9 Hz, 18H), 0.81-0.25(m, 6H);.sup.13C NMR (101 MHz, Chloroform-d) δ 73.67, 70.12, 28.34, 28.08, 25.71, 22.58, 22.26.; .sup.31P NMR (162 MHz, Chloroform-d) δ 59.04. ESI-MS: m/z 321.21 [M+H].sup.+.

[0284] Preparation of (2S, 2′S, 3R, 3′R)-3,3′-Di-Tert-Butyl-2,2′-Bis(1,3-Oxaphospholanyl)

[0285] Under the protection of nitrogen, 100 mg (0.31 mmol, 1 equivalent) of (2S,2′S,3R,3′R)-3,3′-di-tert-butyl-2,2′-bis(1,3-oxaphospholanyl)-3,3′-diborane was placed in a Schlenk line, 6 mL of toluene, 105 mg of 1,4-diazabicyclo [2.2.2]octane (0.94 mmol, 3 equivalent) were added. The mixture was magnetic stirred for about 2 h at an external temperature of 60° C. Most of the toluene solvent was removed by the vacuum pump under reduced pressure. Degassed water (5 mL) was carefully added to the residue. Degassed ether (5 mL) was added to the mixed system at room temperature, and mixture was stirred at 60° C. for 0.5 hours, then separated to afford the organic phase. The organic phase was dried over with sodium sulfate, concentrated, and column chromatography purified on anhydrous oxygen-free neutral alumina (petroleum ether/ether=3: 1) to obtain the colorless oily target ligand (2S, 2′S, 3R, 3′R)-3,3′-di-tert-butyl-2,2′-bis(1,3-oxaphospholanyl) (68 mg, 75%).

[0286] 2: .sup.1H NMR (500 MHz, Chloroform-d) δ 4.79-4.77 (d, J=3.72, 2H), 4.20-4.17 (m, 4H), 2.16(m, 4H), 1.24-1.19 (d, J=15); .sup.31P NMR (162 MHz, Chloroform-d) δ 2.51. ESI-MS: m/z 291.21 [M+H].sup.+.

[0287] Preparation of Metal Complex {(Norbornadiene)[(2S,2′S,3R,3′R)-3,3′-Di-Tert-Butyl-2,2′-Bis(1,3-Oxaphospholanyl)]}Rhodium Tetrafluoroborate, Namely Rh(nbd)(1)BF.sub.4

[0288] Under the protection of nitrogen, bis(norbornadiene)rhodium(I) tetrafluoroborate (18.7 mg, 0.05 mmol, 1 equivalent) was dissolved in tetrahydrofuran (0.5 mL).The tetrahydrofuran (0.5 mL) solution of ligand (2S,2′S,3R,3′R)-3,3′-di-tert-butyl-2,2′-bis(1,3-oxaphospholanyl) (1, 16 mg, 0.055 mmol, 1.1 equivalent) was added with stirring at 0° C. The reaction system was stirred at room temperature for 0.5 hours, then concentrated under reduced pressure by vacuum pump to remove most of solvent. Degassed ether (10 mL) was added and stirred for 10 minutes, then the mixture was filtered under nitrogen protection to obtain the target compound {(norbornadiene)[ (2S,2′S,3R,3′R)-3,3′-di-tert-butyl-2,2′-bis(1,3-oxaphospholanyl)]} rhodium tetrafluoroborate, namely Rh(nbd)(2)BF.sub.4 (43.4 mg, 0.0425 mmol, 85%).

[0289] Rh(nbd)(2)BF.sub.4: .sup.1H NMR (400 MHz, Chloroform-d) δ 6.98 (br s, 2H), 5.26 (s, 2H), 4.58-4.50 (m, 2H), 4.40-4.38 (d, J=10 Hz, 2H), 2.35 (br s, 2H), 2.17 (br s, 2H), 1.23-1.21 (d, J=10 Hz, 18H); .sup.31P NMR (162 MHz, CDCl.sub.3) δ 92.3-91.3, (d, 2J RhP=160 Hz).

EXAMPLE 3

[0290] ##STR00076##

[0291] Methyl (Z)-2-acetamido-3-phenyl acrylate was used as the hydrogenation substrate and the chiral metal rhodium complex Rh(nbd)(1)BF.sub.4 was used as the catalyst to prepare the optically active N-acetyl-L-phenylalanine methyl ester (S).

[0292] In a glove box, The reaction is as follows: under nitrogen atmosphere, methyl (Z)-2-acetamido-3-phenyl acrylate (22 mg, 0.1 mmol), Rh(nbd)(1)BF.sub.4 (0.24 mg, 0.5 μmol), 0.5 mL of anhydrous dichloromethane were added to the hydrogenation flask, and transferred to the autoclave. After sealed, the autoclave was replaced with hydrogen for three times, and was charged with hydrogen to 750 psi. The system was reacted at 50° C. for 12 hours, and then cooled to room temperature. Hydrogen was discharged and the reactor was opened. The crude reaction product solution was filtered through microporous membrane to remove metal ions. After the solution was diluted by isopropanol, chiral AD-H column high performance liquid chromatography was used to measure the conversion rate and ee value of the product N-acetyl-L-phenylalanine methyl ester, which was 97%.

[0293] N-acetyl-L-phenylalanine methyl ester [(S)-3a]: white solid (yield>99%); 97% ee.

[0294] The ee value was determined by chiral high pressure liquid chromatography; high pressure liquid phase conditions: chiral AD-H column, 25° C., flow rate: 1 mL/min, n-hexane/isopropanol: 95/5, 210 nm, t.sub.1=15.2 min (R), t.sub.2=21.8 min (S).

[0295] .sup.1H NMR (500 MHz, CDCl.sub.3) δ 7.35,-7.25 (m, 3H), 7.10-7.08 (d, J=10.45, 2H), 4.91-4.88 (dd, 2H), 3.74 (s, 1H), 3.13 (m, 2H), 1.99 (s, 1H).

EXAMPLE 4

[0296] ##STR00077##

[0297] (Z)-2-acetamido-3-phenylacrylic acid was used as the hydrogenation substrate and the chiral metal rhodium complex Rh(nbd)(1)BF.sub.4 was used as the catalyst to prepare the optically active N-acetyl-L-phenylalanine (S)-3b.

[0298] The reaction was as follows: under nitrogen atmosphere, in a glove box, (Z)-2-acetamido-3-phenylacrylic acid (20.5 mg, 0.1 mmol), Rh(nbd)(1)BF.sub.4 (0.24 mg, 0.5 μmol), 0.5 mL of anhydrous dichloromethane were added to the hydrogenation flask, and transferred to the autoclave. After sealed, the autoclave was replaced with hydrogen for three times, and was charged with hydrogen to 750 psi. The system was reacted at 50° C. for 12 hours, then cooled to room temperature. Hydrogen was discharged and the reactor was opened. The crude reaction product solution was filtered through microporous membrane to remove metal ions. After the solution was diluted by isopropanol, chiral AD-H column high performance liquid chromatography was used to measure the conversion rate and ee value of the product N-acetyl-L-phenylalanine, which was 97%.

[0299] N-acetyl-L-phenylalanine [(S)-3b]: white solid (yield>99%); 98% ee.

[0300] The ee value was determined by chiral high pressure liquid chromatography; N-acetyl-L-phenylalanine was pre-transformed to N-acetyl-L-phenylalanine methyl ester in the presence of trimethylsilyl diazomethane. High pressure liquid phase conditions: chiral AD-H column, 25° C., flow rate: 1 mL/min, n-hexane/isopropanol: 95/5, 210 nm, t.sub.1=15.2 min (S), t.sub.2=21.8 min (R). .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.31-7.15(m, 5H), 4.67-4.62 (dd, J=9.12, 4.98 Hz, 1H), 3.34 (d, J=0.63 Hz, 1H) 3.22-3.16 (dd, J=13.89, 5.04 Hz, 1H), 2.96-2.89 (dd, J=13.8, 9.2 Hz, 1H), 1.89 (s, 1H)

EXAMPLE 5

[0301] ##STR00078##

[0302] N-(2-methyl-3,4-dihydronaphthalene-1-yl)acetamide was used as the hydrogenation substrate and the chiral metal rhodium complex Rh(nbd)(1)BF.sub.4 was used as the catalyst to prepare the optical active chiral amide (1S, 2S)-3f.

[0303] The reaction is as follows: under nitrogen atmosphere, in a glove box, N-(2 -methyl-3,4-dihydronaphthalene-1-yl)acetamide (20.1 mg, 0.1 mmol), Rh(nbd)(1)BF.sub.4 (0.24 mg, 0.5 μmol), 0.5 mL of anhydrous dichloromethane were added to the hydrogenation flask, and transferred to the autoclave. After sealed, the autoclave was replaced with hydrogen for three times, and was charged with hydrogen to 750 psi. The system was reacted at 50° C. for 12 hours, then cooled to room temperature. Hydrogen was discharged and the reactor was opened. The crude reaction product solution was filtered through microporous membrane to remove metal ions. After the solution was diluted by isopropanol, chiral AD-H column high performance liquid chromatography was used to measure the conversion rate and ee value of the product N-((1S,2S)-2-methyl-1,2,3,4-tetrahydronaphthalene-1-yl)acetamide, which was 70%.

[0304] N-((1S,2S)-2-methyl-1,2,3,4-tetrahydronaphthalene-1-yl)acetamide white solid (yield>99%); 70% ee.

[0305] ee value was determined by chiral high pressure liquid chromatography; high pressure liquid phase conditions: chiral AD-H column, 25° C., flow rate: 1 mL/min, n-hexane/isopropanol: 95/5, 210 nm, t.sub.1=8.7 min (S), t.sub.2=11.8 min (R). .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.24-7.00(m, 4H), 5.60-5.42 (br s, 1H), 5.27-5.22 (dd, J=9.45, 4.2 Hz, 1H), 2.87-2.75 (m, 2H), 2.01 (s, 3H), 1.86-1.45 (m, 3H), 1.03-1.01 (d, J=6.8 Hz, 3H)

[0306] 1H NMR (500 MHz, CDCl.sub.3) δ 7.24-7.00 (m, 4H), 6.11 (d, 1H, J=9.3 Hz), 5.20-5.18 (dd, 1H, J=9.7, 4.7 Hz), 2.87-2.75 (m, 2H), 2.01-1.95 (m, 1H), 1.92 (s, 3H), 1.71-1.60 (m, 1H), 1.55-1.40 (m, 1H), 0.98 (d, 3H, J=6.9 Hz)

EXAMPLE 6

[0307] ##STR00079##

[0308] 1-(acetylamino)-1-styrene was used as the hydrogenation substrate and the chiral metal rhodium complex Rh(nbd)(1)BF.sub.4 was used as the catalyst to prepare the optically active chiral (S)-N-(1-phenylethyl)acetamide [(S)-3h].

[0309] The reaction was as follows: under nitrogen atmosphere, in a glove box, 1-(acetylamino)-1-styrene (16 mg, 0.1 mmol), Rh(nbd)(1)BF.sub.4 (0.24 mg, 0.5 μmol), and 0.5 mL of anhydrous dichloromethane were added to the hydrogenation flask and transferred to the autoclave. After sealed, the autoclave was was replaced with hydrogen for three times, and was charged with hydrogen to 750 psi. The system was reacted at 50° C. for 12 hours, and then cooled to room temperature. Hydrogen was discharged and the reactor was opened. The crude reaction product solution was filtered through microporous membrane to remove metal ions. After the solution was diluted by isopropanol, chiral AD-H column high performance liquid chromatography was used to measure the conversion rate and ee value of the product (S)-N-(1-phenylethyl) acetamide [(S)-3h], which was 99%.

[0310] (S)-N-(1-phenylethyl) acetamide: white solid (yield>99%); 99% ee.

[0311] The ee value was determined by chiral high pressure liquid chromatography; high pressure liquid phase conditions: chiral AD-H column, 25° C., flow rate: 1 mL/min, n-hexane/isopropanol: 95/5, 210 nm, t.sub.1=10.1 min (S), t.sub.2=12.8 min (R).

[0312] 1H NMR (500 MHz, CDCl.sub.3) δ 7.30-7.27 (m, 5H) , 6.09 (br, 1H), 5.16-5.04 (m, 1H) , 1.94(s, 3H), 1.46 (d, J=6.8 Hz, 3H).

EXAMPLE 7

[0313] ##STR00080##

[0314] 1-(Acetylamino)-1-styrene was used as the hydrogenation substrate, (2S, 2S, 3R, 3′R) -3,3′-di-tert-butyl-2,2′-bis(1,3-oxaphospholanyl) was used as chiral phosphine ligand, Rh(nbd)2BF.sub.4 was used as metal catalyst to prepare the optically active chiral (R)-N-(1-phenylethyl)acetamide [(R)-3h].

[0315] The reaction is as follows: under nitrogen atmosphere, in a glove box, 1-(acetylamino)-1-styrene (16 mg, 0.1 mmol), Rh(nbd).sub.2BF.sub.4 (0.24 mg, 0.5 μmol), (2S, 2S, 3R, 3′R) -3,3′-di-tert-butyl-2,2′-bis(1,3-oxaphospholanyl) (0.15 mg, 0.2 μmol), 0.5 mL of anhydrous dichloromethane were added to the hydrogenation flask and transferred to the autoclave. After sealed, the autoclave was, replaced with hydrogen for three times, and was charged with hydrogen to 750 psi. The system was reacted at 50° C. for 12 hours, and then cooled to room temperature. Hydrogen was discharged and the reactor was opened. The reaction crude product solution was filtered through microporous membrane to remove metal ions. After the solution was diluted by isopropanol, chiral AD-H column high performance liquid chromatography was used to measure the conversion rate and ee value of the product (S)-N-(1-phenylethyl) acetamide [(R)-3h], which was 99%.

[0316] (S)-N-(1-phenylethyl) acetamide: white solid (yield>99%); 99% ee.

[0317] The ee value was determined by chiral high pressure liquid chromatography; high pressure liquid phase conditions: chiral AD-H column, 25° C., flow rate: 1 mL/min, n-hexane/isopropanol: 95/5, 210 nm, t.sub.1=10.1 min (S), t.sub.2=12.8 min (R). 1H NMR (500 MHz, CDCl.sub.3) δ 7.36-7.20 (m, 5H) , 6.02 (br s, 1H), 5.16-5.04 (m, 1H) , 1.94(s, 1H), 1.47-1.44 (d, J=11.4 Hz, 3H).

EXAMPLE 8

[0318] ##STR00081##

[0319] 1-(4-Bromophenyl)-2-acetamidopropene was used as the hydrogenation substrate, (2R, 2′R, 3S, 3′S) -3,3′-di-tert-butyl-2,2′- bis(1,3-oxaphospholanyl) was used as ligand, Rh(nbd).sub.2BF.sub.4 was used as catalyst to prepare the optically active chiral (S)-1-(4-bromophenyl)-2-acetamido-propane.

[0320] The reaction is as follows: under nitrogen atmosphere, in a glove box, (E)-1-(4-bromophenyl)-2-acetamidopropene (4 g, 16.6 mmol), Rh(nbd).sub.2BF.sub.4 (0.03 mg, 0.1 μmol), (2R, 2′R, 3S, 3′S) -3,3′-di-tert-butyl-2,2′-bis(1,3-oxaphospholanyl) (0.03 mg, 0.1 μmol), 24 mL of anhydrous methanol were added to the hydrogenation flask and transferred to the autoclave. After sealed, the autoclave was replaced with hydrogen for three times, and was charged with hydrogen to 300 psi. The system was reacted at 25° C. for 12 hours, and then cooled to room temperature. Hydrogen was discharged and the reactor was opened. The crude reaction product solution was filtered through microporous membrane to remove metal ions. After the solution was diluted by isopropanol, chiral AD-H column high performance liquid chromatography was used to measure the conversion rate and ee value of the product N-acetyl-L-phenylalanine methyl ester, which was 97%.

[0321] (S)-1-(4-bromophenyl)-2-acetamido-propane: white solid (yield>99%); 98% ee.

[0322] The ee value was determined by chiral high pressure liquid chromatography; high pressure liquid phase conditions: chiral AD-H column, 25° C., flow rate: 1 mL/min, n-hexane/isopropanol: 95/5, 210 nm, t.sub.1=13.4 min (S), t.sub.2=17.9 min (R).

[0323] .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 7.47 (d, J=8 Hz, 2H), 7.21 (d, J=8 Hz, 2H), 5.84 (s, br, 1H), 5.05-5.12 (m, 1H), 2.00 (s, 3H),1.47 (d, J=4 Hz, 3H).

EXAMPLE 9

[0324] ##STR00082##

[0325] 2-Methylcyclohexenyl 1-acetamide was used as hydrogenation substrate, (2R,2′R,3S,3′S) -3,3′-di-tert-butyl-2,2′-bis(1,3-oxaphospholanyl) was used as ligand, and Rh(nbd).sub.2BF.sub.4 was used as catalyst were used to prepare the optically active chiral (1S ,2R)-2 -methylcyclohexyl-1-acetamide.

[0326] The reaction was as follows: under nitrogen atmosphere, in a glove box, 2-methylcyclohexenyl 1-acetamide (0.5g, 3.2 mmol), Rh(nbd).sub.2BF.sub.4 (1 mg, 2.4 μmol), (2R, 2′R, 3S, 3′S)-3,3′-di-tert-butyl-2,2′-bis(1,3-oxaphospholanyl) (0.8 mg, 2.4 μmol), 5 mL of anhydrous methanol were added to the hydrogenation flask and transferred to the autoclave. After sealed, the autoclave was replaced with hydrogen three times, and was charged with hydrogen to 300 psi. The system was reacted at 25° C. for 12 hours, and then cooled to room temperature. Hydrogen was discharged and the reactor was opened. The crude reaction product solution was filtered through microporous membrane to remove metal ions. After the solution was diluted by isopropanol, chiral AD-H column high performance liquid chromatography was used to measure the conversion rate and ee value of the product (1S,2R)-2-methylcyclohexyl-1-acetamide, which was 68%.

[0327] (1S,2R)-2-methylcyclohexyl-1-acetamide: white solid (yield>99%); 68% ee.

[0328] The ee value was determined by chiral high pressure liquid chromatography; high pressure liquid phase conditions: chiral AD-H column, 25° C., flow rate: 1 mL/min, n-hexane/isopropanol: 95/5, 210 nm, t.sub.1=11.2 min (1R,2S), t.sub.2=12.1 min (1S,2R).

[0329] .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 5.53 (s, 1H) , 4.02-4.07 (m, 1H), 1.99 (s, 3H), 1.84 (m, 1H), 1.17-1.65 (m, 8H),0.86 (d, J=7 Hz, 3H).

EXAMPLE 10

[0330] ##STR00083##

[0331] 1,1-Dimethyl-2-acetamidopropene was used as hydrogenation substrate, (2R,2′R,3S,3′S) -3,3′-di-tert-butyl-2,2′-bis(1,3-oxaphospholanyl) was used as ligand, Rh(nbd).sub.2BF.sub.4 was used as catalyst to prepare the optically active chiral (S)-1,1-dimethyl-2-acetamido-propane.

[0332] The reaction was as follows: under nitrogen atmosphere, in a glove box, 1,1-dimethyl-2-acetamidopropene (0.3g, 2.4 mmol), Rh(nbd).sub.2BF.sub.4 (0.7 mg, 2.4 μmol), (2R, 2′R, 3S, 3′S)-3,3′-di-tert-butyl-2,2′-bis(1,3-oxaphospholanyl) (0.7 mg, 2.4 μmol), and 5 mL of anhydrous methanol were added to the hydrogenation flask and transferred to the autoclave. After sealed, the autoclave was replaced with hydrogen for three times, and was charged with hydrogen to 300 psi. The system was reacted at 25° C. for 12 hours, and then cooled to room temperature. Hydrogen was discharged and the reactor was opened. The crude reaction product solution was filtered through microporous membrane to remove metal ions. After the solution was diluted by ethyl acetate, chiral GC-MS column was used to measure the conversion rate and ee value of the product (S)-1-(4-bromophenyl)-2-acetamido-propane, which was 60%.

[0333] (S)-1-(4-bromophenyl)-2-acetamido-propane: white solid (yield>99%); 98% ee.

[0334] The ee value was determined by chiral GC-MS column; Chiral GC-MS conditions: FUSED SILICA Capillary Column, Beta DEX™ 225, 30 m*0.25 mm*0.25 uMfilm thickness. t.sub.1(S)=11.18 min, t.sub.2(R)=11.45 min. .sup.1H NMR (500 MHz, CDCl.sub.3) δ: 5.38 (s, 1H), 3.82-3.89 (m, 1H), 1.97 (s, 3H), 1.63-1.72 (m, 1H), 1.06 (d, J=6.7 Hz, 3H), 0.89 (d, J=5.4 Hz, 3H), 0.88 (d, J=6.2 Hz, 3H).

EXAMPLE 11

[0335] ##STR00084##

[0336] 1-(Acetylamino)-1-styrene was used as hydrogenation substrate, the chiral metal rhodium complex Rh(nbd)(1)BF.sub.4 was used as catalyst to prepare the optically active chiral (S)-N-(1-phenylethyl)acetamide ((S)-3h).

[0337] The reaction was as follows: under nitrogen atmosphere, in a glove box, 1-(acetylamino)-1-styrene (11 g, 68.2 mmol), Rh(nbd)(1)BF.sub.4 (0.4 mg, 0.68 μmol), 110 mL of anhydrous dichloromethane were added to the hydrogenation flask and transferred to the autoclave. After sealed, the autoclave was replaced with hydrogen for three times, and was charged with hydrogen to 750 psi. The system was reacted at 50° C. for 12 hours, and then cooled to room temperature. Hydrogen was discharged and the reactor was opened. The crude reaction product solution was filtered through microporous membrane to remove metal ions. After the solution was diluted by isopropanol, chiral AD-H column high performance liquid chromatography was used to measure the conversion rate and ee value of the product (S)-N-(1-phenylethyl)acetamide [(S)-3h], which was 99%.

[0338] (S)-N-(1-phenylethyl)acetamide: white solid (yield>99%); 99% ee.

[0339] The ee value was determined by chiral high pressure liquid chromatography; high pressure liquid phase conditions: chiral AD-H column, 25° C., flow rate: 1 mL/min, n-hexane/isopropanol: 95/5, 210 nm, t.sub.1=10.1 min (S), t.sub.2=12.8 min (R).

Comparative Example 1

[0340] ##STR00085##

[0341] (Z)-2-acetamido-3-phenylacrylic acid was used as hydrogenation substrate, (2R,25,3S,3′S)-3,3′-di-tert-butyl-2,2′-bis(1,3-oxaphospholanyl) (compound h-3) was used as chiral phosphine ligand, and Rh(nbd).sub.2BF.sub.4 was used as metal catalyst to prepare the optically active chiral amide (S)-3b.

[0342] The reaction was as follows: under nitrogen atmosphere, in a glove box,

[0343] (Z)-2-acetamido-3-phenylacrylic acid (20.5 mg, 0.1 mmol), Rh(nbd).sub.2BF.sub.4 (0.19 mg, 0.5 μmol), (2S,2S,3R,3′R)-3,3′-di-tert-butyl-2,2′-bis(1,3-oxaphospholanyl) (0.15 mg, 0.5 μmol), and 0.5 mL of anhydrous dichloromethane were added to the hydrogenation flask and transferred to the autoclave. After sealed, the autoclave was replaced with hydrogen for three times, and was charged with hydrogen to 750 psi. The system was reacted at 50° C. for 12 hours, then cooled to room temperature. Hydrogen was discharged and the reactor was opened. The crude reaction product solution was filtered through microporous membrane to remove metal ions. After the solution was diluted by isopropanol, chiral AD-H column high performance liquid chromatography was used to measure the conversion rate and ee value of the product N-acetyl-L-phenylalanine, which was 58%.

[0344] N-acetyl-L-phenylalanine [(S)-3b]: white solid (yield>99%); 58% ee.

[0345] The ee value was determined by chiral high pressure liquid chromatography; N-acetyl-L-phenylalanine was pre-transformed to N-acetyl-L-phenylalanine methyl ester in the presence of trimethylsilyl diazomethane. High pressure liquid phase conditions: chiral AD-H column, 25° C., flow rate: 1 mL/min, n-hexane/isopropanol: 95/5, 210 nm, t.sub.1=15.2 min (S), t.sub.2=21.8 min (R). .sup.1H NMR (500 MHz, CD.sub.3OD) δ 7.31-7.15(m, 5H), 4.67-4.62 (dd, J=9.12, 4.98 Hz, 1H), 3.34 (d, J=0.63 Hz, 1H) 3.22-3.16 (dd, J=13.89, 5.04 Hz, 1H), 2.96-2.89 (dd, J=13.8, 9.2 Hz, 1H), 1.89 (s, 1H)

Comparative Example 2

[0346] ##STR00086##

[0347] (E)-1-(4-bromophenyl)-2-acetamidopropene was used as the hydrogenation substrate, (2R,2′R,3R,3′R)-4,4′-bis(9-methoxy)-3,3′-di-tert-butyl-2,2′,3,3′-tetrahydro-2,2′-d ibenzo[d][1,3]oxaphospholanyl was used as ligand, Rh(nbd).sub.2BF.sub.4 was used as catalyst to prepare the optically active chiral

[0348] (S)-1-(4-bromophenyl)-2-acetamido-propane.

[0349] The reaction was as follows: under nitrogen atmosphere, in a glove box, 1-(4-bromophenyl)-2-acetamidopropene (4 g, 16.6 mmol), Rh(nbd).sub.2BF.sub.4 (0.03 mg, 0.1 μmol), (2R,2′R,3R,3′R)-4,4′-bis(9-methoxy)-3,3′-di-tert-butyl-2,2′,3,3′-tetrahydro-2,2′-d ibenzo[d][1,3]oxaphospholanyl (0.04 mg, 0.1 μmol), and 24 mL of anhydrous methanol were added to the hydrogenation flask and transferred to the autoclave. After sealed, the autoclave was replaced with hydrogen for three times, and was charged with hydrogen to 300 psi. The system was reacted at 25° C. for 12 hours, and then cooled to room temperature. Hydrogen was discharged and the reactor was opened. The crude reaction product solution was filtered through microporous membrane to remove metal ions. After the solution was diluted by isopropanol, chiral AD-H column high performance liquid chromatography was used to measure the conversion rate and ee value of the product (S)-1-(4-bromophenyl)-2-acetamido-propane, which was 91%.

[0350] (S)-1-(4-bromophenyl)-2-acetamido-propane: white solid (yield>99%); 91% ee.

[0351] The ee value was determined by chiral high pressure liquid chromatography; high pressure liquid phase conditions: chiral AD-H column, 25° C., flow rate: 1 mL/min, n-hexane/isopropanol: 95/5, 210 nm, t.sub.1=13.4 min (S), t.sub.2=17.9 min (R).

[0352] .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 1.47 (d, J=4 Hz, 3H), 2.00 (s, 3H), 5.05-5.12 (m, 1H), 5.84 (s, br, 1H), 7.21 (d, J=8 Hz, 2H), 7.47 (d, J=8 Hz, 2H).

Comparative Example 3

[0353] ##STR00087##

[0354] 2-Methylcyclohexenyl 1-acetamide was used as the hydrogenation substrate, the metal complex {(norbornadiene)[(2S,2′S,3S,3′S)-4,4′-bis(9-anthryl)-3,3′-di-tert-butyl-2,2′,3,3′-te trahydro-2,2′-dibenzo[d][1,3]oxaphospholanyl}rhodium tetrafluoroborate was used as catalyst to prepare optically active chiral (1R, 2S)-2-methylcyclohexyl 1-acetamide.

[0355] The reaction was as follows: under nitrogen atmosphere, in a glove box, 2-methylcyclohexenyl 1-acetamide (0.5g, 3.2 mmol), the metal complex {(norbornadiene) [(2S,2′S,3S,3′S)-4,4′-bis(9-anthryl)-3,3′-di-tert-butyl-2,2′,3,3′-tetrahydro-2,2′-dib enzo[d][1,3]oxaphospholanyl}rhodium tetrafluoroborate (2.2 mg, 2.4 μmol), 5 mL of anhydrous methanol were added to the hydrogenation flask and transferred to the autoclave. After sealed, the autoclave was replaced with hydrogen for three times, and hydrogen was charged to 300 psi. The system was reacted at 25° C. for 12 hours, and then cooled to room temperature. Hydrogen was discharged and the reactor was opened. The crude reaction product solution was filtered through a microporous membrane to remove metal ions. After the solution was diluted by isopropanol, chiral AD-H column high performance liquid chromatography was used to measure the conversion rate and ee value of the product (1R, 2S)-2-methylcyclohexyl 1-acetamide, which was 20%.

[0356] (1S,2R)-2-methylcyclohexyl-1-acetamide: white solid (yield>99%); 20% ee.

[0357] The ee value was determined by chiral high pressure liquid chromatography; high pressure liquid phase conditions: chiral AD-H column, 25° C., flow rate: 0.7 mL/min, n-hexane/isopropanol: 95/5, 210 nm, t.sub.1=11.2 min (1R,2S), t.sub.2=12.1 min (1S,2R).

[0358] .sup.1H NMR (400 MHz, CDCl.sub.3) δ: 5.53 (s, 1H) , 4.02-4.07 (m, 1H), 1.99 (s, 3H), 1.84 (m, 1H), 1.17-1.65 (m, 8H),0.86 (d, J=7 Hz, 3H).

Comparative Example 4

[0359] ##STR00088##

[0360] 1,1-Dimethyl-2-acetamidopropene was used as the hydrogenation substrate, (2R,2′R,3R,3′R)-4,4′-bis(9-methoxy)-3,3′-di-tert-butyl-2,2′,3,3′-tetrahydro-2,2′-d ibenzo[d][1,3]oxaphospholanyl was used as ligand, Rh(nbd).sub.2BF.sub.4 was used as catalyst to prepare the optically active chiral

[0361] (S)-1,1-dimethyl-2-acetamido-propane.

[0362] The reaction is as follows: under nitrogen atmosphere, in a glove box, 1,1-dimethyl-2-acetamidopropene (0.1 g, 0.8 mmol), Rh(nbd).sub.2BF.sub.4 (2 mg, 6 μmol), (2R,2′R,3R,3′R)-4,4′-bis(9-methoxy)-3,3′-di-tert-butyl-2,2′,3,3′-tetrahydro-2,2′-d ibenzo[d][1,3]oxaphospholanyl (4 mg, 9 μmol), and 5 mL of anhydrous methanol were added to the hydrogenation flask and transferred to the autoclave. After sealed, the autoclave was replaced with hydrogen for three times, and was charged with hydrogen to 300 psi. The system was reacted at 25° C. for 12 hours, and then cooled to room temperature. Hydrogen was discharged and the reactor was opened. The crude reaction product solution was filtered through a microporous membrane to remove metal ions. After the solution was diluted by isopropanol, chiral AD-H column high performance liquid chromatography was used to measure the conversion rate and ee value of the product (S)-1,1-dimethyl-2-acetamido-propane, which was 98%, yield 8%.

Comparative Example 5

[0363] ##STR00089##

[0364] 2-Methylcyclohexenyl 1-acetamide was used as the hydrogenation substrate, the metal complex {(norbornadiene) [(2 S ,2′ S,3R,3′R)-Tangphos]}rhodium tetrafluoroborate was used as the catalyst to prepare optically active chiral (1R, 2S)-2-methylcyclohexyl 1-acetamide.

[0365] The reaction was as follows: under nitrogen atmosphere, in a glove box, 2-methylcyclohexenyl 1-acetamide (0.5 g, 3.2 mmol), the metal complex {(norbornadiene) [(2S,2′S,3R,3′R)-Tangphos]}rhodium tetrafluoroborate (1.4 mg, 2.4 μmol), 5 mL of anhydrous methanol were added to the hydrogenation flask and transferred to the autoclave. After sealed, the autoclave was replaced with hydrogen for three times, and was charged with hydrogen to 300 psi. The system was reacted at 25° C. for 12 hours, and then cooled to room temperature. Hydrogen was discharged and the reactor was opened. The crude reaction product solution was filtered through a microporous membrane to remove metal ions. After the solution was diluted by isopropanol, chiral AD-H column high performance liquid chromatography was used to measure the conversion rate and ee value of the product (1R, 2S)-2-methylcyclohexyl 1-acetamide, which was 53%.

[0366] (1R, 2S)-2-methylcyclohexyl-1-acetamide: white solid (yield>99%); 53% ee.

[0367] The ee value was determined by chiral high pressure liquid chromatography; high pressure liquid phase conditions: chiral AD-H column, 25° C., flow rate: 0.7 mL/min, n-hexane/isopropanol: 95/5, 210 nm, t.sub.1=11.2 min (1R,2S), t.sub.2=12.1 min (1S,2R).