Method for synthesizing chiral α-phosphorus compounds

Abstract

The present invention provides a method for synthesizing a chiral α-phosphorus compound. The chiral α-phosphorus compound is prepared by asymmetric hydrogenation of compound 1 in a catalytic system of inexpensive metal nickel. The reaction formula for preparing the chiral α-phosphorus compound from compound 1 is as follows: R3 is selected from one of phenyl, substituted phenyl, naphthyl, and cyclohexyl; R' is a C1-C6 straight-chain alkyl or H; R1 and R2 are independently selected from hydroxyl, alkoxy, phenyl, and O ‑ The catalyst used in the preparation of the chiral α-phosphorus compound from compound 1 is a catalyst obtained by complexing a chiral ligand (S,S)-Ph-BPE with a nickel salt. This catalyst utilizes abundant and inexpensive nickel salts and a commercial chiral ligand (S,S)-Ph-BPE as a catalytic system. These ligands are readily available, inexpensive, and abundant, with high catalytic activity, efficiency, and good enantioselectivity. The process is simple to operate, environmentally friendly, and has broad prospects for industrialization.

Description

Technical Field

[0001] The patent of this invention relates to the field of organic and pharmaceutical synthesis, and in particular refers to a method for efficiently synthesizing chiral α-phosphorus compounds by catalyzing α-substituted α,β-unsaturated phosphorus oxides, phosphates, and phosphoric acid with cheap metal nickel. Background Art

[0002] Chiral α-phosphorus compounds are not only important backbones for many pharmaceuticals, pesticides, and bioactive molecules, but also crucial intermediates for obtaining chiral organophosphorus compounds. For example, the nonsteroidal anti-inflammatory agent naproxen analog (+)-6-methoxy-α-methyl-2-naphthylmethyl phosphate exhibits excellent anti-inflammatory and analgesic activity; fosmidomycin analogs inhibit the growth of Plasmodium falciparum; (S,R)-alafosfalin is a highly effective antibacterial agent against both Gram-positive and Gram-negative microorganisms; (R)-1-amino-3,4-dichlorobenzylphosphonic acid effectively inhibits phenylalanine ammonia lyase; and (N)-methanocarba phosphonate analogues 5'-AMP are protective agents for the treatment of heart failure. Chiral phosphates can act as both renin inhibitors and antibacterial agents.

[0003]

[0004] Due to the significant application value of chiral α-phosphorus compounds in pharmaceuticals and other fields, methodologies for their synthesis have been intensively studied, and numerous synthetic strategies have been developed. Currently, asymmetric hydrogenation is one of the most direct and efficient methods for synthesizing chiral α-phosphorus compounds. In the past few decades, a few examples have utilized catalysts based on precious metals such as rhodium, iridium, and ruthenium complexed with chiral phosphine ligands to asymmetric hydrogenate α-substituted α,β-unsaturated phosphorus oxides, phosphates, and phosphoric acid to obtain chiral α-phosphorus compounds. However, the high cost, high toxicity, limited crustal reserves, and heavy metal environmental pollution of these precious metal catalytic systems significantly limit their industrial potential. The development of inexpensive, non-toxic, environmentally friendly, and abundant nickel asymmetric catalytic hydrogenation reaction systems is in line with the requirements and trends of sustainable development in modern chemistry. Currently, the synthesis of chiral α-phosphorus compounds using inexpensive nickel catalytic systems for asymmetric hydrogenation remains unreported, presenting significant challenges and requiring the development of efficient catalytic systems.

[0005] Therefore, it is necessary to develop a method for synthesizing chiral α-phosphorus compounds that is easy to industrialize. Summary of the Invention

[0006] The present invention aims to solve, at least to a certain extent, one of the technical problems existing in the prior art. Thus, in a first aspect of the present invention, the present invention provides a method for synthesizing a chiral α-phosphorus compound. The chiral α-phosphorus compound is prepared by subjecting Compound 1 to an asymmetric hydrogenation reaction. The reaction formula for preparing the chiral α-phosphorus compound from Compound 1 is shown below:

[0007]

[0008] R3 is selected from phenyl, substituted phenyl, naphthyl, cyclohexyl, R' is a C1-C6 straight chain alkyl or H, R1 and R2 are independently selected from hydroxyl, alkoxy, phenyl and O - Preferably, the substituted phenyl group is a halogen-substituted phenyl group, an alkyl-substituted phenyl group, an alkoxy-substituted phenyl group or a halogen-alkyl-substituted phenyl group.

[0009] The catalyst used in the preparation of the chiral α-phosphorus compound from the compound 1 is a catalyst obtained by complexing the chiral ligand (S, S)-Ph-BPE with a nickel salt.

[0010] The catalytic system is a catalytic system of cheap metal nickel.

[0011] In one or more embodiments of the present invention, the asymmetric hydrogenation reaction temperature is controlled to be 60-80°C.

[0012] In one or more embodiments of the present invention, the reaction is carried out under a hydrogen atmosphere, the hydrogen pressure is controlled to be 60 to 80 atmospheres, and the reaction time is controlled to be 24 to 36 hours.

[0013] In one or more embodiments of the present invention, the catalyst is obtained by complexing a chiral ligand (S,S)-Ph-BPE with a nickel salt;

[0014] The structure of the chiral ligand (S,S)-Ph-BPE is as follows:

[0015]

[0016] In one or more embodiments of the present invention, the complexation reaction is carried out in a solvent, and the solvent is an alcohol, preferably methanol or ethanol.

[0017] In one or more embodiments of the present invention, the molar ratio of the nickel salt to the chiral ligand (S,S)-Ph-BPE is controlled to be 1:1 to 1.2.

[0018] In one or more embodiments of the present invention, the reaction temperature of the complexation reaction is controlled to be 15-35°C.

[0019] In one or more embodiments of the present invention, the reaction time of the complexation reaction is controlled to be 36 hours.

[0020] In one or more embodiments of the present invention, the nickel salt is Ni(OAc)2.

[0021] In one or more embodiments of the present invention, a method for synthesizing a chiral α-phosphorus compound comprises the following steps:

[0022] Step 1): complexation reaction between the chiral ligand (S,S)-Ph-BPE and nickel salt;

[0023] Step 2): Compound 1 is added to the reaction solution of step 1) to carry out an asymmetric hydrogenation reaction to obtain the chiral α-phosphorus compound.

[0024] The beneficial effects of the present invention are:

[0025] 1. The present invention provides a method for preparing a chiral α-phosphorus compound, which uses abundant and inexpensive metal nickel salts and a commercial chiral ligand (S,S)-Ph-BPE as a catalytic system. The system is rich in source, easily available, low in price, high in catalytic activity and efficiency, and good in enantioselectivity.

[0026] 2. The present invention provides a method for preparing chiral α-phosphorus compounds, which is applicable to most substrates and can achieve 100% complete conversion and over 90% enantioselectivity. In addition, it has high atom economy and a wide range of substrate applicability of the catalytic system. It is currently the first method for obtaining chiral α-phosphorus compounds such as α-phosphorus oxides, α-phosphates and α-phosphoric acid through abundant and inexpensive metal-catalyzed hydrogenation. It is simple to operate, environmentally friendly, and has broad prospects for industrialization. DETAILED DESCRIPTION

[0027] The present invention will be further described below in conjunction with specific examples, but the following examples are only used to illustrate the present invention and should not be considered as limiting the scope of the present invention. In the following examples, if no specific conditions are specified, the conditions according to normal conditions or manufacturer's recommendations are carried out, and the method used, if not otherwise specified, is a conventional method well known in the art, and the consumable materials and reagents used, if not otherwise specified, are commercially available. Unless otherwise indicated, the professional and scientific terms used herein are identical in meaning to those skilled in the art. In addition, any method or material similar or equivalent to the described content can also be applied to the present invention.

[0028] This example is based on the technical solution of the present invention and provides detailed implementation methods and specific operating procedures. However, the scope of protection of the present invention is obviously not limited to the following example. (+)-6-methoxy-α-methyl-2-naphthylmethylphosphonic acid, (S,R)-alafosfalin, (R)-1-amino-3,4-dichlorobenzylphosphonic acid, (N)-methanocarba phosphonate analogues 5'-AMP, the above-mentioned renin inhibitor, and antibacterial agent can also be synthesized using the method of the present invention. In the following examples, "mol %" represents the molar percentage of the substance relative to the α-substituted α,β-unsaturated phosphorus oxide, phosphate ester, and phosphoric acid compound.

[0029] Example 1: Preparation of (S)-diphenyl(1-phenylethyl)phosphine oxide from diphenyl(1-phenylvinyl)phosphine oxide

[0030]

[0031] Under a high-purity argon atmosphere, Ni(OAc)2 (14.14 mg, 0.08 mmol) and the chiral ligand (S,S)-Ph-BPE (44.58 mg, 0.088 mmol) were dissolved in anhydrous hexafluoroisopropanol (7.2 mL) and anhydrous methanol (0.8 mL). The mixture was stirred at 15-35°C for 36 hours to obtain a clear solution. 250 μL of the clear solution was added to diphenyl(1-phenylvinyl)phosphine oxide (0.1 mmol) and hexafluoroisopropanol (0.75 mL). The reaction system was placed in an autoclave and stirred at 70°C under H2 (70 atm) for 36 hours. The solvent was removed under reduced pressure, and the product was separated by column chromatography (silica gel, eluent: ethyl acetate) to obtain pure (S)-diphenyl(1-phenylethyl)phosphine oxide (99% yield). HPLC analysis of the product revealed an ee value of 97%. 1H NMR(400MHz,Chloroform-d)δ7.92–7.85(m,2H),7.58–7.50(m,3H),7.47–7.42(m,2H),7.37–7.3 4(m,1H),7.28–7.27(m,1H),7.25–7.15(m,6H),3.64–3.56(m,1H),1.58(dd,J=16.1,7.4Hz,3H). 13 C NMR (101MHz, Chloroform-d) δ 137.8 (d, J = 5.5Hz), 132.3 (d, J = 14.5Hz), 131.7 (d, J = 2.8Hz), 131.4, 131.3 (d, J = 2.8Hz), 131.1 (d, J = 8.7Hz), 129.2(d,J=5.5Hz), 128.6(d,J=11.2Hz), 128.23, 128.22, 128.0(d,J=11.5Hz), 126.9(d,J=2.5Hz), 40.9(d,J=67.1Hz), 15.4(d,J=2.9Hz). 31 P NMR (162MHz,CDCl3)δ33.61.

[0032] In addition, when the catalyst loading was reduced to 2 mol%, the reaction could be completed even when the amount of the reaction substrate diphenyl(1-phenylvinyl)phosphine oxide was increased from 0.1 mmol to 0.5 mmol, and the target product was obtained with a yield of 95% and 97% ee.

[0033] Example 2: Preparation of (S)-(1-(4-fluorophenyl)ethyl)diphenylphosphine oxide from (1-(4-fluorophenyl)vinyl)diphenylphosphine oxide

[0034]

[0035] Under a high-purity argon atmosphere, Ni(OAc)2 (14.14 mg, 0.08 mmol) and the chiral ligand (S,S)-Ph-BPE (44.58 mg, 0.088 mmol) were dissolved in anhydrous hexafluoroisopropanol (7.2 mL) and anhydrous methanol (0.8 mL). The mixture was stirred at 15-35°C for 36 hours to obtain a clear solution. 250 μL of the clear solution was added to (1-(4-fluorophenyl)vinyl)diphenylphosphine oxide (0.1 mmol) and hexafluoroisopropanol (0.75 mL). The reaction system was placed in an autoclave and stirred at 70°C under H2 (70 atm) for 36 hours. The solvent was removed under reduced pressure, and the product was separated by column chromatography (silica gel column, eluent: ethyl acetate) to obtain pure (S)-(1-(4-fluorophenyl)ethyl)diphenylphosphine oxide (99% yield). The product was analyzed by HPLC, and the ee value was determined to be 98% ee. 1 H NMR(400MHz,Chloroform-d)δ7.93–7.87(m,2H),7.59–7.50(m,3H),7.48–7.42(m,2H),7.39–7.35(m,1H), 7.30–7.27(m,2H),7.20–7.16(m,2H),6.89–6.85(m,2H),3.63–3.55(m,1H),1.55(dd,J=16.0,7.3Hz,3H). 13 C NMR (101MHz, CDCl3) δ161.8 (d, J = 243.9Hz), 133.5, 132.3, 132.0, 131.83, 131.80, 131.42, 131.40, 131.4, 131.33, 131.27, 131.1, 131.0, 130 .9,130.7,130.60,130.57,130.52,128.8,128.7,128.2,128.1,115.2 3,115.21,115.01,114.99,40.1(d,J=67.1Hz),15.5(d,J=2.9Hz).(Due to CP and CF coupling and the complexity of the spectrum,doublets in the aromatic region cannot be assigned and they are listed assinglets). 31 P NMR (162 MHz, CDCl3) δ 33.52.

[0036] Example 3: Preparation of (S)-(1-(3-fluorophenyl)ethyl)diphenylphosphine oxide from (1-(3-fluorophenyl)vinyl)diphenylphosphine oxide

[0037]

[0038] Under a high-purity argon atmosphere, Ni(OAc)2 (14.14 mg, 0.08 mmol) and the chiral ligand (S,S)-Ph-BPE (44.58 mg, 0.088 mmol) were dissolved in anhydrous hexafluoroisopropanol (7.2 mL) and anhydrous methanol (0.8 mL). The mixture was stirred at 15-35°C for 36 hours to obtain a clear solution. 250 μL of the clear solution was added to (1-(3-fluorophenyl)vinyl)diphenylphosphine oxide (0.1 mmol) and hexafluoroisopropanol (0.75 mL). The reaction system was placed in an autoclave and stirred at 70°C under H2 (70 atm) for 36 hours. The solvent was removed under reduced pressure, and the product was separated by column chromatography (silica gel column, eluent: ethyl acetate) to obtain pure (S)-(1-(3-fluorophenyl)ethyl)diphenylphosphine oxide (94% yield). The product was analyzed by HPLC, and the ee value was determined to be 96% ee. 1 H NMR(400MHz,Chloroform-d)δ7.92–7.87(m,2H),7.59–7.45(m,5H),7.40–7.35(m,1H),7.30–7.26(m,2H), 7.16–7.11(m,1H),7.01–6.92(m,2H),6.87–6.82(m,1H),3.63–3.56(m,1H),1.56(dd,J=15.9,7.3Hz,3H). 1313C NMR (101 MHz, Chloroform-d) δ 162.6 (d, J = 246.0 Hz), 140.5 (dd, J = 7.5, 5.5 Hz), 132.1 (d, J = 20.6 Hz), 131.9 (d, J = 2.9 Hz), 131.5 (d, J = 2.8 Hz), 131.3 (d, J = 8.5 Hz), 131.1 (d, J = 16.5 Hz), 131.0 (d, J = 8.8 Hz), 129.6 (dd, J = 8.3, 2.1 Hz), 128.8 (d, J = 11.3 Hz), 128.2 (d, J = 11.5 Hz), 124.9 (dd, J = 5.6, 2.9 Hz), 116.1 (dd, J = 22.0, 5.5 Hz), 113.9 (dd, J = 21.0, 2.6 Hz), 40.8 (dd, J = 66.9, 1.7 Hz), 15.4 (d, J = 2.9 Hz). 31 31P NMR (162 MHz, CDCl3) δ 33.12. HRMS (ESI): [C 20 H 18 FOP + H + Calc. 325.1152, found 325.1146.

[0039] Example 4: Preparation of (S)-(1-(2-fluorophenyl)ethyl)diphenylphosphine oxide from (1-(2-fluorophenyl)vinyl)diphenylphosphine oxide

[0040]

[0041] Under a high-purity argon atmosphere, Ni(OAc)2 (14.14 mg, 0.08 mmol) and the chiral ligand (S,S)-Ph-BPE (44.58 mg, 0.088 mmol) were dissolved in anhydrous hexafluoroisopropanol (7.2 mL) and anhydrous methanol (0.8 mL). The mixture was stirred at 15-35°C for 36 hours to obtain a clear solution. 250 μL of the clear solution was added to (1-(2-fluorophenyl)vinyl)diphenylphosphine oxide (0.1 mmol) and hexafluoroisopropanol (0.75 mL). The reaction system was placed in an autoclave and stirred at 70°C under H2 (70 atm) for 36 hours. The solvent was removed under reduced pressure, and the product was separated by column chromatography (silica gel column, eluent: ethyl acetate) to obtain pure (S)-(1-(2-fluorophenyl)ethyl)diphenylphosphine oxide (98% yield). The product was analyzed by HPLC, and the ee value was determined to be 98% ee. 1 H NMR(400MHz,Chloroform-d)δ7.97–7.92(m,2H),7.75–7.73(m,1H),7.48(m,5H),7.36–7.31(m,1H),7. 27–7.22(m,2H),7.14–7.07(m,2H),6.82–6.77(m,1H),4.14–4.07(m,1H),1.54(dd,J=15.8,7.3Hz,3H). 13 C NMR (101MHz, CDCl3) δ159.7 (dd, J=245.0, 6.8Hz), 132.3 (d, J=11.3Hz), 131.8 (d, J=2.6Hz) ,131.4(d,J=2.9Hz),131.2(d,J=8.6Hz),130.7(d,J=8.9Hz),130.3(d,J=3.7Hz),128.7(d ,J=11.2Hz),128.3(dd,J=8.4,2.4Hz),128.0(d,J=11.7Hz),125.4(dd,J=245.0,5.0Hz),1 24.4(d,J=3.4Hz), 114.7(dd,J=23.2,1.8Hz), 31.1(dd,J=69.0,2.3Hz), 14.8(d,J=2.9Hz). 31 P NMR(162MHz,CDCl3)δ33.53.HRMS(ESI):[C 20 H 18 FOP+H + ]Calc.325.1152,found325.114.

[0042] Example 5: Preparation of (S)-diphenyl(1-(m-tolyl)ethyl)phosphine oxide from diphenyl(1-(m-tolyl)vinyl)phosphine oxide

[0043]

[0044] Under a high-purity argon atmosphere, Ni(OAc)2 (14.14 mg, 0.08 mmol) and the chiral ligand (S,S)-Ph-BPE (44.58 mg, 0.088 mmol) were dissolved in anhydrous hexafluoroisopropanol (7.2 mL) and anhydrous methanol (0.8 mL). The mixture was stirred at 15-35°C for 36 hours to obtain a clear solution. 250 μL of the clear solution was added to diphenyl(1-(m-tolyl)vinyl)phosphine oxide (0.1 mmol) and hexafluoroisopropanol (0.75 mL). The reaction system was placed in an autoclave and stirred at 70°C under H2 (70 atm) for 36 hours. The solvent was removed under reduced pressure, and the product was separated by column chromatography (silica gel column, eluent: ethyl acetate) to obtain pure (S)-diphenyl(1-(m-tolyl)ethyl)phosphine oxide (99% yield). The product was analyzed by HPLC, and the ee value was determined to be 96% ee. 1 H NMR(400MHz,Chloroform-d)δ7.91–7.86(m,2H),7.57–7.50(m,3H),7.47–7.42(m,2H),7.38–7.34(m,1H),7.28– 7.24(m,1H),7.24–7.18(m,1H),7.09–6.96(m,4H),3.60–3.53(m,1H),2.22(s,3H),1.56(dd,J=16.1,7.3Hz,3H). 13C NMR (101MHz, Chloroform-d) δ 137.8 (d, J = 2.2 Hz), 137.6 (d, J = 5.6 Hz), 132.3 (d, J = 9. 9Hz),131.7(d,J=2.7Hz),131.4(d,J=8.2Hz),131.3(d,J=2.5Hz),131.2(d,J=8.8Hz) ,129.9(d,J=5.4Hz),128.6(d,J=11.2Hz),128.1(d,J=2.1Hz),127.9(d,J=11.6Hz), 127.6(d,J=2.6Hz), 126.2(d,J=5.5Hz), 40.9(d,J=67.2Hz), 21.3, 15.3(d,J=2.8Hz). 31 P NMR (162 MHz, CDCl3) δ 33.78.

[0045] Example 6: Preparation of (S)-(1-(4-methoxyphenyl)ethyl)diphenylphosphine oxide from (1-(4-methoxyphenyl)vinyl)diphenylphosphine oxide

[0046]

[0047] Under a high-purity argon atmosphere, Ni(OAc)2 (14.14 mg, 0.08 mmol) and the chiral ligand (S,S)-Ph-BPE (44.58 mg, 0.088 mmol) were dissolved in anhydrous hexafluoroisopropanol (7.2 mL) and anhydrous methanol (0.8 mL). The mixture was stirred at 15-35°C for 36 hours to obtain a clear solution. 250 μL of the clear solution was added to (1-(4-methoxyphenyl)vinyl)diphenylphosphine oxide (0.1 mmol) and hexafluoroisopropanol (0.75 mL). The reaction system was placed in an autoclave and stirred at 70°C under H2 (70 atm) for 36 hours. The solvent was removed under reduced pressure, and the product was separated by column chromatography (silica gel column, eluent: ethyl acetate) to obtain pure (S)-(1-(4-methoxyphenyl)ethyl)diphenylphosphine oxide (95% yield). The product was analyzed by HPLC, and the ee value was measured (94% ee). 11H NMR (400 MHz, Chloroform-d) δ 7.91–7.86 (m, 2H), 7.55–7.43 (m, 5H), 7.39–7.34 (m, 1H), 7.29–7.26 (m, 2H), 7.13–7.11 (m, 2H), 6.74–6.72 (m, 2H), 3.75 (s, 3H), 3.60–3.53 (m, 1H), 1.54 (dd, J = 16.1, 7.3 Hz, 3H). 13 13C NMR (101 MHz, CDCl3) δ 158.5 (d, J = 2.5 Hz), 131.7 (d, J = 2.4 Hz), 131.4 (d, J = 9.0 Hz), 131.2 (d, J = 8.9 Hz), 130.2 (d, J = 5.4 Hz), 129.5 (d, J = 5.7 Hz), 128.6 (d, J = 11.2 Hz), 128.1 (d, J = 11.5 Hz), 127.9, 113.7 (d, J = 2.0 Hz), 55.1, 40.9 (d, J = 67.3 Hz), 15.5 (d, J = 2.4 Hz). 31 31P NMR (162 MHz, CDCl3) δ 33.76.

[0048] Example 7: Preparation of (S)-diphenyl(1-(4-(trifluoromethyl)phenyl)ethyl)phosphine oxide from diphenyl(1-(4-(trifluoromethyl)phenyl)vinyl)phosphine oxide

[0049]

[0050] Under a high-purity argon atmosphere, Ni(OAc)2 (14.14 mg, 0.08 mmol) and the chiral ligand (S,S)-Ph-BPE (44.58 mg, 0.088 mmol) were dissolved in anhydrous hexafluoroisopropanol (7.2 mL) and anhydrous methanol (0.8 mL). The mixture was stirred at 15-35°C for 36 hours to obtain a clear solution. 250 μL of the clear solution was added to diphenyl(1-(4-(trifluoromethyl)phenyl)vinyl)phosphine oxide (0.1 mmol) and hexafluoroisopropanol (0.75 mL). The reaction system was placed in an autoclave and stirred at 70°C under H2 (70 atm) for 36 hours. The solvent was removed under reduced pressure, and the product was separated by column chromatography (silica gel column, eluent: ethyl acetate) to obtain pure (S)-diphenyl(1-(4-(trifluoromethyl)phenyl)ethyl)phosphine oxide (99% yield). The product was analyzed by HPLC, and the ee value was determined to be 96% ee. 1 H NMR(400MHz,Chloroform-d)δ7.93–7.88(m,2H),7.60–7.51(m,3H),7.49–7.42(m,4H), 7.40–7.33(m,3H),7.30–7.28(m,2H),3.71–3.63(m,1H),1.58(dd,J=15.9,7.3Hz,3H). 13 C NMR (101MHz, CDCl3) δ142.2 (d, J = 5.4Hz), 131.92 (d, J = 2.7Hz), 131.90 (d, J = 30.9Hz), 131.6 (d, J = 2.8Hz), 131.3 (d, J = 8.6Hz), 131.1, 130.9 (d, J = 27. 6Hz),130.8,129.4(d,J=5.3Hz),128.8(d,J=11.3Hz),128.2(d,J=11.5Hz ), 124.1 (q, J = 273.2Hz), 125.1 (m), 40.8 (d, J = 65.8Hz), 15.3 (d, J = 2.9Hz). 31 P NMR (162MHz,CDCl3)δ32.93.

[0051] Example 8: Preparation of (S)-(1-(4-pentylphenyl)ethyl)diphenylphosphine oxide from (1-(4-pentylphenyl)vinyl)diphenylphosphine oxide

[0052]

[0053] Under a high-purity argon atmosphere, Ni(OAc)2 (14.14 mg, 0.08 mmol) and the chiral ligand (S,S)-Ph-BPE (44.58 mg, 0.088 mmol) were dissolved in anhydrous hexafluoroisopropanol (7.2 mL) and anhydrous methanol (0.8 mL). The mixture was stirred at 15-35°C for 36 hours to obtain a clear solution. 250 μL of the clear solution was added to (1-(4-pentylphenyl)vinyl)diphenylphosphine oxide (0.1 mmol) and hexafluoroisopropanol (0.75 mL). The reaction system was placed in an autoclave and stirred at 70°C under H2 (70 atm) for 36 hours. The solvent was removed under reduced pressure, and the product was separated by column chromatography (silica gel column, eluent: ethyl acetate) to obtain pure (S)-(1-(4-pentylphenyl)ethyl)diphenylphosphine oxide (99% yield). The product was analyzed by HPLC, and the ee value was determined to be 97% ee. 1 H NMR(400MHz,Chloroform-d)δ7.91–7.86(m,2H),7.57–7.50(m,3H),7.45–7.40(m,2H),7.37–7.33(m,1H),7.25–7.22(m,2H ),7.11–6.98(m,4H),3.61–3.53(m,1H),2.51(t,J=7.7Hz,2H),1.59–1.51(m,3H),1.32–1.22(m,6H),0.88(t,J=7.0Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ141.5(d,J=2.7Hz),134.7(d,J=5.7Hz),132.4(d,J=2 0.0Hz), 131.7 (d, J = 2.7Hz), 131.4 (d, J = 15.7Hz), 131.4 (d, J = 8.4Hz), 131.22, 131. 2(d,J=6.2Hz),129.0(d,J=5.4Hz),128.6(d,J=11.1Hz),128.3(d,J=2.1Hz),127.9 (d,J=11.5Hz),40.5(d,J=67.2Hz),35.4,31.3,31.0,22.5,15.3(d,J=2.6Hz),14.0. 31 P NMR (162 MHz, CDCl3) δ 33.87.

[0054] Example 9: Preparation of (S)-(1-(4-butylphenyl)ethyl)diphenylphosphine oxide from (1-(4-butylphenyl)vinyl)diphenylphosphine oxide

[0055]

[0056] Under a high-purity argon atmosphere, Ni(OAc)2 (14.14 mg, 0.08 mmol) and the chiral ligand (S,S)-Ph-BPE (44.58 mg, 0.088 mmol) were dissolved in anhydrous hexafluoroisopropanol (7.2 mL) and anhydrous methanol (0.8 mL). The mixture was stirred at 15-35°C for 36 hours to obtain a clear solution. 250 μL of the clear solution was added to (1-(4-butylphenyl)vinyl)diphenylphosphine oxide (0.1 mmol) and hexafluoroisopropanol (0.75 mL). The reaction system was placed in an autoclave and stirred at 70°C under H2 (70 atm) for 36 hours. The solvent was removed under reduced pressure, and the product was separated by column chromatography (silica gel column, eluent: ethyl acetate) to obtain pure (S)-(1-(4-butylphenyl)ethyl)diphenylphosphine oxide (99% yield). The product was analyzed by HPLC, and the ee value was determined to be 99%. 1 H NMR(400MHz,Chloroform-d)δ7.91–7.86(m,2H),7.58–7.49(m,3H),7.44–7.33(m,3H),7.25–7.14(m,2H),7.10–6 .98(m,4H),3.61–3.53(m,1H),2.52(t,J=7.7Hz,2H),1.59–1.49(m,2H),1.34–1.25(m,1H),0.90(t,J=7.3Hz,3H). 13C NMR(101MHz,Chloroform-d)δ141.5(d,J=2.9Hz),134.7(d,J=5.8Hz),132.4(d,J=20.5Hz),131.6(d,J=2.7Hz),131.4(d,J=8.3Hz),131.2,131.1,129 .0(d,J=5.4Hz),128.6(d,J=11.1Hz),128.3(d,J=2.2Hz),127.9(d,J=5.1H z),127.85,40.5(d,J=67.0Hz),35.1,33.4,22.2,15.3(d,J=2.8Hz),13.9. 31 P NMR (162 MHz, CDCl3) δ 33.88.

[0057] Example 10: Preparation of (S)-(1-(4-ethylphenyl)ethyl)diphenylphosphine oxide from (1-(4-ethylphenyl)vinyl)diphenylphosphine oxide

[0058]

[0059] Under a high-purity argon atmosphere, Ni(OAc)2 (14.14 mg, 0.08 mmol) and the chiral ligand (S,S)-Ph-BPE (44.58 mg, 0.088 mmol) were dissolved in anhydrous hexafluoroisopropanol (7.2 mL) and anhydrous methanol (0.8 mL). The mixture was stirred at 15-35°C for 36 hours to obtain a clear solution. 250 μL of the clear solution was added to (1-(4-ethylphenyl)vinyl)diphenylphosphine oxide (0.1 mmol) and hexafluoroisopropanol (0.75 mL). The reaction system was placed in an autoclave and stirred at 70°C under H2 (70 atm) for 36 hours. The solvent was removed under reduced pressure, and the product was separated by column chromatography (silica gel column, eluent: ethyl acetate) to obtain pure (S)-(1-(4-ethylphenyl)ethyl)diphenylphosphine oxide (95% yield). The product was analyzed by HPLC, and the ee value was measured (98% ee). 11H NMR (400 MHz, Chloroform-d) δ 7.91–7.86 (m, 2H), 7.57–7.43 (m, 5H), 7.38–7.34 (m, 1H), 7.31–7.26 (m, 1H), 7.25–7.20 (m, 1H), 7.12–7.00 (m, 4H), 3.62–3.55 (m, 1H), 2.56 (q, J = 7.6 Hz, 2H), 1.56 (dd, J = 16.2, 7.4 Hz, 3H), 1.17 (t, J = 7.6 Hz, 3H). 13 13C NMR (101 MHz, Chloroform-d) δ 142.9 (d, J = 2.8 Hz), 134.8 (d, J = 5.6 Hz), 132.4 (d, J = 12.1 Hz), 131.6 (d, J = 2.7 Hz), 131.5 (d, J = 7.7 Hz), 131.4 (d, J = 5.0 Hz), 131.22, 131.19, 129.1 (d, J = 5.4 Hz), 128.6 (d, J = 11.0 Hz), 128.0 (d, J = 11.5 Hz), 127.7 (d, J = 2.1 Hz), 40.4 (d, J = 67.0 Hz), 28.4, 15.5, 15.4 (d, J = 2.7 Hz). 31 31P NMR (162 MHz, CDCl3) δ 33.78. HRMS (ESI): [C 22 H 23 OP+H + Calc. 335.1560, found 335.1553.

[0060] Example 11: Preparation of ((1R,1'R)-1,3-phenylenebis(ethane-1,1-diyl))bis(diphenylphosphine oxide) from (1,3-phenylenebis(ethene-1,1-diyl))bis(diphenylphosphine oxide)

[0061]

[0062] Under a high-purity argon atmosphere, Ni(OAc)2 (14.14 mg, 0.08 mmol) and the chiral ligand (S,S)-Ph-BPE (44.58 mg, 0.088 mmol) were dissolved in anhydrous hexafluoroisopropanol (7.2 mL) and anhydrous methanol (0.8 mL). The mixture was stirred at 15-35°C for 36 hours to obtain a clear solution. 250 μL of the clear solution was added to (1,3-phenylenebis(ethene-1,1-diyl))bis(diphenylphosphine oxide) (0.1 mmol) and hexafluoroisopropanol (0.75 mL). The reaction system was placed in an autoclave and stirred at 70°C under H2 (70 atm) for 36 hours. The solvent was removed under reduced pressure, and the product was separated by column chromatography (silica gel column, eluent: ethyl acetate) to obtain pure product ((1R,1'R)-1,3-phenylenebis(ethane-1,1-diyl))bis(diphenylphosphine oxide) (99% yield). The product was analyzed by HPLC, and the ee value was measured (>99% ee). 1 H NMR(400MHz,Chloroform-d)δ7.89–7.84(m,4H),7.56–7.48(m,6H),7.41–7.36(m,4H),7.32–7.28(m,3H),7.23–7.18(m,4H),7.10–7.05(m,2H),6.99 -6.95(m,1H),3.57–3.50(m,2H),1.49(dd,J=16.1,7.3Hz,1H), 13 C NMR(101MHz,Chloroform-d)δ138.2(d,J=5.7Hz),132.2(d,J=3.7Hz),131.7(d,J=2.5Hz),131.32,131.3,131.23,131.1(d,J=8.9Hz ), 130.1 (d, J = 5.8Hz), 128.6 (d, J = 11.3Hz), 128.4, 128.2 (d, J = 11.7Hz), 127.8 (d, J = 5.3Hz), 40.6 (d, J = 67.5Hz), 15.8 (d, J = 2.8Hz). 31 P NMR (162 MHz, CDCl3) δ 34.25.

[0063] Example 12: Preparation of dimethyl(S)-(1-(o-tolyl)ethyl)phosphonate from dimethyl(1-(o-tolyl)vinyl)phosphonate

[0064]

[0065] Under a high-purity argon atmosphere, Ni(OAc)2 (14.14 mg, 0.08 mmol) and the chiral ligand (S,S)-Ph-BPE (44.58 mg, 0.088 mmol) were dissolved in anhydrous hexafluoroisopropanol (7.2 mL) and anhydrous methanol (0.8 mL). The mixture was stirred at 15-35°C for 36 hours to obtain a clear solution. 250 μL of the clear solution was added to dimethyl(1-(o-tolyl)vinyl)phosphonate (0.1 mmol) and hexafluoroisopropanol (0.75 mL). The reaction system was placed in an autoclave and stirred at 70°C under H2 (70 atm) for 36 hours. The solvent was removed under reduced pressure, and the product was separated by column chromatography (silica gel column, eluent: ethyl acetate) to obtain pure dimethyl(S)-(1-(o-tolyl)ethyl)phosphonate (99% yield). The product was analyzed by HPLC, and the ee value was determined to be 96% ee. 1 H NMR(400MHz,Chloroform-d)δ7.48–7.46(m,1H),7.23–7.12(m,3H),3.69(d,J=10.6Hz,3 H),3.49(d,J=10.3Hz,3H),3.56–3.40(m,1H),2.37(s,3H),1.56(dd,J=18.7,7.3Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ136.2(d,J=8.2Hz),136.0(d,J=6.6Hz),130.4(d,J=2.5Hz),127.8(d,J=4.7Hz),126.9( d,J=3.2Hz), 126.3(d,J=3.2Hz), 53.3(d,J=6.9Hz), 52.8(d,J=7.4Hz), 33.1(d,J=138.4Hz), 19.9, 15.8(d,J=5.0Hz). 31 P NMR (162 MHz, CDCl3) δ 32.86.

[0066] Example 13: Preparation of dimethyl(S)-(1-(4-chlorophenyl)ethyl)phosphonate from dimethyl(1-(4-chlorophenyl)vinyl)phosphonate

[0067]

[0068] Under a high-purity argon atmosphere, Ni(OAc)2 (14.14 mg, 0.08 mmol) and the chiral ligand (S,S)-Ph-BPE (44.58 mg, 0.088 mmol) were dissolved in anhydrous hexafluoroisopropanol (7.2 mL) and anhydrous methanol (0.8 mL). The mixture was stirred at 15-35°C for 36 hours to obtain a clear solution. 250 μL of the clear solution was added to dimethyl(1-(4-chlorophenyl)vinyl)phosphonate (0.1 mmol) and hexafluoroisopropanol (0.75 mL). The reaction system was placed in an autoclave and stirred at 70°C under H2 (70 atm) for 36 hours. The solvent was removed under reduced pressure, and the product was separated by column chromatography (silica gel column, eluent: ethyl acetate) to obtain pure dimethyl(S)-(1-(4-chlorophenyl)ethyl)phosphonate (95% yield). The product was analyzed by HPLC, and the ee value was determined to be 90% ee. 1 H NMR (400MHz, Chloroform-d) δ7.30–7.26(m,4H),3.67(d,J=10.7Hz,3H),3.54(d,J=10.6Hz,3H),3.21–3.10(m,1H),1.55(dd,J=18.5,7.4Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ136.2(d,J=7.0Hz),133.0(d,J=3.9Hz),129.9(d,J=6.6Hz),128 .7(d,J=2.9Hz), 53.4(d,J=7.0Hz), 52.9(d,J=7.2Hz), 37.4(d,J=138.6Hz), 15.4(d,J=5.2Hz). 31 P NMR (162 MHz, CDCl3) δ 31.45.

[0069] Example 14: Preparation of dimethyl(S)-(1-(2-chlorophenyl)ethyl)phosphonate from dimethyl(1-(2-chlorophenyl)vinyl)phosphonate

[0070]

[0071] Under a high-purity argon atmosphere, Ni(OAc)2 (14.14 mg, 0.08 mmol) and the chiral ligand (S,S)-Ph-BPE (44.58 mg, 0.088 mmol) were dissolved in anhydrous hexafluoroisopropanol (7.2 mL) and anhydrous methanol (0.8 mL). The mixture was stirred at 15-35°C for 36 hours to obtain a clear solution. 250 μL of the clear solution was added to dimethyl(1-(2-chlorophenyl)vinyl)phosphonate (0.1 mmol) and hexafluoroisopropanol (0.75 mL). The reaction system was placed in an autoclave and stirred at 70°C under H2 (70 atm) for 36 hours. The solvent was removed under reduced pressure, and the product was separated by column chromatography (silica gel column, eluent: ethyl acetate) to obtain pure dimethyl(S)-(1-(2-chlorophenyl)ethyl)phosphonate (97% yield). The product was analyzed by HPLC, and the ee value was determined to be 84% ee. 1 H NMR(400MHz,Chloroform-d)δ7.62–7.59(m,1H),7.39–7.36(m,1H),7.29–7.27(m,1H),7.21–7.16(m ,1H),3.97–3.86(m,1H),3.75(d,J=10.7Hz,3H),3.54(d,J=10.6Hz,3H)1.56(dd,J=18.4,7.4Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ135.8(d,J=5.5Hz),133.9(d,J=10.0Hz),129.6(d,J=4.7Hz),129.5(d,J=2.2Hz),128 .3(d,J=3.0Hz), 127.1(d,J=2.9Hz), 53.2(d,J=7.0Hz), 52.9(d,J=7.0Hz), 33.3(d,J=140.6Hz), 15.7(d,J=5.2Hz). 31 P NMR (162 MHz, CDCl3) δ 31.73.

[0072] Example 15: Preparation of dimethyl(S)-(1-phenylethyl)phosphonate from dimethyl(1-phenylvinyl)phosphonate

[0073]

[0074] Under a high-purity argon atmosphere, Ni(OAc)2 (14.14 mg, 0.08 mmol) and the chiral ligand (S,S)-Ph-BPE (44.58 mg, 0.088 mmol) were dissolved in anhydrous hexafluoroisopropanol (7.2 mL) and anhydrous methanol (0.8 mL). The mixture was stirred at 15-35°C for 36 hours to obtain a clear solution. 250 μL of the clear solution was added to dimethyl(1-phenylvinyl)phosphonate (0.1 mmol) and hexafluoroisopropanol (0.75 mL). The reaction system was placed in an autoclave and stirred at 70°C under H2 (70 atm) for 36 hours. The solvent was removed under reduced pressure, and the product was separated by column chromatography (silica gel, eluent: ethyl acetate) to obtain pure dimethyl(S)-(1-phenylethyl)phosphonate (98% yield). HPLC analysis of the product revealed an ee value of 93%. 1 H NMR (400MHz, Chloroform-d) δ7.36–7.25(m,5H),3.62(d,J=10.6Hz,3H),3.46(d,J=10.5Hz,3H),3.26–3.09(m,1H),1.58(dd,J=18.6,7.4Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ137.6(d,J=6.9Hz),128.6(d,J=8.9Hz),128.5,127.2(d,J =3.2Hz), 53.3(d,J=6.9Hz), 52.8(d,J=7.2Hz), 38.0(d,J=137.7Hz), 15.5(d,J=5.1Hz). 31 P NMR (162 MHz, CDCl3) δ 32.16.

[0075] Example 16: Preparation of dimethyl(S)-(1-(naphthalen-1-yl)ethyl)phosphonate from dimethyl(1-(naphthalen-1-yl)vinyl)phosphonate

[0076]

[0077] Under a high-purity argon atmosphere, Ni(OAc)2 (14.14 mg, 0.08 mmol) and the chiral ligand (S,S)-Ph-BPE (44.58 mg, 0.088 mmol) were dissolved in anhydrous hexafluoroisopropanol (7.2 mL) and anhydrous methanol (0.8 mL). The mixture was stirred at 15-35°C for 36 hours to obtain a clear solution. 250 μL of the clear solution was added to dimethyl(1-(naphthalen-1-yl)vinyl)phosphonate (0.1 mmol) and hexafluoroisopropanol (0.75 mL). The reaction system was placed in an autoclave and stirred at 70°C under H2 (70 atm) for 36 hours. The solvent was removed under reduced pressure, and the product was separated by column chromatography (silica gel column, eluent: ethyl acetate) to obtain pure dimethyl(S)-(1-(naphthalen-1-yl)ethyl)phosphonate (99% yield). The product was analyzed by HPLC, and the ee value was determined to be 86%. 1 H NMR(400MHz,Chloroform-d)δ8.09–8.07(m,1H),7.88–7.86(m,1H),7.80–7.78(m,1H),7.71–7.68(m,1H),7.57 –7.48(m,3H),4.22–4.08(m,1H),3.69(d,J=10.7Hz,3H),3.37(d,J=10.5Hz,3H),1.71(dd,J=18.5,7.3Hz,3H). 13 C NMR(101MHz,Chloroform-d)δ133.8(d,J=1.9Hz),133.6(d,J=6.6Hz),131.5(d,J=7.2Hz),129.0,127.8(d,J=3.6Hz),126.3,126 .0(d,J=6.4Hz),125.6,125.5(d,J=3.7Hz),122.9,53.4(d,J=7.0Hz),52.9(d,J=7.6Hz),31.9(d,J=137.5Hz),16.2(d,J=5.3Hz), 31 P NMR (162 MHz, CDCl3) δ 32.45.

[0078] Example 17: Preparation of dimethyl(S)-(1-cyclohexylethyl)phosphonate from dimethyl(1-cyclohexylvinyl)phosphonate

[0079]

[0080] Under a high-purity argon atmosphere, Ni(OAc)2 (14.14 mg, 0.08 mmol) and the chiral ligand (S,S)-Ph-BPE (44.58 mg, 0.088 mmol) were dissolved in anhydrous hexafluoroisopropanol (7.2 mL) and anhydrous methanol (0.8 mL). The mixture was stirred at 15-35°C for 36 hours to obtain a clear solution. 250 μL of the clear solution was added to dimethyl(1-cyclohexylvinyl)phosphonate (0.1 mmol) and hexafluoroisopropanol (0.75 mL). The reaction system was placed in an autoclave and stirred at 70°C under H2 (70 atm) for 36 hours. The solvent was removed under reduced pressure, and the product was separated by column chromatography (silica gel, eluent: ethyl acetate) to obtain pure dimethyl(S)-(1-cyclohexylethyl)phosphonate (99% yield). HPLC analysis of the product revealed an ee value of 97%. 1 H NMR(400MHz,Chloroform-d)δ3.74(s,3H),3.72(s,3H),1.82–1.74(m,3H),1.66–1.59(m,2H),1.29–1.22(m,5H),1.15–1.09(m,3H),0.92–0.81(m,2H). 13 C NMR(101MHz,Chloroform-d)δ52.3(d,J=6.8Hz),52.2(d,J=7.1Hz),37.5(d,J=2.6Hz),36.2( d,J=137.1Hz), 31.9(d,J=13.6Hz), 28.8(d,J=3.6Hz), 26.3(d,J=23.7Hz), 9.5(d,J=4.7Hz). 31 P NMR (162 MHz, CDCl3) δ 37.25.

[0081] Example 18: Preparation of dimethyl(S)-(1-phenylpropyl)phosphonate from dimethyl(E)-(1-phenylprop-1-en-1-yl)phosphonate

[0082]

[0083] Under a high-purity argon atmosphere, Ni(OAc)2 (14.14 mg, 0.08 mmol) and the chiral ligand (S,S)-Ph-BPE (44.58 mg, 0.088 mmol) were dissolved in anhydrous hexafluoroisopropanol (7.2 mL) and anhydrous methanol (0.8 mL). The mixture was stirred at 15-35°C for 36 hours to obtain a clear solution. 250 μL of the clear solution was added to dimethyl(E)-(1-phenylprop-1-en-1-yl)phosphonate (0.1 mmol) and hexafluoroisopropanol (0.75 mL). The reaction system was placed in an autoclave and stirred at 70°C under H2 (70 atm) for 36 hours. The solvent was removed under reduced pressure, and the product was separated by column chromatography (silica gel column, eluent: ethyl acetate) to obtain pure dimethyl(S)-(1-phenylpropyl)phosphonate (95% yield). The product was analyzed by HPLC, and the ee value was determined to be 97% ee. 1 H NMR(400MHz,Chloroform-d)δ7.35–7.27(m,5H),3.64(d,J=10.6Hz,3H),3.42( d,J=10.4Hz,3H),2.97–2.87(m,1H),2.24–1.89(m,2H),0.85(t,J=7.4Hz,3H). 13 C NMR (101MHz, Chloroform-d) δ 135.8 (d, J = 6.7Hz), 129.2 (d, J = 6.9Hz), 128.5 (d, J = 2.5Hz), 127.2 (d, J = 3. 1Hz), 53.3 (d, J = 7.0Hz), 52.6 (d, J = 7.3Hz), 46.1 (d, J = 136.5Hz), 23.1 (d, J = 3.4Hz), 12.4 (d, J = 16.1Hz). 31 P NMR (162 MHz, CDCl3) δ 31.36.

[0084] Example 19: Preparation of (S)-(1-(o-tolyl)ethyl)phosphonic acid from (1-(o-tolyl)vinyl)phosphonic acid

[0085]

[0086] Under a high-purity argon atmosphere, Ni(OAc)2 (14.14 mg, 0.08 mmol) and the chiral ligand (S,S)-Ph-BPE (44.58 mg, 0.088 mmol) were dissolved in anhydrous hexafluoroisopropanol (7.2 mL) and anhydrous methanol (0.8 mL). The mixture was stirred at 15-35°C for 36 hours to obtain a clear solution. 250 μL of the clear solution was added to (1-(o-tolyl)vinyl)phosphonicacid (0.1 mmol) and hexafluoroisopropanol (0.75 mL). The reaction system was placed in an autoclave and stirred at 70°C under H2 (70 atm) for 36 hours. The solvent was removed under reduced pressure, and the product was separated by column chromatography (silica gel column, eluent: ethyl acetate) to obtain pure (S)-(1-(o-tolyl)ethyl)phosphonic acid (99% yield). The product was analyzed by HPLC, and the ee value was determined to be 98% ee.

[0087] Example 20: Preparation of (S)-(1-(naphthalen-1-yl)ethyl)phosphonic acid from (1-(naphthalen-1-yl)vinyl)phosphonic acid

[0088]

[0089] Under a high-purity argon atmosphere, Ni(OAc)2 (14.14 mg, 0.08 mmol) and the chiral ligand (S,S)-Ph-BPE (44.58 mg, 0.088 mmol) were dissolved in anhydrous hexafluoroisopropanol (7.2 mL) and anhydrous methanol (0.8 mL). The mixture was stirred at 15-35°C for 36 hours to obtain a clear solution. 250 μL of the clear solution was added to (1-(naphthalen-1-yl)vinyl)phosphonic acid (0.1 mmol) and hexafluoroisopropanol (0.75 mL). The reaction system was placed in an autoclave and stirred at 70°C under H2 (70 atm) for 36 hours. The solvent was removed under reduced pressure, and the product was separated by column chromatography (silica gel column, eluent: ethyl acetate) to obtain pure (S)-(1-(naphthalen-1-yl)ethyl)phosphonic acid (99% yield). The product was analyzed by HPLC, and the ee value was determined to be 92% ee.

[0090] Although the embodiments of the present invention have been shown and described above, it will be understood that the above embodiments are illustrative and are not to be construed as limitations on the present invention. A person skilled in the art may make changes, modifications, substitutions and variations to the above embodiments within the scope of the present invention, and all of these changes shall be included within the scope of protection of the present invention.

Claims

1. A method for synthesizing a chiral α-phosphorus compound, characterized in that: The chiral α-phosphorus compound is prepared by asymmetric hydrogenation of compound 1. The reaction formula for preparing the chiral α-phosphorus compound from compound 1 is as follows: R3 is selected from phenyl, substituted phenyl, naphthyl, cyclohexyl, R' is a C1-C6 straight chain alkyl or H, R1 and R2 are independently selected from one of hydroxyl, alkoxy and phenyl; The catalyst used in the preparation of the chiral α-phosphorus compound from compound 1 is a catalyst obtained by complexing the chiral ligand (S,S)-Ph-BPE with a nickel salt; Control the asymmetric hydrogenation reaction temperature to 60-80°C; The reaction is carried out under a hydrogen atmosphere, the hydrogen pressure is controlled at 60 to 80 atmospheres, and the reaction time is controlled at 24 to 36 hours; The structure of the chiral ligand (S,S)-Ph-BPE is as follows: The nickel salt is Ni(OAc)2; and the solvent for the asymmetric hydrogenation reaction is hexafluoroisopropanol.

2. The method for synthesizing a chiral α-phosphorus compound according to claim 1, characterized in that: The substituted phenyl group is a halogen-substituted phenyl group, an alkyl-substituted phenyl group, an alkoxy-substituted phenyl group or a halogen-alkyl-substituted phenyl group.

3. The method for synthesizing a chiral α-phosphorus compound according to claim 1, characterized in that: The molar ratio of nickel salt to chiral ligand (S,S)-Ph-BPE is controlled to be 1:1 to 1.

2.

4. The method for synthesizing a chiral α-phosphorus compound according to claim 1, characterized in that: The reaction temperature of the complex reaction is controlled to be 15-35°C.

5. The method for synthesizing a chiral α-phosphorus compound according to claim 1, characterized in that: The reaction time of the complex reaction is controlled to be 5 to 36 hours.

6. The method for synthesizing a chiral α-phosphorus compound according to claim 1, characterized in that: The steps include: Step 1): complexation reaction between the chiral ligand (S,S)-Ph-BPE and nickel salt; Step 2): Compound 1 is added to the reaction solution of step 1) to carry out an asymmetric hydrogenation reaction to obtain the chiral α-phosphorus compound.

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