Synthesis method for chiral preparation of phosphine heterocyclic pentane oxide

Abstract

The invention relates to a synthetic method for chiral preparation of a phosphine heterocyclic pentane oxide, and discloses a method for synthesizing a phosphine heterocyclic pentane oxide by using 1-phenyl-2, 5-dihydrophosphinazole-1-oxide and alkyl iodide as substrates, ethylene glycol dimethyl ether cobalt dibromide and (R, S)-BOX as catalysts, dimethoxymethylsilane as a reducing agent and cesium fluoride as alkali through a one-pot method. And reacting at the temperature of 10 DEG C to obtain the phosphine heterocyclic pentane oxide. The method is good in enantioselectivity and regioselectivity and has good functional group tolerance, and an efficient and novel preparation method is provided for the phosphine heterocyclic pentane oxide.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a synthesis method for preparing chiral phosphopentane oxide. Background Art

[0002] Chiral phosphine compounds are widely present in medicine, pesticides, ligands and catalysts, especially in the field of organic synthesis. The ligands currently available on the market, such as TangPhos, LePhos, DuPhos and BPE, have the advantages of high catalytic activity, good selectivity, good substrate tolerance, etc., and have been widely used in asymmetric catalysis. However, the traditional method of constructing a phosphine heterocyclopentane skeleton still relies on chiral auxiliary agents and resolution reagents. These methods have the disadvantages of cumbersome operation, high cost, low yield, severe conditions, and high toxicity. Therefore, it is of great significance to develop a novel, simple and efficient method for synthesizing phosphine heterocyclopentane oxides. In recent years, chemists have discovered a desymmetric strategy that can construct chiral phosphine compounds from prochiral phosphine compounds. These methods mainly rely on open-chain substrates with the same substituents, but can only construct a single phosphine chiral center. The present invention develops a compound that uses a desymmetric strategy to simultaneously construct a compound containing two chiral centers of carbon and phosphine, which provides a faster and more efficient synthesis method for the synthesis of new ligands, and is also of great significance to the development of chiral phosphine chemistry. Summary of the invention

[0003] The purpose of the present invention is to improve the shortcomings of the existing preparation and synthesis methods and provide a method for synthesizing phosphopentane oxides with simple reaction conditions, good enantioselectivity and regioselectivity and a wide range of substrate applicability.

[0004] The technical scheme of the present invention is: a substrate, a catalyst, a (R, S)-Box ligand L1, a reducing agent, and a base are placed in a test tube, a solvent is added, and a phosphopentane oxide is obtained under argon protection and 10° C. The reaction formula is as follows:

[0005]

[0006] (1)R 1 Selected from phenyl, methoxy, methyl, trifluoromethyl, naphthyl, n-octyl, tert-butyl, benzyl, isopropyl, cyclohexyl;

[0007] (2)R 2 Other substituted alkyl iodides selected from p-methoxyphenethyl, p-methylphenethyl, m-methylphenethyl, o-trifluoromethylphenethyl, 2,4,6-trimethylphenethyl, naphthylethyl, etc.;

[0008] (3) the cobalt catalyst used is selected from ethylene glycol dimethyl ether cobalt dibromide, cobalt chloride, cobalt bromide, cobalt iodide, cobalt acetylacetonate, cobalt acetate, etc., preferably ethylene glycol dimethyl ether cobalt dibromide;

[0009] (4) the reducing agent used is selected from triethoxysilane, trimethoxysilane, diethoxymethylsilane, dimethoxymethylsilane, etc., preferably dimethoxymethylsilane;

[0010] (5) The base used is selected from cesium fluoride;

[0011] (6) The temperature used is selected from 10°C;

[0012] (7) The organic solvent used is selected from 1,4-dioxane, ethylene glycol dimethyl ether, anisole, tetrahydrofuran, etc., preferably 1,4-dioxane;

[0013] (8) The molar mass ratio of each substance in the reaction is selected from: 1-phenyl-2,5-dihydrophosphine-1-oxide: alkyl iodide: catalyst: dimethoxymethylsilane: cesium fluoride = 1.5:1:0.1:3:3. BRIEF DESCRIPTION OF THE DRAWINGS

[0014] 1. Figure 1 The following are the synthesis conditions of phosphopentane oxide;

[0015] 2. Figure 2 is the preparation reaction formula of compound 3a;

[0016] 3. Figure 3 is the preparation reaction formula of compound 3b;

[0017] 4. Figure 4 is the preparation reaction formula of compound 3c;

[0018] 5. Figure 5 is the preparation reaction formula of compound 3d;

[0019] 6. Figure 6 is the preparation reaction formula of compound 3e;

[0020] 7. Figure 7 is the preparation reaction formula of compound 3f;

[0021] 8. Figure 8 is the preparation reaction formula of compound 3g;

[0022] 9. Fig. 9 is the preparation reaction formula of compound 3h;

[0023] 10. Fig.10 is the preparation reaction formula of compound 3i;

[0024] 11. Fig.11 is the preparation reaction formula of compound 3j;

[0025] 12. Fig.12 is the preparation reaction formula of compound 3k;

[0026] 13. Fig.13 is the preparation reaction formula of compound 31;

[0027] 14. Fig.14 is the preparation reaction formula of compound 3m;

[0028] 15. Fig.15 is the preparation reaction formula of compound 3n;

[0029] 16. Fig.16 is the preparation reaction formula of compound 3o;

[0030] 17. Fig.17 is the preparation reaction formula of compound 4a;

[0031] 18. Fig.18 is the preparation reaction formula of compound 4b;

[0032] 19. Fig.19 is the preparation reaction formula of compound 4c;

[0033] 20. Fig. 20 is the preparation reaction formula of compound 4d;

[0034] twenty one. Fig.21 is the preparation reaction formula of compound 4e;

[0035] twenty two. Fig. 22 is the preparation reaction formula of compound 4f;

[0036] twenty three. Fig.23 is the preparation reaction formula of compound 4g;

[0037] twenty four. Fig.24 is the preparation reaction formula of compound 4h;

[0038] 25. Fig.25 is the preparation reaction formula of compound 4i;

[0039] 26. Fig.26 is the preparation reaction formula of compound 4j;

[0040] 27. Fig. 27 is the preparation reaction formula of compound 4k;

[0041] 28. Fig.28 is the racemic liquid phase spectrum of compound 3a;

[0042] 29. Fig.29 is the chiral liquid chromatography spectrum of compound 3a;

[0043] 30. Fig.30 is the racemic liquid phase spectrum of compound 3b;

[0044] 31. Fig.31 is the chiral liquid phase spectrum of compound 3b;

[0045] 32. Fig.32 is the racemic liquid phase spectrum of compound 3c;

[0046] 33. Fig.33 is the chiral liquid chromatography spectrum of compound 3c;

[0047] 34. Fig.34 is the racemic liquid phase spectrum of compound 3d;

[0048] 35. Fig.35 is the chiral liquid chromatography spectrum of compound 3d;

[0049] 36. Fig.36 is the racemic liquid phase spectrum of compound 3e;

[0050] 37. Fig.37 is the chiral liquid chromatography spectrum of compound 3e;

[0051] 38. Fig.38 is the racemic liquid phase spectrum of compound 3f;

[0052] 39. Fig.39 is the chiral liquid chromatography spectrum of compound 3f;

[0053] 40. Fig.40 is the racemic liquid phase spectrum of compound 3g;

[0054] 41. Fig.41 is the chiral liquid chromatography spectrum of compound 3g;

[0055] 42. Fig.42 is the racemic liquid phase spectrum of compound 3h;

[0056] 43. Fig.43 is the chiral liquid chromatography spectrum of compound 3h;

[0057] 44. Fig.44 is the racemic liquid phase spectrum of compound 3i;

[0058] 45. Fig.45 is the chiral liquid chromatography spectrum of compound 3i;

[0059] 46. Fig.46 is the racemic liquid phase spectrum of compound 3j;

[0060] 47. Fig.47 is the chiral liquid chromatography spectrum of compound 3j;

[0061] 48. Fig.48is the racemic liquid phase spectrum of compound 3k;

[0062] 49. Fig.49 is the chiral liquid chromatography spectrum of compound 3k;

[0063] 50. Fig.50 is the racemic liquid phase spectrum of compound 31;

[0064] 51. Fig.51 is the chiral liquid chromatography spectrum of compound 3l;

[0065] 52. Fig.52 is the racemic liquid phase spectrum of compound 3m;

[0066] 53. Fig.53 is the chiral liquid chromatography spectrum of compound 3m;

[0067] 54. Fig.54 is the racemic liquid phase spectrum of compound 3n;

[0068] 55. Fig.55 is the chiral liquid chromatography spectrum of compound 3n;

[0069] 56. Fig.56 is the racemic liquid phase spectrum of compound 3o;

[0070] 57. Fig.57 is the chiral liquid chromatography spectrum of compound 3o;

[0071] 58. Fig.58 is the racemic liquid phase spectrum of compound 4a;

[0072] 59. Fig.59 is the chiral liquid chromatography spectrum of compound 4a;

[0073] 60. Fig.60 is the racemic liquid phase spectrum of compound 4b;

[0074] 61. Fig.61 is the chiral liquid chromatography spectrum of compound 4b;

[0075] 62. Fig.62 is the racemic liquid phase spectrum of compound 4c;

[0076] 63. Fig.63 is the chiral liquid chromatography spectrum of compound 4c;

[0077] 64. Fig.64 is the racemic liquid phase spectrum of compound 4d;

[0078] 65. Fig.65 is the chiral liquid chromatography spectrum of compound 4d;

[0079] 66. Fig.66 is the racemic liquid phase spectrum of compound 4e;

[0080] 67. Fig.67 is the chiral liquid chromatography spectrum of compound 4e;

[0081] 68. Fig.68 is the racemic liquid phase spectrum of compound 4f;

[0082] 69. Fig.69 is the chiral liquid chromatography spectrum of compound 4f;

[0083] 70. Fig.70 is the racemic liquid phase spectrum of compound 4g;

[0084] 71. Fig.71 is the chiral liquid chromatography spectrum of compound 4g;

[0085] 72. Fig.72 is the racemic liquid phase spectrum of compound 4h;

[0086] 73. Fig.73 is the chiral liquid chromatography spectrum of compound 4h;

[0087] 74. Fig.74 is the racemic liquid phase spectrum of compound 4i;

[0088] 75. Fig.75 is the chiral liquid chromatography spectrum of compound 4i;

[0089] 76. Fig.76 is the racemic liquid phase spectrum of compound 4j;

[0090] 77. Fig.77 is the chiral liquid chromatography spectrum of compound 4j;

[0091] 78. Fig.78 is the racemic liquid phase spectrum of compound 4k;

[0092] 79. Fig.79 This is the chiral liquid chromatography spectrum of compound 4k. DETAILED DESCRIPTION

[0093] The present invention is further described below through specific embodiments, but this should not be understood as the scope of the above subject matter of the present invention being limited to the following embodiments, and all technologies implemented based on the above content of the present invention belong to the scope of the present invention.

[0094] Example 1: Using 1-phenyl-2,5-dihydrophosphine-1-oxide (1) and alkyl iodide (2a) as raw materials (reaction formula 1)

[0095]

[0096] In an argon-filled glove box, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added into a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), alkyl iodide 2a (0.1 mmol, 1 equiv.) and the corresponding olefin 1 (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product 3a was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0097] The product detection data are as follows: amorphous solid, yield 74%, ee = 94%.

[0098] 1 H NMR (400MHz, CDCl3) δ7.72–7.67(m,2H),7.53–7.46(m,3H),7.09(d,J=8.6Hz,2H),6.83(d,J=8.6Hz,2H),3 .79(s,3H),2.70–2.57(m,2H),2.39-2.32(m,1H),2.27–2.15(m,2H),2.04–1.98(m,1H),1.95–1.74(m,5H); 13 C NMR(100MHz,CDCl3)δ157.9,134.5(d,J C-P =89.5Hz),133.6,131.6(d,J C-P =2.81Hz),129.8(d,J C-P =9.8Hz),129.1,128.6(d,J C-P =11.5Hz),113.8,55.2,39.4(d,J C-P =8.8Hz),38.1(d,J C-P =12.0Hz),36.3(d,J C-P =66.5Hz),33.1,31.0(d,J C-P =6.2Hz),29.6(d,J C-P =66.4Hz); 31P NMR (162MHz, CDCl3) δ59.3; IRν (cm -1 ):2924,1510,1176,1032,745,532; HRMS(EI)m / z:[M+Na] + Calcd for C 19 H 23 O2PNa + 337.1328; Found 337.1337; HPLC analysis: The ee was determined to be 94% on a CHIRALCEL IA-3 column (10% iPrOH in n-hexane, flow rate = 1.0mL / min, λ = 230nm, 30°C); retention times for compound obtained using (R, S)-L1: 18.009min (major), 18.912min (minor).

[0099] Peak Table

[0100] PDA Ch1 230nm

[0101] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 17.019 268.837 11.360 48.533 2 17.766 285.089 11.520 51.467

[0102] Peak Table

[0103] PDA Ch1 230nm

[0104] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 18.009 1842.939 80.842 96.980 2 18.912 57.392 2.414 3.020

[0105] Example 2: Using 1-phenyl-2,5-dihydrophosphine-1-oxide (1) and alkyl iodide (2b) as raw materials (reaction formula 2)

[0106]

[0107] In an argon-filled glove box, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added into a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), alkyl iodide 2b (0.1 mmol, 1 equiv.) and the corresponding olefin 1 (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product 3b was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0108] The product detection data are as follows: amorphous solid, yield 72%, ee = 91%.

[0109] 1 H NMR (400MHz, CDCl3) δ7.72-7.67(m,2H),7.53-7.46(m,3H),7.11-7.05(m,4H),2.70-2.61(m, 2H),2.40–2.35(m,2H),2.32(s,3H),2.26–2.14(m,2H),2.05–2.00(m,1H),1.93–1.72(m,5H); 13 C NMR (100MHz, CDCl3) δ138.5,135.4,134.4(d,J C-P =89.3Hz),131.6(d,J C-P =2.9Hz),129.8(d,J C-P =9.7Hz),129.1,128.6(d,J C-P =11.5Hz),128.1,39.4(d,J C-P =8.8Hz),38.0(d,J C-P =12.1Hz),36.2(d,J C-P =66.5Hz),33.6,30.9(d,J C-P =6.1Hz),29.6(d,J C-P =66.4Hz),21.0; 31 P NMR (162MHz, CDCl3) δ59.4; IRν (cm -1):2922,1516,1112,1178,743,530; HRMS(EI)m / z:[M+Na] + Calcd for C 19 H 23 OPNa + 321.1379; Found 321.1390; HPLC analysis: The ee was determined to be 91% on a CHIRALCEL OJ-H column (5% iPrOH in n-hexane, flow rate = 1.0mL / min, λ = 230nm, 30°C); retention times for compound obtained using(R,S)-L1:29.043min(major),38.282min(minor).

[0110] Peak Table

[0111] PDA Ch1 230nm

[0112] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 29.275 212.239 4.096 49.589 2 38.006 215.759 3.237 50.411

[0113] Peak Table

[0114] PDA Ch1 230nm

[0115] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 29.043 1649.843 29.203 95.566 2 38.282 76.548 1.177 4.434

[0116] Implementation Case 3

[0117] Using 1-phenyl-2,5-dihydrophosphine-1-oxide (1) and alkyl iodide (2c) as raw materials (reaction formula 3)

[0118]

[0119]

[0120] In an argon-filled glove box, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added into a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), alkyl iodide 2c (0.1 mmol, 1 equiv.) and the corresponding olefin 1 (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product 3c was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0121] The product detection data are as follows: amorphous solid, yield 75%, ee = 90%.

[0122] 1 H NMR (400MHz, CDCl3) δ7.73-7.68(m,2H),7.53–7.46(m,3H),7.18(t,J=7.5Hz,1H),7.03–6.96(m,3H),2.7 1–2.61(m,2H),2.41–2.34(m,1H),2.33(s,3H),2.27–2.15(m,2H),2.05-1.99(m,1H),1.96–1.73(m,5H); 13 C NMR(100MHz,CDCl3)δ141.5,138.0,134.6(d,J C-P =89.4Hz),131.6(d,J C-P =2.8Hz),129.8(d,J C-P =9.7Hz),129.1,128.6(d,J C-P =11.5Hz),128.3,126.7,125.3,39.4(d,J C-P =8.7Hz),37.9(d,J C-P =12.1Hz),36.3(d,J C-P =66.5Hz),34.0,31.0(d,J C-P =6.2Hz),29.6(d,J C-P =66.4Hz),21.4; 31P NMR (162MHz, CDCl3) δ59.2; IRν (cm -1 ):3022,1437,1214,1112,743,534; HRMS(EI)m / z:[M+Na] + Calcd for C 19 H 23 OPNa + 321.1379; Found 321.1392; HPLC analysis:The ee was determined to be90% on a CHIRALCEL Amy-D column (15% iPrOH in n-hexane, flow rate=0.8mL / min, λ=230nm, 30℃); retention times for compound obtained using (R, S)-L1: 11.063min (minor), 12.122min (major).

[0123] Peak Table

[0124] PDA Ch1 230nm

[0125] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 10.969 74.811 3.599 50.824 2 12.018 72.386 3.156 49.176

[0126] Peak Table

[0127] PDA Ch1 230nm

[0128] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 11.063 4.576 0.292 4.993 2 12.122 87.071 3.644 95.007

[0129] Implementation Case 4

[0130] Using 1-phenyl-2,5-dihydrophosphine-1-oxide (1) and alkyl iodide (2d) as raw materials (reaction formula 4)

[0131]

[0132] In an argon-filled glove box, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added into a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), alkyl iodide 2d (0.1 mmol, 1 equiv.) and the corresponding olefin 1 (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product 3d was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0133] The product detection data are as follows: amorphous solid, yield 68%, ee = 91%.

[0134] 1 H NMR (400MHz, CDCl3) δ7.77–7.72(m,2H),7.61(d,J=7.9Hz,1H),7.56–7.45(m,4H),7.32–7.27(m,2 H),2.90–2.78(m,2H),2.36–2.43(m,1H),2.34–2.21(m,2H),2.19–2.08(m,1H),2.01–1.78(m,5H); 13 C NMR(100MHz,CDCl3)δ140.5(d,J C-P =2.1Hz),134.3(d,J C-P =89.6Hz),133.9,131.7(d,J C-P =2.9Hz),130.8,129.8(d,J C-P =9.4Hz),128.7(d,J C-P =11.6Hz),128.2(q,J C-F =29.6Hz),126.1,126.0(q,J C-F =6.0Hz),124.6(q,J C-F =272.2Hz),40.1(d,J C-P =9.4Hz),38.4(d,J C-P =11.6Hz),36.4(d,J C-P=66.4Hz),31.0,30.9(d,J C-P =6.5Hz),29.5(d,J C-P =65.7Hz); 31 P NMR (162 MHz, CDCl3) δ 59.2; 19 F NMR (377MHz, CDCl3) δ-59.5; IRν (cm -1 ):2963,1440,1312,1113,747,537; HRMS(EI)m / z:[M+Na] + Calcd for C 19 H 20 F3OP + 375.1096; Found 375.1105; HPLC analysis: The ee was determined to be 91% on a CHIRALCEL Amy-D column (15% iPrOH in n-hexane, flow rate = 0.8mL / min, λ = 210nm, 30°C); retention times for compound obtained using(R,S)-L1:11.650min(minor),12.722min(major).

[0135] Peak Table

[0136] PDA Ch1 210nm

[0137] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 11.649 1241.975 54.620 50.091 2 12.702 1237.446 50.078 49.909

[0138] Peak Table

[0139] PDA Ch1 210nm

[0140] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 11.650 46.293 1.946 4.471 2 12.722 989.206 39.106 95.529

[0141] Implementation Case 5

[0142] Using 1-phenyl-2,5-dihydrophosphine-1-oxide (1) and alkyl iodide (2e) as raw materials (reaction formula 5)

[0143]

[0144] In an argon-filled glove box, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added into a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), alkyl iodide 2e (0.1 mmol, 1 equiv.) and the corresponding olefin 1 (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product 3e was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0145] The product detection data are as follows: amorphous solid, yield 56%, ee = 90%.

[0146] 1 H NMR (400MHz, CDCl3) δ7.80–7.74(m,2H),7.55–7.49(m,3H),6.83(s,2H),2.66–2.62(m, 2H),2.48-2.33(m,1H),2.28(s,6H),2.24(s,3H),2.36–2.12(m,3H),2.00–1.61(m,5H); 13 C NMR (100MHz, CDCl3) δ135.6,135.4,135.2,134.4(d,J C-P =89.5Hz),131.7(d,J C-P =2.8Hz),129.9(d,J C-P =9.6Hz),128.7(d,J C-P =11.6Hz),113.8,40.6(d,J C-P =8.4Hz),36.7(d,J C-P =66.5Hz),36.7(d,J C-P =11.9Hz),31.0(d,J C-P =6.2Hz),29.6(d,J C-P =66.4Hz),20.7,19.6; 31 P NMR (162MHz, CDCl3) δ59.7; IRν (cm -1):2971,1437,1214,1110,744,538; HRMS(EI)m / z:[M+Na] + Calcd for C 21 H 27 OPNa + 349.1692; Found 349.1704; HPLC analysis: Theee was determined to be 90% on a CHIRALCEL OJ-H column (15% iPrOH in n-hexane, flow rate = 0.8mL / min, λ = 210nm, 30℃); retention times for compound obtained using (R, S)-L1: 7.139min (minor), 8.164min (major).

[0147] Peak Table

[0148] PDA Ch1 210nm

[0149] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 7.118 1392.962 97.656 50.516 2 8.149 1364.516 67.102 49.484

[0150] Peak Table

[0151] PDA Ch1 210nm

[0152] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 7.139 12.879 1.143 4.770 2 8.164 257.143 12.770 95.230

[0153] Implementation Case 6

[0154] Using 1-phenyl-2,5-dihydrophosphine-1-oxide (1) and alkyl iodide (2f) as raw materials (reaction formula 6)

[0155]

[0156] In an argon-filled glove box, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added into a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), alkyl iodide 2f (0.1 mmol, 1 equiv.) and the corresponding olefin 1 (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product 3f was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0157] The product detection data are as follows: amorphous solid, yield 80%, ee = 93%.

[0158] 1 H NMR(400MHz, CDCl3)δ7.83–7.76(m,3H),7.70–7.65(m,2H),7.61(s,1H),7.54–7.42(m,5H),7 .34-7.31(m,1H),2.94–2.80(m,2H),2.45–2.38(m,1H),2.28–2.13(m,2H),2.08–1.76(m,6H); 13 C NMR(100MHz,CDCl3)δ139.0,134.4(d,J C-P =89.5Hz),133.5,132.0,131.6(d,J C-P =2.9Hz),129.8(d,J C-P =10.1Hz),128.6(d,J C-P =11.6Hz),128.1,127.6,127.3,127.0,126.3,126.0,125.2,39.3(d,J C-P =8.7Hz),37.6(d,J C-P =12.3Hz),36.2(d,J C-P =66.4Hz),34.1,31.0(d,J C-P =6.5Hz),29.6(d,J C-P =66.4Hz); 31P NMR (162MHz, CDCl3) δ59.3; IRν (cm -1 ):2934,1435,1212,1177,742,478; HRMS(EI)m / z:[M+Na] + Calcd for C 22 H 23 OPNa + 357.1379; Found 357.1385; HPLC analysis: The ee was determined to be 93% on a CHIRALCEL Amy-D column (15% iPrOH in n-hexane, flow rate = 0.8mL / min, λ = 210nm, 30°C); retention times for compound obtained using(R,S)-L1:17.607min(minor),19.229min(major).

[0159] Peak Table

[0160] PDA Ch1 210nm

[0161] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 17.823 1452.249 39.068 49.647 2 19.361 1472.929 38.836 50.353

[0162] Peak Table

[0163] PDA Ch1 210nm

[0164] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 17.607 48.261 1.335 3.349 2 19.229 1392.988 36.892 96.651

[0165] Implementation Case 7

[0166] Using 1-phenyl-2,5-dihydrophosphine-1-oxide (1) and alkyl iodide (2g) as raw materials (reaction formula 7)

[0167]

[0168] In an argon-filled glove box, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added to a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), 2 g of alkyl iodide (0.1 mmol, 1 equiv.) and the corresponding olefin 1 (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product 3 g was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0169] The product detection data are as follows: amorphous solid, yield 70%, ee = 93%.

[0170] 1 H NMR(400MHz, CDCl3)δ7.77–7.70(m,5H),7.55–7.46(m,3H),7.45-7.41(m,1H),7.34-7.31(m,1H), 7.15–7.10(m,2H),4.07(d,J=6.0Hz,2H),2.42–2.36(m,1H),2.27–2.08(m,3H),2.00–1.70(m,7H); 13 C NMR (100MHz, CDCl3) δ156.8,134.5,134.4(d,J C-P =90.0Hz),131.6(d,J C-P =2.8Hz),129.8(d,J C-P =9.4Hz),129.4,128.9,128.6(d,J C-P =11.6Hz),127.6,126.6,126.3,123.5,118.8,106.5,67.6,39.8(d,J C-P =8.7Hz),36.4(d,J C-P =67.2Hz),32.9(d,J C-P =13.0Hz),31.0(d,J C-P =5.8Hz),29.5(d,J C-P =66.4Hz),27.5; 31PNMR (162MHz, CDCl3) δ59.4; IRν (cm -1 ):2931,1627,1257,1180,743,474; HRMS(EI)m / z:[M+Na] + Calcd for C 23 H 25 O2PNa + 387.1484; Found 387.1500; HPLC analysis: The ee was determined to be 93% on a CHIRALCEL Amy-D column (10% iPrOH in n-hexane, flowrate=0.8mL / min, λ=230nm, 30℃); retention times for compound obtained using (R, S)-L1: 64.315min (major), 73.762min (minor).

[0171] Peak Table

[0172] PDA Ch1 230nm

[0173] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 63.982 2825.585 21.666 50.403 2 73.096 2780.368 19.610 49.597

[0174] Peak Table

[0175] PDA Ch1 230nm

[0176] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 64.315 26324.763 200.851 96.417 2 73.762 978.221 7.518 3.583

[0177] Implementation Case 8

[0178] Using 1-phenyl-2,5-dihydrophosphine-1-oxide (1) and alkyl iodide (2h) as raw materials (reaction formula 8)

[0179]

[0180] In an argon-filled glove box, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added to a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), alkyl iodide 2h (0.1 mmol, 1 equiv.) and the corresponding olefin 1 (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product 3h was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0181] The product detection data are as follows: amorphous solid, yield 51%, ee = 91%.

[0182] 1 H NMR (400MHz, CDCl3) δ7.76–7.71(m,2H),7.54–7.47(m,3H),7.24–7.20(m,2H),6.82–6.77(m,2H), 3.94(t,J=6.0Hz,2H),2.41–2.34(m,1H),2.30–2.16(m,2H),2.12–2.06(m,1H),1.96–1.72(m,7H); 13 C NMR(100MHz,CDCl3)δ157.4,134.4(d,J C-P =89.5Hz),131.7(d,J C-P =2.9Hz),129.8(d,J C-P =9.4Hz),129.3,128.7(d,J C-P =11.6Hz),125.5,115.7,68.0,39.8(d,J C-P =8.7Hz),36.4(d,J C-P =66.4Hz),32.8(d,J C-P =12.3Hz),31.0(d,J C-P =6.5Hz),29.5(d,J C-P =65.7Hz),27.6; 31 P NMR (162MHz, CDCl3) δ59.38; IRν (cm -1):2963,1491,1242,1092,743,531; HRMS(EI)m / z:[M+Na] + Calcd for C 19 H 22 ClO2PNa + 371.0938; Found 371.0939; HPLC analysis: The ee was determined to be 91% on a CHIRALCELMD column (15% iPrOH in n-hexane, flow rate = 0.8mL / min, λ = 230nm, 30°C); retention times for compound obtained using(R,S)-L1:16.717min(major),18.637min(minor).

[0183] Peak Table

[0184] PDA Ch1 230nm

[0185] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 16.759 625.349 28.288 49.886 2 18.640 628.202 47.25 50.114

[0186] Peak Table

[0187] PDA Ch1 230nm

[0188] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 16.717 2573.004 117.676 95.404 2 18.637 123.966 5.315 4.596

[0189] Example 9: Using 1-phenyl-2,5-dihydrophosphine-1-oxide (1) and alkyl iodide (2i) as raw materials (reaction formula 9)

[0190]

[0191] In an argon-filled glove box, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added into a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), alkyl iodide 2i (0.1 mmol, 1 equiv.) and the corresponding olefin 1 (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product 3i was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0192] The product detection data are as follows: amorphous solid, yield 52%, ee = 93%.

[0193] 1 H NMR (400MHz, CDCl3) δ7.75–7.70(m,2H),7.54–7.46(m,3H),6.85(s,2H),4.32(t,J=6.4Hz,2H),2.37 –2.14(m,3H),2.283(s,6H),2.275(s,3H),2.09–2.03(m,1H),1.99–1.79(m,4H),1.76–1.64(m,3H); 13 C NMR (100MHz, CDCl3) δ170.1,139.3,135.0,134.3(d,J C-P =90.2Hz),131.7(d,J C-P =2.9Hz),130.9,129.8(d,J C-P =9.4Hz),128.7(d,J C-P =11.6Hz),128.4,64.5,39.7(d,J C-P =8.7Hz),36.4(d,J C-P =66.4Hz),32.7(d,J C-P =12.3Hz),30.8(d,J C-P =5.8Hz),29.5(d,J C-P =66.4Hz),27.0,21.1,19.8,19.7; 31P NMR (162MHz, CDCl3) δ59.1; IR ν (cm -1 ):2961,1719,1435,1084,744,484; HRMS(EI)m / z:[M+Na] + Calcd for C 23 H 29 O3PNa + 407.1747; Found 407.1758; HPLC analysis: The ee was determined to be 93% on a CHIRALCEL OJ-H column (15% iPrOH in n-hexane, flow rate = 0.8mL / min, λ = 230nm, 30°C); retention times for compound obtained using (R, S)-L1: 15.244min (major), 22.398min (minor).

[0194] Peak Table

[0195] PDA Ch1 230nm

[0196] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 15.256 404.002 10.883 50.287 2 22.302 399.384 5.957 49.713

[0197] Peak Table

[0198] PDA Ch1 230nm

[0199] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 15.244 396.761 10.558 96.724 2 22.398 13.437 0.236 3.276

[0200] Implementation Case 10

[0201] Using 1-phenyl-2,5-dihydrophosphine-1-oxide (1) and alkyl iodide (2j) as raw materials (reaction formula 10):

[0202]

[0203]

[0204] In an argon-filled glove box, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added into a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), alkyl iodide 2j (0.1 mmol, 1 equiv.) and the corresponding olefin 1 (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product 3j was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0205] The product detection data are as follows: amorphous solid, yield 66%, ee = 94%.

[0206] 1 H NMR (400MHz, CDCl3) δ7.75–7.70(m,2H),7.53–7.48(m,3H),6.92-6.91(m,1H),6.78(t,J=2.2Hz,1H),6.11 -6.09(m,1H),4.23(t,J=6.4Hz,2H),3.91(s,3H),2.38–2.15(m,3H),2.09–2.04(m,1H),2.03–1.63(m,7H); 13 C NMR(100MHz,CDCl3)δ161.2,134.3(d,J C-P =89.5Hz),131.6(d,J C-P =2.9Hz),129.8(d,J C-P =9.4Hz),129.5,128.6(d,J C-P =11.6Hz),122.4,117.7,107.8,63.4,39.7(d,J C-P =8.7Hz),36.8,36.4(d,J C-P =66.4Hz),32.7(d,J C-P =12.3Hz),30.9(d,J C-P =6.5Hz),29.5(d,J C-P =66.4Hz),27.2; 31P NMR (162MHz, CDCl3) δ59.3; IRν (cm -1 ):2967,1696,1413,1111,741,537; HRMS(EI)m / z:[M+Na] + Calcd for C 19 H 24 NO3PNa + 368.1386; Found 368.1399; HPLC analysis: The ee was determined to be 94% on a CHIRALCEL Amy-D column (15% iPrOH in n-hexane, flow rate = 0.8mL / min, λ = 230nm, 30°C); retention times for compound obtained using (R, S)-L1: 26.488min (minor), 30.613min (major).

[0207] Peak Table

[0208] PDA Ch1 230nm

[0209] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 26.676 731.350 14.212 49.433 2 30.987 748.139 12.021 50.567

[0210] Peak Table

[0211] PDA Ch1 230nm

[0212] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 26.488 16.363 0.384 2.856 2 30.613 556.502 8.970 97.144

[0213] Implementation Case 11

[0214] Using 1-phenyl-2,5-dihydrophosphine-1-oxide (1) and alkyl iodide (2k) as raw materials (reaction formula 11)

[0215]

[0216] In an argon-filled glove box, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added into a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), alkyl iodide 2k (0.1 mmol, 1 equiv.) and the corresponding olefin 1 (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product 3k was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0217] The product detection data are as follows: amorphous solid, yield 66%, de = 92:8.

[0218] 1 H NMR (400MHz, CDCl3) δ7.70–7.64(m,5H),7.52–7.45(m,3H),7.40-7.38(m,1H),7.13–7.08(m,2H),4.13–4.02(m,2H ),3.88(s,3H),3.83(q,J=7.2Hz,1H),2.20–1.99(m,3H),1.85–1.76(m,2H),1.66–1.51(m,7H),1.43–1.33(m,2H); 13 C NMR (100MHz, CDCl3) δ174.6,157.6,135.7,134.4(d,J C-P =89.5Hz),133.6,131.6(d,J C-P =2.8Hz),129.8(d,J C-P =9.7Hz),129.1,128.8,128.6(d,J C-P =11.4Hz),127.1,126.2,125.8,119.0,105.5,64.2,55.2,45.4,39.4(d,J C-P =8.9Hz),36.2(d,J C-P =66.7Hz),32.2(d,J C-P =12.5Hz),30.7(d,J C-P =6.0Hz),29.3(d,JC-P =66.3Hz),26.6,18.2; 31 P NMR (162MHz, CDCl3) δ59.1; IRν (cm -1 ):2973,1727,1608,1214,743,474; HRMS(EI)m / z:[M+Na] + Calcd for C 27 H 31 O4PNa + 473.1852; Found 473.1865; HPLC analysis:The ee was determined to be 92% on a CHIRALCELIA-3column (10% iPrOH in n-hexane, flow rate=0.8mL / min, λ=230nm, 30℃); retention times for compound obtained using(R,S)-L1:31.120min(major),34.910min(minor).

[0219] Peak Table

[0220] PDA Ch1 230nm

[0221] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 30.770 3925.619 100.849 51.317 2 34.349 3724.166 89.403 48.683

[0222] Peak Table

[0223] PDA Ch1 230nm

[0224] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 31.120 5137.206 132.899 96.046 2 34.910 211.465 5.125 3.954

[0225] Implementation Case 12

[0226] Using 1-phenyl-2,5-dihydrophosphine-1-oxide (1) and alkyl iodide (2l) as raw materials (reaction formula 12)

[0227]

[0228] In an argon-filled glove box, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added into a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), alkyl iodide 2l (0.1 mmol, 1 equiv.) and the corresponding olefin 1 (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product 3l was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0229] The product detection data are as follows: amorphous solid, yield 71%, de = 93:7.

[0230] 1 H NMR (400MHz, CDCl3) δ7.73–7.68(m,2H),7.53–7.48(m,3H),7.18(d,J=8.0Hz,2H),7.07(d,J=8.4Hz,2H),4.12–4.01(m,2H) ,3.67(q,J=7.2Hz,1H),2.43–2.40(m,2H),2.28–2.14(m,3H),1.95–1.60(m,7H),1.50–1.44(m,5H),0.87(d,J=6.6Hz,6H); 13 C NMR (100MHz, CDCl3) δ174.7,140.5,137.7,134.4(d,J C-P =89.5Hz),131.7(d,J C-P =2.9Hz),129.8(d,J C-P =9.4Hz),129.3,128.7,128.6(d,J C-P =11.6Hz),127.1,64.1,45.1,45.0,39.5(d,J C-P =8.7Hz),36.3(d,J C-P =67.2Hz),32.2(d,J C-P =12.3Hz),30.8(d,J C-P =5.8Hz),30.1,29.4(d,J C-P=66.5Hz),26.8,22.3,18.3; 31 P NMR (162MHz, CDCl3) δ59.2; IRν (cm -1 ):2962,1726,1437,1214,744,531; HRMS(EI)m / z:[M+Na] + Calcd for C 26 H 35 O3PNa + 449.2216; Found 449.2224; HPLC analysis: The ee was determined to be 93% on aCHIRALCEL Amy-D column (15% iPrOH in n-hexane, flow rate = 0.8mL / min, λ = 230nm, 30°C); retention times for compound obtained using(R,S)-L1:14.282min(major),15.603min(minor).

[0231] Peak Table

[0232] PDA Ch1 230nm

[0233] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 14.302 230.552 7.856 49.881 2 15.589 231.652 7.220 50.119

[0234] Peak Table

[0235] PDA Ch1 230nm

[0236] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 14.282 1041.738 35.207 96.614 2 15.603 36.513 1.244 3.386

[0237] Implementation Case 13

[0238] Using 1-phenyl-2,5-dihydrophosphine-1-oxide (1) and alkyl iodide (2m) as raw materials (reaction formula 13)

[0239]

[0240] In an argon-filled glove box, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added to a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), alkyl iodide 2m (0.1 mmol, 1 equiv.) and the corresponding olefin 1 (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product 3m was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0241] The product detection data are as follows: amorphous solid, yield 56%, ee = 90%.

[0242] 1 H NMR (400MHz, CDCl3) δ7.75–7.69(m,2H),7.53–7.46(m,3H),6.98(d,J=7.4Hz,1H),6.65–6.63(m,1H),6.60(s,1H) ,4.07(t,J=6.4Hz,2H),3.92–3.89(m,2H),2.36–2.16(m,9H),2.04–1.99(m,1H),1.92–1.57(m,11H),1.21(s,6H); 13 C NMR (100MHz, CDCl3) δ177.7,156.8,136.4,134.2(d,J C-P =89.6Hz),131.7(d,J C-P =2.8Hz),130.2,129.7(d,J C-P =9.7Hz),128.6(d,J C-P =11.5Hz),123.4,120.6,111.9,67.8,64.0,42.0,39.6(d,J C-P =8.7Hz),36.9,36.3(d,J C-P =66.7Hz),32.5(d,J C-P =12.3Hz),30.8(d,J C-P =6.0Hz),29.4(d,J C-P=66.3Hz),27.0,25.13,25.10,21.3,15.7; 31 P NMR (162MHz, CDCl3) δ59.0; IRν (cm -1 ):2974,1719,1214,1178,744,417; HRMS(EI)m / z:[M+Na] + Calcd for C 28 H 39 O4PNa + 493.2478; Found 493.2499; HPLC analysis: The ee was determined to be 90% on aCHIRALCEL OJ-H column (8% iPrOH in n-hexane, flow rate = 0.8mL / min, λ = 230nm, 30°C); retention times for compound obtained using(R,S)-L1:69.113min(minor),73.034min(major).

[0243] Peak Table

[0244] PDA Ch1 230nm

[0245] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 69.011 757.085 3.975 49.975 2 74.890 757.856 3.796 50.025

[0246] Peak Table

[0247] PDA Ch1 230nm

[0248] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 69.113 385.989 2.645 5.242 2 73.034 6977.180 32.862 94.758

[0249] Implementation Case 14

[0250] Using 1-phenyl-2,5-dihydrophosphine-1-oxide (1) and alkyl iodide (2n) as raw materials (reaction formula 14):

[0251]

[0252] In an argon-filled glove box, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added into a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), alkyl iodide 2n (0.1 mmol, 1 equiv.) and the corresponding olefin 1 (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product 3n was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0253] The product detection data are as follows: amorphous solid, yield 68%, ee = 93%.

[0254] 1 H NMR (400MHz, CDCl3) δ7.72–7.67(m,2H),7.63–7.60(m,2H),7.57–7.5(m,2H),7.51–7.45(m,3H),7.36–7.27( m,6H),4.15–4.11(m,2H),3.17(t,J=7.4Hz,2H),2.90(t,J=7.4Hz,2H),2.30–2.07(m,3H),2.00-1.38(m,8H); 13 C NMR (100MHz, CDCl3) δ171.9,161.6,145.3,135.0,134.4(d,J C-P =89.6Hz),132.4,131.6(d,J C-P =2.8Hz),129.8(d,J C-P =9.7Hz),128.9,128.7,128.6(d,J C-P =10.2Hz),128.5,128.4,128.0,127.8,126.4,64.4,39.6(d,J C-P =8.8Hz),36.3(d,J C-P =66.7Hz),32.4(d,J C-P =12.4Hz),31.0,30.8(d,J C-P =6.0Hz),29.4(d,J C-P=66.3Hz),26.9,23.5; 31 P NMR (162MHz, CDCl3) δ59.1; IRν (cm -1 ):2925,1628,1464,1258,1180,742; HRMS(EI)m / z:[M+Na] + Calcd for C 31 H 32 NO4PNa + 536.1961; Found 536.1952; HPLC analysis: The ee was determined to be 93% on a CHIRALCELMD column (8% iPrOH in n-hexane, flow rate = 0.8mL / min, λ = 280nm, 30°C); retention times for compound obtained using(R,S)-L1:75.556min(major),80.636min(minor).

[0255] Peak Table

[0256] PDA Ch1 280nm

[0257] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 75.048 88.425 0.831 49.065 2 79.576 91.796 0.787 50.935

[0258] Peak Table

[0259] PDA Ch1 280nm

[0260] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 75.556 1723.919 14.911 96.605 2 80.636 60.593 0.592 3.395

[0261] Implementation Case 15

[0262] Using 1-phenyl-2,5-dihydrophosphine-1-oxide (1) and alkyl iodide (2o) as raw materials (reaction formula 15)

[0263]

[0264] In an argon-filled glove box, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added into a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), alkyl iodide 2o (0.1 mmol, 1 equiv.) and the corresponding olefin 1 (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product 3o was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0265] The product detection data are as follows: amorphous solid, yield 70%, ee = 91%.

[0266] 1 H NMR (400MHz, CDCl3) δ7.74–7.69(m,2H),7.65(d,J=8.5Hz,2H),7.54–7.46(m,5H),6.97(d,J=2.5Hz,1H),6.86(d,J=9.0Hz,1H),6.66(dd,J=9.0,2. 5Hz,1H),4.12(t,J=6.5Hz,2H),3.82(s,3H),3.66(s,2H),2.39(s,3H),2. 28–2.12(m,3H),2.02–1.87(m,3H),1.70–1.67(m,5H),1.54–1.48(m,2H); 13 C NMR (100MHz, CDCl3) δ170.8,168.3,156.0,139.3,136.0,134.4(d,J C-P =89.4Hz),133.9,131.7(d,J C-P =2.9Hz),131.2,130.8,130.6,129.8(d,J C-P =9.8Hz),129.1,128.7(d,J C-P =11.5Hz),114.9,112.6,111.4,101.6,64.6,55.7,39.6(d,J C-P =8.8Hz),36.3(d,J C-P=66.7Hz),32.4(d,J C-P =12.3Hz),30.8(d,J C-P =6.2Hz),30.4,29.4(d,J C-P =66.1Hz),27.0,13.33; 31 P NMR (162MHz, CDCl3) δ59.1; IRν (cm -1 ):2926,1680,1316,1088,800,484; HRMS(EI)m / z:[M+Na] + Calcd for C 32 H 33 ClNO5PNa + 600.1677; Found 600.1679; HPLC analysis: The ee was determined to be 91% on aCHIRALCEL OJH column (20% iPrOH in n-hexane, flow rate = 0.8mL / min, λ = 230nm, 30°C); retention times for compound obtained using(R,S)-L1:34.054min(minor),38.425min.

[0267] Peak Table

[0268] PDA Ch1 230nm

[0269] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 33.210 6087.557 63.454 50.522 2 37.635 5961.801 55.131 49.478

[0270] Peak Table

[0271] PDA Ch1 230nm

[0272]

[0273]

[0274] Implementation Case 16

[0275] Using 1-biphenyl-2,5-dihydrophosphine-1-oxide (1a) and alkyl iodide (2a) as raw materials (reaction formula 16)

[0276]

[0277] In an argon-filled glove box, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added into a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), alkyl iodide 2a (0.1 mmol, 1 equiv.) and the corresponding olefin 1a (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product 4a was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0278] The product detection data are as follows: amorphous solid, yield 84%, ee = 90%.

[0279] 1 H NMR (400MHz, CDCl3) δ7.79–7.74(m,2H),7.71-7.68(m,2H),7.62-7.60(m,2H),7.49–7.45(m,2H),7.42–7.38(m,1H),7.10(d,J=8.6Hz, 2H),6.84(d,J=8.6Hz,2H),3.79(s,3H),2.68–2.63(m,2H),2.42–2.36(m,1H),2.29–2.17(m,2H),2.09–2.06(m,1H),1.99–1.72(m,5H); 13 C NMR(100MHz,CDCl3)δ157.9,144.5(d,J C-P =2.9Hz),139.9,133.6,133.0(d,J C-P =90.3Hz),130.3(d,J C-P =9.9Hz),129.1,128.9,128.1,127.3(d,J C-P =10.8Hz),127.2,113.8,55.2,39.3(d,J C-P =89.5Hz),38.1(d,J C-P =12.2Hz),36.3(d,J C-P =66.8Hz),33.1,30.9(d,J C-P=6.1Hz),29.6(d,J C-P =66.4Hz); 31 P NMR (162MHz, CDCl3) δ59.2; IRν (cm -1 ):2924,1510,1243,1177,762,557; HRMS(EI)m / z:[M+Na] + Calcd for C 25 H 27 O2PNa + 413.1641; Found 413.1648; HPLC analysis: The ee was determined to be 90% on aCHIRALCEL Amy-D column (15% iPrOH in n-hexane, flow rate = 0.8mL / min, λ = 230nm, 30°C); retention times for compound obtained using(R,S)-L1:28.132min(minor),34.735min(major).

[0280] Peak Table

[0281] PDA Ch1 230nm

[0282] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 28.673 675.357 11.416 50.318 2 35.352 666.822 9.273 49.682

[0283] Peak Table

[0284] PDA Ch1 230nm

[0285] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 28.132 59.237 1.102 4.849 2 34.735 1162.290 16.179 95.151

[0286] Implementation Case 17

[0287] Using 1-(4'-methoxy)phenyl-2,5-dihydrophosphine-1-oxide (1b) and alkyl iodide (2a) as raw materials (reaction formula 17)

[0288]

[0289] In an argon-filled glove box, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added into a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), alkyl iodide 2a (0.1 mmol, 1 equiv.) and the corresponding olefin 1b (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product 4b was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0290] The product detection data are as follows: amorphous solid, yield 69%, ee = 95%.

[0291] 1 H NMR (400MHz, CDCl3) δ7.64–7.59(m,2H),7.08(d,J=8.8Hz,2H),6.99–6.96(m,2H),6.82(d,J=8 .0Hz,2H),3.84(s,3H),3.78(s,3H),2.65–2.59(m,2H),2.34–2.11(m,3H),2.01-1.65(m,6H); 13 C NMR(100MHz,CDCl3)δ162.2(d,J C-P =2.9Hz),157.8,133.6,131.6(d,J C-P =11.6Hz),129.1,125.5(d,J C-P =95.3Hz),114.2(d,J C-P =12.3Hz),113.8,55.3(d,J C-P =8.7Hz),39.2(d,J C-P =8.7Hz),38.1(d,J C-P =12.3Hz),36.7,36.0,33.1,30.9(d,J C-P =6.5Hz),29.6(d,J C-P =67.2Hz); 31 P NMR (162MHz, CDCl3) δ59.3; IRν (cm -1):2927,1510,1243,1175,829,525; HRMS(EI)m / z:[M+Na] + Calcd for C 20 H 25 O3PNa + 367.1434; Found367.1439; HPLC analysis: The ee was determined to be 95% on a CHIRALCEL Amy-Dcolumn (10% iPrOH in n-hexane, flow rate = 1.0mL / min, λ = 230nm, 30°C); retention times for compound obtained using(R,S)-L1:26.300min(minor),29.898min(major).

[0292] Peak Table

[0293] PDA Ch1 230nm

[0294] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 26.225 584.840 10.835 50.010 2 29.925 584.618 9.632 49.990

[0295] Peak Table

[0296] PDA Ch1 230nm

[0297] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 26.300 118.156 2.900 2.593 2 29.898 4438.242 74.173 97.407

[0298] Implementation Case 18

[0299] Using 1-(4'-methyl)phenyl-2,5-dihydrophosphine-1-oxide (1c) and alkyl iodide (2a) as raw materials (reaction formula 18)

[0300]

[0301] In an argon-filled glove box, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added into a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), alkyl iodide 2a (0.1 mmol, 1 equiv.) and the corresponding olefin 1c (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product 4c was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0302] The product detection data are as follows: amorphous solid, yield 76%, ee = 93%.

[0303] 1 H NMR (400MHz, CDCl3) δ7.61–7.56(m,2H),7.28(d,J=7.0Hz,2H),7.09(d,J=6.6Hz,2H),6.83(d,J=8.4Hz,2H),3.78( s,3H),2.68–2.57(m,2H),2.40(s,3H),2.66–2.60(m,1H),2.25–2.12(m,2H),2.04–1.96(m,1H),1.93–1.70(m,5H); 13 C NMR(100MHz,CDCl3)δ157.8,142.1(d,J C-P =2.9Hz),133.6,131.1(d,J C-P =92.4Hz),129.8(d,J C-P =10.1Hz),129.4(d,J C-P =11.6Hz),129.1,113.8,55.2,39.3(d,J C-P =8.7Hz),38.1(d,J C-P =12.3Hz),36.3(d,J C-P =66.4Hz),33.1,30.9(d,J C-P =5.8Hz),29.6(d,J C-P =66.4Hz),21.5; 31P NMR (162MHz, CDCl3) δ59.6; IRν (cm -1 ):2924,1511,1243,1176,748,499; HRMS(EI)m / z:[M+Na] + Calcd for C 20 H 25 O2PNa + 351.1484; Found 351.1492; HPLC analysis: The ee was determined to be 93% on a CHIRALCEL Amy-D column (8% iPrOH in n-hexane, flowrate=1.0mL / min, λ=230nm, 30℃); retention times for compound obtained using (R, S)-L1: 35.609min (minor), 40.655min (major).

[0304] Peak Table

[0305] Detector A Ch1 230nm

[0306] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 35.635 1375.792 18.311 50.870 2 40.882 1328.738 16.001 49.130

[0307] Peak Table

[0308] Detector A Ch1 230nm

[0309] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 35.609 597.880 4.60 3.264 2 40.655 17719.247 95.40 96.736

[0310] Implementation Case 19

[0311] Using 1-(3'-methyl)phenyl-2,5-dihydrophosphine-1-oxide (1d) and alkyl iodide (2a) as raw materials (reaction formula 19)

[0312]

[0313] In an argon-filled glove box, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added into a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), alkyl iodide 2a (0.1 mmol, 1 equiv.) and the corresponding olefin 1d (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product 4d was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0314] The product detection data are as follows: amorphous solid, yield 67%, ee = 91%.

[0315] 1 H NMR (400MHz, CDCl3) δ7.54(d,J=12.0Hz,1H),7.47–7.42(m,1H),7.39–7.35(m,1H),7.34–7.32(m,1H),7.09(d,J=8.6Hz,2H), 6.83(d,J=8.6Hz,2H),3.79(s,3H),2.67–2.61(m,2H),2.40(s,3H),2.38–2.13(m,3H),2.04–1.97(m,1H),1.94–1.68(m,5H); 13 C NMR(100MHz,CDCl3)δ157.8,138.5(d,J C-P =11.6Hz),134.3(d,J C-P =89.5Hz),133.6,132.4(d,J C-P =2.9Hz),130.5(d,J C-P =9.4Hz),129.1,128.5(d,J C-P =12.3Hz),126.7(d,J C-P =10.1Hz),113.8,55.2,39.4(d,J C-P =8.7Hz),38.1(d,J C-P =12.3Hz),36.2(d,J C-P =66.4Hz),33.1,31.0(d,JC-P =5.8Hz),29.6(d,J C-P =65.7Hz),21.4; 31 P NMR (162MHz, CDCl3) δ59.6; IRν (cm -1 ):2967,1511,1215,1176,744,519; HRMS(EI)m / z:[M+Na] + Calcd for C 20 H 25 O2PNa + 351.1484; Found 351.1485; HPLC analysis: The ee was determined to be 91% on a CHIRALCEL OJ-H column (15% iPrOH in n-hexane, flow rate = 0.8mL / min, λ = 230nm, 30°C); retention times for compound obtained using(R,S)-L1:14.637min(major),17.589min(minor).

[0316] Peak Table

[0317] PDA Ch1 230nm

[0318] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 14.626 811.448 28.170 51.136 2 17.553 775.387 22.679 48.864

[0319] Peak Table

[0320] PDA Ch1 230nm

[0321] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 14.637 631.130 21.904 95.559 2 17.589 29.330 0.914 4.441

[0322] Implementation Case 20

[0323] Using 1-(4'-trifluoromethyl)phenyl-2,5-dihydrophosphine-1-oxide (1e) and alkyl iodide (2a) as raw materials (reaction formula 20)

[0324]

[0325] In an argon-filled glove box, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added into a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), alkyl iodide 2a (0.1 mmol, 1 equiv.) and the corresponding olefin 1e (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product 4e was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0326] The product detection data are as follows: amorphous solid, yield 90%, ee = 89%.

[0327] 1 H NMR (400MHz, CDCl3) δ7.88-7.78(m,2H),7.72(d,J=8.0Hz,2H),7.07(d,J=8.5Hz,2H),6.82(d,J=8. 4Hz,2H),3.77(s,3H),2.69–2.56(m,2H),2.37–2.16(m,3H),2.03–1.97(m,1H),1.92–1.74(m,5H); 13 C NMR(100MHz,CDCl3)δ157.9,138.8(d,J C-P =86.6Hz),133.5(dq,J C-F =31.5Hz,J C-P =2.9Hz),133.3,130.3(d,J C-P =9.4Hz),129.0,125.4(dq,J C-P =11.5Hz,J C-F =3.6Hz),123.5(q,J C-F =271.5Hz),113.8,55.2,39.3(d,J C-P =8.7Hz),37.8(d,J C-P =12.3Hz),36.1(d,J C-P =67.2Hz),33.0,30.8(d,J C-P =6.5Hz),29.4(d,JC-P =66.4Hz); 31 P NMR (162 MHz, CDCl3) δ 58.7; 19 F NMR (377MHz, CDCl3) δ-63.1; IRν (cm -1 ):2926,1511,1322,1127,749,543; HRMS(EI)m / z:[M+Na] + Calcd for C 20 H 22 F3O2PNa + 405.1202; Found 405.1220; HPLC analysis: The ee was determined to be 89% on aCHIRALCEL Amy-D column (15% iPrOH in n-hexane, flow rate = 0.8mL / min, λ = 230nm, 30°C); retention times for compound obtained using(R,S)-L1:15.422min(minor),17.243min(major).

[0328] Peak Table

[0329] PDA Ch1 230nm

[0330] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 15.473 699.177 22.593 50.687 2 17.457 680.237 19.760 49.313

[0331] Peak Table

[0332] PDA Ch1 230nm

[0333] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 15.422 16.659 0.592 5.697 2 17.243 275.770 8.067 94.303

[0334] Implementation Case 21

[0335] Using 1-naphthyl-2,5-dihydrophosphine-1-oxide (1f) and alkyl iodide (2a) as raw materials (reaction formula 21)

[0336]

[0337] In an argon-filled glove box, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added into a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), alkyl iodide 2a (0.1 mmol, 1 equiv.) and the corresponding olefin 1f (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product 4f was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0338] The product detection data are as follows: amorphous solid, yield 82%, ee = 95%.

[0339] 1 H NMR (400MHz, CDCl3) δ8.56(d,J=8.4Hz,1H),8.00(d,J=8.4Hz,1H),7.91(d,J=8.2Hz,1H),7.80-7.75(m,1H),7.64–7.55(m,2H),7.5 1–7.47(m,1H),7.09(d,J=8.4Hz,2H),6.82(d,J=8.4Hz,2H),3.78(s,3H),2.78–2.59(m,3H),2.39–2.14(m,3H),2.00–1.81(m,5H); 13 C NMR(100MHz,CDCl3)δ157.8,133.8(d,J C-P =8.7Hz),133.6,132.83,132.8(d,J C-P =2.9Hz),130.2(d,J C-P =86.6Hz),129.6(d,J C-P =10.1Hz),129.12,129.09,127.5,126.5,126.2(d,J C-P =5.8Hz),124.4(d,J C-P =13.0Hz),113.8,55.2,38.0(d,J C-P =11.6Hz),37.99,35,1(d,J C-P=67.2Hz),33.1,30.6(d,J C-P =5.8Hz),28.8(d,J C-P =67.2Hz); 31 P NMR (162MHz, CDCl3) δ62.1; IRν (cm -1 ):2926,1510,1243,1175,746,523; HRMS(EI)m / z:[M+Na] + Calcd for C 23 H 25 O2PNa + 387.1484; Found 387.1484; HPLC analysis: Theee was determined to be 95% on a CHIRALCEL OJ-H column (10% iPrOH in n-hexane, flow rate = 0.8mL / min, λ = 230nm, 30℃); retention times for compoundobtainedusing(R,S)-L1:23.761min(major),34.868min(minor).

[0340] Peak Table

[0341] PDA Ch1 230nm

[0342] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 24.187 1090.849 16.755 50.767 2 33.085 1057.870 15.543 49.233

[0343] Peak Table

[0344] PDA Ch1 230nm

[0345] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 23.761 5306.700 90.646 97.594 2 34.868 130.822 2.284 2.406

[0346] Implementation Case 22

[0347] Using 1-octyl-2,5-dihydrophosphine-1-oxide (1g) and alkyl iodide (2a) as raw materials (reaction formula 22)

[0348]

[0349] In a glove box filled with argon, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added to a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), alkyl iodide 2a (0.1 mmol, 1 equiv.) and the corresponding olefin 1a (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product (4 g) was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0350] The product detection data are as follows: amorphous solid, yield 91%, ee = 90%.

[0351] 1 H NMR(400MHz, CDCl3)δ7.06(d,J=8.6Hz,2H),6.82(d,J=8.6Hz,2H),3.77(s,3H),2.64–2.52(m,2H ),2.14–1.91(m,3H),1.78–1.55(m,9H),1.46–1.36(m,3H),1.33–1.21(m,8H),0.89–0.85(m,3H); 13 C NMR (100MHz, CDCl3) δ157.8,133.6,129.1,113.8,55.2,38.0(d,J C-P =9.0Hz),37.9(d,J C-P =11.6Hz),33.8(d,J C-P =63.5Hz),33.0,31.7,31.3(d,J C-P =62.1Hz),31.0(d,J C-P =13.8Hz),30.5(d,J C-P =5.8Hz),29.1,29.0,26.7(d,J C-P =63.5Hz),22.6,22.1(d,J C-P =4.3Hz),14.0; 31 P NMR (162MHz, CDCl3) δ70.1; IRν (cm -1):2925,1511,1244,1037,747,521; HRMS(EI)m / z:[M+Na] + Calcd for C 21 H 35 O2PNa + 373.2267; Found373.2273; HPLC analysis: The ee was determined to be 90% on a CHIRALCEL OJ-H column (15% iPrOH in n-hexane, flow rate = 0.8mL / min, λ = 230nm, 30°C); retention times for compound obtained using(R,S)-L1:6.750min(major),7.202min(minor).

[0352] Peak Table

[0353] PDA Ch1 230nm

[0354] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 6.733 2115.759 187.972 49.819 2 7.183 2131.166 175.592 50.181

[0355] Peak Table

[0356] PDA Ch1 230nm

[0357]

[0358]

[0359] Implementation Case 23

[0360] Using 1-tert-butyl-2,5-dihydrophosphine-1-oxide (1h) and alkyl iodide (2a) as raw materials (reaction formula 23)

[0361]

[0362] In an argon-filled glove box, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added into a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), alkyl iodide 2a (0.1 mmol, 1 equiv.) and the corresponding olefin 1h (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product 4h was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0363] The product detection data are as follows: amorphous solid, yield 65%, ee = 96%.

[0364] 1 H NMR(400MHz, CDCl3)δ7.07(d,J=8.4Hz,2H),6.82(d,J=6.6Hz,2H),3.78(s,3H),2.66–2 .53(m,2H),2.23–2.18(m,1H),2.10–1.99(m,2H),1.82–1.71(m,6H),1.19-1.15(m,9H); 13 C NMR (100MHz, CDCl3) δ157.8,133.7,129.1,113.8,55.2,39.5(d,J C-P =7.2Hz),38.2(d,J C-P =10.8Hz),33.2,31.7(d,J C-P =62.8Hz),30.7(d,J C-P =5.1Hz),30.6(d,J C-P =59.9Hz),24.2,23.1(d,J C-P =59.9Hz); 31 P NMR (162MHz, CDCl3) δ82.4; IRν (cm -1 ):2927,1512,1245,1140,764,564; HRMS(EI)m / z:[M+Na] + Calcd for C 17 H 27 O2PNa+ 317.1641; Found317.1652; HPLC analysis: The ee was determined to be 96% on a CHIRALCEL Amy-Dcolumn (15% iPrOH in n-hexane, flow rate = 0.8mL / min, λ = 230nm, 30°C); retention times for compound obtained using (R, S)-L1: 8.918min (major), 10.411min (minor).

[0365] Peak Table

[0366] PDA Ch1 230nm

[0367] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 8.938 213.127 11.767 49.791 2 10.403 214.913 10.198 50.209

[0368] Peak Table

[0369] PDA Ch1 230nm

[0370] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 8.918 2868.195 163.906 98.211 2 10.411 52.234 2.608 1.789

[0371] Implementation Case 24

[0372] Using 1-isopropyl-2,5-dihydrophosphine-1-oxide (1i) and alkyl iodide (2a) as raw materials (reaction formula 24)

[0373]

[0374] In an argon-filled glove box, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added into a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), alkyl iodide 2a (0.1 mmol, 1 equiv.) and the corresponding olefin 1i (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product 4i was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0375] The product detection data are as follows: amorphous solid, yield 58%, ee = 95%.

[0376] 1 H NMR(400MHz, CDCl3)δ7.05(d,J=6.2Hz,2H),6.80(d,J=8.3Hz,2H),3.76(s,3H),2.62–2 .53(m,2H),2.23–1.98(m,4H),1.88–1.62(m,5H),1.43–1.31(m,1H),1.25–1.14(m,6H); 13 C NMR (100MHz, CDCl3) δ157.8,133.6,129.0,113.8,55.2,38.6(d,J C-P =8.0Hz),38.0(d,J C-P =11.2Hz),33.0,31.8(d,J C-P =61.6Hz),30.5(d,J C-P =5.3Hz),28.8(d,J C-P =63.1Hz),24.5(d,J C-P =62.0Hz),15.7(d,J C-P =2.8Hz),15.4(d,J C-P =2.7Hz); 31 P NMR (162MHz, CDCl3) δ77.3; IRν (cm -1 ):2924,1512,1245,1176,776,537; HRMS(EI)m / z:[M+Na] + Calcd for C 16 H 25 O2PNa + 303.1484; Found 303.1492; HPLC analysis: The ee was determined to be 95% on a CHIRALCEL OJH column (15% iPrOH in n-hexane, flowrate=0.8mL / min, λ=230nm, 30℃); retention times for compound obtained using (R, S)-L1: 9.293min (major), 14.232min (minor).

[0377] Peak Table

[0378] PDA Ch1 230nm

[0379] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 10.067 1962.898 103.745 51.210 2 14.807 1870.103 76.652 48.790

[0380] Peak Table

[0381] PDA Ch1 230nm

[0382] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 9.293 23652.373 1132.491 97.433 2 14.232 623.058 25.311 2.567

[0383] Implementation Case 25

[0384] Using 1-cyclohexyl-2,5-dihydrophosphine-1-oxide (1j) and alkyl iodide (2a) as raw materials (reaction formula 25)

[0385]

[0386] In an argon-filled glove box, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added into a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), alkyl iodide 2a (0.1 mmol, 1 equiv.) and the corresponding olefin 1j (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product 4j was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0387] The product detection data are as follows: amorphous solid, yield 77%, ee = 86%.

[0388] 1 H NMR(400MHz, CDCl3)δ7.06(d,J=8.6Hz,2H),6.82(d,J=8.6Hz,2H),3.78(s,3H),2.61–2 .56(m,2H),2.20–2.14(m,1H),2.00–1.83(m,6H),1.76–1.58(m,7H),1.38–1.24(m,6H); 13 C NMR (100MHz, CDCl3) δ157.8,133.7,129.1,113.8,55.2,39.1(d,J C-P=63.3Hz),38.5(d,J C-P =11.6Hz),38.0(d,J C-P =11.6Hz),33.1,31.7(d,J C-P =61.7Hz),30.5(d,J C-P =5.0Hz),26.3(d,J C-P =2.4Hz),25.8,25.6(d,J C-P =3.2Hz),25.3(d,J C-P =2.9Hz),24.6(d,J C-P =61.9Hz); 31 P NMR (162MHz, CDCl3) δ73.8; IRν (cm -1 ):2926,1512,1245,1031,749,533; HRMS(EI)m / z:[M+Na] + Calcd for C 19 H 29 O2PNa + 343.1797; Found 343.1805; HPLC analysis: The ee was determined to be 86% on a CHIRALCEL Amy-D column (10% iPrOH in n-hexane, flow rate = 0.8mL / min, λ = 230nm, 30℃); retention times for compoundobtained using(R,S)-L1:24.706min(minor),29.539min(major).

[0389] Peak Table

[0390] PDA Ch1 230nm

[0391] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 25.467 1676.319 31.027 52.534 2 29.955 1514.602 26.569 47.466

[0392] Peak Table

[0393] PDA Ch1 230nm

[0394] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 24.706 230.556 4.421 6.743 2 29.539 3188.825 54.673 93.257

[0395] Implementation Case 26

[0396] Using 1-benzyl-2,5-dihydrophosphine-1-oxide (1k) and alkyl iodide (2j) as raw materials (reaction formula 26)

[0397]

[0398] In an argon-filled glove box, CoBr2·(DME) (0.01 mmol, 0.1 equiv.), (R,S)-Box ligand L1 (0.012 mmol, 0.12 equiv.) and 1,4-dioxane (1 mL) were added into a 10 mL dry Schlenk tube, and the mixture was stirred at room temperature for 30 min. Then, cesium fluoride (0.3 mmol, 3 equiv.), alkyl iodide 2j (0.1 mmol, 1 equiv.) and the corresponding olefin 1k (0.15 mmol, 1.5 equiv.) were added. The Schlenk tube was sealed and removed from the glove box. Dimethoxymethylsilane (0.3 mmol, 3 equiv.) was added thereto at 0°C. The reaction was stirred at 10°C for 12 h. After the reaction was completed, the reaction mixture was diluted with water, extracted with ethyl acetate, dried over sodium sulfate, and the solvent was dried under vacuum. The target product 4k was purified and separated by column chromatography (eluent: dichloromethane: methanol = 20:1).

[0399] The product detection data are as follows: amorphous solid, yield 66%, ee = 93%.

[0400] 1 H NMR (400MHz, CDCl3) δ7.35–7.24(m,5H),6.91–6.90(m,1H),6.78(t,J=2.2Hz,1H),6.12–6.10(m,1H),4.1 7–4.14(m,2H),3.92(s,3H),3.31-3.19(m,2H),2.21–2.16(m,1H),1.92–1.61(m,8H),1.59–1.44(m,2H); 13 C NMR(100MHz,CDCl3)δ161.2,132.1(d,J C-P =7.2Hz),129.6,129.5(d,J C-P =5.1Hz),128.9(d,J C-P =2.9Hz),127.1(d,J C-P =2.9Hz),122.4,117.7,107.8,63.3,39.0(d,J C-P =55.6Hz),38.2(d,J C-P =9.4 Hz),36.8,33.3(d,J C-P =64.3Hz),32.4(d,J C-P =13.0Hz),30.4(d,JC-P =5.8Hz),27.0,25.6(d,J C-P =64.3Hz); 31 P NMR(162MHz,CDCl3)δ68.3;IRν(cm -1 ):2925,1696,1412,1243,1109,745;HRMS(EI)m / z:[M+Na] + Calcd for C 20 H 26 NO3PNa + 382.1543;Found 382.1558;HPLC analysis:The ee wasdetermined to be 93%on a CHIRALCEL Amy-D column(15%iPrOH in n-hexane,flowrate=0.8mL / min,λ=230nm,30℃);retention times for compound obtainedusing(R,S)-L1:22.986min(major),27.267min(minor)。

[0401] Peak Table

[0402] PDA Ch1 230nm

[0403] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 22.823 568.492 12.215 50.444 2 26.979 558.477 10.234 49.556

[0404] Peak Table

[0405] PDA Ch1 230nm

[0406] Peak[#] Ret.Time[min] Area[mAV*s] Height[mAV] Area[%] 1 22.986 429.684 9.162 96.261 2 27.267 16.688 0.375 3.739

Claims

1. A chiral synthesis method for preparing phosphopentane oxide, characterized in that 1-phenyl-2,5-dihydrophosphinazole-1-oxide and alkyl iodide are used as substrates, ethylene glycol dimethyl ether cobalt dibromide and (R,S)-BOX are used as catalysts, dimethoxymethylsilane is used as a reducing agent, and cesium fluoride is used as a base, and the phosphopentane oxide is obtained by reaction at 10°C. The reaction formula is as follows: in: R 1 is selected from phenyl, methoxy, methyl, trifluoromethyl, naphthyl, n-octyl, tert-butyl, benzyl, isopropyl, cyclohexyl, R 2 The alkyl iodide is selected from p-methoxyphenethyl, p-methylphenethyl, m-methylphenethyl, o-trifluoromethylphenethyl, 2,4,6-trimethylphenethyl, naphthylethyl and other substituted alkyl iodides.

2. A method for synthesizing chiral phosphopentane oxide according to claim 1, characterized in that: The cobalt catalyst used is selected from ethylene glycol dimethyl ether cobalt dibromide, cobalt chloride, cobalt bromide, cobalt iodide, cobalt acetylacetonate, cobalt acetate, etc., preferably ethylene glycol dimethyl ether cobalt dibromide.

3. A method for synthesizing chiral phosphopentane oxide according to claim 1, characterized in that: The reducing agent used is selected from triethoxysilane, trimethoxysilane, diethoxymethylsilane, dimethoxymethylsilane, etc., preferably dimethoxymethylsilane.

4. A method for synthesizing chiral phosphopentane oxide according to claim 1, characterized in that: The base used is selected from cesium fluoride.

5. A method for synthesizing chiral phospholane oxide according to claim 1, characterized in that: The temperature used was selected from 10°C.

6. A method for synthesizing chiral phosphopentane oxide according to claim 1, characterized in that: The organic solvent used is selected from 1,4-dioxane, ethylene glycol dimethyl ether, anisole, tetrahydrofuran, etc., preferably 1,4-dioxane.

7. A method for synthesizing chiral phospholane oxide according to claim 1, characterized in that: The molar mass ratio of each substance in the reaction is selected from: 1-phenyl-2,5-dihydrophosphine-1-oxide: alkyl iodide: catalyst: dimethoxymethylsilane: cesium fluoride = 1.5:1:0.1:3:3.

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