Chiral nitrile compound and preparation method thereof

Abstract

The invention belongs to the technical field of preparation of organic compounds, and particularly relates to a preparation method of a chiral nitrile compound. In order to reduce the raw material cost and broaden the substrate selection range, trialkyl phosphite mediated visible light / copper is adopted to synergistically catalyze alkoxy free radical deoxidation to participate in asymmetric cyanation alkylation reaction of alkene, and various cheap and easily available alkene and cyanotrimethylsilane are used as starting raw materials to prepare the chiral nitrile compound in one step. The chiral nitrile compound obtained by the method has various types, can be directly used, and can also be used for further preparing compounds such as chiral amide and chiral carboxylic acid. The reaction conditions for preparing the chiral nitrile compound are mild, the reaction operation and post-treatment are simple, the production cost can be greatly reduced, and the production efficiency is improved.

Description

Technical Field

[0001] The invention belongs to the technical field of preparation of organic compounds, and specifically relates to a method for preparing chiral nitrile compounds. Background Art

[0002] Chiral nitrile compounds have a wide range of applications in synthetic chemistry, medicinal chemistry and natural products. At the same time, under certain conditions, they can be efficiently converted into chiral carboxylic acids, chiral amides, chiral ester compounds, etc. In addition, chiral nitrile compounds are the synthetic precursors of many drug molecules, such as the common carboxylic acid structure in the structure of non-steroidal anti-inflammatory drugs, which can be obtained by simple and efficient conversion of chiral nitrile compounds. Therefore, the efficient synthesis of chiral nitrile compounds and their derivatives has attracted the attention of organic chemists and medicinal chemists. In recent years, the research on transition metal-catalyzed asymmetric cyanation reactions has developed rapidly, such as asymmetric cyanation reactions of carbon-hydrogen bonds and asymmetric cyanation reactions of olefins, but overall it still faces some challenges, such as substrate limitations and expensive raw materials, and there are no reports of examples of trialkylphosphite-mediated visible light / copper-catalyzed alkoxy radical deoxygenation participating in asymmetric cyanation alkylation reactions of olefins.

[0003] Therefore, from a synthetic point of view, the efficient preparation of asymmetric cyanoalkylation reactions involving trialkylphosphite-mediated visible light / copper-catalyzed alkoxyl radical deoxygenation under mild conditions using cheap and readily available olefin feedstocks is still highly desirable. Summary of the invention

[0004] In view of the above technical problems, the present invention provides a chiral nitrile compound and a preparation method thereof.

[0005] The following technical solutions are used to achieve this:

[0006] A chiral nitrile compound, the general structural formula of which is:

[0007] Wherein R is selected from one of aromatic derivatives containing 1 to 3 benzene rings, R 1 One selected from an alkyl group having 2 to 6 carbon atoms, a fluorine-substituted alkyl group, a cyano-substituted alkyl group or an ester group having 3 to 7 carbon atoms;

[0008] Specifically, R is selected from one of naphthalene-1-yl, naphthalene-2-yl, 6-methoxynaphthalene-2-yl, phenyl, p-methoxyphenyl, p-methoxycarbonylphenyl, p-trifluoromethylphenyl, p-cyanophenyl, p-bromophenyl, p-fluorophenyl, p-chlorophenyl, m-bromophenyl, o-bromophenyl, biphenyl, m-benzoylphenyl, N-(4-trifluoromethyl)phenylcarbamoylphenyl, N-methyl-N-(4-trifluoromethylphenyl)carbamoylphenyl, pentafluorophenyl, p-trifluoromethylbiphenyl or p-estroneoxycarbonylphenyl; R 1 One selected from trifluoroethyl, difluoroethyl, pentafluoropropyl, 2-methoxy-2-oxoethyl-1-yl, cyanomethyl or ethyl;

[0009] Specifically, the chiral nitrile compound is selected from one of the following structural compounds:

[0010]

[0011] The chiral nitrile compound is prepared by the following preparation method, comprising the following steps: under nitrogen or inert gas protection conditions, a copper catalyst, a chiral oxazoline ligand, tris(2-phenylpyridine)iridium, an olefin, cyanotrimethylsilane, a trialkylphosphite and an N-hydroxyphthalimide alkyl ether are dissolved in a solvent, and the reaction is carried out under light. After the reaction is completed, a saturated sodium chloride solution is added for dilution, and the solvent is removed by distillation under reduced pressure after extraction with dichloromethane, and the chiral nitrile compound is obtained after column chromatography separation;

[0012] The olefin is:

[0013] The N-hydroxyphthalimide alkyl ether is:

[0014] The copper catalyst is selected from one of tetraacetonitrile copper hexafluorophosphate, tetraacetonitrile copper, tetraacetonitrile copper tetrafluoroborate, cuprous acetate, cuprous bromide, cuprous chloride, cupric chloride, cupric bromide or cupric sulfate;

[0015] The selected oxazoline ligand is selected from one of the following structural compounds, wherein n is an integer of 1 to 5:

[0016]

[0017] The trialkyl phosphite is selected from one of trimethyl phosphite, triethyl phosphite or triphenyl phosphorous acid;

[0018] The solvent is selected from one of 1,2-dichloroethane, dichloromethane or acetonitrile;

[0019] In the scheme, the molar ratio of olefin: cyanotrimethylsilane: copper catalyst: chiral oxazoline ligand: N-hydroxyphthalimide alkyl ether: trialkyl phosphite is 1:2-4:1%-5%:3%-6%:2:2;

[0020] The scheme is characterized in that the reaction temperature is 0°C to 50°C, the reaction time is 6h to 12h, and the light source is blue light.

[0021] The reaction process of the technical solution can be expressed as:

[0022]

[0023] Beneficial results

[0024] Due to the application of the above technical solution, the present invention has the following advantages compared with the prior art:

[0025] 1. The present invention uses olefins as starting materials, and the raw materials are easily available and of many types, and the products obtained therefrom are of various types and can be used directly or for other further reactions.

[0026] 2. The present invention only uses a catalytic amount of cheap and readily available copper catalyst, photocatalyst and oxazoline chiral ligand, with high raw material utilization, high product yield, high ee value, and almost no by-products, which is conducive to purification after the reaction.

[0027] 3. The preparation method disclosed in the present invention has mild reaction conditions, simple reaction operation and post-processing process, stable and controllable reaction process, high catalytic efficiency, greatly reduces the amount of reagents used and the generation and emission of reaction waste, has a high product yield, and is suitable for large-scale production. DETAILED DESCRIPTION

[0028] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution of the present invention is clearly and completely described below using embodiments. Obviously, the described embodiments are part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0029] Example 1: Preparation of (S)-5,5,5-trifluoro-2-(naphthalene-2-yl)pentanenitrile

[0030]

[0031] Using 2-vinylnaphthalene, cyanotrimethylsilane, and N-phthalimide trifluoroethoxy ether as raw materials, the reaction steps are as follows:

[0032] In a Schlenk tube, 2-vinylnaphthalene (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (2mol%), Ligand 1 (3mol%), tris(2-phenylpyridine)iridium (1mol%), cyanotrimethylsilane (2 equivalents), N-phthalimide trifluoroethoxy ether (2 equivalents) and DCM (2mL), under nitrogen protection, stirred and reacted for 24 hours at room temperature under blue light irradiation. Saturated sodium chloride solution and dichloromethane were added to the reaction solution for extraction, the organic phase was subjected to a rotary evaporator to remove the solvent, and column chromatography was performed to obtain (S)-5,5,5-trifluoro-2-(naphthalene-2-yl)pentanenitrile (yield 65%), and the ee value was determined by high performance liquid chromatography (92% ee).

[0033] The analytical data of the product are as follows: 1 H NMR (600 MHz, CDCl 3 )δ7.91(d,J=8.4Hz,1H),7.89-7.85(m,2H),7.84(s,1H),7.59-7.52(m,2H ),7.40(dd,J=8.4Hz,2.4Hz,1H),4.09(d,J=7.2Hz,1H),2.35-2.25(m,4H). 13 C NMR (150 MHz, CDCl 3 )δ133.2,133.0,131.3,129.6,127.9,127.8,127.0,126.9,126.5,126.4(q,J=275.1Hz),124.2,119.6,36 .2,31.1(q,J=29.3Hz),28.1(q,J=3.3Hz).HPLC(AY-3,0.46*15cm,5μm,hexane / isopropanol=90 / 10,flow 0.7mL / min, detection at 214nm).

[0034] Example 2: Preparation of (S)-5,5,5-trifluoro-2-(naphthalen-1-yl)valeronitrile

[0035]

[0036] Using 1-vinylnaphthalene, cyanotrimethylsilane, and N-phthalimide trifluoroethoxy ether as raw materials, the reaction steps are as follows:

[0037] In a Schlenk tube, 1-vinylnaphthalene (0.2 mmol), Cu(CH 3 CN) 4 PF6 (2mol%), Ligand 1 (3mol%), tris(2-phenylpyridine)iridium (1mol%), cyanotrimethylsilane (2 equivalents), N-phthalimide trifluoroethoxy ether (2 equivalents) and DCM (2mL), under nitrogen protection, stirred and reacted for 24 hours at room temperature under blue light irradiation. Saturated sodium chloride solution and dichloromethane were added to the reaction solution for extraction, the organic phase was subjected to a rotary evaporator to remove the solvent, and column chromatography was performed to obtain (S)-5,5,5-trifluoro-2-(naphthalen-1-yl)pentanenitrile (yield 62%), and the ee value was determined by high performance liquid chromatography (91% ee).

[0038] The analytical data of the product are as follows: 1 H NMR (600 MHz, CDCl 3 )δ7.94(d,J=7.8Hz,1H),7.88(t,J=8.4Hz,2H),7.70(d,J=7.2Hz,1H),7.64-7.60(m,1H),7. 57(t,J=7.2Hz,1H),7.51(t,J=7.8Hz,1H),4.69(dd,J=3.6Hz,8.4Hz,1H),2.45-2.25(m,4H). 13 C NMR (150 MHz, CDCl 3 )δ134.1,129.8,129.7,129.6,129.5,127.4,126.4(q,J=275.1Hz),126.4,125.7,125.5,121.5,119.8,33.2,31.5(q ,J=29.3Hz),27.1(q,J=3.3Hz).HPLC(AY-3,0.46*15cm,5μm,hexane / isopropanol=90 / 10,flow0.7mL / min,detection at 214nm).

[0039] Example 3: Preparation of (S)-5,5,5-trifluoro-2-(6-methoxy-naphthalen-2-yl)pentanenitrile

[0040]

[0041] Using 2-vinyl-6-methoxynaphthalene, cyanotrimethylsilane, and N-phthalimide trifluoroethoxy ether as raw materials, the reaction steps are as follows:

[0042] In a Schlenk tube, 2-vinyl-6-methoxynaphthalene (0.2 mmol), Cu(CH 3 CN) 4 PF 6(2mol%), Ligand 1 (3mol%), tris(2-phenylpyridine)iridium (1mol%), cyanotrimethylsilane (2 equivalents), N-phthalimide trifluoroethoxy ether (2 equivalents) and DCM (2mL), under nitrogen protection, stirred and reacted for 24 hours at room temperature under blue light irradiation. Saturated sodium chloride solution and dichloromethane were added to the reaction solution for extraction, the organic phase was subjected to a rotary evaporator to remove the solvent, and column chromatography was performed to obtain (S)-5,5,5-trifluoro-2-(6-methoxy-naphthalen-2-yl)pentanenitrile (yield 60%), and the ee value was determined by high performance liquid chromatography (88% ee).

[0043] The analytical data of the product are as follows: 1 H NMR (600 MHz, CDCl 3 )δ7.79(d,J=8.4Hz,1H),7.75(t,J=8.4Hz,1H),7.74(s,1H),7.36(dd,J=8.4,1.8Hz,1H),7.21(dd ,J=9.0,2.4Hz,1H),7.36(d,J=2.4Hz,1H),4.05(t,J=6.6Hz,1H),3.93(s,3H),2.34-2.23(m,4H). 13 C NMR (150 MHz, CDCl 3 )δ158.4,134.3,129.3,129.1,128.3,126.4(q,J=275.1Hz),126.3,124.8,119.9,119.7,105.6,55.4,36 .1,31.1(q,J=29.2Hz),28.1(q,J=3.3Hz).HPLC(AY-3,0.46*15cm,5μm,hexane / isopropanol=90 / 10,flow 0.7mL / min, detection at 214nm).

[0044] Example 4: Preparation of (S)-5,5,5-trifluoro-2-phenylvaleronitrile

[0045]

[0046] Using styrene, cyanotrimethylsilane and N-phthalimide trifluoroethoxy ether as raw materials, the reaction steps are as follows:

[0047] Styrene (0.2 mmol), Cu(CH 3 CN) 4 PF 6(2mol%), Ligand 1 (3mol%), tris(2-phenylpyridine)iridium (1mol%), cyanotrimethylsilane (2 equivalents), N-phthalimide trifluoroethoxy ether (2 equivalents) and DCM (2mL), under nitrogen protection, stirred and reacted for 24 hours at room temperature under blue light irradiation. Saturated sodium chloride solution and dichloromethane were added to the reaction solution for extraction, the organic phase was subjected to a rotary evaporator to remove the solvent, and column chromatography was used for separation to obtain (S)-5,5,5-trifluoro-2-phenylpentanenitrile (yield 82%), and the ee value was determined by high performance liquid chromatography (88% ee).

[0048] The analytical data of the product are as follows: 1 H NMR (600 MHz, CDCl 3 )δ7.42(t,J=7.2Hz,2H),7.37(t,J=7.2Hz,1H),7.34(d,J=7.8Hz,1H),3.91(t,J=7.2Hz,1H),2.28-

[0049] 2.21(m,2H),2.20-2.16(m,2H). 13 C NMR (150 MHz, CDCl 3 )δ134.1,129.4,129.0(q,J=274.1Hz),127.1,128.5,119.5,36.1,31.4(q,J=30.3Hz ),28.2(d,J=3.3Hz).HPLC(AY-3,0.46*15cm,5μm,hexane / isopropanol=90 / 10,flow 0.7mL / min, detection at 214nm).

[0050] Example 5: Preparation of (S)-5,5,5-trifluoro-2-(4-bromophenyl)pentanenitrile

[0051]

[0052] Using 4-bromostyrene, cyanotrimethylsilane, and N-phthalimide trifluoroethoxy ether as raw materials, the reaction steps are as follows:

[0053] In a Schlenk tube, 4-bromostyrene (0.2 mmol), Cu(CH 3 CN) 4 PF 6(2mol%), Ligand 1 (3mol%), tris(2-phenylpyridine)iridium (1mol%), cyanotrimethylsilane (2 equivalents), N-phthalimide trifluoroethoxy ether (2 equivalents) and DCM (2mL), under nitrogen protection, stirred and reacted for 24 hours at room temperature under blue light irradiation. Saturated sodium chloride solution and dichloromethane were added to the reaction solution for extraction, the organic phase was subjected to a rotary evaporator to remove the solvent, and column chromatography was performed to obtain (S)-5,5,5-trifluoro-2-(4-bromophenyl)pentanenitrile (yield 70%), and the ee value was determined by high performance liquid chromatography (92% ee).

[0054] The analytical data of the product are as follows: 1 H NMR (600 MHz, CDCl 3 )δ7.56(d,J=8.4Hz,2H),7.22(t,J=8.4Hz,2H),3.88(dd,J=7.2Hz,1H),2.30-2.20(m,2H),2.18-2.10(m,2H). 13 C NMR (150 MHz, CDCl 3 )δ133.2,132.6,128.8,126.2(q,J=274.1Hz),122.9,119.0,35.7,31.1(q,J=29.3Hz ),28.1(q,J=2.2Hz).HPLC(AY-3,0.46*15cm,5μm,hexane / isopropanol=90 / 10,flow 0.7mL / min, detection at 214nm).

[0055] Example 6: Preparation of (S)-5,5,5-trifluoro-2-(4-chlorophenyl)valeronitrile

[0056]

[0057] Using 4-chlorostyrene, cyanotrimethylsilane, and N-phthalimide trifluoroethoxy ether as raw materials, the reaction steps are as follows:

[0058] In a Schlenk tube, 4-chlorostyrene (0.2 mmol), Cu(CH 3 CN) 4 PF 6(2mol%), Ligand 1 (3mol%), tris(2-phenylpyridine)iridium (1mol%), cyanotrimethylsilane (2 equivalents), N-phthalimide trifluoroethoxy ether (2 equivalents) and DCM (2mL), under nitrogen protection, stirred and reacted for 24 hours at room temperature under blue light irradiation. Saturated sodium chloride solution and dichloromethane were added to the reaction solution for extraction, the organic phase was subjected to a rotary evaporator to remove the solvent, and column chromatography was used for separation to obtain (S)-5,5,5-trifluoro-2-(4-chlorophenyl)pentanenitrile (yield 73%), and the ee value was determined by high performance liquid chromatography (91% ee).

[0059] The analytical data of the product are as follows: 1 H NMR (600 MHz, CDCl 3 )δ7.41-7.39(m,2H),7.29-7.27(m,2H),3.88(t,J=7.8Hz,1H),2.28-2.22(m,2H),2.18-2.14(m,2H). 13 C NMR (150 MHz, CDCl 3 )δ134.8,132.6,129.6,128.9(q,J=275.1Hz),128.5,119.0,35.6,31.3(q,J=29.2Hz ),28.2(q,J=3.3Hz).HPLC(AY-3,0.46*15cm,5μm,hexane / isopropanol=90 / 10,flow 0.7mL / min, detection at 214nm).

[0060] Example 7: Preparation of (S)-5,5,5-trifluoro-2-(4-fluorophenyl)pentanenitrile

[0061]

[0062] Using 4-fluorostyrene, cyanotrimethylsilane, and N-phthalimide trifluoroethoxy ether as raw materials, the reaction steps are as follows:

[0063] In a Schlenk tube, 4-bromostyrene (0.2 mmol), Cu(CH 3 CN) 4 PF 6(2mol%), Ligand 1 (3mol%), tris(2-phenylpyridine)iridium (1mol%), cyanotrimethylsilane (2 equivalents), N-phthalimide trifluoroethoxy ether (2 equivalents) and DCM (2mL), under nitrogen protection, stirred and reacted for 24 hours at room temperature under blue light irradiation. Saturated sodium chloride solution and dichloromethane were added to the reaction solution for extraction, the organic phase was subjected to a rotary evaporator to remove the solvent, and column chromatography was used for separation to obtain (S)-5,5,5-trifluoro-2-(4-fluorophenyl)pentanenitrile (yield 71%), and the ee value was determined by high performance liquid chromatography (90% ee).

[0064] The analytical data of the product are as follows: 1 H NMR (600 MHz, CDCl 3 )δ7.36-7.30(m,2H),7.14-7.08(m,2H),3.90(t,J=7.2Hz,1H),2.31-2.22(m,2H),2.20-2.12(m,2H). 13 C NMR (150 MHz, CDCl 3 )δ162.7(d,J=247.1Hz),130.0(d,J=3.3Hz),128.9(d,J=8.7Hz),126.3(q,J=275.3Hz),119.3,116.5(d,J=21.8 Hz),35.5,31.1(q,J=29.3Hz),28.3(q,J=3.3Hz).HPLC(AY-3,0.46*15cm,5μm,hexane / isopropanol=90 / 10,flow 0.7mL / min, detection at 214nm).

[0065] Example 8: Preparation of (S)-5,5,5-trifluoro-2-(4-methoxyphenyl)valeronitrile

[0066]

[0067] Using 4-methoxystyrene, cyanotrimethylsilane, and N-phthalimide trifluoroethoxy ether as raw materials, the reaction steps are as follows:

[0068] In a Schlenk tube, 4-methoxystyrene (0.2 mmol), Cu(CH 3 CN) 4 PF 6(2mol%), Ligand1 (3mol%), tris(2-phenylpyridine)iridium (1mol%), cyanotrimethylsilane (2 equivalents), N-phthalimide trifluoroethoxy ether (2 equivalents) and DCM (2mL), under nitrogen protection, stirred and reacted for 24 hours at room temperature under blue light irradiation. Saturated sodium chloride solution and dichloromethane were added to the reaction solution for extraction, the organic phase was subjected to a rotary evaporator to remove the solvent, and column chromatography was used for separation to obtain (S)-5,5,5-trifluoro-2-(4-methoxyphenyl)pentanenitrile (yield 54%), and the ee value was determined by high performance liquid chromatography (77% ee).

[0069] The analytical data of the product are as follows: 1 H NMR (600 MHz, CDCl 3 )δ7.25(d,J=8.4Hz,2H),6.93(t,J=8.4Hz,2H),3.86(t,J=7.2Hz,1H),3.82(s,3H),2.28-2.20(m,2H),2.19-2.10(m,2H). 13 CNMR (150MHz, CDCl 3 )δ159.7,129.1,126.4(q,J=275.1Hz),126.0,119.8,114.7,55.4,36.1,31.1(q,J=29. 3Hz),28.2(q,J=2.1Hz).HPLC(AY-3,0.46*15cm,5μm,hexane / isopropanol=90 / 10,flow 0.7mL / min, detection at 214nm).

[0070] Example 9: Preparation of (S)-5,5,5-trifluoro-2-(4-trifluoromethylphenyl)valeronitrile

[0071]

[0072] Using 4-trifluoromethylstyrene, cyanotrimethylsilane, and N-phthalimide trifluoroethoxy ether as raw materials, the reaction steps are as follows:

[0073] In a Schlenk tube, 4-trifluoromethylstyrene (0.2 mmol), Cu(CH 3 CN) 4 PF 6(2mol%), Ligand 1 (3mol%), tris(2-phenylpyridine)iridium (1mol%), cyanotrimethylsilane (2 equivalents), N-phthalimide trifluoroethoxy ether (2 equivalents) and DCM (2mL), under nitrogen protection, stirred and reacted for 24 hours at room temperature under blue light irradiation. Saturated sodium chloride solution and dichloromethane were added to the reaction solution for extraction, the organic phase was subjected to a rotary evaporator to remove the solvent, and column chromatography was used for separation to obtain (S)-5,5,5-trifluoro-2-(4-trifluoromethylphenyl)pentanenitrile (yield 83%), and the ee value was determined by high performance liquid chromatography (90% ee).

[0074] The analytical data of the product are as follows: 1 H NMR (600 MHz, CDCl 3 )δ7.70(d,J=8.4Hz,2H),7.50(t,J=8.4Hz,2H),3.99(dd,J=7.2Hz,1H),2.36-2.24(m,2H),2.23-2.16(m,2H). 13 C NMR (150 MHz, CDCl 3 )δ138.1,131.2(q,J=32.6Hz),127.7,126.5(q,J=4.4Hz),126.2(q,J=274.1Hz),123.6(q,J=270.8Hz),118.7 ,36.0,31.1(q,J=29.3Hz),28.2(q,J=2.3Hz).HPLC(AY-3,0.46*15cm,5μm,hexane / isopropanol=90 / 10,flow 0.7mL / min, detection at 214nm).

[0075] Example 10: Preparation of (S)-5,5,5-trifluoro-2-(4-cyanophenyl)pentanenitrile

[0076]

[0077] Using 4-cyanostyrene, cyanotrimethylsilane, and N-phthalimide trifluoroethoxy ether as raw materials, the reaction steps are as follows:

[0078] In a Schlenk tube, 4-cyanostyrene (0.2 mmol), Cu(CH 3 CN) 4 PF 6(2mol%), Ligand 1 (3mol%), tris(2-phenylpyridine)iridium (1mol%), cyanotrimethylsilane (2 equivalents), N-phthalimide trifluoroethoxy ether (2 equivalents) and DCM (2mL), under nitrogen protection, stirred and reacted for 24 hours at room temperature under blue light irradiation. Saturated sodium chloride solution and dichloromethane were added to the reaction solution for extraction, the organic phase was subjected to a rotary evaporator to remove the solvent, and column chromatography was performed to obtain (S)-5,5,5-trifluoro-2-(4-cyanophenyl)pentanenitrile (yield 75%), and the ee value was determined by high performance liquid chromatography (82% ee).

[0079] The analytical data of the product are as follows: 1 H NMR (600 MHz, CDCl 3 )δ7.74(d,J=8.4Hz,2H),7.50(d,J=8.4Hz,2H),3.99(t,J=7.2Hz,1H),2.33-2.27(m,2H),2.21-2.17(m,2H). 13 C NMR (150 MHz, CDCl 3 )δ139.3,133.2,128.8(q,J=274.0Hz),128.0,118.3,117.8,113.0,36.2,31.4(q,J=29. 2Hz),28.1(q,J=3.3Hz).HPLC(AY-3,0.46*15cm,5μm,hexane / isopropanol=90 / 10,flow 0.7mL / min, detection at 214nm).

[0080] Example 11: Preparation of (S)-5,5,5-trifluoro-2-(4-methoxycarbonylphenyl)pentanenitrile

[0081]

[0082] Using 4-methoxycarbonylstyrene, cyanotrimethylsilane, and N-phthalimide trifluoroethoxy ether as raw materials, the reaction steps are as follows:

[0083] In a Schlenk tube, 4-methoxycarbonylstyrene (0.2 mmol), Cu(CH 3 CN) 4 PF 6(2mol%), Ligand 1 (3mol%), tris(2-phenylpyridine)iridium (1mol%), cyanotrimethylsilane (2 equivalents), N-phthalimide trifluoroethoxy ether (2 equivalents) and DCM (2mL), under nitrogen protection, stirred and reacted for 24 hours at room temperature under blue light irradiation. Saturated sodium chloride solution and dichloromethane were added to the reaction solution for extraction, the organic phase was subjected to a rotary evaporator to remove the solvent, and column chromatography was performed to obtain (S)-5,5,5-trifluoro-2-(4-methoxycarbonylphenyl)pentanenitrile (yield 80%), and the ee value was determined by high performance liquid chromatography (95% ee).

[0084] The analytical data of the product are as follows: 1 H NMR (600 MHz, CDCl 3 )δ8.10(d,J=8.4Hz,2H),7.44(t,J=8.4Hz,2H),3.99(t,J=7.2Hz,1H),3.94(s,3H),2.34-2.24(m,2H),2.23-2.14(m,2H). 13 CNMR (150MHz, CDCl 3 )δ166.2,138.9,130.7,127.3,126.2(q,J=275.1Hz),118.9,52.3,36.1,31.1(q,J=30. 3Hz),28.1(q,J=3.3Hz).HPLC(AY-3,0.46*15cm,5μm,hexane / isopropanol=90 / 10,flow 0.7mL / min, detection at 214nm).

[0085] Example 12: Preparation of (S)-5,5,5-trifluoro-2-(3-bromophenyl)pentanenitrile

[0086]

[0087] Using 3-bromostyrene, cyanotrimethylsilane, and N-phthalimide trifluoroethoxy ether as raw materials, the reaction steps are as follows:

[0088] In a Schlenk tube, 3-bromostyrene (0.2 mmol), Cu(CH 3 CN) 4 PF 6(2mol%), Ligand 1 (3mol%), tris(2-phenylpyridine)iridium (1mol%), cyanotrimethylsilane (2 equivalents), N-phthalimide trifluoroethoxy ether (2 equivalents) and DCM (2mL), under nitrogen protection, stirred and reacted for 24 hours at room temperature under blue light irradiation. Saturated sodium chloride solution and dichloromethane were added to the reaction solution for extraction, the organic phase was subjected to a rotary evaporator to remove the solvent, and column chromatography was used for separation to obtain (S)-5,5,5-trifluoro-2-(3-bromophenyl)pentanenitrile (yield 71%), and the ee value was determined by high performance liquid chromatography (90% ee).

[0089] The analytical data of the product are as follows: 1 H NMR (600 MHz, CDCl 3 )δ7.52-7.50(m,2H),7.31-7.29(m,2H),3.88(t,J=7.2Hz,1H),2.29-2.25(m,2H),2.19-2.15(m,2H). 13 C NMR (150 MHz, CDCl 3 )δ136.3,131.9,130.9,130.2,128.9(q,J=275.1Hz),125.8,123.4,118.8,35.7,31.4(q,J= 29.2Hz),28.2(q,J=2.1Hz).HPLC(AY-3,0.46*15cm,5μm,hexane / isopropanol=90 / 10,flow 0.7mL / min, detection at 214nm).

[0090] Example 13: Preparation of (S)-5,5,5-trifluoro-2-(2-bromophenyl)pentanenitrile

[0091]

[0092] Using 2-bromostyrene, cyanotrimethylsilane, and N-phthalimide trifluoroethoxy ether as raw materials, the reaction steps are as follows:

[0093] In a Schlenk tube, 2-bromostyrene (0.2 mmol), Cu(CH 3 CN) 4 PF 6(2mol%), Ligand 1 (3mol%), tris(2-phenylpyridine)iridium (1mol%), cyanotrimethylsilane (2 equivalents), N-phthalimide trifluoroethoxy ether (2 equivalents) and DCM (2mL), under nitrogen protection, stirred and reacted for 24 hours at room temperature under blue light irradiation. Saturated sodium chloride solution and dichloromethane were added to the reaction solution for extraction, the organic phase was subjected to a rotary evaporator to remove the solvent, and column chromatography was used for separation to obtain (S)-5,5,5-trifluoro-2-(2-bromophenyl)pentanenitrile (yield 75%), and the ee value was determined by high performance liquid chromatography (95% ee).

[0094] The analytical data of the product are as follows: 1 H NMR (600 MHz, CDCl 3 )δ7.62(dd,J=7.8,1.2Hz,1H),7.58(dd,J=7.8,1.2Hz,1H),7.41(t,J=7.8Hz,1H),7.25(dd,J=7. 8,1.2Hz,1H),4.41(dd,J=9,4.8Hz,1H),2.37-2.31(m,2H),2.25-2.20(m,1H),2.13-2.08(m,1H). 13 C NMR (150 MHz, CDCl 3 )δ133.8,133.6,130.3,128.9(q,J=275.1Hz),128.8,128.5,122.9,119.0,36.1,31.6(q,J= 30.3Hz),26.8(q,J=3.3Hz).HPLC(AY-3,0.46*15cm,5μm,hexane / isopropanol=90 / 10,flow 0.7mL / min, detection at 214nm).

[0095] Example 14: Preparation of (S)-5,5,5-trifluoro-2-(biphenyl-4-yl)valeronitrile

[0096]

[0097] Using 4-biphenylethylene, cyanotrimethylsilane, and N-phthalimide trifluoroethoxy ether as raw materials, the reaction steps are as follows:

[0098] In a Schlenk tube, 4-biphenylethylene (0.2 mmol), Cu(CH 3 CN) 4 PF 6(2mol%), Ligand 1 (3mol%), tris(2-phenylpyridine)iridium (1mol%), cyanotrimethylsilane (2 equivalents), N-phthalimide trifluoroethoxy ether (2 equivalents) and DCM (2mL), under nitrogen protection, stirred and reacted for 24 hours at room temperature under blue light irradiation. Saturated sodium chloride solution and dichloromethane were added to the reaction solution for extraction, the organic phase was subjected to a rotary evaporator to remove the solvent, and column chromatography was performed to obtain (S)-5,5,5-trifluoro-2-(biphenyl-4-yl)pentanenitrile (yield 65%), and the ee value was determined by high performance liquid chromatography (90% ee).

[0099] The analytical data of the product are as follows: 1 H NMR (600 MHz, CDCl 3 )δ7.64(d,J=8.4Hz,2H),7.58(d,J=7.8Hz,2H),7.46(t,J=7.8Hz,2H),7.42(d,J=7.8Hz, 2H),7.38(t,J=7.8Hz,1H),3.98(t,J=7.2Hz,1H),2.35-2.27(m,2H),2.25-2.20(m,2H). 13 CNMR (150MHz, CDCl 3 )δ141.8,140.0,133.0,128.9,128.1,127.8,127.6,127.1,126.4(q,J=274.1Hz),119.5,35.7,31. 2(q,J=29.3Hz),28.2(q,J=3.3Hz).HPLC(AY-3,0.46*15cm,5μm,hexane / isopropanol=90 / 10,flow 0.7mL / min, detection at 214nm).

[0100] Example 15: Preparation of (S)-5,5,5-trifluoro-2-(4'-trifluoromethylbiphenyl-4-yl)valeronitrile

[0101]

[0102] Using 4'-trifluoromethyl-4-distyryl, cyanotrimethylsilane, and N-phthalimide trifluoroethoxy ether as raw materials, the reaction steps are as follows:

[0103] In a Schlenk tube, 4'-trifluoromethyl-4-distyrene (0.2 mmol), Cu(CH 3 CN) 4 PF 6(2mol%), Ligand 1 (3mol%), tris(2-phenylpyridine)iridium (1mol%), cyanotrimethylsilane (2 equivalents), N-phthalimide trifluoroethoxy ether (2 equivalents) and DCM (2mL), under nitrogen protection, stirred and reacted for 24 hours at room temperature under blue light irradiation. Saturated sodium chloride solution and dichloromethane were added to the reaction solution for extraction, and the organic phase was subjected to a rotary evaporator to remove the solvent, and column chromatography was performed to obtain (S)-5,5,5-trifluoro-2-(4'-trifluoromethylbiphenyl-4-yl)pentanenitrile (yield 62%), and the ee value was determined by high performance liquid chromatography (91% ee).

[0104] The analytical data of the product are as follows: 1 H NMR (600 MHz, CDCl 3 )δ7.20(d,J=8.4Hz,2H),7.68(d,J=7.8Hz,2H),7.65(t,J=7.8Hz,2H),7.46(d,J=7.8Hz,2H),3.98(t,J=7.8Hz,1H),2.35-2.20(m,4H). 13 C NMR (150 MHz, CDCl 3 )δ143.5,140.3,134.1,128.9(q,J=32.4Hz),128.3,127.9,127.4,126.3(q,J=275.1Hz),125.9(q,J=4.4Hz),124.2(q,J=26 9.7Hz),119.3,35.9,31.2(q,J=29.3Hz),28.2(q,J=3.2Hz).HPLC(AY-3,0.46*15cm,5μm,hexane / isopropanol=90 / 10,flow 0.7mL / min, detection at 214nm).

[0105] Example 16: Preparation of (S)-4-(1-cyano-4,4,4-trifluorobutyl)-N-(4-(trifluoromethyl)phenyl)benzamide

[0106]

[0107] Using N-(4-(trifluoromethyl)phenyl)-4-vinylbenzamide, cyanotrimethylsilane, and N-phthalimide trifluoroethoxy ether as raw materials, the reaction steps are as follows:

[0108] In a Schlenk tube, N-(4-(trifluoromethyl)phenyl)-4-vinylbenzamide (0.2 mmol), Cu(CH 3 CN) 4 PF6 (2mol%), Ligand 1 (3mol%), tris(2-phenylpyridine)iridium (1mol%), cyanotrimethylsilane (2 equivalents), N-phthalimide trifluoroethoxy ether (2 equivalents) and DCM (2mL), under nitrogen protection, stirred and reacted for 24 hours at room temperature under blue light irradiation. Saturated sodium chloride solution and dichloromethane were added to the reaction solution for extraction, and the organic phase was subjected to a rotary evaporator to remove the solvent, and column chromatography was used for separation to obtain (S)-4-(1-cyano-4,4,4-trifluorobutyl)-N-(4-(trifluoromethyl)phenyl)benzamide (yield 80%), and the ee value was determined by high performance liquid chromatography (93% ee).

[0109] The analytical data of the product are as follows: 1 H NMR (600 MHz, CDCl 3 )δ8.02(s,1H),7.94(d,J=7.8Hz,2H),7.79(d,J=7.8Hz,2H),7.64(d,J=7.2Hz,2H), 7.49(d,J=7.8Hz,2H),4.00(t,J=7.2Hz,1H),2.31-2.26(m,2H),2.23-2.19(m,2H). 13 C NMR (150 MHz, CDCl 3 )δ169.4,147.6,136.0,135.8,129.7,129.0(q,J=32.5Hz),126.9,126.8,126.5(q,J=3.3Hz),126.2(q,J=154.9Hz),122.6 ,118.8,28.2,35.8,31.2(q,J=30.3Hz),27.9(d,J=3.1Hz).HPLC(AY-3,0.46*15cm,5μm,hexane / isopropanol=80 / 20,flow 0.7mL / min, detection at 214nm).

[0110] Example 17: Preparation of (S)-4-(1-cyano-4,4,4-trifluorobutyl)-N-methyl-N-(4-(trifluoromethyl)phenyl)benzamide

[0111]

[0112] Using N-methyl-N-(4-(trifluoromethyl)phenyl)-4-vinylbenzamide, cyanotrimethylsilane, and N-phthalimide trifluoroethoxy ether as raw materials, the reaction steps are as follows:

[0113] In a Schlenk tube, N-methyl-N-(4-(trifluoromethyl)phenyl)-4-vinylbenzamide (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (2mol%), Ligand 1 (3mol%), tris(2-phenylpyridine)iridium (1mol%), cyanotrimethylsilane (2 equivalents), N-phthalimide trifluoroethoxy ether (2 equivalents) and DCM (2mL), under nitrogen protection, stirred and reacted for 24 hours at room temperature under blue light irradiation. Saturated sodium chloride solution and dichloromethane were added to the reaction solution for extraction, and the organic phase was subjected to a rotary evaporator to remove the solvent, and column chromatography was performed to obtain (S)-4-(1-cyano-4,4,4-trifluorobutyl)-N-methyl-N-(4-(trifluoromethyl)phenyl)benzamide (yield 81%), and the ee value was determined by high performance liquid chromatography (92% ee).

[0114] The analytical data of the product are as follows: 1 H NMR (600 MHz, CDCl 3 )δ7.51(d,J=7.8Hz,2H),7.35(d,J=7.8Hz,2H),7.21(d,J=8.4Hz,2H),7.15(d,J=8. 4Hz,2H),3.86(t,J=7.2Hz,1H),3.52(s,3H),2.21-2.13(m,2H),2.12-2.08(m,2H). 13 C NMR (150 MHz, CDCl 3 )δ169.4,147.6,136.0,135.8,129.7,129.0(q,J=32.5Hz),126.9,126.8,126.5(q,J=3.3H z), 126.2 (q, J = 154.9Hz), 122.6, 118.8, 28.2, 35.8, 31.2 (q, J = 30.3Hz), 27.9 (d, J = 3.1Hz). 1 H NMR (600 MHz, CDCl 3 )δ7.51(d,J=7.8Hz,2H),7.35(d,J=7.8Hz,2H),7.21(d,J=8.4Hz,2H),7.15(d,J=8. 4Hz,2H),3.86(t,J=7.2Hz,1H),3.52(s,3H),2.21-2.13(m,2H),2.12-2.08(m,2H). 13 CNMR (150MHz, CDCl 3)δ169.4,147.6,136.0,135.8,129.7,129.0(q,J=32.5Hz),126.9,126.8,126.5(q,J=3.3Hz),126.2(q,J=154.9Hz),122.6 ,118.8,28.2,35.8,31.2(q,J=30.3Hz),27.9(d,J=3.1Hz).HPLC(AY-3,0.46*15cm,5μm,hexane / isopropanol=80 / 20,flow 0.7mL / min, detection at 214nm).

[0115] Example 18: Preparation of (S)-2-(3-benzoylphenyl)-5,5,5-trifluorovaleronitrile

[0116]

[0117] Using 4-benzoylstyrene, cyanotrimethylsilane, and N-phthalimide trifluoroethoxy ether as raw materials, the reaction steps are as follows:

[0118] In a Schlenk tube, 4-benzoylstyrene (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (2mol%), Ligand 1 (3mol%), tris(2-phenylpyridine)iridium (1mol%), cyanotrimethylsilane (2 equivalents), N-phthalimide trifluoroethoxy ether (2 equivalents) and DCM (2mL), under nitrogen protection, stirred and reacted for 24 hours at room temperature under blue light irradiation. Saturated sodium chloride solution and dichloromethane were added to the reaction solution for extraction, the organic phase was subjected to a rotary evaporator to remove the solvent, and column chromatography was used for separation to obtain (S)-2-(3-benzoylphenyl)-5,5,5-trifluorovaleronitrile (yield 83%), and the ee value was determined by high performance liquid chromatography (60% ee).

[0119] The analytical data of the product are as follows: 1 H NMR (600 MHz, CDCl 3 )δ7.79(d,J=7.8Hz,4H),7.63(dd,J=13.8,7.8Hz,2H),7.55(t,J=7.8Hz,1H),7. 51(t,J=7.2Hz,2H),3.99(t,J=7.2Hz,1H),2.32-2.26(m,2H),2.23-2.19(m,2H). 13 C NMR (150 MHz, CDCl 3)δ195.7,138.8,136.9,134.8,132.9,130.8,130.4,130.0,129.4,128.9(q,J=275.2Hz),128.5,128.4,119.0 ,36.0,31.5(q,J=29.2Hz),28.1(q,J=3.3Hz).HPLC(AY-3,0.46*15cm,5μm,hexane / isopropanol=90 / 10,flow 0.7mL / min, detection at 214nm).

[0120] Example 19: Preparation of (S)-2-pentafluorophenyl-5,5,5-trifluorovaleronitrile

[0121]

[0122] With pentafluorostyrene, cyanotrimethylsilane and N-phthalimide trifluoroethoxy ether as raw materials, the reaction steps are as follows:

[0123] Pentafluorostyrene (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (2mol%), Ligand 1 (3mol%), tris(2-phenylpyridine)iridium (1mol%), cyanotrimethylsilane (2 equivalents), N-phthalimide trifluoroethoxy ether (2 equivalents) and DCM (2mL), under nitrogen protection, stirred and reacted for 24 hours at room temperature under blue light irradiation. Saturated sodium chloride solution and dichloromethane were added to the reaction solution for extraction, the organic phase was subjected to a rotary evaporator to remove the solvent, and column chromatography was used for separation to obtain (S)-2-pentafluorophenyl-5,5,5-trifluorovaleronitrile (yield 72%), and the ee value was determined by high performance liquid chromatography (88% ee).

[0124] The analytical data of the product are as follows: 1 H NMR (600 MHz, CDCl 3 )δ4.22(t,J=7.8Hz,1H),2.41-2.35(m,2H),2.32-2.27(m,1H),2.17-2.13(m,1H). 13 C NMR (150 MHz, CDCl 3)δ144.7(dm,J=253.7Hz),141.9(dm,J=256.8Hz),138.0(dm,J=254.7Hz),125.9(q,J=274.1Hz),116.1,108.3(dt,J=15.3, 4.2Hz),31.4(q,J=29.2Hz),31.7(q,J=29.2Hz),25.5,25.0.HPLC(AY-3,0.46*15cm,5μm,hexane / isopropanol=90 / 10,flow 0.7mL / min, detection at214nm).

[0125] Example 20: Preparation of (8R, 9S, 13S, 14S)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3-yl 4-((S)-1-cyano-4,4,4-trifluorobutyl)benzoate

[0126]

[0127] Using vinyl estrogenstol benzoate, cyanotrimethylsilane, and N-phthalimide trifluoroethoxy ether as raw materials, the reaction steps are as follows:

[0128] Add vinyl estrogenstolone benzoate (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (2mol%), Ligand 1 (3mol%), tris(2-phenylpyridine)iridium (1mol%), cyanotrimethylsilane (2 equivalents), N-phthalimide trifluoroethoxy ether (2 equivalents) and DCM (2mL), under nitrogen protection, stirred and reacted for 24 hours at room temperature under blue light irradiation. Saturated sodium chloride solution and dichloromethane were added to the reaction solution for extraction, and the organic phase was subjected to a rotary evaporator to remove the solvent, and column chromatography was performed to obtain (8R, 9S, 13S, 14S)-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-3-yl 4-((S)-1-cyano-4,4,4-trifluorobutyl)benzoate (yield 71%), and the ee value was determined by high performance liquid chromatography (92% ee).

[0129] The analytical data of the product are as follows: 1 H NMR (600 MHz, CDCl 3)δ8.25(d,J=7.8Hz,2H),7.51(d,J=8.4Hz,2H),7.35(d,J=8.4Hz,1H),6.99(d d, J=8.4Hz, 2.4Hz, 1H), 6.94 (s, 1H), 4.02 (t, J=7.2Hz, 1H), 2.95 (dd, J=9Hz, 4. 2Hz, 2H), 2.54 (dd, J=18.6Hz, 8.4Hz, 1H), 2.34-1.96 (m, 9H), 1.66–1.46 (m, 7H), 0.92 (s, 3H). HPLC (AY-3, 0.46*15cm, 5μm, hexane / isopropanol=90 / 10, flow 0.7mL / min, detection at 214nm).

[0130] Example 21: Preparation of (S)-5,5,6,6,6-pentafluoro-2-(naphthalene-2-yl)hexanenitrile

[0131]

[0132] Using 2-naphthylethylene, cyanotrimethylsilane, and N-phthalimide pentafluoropropoxy ether as raw materials, the reaction steps are as follows:

[0133] In a Schlenk tube, 2-naphthylene (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (2mol%), Ligand1 (3mol%), tris(2-phenylpyridine)iridium (1mol%), cyanotrimethylsilane (2 equivalents), N-phthalimide pentafluoropropoxy ether (2 equivalents) and DCM (2mL), under nitrogen protection, stirred and reacted for 24 hours at room temperature under blue light irradiation. Saturated sodium chloride solution and dichloromethane were added to the reaction solution for extraction, the organic phase was subjected to a rotary evaporator to remove the solvent, and column chromatography was performed to obtain (S)-5,5,6,6,6-pentafluoro-2-(naphthalene-2-yl)hexanenitrile (yield 75%), and the ee value was determined by high performance liquid chromatography (93% ee).

[0134] The analytical data of the product are as follows: 1 H NMR (600 MHz, CDCl 3)δ7.92(d,J=8.4Hz,1H),7.87(dd,J=5.4Hz,3.0Hz,2H),7.84(s,1H),7.57-7.53(m,2H),7 .40(dd,J=8.4Hz,1.8Hz,1H),4.10(t,J=6.6Hz,1H),2.34-2.30(m,2H),2.28-2.19(m,2H). 13 C NMR (150 MHz, CDCl 3 )δ133.2,133.0,131.2,129.6,127.8,127.7,127.0,126.9,126.5,124.1,121.6(qt,J=35.7Hz,35.8Hz,35.8Hz,35.7Hz),119.5,117.2(tq ,J=37.9Hz,37.9Hz,37.9Hz),36.5,28.0(t,J=22.8Hz),26.6(d,J=3.3Hz).HPLC(AY-3,0.46*15cm,5μm,hexane / isopropanol=90 / 10,flow 0.7mL / min, detection at 214nm).

[0135] Example 22: Preparation of (S)-5,5-difluoro-2-(naphthalen-2-yl)pentanenitrile

[0136]

[0137] Using 2-naphthylethylene, cyanotrimethylsilane, and N-phthalimide difluoroethoxy ether as raw materials, the reaction steps are as follows:

[0138] In a Schlenk tube, 2-naphthylene (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (2mol%), Ligand1 (3mol%), tris(2-phenylpyridine)iridium (1mol%), cyanotrimethylsilane (2 equivalents), N-phthalimide difluoroethoxy ether (2 equivalents) and DCM (2mL), under nitrogen protection, stirred and reacted for 24 hours at room temperature under blue light irradiation. Saturated sodium chloride solution and dichloromethane were added to the reaction solution for extraction, the organic phase was subjected to a rotary evaporator to remove the solvent, and column chromatography was performed to obtain (S)-5,5-difluoro-2-(naphthalene-2-yl)pentanenitrile (yield 76%), and the ee value was determined by high performance liquid chromatography (92% ee).

[0139] The analytical data of the product are as follows: 1 H NMR (600 MHz, CDCl3 )δ7.90(d,J=8.4Hz,1H),7.86(dd,J=4.8Hz,2.4Hz,2H),7.83(s,1H),7.55–7.51(m,2H),7.41(dd,J =8.4Hz,1.8Hz,1H),5.97-5.77(m,1H),4.07(t,J=7.2Hz,1H),2.22-2.18(m,2H),2.08-2.01(m,2H). 13 C NMR (150 MHz, CDCl 3 )δ133.2,132.9,131.8,129.4,127.8,127.7,126.9,126.7,126.4,124.4,119.9,116.0(t,J=238.3Hz),36 .7,31.1(t,J=21.7Hz),27.8(t,J=5.4Hz).HPLC(AY-3,0.46*15cm,5μm,hexane / isopropanol=90 / 10,flow 0.7mL / min, detection at 214nm).

[0140] Example 23: Preparation of (S)-4-(1-cyano-4-ethoxy-4-oxobutyl)benzoic acid methyl ester

[0141]

[0142] Using 4-vinylbenzoic acid methyl ester, cyanotrimethylsilane, and N-phthalimide trifluoroethoxy ether as raw materials, the reaction steps are as follows:

[0143] In a Schlenk tube, methyl 4-vinylbenzoate (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (2mol%), Ligand 1 (3mol%), tris(2-phenylpyridine)iridium (1mol%), cyanotrimethylsilane (2 equivalents), ethyl 2-((1,3-dihydroisoindolin-2-yl)oxy)acetate (2 equivalents) and DCM (2mL), under nitrogen protection, stirred and reacted for 24 hours at room temperature under blue light irradiation. Saturated sodium chloride solution and dichloromethane were added to the reaction solution for extraction, the organic phase was subjected to a rotary evaporator to remove the solvent, and column chromatography was performed to obtain (S)-4-(1-cyano-4-ethoxy-4-oxobutyl)benzoic acid methyl ester valeronitrile (yield 70%), and the ee value (90% ee) was determined by high performance liquid chromatography.

[0144] The analytical data of the product are as follows: 1H NMR (600 MHz, CDCl 3 )δ8.07(d,J=8.4Hz,2H),7.44(d,J=8.4Hz,2H),4.16(q,J=7.2Hz,2H),4.07(qq,J=7.8,7.2Hz,1 H),3.9(s,3H),2.56-2.51(m,1H),2.48-2.42(m,1H),2.24-2.21(m,2H),1.26(t,J=7.2Hz,3H). 13 C NMR (150 MHz, CDCl 3 )δ171.8,166.3,139.9,130.4,130.2,127.4,119.6,60.9,52.2,36.2,30.9,14.1.HPLC(AY-3,0.46*15cm,5μm,hexane / isopropanol=90 / 10,flow 0.7mL / min,detection at 214nm).

[0145] Example 24: Preparation of (S)-2-(naphthalene-2-yl)pentanenitrile

[0146]

[0147] Using 2-naphthylene benzoic acid methyl ester, cyanotrimethylsilane, and N-phthalimide trifluoroethoxy ether as raw materials, the reaction steps are as follows:

[0148] In a Schlenk tube, 2-naphthylene (0.2 mmol), Cu(CH 3 CN) 4 PF 6 (2mol%), Ligand1 (3mol%), tris(2-phenylpyridine)iridium (1mol%), cyanotrimethylsilane (2 equivalents), N-phthalimide ethoxy ether (2 equivalents) and DCM (2mL), under nitrogen protection, stirred and reacted for 24 hours at room temperature under blue light irradiation. Saturated sodium chloride solution and dichloromethane were added to the reaction solution for extraction, the organic phase was subjected to a rotary evaporator to remove the solvent, and column chromatography was performed to obtain (S)-2-(naphthalene-2-yl)pentanenitrile (yield 65%), and the ee value was determined by high performance liquid chromatography (91% ee).

[0149] The analytical data of the product are as follows: 1 H NMR (600 MHz, CDCl 3)δ7.83-7.55(m,4H),7.41-7.37(m,2H),7.27(d,J=8.5 Hz,1H),3.81(t,J=6.0 Hz,1H),1.85-1.76(m,2H),1.45-1.38(m,2H),0.84(t,J=7.3 Hz,3H); 13 C NMR(75 MHz,CDCl3)δ133.5,133.0,129.3,128.1,128.0,126.9,126.7,126.5,125.1,121.2,38.0,37.5,20.6,13.7.HPLC(AY-3,0.46*15 cm,5μm,hexane / isopropanol=90 / 10,flow 0.7 mL / min,detection at 214 nm).

Claims

1. A chiral nitrile compound, characterized in that: The general structural formula of the chiral nitrile compound is: Wherein R is selected from one of aromatic derivatives containing 1 to 3 benzene rings, and R1 is selected from one of an alkyl group containing 2 to 6 carbon atoms, a fluorine-substituted alkyl group, a cyano-substituted alkyl group or an ester group containing 3 to 7 carbon atoms.

2. The chiral nitrile compound according to claim 1, characterized in that R is selected from one of naphthalene-1-yl, naphthalene-2-yl, 6-methoxynaphthalene-2-yl, phenyl, p-methoxyphenyl, p-methoxycarbonylphenyl, p-trifluoromethylphenyl, p-cyanophenyl, p-bromophenyl, p-fluorophenyl, p-chlorophenyl, m-bromophenyl, o-bromophenyl, biphenyl, m-benzoylphenyl, N-(4-trifluoromethyl)phenylcarbamoylphenyl, N-methyl-N-(4-trifluoromethylphenyl)carbamoylphenyl, pentafluorophenyl, p-trifluoromethylbiphenyl or p-estroneoxycarbonylphenyl; R1 is selected from one of trifluoroethyl, difluoroethyl, pentafluoropropyl, 2-methoxy-2-oxyethyl-1-yl, cyanomethyl or ethyl.

3. The chiral nitrile compound according to claim 1, characterized in that Selected from one of the following structural compounds:

4. A method for preparing a chiral nitrile compound according to any one of claims 1 to 3, characterized in that: The following steps are involved: Under the protection of nitrogen or inert gas, a copper catalyst, a chiral oxazoline ligand, tris(2-phenylpyridine)iridium, an olefin, cyanotrimethylsilane, a trialkylphosphite and an N-hydroxyphthalimide alkyl ether are dissolved in a solvent, and the reaction is carried out under light. After the reaction is completed, a saturated sodium chloride solution and dichloromethane are added, extraction is carried out, the solvent is removed, and separation is carried out to obtain a chiral nitrile compound; The olefin is: The N-hydroxyphthalimide alkyl ether is:

5. The preparation method according to claim 4, characterized in that: The copper catalyst is selected from one of tetraacetonitrile copper hexafluorophosphate, tetraacetonitrile copper tetrafluoroborate, cuprous acetate, cuprous bromide, cuprous chloride, cupric chloride, cupric bromide or cupric sulfate.

6. The preparation method according to claim 4, characterized in that: The chiral oxazoline ligand is selected from One of the following, wherein n is an integer from 1 to 5.

7. The preparation method according to claim 4, characterized in that: The trialkyl phosphite is selected from one of trimethyl phosphite, triethyl phosphite or triphenyl phosphite.

8. The preparation method according to claim 4, characterized in that: The solvent is selected from one of 1,2-dichloroethane, dichloromethane or acetonitrile.

9. The preparation method according to claim 4, characterized in that: In terms of molar ratio, olefin: cyanotrimethylsilane: copper catalyst: chiral oxazoline ligand: N-hydroxyphthalimide alkyl ether: trialkyl phosphite is 1:2-4:0.01-0.05:0.03-0.06:2:

2.

10. The preparation method according to claim 4, characterized in that: The reaction temperature is 0-50°C, the reaction time is 6-12h, and the light source is blue light.

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