Synthetic method of organosilicon compound

Abstract

The invention belongs to the technical field of organic chemical synthesis, and discloses a synthesis method of an organosilicon compound. According to the invention, successful synthesis of the 1, 3-site double-silicon compound from acrylonitrile, chlorosilane and alkyl bromide at room temperature is realized for the first time, and the blank in the prior art is filled. The method provided by the invention has the advantages of mild process conditions, short flow, simple steps and wide substrate applicability, and meets industrial production requirements. Research finds that the yield of the product can reach 85%, and the generated alkyl silicon compound has wide application prospects in organic synthesis and drug research and development. Therefore, the method has important application value.

Description

Technical Field

[0001] This invention belongs to the field of organic chemical synthesis technology and relates to a method for synthesizing organosilicon compounds. Background Technology

[0002] Organosilicon compounds are widely found in natural products, bioactive molecules, and drug molecules. Examples include Silperisone, Zifrosilone, and Karenitecin BNP1350, which have shown promising efficacy in treating muscle spasms and Alzheimer's disease. Furthermore, organosilicon compounds play crucial roles in materials science, pharmaceuticals, chemical sensors, catalysis, and polymer chemistry. Therefore, developing efficient new synthetic methods for organosilicon compounds is of great significance.

[0003] Currently, many synthetic methods for organosilicon compounds have been reported [see: (a) Copper-catalyzed substitution of α-triflyloxy nitriles and esters with siliconnucleophiles under inversion of the configuration, Organic Letters. 2017, 19, 6562–6565. (b) C (sp 3 )-Si cross-coupling, ACS Catalysis. 2018, 9, 16–24. (c)Nickel‐Catalyzed Reductive C (sp 2)-Si Coupling of Chlorohydrosilanes via Si-Cl Cleavage, Angewandte Chemie. 2022, 134, e202200215. (d) Palladium-catalyzed enantioselective carbene insertion into carbon-silicon bonds ofsilacyclobutanes, Am. Chem.Soc. 2021, 143, 12968–12973. (e) Enantioselective construction of six- and seven-membered triorgano-substituted silicon-stereogenic heterocycles, Nat. Commun. 2021, 12, 1249. (f) Grimme, S.&Oestreich, M. Inter-molecular carbosilylation of α-olefins with C(sp3)-C(sp)bond for-mation involving silylium-ion regeneration, Angew. Chem. Int. [Ed. 2022, 61, e202203347.] The methods are summarized as nucleophilic substitution reactions, cross-coupling reactions, carbon-alkane insertion reactions, carbon-hydrogen bond silanization reactions, and unsaturated carbon-carbon bond bifunctionalization reactions. However, the above reactions still have some drawbacks, such as harsh reaction conditions, limited substrate range, and expensive catalysts. Therefore, developing a simple reaction system to synthesize alkyl bromides from inexpensive and readily available aldehydes, and then reacting them with silanes and alkenes as raw materials under nickel catalysis to synthesize organosilicon compounds with complex structures has important research significance and application potential.

[0004] Alkyl aldehydes are a class of abundant raw material chemicals, commonly found in simple structural units, natural products, and pharmaceutical molecules. Alkyl aldehydes are converted into corresponding silane bromides via steps such as using silane-based lithium reagents. Under conditions of Ni as a catalyst and Zn as a reducing agent, alkyl radicals can be generated. Furthermore, alkenes are the most common structural units in organic compounds, and their bifunctionalization has become one of the most researched directions in organic synthesis methodology in recent years, exhibiting high atom and step economy. Therefore, the strategy of converting alkyl bromides into alkyl radicals under conditions of Zn as a reducing agent and Ni as a catalyst, followed by capture by acrylonitrile, and then oxidative addition to chlorosilanes under the action of Ni catalyst and Zn reducing agent to generate alkylsilyl compounds, achieves both the bifunctionalization of alkenes and the construction of complex organosilanes. This method is a synthetic approach of significant research value.

[0005] This invention utilizes readily available and inexpensive alkyl aldehydes as raw materials, converting them into stable alkylsilane bromides through steps such as alkyllithium reagents. Without complex post-treatment, a one-pot process using readily available and inexpensive Zn powder reduction, catalyzed by Ni catalyst ethylene glycol dimethyl ether nickel bromide, generates alkyl radicals through a single-electron transfer process. These radicals then react with alkenes and halosilanes to produce a series of organosilicon compounds. Compared to traditional synthetic methods, thermocatalysis, as a green energy source, offers milder reaction conditions and better functional group compatibility, thus providing a new approach for the green and efficient synthesis of organosilicon compounds. Summary of the Invention

[0006] This invention provides a novel synthetic method for organosilicon compounds, using easily synthesized alkylsilane bromides as model substrates, inexpensive and readily available ethylene glycol dimethyl ether nickel bromide as a catalyst, and Zn powder as a reducing agent, to promote the reaction of alkylsilane bromides with olefins and halosilanes under thermal excitation. This method has advantages such as convenient experimental operation, good substrate compatibility, and inexpensive and readily available raw materials, thus possessing significant application value and socio-economic benefits.

[0007] The technical solution of this invention: A method for synthesizing organosilicon compounds, using alkyl bromide (1), acrylonitrile (2), and halosilane (3) as raw materials, and adding a reducing agent, catalyst, and ligand, synthesizes a series of organosilicon compounds in a one-pot process at room temperature; the synthetic route is as follows: Where Ph is a benzene ring; Me is a methyl group; R represents ethylbenzene, 4-ethyl anisole, p-fluoroethylbenzene, p-chloroethylbenzene, p-trifluoromethylethylbenzene, methyl, pentyl, hydrogen atom, 1-decene, and methyl ethyl sulfide, respectively. Under nitrogen conditions, the reducing agent, ligand, catalyst, solvent, acrylonitrile (2), chlorosilane (3) and alkyl bromide (1) were added sequentially to the reaction flask. The mixture was then stirred at 15 ℃-45 ℃ for 8 h-24 h. After the reaction was completed, the reaction was quenched with water and stirred for another 1 h. The mixture was extracted with ethyl acetate and saturated brine, dried over anhydrous sodium sulfate, filtered through diatomaceous earth, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the organosilicon compound.

[0008] The reducing agent is selected from Zn, Mn or Mg, with Zn being preferred.

[0009] The ligand is 2,2′-bipyridine, 1,10-phenanthroline, 2,9-dimethyl-1,10-phenanthroline, 3-(2-pyridyl)-1,2,4-triazole, 2,6-bis(1-pyrazolyl)pyridine, 2,6-bis(2-phenylimidazolium) or 2,6-bis(4,5-dihydrooxazol-2-yl)pyridine, preferably 2,2′-bipyridine; The catalyst is nickel ethylene glycol dimethyl ether bromide, nickel ethylene glycol dimethyl ether chloride, nickel bromide, nickel chloride, nickel iodide, nickel fluoride, nickel acetylacetone, nickel trifluoromethanesulfonate, or nickel tetrafluoroborate hexahydrate, preferably nickel ethylene glycol dimethyl ether bromide.

[0010] Solvents are selected from ethyl acetate, toluene, tetrahydrofuran, etc. N,N -Dimethylformamide, N,N - One or more of dimethylacetamide, dimethyl sulfoxide, dichloromethane, acetone, and acetonitrile, preferably dichloromethane.

[0011] The beneficial effects of this invention are as follows: This invention provides a method for synthesizing organosilicon compounds, achieving for the first time the synthesis of organosilicon compounds through the nickel-catalyzed reaction of alkyl bromides with alkenes and chlorosilanes, filling a gap in existing technologies. The method of this invention features mild process conditions, a short process flow, simple steps, and broad substrate applicability, meeting the requirements of industrial production. Studies have shown that the product yield can reach 85%, and the generated organosilicon compounds have broad application prospects in organic synthesis and drug development. Therefore, this invention has significant application value. Attached Figure Description

[0012] Figure 1 For compound 3a 1 H-NMR spectrum.

[0013] Figure 2 For compound 3a 13 C-NMR spectrum.

[0014] Figure 3 For compound 3b 1 H-NMR spectrum.

[0015] Figure 4For compound 3b 13 C-NMR spectrum.

[0016] Figure 5 For compound 3c 1 H-NMR spectrum.

[0017] Figure 6 For compound 3c 13 C-NMR spectrum.

[0018] Figure 7 For compound 3d 1 H-NMR spectrum.

[0019] Figure 8 For compound 3d 13 C-NMR spectrum.

[0020] Figure 9 For compound 3e 1 H-NMR spectrum.

[0021] Figure 10 For compound 3e 13 C-NMR spectrum.

[0022] Figure 11 For compound 3f 1 H-NMR spectrum.

[0023] Figure 12 For compound 3f 13 C-NMR spectrum.

[0024] Figure 13 3g of compound 1 H-NMR spectrum.

[0025] Figure 14 3g of compound 13 C-NMR spectrum.

[0026] Figure 15 For compound 3h 1 H-NMR spectrum.

[0027] Figure 16 For compound 3h 13 C-NMR spectrum.

[0028] Figure 17 For compound 3i 1 H-NMR spectrum.

[0029] Figure 18 For compound 3i 13 C-NMR spectrum.

[0030] Figure 19 For compound 3j1 H-NMR spectrum.

[0031] Figure 20 For compound 3j 13 C-NMR spectrum. Detailed Implementation

[0032] The specific embodiments of the present invention will be further described below with reference to the accompanying drawings and technical solutions.

[0033] Example 1: Synthesis of 4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)-6-phenylhexanenitrile (3a) (1) In a flame-dried 50 mL three-necked flask, a magnetic stir bar and lithium scrap (468 mg, 67.5 mmol, 4.5 equivalents) were added. The system was evacuated and backfilled with argon, repeated three times. Anhydrous tetrahydrofuran (15 mL, prepared to a concentration of about 1 mol / L) was added via syringe. R3SiCl (15 mmol, 1.0 equivalents) was added at 0 °C, and the mixture was stirred at room temperature for 12 h. The generated silane-based lithium reagent was titrated with diphenylacetic acid (usually to a concentration of about 1 mol / L) according to the method reported by Kofron. Subsequently, an alkyl aldehyde (10.0 mmol, 1.0 equivalents) was dissolved in tetrahydrofuran (50 mL), and dimethylphenylchlorosilane (15.0 mmol, 1.5 equivalents) was added at -78 °C. The reaction mixture was gradually heated to room temperature and allowed to react for 16 h. The reaction was quenched with water and then extracted with ethyl acetate (3 × 50 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was then rapidly purified by column chromatography (silica gel, eluent: cyclohexane / ethyl acetate = 20:1) to give the target product, α-hydroxyalkylsilane S2 (a yellow oil).

[0034] (2) Triphenylphosphine (1.5 equivalents) and imidazole (1.5 equivalents) were dissolved in anhydrous dichloromethane (to prepare a 0.3 mol / L solution), and bromine (1.5 equivalents) was slowly added at 0°C. The mixture was stirred rapidly at 0°C for 10 minutes. Then, α-hydroxyalkylsilane S2 (1.0 equivalents) obtained in the previous step was dissolved in dichloromethane (5 mL) and added dropwise to the above mixture. The mixture was stirred at 0°C for 1 hour, then allowed to warm naturally to room temperature and reacted for another 12 hours. The reaction was quenched with water and extracted with ethyl acetate (3 × 30 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by rapid column chromatography (silica gel, eluent cyclohexane) to give the desired target product, alkyl bromide 1.

[0035] (3) Accurately weigh Zn powder (23.2 mg, 0.4 mmol) into a glove box, then add 2,2'-bipyridine (3.75 mg, 0.024 mmol), ethylene glycol dimethyl ether nickel bromide (6.2 mg, 0.02 mmol), dichloromethane (2 mL), acrylonitrile (39 μL, 0.6 mmol), dimethylphenylchlorosilane (83 μL, 0.6 mmol), and alkyl bromide (0.2 mmol). Stir at 35 °C for 12 h. After the reaction is complete, add 2 mL of distilled water and stir for 1 h. Then, extract the organic layer with DCM, dry with anhydrous Na2SO4, filter, and concentrate under reduced pressure. The residue is purified by rapid chromatography. The yield of 4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)-6-phenylhexanonitrile is 85%. 11H NMR (400 MHz, Chloroform-d) δ 7.58 – 7.51 (m, 2H), 7.42 – 7.39 (m, 3H), 7.33 – 7.25 (m, 2H), 7.23 – 7.18 (m, 2H), 7.12 – 7.08 (m, 1H), 6.16 – 5.98 (m, 2H), 5.89 – 5.74 (m, 1H), 2.76 (ddd, J = 13.6, 10.7, 5.4 Hz, 0.5H), 2.66 – 2.44 (m, 1.5H), 2.02 (dd, J = 12.3, 3.5 Hz, 0.5H), 1.90 (dddd, J = 14.8, 10.4, 6.0, 4.2 Hz, 0.5H), 1.84 – 1.66 (m, 2H), 1.65 – 1.53 (m, 1H), 1.47 – 1.38 (m, 1H), 1.37 – 1.30 (m, 0.5H), 1.16 (tt, J = 8.7, 4.5 Hz, 0.5H), 0.39 (d, J = 2.9 Hz, 3H), 0.36 (d, J = 10.4 Hz, 3H), 0.26 (d, J = 1.8 Hz, 3H), 0.17 (d, J = 4.8 Hz, 3H). 13C NMR (101 MHz, Chloroform-d) δ 142.46, 142.37, 138.05, 137.77, 135.46, 135.31, 133.98, 133.94, 133.91, 133.87, 129.37, 129.27, 128.53, 128.45, 128.42, 128.25, 128.10, 128.00, 125.94, 125.87, 122.46, 121.84, 77.48, 77.16, 76.84, 35.71, 35.33, 32.95, 31.21, 27.56, 27.03, 26.39, 24.84, 18.75, 17.15, -3.51, -3.83, -3.86, -4.67, -4.91, -4.98, -5.30, -5.41. Example ②: Synthesis of 4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)-6-(4-methoxyphenyl)hexanenitrile (3b) (1) In a flame-dried 50 mL three-necked flask, a magnetic stir bar and lithium scrap (468 mg, 67.5 mmol, 4.5 equivalents) were added. The system was evacuated and backfilled with argon, repeated three times. Anhydrous tetrahydrofuran (15 mL, prepared to a concentration of about 1 mol / L) was added via syringe. R3SiCl (15 mmol, 1.0 equivalents) was added at 0 °C, and the mixture was stirred at room temperature for 12 h. The generated silane-based lithium reagent was titrated with diphenylacetic acid (usually to a concentration of about 1 mol / L) according to the method reported by Kofron. Subsequently, an alkyl aldehyde (10.0 mmol, 1.0 equivalents) was dissolved in tetrahydrofuran (50 mL), and dimethylphenylchlorosilane (15.0 mmol, 1.5 equivalents) was added at -78 °C. The reaction mixture was gradually heated to room temperature and allowed to react for 16 h. The reaction was quenched with water and then extracted with ethyl acetate (3 × 50 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was then rapidly purified by column chromatography (silica gel, eluent: cyclohexane / ethyl acetate = 20:1) to give the target product, α-hydroxyalkylsilane S2 (a yellow oil).

[0036] (2) Triphenylphosphine (1.5 equivalents) and imidazole (1.5 equivalents) were dissolved in anhydrous dichloromethane (to prepare a 0.3 mol / L solution), and bromine (1.5 equivalents) was slowly added at 0°C. The mixture was stirred rapidly at 0°C for 10 minutes. Then, α-hydroxyalkylsilane S2 (1.0 equivalents) obtained in the previous step was dissolved in dichloromethane (5 mL) and added dropwise to the above mixture. The mixture was stirred at 0°C for 1 hour, then allowed to warm naturally to room temperature and reacted for another 12 hours. The reaction was quenched with water and extracted with ethyl acetate (3 × 30 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by rapid column chromatography (silica gel, eluent cyclohexane) to give the desired target product, alkyl bromide 1.

[0037] (3) Accurately weigh Zn powder (23.2 mg, 0.4 mmol) into a glove box, then add 2,2'-bipyridine (3.75 mg, 0.024 mmol), ethylene glycol dimethyl ether nickel bromide (6.2 mg, 0.02 mmol), dichloromethane (0.2 mL), acrylonitrile (39 μL, 0.6 mmol), dimethylphenylchlorosilane (54 μL, 0.4 mmol), and alkyl bromide (0.2 mmol). Stir at 35 °C for 8 h. After the reaction is complete, add 2 mL of distilled water and stir for 1 h. Then, extract the organic layer with DCM, dry with anhydrous Na2SO4, filter, and concentrate under reduced pressure. The residue is purified by rapid chromatography. The yield of 4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)-6-(4-methoxyphenyl)hexanonitrile is 75%. 1 H NMR (500 MHz, Chloroform- d )δ 7.53 – 7.52 (m, 2H), 7.40 – 7.34 (m, 3H), 7.06 (d, J = 8.1 Hz, 1H), 6.97 (d, J = 8.2 Hz, 1H), 6.81 (dd, J = 12.3, 8.3 Hz, 2H), 6.14 – 5.95 (m,2H), 5.83 – 5.71 (m, 1H), 3.78 (d, J = 5.7 Hz, 3H), 2.69 – 2.63 (m, 0.5H), 2.54 – 2.37 (m, 1.5H), 1.98 (dd, J = 12.3, 3.6 Hz, 0.5H), 1.86 – 1.75 (m, 1H),1.73 – 1.63 (m, 1.5H), 1.61 – 1.48 (m, 1H), 1.39 (ddd, J = 21.8, 12.9, 3.7 Hz,1H), 1.31 – 1.27 (m, 0.5H), 1.11 (tt, J = 8.7, 4.5 Hz, 1H), 0.35 (d, J = 3.8 Hz, 3H), 0.32 (d, J = 12.6 Hz, 3H), 0.22 (d, J = 2.6 Hz, 3H), 0.13 (d, J = 5.2 Hz, 3H).13 C NMR (101 MHz, Chloroform- d )δ 157.89, 157.85, 138.14, 137.85, 135.44,135.29, 134.58, 134.47, 134.04, 134.01, 133.94, 133.90, 129.44, 129.37,129.27, 129.15, 128.11, 128.01, 122.49, 121.88, 113.89, 113.86, 77.48, 77.16,76.84, 55.33, 55.32, 34.84, 34.41, 33.16, 31.50, 27.61, 27.12, 26.33, 24.83, 18.79, 17.24, -3.49, -3.81, -3.83, -4.61, -4.89, -4.96, -5.27, -5.38. Example 3: Synthesis of 4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)-6-(4-fluorophenyl)hexanenitrile (3c) (1) In a flame-dried 50 mL three-necked flask, a magnetic stir bar and lithium scrap (468 mg, 67.5 mmol, 4.5 equivalents) were added. The system was evacuated and backfilled with argon, repeated three times. Anhydrous tetrahydrofuran (15 mL, prepared to a concentration of about 1 mol / L) was added via syringe. R3SiCl (15 mmol, 1.0 equivalents) was added at 0 °C, and the mixture was stirred at room temperature for 12 h. The generated silane-based lithium reagent was titrated with diphenylacetic acid (usually to a concentration of about 1 mol / L) according to the method reported by Kofron. Subsequently, an alkyl aldehyde (10.0 mmol, 1.0 equivalents) was dissolved in tetrahydrofuran (50 mL), and dimethylphenylchlorosilane (15.0 mmol, 1.5 equivalents) was added at -78 °C. The reaction mixture was gradually heated to room temperature and allowed to react for 16 h. The reaction was quenched with water and then extracted with ethyl acetate (3 × 50 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was then rapidly purified by column chromatography (silica gel, eluent: cyclohexane / ethyl acetate = 20:1) to give the target product, α-hydroxyalkylsilane S2 (a yellow oil).

[0038] (2) Triphenylphosphine (1.5 equivalents) and imidazole (1.5 equivalents) were dissolved in anhydrous dichloromethane (to prepare a 0.3 mol / L solution), and bromine (1.5 equivalents) was slowly added at 0°C. The mixture was stirred rapidly at 0°C for 10 minutes. Then, α-hydroxyalkylsilane S2 (1.0 equivalents) obtained in the previous step was dissolved in dichloromethane (5 mL) and added dropwise to the above mixture. The mixture was stirred at 0°C for 1 hour, then allowed to warm naturally to room temperature and reacted for another 12 hours. The reaction was quenched with water and extracted with ethyl acetate (3 × 30 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by rapid column chromatography (silica gel, eluent cyclohexane) to give the desired target product, alkyl bromide 1.

[0039] (3) Accurately weigh 22.0 mg (0.4 mmol) of Mn powder into a glove box, then add 3.75 mg (0.024 mmol) of 2,2'-bipyridine, 6.2 mg (0.02 mmol) of ethylene glycol dimethyl ether nickel bromide, 0.2 mL of dichloromethane, 39 μL (0.6 mmol) of acrylonitrile, 54 μL (0.4 mmol) of dimethylphenylchlorosilane, and 0.2 mmol of alkyl bromide. Stir at 25 °C for 10 h. After the reaction is complete, add 2 mL of distilled water and stir for 1 h. Then, extract the organic layer with DCM, dry with anhydrous Na2SO4, filter, and concentrate under reduced pressure. The residue is purified by rapid chromatography. The yield of 4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)-6-(4-fluorophenyl)hexanonitrile is 70%. 1 H NMR (400 MHz, Chloroform- d )δ7.55 – 7.49 (m, 2H), 7.40 – 7.36 (m, 3H), 7.11 (dd, J = 8.3, 5.5Hz, 1H), 7.12 – 6.91 (m, 3H), 6.15 – 5.97 (m, 2H), 5.88 – 5.73 (m, 2H), 2.74– 2.67 (m, 0.5H), 2.59 – 2.39 (m, 1.5H), 1.99 (dd, J = 12.2, 3.6 Hz, 1H), 1.88– 1.76 (m, 1H), 1.74 – 1.58 (m, 2H), 1.57 – 1.49 (m, 0.5H), 1.45 – 1.37 (m,1H), 1.33 – 1.27 (m, 0.5H), 1.11 (tt, J = 8.6, 4.4 Hz, 1H), 0.36 (d, J = 3.5 Hz, 3H), 0.33 (d, J = 7.7 Hz, 3H), 0.24 (d, J = 1.7 Hz, 3H), 0.16 (d, J = 4.5 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d)δ 162.54, 160.12, 138.08, 138.04, 137.98,137.94, 137.74, 135.51, 135.37, 133.98, 133.96, 133.93, 133.88, 129.94,129.86, 129.65, 129.57, 129.43, 129.34, 128.14, 128.05, 122.48, 121.83,115.27, 115.24, 115.06, 115.03, 77.48, 77.16, 76.84, 34.97, 34.45, 33.07, 31.36, 27.59, 27.09, 26.34, 24.81, 18.94, 17.21, -3.60, -3.80, -3.94, -4.59, -4.89, -4.97, -5.28, -5.39. Example 4: 6-(4-chlorophenyl)-4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)hexanonitrile Synthesis of 6-(4-chlorophenyl)-4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)hexanenitrile (3d) (1) In a flame-dried 50 mL three-necked flask, a magnetic stir bar and lithium scrap (468 mg, 67.5 mmol, 4.5 equivalents) were added. The system was evacuated and backfilled with argon, repeated three times. Anhydrous tetrahydrofuran (15 mL, prepared to a concentration of about 1 mol / L) was added via syringe. R3SiCl (15 mmol, 1.0 equivalents) was added at 0 °C, and the mixture was stirred at room temperature for 12 h. The generated silane-based lithium reagent was titrated with diphenylacetic acid (usually to a concentration of about 1 mol / L) according to the method reported by Kofron. Subsequently, an alkyl aldehyde (10.0 mmol, 1.0 equivalents) was dissolved in tetrahydrofuran (50 mL), and dimethylphenylchlorosilane (15.0 mmol, 1.5 equivalents) was added at -78 °C. The reaction mixture was gradually heated to room temperature and allowed to react for 16 h. The reaction was quenched with water and then extracted with ethyl acetate (3 × 50 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was then rapidly purified by column chromatography (silica gel, eluent: cyclohexane / ethyl acetate = 20:1) to give the target product, α-hydroxyalkylsilane S2 (a yellow oil).

[0040] (2) Triphenylphosphine (1.5 equivalents) and imidazole (1.5 equivalents) were dissolved in anhydrous dichloromethane (to prepare a 0.3 mol / L solution), and bromine (1.5 equivalents) was slowly added at 0°C. The mixture was stirred rapidly at 0°C for 10 minutes. Then, α-hydroxyalkylsilane S2 (1.0 equivalents) obtained in the previous step was dissolved in dichloromethane (5 mL) and added dropwise to the above mixture. The mixture was stirred at 0°C for 1 hour, then allowed to warm naturally to room temperature and reacted for another 12 hours. The reaction was quenched with water and extracted with ethyl acetate (3 × 30 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by rapid column chromatography (silica gel, eluent cyclohexane) to give the desired target product, alkyl bromide 1.

[0041] (3) Accurately weigh Zn powder (11.0 mg, 0.2 mmol) into a glove box, then add 2,9-dimethyl-1,10-phenanthroline (5.21 mg, 0.024 mmol), ethylene glycol dimethyl ether nickel bromide (6.2 mg, 0.02 mmol), dichloromethane (0.2 mL), acrylonitrile (26 μL, 0.4 mmol), dimethylphenylchlorosilane (83 μL, 0.6 mmol), and alkyl bromide (0.2 mmol). Stir at 15 °C for 12 h. After the reaction is complete, add 2 mL of distilled water and stir for 1 h. Then, extract the organic layer with DCM, dry with anhydrous Na2SO4, filter, and concentrate under reduced pressure. The residue is purified by rapid chromatography. The yield of 6-(4-chlorophenyl)-4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)hexanonitrile is 68%. 1 H NMR (400 MHz, Chloroform- d )δ 7.54 – 7.48 (m, 2H), 7.40 – 7.35 (m, 3H), 7.26 –7.20 (m, 2H), 7.07 (d, J = 8.2 Hz, 1H), 6.97 (d, J = 8.2 Hz, 1H), 6.16 – 5.96 (m,2H), 5.87 – 5.72 (m, 1H), 2.73 – 2.66 (m, 0.5H), 2.58 – 2.38 (m, 1.5H), 1.98(dd, J= 12.3, 3.6 Hz, 0.5H), 1.87 – 1.75 (m, 1H), 1.73 – 1.58 (m, 2H), 1.57 –1.48 (m, 0.5H), 1.44 – 1.36 (m, 1H), 1.33 – 1.23 (m, 0.5H), 1.13 (tt, J = 8.7, 4.5 Hz, 0.5H), 0.35 (d, J = 3.7 Hz, 3H), 0.32 (d, J = 8.1 Hz, 3H), 0.24 (d, J = 1.7Hz, 3H), 0.15 (d, J = 4.6 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d )δ 140.87,140.80, 137.91, 137.67, 135.53, 135.39, 133.95, 133.92, 133.87, 131.63,131.57, 129.94, 129.64, 129.44, 129.36, 128.53, 128.51, 128.15, 128.06,122.47, 121.82, 77.48, 77.16, 76.84, 35.14, 34.63, 32.88, 31.13, 27.57,27.06, 26.39, 24.86, 18.96, 17.21, -3.63, -3.79, -3.98, -4.57, -4.89, -4.97, -5.28, -5.39. Example 5: 4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)-6-(4-(trifluoromethyl)phenyl)hexanonitrile) Synthesis of 4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)-6-(4-(trifluoromethyl)phenyl)hexanenitrile (3f) (1) In a flame-dried 50 mL three-necked flask, a magnetic stir bar and lithium scrap (468 mg, 67.5 mmol, 4.5 equivalents) were added. The system was evacuated and backfilled with argon, repeated three times. Anhydrous tetrahydrofuran (15 mL, prepared to a concentration of about 1 mol / L) was added via syringe. R3SiCl (15 mmol, 1.0 equivalents) was added at 0 °C, and the mixture was stirred at room temperature for 12 h. The generated silane-based lithium reagent was titrated with diphenylacetic acid (usually to a concentration of about 1 mol / L) according to the method reported by Kofron. Subsequently, an alkyl aldehyde (10.0 mmol, 1.0 equivalents) was dissolved in tetrahydrofuran (50 mL), and dimethylphenylchlorosilane (15.0 mmol, 1.5 equivalents) was added at -78 °C. The reaction mixture was gradually heated to room temperature and allowed to react for 16 h. The reaction was quenched with water and then extracted with ethyl acetate (3 × 50 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was then rapidly purified by column chromatography (silica gel, eluent: cyclohexane / ethyl acetate = 20:1) to give the target product, α-hydroxyalkylsilane S2 (a yellow oil).

[0042] (2) Triphenylphosphine (1.5 equivalents) and imidazole (1.5 equivalents) were dissolved in anhydrous dichloromethane (to prepare a 0.3 mol / L solution), and bromine (1.5 equivalents) was slowly added at 0°C. The mixture was stirred rapidly at 0°C for 10 minutes. Then, α-hydroxyalkylsilane S2 (1.0 equivalents) obtained in the previous step was dissolved in dichloromethane (5 mL) and added dropwise to the above mixture. The mixture was stirred at 0°C for 1 hour, then allowed to warm naturally to room temperature and reacted for another 12 hours. The reaction was quenched with water and extracted with ethyl acetate (3 × 30 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by rapid column chromatography (silica gel, eluent cyclohexane) to give the desired target product, alkyl bromide 1.

[0043] (3) Accurately weigh Zn powder (13.1 mg, 0.2 mmol) into a glove box, then add 2,2'-bipyridine (3.75 mg, 0.024 mmol), ethylene glycol dimethyl ether nickel bromide (6.2 mg, 0.02 mmol), dichloromethane (0.2 mL), acrylonitrile (26 μL, 0.4 mmol), dimethylphenylchlorosilane (83 μL, 0.6 mmol), and alkyl bromide (0.2 mmol). Stir at 45 °C for 12 h. After the reaction is complete, add 2 mL of distilled water and stir for 1 h. Then, extract the organic layer with DCM, dry with anhydrous Na2SO4, filter, and concentrate under reduced pressure. The residue is purified by rapid chromatography. The yield of 4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)-6-(4-(trifluoromethyl)phenyl)hexanonitrile) is 71%. 1 H NMR (400 MHz, Chloroform- d )δ 7.55 – 7.48 (m, 4H), 7.43 – 7.35 (m, 3H), 7.25 (d, J =7.8 Hz, 1H), 7.14 (d, J = 8.0 Hz, 1H), 6.17 – 5.97 (m, 2H), 5.88 – 5.73 (m,1H), 2.82 – 2.75 (m, 0.5H), 2.67 – 2.46 (m, 1.5H), 1.99 (dd, J = 12.3, 3.6 Hz,0.5H), 1.91 – 1.75 (m, 1H), 1.74 – 1.66 (m, 1H), 1.65 – 1.52 (m, 1.5H), 1.46 – 1.37 (m, 1H), 1.34 – 1.28 (m, 0.5H), 1.12 (tt, J = 8.7, 4.5 Hz, 1H), 0.37 (d, J = 3.7 Hz, 3H), 0.33 (d, J = 8.1 Hz, 3H), 0.25 (d, J = 1.3 Hz, 3H), 0.16 (d, J =4.6 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d)δ 146.55, 146.53, 137.83, 137.63,135.61, 135.47, 133.95, 133.93, 133.90, 129.52, 129.45, 128.91, 128.63,128.21, 128.13, 125.46, 125.45, 125.42, 125.41, 125.38, 125.37, 125.35,125.33, 122.51, 121.83, 77.48, 77.16, 76.84, 35.70, 35.18, 32.76, 30.98, 27.61, 27.09, 26.58, 24.99, 19.08, 17.24, -3.70, -3.74, -4.05, -4.51, -4.87, -4.95, -5.26, -5.38. Example 6: 4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)pentonitrile Synthesis of 4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)pentanenitrile (3f) (1) In a flame-dried 50 mL three-necked flask, a magnetic stir bar and lithium scrap (468 mg, 67.5 mmol, 4.5 equivalents) were added. The system was evacuated and backfilled with argon, repeated three times. Anhydrous tetrahydrofuran (15 mL, prepared to a concentration of about 1 mol / L) was added via syringe. R3SiCl (15 mmol, 1.0 equivalents) was added at 0 °C, and the mixture was stirred at room temperature for 12 h. The generated silane-based lithium reagent was titrated with diphenylacetic acid (usually to a concentration of about 1 mol / L) according to the method reported by Kofron. Subsequently, an alkyl aldehyde (10.0 mmol, 1.0 equivalents) was dissolved in tetrahydrofuran (50 mL), and dimethylphenylchlorosilane (15.0 mmol, 1.5 equivalents) was added at -78 °C. The reaction mixture was gradually heated to room temperature and allowed to react for 16 h. The reaction was quenched with water and then extracted with ethyl acetate (3 × 50 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was then rapidly purified by column chromatography (silica gel, eluent: cyclohexane / ethyl acetate = 20:1) to give the target product, α-hydroxyalkylsilane S2 (a yellow oil).

[0044] (2) Triphenylphosphine (1.5 equivalents) and imidazole (1.5 equivalents) were dissolved in anhydrous dichloromethane (to prepare a 0.3 mol / L solution), and bromine (1.5 equivalents) was slowly added at 0°C. The mixture was stirred rapidly at 0°C for 10 minutes. Then, α-hydroxyalkylsilane S2 (1.0 equivalents) obtained in the previous step was dissolved in dichloromethane (5 mL) and added dropwise to the above mixture. The mixture was stirred at 0°C for 1 hour, then allowed to warm naturally to room temperature and reacted for another 12 hours. The reaction was quenched with water and extracted with ethyl acetate (3 × 30 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by rapid column chromatography (silica gel, eluent cyclohexane) to give the desired target product, alkyl bromide 1.

[0045] (3) Accurately weigh Zn powder (13.1 mg, 0.2 mmol) into a glove box, then add 2,9-dimethyl-1,10-phenanthroline (5.21 mg, 0.024 mmol), nickel chloride (2.6 mg, 0.02 mmol), tetrahydrofuran (0.5 mL), acrylonitrile (26 μL, 0.4 mmol), dimethylphenylchlorosilane (83 μL, 0.6 mmol), and alkyl bromide (0.2 mmol). Stir at 30 °C for 9 h. After the reaction is complete, add 2 mL of distilled water and stir for 1 h. Then, extract the organic layer with DCM, dry with anhydrous Na2SO4, filter, and concentrate under reduced pressure. The residue is purified by rapid chromatography. The yield of 4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)pentanonitrile is 83%. 1 H NMR (500 MHz, Chloroform- d )δ751 – 7.48 (m, 2H), 7.40 – 7.34 (m, 3H), 6.12 – 5.98 (m, 2H), 5.84 – 5.71 (m,1H), 2.06 (dd, J = 12.4, 3.8 Hz, 0.5H), 1.78 – 1.65 (m, 1H), 1.57 (dd, J = 10.2,4.2 Hz, 0.5H), 1.48 – 1.42 (m, 0.5H), 1.29 – 1.15 (m, 1H), 1.10 – 1.07 (m,2H), 0.94 (d, J = 7.0 Hz, 1H), 0.31 (s, 2H), 0.29 (s, 4H), 0.23 (d, J= 3.6 Hz, 3H), 0.16 (s, 3H). 13 C NMR (101 MHz, Chloroform- d )δ 137.81, 137.38, 135.30,135.20, 134.16, 134.11, 133.98, 133.88, 129.30, 129.18, 128.01, 127.90,122.85, 121.71, 77.48, 77.16, 76.84, 30.38, 28.43, 21.18, 18.42, 18.24,16.31, 15.54, 12.65, -4.21, -4.83, -4.88, -4.99, -5.04, -5.19, -5.34, -5.43. Example 7: 4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)nononitrile Synthesis of 4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)nonanenitrile (3g) (1) In a flame-dried 50 mL three-necked flask, a magnetic stir bar and lithium scrap (468 mg, 67.5 mmol, 4.5 equivalents) were added. The system was evacuated and backfilled with argon, repeated three times. Anhydrous tetrahydrofuran (15 mL, prepared to a concentration of about 1 mol / L) was added via syringe. R3SiCl (15 mmol, 1.0 equivalents) was added at 0 °C, and the mixture was stirred at room temperature for 12 h. The generated silane-based lithium reagent was titrated with diphenylacetic acid (usually to a concentration of about 1 mol / L) according to the method reported by Kofron. Subsequently, an alkyl aldehyde (10.0 mmol, 1.0 equivalents) was dissolved in tetrahydrofuran (50 mL), and dimethylphenylchlorosilane (15.0 mmol, 1.5 equivalents) was added at -78 °C. The reaction mixture was gradually heated to room temperature and allowed to react for 16 h. The reaction was quenched with water and then extracted with ethyl acetate (3 × 50 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was then rapidly purified by column chromatography (silica gel, eluent: cyclohexane / ethyl acetate = 20:1) to give the target product, α-hydroxyalkylsilane S2 (a yellow oil).

[0046] (2) Triphenylphosphine (1.5 equivalents) and imidazole (1.5 equivalents) were dissolved in anhydrous dichloromethane (to prepare a 0.3 mol / L solution), and bromine (1.5 equivalents) was slowly added at 0°C. The mixture was stirred rapidly at 0°C for 10 minutes. Then, α-hydroxyalkylsilane S2 (1.0 equivalents) obtained in the previous step was dissolved in dichloromethane (5 mL) and added dropwise to the above mixture. The mixture was stirred at 0°C for 1 hour, then allowed to warm naturally to room temperature and reacted for another 12 hours. The reaction was quenched with water and extracted with ethyl acetate (3 × 30 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by rapid column chromatography (silica gel, eluent cyclohexane) to give the desired target product, alkyl bromide 1.

[0047] (3) Accurately weigh Zn powder (13.1 mg, 0.2 mmol) into a glove box, then add 2,2'-bipyridine (3.75 mg, 0.024 mmol), ethylene glycol dimethyl ether nickel bromide (6.2 mg, 0.02 mmol), dichloromethane (2 mL), acrylonitrile (39 μL, 0.6 mmol), dimethylphenylchlorosilane (83 μL, 0.6 mmol), and alkyl bromide (0.2 mmol). Stir at 25 °C for 12 h. After the reaction is complete, add 2 mL of distilled water and stir for 1 h. Then, extract the organic layer with DCM, dry with anhydrous Na2SO4, filter, and concentrate under reduced pressure. The residue is purified by rapid chromatography. The yield of 4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)nononitrile is 54%. 1 H NMR (400 MHz, Chloroform- d )δ7.51 – 7.49 (m, 2H), 7.37 – 7.34 (m, 3H), 6.12 – 5.94 (m, 2H), 5.84 – 5.69(m, 1H), 1.99 (dd, J = 12.3, 3.7 Hz, 1H), 1.73 – 1.66 (m, 0.5H), 1.64 – 1.46(m, 2H), 1.46 – 1.35 (m, 2H), 1.34 – 1.24 (m, 3.5H), 1.23 – 1.18 (m, 3H),1.04 (tt, J = 8.4, 4.4 Hz, 0.5H), 0.89 – 0.82 (m, 3H), 0.32 (d, J = 5.7 Hz, 3H), 0.30 (d, J= 5.1 Hz, 3H), 0.22 (d, J = 3.2 Hz, 3H), 0.12 (d, J = 2.6 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d )δ 138.53, 138.16, 135.33, 135.18, 134.16, 134.12,133.92, 133.90, 129.28, 129.12, 128.07, 127.91, 122.50, 121.93, 77.48, 77.16,76.84, 32.42, 32.15, 30.68, 28.83, 28.74, 28.51, 27.58, 27.04, 26.45, 24.66,22.62, 22.57, 18.83, 17.28, 14.20, 14.13, -3.27, -3.62, -3.91, -4.71, -4.87, -4.94, -5.24, -5.36. Example 8: 4-Cyclobutyl-4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)butyronitrile Synthesis of 4-cyclobutyl-4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)butanenitrile (3h) (1) In a flame-dried 50 mL three-necked flask, a magnetic stir bar and lithium scrap (468 mg, 67.5 mmol, 4.5 equivalents) were added. The system was evacuated and backfilled with argon, repeated three times. Anhydrous tetrahydrofuran (15 mL, prepared to a concentration of about 1 mol / L) was added via syringe. R3SiCl (15 mmol, 1.0 equivalents) was added at 0 °C, and the mixture was stirred at room temperature for 12 h. The generated silane-based lithium reagent was titrated with diphenylacetic acid (usually to a concentration of about 1 mol / L) according to the method reported by Kofron. Subsequently, an alkyl aldehyde (10.0 mmol, 1.0 equivalents) was dissolved in tetrahydrofuran (50 mL), and dimethylphenylchlorosilane (15.0 mmol, 1.5 equivalents) was added at -78 °C. The reaction mixture was gradually heated to room temperature and allowed to react for 16 h. The reaction was quenched with water and then extracted with ethyl acetate (3 × 50 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was then rapidly purified by column chromatography (silica gel, eluent: cyclohexane / ethyl acetate = 20:1) to give the target product, α-hydroxyalkylsilane S2 (a yellow oil).

[0048] (2) Triphenylphosphine (1.5 equivalents) and imidazole (1.5 equivalents) were dissolved in anhydrous dichloromethane (to prepare a 0.3 mol / L solution), and bromine (1.5 equivalents) was slowly added at 0°C. The mixture was stirred rapidly at 0°C for 10 minutes. Then, α-hydroxyalkylsilane S2 (1.0 equivalents) obtained in the previous step was dissolved in dichloromethane (5 mL) and added dropwise to the above mixture. The mixture was stirred at 0°C for 1 hour, then allowed to warm naturally to room temperature and reacted for another 12 hours. The reaction was quenched with water and extracted with ethyl acetate (3 × 30 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by rapid column chromatography (silica gel, eluent cyclohexane) to give the desired target product, alkyl bromide 1.

[0049] (3) Accurately weigh Zn powder (13.1 mg, 0.2 mmol) into a glove box, then add 2,2'-bipyridine (3.75 mg, 0.024 mmol), nickel bromide (4.3 mg, 0.02 mmol), dichloromethane (1 mL), acrylonitrile (26 μL, 0.4 mmol), dimethylphenylchlorosilane (83 μL, 0.6 mmol), and alkyl bromide (0.2 mmol). Stir at 25 °C for 12 h. After the reaction is complete, add 2 mL of distilled water and stir for 1 h. Then, extract the organic layer with DCM, dry with anhydrous Na2SO4, filter, and concentrate under reduced pressure. The residue is purified by rapid chromatography. The yield of 4-cyclobutyl-4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)butyronitrile is 59%. 1 H NMR (500 MHz, Chloroform- d )δ7.51– 7.47 (m, 2H), 7.38 – 7.34 (m, 3H), 6.14 – 6.03 (m, 2H), 5.84 – 5.75 (m,1H), 1.77 (dd, J = 8.4, 6.4 Hz, 1H), 1.58 – 1.53 (m, 2H), 1.23 – 1.14 (m, 1H), 0.89 – 0.80 (m, 1H), 0.28 (d, J = 1.8 Hz, 6H), 0.22 (d, J = 1.5 Hz, 6H). 13 C NMR (101 MHz, Chloroform- d )δ 138.42, 135.29, 134.28, 133.63, 129.26, 128.03,122.17, 77.48, 77.16, 76.84, 22.29, 21.87, 16.63, -2.99, -3.10, -4.64, -4.97. Example 9: 4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)tetradec-13-enonitrile Synthesis of 4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)tetradec-13-enenitrile (3i) (1) In a flame-dried 50 mL three-necked flask, a magnetic stir bar and lithium scrap (468 mg, 67.5 mmol, 4.5 equivalents) were added. The system was evacuated and backfilled with argon, repeated three times. Anhydrous tetrahydrofuran (15 mL, prepared to a concentration of about 1 mol / L) was added via syringe. R3SiCl (15 mmol, 1.0 equivalents) was added at 0 °C, and the mixture was stirred at room temperature for 12 h. The generated silane-based lithium reagent was titrated with diphenylacetic acid (usually to a concentration of about 1 mol / L) according to the method reported by Kofron. Subsequently, an alkyl aldehyde (10.0 mmol, 1.0 equivalents) was dissolved in tetrahydrofuran (50 mL), and dimethylphenylchlorosilane (15.0 mmol, 1.5 equivalents) was added at -78 °C. The reaction mixture was gradually heated to room temperature and allowed to react for 16 h. The reaction was quenched with water and then extracted with ethyl acetate (3 × 50 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was then rapidly purified by column chromatography (silica gel, eluent: cyclohexane / ethyl acetate = 20:1) to give the target product, α-hydroxyalkylsilane S2 (a yellow oil).

[0050] (2) Triphenylphosphine (1.5 equivalents) and imidazole (1.5 equivalents) were dissolved in anhydrous dichloromethane (to prepare a 0.3 mol / L solution), and bromine (1.5 equivalents) was slowly added at 0°C. The mixture was stirred rapidly at 0°C for 10 minutes. Then, α-hydroxyalkylsilane S2 (1.0 equivalents) obtained in the previous step was dissolved in dichloromethane (5 mL) and added dropwise to the above mixture. The mixture was stirred at 0°C for 1 hour, then allowed to warm naturally to room temperature and reacted for another 12 hours. The reaction was quenched with water and extracted with ethyl acetate (3 × 30 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by rapid column chromatography (silica gel, eluent cyclohexane) to give the desired target product, alkyl bromide 1.

[0051] (3) Accurately weigh Zn powder (13.1 mg, 0.2 mmol) into a glove box, then add 1,10-phenanthroline (3.46 mg, 0.024 mmol), ethylene glycol dimethyl ether nickel bromide (6.2 mg, 0.02 mmol), dimethyl sulfoxide (0.2 mL), acrylonitrile (39 μL, 0.6 mmol), dimethylphenylchlorosilane (83 μL, 0.6 mmol), and alkyl bromide (0.2 mmol). Stir at 45 °C for 20 h. After the reaction is complete, add 2 mL of distilled water and stir for 1 h. Then, extract the organic layer with DCM, dry with anhydrous Na2SO4, filter, and concentrate under reduced pressure. The residue is purified by rapid chromatography. The yield of 4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)tetradec-13-enonitrile is 42%. 1 H NMR (500 MHz, Chloroform- d )δ 7.55 – 7.45 (m, 2H), 7.37 – 7.35 (m, 3H), 6.17 – 5.94 (m, 2H), 5.90 – 5.67 (m, 2H), 4.98 (dd, J = 32.0, 13.7 Hz, 2H), 2.10 – 1.97 (m, 2.5H), 1.71 (t, J = 13.1 Hz, 0.5H), 1.65 – 1.47 (m, 2H), 1.44 – 1.36 (m, 4H), 1.35 –1.33 (m, 0.5H), 1.32 – 1.25 (m, 6H), 1.24 – 1.17 (m, 4H), 1.05 (tt, J = 8.5,4.4 Hz, 0.5H), 0.36 – 0.28 (m, 6H), 0.23 (d, J = 3.9 Hz, 3H), 0.13 (d, J = 3.4Hz, 3H). 13 C NMR (101 MHz, Chloroform- d)δ 139.25, 139.21, 138.42, 138.06,135.24, 135.09, 134.06, 134.03, 133.83, 133.81, 129.19, 129.04, 127.99,127.83, 122.38, 121.80, 114.17, 114.14, 77.43, 77.11, 76.79, 33.85, 33.84,30.62, 30.09, 29.83, 29.50, 29.44, 29.42, 29.39, 29.15, 29.12, 29.07, 28.96, 28.95, 28.74, 28.69, 27.50, 26.96, 26.36, 24.57, 18.75, 17.19, -3.36, -3.72, -3.97, -4.78, -4.95, -5.02, -5.32, -5.44. Example 10: 4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)-6-(methylthio)hexanonitrile Synthesis of 4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)-6-(methylthio)hexanenitrile (3j) (1) In a flame-dried 50 mL three-necked flask, a magnetic stir bar and lithium scrap (468 mg, 67.5 mmol, 4.5 equivalents) were added. The system was evacuated and backfilled with argon, repeated three times. Anhydrous tetrahydrofuran (15 mL, prepared to a concentration of about 1 mol / L) was added via syringe. R3SiCl (15 mmol, 1.0 equivalents) was added at 0 °C, and the mixture was stirred at room temperature for 12 h. The generated silane-based lithium reagent was titrated with diphenylacetic acid (usually to a concentration of about 1 mol / L) according to the method reported by Kofron. Subsequently, an alkyl aldehyde (10.0 mmol, 1.0 equivalents) was dissolved in tetrahydrofuran (50 mL), and dimethylphenylchlorosilane (15.0 mmol, 1.5 equivalents) was added at -78 °C. The reaction mixture was gradually heated to room temperature and allowed to react for 16 h. The reaction was quenched with water and then extracted with ethyl acetate (3 × 50 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was then rapidly purified by column chromatography (silica gel, eluent: cyclohexane / ethyl acetate = 20:1) to give the target product, α-hydroxyalkylsilane S2 (a yellow oil).

[0052] (2) Triphenylphosphine (1.5 equivalents) and imidazole (1.5 equivalents) were dissolved in anhydrous dichloromethane (to prepare a 0.3 mol / L solution), and bromine (1.5 equivalents) was slowly added at 0°C. The mixture was stirred rapidly at 0°C for 10 minutes. Then, α-hydroxyalkylsilane S2 (1.0 equivalents) obtained in the previous step was dissolved in dichloromethane (5 mL) and added dropwise to the above mixture. The mixture was stirred at 0°C for 1 hour, then allowed to warm naturally to room temperature and reacted for another 12 hours. The reaction was quenched with water and extracted with ethyl acetate (3 × 30 mL). The combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by rapid column chromatography (silica gel, eluent cyclohexane) to give the desired target product, alkyl bromide 1.

[0053] (3) Accurately weigh 22 mg (0.4 mmol) of Mn powder into a glove box, then add 3.75 mg (0.024 mmol) of 2,2'-bipyridine, 4.3 mg (0.02 mmol) of nickel bromide, 1 mL of toluene, 39 μL (0.6 mmol) of acrylonitrile, 83 μL (0.6 mmol) of dimethylphenylchlorosilane, and 0.2 mmol of alkyl bromide. Stir at 25 °C for 12 h. After the reaction is complete, add 2 mL of distilled water and stir for 1 h. Then, extract the organic layer with DCM, dry with anhydrous Na2SO4, filter, and concentrate under reduced pressure. The residue is purified by rapid chromatography. The yield of 4-(dimethyl(phenyl)silyl)-2-(dimethyl(vinyl)silyl)-6-(methylthio)hexanonitrile is 49%. 1 H NMR (500 MHz, Chloroform- d)δ 7.55 –7.43 (m, 2H), 7.41 – 7.31 (m, 3H), 6.14 – 5.93 (m, 2H), 5.85 – 5.69 (m, 1H),2.63 – 2.54 (m, 0.5H), 2.47 – 2.26 (m, 1.5H), 2.09 – 1.92 (m, 3.5H), 1.87 –1.79 (m, 0.5H), 1.77 – 1.68 (m, 1H), 1.68 – 1.61 (m, 0.5H), 1.60 – 1.54 (m,1H), 1.52 – 1.45 (m, 0.5H), 1.44 – 1.39 (m, 0.5H), 1.37 – 1.25 (m, 1H), 1.18– 1.11 (m, 0.5H), 0.33 (d, J = 5.3 Hz, 3H), 0.31 (d, J = 6.0 Hz, 3H), 0.22 (d, J =3.0 Hz, 3H), 0.13 (d, J = 5.0 Hz, 3H). 13 C NMR (101 MHz, Chloroform- d )δ 137.50,135.57, 135.43, 133.96, 133.94, 133.92, 133.90, 129.52, 129.42, 128.20,128.08, 77.48, 77.16, 76.84, 33.84, 33.66, 30.55, 28.85, 27.57, 27.02, 26.21,24.66, 18.97, 17.48, 15.61, 15.55, -3.56, -3.87, -4.06, -4.67, -4.86, -4.94,-5.26, -5.37。

Claims

1. A method for synthesizing an organosilicon compound, characterized in that, The steps are as follows: Under nitrogen conditions, reducing agent, ligand, catalyst, solvent, acrylonitrile (2), chlorosilane (3) and alkyl bromide (1) were added sequentially to the reaction flask, and then stirred at 15 ℃-45 ℃ for 8 h-24 h. After the reaction was completed, the reaction was quenched with water and stirred for another 1 h. The mixture was extracted with ethyl acetate and saturated brine, dried with anhydrous sodium sulfate, filtered with diatomaceous earth, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain organosilicon compounds. The synthesis route is as follows: Where Ph is a benzene ring; Me is a methyl group; R represents ethylbenzene, 4-ethyl anisole, p-fluoroethylbenzene, p-chloroethylbenzene, p-trifluoromethylethylbenzene, methyl, pentyl, hydrogen atom, 1-decene, and methyl ethyl sulfide, respectively. The concentration of the alkyl bromide in the reaction system is 0.1 M-1 M; The molar ratio of alkyl bromide to reducing agent is 1:3; The molar ratio of alkyl bromide to ligand is 1:0.12; The molar ratio of alkyl bromide to catalyst is 1:0.1; The molar ratio of alkyl bromide to acrylonitrile is 1:3; The molar ratio of alkyl bromide to chlorosilane is 1:

3.

2. The method for synthesizing organosilicon compounds according to claim 1, characterized in that, The solvent is ethyl acetate, toluene, tetrahydrofuran, etc. N,N -Dimethylformamide, N,N - One or more of dimethylacetamide, dimethyl sulfoxide, dichloromethane, acetone, and acetonitrile.

3. The method for synthesizing organosilicon compounds according to claim 1, characterized in that, The reducing agent is Zn, Mn or Mg.

4. The method for synthesizing organosilicon compounds according to claim 1, characterized in that, The catalyst is nickel bromide in ethylene glycol dimethyl ether, nickel chloride in ethylene glycol dimethyl ether, nickel bromide, nickel chloride, nickel iodide, nickel fluoride, nickel acetylacetone, nickel trifluoromethanesulfonate, or nickel tetrafluoroborate hexahydrate.

5. The method for synthesizing organosilicon compounds according to claim 1, characterized in that, The ligand is 2,2′-bipyridine, 1,10-phenanthroline, 2,9-dimethyl-1,10-phenanthroline, 3-(2-pyridyl)-1,2,4-triazole, 2,6-bis(1-pyrazolyl)pyridine, 2,6-bis(2-phenylimidazolium)pyridine, or 2,6-bis(4,5-dihydrooxazol-2-yl)pyridine.

Images