Method for reductive silanization of activated olefin by using nickel-catalyzed alpha-benzoyl alkyl bromide and chlorosilane

Abstract

The invention belongs to a preparation method of pharmaceutical and chemical intermediates, and discloses a method for reductive silanization of activated olefin by nickel-catalyzed alpha-benzoyl alkyl bromide and chlorosilane, which comprises the following steps of: synthesizing the alpha-benzoyl alkyl bromide from alkyl aldehyde, reacting the alpha-benzoyl alkyl bromide serving as a reaction substrate and chlorosilane serving as a catalyst in the presence of a catalyst; a nickel catalysis technology is adopted to realize reductive silanization reaction of activated olefin. Compared with other synthesis methods, the alpha-benzoyl alkyl bromide synthesized by aldehyde is used as a reaction substrate and is a chemical which is wide and easy to obtain. Compared with a traditional synthesis method, nickel catalysis serves as a green energy source, the reaction condition where nickel catalysis participates is milder, functional group compatibility is better, and therefore a new thought is provided for efficient synthesis of the alkylsilane compound.

Description

Technical Field

[0001] This invention pertains to the preparation methods of pharmaceutical and chemical intermediates, and relates to a method for the reductive silanization of activated olefins by nickel-catalyzed α-benzoylalkyl bromide and chlorosilane. Background Technology

[0002] Silicon is located in the third period of the periodic table and is a metalloid element in group IVA. It is the second most abundant element in the Earth's crust after oxygen. Although silicon and carbon both have four electrons in their outermost shell, their properties are very different. Compared with carbon, silicon has a much larger atomic radius, making it unable to form stable π bonds. Furthermore, the Si-O bond has a higher bond energy and is more stable. Therefore, silicon exists widely in nature in the form of complex silicates or silicon dioxide in dust, gravel, and rocks.

[0003] Organosilicon compounds have wide applications in materials, medicine, agrochemicals, and organic synthesis due to their unique properties. For example, silicon, as a bioisostere of carbon atoms in medicine, exhibits different physical and electronic properties, resulting in lower toxicity, higher lipid solubility, significantly tunable polarization, and metabolic characteristics compared to carbon analogs. On the other hand, silicon-containing molecules have impressive applications in advanced hybrid materials. In addition to surface modification, organosilanes are important building blocks for organic catalysts and are involved in selective C-Si bond formation. Therefore, developing C-Si bond formation reactions that incorporate silicon atoms into organic molecules is not only a prerequisite for unleashing the full potential of organosilicon compounds, but also a driving force.

[0004] 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, etc.

[0005] Significant progress has been made in the study of transition metal-catalyzed silicon-carbon bond construction of halosilanes. Because halosilanes are widely available, inexpensive, and are one of the raw materials for the synthesis of hydrosilanes, directly utilizing halosilanes to construct silicon-carbon bonds can not only shorten intermediate steps but also improve atom utilization efficiency. Common halosilanes include chlorosilanes and iodosilanes, among which chlorosilanes have lower air sensitivity and stronger functional group tolerance than iodosilanes, making them more ideal halosilane reagents.

[0006] This invention proposes the synthesis of alkyl aldehydes. α -benzoylalkyl bromide, α - Benzoylalkyl bromide was used as the substrate to achieve the reductive silanization of activated olefins using nickel catalysis. The underlying idea was that, compared to other synthetic methods, aldehyde synthesis... αBenzoyl alkyl bromides are a class of readily available and widely distributed chemicals that serve as reaction substrates. Compared to traditional synthetic methods, nickel catalysis, as a green energy source, offers milder reaction conditions and better functional group compatibility, thus providing a new approach for the efficient synthesis of alkylsilane compounds. Summary of the Invention

[0007] This invention provides a method for pre-synthesizing alkyl aldehydes under nickel-catalyzed conditions. α A method for the reductive silanization of activated olefins using benzoylalkyl bromide and chlorosilane. This method has the advantages of mild reaction conditions, convenient experimental operation, good substrate compatibility, and easy scale-up. Therefore, this invention has great application value and social and economic benefits.

[0008] The technical solution of this invention: A method for the reductive silylation of activated olefins by nickel-catalyzed α-benzoylalkyl bromide and chlorosilane. by α Using benzoyl alkyl bromide (1), acrylonitrile (2), and dimethylvinylchlorosilane (3) as raw materials, a series of alkylsilane compounds were synthesized in a one-pot process at room temperature with the addition of a catalyst, reducing agent, and ligand; the synthetic route is as follows: The steps are as follows: This operation was performed in a nitrogen-filled glove box; the catalyst, reducing agent, ligand, acrylonitrile, and dimethylvinylchlorosilane were added to a reaction flask equipped with a magnetic stirrer, and the solvent was added and stirred for 30 minutes; then... α - Add benzoyl alkyl bromide to the mixed solution; seal the reaction flask and remove it from the glove box; stir at 15 ℃-45 ℃ for 8 h-24 h; after the reaction is completed, quench the reaction with water and continue stirring for 1 h; dilute the reaction mixture with ethyl acetate, wash with brine, dry with anhydrous sodium sulfate, and concentrate under reduced pressure.

[0009] R is selected from one of alkanes, alkenes, aryl groups, and heterocycles; The catalyst is selected from one of ethylene glycol dimethyl ether nickel bromide, ethylene glycol dimethyl ether nickel chloride, nickel bromide, nickel chloride, nickel iodide, nickel fluoride, nickel acetylacetone, nickel trifluoromethanesulfonate, and nickel tetrafluoroborate hexahydrate, preferably ethylene glycol dimethyl ether nickel bromide; The ligand is selected from one of 2,6-bis(1-pyrazolyl)pyridine, 2,6-bis(3-methyl-1H-pyrazol-1-yl)pyridine, 2,6-bis(3,5-dimethylpyrazol-1-yl)pyridine, o-phenanthroline and 2-(1H-1,2,4-triazol-3-yl)pyridine, preferably 2,6-bis(3,5-dimethylpyrazol-1-yl)pyridine; The reducing agent is selected from one of Mn powder, Zn powder and Mg powder, with Zn powder being preferred; Solvent selected from N,N -Dimethylformamide, N,N - One or more of the following: dimethylacetamide, dichloromethane, tetrahydrofuran, toluene, 1,4-dioxane, dimethyl sulfoxide, acetone, and acetonitrile, preferably. N,N - Dimethylacetamide; The concentration of benzoylalkyl bromide in the reaction system was 0.1 M; The molar ratio of benzoyl alkyl bromide to reducing agent is 1:3; The molar ratio of benzoylalkyl bromide to ligand is 1:0.05; The molar ratio of benzoylalkyl bromide to catalyst is 1:0.1; The molar ratio of benzoyl alkyl bromide to acrylonitrile is 1:3; The molar ratio of benzoylalkyl bromide to dimethylvinylchlorosilane is 1:3; The reaction time range is 10 h to 24 h; The reaction temperature is 15 ℃~45 ℃.

[0010] The beneficial effects of this invention are: the method of this invention has the advantages of mild reaction conditions, simple steps, readily available raw materials, and a wide substrate range. Aldehydes are extremely widely available bulk chemicals. This invention has significant practical value and socio-economic benefits, and can meet the requirements of industrial production. Studies have found that the product yield can be as high as 82%, and the alkylsilane compounds synthesized by the reaction are important components of many bioactive molecules and intermediates in organic synthesis, with broad application prospects. Therefore, this invention has important application value. Attached Figure Description

[0011] Figure 1 For compound 4a 1 H-NMR spectrum.

[0012] Figure 2 For compound 4a 13 C-NMR spectrum.

[0013] Figure 3 For compound 4b 1 H-NMR spectrum.

[0014] Figure 4 For compound 4b 13 C-NMR spectrum.

[0015] Figure 5 For compound 4c 1 H-NMR spectrum.

[0016] Figure 6 For compound 4c 13 C-NMR spectrum.

[0017] Figure 7 For compound 4d 1 H-NMR spectrum.

[0018] Figure 8 For compound 4d 13 C-NMR spectrum.

[0019] Figure 9 For compound 4e 1 H-NMR spectrum.

[0020] Figure 10 For compound 4e 13 C-NMR spectrum.

[0021] Figure 11 For compound 4f 1 H-NMR spectrum.

[0022] Figure 12 For compound 4f 13 C-NMR spectrum.

[0023] Figure 13 4g of compound 1 H-NMR spectrum.

[0024] Figure 14 4g of compound 13 C-NMR spectrum.

[0025] Figure 15 For compound 4h 1 H-NMR spectrum.

[0026] Figure 16 For compound 4h 13 C-NMR spectrum.

[0027] Figure 17 For compound 4h 19 F NMR spectrum Figure 18 For compound 4i 1 H-NMR spectrum.

[0028] Figure 19 For compound 4i 13 C-NMR spectrum.

[0029] Figure 20 For compound 4j 1 H-NMR spectrum.

[0030] Figure 21 For compound 4j 13 C-NMR spectrum. Detailed Implementation

[0031] The specific embodiments of the present invention will be further described below with reference to the accompanying drawings and technical solutions.

[0032] Example 1: Synthesis of 1-cyano-1-(dimethyl(vinyl)silyl)-5-phenylpentan-3-yl benzoate (4a) 4a (1) Zinc bromide (56.3 mg, 0.25 mmol) was added to an oven-dried vial in a glove box. Next, the sealed vial was removed from the glove box, and dry dichloromethane (1 mL) was added to the vial under N2, followed by benzoyl bromide (1.5 g, 7.5 mmol). After stirring at -10 °C for 10 minutes, the aldehyde (5 mmol) was added dropwise, and the reaction was stirred overnight at -10 °C. The reaction mixture was filtered through a small column of neutral alumina using dichloromethane washings. The filtrate was concentrated under reduced pressure. The product was purified by silica gel column chromatography.

[0033] (2) Accurately weigh Zn powder (48.4 mg, 0.8 mmol), 2,6-bis(3,5-dimethylpyrazol-1-yl)pyridine (5.2 mg, 5 mol%), ethylene glycol dimethyl ether nickel bromide (12.4 mg, 10 mol%), and add ultradry N,N-dimethylformamide (0.4 mL), acrylonitrile (80 μL, 1.2 mmol), dimethylphenylchlorosilane (140 μL, 1.2 mmol), and alkyl bromide (127.2 mg, 0.4 mmol) into a glove box. Then stir at 25 °C for 18 h. After the reaction is complete, add 2 mL of distilled water and stir for 1 hour. Then extract the organic layer with ethyl acetate, dry with anhydrous sodium sulfate, filter, and concentrate under reduced pressure. The residue is purified by rapid chromatography. The yield of product 4a is 85%.

[0034] 1 H NMR (500 MHz, Chloroform-d) δ 8.11 (dd, J = 7.8, 4.5 Hz, 2H), 7.62(td, J = 7.7, 2.9 Hz, 1H), 7.50 (t, J= 7.5 Hz, 2H), 7.31 (t, J = 7.8 Hz, 2H),7.25-7.18 (m, 3H), 6.25-6.05 (m, 2H), 5.87 (ddd, J = 17.1, 11.4, 5.7 Hz, 1H),5.46-5.27 (m, 1H), 2.86-2.69 (m, J = 7.7, 7.0 Hz, 2H), 2.26-2.01 (m, 3H), 2.00-1.88 (m, 2H), 0.31 (dd, J = 8.8, 2.5 Hz, 6H). 13 C NMR (101 MHz, Chloroform- d ) δ 166.26, 166.06, 141.06, 141.00, 135.97, 135.93, 133.48, 133.43, 133.16, 130.07, 130.05, 129.78, 129.76, 128.60, 128.55, 128.48, 128.45, 128.38, 128.34, 128.32, 126.15, 126.13, 73.99, 73.60, 35.79, 35.15, 31.71, 31.67, 31.02, 14.41, 14.04, -4.95, -5.43, -5.50. Example 2: Synthesis of 4-cyano-4-(dimethyl(vinyl)silyl)butan-2-yl benzoate (4b) 4b (1) Zinc bromide (56.3 mg, 0.25 mmol) was added to an oven-dried vial in a glove box. Next, the sealed vial was removed from the glove box, and dry dichloromethane (1 mL) was added to the vial under N2, followed by benzoyl bromide (1.5 g, 7.5 mmol). After stirring at -10 °C for 10 minutes, the aldehyde (5 mmol) was added dropwise, and the reaction was stirred overnight at -10 °C. The reaction mixture was filtered through a small column of neutral alumina using dichloromethane washings. The filtrate was concentrated under reduced pressure. The product was purified by silica gel column chromatography.

[0035] (2) Accurately weigh Mn powder (44.0 mg, 0.8 mmol), 2,6-bis(1-pyrazolyl)pyridine (4.2 mg, 5 mol%), and nickel bromide (8.7 mg, 10 mol%) into a glove box. Add ultra-dry dichloromethane (0.4 mL), acrylonitrile (80 μL, 1.2 mmol), dimethylphenylchlorosilane (140 μL, 1.2 mmol), and alkyl bromide (91.2 mg, 0.4 mmol). Then stir at 35 °C for 12 h. After the reaction is complete, add 2 mL of distilled water and stir for 1 hour. Then extract the organic layer with ethyl acetate, dry with anhydrous sodium sulfate, filter, and concentrate under reduced pressure. Purify the residue by rapid chromatography. The yield of product 4b is 65%.

[0036] 1 H NMR (500 MHz, Chloroform-d) δ 7.88 (dd, J = 16.6, 7.7 Hz, 2H), 7.38(td, J = 7.5, 4.6 Hz, 1H), 7.26 (td, J = 7.9, 2.2 Hz, 2H), 6.07-5.87 (m, 2H),5.69 (dq, J = 15.2, 8.0 Hz, 1H), 5.11 (ddt, J = 29.8, 12.5, 6.2 Hz, 1H), 1.98-1.78 (m, 1H), 1.78-1.61 (m, 2H), 1.24 (d, J = 6.2 Hz, 3H), 0.12 (dd, J = 4.6, 2.1Hz, 6H). 13 C NMR (126 MHz, Chloroform-d) δ 166.02, 165.85, 135.93, 135.87, 133.50, 133.47, 133.03, 133.02, 130.28, 130.26, 129.72, 129.61, 128.41, 128.36, 121.68, 121.40, 71.23, 70.55, 33.33, 32.77, 19.98, 19.49, 14.51, 14.43, -4.94, -4.96, -5.41, -5.47. Example 3: Synthesis of 1-cyano-1-(dimethyl(vinyl)silyl)-4,4-dimethylpentan-3-ylbenzoate (4c) 4c (1) Zinc bromide (56.3 mg, 0.25 mmol) was added to an oven-dried vial in a glove box. Next, the sealed vial was removed from the glove box, and dry dichloromethane (1 mL) was added to the vial under N2, followed by benzoyl bromide (1.5 g, 7.5 mmol). After stirring at -10 °C for 10 minutes, the aldehyde (5 mmol) was added dropwise, and the reaction was stirred overnight at -10 °C. The reaction mixture was filtered through a small column of neutral alumina using dichloromethane washings. The filtrate was concentrated under reduced pressure. The product was purified by silica gel column chromatography.

[0037] (2) Accurately weigh Zn powder (48.4 mg, 0.8 mmol), 2,6-bis(3-methyl-1H-pyrazol-1-yl)pyridine (4.8 mg, 5 mol%), ethylene glycol dimethyl ether nickel bromide (12.4 mg, 10 mol%), and add ultradry N,N-dimethylformamide (0.4 mL), acrylonitrile (80 μL, 1.2 mmol), dimethylvinylchlorosilane (140 μL, 1.2 mmol), and alkyl bromide (108.0 mg, 0.4 mmol) into a glove box. Then stir at 25 °C for 12 h. After the reaction is complete, add 2 mL of distilled water and stir for 1 hour. Then extract the organic layer with ethyl acetate, dry with anhydrous sodium sulfate, filter, and concentrate under reduced pressure. The residue is purified by rapid chromatography. The yield of the product is 82%.

[0038] 1 H NMR (500 MHz, Chloroform-d) δ 8.19-8.05 (m, 2H), 7.66-7.54 (m, 1H),7.54-7.41 (m, 2H), 6.22-6.06 (m, 2H), 5.95-5.79 (m, 1H), 5.33-5.00 (m, 1H),2.02-1.70 (m, 3H), 1.01 (d, J = 14.0 Hz, 9H), 0.43-0.21 (m, 6H). 13 C NMR (126MHz, Chloroform-d) δ167.13, 166.15, 135.79, 135.69, 133.74, 133.59, 133.11, 133.05, 130.05, 130.02, 129.95, 129.75, 128.50, 128.38, 122.04, 121.47, 81.48, 80.27, 35.32, 35.06, 27.96, 27.41, 25.98, 25.93, 15.41, 15.23, -4.79, -4.93, -5.38, -5.53. Example 4: Synthesis of 1-cyano-1-(dimethyl(vinyl)silyl)-5-(5-methylfuran-2-yl)pentan-3-yl benzoate (4d) 4d (1) Zinc bromide (56.3 mg, 0.25 mmol) was added to an oven-dried vial in a glove box. Next, the sealed vial was removed from the glove box, and dry dichloromethane (1 mL) was added to the vial under N2, followed by benzoyl bromide (1.5 g, 7.5 mmol). After stirring at -10 °C for 10 minutes, the aldehyde (5 mmol) was added dropwise, and the reaction was stirred overnight at -10 °C. The reaction mixture was filtered through a small column of neutral alumina using dichloromethane washings. The filtrate was concentrated under reduced pressure. The product was purified by silica gel column chromatography.

[0039] (2) Accurately weigh Zn powder (48.4 mg, 0.8 mmol), 2,6-bis(3,5-dimethylpyrazol-1-yl)pyridine (5.2 mg, 5 mol%), ethylene glycol dimethyl ether nickel bromide (12.4 mg, 10 mol%), and add ultradry N,N-dimethylacetamide (0.4 mL), acrylonitrile (80 μL, 1.2 mmol), dimethylvinylchlorosilane (140 μL, 1.2 mmol), and alkyl bromide (128.8 mg, 0.4 mmol) into a glove box. Then stir at 15 °C for 24 h. After the reaction is complete, add 2 mL of distilled water and stir for 1 hour. Then extract the organic layer with ethyl acetate, dry with anhydrous sodium sulfate, filter, and concentrate under reduced pressure. The residue is purified by rapid chromatography. The product yield is 58% after 4 days.

[0040] 1 H NMR (500 MHz, Chloroform-d) δ 8.07 (t,J = 7.7 Hz, 2H), 7.57 (td, J =7.5, 3.4 Hz, 1H), 7.45 (t, J = 7.6 Hz, 2H), 6.24-6.04 (m, 2H), 5.91-5.78 (m,3H), 5.42-5.24 (m, 1H), 2.70 (hept, J = 7.5 Hz, 2H), 2.22 (s, 3H), 2.16-1.96(m, 3H), 1.90 (dddt, J = 21.1, 13.6, 10.4, 3.9 Hz, 2H), 0.28 (dd, J = 5.9, 2.4Hz, 6H). 13 C NMR (126 MHz, Chloroform-d) δ 166.21, 165.98, 152.62, 152.59, 150.60, 150.56, 135.94, 135.89, 133.47, 133.43, 133.12, 130.03, 130.01, 129.77, 129.74, 128.43, 128.39, 106.04, 105.99, 105.96, 73.79, 73.28, 32.52, 31.97, 31.59, 30.97, 24.10, 24.05, 14.39, 14.13, 13.47, -4.98, -5.45, -5.52. Example 5: Synthesis of 7-chloro-1-cyano-1-(dimethyl(vinyl)silyl)heptan-3-yl benzoate (4e) 4e (1) Zinc bromide (56.3 mg, 0.25 mmol) was added to an oven-dried vial in a glove box. Next, the sealed vial was removed from the glove box, and dry dichloromethane (1 mL) was added to the vial under N2, followed by benzoyl bromide (1.5 g, 7.5 mmol). After stirring at -10 °C for 10 minutes, the aldehyde (5 mmol) was added dropwise, and the reaction was stirred overnight at -10 °C. The reaction mixture was filtered through a small column of neutral alumina using dichloromethane washings. The filtrate was concentrated under reduced pressure. The product was purified by silica gel column chromatography.

[0041] (2) Accurately weigh Mg powder (19.4 mg, 0.8 mmol), 2-(1H-1,2,4-triazol-3-yl)pyridine (2.9 mg, 5 mol%), ethylene glycol dimethyl ether nickel bromide (12.4 mg, 10 mol%), and add ultra-dry dichloromethane (0.4 mL), acrylonitrile (80 μL, 1.2 mmol), dimethylphenylchlorosilane (140 μL, 1.2 mmol), and alkyl bromide (121.6 mg, 0.4 mmol) into a glove box. Stir at 25 °C for 24 h. After the reaction is complete, add 2 mL of distilled water and stir for 1 hour. Then, extract the organic layer with ethyl acetate, dry to anhydrous sodium sulfate, filter, and concentrate under reduced pressure. Purify the residue by rapid chromatography. The yield of the product 4e is 66%.

[0042] Example 6: Synthesis of 3-cyano-3-(dimethyl(vinyl)silyl)-1-(tetrahydro-2H-pyran-4-yl)propylbenzoate (4f) 4f (1) Zinc bromide (56.3 mg, 0.25 mmol) was added to an oven-dried vial in a glove box. Next, the sealed vial was removed from the glove box, and dry dichloromethane (1 mL) was added to the vial under N2, followed by benzoyl bromide (1.5 g, 7.5 mmol). After stirring at -10 °C for 10 minutes, the aldehyde (5 mmol) was added dropwise, and the reaction was stirred overnight at -10 °C. The reaction mixture was filtered through a small column of neutral alumina using dichloromethane washings. The filtrate was concentrated under reduced pressure. The product was purified by silica gel column chromatography.

[0043] (2) Accurately weigh Zn powder (48.4 mg, 0.8 mmol), 2,6-bis(1-pyrazolyl)pyridine (4.2 mg, 5 mol%), ethylene glycol dimethyl ether nickel chloride (8.8 mg, 10 mol%), and add ultradry N,N-dimethylacetamide (0.4 mL), acrylonitrile (80 μL, 1.2 mmol), dimethylphenylchlorosilane (140 μL, 1.2 mmol), and alkyl bromide (119.0 mg, 0.4 mmol) into a glove box. Then stir at 45 °C for 18 h. After the reaction is complete, add 2 mL of distilled water and stir for 1 hour. Then extract the organic layer with ethyl acetate, dry with anhydrous sodium sulfate, filter, and concentrate under reduced pressure. The residue is purified by rapid chromatography. The yield of the product is 64%.

[0044] 1 H NMR (400 MHz, Chloroform-d) δ 8.06 (dd, J J = 7.8, 6.0 Hz, 2H), 7.57(td, J J = 7.4, 4.5 Hz, 1H), 7.45 (td, J J = 7.8, 1.9 Hz, 2H), 6.26 - 6.00 (m, 2H), 5.94 - 5.76 (m, 1H), 5.29 - 5.05 (m, 1H), 3.98 (dt, J J = 10.6, 4.7 Hz, 2H), 3.38(qd, J J = 11.7, 2.4 Hz, 2H), 2.13 - 1.78 (m, 4H), 1.70 - 1.42 (m, 4H), 0.27 (t, J J = 3.3 Hz, 6H). 13 C NMR (101 MHz, Chloroform-d) δ 166.32, 165.99, 136.04, 135.98, 133.41, 133.39, 133.27, 133.25, 129.82, 129.79, 129.75, 128.52, 128.48, 121.73, 121.34, 77.18, 76.39, 67.71, 67.65, 67.54, 67.47, 38.85, 38.02, 29.01, 28.90, 28.79, 28.07, 27.97, 27.84, 14.56, – 4.93, – 4.94, – 5.42, – 5.54. Example 7: Synthesis of 1 - cyano - 1 - (dimethyl(vinyl)silyl) - 5,5 - dimethylhexan - 3 - ylbenzoate (4g) 4g (1) Zinc bromide (56.3 mg, 0.25 mmol) was added to an oven-dried vial in a glove box. Next, the sealed vial was removed from the glove box, and dry dichloromethane (1 mL) was added to the vial under N2, followed by benzoyl bromide (1.5 g, 7.5 mmol). After stirring at -10 °C for 10 minutes, the aldehyde (5 mmol) was added dropwise, and the reaction was stirred overnight at -10 °C. The reaction mixture was filtered through a small column of neutral alumina using dichloromethane washings. The filtrate was concentrated under reduced pressure. The product was purified by silica gel column chromatography.

[0045] (2) Accurately weigh Mn powder (44.0 mg, 0.8 mmol), 2,6-bis(3,5-dimethylpyrazol-1-yl)pyridine (5.2 mg, 5 mol%), and nickel iodide (12.5 mg, 10 mol%) into a glove box. Add ultra-dry N,N-dimethylformamide (0.4 mL), acrylonitrile (80 μL, 1.2 mmol), dimethylphenylchlorosilane (140 μL, 1.2 mmol), and alkyl bromide (113.6 mg, 0.4 mmol). Then stir at 15 °C for 12 h. After the reaction is complete, add 2 mL of distilled water and stir for 1 hour. Then extract the organic layer with ethyl acetate, dry with anhydrous sodium sulfate, filter, and concentrate under reduced pressure. Purify the residue by rapid chromatography. The yield of 4 g of product is 66%.

[0046] 1 H NMR (400 MHz, Chloroform-d) δ 8.13-7.98 (m, 2H), 7.64-7.52 (m, 1H),7.45 (t, J = 7.6 Hz, 2H), 6.21-6.03 (m, 2H), 5.91-5.77 (m, 1H), 5.48-5.35 (m,1H), 1.98-1.76 (m, 4H), 1.54 (ddd, J = 14.7, 4.7, 2.5 Hz, 1H), 0.95 (d, J = 2.9Hz, 10H), 0.34-0.22 (m, 6H). 13 C NMR (101 MHz, Chloroform-d) δ166.03, 135.89, 133.49, 133.45, 133.08, 130.19, 129.80, 129.72, 128.43, 121.64, 72.08, 71.85, 47.49, 46.73, 33.67, 32.72, 30.34, 30.28, 29.95, 29.91, 14.24, 13.78, -4.99, -5.45, -5.55. Example 8: 1-cyano-1-(dimethyl(vinyl)silyl)-5-(4-fluorophenyl)pentan-3- Synthesis of yl benzoate (4h) 4h (1) Zinc bromide (56.3 mg, 0.25 mmol) was added to an oven-dried vial in a glove box. Next, the sealed vial was removed from the glove box, and dry dichloromethane (1 mL) was added to the vial under N2, followed by benzoyl bromide (1.5 g, 7.5 mmol). After stirring at -10 °C for 10 minutes, the aldehyde (5 mmol) was added dropwise, and the reaction was stirred overnight at -10 °C. The reaction mixture was filtered through a small column of neutral alumina using dichloromethane washings. The filtrate was concentrated under reduced pressure. The product was purified by silica gel column chromatography.

[0047] (2) Accurately weigh Mg powder (19.4 mg, 0.8 mmol), 2,6-bis(3,5-dimethylpyrazol-1-yl)pyridine (5.2 mg, 5 mol%), and nickel acetylacetonate (10.3 mg, 10 mol%) into a glove box. Add ultra-dry tetrahydrofuran (0.4 mL), acrylonitrile (80 μL, 1.2 mmol), dimethylphenylchlorosilane (140 μL, 1.2 mmol), and alkyl bromide (134.4 mg, 0.4 mmol). Then stir at 25 °C for 10 h. After the reaction is complete, add 2 mL of distilled water and stir for 1 hour. Then extract the organic layer with ethyl acetate, dry with anhydrous sodium sulfate, filter, and concentrate under reduced pressure. Purify the residue by rapid chromatography. The product yield is 63% after 4 h.

[0048] 1 H NMR (500 MHz, Chloroform-d) δ 8.07 (dd, J = 7.9, 4.5 Hz, 2H), 7.58(td,J = 7.6, 3.1 Hz, 1H), 7.47 (t, J = 7.6 Hz, 2H), 7.13 (ddd, J = 8.6, 5.0, 2.6Hz, 2H), 6.95 (t, J = 8.5 Hz, 2H), 6.24 - 6.04 (m, 2H), 5.84 (ddd, J = 16.9, 11.3,5.7 Hz, 1H), 5.42 - 5.23 (m, 1H), 2.72 (qd, J = 12.2, 9.9, 6.0 Hz, 2H), 2.21 - 1.83(m, 5H), 0.28 (dd, J = 8.5, 2.9 Hz, 6H). 13 C NMR (126 MHz, Chloroform-d) δ 166.21,166.02, 162.37, 160.43, 136.66, 136.61, 136.61 (d, J = 6.0 Hz), 135.98,135.94, 133.43, 133.39, 133.20, 129.99, 129.97, 129.77, 129.74, 129.72,129.68, 128.48, 128.45, 121.74, 121.40, 115.35, 115.18, 73.81, 73.47, 35.91,35.20, 31.75, 31.00, 30.93, 30.90, 14.47, 13.96, -4.98, -5.45, -5.53. 19 F NMR(470 MHz, Chloroform-d) δ -117.25 (d, J = 13.8 Hz). Example 9: Synthesis of 1-cyano-1-(dimethyl(vinyl)silyl)-5-(4-methoxyphenyl)pentan-3- yl benzoate (4i) 4i (1) Zinc bromide (56.3 mg, 0.25 mmol) was added to an oven-dried vial in a glove box. Next, the sealed vial was removed from the glove box, and dry dichloromethane (1 mL) was added to the vial under N2, followed by benzoyl bromide (1.5 g, 7.5 mmol). After stirring at -10 °C for 10 minutes, the aldehyde (5 mmol) was added dropwise, and the reaction was stirred overnight at -10 °C. The reaction mixture was filtered through a small column of neutral alumina using dichloromethane washings. The filtrate was concentrated under reduced pressure. The product was purified by silica gel column chromatography.

[0049] (2) Accurately weigh Zn powder (48.4 mg, 0.8 mmol), 2,6-bis(3,5-dimethylpyrazol-1-yl)pyridine (5.2 mg, 5 mol%), and nickel bromide (8.7 mg, 10 mol%) into a glove box. Add ultra-dry dichloromethane (0.4 mL), acrylonitrile (80 μL, 1.2 mmol), dimethylphenylchlorosilane (140 μL, 1.2 mmol), and alkyl bromide (139.2 mg, 0.4 mmol). Then stir at 35 °C for 12 h. After the reaction is complete, add 2 mL of distilled water and stir for 1 hour. Then extract the organic layer with ethyl acetate, dry with anhydrous sodium sulfate, filter, and concentrate under reduced pressure. Purify the residue by rapid chromatography. The yield of product 4i is 65%.

[0050] 1 H NMR (500 MHz, Chloroform-d) δ 8.08 (dd, J = 8.0, 3.9 Hz, 2H), 7.58(dt, J = 7.8, 3.9 Hz, 1H), 7.47 (t, J = 7.6 Hz, 2H), 7.20-7.06 (m, 2H), 6.82 (d, J = 8.1 Hz, 2H), 6.26-6.01 (m, 2H), 5.84 (ddd, J = 16.9, 11.1, 5.8 Hz, 1H), 5.50-5.21 (m, 1H), 3.76 (s, 3H), 2.68 (tq, J = 13.4, 7.8, 6.5 Hz, 2H), 2.21-1.82 (m,5H), 0.28 (dd, J = 8.8, 2.6 Hz, 6H). 13C NMR (126 MHz, Chloroform-d) δ 166.24, 166.05, 158.00, 135.93, 135.89, 133.49, 133.45, 133.13, 133.07, 133.01, 130.09, 129.76, 129.74, 129.28, 129.25, 128.45, 128.42, 121.77, 121.44, 113.96, 73.99, 73.59, 55.25, 35.98, 35.34, 31.71, 31.03, 30.81, 30.76, 14.39, 14.02, -4.96, -5.43, -5.50. Example 10: 5-(2-bromophenyl)-1-cyano-1-(dimethyl(vinyl)silyl)pentan-3- Synthesis of yl benzoate (4j) 4j (1) Zinc bromide (56.3 mg, 0.25 mmol) was added to an oven-dried vial in a glove box. Next, the sealed vial was removed from the glove box, and dry dichloromethane (1 mL) was added to the vial under N2, followed by benzoyl bromide (1.5 g, 7.5 mmol). After stirring at -10 °C for 10 minutes, the aldehyde (5 mmol) was added dropwise, and the reaction was stirred overnight at -10 °C. The reaction mixture was filtered through a small column of neutral alumina using dichloromethane washings. The filtrate was concentrated under reduced pressure. The product was purified by silica gel column chromatography.

[0051] (2) Accurately weigh Mn powder (44.0 mg, 0.8 mmol), o-phenanthroline (3.6 mg, 5 mol%), nickel acetylacetonate (10.3 mg, 10 mol%), and add ultra-dry toluene (0.4 mL), acrylonitrile (80 μL, 1.2 mmol), dimethylphenylchlorosilane (140 μL, 1.2 mmol), and alkyl bromide (158.9 mg, 0.4 mmol) into a glove box. Then stir at 25 °C for 24 h. After the reaction is complete, add 2 mL of distilled water and stir for 1 hour. Then extract the organic layer with ethyl acetate, dry with anhydrous sodium sulfate, filter, and concentrate under reduced pressure. The residue is purified by rapid chromatography. The yield of product 4j is 75%.

[0052] 1H NMR (500 MHz, Chloroform-d) δ 8.10 (t, J = 6.6 Hz, 2H), 7.58 (t, J = 7.4Hz, 1H), 7.55-7.40 (m, 3H), 7.36-7.17 (m, 2H), 7.04 (ddt, J = 8.9, 6.3, 3.2 Hz,1H), 6.26-6.06 (m, 2H), 5.94-5.77 (m, 1H), 5.46-5.27 (m, 1H), 2.86 (ddddd, J =24.1, 19.2, 13.9, 10.4, 5.7 Hz, 2H), 2.20-1.86 (m, 5H), 0.29 (dd, J = 6.6, 2.7Hz, 6H). 13 C NMR (126 MHz, Chloroform-d) δ 166.24, 166.08, 140.37, 140.33,135.99, 135.94, 133.47, 133.43, 133.16, 132.93, 132.91, 130.49, 130.07,130.02, 129.79, 128.46, 128.44, 127.97, 127.95, 127.69, 124.30, 124.24,121.60, 121.42, 73.90, 73.44, 34.20, 33.52, 32.13, 32.01, 31.59, 30.89,14.41, 14.16, -4.94, -5.40, -5.48。

Claims

1. A method for the reductive silanization of activated olefins by nickel-catalyzed α-benzoylalkyl bromide and chlorosilane, characterized in that, Using benzoyl alkyl bromide (1), acrylonitrile (2), and dimethylvinylchlorosilane (3) as raw materials, a series of alkylsilane compounds were synthesized in a one-pot process at room temperature with the addition of a catalyst, reducing agent, and ligand; the synthetic route is as follows: The steps are as follows: This operation was performed in a nitrogen-filled glove box; the catalyst, reducing agent, ligand, acrylonitrile, and dimethylvinylchlorosilane were added to a reaction flask equipped with a magnetic stirrer, and the solvent was added and stirred for 30 minutes; then... α - Add benzoylalkyl bromide to the mixed solution; seal the reaction flask and remove it from the glove box; stir at 15 ℃-45 ℃ for 8 h-24 h; after the reaction is completed, quench the reaction with water and continue stirring for 1 h; dilute the reaction mixture with ethyl acetate, wash with brine, dry with anhydrous sodium sulfate, and concentrate under reduced pressure; R is selected from one of alkanes, alkenes, aryl groups, and heterocycles.

2. The method for the reductive silanization of activated olefins by nickel-catalyzed α-benzoylalkyl bromide and chlorosilane according to claim 1, characterized in that, The catalyst is selected from one of the following: nickel bromide of ethylene glycol dimethyl ether, nickel chloride of ethylene glycol dimethyl ether, nickel bromide, nickel chloride, nickel iodide, nickel fluoride, nickel acetylacetone, nickel trifluoromethanesulfonate, and nickel tetrafluoroborate hexahydrate.

3. The method for the reductive silanization of activated olefins by nickel-catalyzed α-benzoylalkyl bromide and chlorosilane according to claim 1, characterized in that, The ligand is selected from one of 2,6-bis(1-pyrazolyl)pyridine, 2,6-bis(3-methyl-1H-pyrazol-1-yl)pyridine, 2,6-bis(3,5-dimethylpyrazol-1-yl)pyridine, o-phenanthroline and 2-(1H-1,2,4-triazol-3-yl)pyridine.

4. The method for the reductive silanization of activated olefins by nickel-catalyzed α-benzoylalkyl bromide and chlorosilane according to claim 1, characterized in that, The reducing agent is selected from one of Mn powder, Zn powder, and Mg powder.

5. The method for the reductive silanization of activated olefins by nickel-catalyzed α-benzoylalkyl bromide and chlorosilane according to claim 1, characterized in that, Solvent selected from N,N -Dimethylformamide, N,N - One or more of the following: dimethylacetamide, dichloromethane, tetrahydrofuran, toluene, 1,4-dioxane, dimethyl sulfoxide, acetone, and acetonitrile.

6. The method for the reductive silanization of activated olefins by nickel-catalyzed α-benzoylalkyl bromide and chlorosilane according to claim 1, characterized in that, The concentration of benzoylalkyl bromide in the reaction system was 0.1 M; The molar ratio of benzoyl alkyl bromide to reducing agent is 1:3; The molar ratio of benzoylalkyl bromide to ligand is 1:0.05; The molar ratio of benzoylalkyl bromide to catalyst is 1:0.1; The molar ratio of benzoyl alkyl bromide to acrylonitrile is 1:3; The molar ratio of benzoylalkyl bromide to dimethylvinylchlorosilane is 1:3.

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