A method for efficiently preparing 1-silyl-2-alkyl compounds

Abstract

The application relates to the technical field of organic synthesis, in particular to a method for efficiently preparing 1-silicon-based-2-alkyl compounds, which comprises the following steps: reacting a compound of formula 2, a compound of formula 3 and a compound of formula 4 in the presence of a nickel salt catalyst, a copper salt catalyst, a diamine ligand and a base or in the presence of a nickel salt catalyst, a copper salt catalyst, a diamine ligand, a base and an additive, to obtain a compound of formula 1; wherein the compound of formula 2 is the compound of formula 3 is R 3 R 2 R 1 Si-Bpin, the compound of formula 4 is Alkyl-X, and the compound of formula 1 is wherein R is any one of a hydroxyl group, an ester group, an alkoxy group, an alkenyl group, an alkyl-substituted amine group, an alkyl-substituted amide group and an ether group, n is any integer within the range of 1-4, R 1 , R 2 , R 3 is a methyl group, an ethyl group, a phenyl group or a tert-butyl group, Alkyl represents an alkyl substituent, and X is a halogen.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic synthesis, and particularly relates to a method for efficiently preparing 1-silyl-2-alkyl compounds. BACKGROUND

[0002] 1-silyl-2-alkyl compounds are widely present in natural products and drug molecules [a) X. Du, Z. Huang. ACS Catal. 2017, 7, 1227-1243; b.) Sean O. Wilson, Annaliese K. Franz. J. Med. Chem. 2013, 56, 388-405; c.) Robert. West, Stephen, Gately. Drug Dev. Res. 2007, 68, 156-163; d.) Markus. Merget, Rudiger. Bertermann, Michael. Bernd, Thomas. Beckers, Thomas. Reissmann, Reinhold, Tacke. Organometallics. 2000, 19, 3486-3497; e.) Hiroshi. Fukasawa, Hideaki. Muratake, Ai. Ito, Hideyuki. Suzuki, Yohei Amano, Marina. Nagae, Kiyoshi. Sugiyama, Koichi. Shudo. ACS Chem. Neurosci. 2014, 5, 525-532; f.) Remya. Ramesh, D. Srinivasa. Reddy. J. Med. Chem. 2018, 61, 3779-3798].

[0003] Based on the important application of this fragment in natural products and drugs, the current methods for synthesizing 1-silyl-2-alkyl compounds: [a) Z. Zhang, X. Hu. ACS Catal. 2020, 10, 777-782; b.) B. Zhao, Y. Li, H. Li, Md. Belal, L. Zhu, G. Yin. Science Bulletin. 2021, 66, 570-577; c.) D. Ni, M. Kevin. Brown. ACS Catal. 2021, 11, 1858-1862; d.) J. Wang, Z. Duan, X. Liu, S. Dong, K. Chen, J. Li. Angew. Chem. Int. Ed. 2022, 61, e202202379; e.) Stefanie. Ploger, Armido. Studer. Org. Lett. 2022, 24, 8568-8572; f.) J. Ke, W. Liu, X. Zhu, X. Tan, C. He. Angew. Chem. Int. Ed. 2021, 60, 8744-8749; g.) H. Qrareya, D. Dondi, D. Ravelli, M. Fagnoni. ChemCatChem, 2015, 7, 3350-3357; h.) M. Zheng, J. Hou, L. L. Hua, W.-Y. Tang, L.-W. Zhan, B.-D. Li. Org. Lett., 2021, 23, 5128-5132; i.) R. Zhou, Y. Y. Goh, H. Liu, H. Tao, L. Li, J. Wu. Angew. Chem., Int. Ed. 2017, 56, 16621-16625; j.) J. Zhu, W.-C. Cui, S. Wang and Z.-J. Yao. J. Org. Chem. 2018, 83, 14600-14609].

[0004] The existing methods for constructing such compounds are usually limited by the raw materials, and the substrate range is extremely limited, which does not meet the diversity of chemical synthesis and cannot meet the needs of modern high-throughput drug screening.

[0005] Therefore, it is necessary to study a method for efficiently synthesizing 1-silyl-2-alkyl compounds with simple reaction steps, wide and easily available substrate range, high efficiency, and introduction of silicon-containing functional groups. SUMMARY

[0006] The application aims to provide a method for efficiently preparing 1-silyl-2-alkyl compounds, which is simple in operation, cheap in raw materials, good in functional group compatibility of substrates and has good efficiency.

[0007] The method for efficiently preparing 1-silyl-2-alkyl compounds comprises the following steps: reacting a compound of formula 2, a compound of formula 3 and a compound of formula 4 in a nickel salt catalyst, a copper salt catalyst, a diamine ligand and a base or reacting the compound of formula 2, the compound of formula 3 and the compound of formula 4 in a nickel salt catalyst, a copper salt catalyst, a diamine ligand, a base and an additive to obtain a compound of formula 1.

[0008] The compound of formula 2 is

[0009] The compound of formula 3 is R 3 R 2 R 1 Si-Bpin,

[0010] The compound of formula 4 is Alkyl-X,

[0011] The compound of formula 1 is

[0012] The compound of formula 1 is 1 , R 2 , R 3 is methyl, ethyl, phenyl or tert-butyl, Alkyl represents an alkyl substituent, and X is halogen.

[0013] Preferably, in the nickel salt catalyst, the cation is Ni 2+ , and the anion is selected from any one of Br – , Cl – , I – , [CH3COO] – , [CF3COO] – , [acac] – and dibenzalacetone.

[0014] Preferably, in the copper salt catalyst, the cation is Cu + , and the anion is selected from any one of Br – , Cl – , I – and [CH3COO] – .

[0015] Preferably, the cation of the base is selected from Li + , Na +, K + , and Cs + ; the anion of the base is selected from any one of F – , CO3 2– , [CH3COO] – , [CF3COO] – , [OMe] – , [O t Bu] – .

[0016] Preferably, the additive is a salt, the cation of the salt is any one of Li + , Na + , K + , Cs + , and Mg 2+ ; the anion of the salt is selected from any one of F – , Cl – , Br – , I – , and SO4 2– .

[0017] Preferably, the diamine ligand is selected from one of the following compounds:

[0018]

[0019] Preferably, Alkyl is selected from any one of hydroxyl, ester, carbonyl, alkoxy, aryl, amine, cyano, and alkenyl-substituted alkyl.

[0020] Preferably, the compound of Formula 3 is selected from one of PhMe2SiBpin, Et3SiBpin.

[0021] Preferably, the reaction is carried out in a solvent; the solvent is selected from any one of tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, diethyl ether, methyl tert-butyl ether, N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, and acetone.

[0022] Preferably, the molar ratio of the compound of Formula 2, the compound of Formula 3, and the compound of Formula 4 is 1:(1.0-3.0):(1.0-3.0); the molar ratio of the nickel salt catalyst, the copper salt catalyst, the diamine ligand, the base, the additive, and the compound of Formula 2 is (0.03-0.15):(0.15-1.0):(0.03-0.15):(1.0-3.0):(0-1.0):1.

[0023] The method synthesis route is as follows:

[0024]

[0025] The present application has the following advantages and beneficial effects:

[0026] 1. The present application provides a method for efficiently preparing 1-silyl-2-alkyl compounds, which uses olefins, alkyl halides and silicon boron reagents to react in one pot under the joint action of metal nickel catalyst and copper catalyst to prepare 1-silyl-2-alkyl compounds. The method can not only efficiently synthesize target compounds, but also has mild reaction conditions, strong substrate applicability and good functional group compatibility.

[0027] 2. The raw materials used in the method for efficiently preparing 1-silyl-2-alkyl compounds provided by the present application are cheap and easy to obtain, and the operation is simple.

[0028] 3. The product synthesized by the method for efficiently preparing 1-silyl-2-alkyl compounds provided by the present application contains a silicon group, and the target compound can be further converted to simply and efficiently synthesize other functional group organic compounds, thereby providing a new method for synthesizing complex drug molecules and drug lead compounds. DETAILED DESCRIPTION

[0029] The following examples are further illustrations of the present application for better understanding of the present application, but the content of the present application is not limited to the following examples.

[0030] In the following examples, PhMe2SiBpin refers to (dimethylphenylsilyl)boronic acid pinacol ester; NiBr2·DME refers to bis(ethylene glycol dimethyl ether) nickel bromide, CuI refers to cuprous iodide, LiOMe refers to lithium methoxide, KI refers to potassium iodide, NMP refers to N-methyl pyrrolidone. L represents a diamine ligand selected from one of the following compounds:

[0031]

[0032] Example 1

[0033] The reaction formula for preparing 1-silyl-2-alkyl compounds is as follows:

[0034]

[0035] According to the above reaction formula, the following Table 1 schemes 1-9, the common reaction conditions are as follows: compound 2a (1.0 equiv), compound 3a (2.0 equiv), compound 4a (1.5 equiv), NiBr2·DME (5 mol%), L (7 mol%), LiOMe (2.0 equiv), CuI (15 mol%), NMP, 5℃, 36h;

[0036] Condition b: Add additive KI (0.5 equiv).

[0037] The alternative materials of nickel salt catalysts are NiBr2DME, NiCl2DME, NiI2, and the change of catalyst type has little effect on the reaction, so they are not listed one by one. The temperature range is 5-40℃, which is effective in organic synthesis with high yield.

[0038] The yield and rr of different diamine ligands, solvents and temperatures are shown in Table 1 below:

[0039] Table 1 Yield and rr of different diamine ligands and solvents

[0040]

[0041] Example 2

[0042]

[0043] In an argon-filled glove box, bis(ethylene glycol dimethyl ether) nickel bromide (6.2 mg, 0.02 mmol), L2(10.0 mg, 0.02 mmol), lithium methoxide (30.4 mg, 0.8 mmol), copper iodide (11.4 mg, 0.06 mmol), potassium iodide (33.0 mg, 0.20 mmol) and (dimethyl(phenyl)silyl)boronic acid pinacol ester (220.8 mg, 0.8 mmol) were dissolved in 1 mL of dry N-methylpyrrolidine solvent, then 1-octene (64 μL, 0.4 mmol) and 4-bromo-2,2-diphenylbutyronitrile (180.0 mg, 0.6 mmol) were added, followed by 1 mL of dry N-methylpyrrolidine solvent, the reaction tube was sealed and taken out of the glove box, and reacted at 5℃ for 36 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography was used for separation and purification to obtain the product 5-((dimethyl(phenyl)silyl)methyl)-2,2-diphenyloctanenitrile (colorless oily liquid, yield 50%, rr>20:1). 1 H NMR (400 MHz, Chloroform-d) δ 7.52-7.48 (m, 2H), 7.41-7.31 (m, 11H), 7.30-7.22 (m, 2H), 2.39-2.28 (m, 2H), 1.48-1.37 (m, 2H), 1.37-1.16 (m, 14H), 0.76-0.69 (m, 2H), 0.25 (s, 6H) ppm; 13C NMR (101 MHz, Chloroform-d) δ 140.5, 139.9, 133.7, 129.0, 128.8, 127.9, 127.8, 127.0, 122.6, 51.9, 39.8, 33.7, 29.64, 29.60, 29.39, 29.35, 25.8, 24.0, 15.8, -2.9 ppm; 29 Si NMR (79 MHz, Chloroform-d) δ -2.59 ppm; HRMS (ESI) calculated [M-C6H5] + for C 26 H 36 NSi + = 390.2612, found: 390.2604.

[0044] Example 3

[0045]

[0046] In an argon-filled glove box, bis(ethylene glycol dimethyl ether) nickel bromide (6.2 mg, 0.02 mmol), L2(10.0 mg, 0.02 mmol), lithium methoxide (30.4 mg, 0.8 mmol), copper iodide (11.4 mg, 0.06 mmol), potassium iodide (33.0 mg, 0.20 mmol) and (dimethylphenylsilyl)boronic acid pinacol ester (220.8 mg, 0.8 mmol) were dissolved in 1 mL of dry N-methylpyrrolidine solvent, then 1-octene (64 μL, 0.4 mmol) and tert-butyl 4-bromopiperidine-1-carboxylate (158.5 mg, 0.6 mmol) were added, followed by 1 mL of dry N-methylpyrrolidine solvent, the reaction tube was sealed and taken out of the glove box, and reacted at 5 °C for 36 h. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography separation and purification to obtain the product tert-butyl 4-(1-(dimethyl(phenyl)silyl)pentan-2-yl)piperidine-1-carboxylate (colorless oily liquid, yield 57%, dr > 20:1, rr > 20:1). 1H NMR (400 MHz, Chloroform-d) δ 7.53 - 7.48 (m, 2H), 7.37 - 7.30 (m, 3H), 4.06 (s, 2H), 2.66 (t, J = 12.8 Hz, 2H), 1.62 - 1.61 (m, 1H), 1.45 (s, 9H), 1.33 - 1.16 (m, 16H), 1.05 (qd, J = 12.5, 4.4 Hz, 2H), 0.75 - 0.70 (m, 2H), 0.25 (s, 6H) ppm; 13 C NMR (151 MHz, Chloroform-d) δ 155.1, 139.9, 133.7, 128.9, 127.8, 79.3, 44.6, 43.8, 36.7, 36.1, 33.7, 32.4, 30.0, 29.7, 29.4, 28.6, 26.7, 24.0, 15.8, -2.9 ppm; 29 Si NMR (79 MHz, Chloroform-d) δ -2.62 ppm; HRMS (ESI) calculated [M+H] + for C 26 H 46 O2NSi + = 432.3292, found: 432.3277.

[0047] Example 4

[0048]

[0049] In an argon-filled glove box, bis(ethyleneglycol dimethyl ether) nickel bromide (6.2 mg, 0.02 mmol), L2(10.0 mg, 0.02 mmol), lithium methoxide (30.4 mg, 0.8 mmol), copper iodide (11.4 mg, 0.06 mmol), potassium iodide (33.0 mg, 0.20 mmol) and (dimethylphenylsilyl)boronic acid pinacol ester (220.8 mg, 0.8 mmol) were dissolved in 1 mL of dry N-methylpyrrolidine solvent, then 4-allyltetrahydro-2H-pyran-4-ol (56.9 mg, 0.4 mmol) and 1-bromo-3-phenylpropane (93 μΐ, 0.6 mmol) were added, followed by 1 mL of dry N-methylpyrrolidine solvent, the reaction tube was sealed and removed from the glove box, and reacted at 5 °C for 36 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography was used for separation and purification to obtain the product 4-(2-((dimethyl-(phenyl)-silyl)-methyl)-5-phenylpentyl)-tetrahydro-2H-pyran-4-ol (colorless oily liquid, yield 92%, rr > 20:1). 1 H NMR (600 MHz, Chloroform-d) δ 7.52-7.47 (m, 2H), 7.38-7.31 (m, 3H), 7.28-7.21 (m, 2H), 7.19-7.08 (m, 3H), 3.62 (ddd, J = 10.3, 7.7, 2.9 Hz, 4H), 2.53-2.40 (m, 2H), 1.74 (td, J = 11.8, 10.4, 4.4 Hz, 1H), 1.51 (ddtd, J = 23.6, 13.4, 9.9, 9.5, 6.5 Hz, 4H), 1.42 - 1.22 (m, 6H), 0.93-0.81 (m, 3H), 0.28 (d, J = 1.7 Hz, 6H). 13 C NMR (101 MHz, Chloroform-d) δ 142.70, 139.90, 133.74, 129.06, 128.50, 128.38, 127.99, 125.80, 69.56, 63.80, 50.34, 38.38, 38.20, 37.98, 36.20, 28.94, 28.56, 23.77, -1.83, -2.12. 29 Si NMR (79 MHz, Chloroform-d) δ -3.53. HRMS (ESI) calculated [M-H2O+H] + for C 25 H 35 OSi += 379.2452, found: 379.2442.

[0050] Example 5

[0051]

[0052] In an argon-filled glove box, bis(ethylene glycol dimethyl ether) nickel bromide (6.2 mg, 0.02 mmol), L2(10.0 mg, 0.02 mmol), lithium methoxide (30.4 mg, 0.8 mmol), copper iodide (11.4 mg, 0.06 mmol), potassium iodide (33.0 mg, 0.20 mmol) and (dimethylphenylsilyl)boronic acid pinacol ester (220.8 mg, 0.8 mmol) were dissolved in 1 mL of dry N-methylpyrrolidine solvent, then tert-butyl vinylcarbamate (57.3 mg, 0.4 mmol) and tert-butyl N-(4-bromobutyl)carbamate (151.3 mg, 0.6 mmol) were added, followed by 1 mL of dry N-methylpyrrolidine solvent, the reaction tube was sealed and taken out of the glove box, and reacted at 5 °C for 36 h. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography was used for separation and purification to obtain the product di-tert-butyl(6-(dimethyl(phenyl)silyl)hexane-1,5-diyl)dicarbamate (colorless oily liquid, yield 69%, rr > 20:1). 1 H NMR (600 MHz, Chloroform-d) δ 7.51-7.48 (m, 2H), 7.36-7.33 (m, 3H), 4.57 (s, 1H), 4.20 (d, J = 9.2 Hz, 1H), 3.72 (hept, J = 5.3, 4.6 Hz, 1H), 3.08-3.00 (m, 2H), 1.45-1.42 (m, 11H), 1.41 (s, 9H), 1.37-1.32 (m, 2H), 1.27 (dd, J = 11.2, 5.6 Hz, 2H), 1.04-0.93 (m, 2H), 0.32 (s, 6H); 13 CNMR (151 MHz, Chloroform-d) δ 156.1, 155.2, 139.3, 133.6, 129.1, 128.0, 79.0, 78.9, 47.7, 40.5, 39.0, 29.6, 28.6, 28.5, 23.6, 23.0, -2.4, -2.6; 29 Si NMR (119 MHz, Chloroform-d) δ -4.67; HRMS (ESI) calculated [M+H] + for C 24H 43 O4N2Si + = 451.2987, found: 451.2977.

[0053] Example 6

[0054]

[0055] In an argon-filled glove box, bis(ethyleneglycol dimethyl ether) nickel bromide (6.2 mg, 0.02 mmol), L2(10.0 mg, 0.02 mmol), lithium methoxide (30.4 mg, 0.8 mmol), copper iodide (11.4 mg, 0.06 mmol), potassium iodide (33.0 mg, 0.20 mmol) and (dimethylphenylsilyl)boronic acid pinacol ester (220.8 mg, 0.8 mmol) were dissolved in 1 mL of dry N-methylpyrrolidine solvent, then N-benzyl-3-butenamide (70.1 mg, 0.4 mmol) and ethyl 4-bromobutanoate (117.0 mg, 0.6 mmol) were added, followed by 1 mL of dry N-methylpyrrolidine solvent, the reaction tube was sealed and taken out of the glove box, and reacted at 5 °C for 36 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography was used for separation and purification to obtain the product ethyl 7-(benzylamino)-5-((dimethyl(phenyl)silyl)methyl)-7-oxoheptanoate (colorless oily liquid, yield 87%, rr > 20: 1). 1 H NMR (400 MHz, Chloroform-d) δ 7.48 (ddt, J = 5.7, 3.8, 2.2 Hz, 2H), 7.34 - 7.26 (m, 6H), 7.25 - 7.21 (m, 2H), 5.59 (t, J = 5.7 Hz, 1H), 4.35 (d, J = 5.7 Hz, 2H), 4.07 (q, J = 7.2 Hz, 2H), 2.16 - 1.98 (m, 5H), 1.60 - 1.48 (m, 2H), 1.31 - 1.26 (m, 2H), 1.23 (t, J = 7.1 Hz, 3H), 0.84 (d, J = 6.3 Hz, 2H), 0.30 (d, J = 2.9 Hz, 6H) ppm; 13 C NMR (101 MHz, Chloroform-d) δ 173.9, 172.2, 139.6, 138.6, 133.7, 129.1, 128.7, 128.0, 127.9, 127.5, 60.3, 44.0, 43.6, 36.0, 34.3, 32.2, 21.7, 21.1, 14.3, -2.1, -2.2 ppm; 29Si NMR (79 MHz, Chloroform-d) δ -3.43 ppm; HRMS (ESI) calculated [M+H] + for C 25 H 36 O3NSi + = 426.2459, found: 426.2444.

[0056] Example 7

[0057]

[0058] In an argon-filled glove box, bis(ethylene glycol dimethyl ether) nickel bromide (6.2 mg, 0.02 mmol), L2(10.0 mg, 0.02 mmol), lithium methoxide (30.4 mg, 0.8 mmol), copper iodide (11.4 mg, 0.06 mmol), potassium iodide (33.0 mg, 0.20 mmol) and (dimethylphenylsilyl)boronic acid pinacol ester (220.8 mg, 0.8 mmol) were dissolved in 1 mL of dry N-methylpyrrolidine solvent, then ethyl allyl ether (34.5 mg, 0.4 mmol) and ethyl 4-bromobutyrate (117.0 mg, 0.6 mmol) were added, followed by 1 mL of dry N-methylpyrrolidine solvent, the reaction tube was sealed and taken out of the glove box, and reacted at 5 °C for 36 h. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography was used for separation and purification to obtain the product ethyl 7-(dimethyl(phenyl)silyl)-5-ethoxyheptanoate (colorless oily liquid, yield 54%, rr > 20: 1). 1 H NMR (400 MHz, Chloroform-d) δ 7.54-7.47 (m, 2H), 7.36-7.33 (m, 3H), 4.12 (q, J = 7.1 Hz, 2H), 3.50-3.33 (m, 2H), 3.21-3.11 (m, 1H), 2.34-2.22 (m, 2H), 1.76-1.65 (m, 1H), 1.63-1.55 (m, 1H), 1.51-1.43 (m, 4H), 1.25 (t, J = 7.1 Hz, 3H), 1.16 (t, J = 7.0 Hz, 3H), 0.85-0.61 (m, 2H), 0.26 (s, 6H) ppm; 13C NMR (151 MHz, Chloroform-d) δ 173.9, 139.4, 133.7, 129.0, 127.9, 81.0, 64.3, 60.3, 34.6, 33.0, 27.8, 21.1, 15.8, 14.4, 10.7, -3.0 -3.1 ppm; 29 Si NMR (79 MHz, Chloroform-d) δ -1.87 ppm; HRMS (ESI) calculated [M-C6H5] + for C 13 H 27 O3Si + = 259.1724, found: 259.1718.

[0059] The synthesis of 1-silyl-2-alkyl compounds in the following examples 9-16 were carried out according to the method steps described above in example 2, and the compounds 4Alkyl-X used in examples 9-16, X is Br, the structure and name of the synthesized compounds, NMR, HRMS data and yield are shown in Table 2 below:

[0060] Table 2 Product structure, name, NMR, HRMS and yield of examples 9-16

[0061]

[0062]

[0063]

[0064]

[0065] The above is only a preferred embodiment of the present application, of course, cannot be limited to the scope of the present invention, should be noted that for those skilled in the art, without departing from the principles of the present invention, can also make a number of improvements and changes, these improvements and changes are also considered to be within the scope of the present application.

Claims

1. A process for the preparation of 1-silyl-2-alkyl compounds, characterized in that: The compound of formula 2, the compound of formula 3 and the compound of formula 4 are reacted in the presence of a nickel salt catalyst, a copper salt catalyst, a diamine ligand, a base or an additive to obtain the compound of formula 1. wherein the compound of formula 2 is , The compound of formula 3 is , The compound of formula 4 is , Compounds of Formula 1 are , wherein R is any one of hydroxyl, ester, alkenyl, alkyl substituted amine, alkyl substituted amide, ether, n is any integer from 1 to 4, R 1 , R 2 , R 3 is methyl, ethyl, phenyl, t-butyl, Alkyl represents an alkyl substituent, and X is halogen; In the nickel salt catalyst, the cation is Ni 2+ and the anion is selected from any one of Br – , Cl – , I – , [CH3COO] – , [CF3COO] – , [acac] – and dibenzalacetone. In the copper salt catalyst, the cation is Cu + and the anion is selected from any one of Br – , Cl – , I – and [CH3COO] – . the cation of the base is selected from any one of Li + , Na + , K + , and Cs + ; the anion of the base is selected from any one of F – , CO3 2– , [CH3COO] – , [CF3COO] – , [OMe] – , [O t Bu] – ; The additive is a salt, the cation of the salt is any one of Li + , Na + , K + , Cs + and Mg 2+ ; the anion of the salt is selected from any one of F – , Cl – , Br – , I – and SO4 2– ; The diamine ligand is selected from one of the following compounds: ； The reaction is carried out in a solvent selected from any one of tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, diethyl ether, methyl tert-butyl ether, N-methylpyrrolidone, N,N-dimethylacetamide and acetone.

2. The method of claim 1, wherein the 1-silyl-2-alkyl compound is prepared by the reaction of a compound of formula (II) with a compound of formula (III) in the presence of a base. Alkyl is selected from any one of hydroxyl, ester, carbonyl, alkoxy, aryl, amine, cyano, alkenyl-substituted alkyl.

3. The method of claim 1, wherein the 1-silyl-2-alkyl compound is prepared by the reaction of a compound of formula (II) with a compound of formula (III) in the presence of a base. The compound of formula 3 is selected from one of PhMe2SiBpin, Et3SiBpin.

4. The method for preparing 1-silyl-2-alkyl compounds according to claim 1, characterized in that: The molar ratio of the compound of formula 2, the compound of formula 3 and the compound of formula 4 is 1: (1.0~3.0): (1.0~3.0); and the molar ratio of the nickel salt catalyst, the copper salt catalyst, the diamine ligand, the base and the additive to the compound of formula 2 is (0.03~0.15): (0.15~1.0):(0.03~0.15): (1.0~3.0): (0~1.0):1.

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