Method for synthesizing propargyl silane derivative through nickel catalytic reduction coupling

Abstract

The invention belongs to the technical field of organic synthesis, and discloses a method for synthesizing propargyl silane derivatives through nickel catalytic reduction coupling. The method comprises the following steps: in a protective atmosphere, taking an organic solvent as a reaction medium, and reacting a halogen-containing butyne compound with chlorosilane under the action of a catalyst, a ligand and a reducing agent to obtain the propargyl silane derivative. The structural formula of the propargyl silane derivative is I, the catalyst is a nickel catalyst, and the ligand is a nitrogen or phosphine ligand. The method disclosed by the invention is simple, low in cost, efficient in reaction, few in byproducts, easy to separate and purify and high in yield.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for nickel-catalyzed reduction coupling to synthesize propargylsilane derivatives. Background Technology

[0002] Organosilanes have wide applications in organic synthesis and materials science. Among them, propargyl silane is an important alkynyl silicide that can serve as a crucial multifunctional building block in the synthesis of pharmaceuticals and natural products. Traditional methods for synthesizing propargyl silanes require harsh reaction conditions and highly reactive propargyl Grignard reagents or alkynyl lithium reagents. These propargyl Grignard reagents or alkynyl lithium reagents are extremely unstable and must be stored in nitrogen or used under a nitrogen atmosphere (Hayashi T.; Konishi M.; Okamoto Y., et al. J. Org. Chem., 1986, 51, 3772; Reich HJ; Holladay JE; Walker TG, et al. J. Am. Chem. Soc., 1999, 121, 9769; Hammond G. BJ Fluorine Chem., 2006, 127, 476). Moreover, these methods also generate allenylsilane byproducts. Prolylsilane and allenylsilane have similar physicochemical properties, making it difficult to separate the two. At the same time, the above methods can only synthesize propynylsilanes without substitution at the propynyl position, thus limiting the structural diversity of propynylsilanes. Summary of the Invention

[0003] To address the shortcomings of existing methods for synthesizing propargylsilanes, such as harsh reaction conditions, cumbersome operations, limited raw material range, and low yields and difficulty in separating products with simple structures, this invention aims to provide a nickel-catalyzed reduction coupling method for synthesizing propargylsilane derivatives. This invention utilizes a nickel-catalyzed reduction coupling reaction to efficiently synthesize structurally diverse propargylsilanes by reacting halogen-containing butyne compounds with chlorosilanes.

[0004] The objective of this invention is achieved through the following technical solution:

[0005] A method for synthesizing propargylsilane derivatives by nickel-catalyzed reduction coupling includes the following steps:

[0006] Under a protective atmosphere, using an organic solvent as the reaction medium, halogen-containing butyne compounds are reacted with chlorosilanes in the presence of a catalyst, ligand, and reducing agent to obtain propargylsilane derivatives.

[0007] The structure of the halogen-containing butyne compound is as follows:

[0008]

[0009] The structure of the chlorosilane is as follows:

[0010]

[0011] The structure of propargylsilane derivatives is as follows:

[0012]

[0013] Where R is phenyl, substituted phenyl, naphthyl, styryl, indolyl, quinolinyl, benzofuranyl, isobenzofuran-1(3H)-one, benzothiophene, or 1,2-methylenedioxybenzene; X is Cl, Br, or I.

[0014] The substituted phenyl group in R is

[0015] R 1 R is an ester group (e.g., COOR', where R' is an alkyl group, e.g., C). 1-6 Alkyl groups), halogens (F, Cl, Br, I), CN, acyl groups (COR', R' is an alkyl group (e.g., C 1-6 Alkyl groups (or phenyl groups), amino groups.

[0016] R 2 The aryl group is hydrogen (H), alkyl, aryl, or a substituted aryl group. The aryl group is phenyl, naphthyl, or biphenyl. The substituted aryl group has one, two, or three of the following substituents: alkyl, F, Cl, amino, or amide. The substituent in the aryl group is monosubstituted, disubstituted, or trisubstituted.

[0017] R 3 The aryl group is hydrogen (H), alkyl, aryl, or a substituted aryl group. The aryl group is phenyl, naphthyl, or biphenyl. The substituted aryl group contains one, two, or three of the following substituents: alkyl, F, Cl, amino, and amide. The substituent in the aryl group can be monosubstituted, disubstituted, or trisubstituted.

[0018] R 4 R 5 and R 6 Each is an alkyl group (e.g., C10, C20, C30, C40, C50, C60, C7 ... 1～6 Alkyl), phenyl, alkenyl (e.g., vinyl, propenyl, butenyl, etc.), alkynyl (e.g., ethynyl, propynyl, etc.).

[0019] In the halogen-containing butyne compounds, X is preferably Br. The chlorine or bromine of 1-phenylbutyne is preferably 1-phenylbutyne bromide.

[0020] The catalyst is a nickel catalyst; the nickel catalyst is one or more of the following: nickel chloride, nickel bromide, nickel iodide, nickel chloride with ethylene glycol dimethyl ether, nickel bromide with ethylene glycol dimethyl ether, nickel bis(triphenylphosphine) dichloride, nickel tetra(triphenylphosphine) tetrachloride, nickel dibromobis(pyridine) dichloride, nickel acetate tetrahydrate, nickel acetylacetone, nickel trifluoromethanesulfonate, nickel fluoroborate hexahydrate, and nickel perchlorate hexahydrate; preferably one or more of the following: nickel iodide, nickel bromide, nickel chloride, nickel dibromobis(pyridine) dichloride, nickel chloride with ethylene glycol dimethyl ether, nickel trifluoromethanesulfonate, nickel acetate tetrahydrate, nickel acetylacetone, nickel perchlorate hexahydrate, and nickel bromide with ethylene glycol dimethyl ether.

[0021] The ligand is a nitrogen or phosphine compound. Specifically, the nitrogen ligand is one or more of pyridine (Py), 2,2'-bipyridine (bpy), 4,4-di-tert-butyl-2,2-bipyridine (dtbpy), 1,10-phenanthroline (Phen), 4,7-diphenyl-1,10-phenanthroline (4,7-dpPhen), and 4,4'-dimethyl-2,2'-bipyridine. The phosphine ligand is one or more of bis(diphenylphosphine)methane (DPPM), bis(diphenylphosphine)ethane (DPPE), bis(diphenylphosphine)propane (DPPB), bis(diphenylphosphine)butane (DPPP), bis(diphenylphosphine)benzene (DPPBz), bis(diphenylphosphine)pyridine (DPPy), triphenylphosphine (PPh3), tributylphosphine (PBu3), and tricyclohexylphosphine (PCy3).

[0022] The ligand is preferably one or more of pyridine, 2,2'-bipyridine, 1,10-phenoroline, 4,4-di-tert-butyl-2,2-bipyridine, 4,4'-dimethyl-2,2'-bipyridine, bis(diphenylphosphine)pyridine, and bis(diphenylphosphine)butane.

[0023] The reducing agent is a metal reducing agent or an organic reducing agent; the metal reducing agent is one or more of zinc (Zn) and manganese (Mn); the organic reducing agent is one or more of tetrakis(dimethylamino)ethylene (TDAE), bis(pinacol)diboron (B2Pin2), triethylsilane (Et3SiH), and triphenylsilane (Ph3SiH).

[0024] The reducing agent is preferably a metallic reducing agent such as zinc or manganese.

[0025] The organic solvent is at least one selected from tetrahydrofuran, acetonitrile, acetone, toluene, ethylene glycol dimethyl ether, 1,4-dioxane, dichloromethane, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, and dimethyl sulfoxide; preferably, one or more selected from tetrahydrofuran, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, and 1,4-dioxane.

[0026] The molar ratio of halogenated butyne compounds to chlorosilanes is 1:1.05–2.5. The reaction temperature is 20–60°C, preferably room temperature–40°C. The reaction time is 4–15 h.

[0027] The amount of catalyst used is 10 to 15% of the molar amount of the halogen-containing butyne compound.

[0028] The amount of the ligand used is 10 to 15% of the molar amount of the halogen-containing butyne compound.

[0029] The amount of the reducing agent is 2 to 2.5 times the molar amount of the halogen-containing butyne compound.

[0030] After the reaction was complete, water was added to quench the reaction, and the mixture was extracted with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the ethyl acetate was removed by rotary evaporation. The mixture was then separated by column chromatography with silica gel.

[0031] Compared with the prior art, the present invention has the following advantages:

[0032] (1) In the preparation method of propargyl silane derivatives of the present invention, the nickel catalyst is inexpensive and can be stored stably. The halogen-containing butyne compounds and chlorosilane reagents used are stable, structurally diverse and readily available, and can synthesize propargyl silane derivatives with rich and diverse structures.

[0033] (2) The reaction conditions of the present invention are mild, the operation is simple, the reagents used are safe and easy to store, and there is no pollution from waste.

[0034] (3) The method of the present invention has the advantages of high reaction efficiency, few by-products, and easy separation and purification. The whole method can synthesize structurally complex propargyl silane derivatives with low consumption and high efficiency, and has good applicability. Attached Figure Description

[0035] Figure 1 The proton spectrum of 2-(4-bromo-1-butyne)naphthalene (4a) 1 H NMR (400MHz, CDCl3) figure;

[0036] Figure 2 The proton spectrum of (E)-6-bromo-1,3-enyne-1-benzene (4b) 1 H NMR (400MHz, CDCl3) figure;

[0037] Figure 3 The 1H NMR spectrum of ethyl 4-(4-bromo-1-butyne)benzoate (4c) 1 H NMR (400MHz, CDCl3) figure;

[0038] Figure 4The proton NMR spectrum of dimethyl(4-(naphth-2-yl)but-3-yn-2-yl)(vinyl)silane (6a) 1 H NMR (500MHz, CDCl3) figure;

[0039] Figure 5 The carbon spectrum of dimethyl(4-(naphth-2-yl)but-3-yn-2-yl)(vinyl)silane (6a) 13 C NMR (126MHz, CDCl3) figure;

[0040] Figure 6 The proton NMR spectrum of methyl(4-(naphth-2-yl)but-3-yn-2-yl)(phenyl)(vinyl)silane (6b) 1 HNMR (500MHz, CDCl3) plot;

[0041] Figure 7 The carbon spectrum of methyl(4-(naphth-2-yl)but-3-yn-2-yl)(phenyl)(vinyl)silane (6b) 13 CNMR: 126MHz, CDCl3) Figure;

[0042] Figure 8 The proton NMR spectrum of (E)-dimethyl(6-phenylhex-5-en-3-yn-2-yl)(vinyl)silane (6c) 1 HNMR (500MHz, CDCl3) plot;

[0043] Figure 9 The carbon spectrum of (E)-dimethyl(6-phenylhex-5-en-3-yn-2-yl)(vinyl)silane (6c) 13 CNMR: 126MHz, CDCl3) Figure;

[0044] Figure 10 The 1H NMR spectrum of ethyl 4-(3-(dimethyl(vinyl)silyl)but-1-yn-1-yl)benzoate (6d) 1 HNMR (500MHz, CDCl3) plot;

[0045] Figure 11 The carbon spectrum of ethyl 4-(3-(dimethyl(vinyl)silyl)but-1-yn-1-yl)benzoate (6d) 13 CNMR: 126MHz, CDCl3) Figure. Detailed Implementation

[0046] To better understand this invention, the following examples are provided. The examples and corresponding data below are only used to further describe the technical solutions of this invention in detail and should not be construed as limiting the scope of protection of this invention. The raw materials, reagents, solvents, reducing agents, and ligands used in this invention are all commercially available bulk products.

[0047] The halogen-containing butyne compounds of the present invention, such as 1-phenylbutyne bromine or chlorine, can be prepared by the following method: using an organic solvent as the reaction medium, a compound containing an alcohol hydroxyl group is reacted with a chlorinated or brominated reagent to obtain 1-phenylbutyne bromine or chlorine.

[0048] The structure of chlorine or bromine in 1-phenylbutyne is as follows:

[0049]

[0050] The structure of the compound containing an alcohol hydroxyl group:

[0051]

[0052] R 1 R 2 R 3 Similar to the halogenated butyne compounds mentioned above.

[0053] The chlorinated or brominated reagent is dichlorohydantoin, N-chlorosuccinimide, carbon tetrachloride, carbon tetrabromide, or bromine. The organic solvent is one or more of dichloromethane, chloroform, acetonitrile, tetrahydrofuran, toluene, or o-xylene.

[0054] The reaction also requires the use of triphenylphosphine, in an amount 1.2 to 2.5 times the molar amount of the compound containing the alcohol hydroxyl group.

[0055] The molar ratio of the compound containing the alcohol hydroxyl group to the chlorinated or brominated reagent is 1:1.1 to 2, and the reaction temperature is room temperature.

[0056] The method for preparing the compound containing the alcohol hydroxyl group is as follows: Compound 1 and Compound 2 are reacted in the presence of a catalyst using an organic solvent as the reaction medium to obtain the compound containing the alcohol hydroxyl group. The catalyst is tetrakis(triphenylphosphine)palladium or di(triphenylphosphine)palladium dichloride (0.5–2% of the molar amount of Compound 2) and cuprous iodide (0.5–2% of the molar amount of Compound 2).

[0057] Compound 1: Compound 2:

[0058] The molar ratio of compound 1 to compound 2 is 1:1.2 to 1.5, the reaction temperature is 25 to 60°C, the organic solvent is one or more of tetrahydrofuran, triethylamine, N,N-dimethylformamide, N,N-dimethylacetamide, and toluene, and the reaction time is 4 to 12 h.

[0059] The reaction equations for the synthesis of chlorine or bromine from 1-phenylbutyne are as follows:

[0060]

[0061] Preparation of halogenated butyne compounds:

[0062] (1) Synthesis reaction equation for halogen-containing butyne compound 2-(4-bromo-1-butyne)naphthalene (4a):

[0063]

[0064] (1-1) Under nitrogen atmosphere, 1.5 equivalents of 2-bromonaphthalene (1a), 10 mmol of 4-hydroxy-1-yne (2a) (compound 1a:compound 2a molar ratio of 1:1.5), 1% (1% of the molar amount of compound 2a) of tetra(triphenylphosphine)palladium, and 1% (1% of the molar amount of compound 2a) of cuprous iodide were added to a reaction flask. Finally, triethylamine and tetrahydrofuran (Et3N / THF = 1 / 1, volume ratio) were added as the reaction solvent (25 mL). The reaction was carried out at 60 °C for 8 h. After the reaction was completed, the mixture was filtered, and the filtrate was removed by vacuum distillation before proceeding to the next step of the reaction.

[0065] (1-2) Under air conditions, 1.5 equivalents of carbon tetrabromide (CBr4) and 1.2 equivalents of triphenylphosphine (PPh3) were added to the crude product from the previous step. Finally, dichloromethane (DCM) was added as the reaction solvent (25 mL), and the reaction was carried out at room temperature for 3 h. After the reaction was completed, the dichloromethane was removed by vacuum distillation to obtain the crude product, which was then separated by silica gel column chromatography to obtain 2.53 g of 2-(4-bromo-1-butyne)naphthalene (4a), with a separation yield of 98%.

[0066] Characterization data for 2-(4-bromo-1-butynedi)naphthalene (4a): 1 ¹H NMR (400MHz, Chloroform-d) δ 7.97 (s, 1H), 7.81–7.77 (m, 3H), 7.51–7.48 (m, 3H), 3.58 (t, J = 7.2Hz, 2H), 3.05 (t, J = 7.2Hz, 2H). The proton NMR spectrum is shown below. Figure 1 As shown.

[0067] (2) Synthesis reaction equation for the halogen-containing butyne compound (E)-6-bromo-1,3-enyne-1-benzene (4b):

[0068]

[0069] (2-1) Under nitrogen atmosphere, 1.8 equivalents of (E)-2-bromostyrene (1b), 10 mmol of 4-hydroxy-1-yne (2a) (compound 1b:compound 2a molar ratio of 1:1.8), 1% (1% of the molar amount of compound 2a) of tetra(triphenylphosphine)palladium, and 1% (1% of the molar amount of compound 2a) of cuprous iodide were added to a reaction flask. Finally, 20 mL of triethylamine (Et3N) was added as the reaction solvent, and the reaction was carried out at 50 °C for 8 h. After the reaction was completed, the mixture was filtered, and the filtrate was removed by vacuum distillation before proceeding to the next step of the reaction.

[0070] (2-2) Under air conditions, 2.0 equivalents of carbon tetrabromide (CBr4) and 1.2 equivalents of triphenylphosphine (PPh3) were added to the crude product from the previous step. Finally, dichloromethane (DCM) was added as the reaction solvent (20 mL), and the reaction was carried out at room temperature for 3 h. After the reaction was completed, the dichloromethane was removed by vacuum distillation to obtain the crude product, which was then separated by silica gel column chromatography to obtain 2.22 g of (E)-6-bromo-1,3-enyne-1-benzene (4b), with a separation yield of 95%.

[0071] Characterization data for (E)-6-bromo-1,3-enyne-1-benzene (4b): 1 ¹H NMR (400MHz, Chloroform-d) δ 7.91 (d, J = 7.8 Hz, 2H), 7.40 (t, J = 7.5 Hz, 2H), 7.33 (d, J = 7.4 Hz, 1H), 6.66 (d, J = 11.9 Hz, 1H), 5.72 (dd, J = 11.9, 2.3 Hz, 1H), 3.54 (t, J = 7.1 Hz, 2H), 3.04 (t, J = 7.1 Hz, 2H). The proton NMR spectrum is shown below. Figure 2 As shown.

[0072] (3) Synthesis of ethyl 4-(4-bromo-1-butynedi)benzoate (4c), a halogenated butyne compound, with the following reaction equation:

[0073]

[0074] (3-1) Under nitrogen atmosphere, 1.2 equivalents of ethyl 4-iodobenzoate (1c), 10 mmol of 4-hydroxy-1-yne (2a) (compound 2a: compound 1c molar ratio of 1:1.2), 1% (1% of the molar amount of compound 2a) of palladium di(triphenylphosphine) chloride, and 1% (1% of the molar amount of compound 2a) of cuprous iodide were added to a reaction flask. Finally, triethylamine was added as the reaction solvent (25 mL), and the reaction was carried out at room temperature for 12 h. After the reaction was completed, the mixture was filtered, and the filtrate was removed by vacuum distillation before proceeding to the next step of the reaction.

[0075] (3-2) Under air conditions, 1.6 equivalents of carbon tetrabromide (CBr4) and 2 equivalents of triphenylphosphine (PPh3) were added to the crude product from the previous step. Finally, dichloromethane (DCM) was added as the reaction solvent (25 mL), and the reaction was carried out at room temperature for 3 h. After the reaction was completed, the dichloromethane was removed by vacuum distillation to obtain the crude product, which was separated by silica gel column chromatography to obtain 2.72 g of ethyl 4-(4-bromo-1-butyne)benzoate (4c), with a separation yield of 97%.

[0076] Characterization data for ethyl 4-(4-bromo-1-butynedi)benzoate (4c): 1 ¹H NMR (400MHz, Chloroform-d) δ 7.96 (d, J = 8.3Hz, 2H), 7.46 (d, J = 8.4Hz, 2H), 4.36 (q, J = 7.1Hz, 2H), 3.52 (t, J = 7.2Hz, 2H), 2.99 (t, J = 7.2Hz, 2H), 1.38 (t, J = 7.1Hz, 3H). The proton NMR spectrum is shown below. Figure 3 As shown.

[0077] Example 1: Dimethyl(4-(naphth-2-yl)but-3-yn-2-yl)(vinyl)silane (6a)

[0078] Synthesis reaction equation:

[0079]

[0080] Under nitrogen atmosphere, 77.4 mg (0.30 mmol) of 2-(4-bromo-1-butyne)naphthalene (4a), 1.5 equivalents of vinylchlorosilane (meaning the amount of vinylchlorosilane used is 1.5 times the molar amount of compound 4a), 10% (10% of the molar amount of compound 4a) of nickel iodide as catalyst, 10% (10% of the molar amount of compound 4a) of 2,2'-bipyridine (bpy) as ligand, 2.5 equivalents of Mn as reducing agent, and 1.5 mL of N,N-dimethylacetamide as solvent were added sequentially to a reaction flask, and the reaction was carried out at room temperature (25 °C) for 12 h. After the reaction was completed, the mixture was cooled to room temperature, quenched with water, extracted with ethyl acetate, the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the ethyl acetate was removed by rotary evaporation. The mixture was then separated by silica gel column chromatography to obtain 72 mg of dimethyl(4-(naphth-2-yl)but-3-yn-2-yl)(vinyl)silane (6a), with a separation yield of 91%.

[0081] Characterization data for dimethyl(4-(naphth-2-yl)but-3-yn-2-yl)(vinyl)silane (6a): 1H NMR(500MHz,Chloroform-d)δ7.87(s,1H),7.79-7.72(m,3H),7.47-7.42(m,3H),6.25(dd,J=20.3,14.7Hz,1 H), 6.09 (d, J = 18.5Hz, 1H), 5.83 (d, J = 24.1Hz, 1H), 2.01 (q, J = 7.3Hz, 1H), 1.30 (d, J = 7.3Hz, 3H), 0.25 (s, 6H). 13 C NMR (126 MHz, Chloroform-d) δ 136.5, 133.6, 133.2, 132.4, 130.8, 129.0, 127.82, 127.80, 127.6, 126.4, 126.1, 122.2, 94.3, 80.9, 14.9, 13.4, -4.9, -5.3. Proton and carbon spectra are shown below. Figure 4 and 5 As shown.

[0082] Example 2: Methyl(4-(naphth-2-yl)but-3-yn-2-yl)(phenyl)(vinyl)silane (6b)

[0083] Synthesis reaction equation:

[0084]

[0085] All amounts added below are based on the molar amount of 4a. Under nitrogen atmosphere, 77.4 mg (0.30 mmol) of 2-(4-bromo-1-butyne)naphthalene (4a), 1.8 equivalents of methylphenylvinylchlorosilane, 10% nickel dimethyl ether ethylene glycol bromide as catalyst, 10% 4,4'-dimethyl-2,2'-bipyridine (dmbpy) as ligand, 2.5 equivalents of Mn as reducing agent, and 1.5 mL of N,N-dimethylformamide as solvent were added sequentially to the reaction flask. The reaction was carried out at room temperature (25 °C) for 8 h. After the reaction was completed, the mixture was cooled to room temperature, the reaction was quenched with water, extracted with ethyl acetate, the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the ethyl acetate was removed by rotary evaporation. 90 mg of methyl(4-(naphthyl-2-yl)but-3-yne-2-yl)(phenyl)(vinyl)silane (6b) was obtained by column chromatography with silica gel, with a separation yield of 92%.

[0086] Characterization data for methyl(4-(naphth-2-yl)but-3-yn-2-yl)(phenyl)(vinyl)silane (6b): 1H NMR(500MHz,Chloroform-d)δ7.84(s,1H),7.80-7.73(m,3H),7.69(d,J=5.6Hz,2H),7.49-7.39(m,6H),6.44(dd,J=20.3,14.7 Hz,1H),6.24(dd,J=14.7,3.6Hz,1H),5.96(dd,J=20.4,3.6Hz,1H),2.29(q,J=7.4Hz,1H),1.33(d,J=7.4Hz,3H),0.54(s,3H). 13 C NMR (126MHz, Chloroform-d) δ 135.6, 135.2, 134.8, 133.9, 133.1, 132.3, 130.8, 129.7, 128.9, 127.9, 127.8, 127.8, 127.6, 126.4, 126.2, 121.9, 93.9, 81.4, 15.2, 12.9, -6.7. Proton and carbon spectra are shown below. Figure 6 and 7 As shown.

[0087] Example 3: (E)-Dimethyl(6-phenylhex-5-en-3-yn-2-yl)(vinyl)silane (6c)

[0088] Synthesis reaction equation:

[0089]

[0090] All amounts added below are based on the molar amount of 4b. Under nitrogen atmosphere, 70.2 mg (0.30 mmol) of (E)-6-bromo-1,3-enyne-1-benzene (4b), 2.0 equivalents of dimethylvinylchlorosilane, 10% nickel perchlorate hexahydrate as catalyst, 10% 2,2'-bipyridine (bpy) as ligand, 2.5 equivalents of Zn as reducing agent, and 1.5 mL of dimethyl sulfoxide as solvent were added sequentially to a reaction flask. The reaction was carried out at room temperature (25 °C) for 4 h. After the reaction was completed, the mixture was cooled to room temperature, the reaction was quenched with water, extracted with ethyl acetate, the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the ethyl acetate was removed by rotary evaporation. 64 mg of (E)-dimethyl(6-phenylhex-5-en-3-yne-2-yl)vinylsilane (6c) was obtained by column chromatography with silica gel, with a separation yield of 89%.

[0091] Characterization data for (E)-dimethyl(6-phenylhex-5-en-3-yn-2-yl)(vinyl)silane (6c): 1H NMR(500MHz,Chloroform-d)δ7.89(d,J=7.2Hz,2H),7.33(t,J=7.6Hz,2H),7.26(t,J=7.6Hz,1H),6.50(d,J=11.9Hz,1H),6.21(dd ,J=20.3,14.7Hz,1H),6.06(dd,J=14.7,3.8Hz,1H),5.81-5.72(m,2H),2.02(q,J=7.2Hz,1H),1.27(d,J=7.2Hz,3H),0.20(s,6H). 13 C NMR (126MHz, Chloroform-d) δ 136.9, 136.3, 136.1, 133.7, 128.5, 128.2, 128.0, 108.8, 101.7, 79.3, 14.8, 14.1, -4.9, -5.3. Proton and carbon spectra are shown below. Figure 8 and 9 As shown.

[0092] Example 4: Synthetic reaction equation for ethyl 4-(3-(dimethyl(vinyl)silyl)but-1-yn-1-yl)benzoate (6d):

[0093]

[0094] All amounts added below are based on the molar mass of 4c. Under nitrogen atmosphere, 84.0 mg (0.30 mmol) of ethyl 4-(4-bromo-1-butynedi)benzoate (4a), 1.5 equivalents of dimethylvinylchlorosilane, 10% nickel bromide as catalyst, 10% 1,10-phenoroline (Phen) as ligand, 2.5 equivalents of Mn as reducing agent, and 1.0 mL of acetonitrile as solvent were added sequentially to a reaction flask. The reaction was carried out at 35 °C for 4 h. After the reaction was completed, the mixture was cooled to room temperature, the reaction was quenched with water, extracted with ethyl acetate, the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the ethyl acetate was removed by rotary evaporation. 81 mg of ethyl 4-(3-(dimethyl(vinyl)silyl)buty-1-yn-1-yl)benzoate (6d) was obtained by column chromatography with silica gel, yielding 94%.

[0095] Characterization data for ethyl 4-(3-(dimethyl(vinyl)silyl)but-1-yn-1-yl)benzoate (6d): 1H NMR(500MHz,Chloroform-d)δ7.94(d,J=8.2Hz,2H),7.40(d,J=8.2Hz,2H),6.24-6.17(m,1H),6.07(dd,J=14.6,3.6Hz,1H),5.80(dd, J=20.2,3.9Hz,1H),4.37(q,J=7.2Hz,2H),1.98(q,J=7.2Hz,1H),1.39(t,J=7.2Hz,3H),1.26(d,J=6.9Hz,3H),0.22(d,J=2.5Hz,6H). 13 C NMR (126MHz, Chloroform-d) δ 166.4, 136.3, 133.7, 131.4, 129.6, 129.5, 128.8, 97.6, 80.3, 61.1, 14.8, 14.5, 13.6, -4.9, -5.4. Proton and carbon spectra are shown below. Figure 10 and 11 As shown.

[0096] Comparative Example 1

[0097] Reaction equation:

[0098]

[0099] Under nitrogen atmosphere, using diethyl ether (Et2O) as the reaction solvent, phenylacetylene bromide and trimethylsilylbenzylmagnesium bromide Grignard reagent (molar ratio of the two substances 1:2) were reacted at -70℃ for 20 h with the catalysis of PdCl2[(R)-(S)-PPFA] (5.6% of the molar amount of phenylacetylene bromide) to obtain a product with a yield of 63%.

[0100] Comparative Example 2

[0101] Reaction equation:

[0102]

[0103] Under nitrogen atmosphere, tetrahydrofuran (THF) was used as the reaction solvent. Trimethylchlorosilane and magnesium strip (the amount of magnesium strip was 8 times the molar amount of difluoropropynyl bromide) were first added to the reaction flask. Difluoropropynyl bromide (the molar ratio of difluoropropynyl bromide to trimethylchlorosilane was 1:4) was slowly added dropwise while stirring. The reaction was carried out at 0°C for 0.5 h to obtain a product with a yield of 77%.

[0104] Comparative Example 3

[0105] Reaction equation:

[0106]

[0107] Under nitrogen atmosphere, N-methylpyrrolidone (NMP) was used as the reaction solvent, and elemental calcium was used as the reducing agent (the amount of calcium was 4 times the molar amount of propargyl tervaline). Proargyl tervaline and trimethylchlorosilane (the molar ratio of propargyl tervaline to trimethylchlorosilane was 1:8) were reacted at room temperature for 48 h to obtain a product with a yield of 69%.

[0108] Comparative Example 4

[0109] Reaction equation:

[0110]

[0111] Under nitrogen atmosphere, using 1,2-dichloroethane (DCE) as the reaction solvent, phenylenyne and phenylhydrosilane (molar ratio of phenylenyne to phenylhydrosilane 1:4) reacted at 40 °C for 1 h with ligand and catalyst thiophene copper (10% of the molar amount of phenylenyne) to obtain a product with a yield of 80%. However, allene byproducts were also generated in the reaction. The physicochemical properties of the product and the byproducts were similar, making them difficult to separate and purify.

Claims

1. A method for synthesizing propargylsilane derivatives by nickel-catalyzed reduction coupling, characterized in that: Includes the following steps: Under a protective atmosphere, using an organic solvent as the reaction medium, halogen-containing butyne compounds are reacted with chlorosilanes in the presence of a catalyst, ligand, and reducing agent to obtain propargylsilane derivatives. The structure of the halogen-containing butyne compound is as follows: The structure of the chlorosilane is as follows: The structure of propargylsilane derivatives is shown in Formula I: Where R is phenyl, substituted phenyl, naphthyl, styryl, indolyl, quinolinyl, benzofuranyl, isobenzofuran-1(3H)-keto, benzothiophene, or 1,2-methylenedioxyphenyl; The substituted phenyl group in R is R 1 It can be an ester group, halogen, CN, acyl group, or amino group; R 2 It is hydrogen, alkyl, aryl, or substituted aryl; wherein the aryl or substituted aryl group is phenyl, naphthyl, or biphenyl, and the substituent is one, two, or three of the following: alkyl, F, Cl, amino, or amide; and the substitution position is monosubstituted, disubstituted, or trisubstituted. R 3 The aryl group is hydrogen, alkyl, aryl, or substituted aryl; wherein the aryl group or substituted aryl group is phenyl, naphthyl, or biphenyl, and the substituted aryl group is one, two, or three of the following: alkyl, F, Cl, amino, or amide; and the substitution position is monosubstituted, disubstituted, or trisubstituted. R 4 R 5 and R 6 Each is alkyl, phenyl, alkenyl, or ynyl; The catalyst is a nickel catalyst; The nickel catalyst is one or more of the following: nickel chloride, nickel bromide, nickel iodide, nickel chloride with ethylene glycol dimethyl ether, nickel bromide with ethylene glycol dimethyl ether, nickel bis(triphenylphosphine) dichloride, nickel tetra(triphenylphosphine) tetrachloride, nickel dibromobis(pyridine) dichloride, nickel acetate tetrahydrate, nickel acetylacetone, nickel trifluoromethanesulfonate, nickel fluoroborate hexahydrate, and nickel perchlorate hexahydrate. The ligand is a nitrogen or phosphine ligand, specifically one or more of the following: pyridine, 2,2'-bipyridine, 4,4-di-tert-butyl-2,2-bipyridine, 1,10-phenoroline, 4,7-diphenyl-1,10-phenoroline, and 4,4'-dimethyl-2,2'-bipyridine; and specifically one or more of the following: bis(diphenylphosphine)methane, bis(diphenylphosphine)ethane, bis(diphenylphosphine)propane, bis(diphenylphosphine)butane, bis(diphenylphosphine)benzene, bis(diphenylphosphine)pyridine, triphenylphosphine, tributylphosphine, and tricyclohexylphosphine. The organic solvent is at least one selected from tetrahydrofuran, acetonitrile, acetone, toluene, ethylene glycol dimethyl ether, 1,4-dioxane, dichloromethane, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, and dimethyl sulfoxide.

2. The method for synthesizing propargylsilane derivatives by nickel-catalyzed reduction coupling according to claim 1, characterized in that: R 1 The ester group is COOR', and R' is an alkyl group; the halogen is F, Cl, Br, or I; the acyl group is COR', and R' is an alkyl or phenyl group. R 4 R 5 and R 6 Three of them are alkyl, or two are alkyl and the other is alkenyl, or two are alkyl and the other is phenyl, or one is alkyl, one is phenyl and the other is alkenyl.

3. The method for synthesizing propargylsilane derivatives by nickel-catalyzed reduction coupling according to claim 1, characterized in that: In the halogen-containing butyne compounds, X is Br; The nickel catalyst is one or more of the following: nickel iodide, nickel bromide, nickel chloride, nickel dibromobis(pyridine), nickel chloride with ethylene glycol dimethyl ether, nickel trifluoromethanesulfonate, nickel acetate tetrahydrate, nickel acetylacetone, nickel perchlorate hexahydrate, and nickel bromide with ethylene glycol dimethyl ether. The ligand is one or more of pyridine, 2,2'-bipyridine, 1,10-phenoroline, 4,4-di-tert-butyl-2,2-bipyridine, bis(diphenylphosphine)pyridine, bis(diphenylphosphine)butane, and 4,4'-dimethyl-2,2'-bipyridine.

4. The method for synthesizing propargylsilane derivatives by nickel-catalyzed reduction coupling according to claim 1, characterized in that: The reducing agent is a metal reducing agent or an organic reducing agent; the metal reducing agent is one or more of zinc and manganese; the organic reducing agent is one or more of tetra(dimethylamino)ethylene, bis(pinacol)diboron, triethylsilane, and triphenylsilane.

5. The method for synthesizing propargylsilane derivatives by nickel-catalyzed reduction coupling according to claim 4, characterized in that: The reducing agent is a metallic reducing agent, such as zinc or manganese.

6. The method for synthesizing propargylsilane derivatives by nickel-catalyzed reduction coupling according to claim 1, characterized in that: The organic solvent is one or more of tetrahydrofuran, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, dimethyl sulfoxide, and 1,4-dioxane.

7. The method for synthesizing propargylsilane derivatives by nickel-catalyzed reduction coupling according to claim 1, characterized in that: The molar ratio of the halogen-containing butyne compound to the chlorosilane is 1:1.05–2.5; the reaction temperature is 20–60°C, and the reaction time is 4–15 h.

8. The method for synthesizing propargylsilane derivatives by nickel-catalyzed reduction coupling according to claim 1, characterized in that: The amount of catalyst used is 10 to 15% of the molar amount of the halogen-containing butyne compound.

9. The method for synthesizing propargylsilane derivatives by nickel-catalyzed reduction coupling according to claim 1, characterized in that: The amount of the reducing agent is 2 to 2.5 times the molar amount of the halogen-containing butyne compound; the amount of the ligand is 10 to 15% of the molar amount of the halogen-containing butyne compound.

10. The method for synthesizing propargylsilane derivatives by nickel-catalyzed reduction coupling according to claim 1, characterized in that: After the reaction was complete, water was added to quench the reaction, and the mixture was extracted with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and the ethyl acetate was removed by rotary evaporation. The mixture was then separated by column chromatography with silica gel.

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