Synthesis method and application of chiral homoallylamine compound

Abstract

The invention discloses a synthesis method and application of a chiral homoallylamine compound, and belongs to the technical field of synthesis of drug intermediates, and the synthesis method comprises the following steps: under the protection of inert gas, dissolving a copper salt catalyst, a phosphine ligand, imine, allene silane and tert-butyl alcohol in tetrahydrofuran, stirring and mixing; adding phenyl silane, and reacting at 20-30 DEG C for 12-20 hours; after the reaction is finished, adding a saturated ammonium fluoride methanol solution to quench the reaction; and continuously stirring the mixture, carrying out reduced pressure rotary evaporation to remove the solvent, and separating a crude product by column chromatography to obtain a target product. When THF is used as a solvent and copper acetate is used as a catalyst, the chiral homoallylamine compound can be obtained at room temperature with the highest yield of 78% and diastereoselectivity greater than 20: 1.

Description

Technical Field

[0001] The present invention relates to the technical field of drug intermediate synthesis, and particularly relates to a method for synthesizing chiral homoallylic amine compounds and its applications. Background Art

[0002] The synthesis of chiral homoallylic amine compounds has always been an important field of research for organic chemists and medicinal chemists. The homoallylic amine structural fragment widely exists in natural products and drug molecules, such as: amprenavir, an HIV protease inhibitor; manzacidin C, an adrenergic receptor blocker; cryptophycin 337 with anti-cancer activity; and natural product hitamycin, etc. At the same time, this structure plays an important role in asymmetric organocatalysis and is widely present in the structures of chiral organocatalysts and ligands.

[0003]

[0004] In addition, chiral homoallylic amines, as important synthetic building blocks in medicinal chemistry and organic chemistry, play a crucial role in the total synthesis of natural products, new drug research and development, and other fields. For example, using chiral homoallylic amines as key intermediates, the total synthesis of alkaloid spongistatin, (+)-desoxypipradrol, and broad-spectrum antibiotic vancomycin can be achieved.

[0005]

[0006] In addition to the above two points, chiral homoallylic amine compounds can also be further derivatized to obtain a large number of derivative compounds, such as: piperidine, aminocyclopropane, γ-lactam, amino alcohol, etc. At the same time, the corresponding piperidine alkaloids can be easily prepared from amino dienes through olefin metathesis reactions.

[0007]

[0008] Chiral amine compounds are a class of important and widely used organic compounds, playing a crucial role in the fields of materials and medicinal chemistry. Among numerous chiral amine compounds, chiral homoallylic amine compounds are favored by chemists because they have both an allyl group and can be simply and efficiently derivatized into other functional groups. Currently, the commonly used method for preparing homoallylic amines is the nucleophilic addition of allyl metal reagents to imine compounds. However, since structurally complex allyl metal reagents are not easy to prepare, to a certain extent, this limits the wide application of this synthetic strategy. Therefore, it is urgent to develop new, simple, and efficient methods for synthesizing chiral homoallylic amine compounds with a wide range of substrate applicability. Summary of the Invention

[0009] Therefore, the technical problem to be solved by the present invention is to overcome the limitation in the wide application of this synthetic strategy to a certain extent due to the difficulty in preparing allyl metal reagents with complex structures in the prior art.

[0010] To solve the above technical problem, on the one hand, the present invention provides a method for synthesizing chiral homoallylic amine compounds, comprising the following steps: Under the protection of an inert gas, a copper salt catalyst, a phosphine ligand, an imine, an allenylsilane and tert-butanol are dissolved in tetrahydrofuran and stirred and mixed. Phenylsilane is added and the reaction is carried out at 20 - 30 °C for 12 - 20 hours. After the reaction is completed, a saturated ammonium fluoride methanol solution is added to quench the reaction. The mixture is continuously stirred, the solvent is removed by rotary evaporation under reduced pressure, and the crude product is separated by column chromatography to obtain the target product. The structure of the imine is shown in formula (1):

[0011] The structure of the allenylsilane is shown in formula (2):

[0012] The structure of the target product is shown in formula (3):

[0013] In formulas (1) to (3), R is isobutyl, n-butyl, n-pentyl, cyclopropyl, 5-chloropentyl, benzyl, 2-phenylethyl, 2-phenylethenyl, phenyl, 4-methylphenyl, 4-fluorophenyl, 4-methoxyphenyl, 3-methoxyphenyl, 3-chlorophenyl, 2-fluorophenyl, 2-furyl, and [Si] is dimethylbenzylsilane, diphenylmethylsilane, triphenylsilane.

[0014] Preferably, the copper salt catalyst is copper acetate and its dosage is 5 mol% of the molar amount of the reaction substrate.

[0015] Preferably, the phosphine ligand is tricyclohexylphosphine and its dosage is 12 mol% of the molar amount of the reaction substrate.

[0016] Preferably, the imine is one of (S,E)-2-methyl-N-(3-methylbutylidene)propane-2-sulfonamide, (S,E)-N-butyl-2-methylpropane-2-sulfonamide, (S,E)-N-hexylidene-2-methylpropane-2-sulfonamide, (S,E)-N-(cyclopropylmethylene)-2-methylpropane-2-sulfonamide, (S,E)-N-(5-chloropentylidene)-2-methylpropane-2-sulfonamide, (S,E)-2-methyl-N-(2-phenylethylidene)propane-2-sulfonamide, (S,E)-2-methyl-N-(3-phenylpropylidene)propane-2-sulfonamide, (S)-2-methyl-N-((1E,2E)-3-phenylallylidene)propane-2-sulfonamide, (S,E)-N-benzylidene-2-methylpropane-2-sulfinamide, (S,E)-2-methyl-N-(4-methylbenzylidene)propane-2-sulfonamide, (S,E)-N-(4-fluorobenzylidene)-2-methylpropane-2-sulfonamide, (S,E)-N-(4-methoxybenzylidene)-2-methylpropane-2-sulfonamide, (S,E)-N-(3-methoxybenzylidene)-2-methylpropane-2-sulfonamide, (S,E)-N-(3-chlorobenzylidene)-2-methylpropane-2-sulfonamide, (S,E)-N-(2-fluorobenzylidene)-2-methylpropane-2-sulfonamide, and (S,E)-N-(furan-2-ylmethylene)-2-methylpropane-2-sulfonamide.

[0017] Preferably, the allenyldisilane is one of dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, dimethyl(benzyl)(prop-1,2-dien-1-yl)silane, methyl(diphenyl)(prop-1,2-dien-1-yl)silane, and triphenyl(prop-1,2-dien-1-yl)silane.

[0018] Preferably, the amount of tert-butanol used is 2.0 equivalents of the molar amount of the reaction substrate.

[0019] Preferably, the amount of phenylsilane used is 5.0 equivalents of the molar amount of the reaction substrate.

[0020] Preferably, the column chromatography uses silica gel for column chromatography with 200 - 300 mesh, and the eluent is petroleum ether with a boiling range of 60 - 90 °C.

[0021] On the other hand, the present invention provides an application of a chiral homoallylamine compound in the preparation of an HIV protease inhibitor, an adrenergic receptor blocker, or an anticancer drug.

[0022] The technical solution of the present invention has the following advantages: The present invention provides a method for synthesizing chiral homoallylic amine compounds and their applications. Under the condition of copper catalysis, allenylsilane can react with N-tert-butanesulfinimine to obtain a group of diastereoisomers. When using tetrahydrofuran as the solvent and copper acetate as the catalyst, chiral homoallylic amine compounds can be obtained at a yield of up to 78% and a diastereoselectivity greater than 20:1 at room temperature. Description of the Drawings

[0023] Figure 1 1H NMR spectrum of the compound prepared in Example 1 1 1H NMR spectrum Figure 2 13C NMR spectrum of the compound prepared in Example 1 13 13C NMR spectrum Figure 3 1H NMR spectrum of the compound prepared in Example 2 1 1H NMR spectrum Figure 4 13C NMR spectrum of the compound prepared in Example 2 13 13C NMR spectrum Figure 5 1H NMR spectrum of the compound prepared in Example 3 1 1H NMR spectrum Figure 6 13C NMR spectrum of the compound prepared in Example 3 13 13C NMR spectrum Figure 7 1H NMR spectrum of the compound prepared in Example 4 1 1H NMR spectrum Figure 8 13C NMR spectrum of the compound prepared in Example 4 13 13C NMR spectrum Figure 9 1H NMR spectrum of the compound prepared in Example 5 1 1H NMR spectrum Figure 10 13C NMR spectrum of the compound prepared in Example 5 13 13C NMR spectrum Figure 11 1H NMR spectrum of the compound prepared in Example 6 1 1H NMR spectrum Figure 12 13C NMR spectrum of the compound prepared in Example 6 13 13C NMR spectrum Figure 13 1H NMR spectrum of the compound prepared in Example 7 1 1H NMR spectrum Figure 14 13C NMR spectrum of the compound prepared in Example 7 13 13C NMR spectrum Figure 15 1H NMR spectrum of the compound prepared in Example 8 1 1H NMR spectrum Figure 16 13C spectrum of the compound prepared in Example 8 13 13C spectrum; Figure 17 1H spectrum of the compound prepared in Example 9 1 1H spectrum; Figure 18 13C spectrum of the compound prepared in Example 9 13 13C spectrum; Figure 19 1H spectrum of the compound prepared in Example 10 1 1H spectrum; Figure 20 13C spectrum of the compound prepared in Example 10 13 13C spectrum; Figure 21 1H spectrum of the compound prepared in Example 11 1 1H spectrum; Figure 22 13C spectrum of the compound prepared in Example 11 13 13C spectrum; Figure 23 19F spectrum of the compound prepared in Example 11 19 19F spectrum; Figure 24 1H spectrum of the compound prepared in Example 12 1 1H spectrum; Figure 25 13C spectrum of the compound prepared in Example 12 13 13C spectrum; Figure 26 1H spectrum of the compound prepared in Example 13 1 1H spectrum; Figure 27 13C spectrum of the compound prepared in Example 13 13 13C spectrum; Figure 28 1H spectrum of the compound prepared in Example 14 1 1H spectrum; Figure 29 13C spectrum of the compound prepared in Example 14 13 13C spectrum; Figure 30 1H spectrum of the compound prepared in Example 15 1 1H spectrum; Figure 31 13C spectrum of the compound prepared in Example 15 13 13C spectrum; Figure 32 19F spectrum of the compound prepared in Example 15 19 19F spectrum; Figure 33 1H spectrum of the compound prepared in Example 16 1 1H spectrum; Figure 34For the compound prepared in Example 16 13 13C spectrum; Figure 35 For the compound prepared in Example 17 1 1H spectrum; Figure 36 For the compound prepared in Example 17 13 13C spectrum; Figure 37 For the compound prepared in Example 18 1 1H spectrum; Figure 38 For the compound prepared in Example 18 13 13C spectrum; Figure 39 For the compound prepared in Example 19 1 1H spectrum; Figure 40 For the compound prepared in Example 19 13 13C spectrum. Detailed implementation mode

[0024] The following examples are provided to better understand the present invention further. It is not limited to the best implementation mode, and does not constitute a limitation to the content and protection scope of the present invention. Any product identical or similar to the present invention obtained by anyone under the inspiration of the present invention or by combining the features of the present invention with other prior art features falls within the protection scope of the present invention.

[0025] For those not specifying specific experimental steps or conditions in the examples, the operations or conditions of the conventional experimental steps described in the literature in this field can be followed. For reagents or instruments not specifying the manufacturer, they are all conventional reagent products that can be obtained through commercial purchase.

[0026] Detection means: The melting point was determined using a MEL-TEMP II or XT-4 binocular microscopic melting point apparatus, and the thermometer was not calibrated; the nuclear magnetic resonance spectrometers were BRUKER-ACF-300 type and BRUKER-ACF-400 type, with TMS as the internal standard; the high-resolution mass spectrometry (HRMS) was determined using an Agilent Q-TOF 6520 type mass spectrometer, using an electrospray ionization source (ESI) or an electron impact source (EI). 1 1H NMR data are chemical shifts (δ) in ppm, and CDCl3, CD3OD, DMSO- d 6, or Acetone- d 6 was used as the solvent. The split peak patterns (s is a singlet, d is a doublet, t is a triplet, dd is two doublets, brs is a broad singlet, m is a multiplet), and the coupling constant unit is Hz.13 The chemical shifts in 13C NMR are also in ppm, with the solvents CDCl3: δ = 77.16 ppm; CD3OD: δ = 48.80 ppm; DMSO- d d6: 39.52 ppm; Acetone- d d6: 206.26 ppm as the internal standard.

[0027] The thin-layer chromatography (TLC) plates are prefabricated silica gel TLC plates GF directly purchased from 254 (Yantai Chemical Industry Research Institute), developed with ultraviolet or potassium permanganate developer; column chromatography uses 200 - 300 mesh column chromatography silica gel (Qingdao Marine Chemical Factory), packed by dry method. The solvent ratio for column chromatography is by volume ratio ( v / v ), and the boiling range of petroleum ether is 60 - 90 °C. Unless otherwise specified, the reagents are commercially available chemical pure or analytical pure products.

[0028] General synthesis method of this application:

[0029] Take a clean 10 mL Schlenk tube and a magnetic stir bar, weigh copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %), tricyclohexylphosphine C 18 H 33 P (6.7 mg, 0.012 mmol, 12 mol %), and mix to obtain a mixture. After purging with argon three times, dissolve the imine (1, 0.5 mmol, 1.0 equivalent), allenylsilane (2, 1.0 mmol, 2.0 equivalents), and tert-butanol (29.6 mg, 0.4 mmol, 2.0 equivalents) in tetrahydrofuran (0.8 mL) to obtain a mixed solution, and slowly add the mixed solution to the above mixture, and stir for 10 min (at the end of stirring, a green solution is formed). Then add phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equivalents), and the reaction solution turns yellow. Then, the reaction system is stirred at room temperature for 16 h. After the reaction is completed, slowly add saturated NH4F methanol solution (0.5 mL) to quench the reaction (Note: gas is generated). After continuing to stir the mixture for 30 min, transfer it to a 50 mL round-bottom flask, and remove the solvent by rotary evaporation under reduced pressure. The crude product is separated by column chromatography to obtain the target product 3.

[0030] Example 1:

[0031] Take a 10 mL clean Schlenk tube and a magnetic stir bar, weigh copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %), tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %), and mix them to obtain a mixture. After purging with argon three times, add a mixed solution prepared by dissolving (S,E)-2-methyl-N-(3-methylbut-1-en-2-yl)propane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butanol (29.6 mg, 0.4 mmol, 2.0 equiv) in tetrahydrofuran (0.8 mL) slowly to the above mixture, and stir for 10 min (after stirring, a green solution is formed). Then add phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv), and the reaction solution turns yellow. Then, stir the reaction system at room temperature for 16 h. After the reaction is completed, slowly add saturated NH4F methanol solution (0.5 mL) to quench the reaction (Note: gas is generated). After stirring the mixture for another 30 min, transfer it to a 50 mL round-bottom flask, and remove the solvent by rotary evaporation under reduced pressure. The crude product is separated by column chromatography to obtain the target product. The weight of the obtained target product is 133.5 mg, the yield is 73%, and the diastereoselectivity d.r. > 20:1, and the product is a white solid; melting point 62 – 63 °C; 1 1H NMR (300 MHz, CDCl3) δ 7.52 –7.48 (m, 2H), 7.37 – 7.35 (m, 3H), 5.76 (dt, J J = 16.9, 10.4 Hz, 1H), 5.04 (d, J J = 9.7 Hz, 1H), 4.90 (d, J J = 16.7 Hz, 1H), 3.50 – 3.42 (m, 1H), 3.03 (d, J J =6.7 Hz, 1H), 2.20 (dd, J J = 10.9, 3.1 Hz, 1H), 1.78 – 1.71 (m, 1H), 1.44 –1.35 (m, 1H), 1.20–1.16 (m, 1H), 1.13 (s, 9H), 0.84 (d, J J = 6.5 Hz, 3H), 0.73(d, J J = 6.4 Hz, 3H), 0.34 (s, 6H) ppm. 1313C NMR (75 MHz, CDCl3) δ 137.4, 135.1, 134.3, 129.5, 128.1, 116.6, 55.6, 43.6, 43.3, 24.6, 23.9, 22.9, 21.2, –3.0, –3.4 ppm, as Figure 1 and Figure 2 shown.

[0032] Example 2:

[0033] Take a 10 mL clean Schlenk tube and a magnetic stir bar, weigh copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %), tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %), and mix to obtain a mixture. After purging with argon three times, add a mixed solution prepared by dissolving (S,E)-N-butyl-2-methylpropane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butanol (29.6 mg, 0.4 mmol, 2.0 equiv) in tetrahydrofuran (0.8 mL) slowly to the above mixture, and stir for 10 min (at the end of stirring, a green solution is formed). Then add phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv), and the reaction solution turns yellow. Then, stir the reaction system at room temperature for 16 h. After the reaction is completed, slowly add saturated NH4F methanol solution (0.5 mL) to quench the reaction (Note: gas is generated). After stirring the mixture for another 30 min, transfer it to a 50 mL round-bottom flask, and remove the solvent by rotary evaporation under reduced pressure. The crude product is separated by column chromatography to obtain the target product. The weight of the obtained target product is 131.9 mg, the yield is 75%, the diastereoselectivity d.r. >20:1, and the product is a colorless oil; 1 1H NMR (300 MHz, CDCl3) δ 7.51 – 7.48 (m, 2H), 7.38 – 7.35 (m, 3H), 5.74 (dt, J J = 16.7, 10.5 Hz, 1H), 5.04 (d, J J = 10.1 Hz, 1H), 4.91 (d, J J = 17.0 Hz, 1H), 3.39 – 3.32 (m, 1H), 3.04 (d, J J = 7.4 Hz, 1H), 2.19 (dd, J= 10.9, 3.8 Hz, 1H), 1.65 (s, 1H), 1.56 – 1.39 (m, 3H), 1.32 –1.13 (m, 2H), 1.11 (s, 9H), 0.81 (t, J = 6.6 Hz, 3H), 0.33 (s, 6H) ppm. 13 C NMR (75 MHz, CDCl3) δ 137.5, 135.1, 134.0, 129.4, 128.0, 116.4, 57.7, 55.8,42.87, 36.8, 22.7, 19.5, 13.9, – 3.0, – 3.7 ppm, as Figure 3 and Figure 4 shown.

[0034] Example 3:

[0035] Take a 10 mL clean Schlenk tube and a magnetic stir bar, weigh copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %), tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %), and mix to obtain a mixture. After purging with argon three times, add a mixed solution prepared by dissolving (S,E)-N-hexylidene-2-methylpropane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butanol (29.6 mg, 0.4 mmol, 2.0 equiv) in tetrahydrofuran (0.8 mL) dropwise to the above mixture, and stir for 10 min (the mixture turns into a green solution at the end of stirring). Then add phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv), and the reaction solution turns yellow. Then, stir the reaction system at room temperature for 16 h. After completion of the reaction, slowly add saturated NH4F methanol solution (0.5 mL) to quench the reaction (note: gas is generated). After stirring the mixture for another 30 min, transfer it to a 50 mL round-bottom flask, and remove the solvent by rotary evaporation under reduced pressure. The crude product is separated by column chromatography to obtain the target product. The weight of the obtained target product is 115.8 mg, the yield is 61%, the diastereoselectivity d.r. > 20:1, and the product is a colorless oil; 1 1H NMR (300 MHz, CDCl3) δ 7.52 – 7.46 (m, 2H), 7.38 –7.33 (m, 3H), 5.74 (dt, J = 16.8, 10.5 Hz, 1H), 5.03 (dd,J = 10.1, 2.1 Hz, 1H), 4.91 (dd, J = 16.9, 2.1 Hz, 1H), 3.38 – 3.30 (m, 1H), 3.04 (d, J = 7.3Hz, 1H), 2.20 (dd, J = 10.9, 3.9 Hz, 1H), 1.51 – 1.38 (m, 3H), 1.28 – 1.16 (m, 5H), 1.10 (s, 9H), 0.85 (t, J = 7.0 Hz, 3H), 0.332 (s, 3H), 0.327 (s, 3H) ppm. 13 C NMR (75 MHz, CDCl3) δ 137.4, 135.1, 133.9, 129.3, 128.0, 116.2, 57.9, 55.7, 42.7, 34.5, 31.6, 25.9, 22.71, 22.65, 22.5, 14.1, –3.1, –3.7 ppm, as Figure 5 and Figure 6 shown.

[0036] Example 4:

[0037] Take a 10 mL clean Schlenk tube and a magnetic stir bar, weigh copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %), tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %), and mix them to obtain a mixture. After purging with argon three times, add a mixed solution prepared by dissolving (S,E)-N-(cyclopropylmethylene)-2-methylpropane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butanol (29.6 mg, 0.4 mmol, 2.0 equiv) in tetrahydrofuran (0.8 mL) slowly to the above mixture, and stir for 10 min (at the end of stirring, a green solution is formed). Then add phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv), and the reaction solution turns yellow. Then, stir the reaction system at room temperature for 16 h. After the reaction is completed, slowly add saturated NH4F methanol solution (0.5 mL) to quench the reaction (note: gas is generated). After stirring the mixture for another 30 min, transfer it to a 50 mL round-bottom flask, and remove the solvent by rotary evaporation under reduced pressure. The crude product is separated by column chromatography to obtain the target product. The weight of the obtained target product is 118.8 mg, the yield is 82%, the diastereoselectivity d.r. > 20:1, and the product is a colorless oil; 1 1H NMR (300 MHz, CDCl3) δ 7.56 – 7.48 (m, 2H),7.38 – 7.33 (m, 3H), 5.93 (dt, J J = 16.9, 10.4 Hz, 1H), 5.06 (dd, J J = 10.1,2.1 Hz, 1H), 4.90 (dd, J J = 16.9, 1.6 Hz, 1H), 3.21 (d, J J = 5.8 Hz, 1H), 2.65(ddd, J J = 9.4, 5.8, 3.6 Hz, 1H), 2.39 (dd, J J = 10.8, 3.6 Hz, 1H), 1.13 (s,9H), 1.02 – 0.89 (m, 1H), 0.60 – 0.46 (m, 2H), 0.38 (s, 3H), 0.33 (s, 3H),0.34 – 0.20 (m, 2H) ppm. 1313C NMR (75 MHz, CDCl3) δ 137.8, 135.2, 134.0, 129.3, 128.0, 116.5, 61.9, 55.7, 42.2, 22.7, 15.9, 6.9, 5.1, –2.5, –3.6 ppm, as Figure 7 and Figure 8 shown.

[0038] Example 5:

[0039] Take a 10 mL clean Schlenk tube and a magnetic stir bar, weigh copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %), tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %), and mix to obtain a mixture. After purging with argon three times, add a mixed solution prepared by dissolving (S,E)-N-(5-chloropent-1-en-1-yl)-2-methylpropane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butanol (29.6 mg, 0.4 mmol, 2.0 equiv) in tetrahydrofuran (0.8 mL) slowly into the above mixture, and stir for 10 min (the mixture turns into a green solution at the end of stirring). Then add phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv), and the reaction solution turns yellow. Then, stir the reaction system at room temperature for 16 h. After the reaction is completed, slowly add saturated NH4F methanol solution (0.5 mL) to quench the reaction (Note: gas is generated). After stirring the mixture for another 30 min, transfer it to a 50 mL round-bottom flask, and remove the solvent by rotary evaporation under reduced pressure. The crude product is separated by column chromatography to obtain the target product. The weight of the obtained target product is 144.0 mg, the yield is 72%, the diastereoselectivity d.r. > 20:1, and the product is a colorless oil; 1 1H NMR (300 MHz, Acetone- d d6) δ 7.60 – 7.57 (m, 2H), 7.41 – 7.37 (m, 3H), 5.83 (dt, J J = 16.8, 10.5 Hz, 1H), 5.02 (dd, J J = 10.1, 2.3 Hz, 1H), 4.94 (dd, J J = 16.9, 2.1 Hz, 1H), 3.50 (td, J= 6.7, 1.4 Hz, 2H), 3.36 – 3.29 (m, 1H), 2.31 (dd, J = 10.8, 4.4 Hz, 1H), 1.71 – 1.51(m, 5H), 1.43 – 1.29 (m, 1H), 1.09 (s, 9H), 0.37 (s, 3H), 0.34 (s, 3H) ppm. 13 C NMR (75 MHz, Acetone- d 6) δ 137.6, 135.6, 134.0, 129.2, 127.9, 115.2, 57.8, 55.2, 44.7, 43.0, 33.1, 32.2, 23.0, 22.2, – 3.7, – 4.3 ppm, as Figure 9 and Figure 10 shown.

[0040] Example 6:

[0041] Take a 10 mL clean Schlenk tube and a magnetic stir bar, weigh copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %), tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %), and mix to obtain a mixture. After purging with argon three times, a mixed solution of (S,E)-2-methyl-N-(2-phenylethylidene)propane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butanol (29.6 mg, 0.4 mmol, 2.0 equiv) dissolved in tetrahydrofuran (0.8 mL) was slowly added to the above mixture, and the mixture was stirred for 10 min (at the end of stirring, a green solution was formed). Then phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv) was added, and the reaction solution turned yellow. Then, the reaction system was stirred at room temperature for 16 h. After the reaction was completed, saturated NH4F methanol solution (0.5 mL) was slowly added to quench the reaction (Note: gas was generated). After the mixture was stirred for another 30 min, it was transferred to a 50 mL round-bottom flask, and the solvent was removed by rotary evaporation under reduced pressure. The crude product was separated by column chromatography to obtain the target product. The weight of the obtained target product was 111.9 mg, the yield was 56%, the diastereoselectivity d.r. = 11:1, and the product was a colorless oil; 11H NMR (300 MHz, CDCl3) δ 7.49 – 7.45 (m, 2H), 7.37 – 7.19 (m, 7H), 7.05 – 7.02 (m, 2H), 5.82 (dt, J J = 17.0, 10.3 Hz, 1H), 5.10 (dd, J J = 10.2, 2.0 Hz, 1H), 4.96 (dd, J J = 17.1, 2.0 Hz, 1H), 3.75 – 3.65 (m, 1H), 3.10 (d, J J = 5.0 Hz, 1H), 2.96 (dd, J J = 13.5, 3.7 Hz, 1H), 2.68 (dd, J J = 13.5, 9.3 Hz, 1H), 2.58 (dd, J J = 10.4, 4.9 Hz, 1H), 0.98 (s, 9H), 0.39 (s, 3H), 0.35 (s, 3H) ppm. 13 13C NMR (75 MHz, CDCl3) δ 137.7, 137.5, 135.0, 134.0, 129.8, 129.3, 128.7, 128.1, 126.9, 116.3, 56.1, 55.6, 39.4, 38.4, 22.7, – 2.5, – 3.8 ppm, as Figure 11 and Figure 12 shown.

[0042] Example 7:

[0043] Take a 10 mL clean Schlenk tube and a magnetic stir bar, weigh copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %), tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %), and mix them to obtain a mixture. After purging with argon three times, add a mixed solution prepared by dissolving (S,E)-2-methyl-N-(3-phenylpropylidene)propane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butanol (29.6 mg, 0.4 mmol, 2.0 equiv) in tetrahydrofuran (0.8 mL) slowly to the above mixture, and stir for 10 min (after stirring, a green solution is formed). Then add phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv), and the reaction solution turns yellow. Then, stir the reaction system at room temperature for 16 h. After the reaction is completed, slowly add saturated NH4F methanol solution (0.5 mL) to quench the reaction (Note: gas is generated). After stirring the mixture for another 30 min, transfer it to a 50 mL round-bottom flask, and remove the solvent by rotary evaporation under reduced pressure. The crude product is separated by column chromatography to obtain the target product. The weight of the obtained target product is 109.6 mg, the yield is 53%, the diastereoselectivity d.r. = 11:1, and the product is a colorless oil; 1 1H NMR (300 MHz, CDCl3) δ 7.45 – 7.40 (m, 2H),7.38 – 7.33 (m, 3H), 7.29 – 7.24 (m, 2H), 7.21 – 7.14 (m, 3H), 5.72 (dt, J J =16.8, 10.5 Hz, 1H), 5.05 (dd, J J = 10.0, 2.1 Hz, 1H), 4.93 (dd, J J = 16.7, 2.1Hz, 1H), 3.44 – 3.36 (m, 1H), 3.15 (d, J J = 7.7 Hz, 1H), 2.82 – 2.75 (m, 1H),2.65 – 2.55 (m, 1H), 2.16 (dd, J J = 10.9, 3.9 Hz, 1H), 1.87 – 1.63 (m, 2H),1.12 (s, 9H), 0.24 (s, 3H), 0.22 (s, 3H) ppm. 13 13C NMR (75 MHz, CDCl3) δ 141.7, 137.4, 134.8, 134.1, 129.4, 128.9, 128.5, 128.0, 126.0, 116.7, 57.2, 55.9, 43.4, 36.7, 32.2, 22.7, –3.4, –3.8 ppm, such as Figure 13 and Figure 14 shown.

[0044] Example 8:

[0045] Take a 10 mL clean Schlenk tube and a magnetic stir bar, weigh copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %), tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %), and mix to obtain a mixture. After purging with argon three times, add a mixed solution prepared by dissolving (S)-2-methyl-N-((1E,2E)-3-phenylallylidene)propane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butanol (29.6 mg, 0.4 mmol, 2.0 equiv) in tetrahydrofuran (0.8 mL) to the above mixture slowly, and stir for 10 min (at the end of stirring, a green solution is formed). Then add phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv), and the reaction solution turns yellow. Then, stir the reaction system at room temperature for 16 h. After the reaction is completed, slowly add saturated NH4F methanol solution (0.5 mL) to quench the reaction (Note: gas is generated). After stirring the mixture for another 30 min, transfer it to a 50 mL round-bottom flask, and remove the solvent by rotary evaporation under reduced pressure. The crude product is separated by column chromatography to obtain the target product. The weight of the obtained target product is 129.6 mg, the yield is 63%, the diastereoselectivity d.r. = 2:1, and the product is a colorless oil; 1 1H NMR (300 MHz, Acetone- d δ 7.59–7.56 (m, 2H), 7.41 – 7.32 (m, 8H), 6.46 (dd, J J = 15.8, 0.8 Hz, 1H), 6.30(dd, J J = 15.8, 7.9 Hz, 1H), 5.92 (dt, J J = 16.9, 10.5 Hz, 1H), 5.09 (dd, Jδ = 10.2, 2.2 Hz, 1H), 5.01 (dd, J δ = 16.9, 2.2 Hz, 1H), 4.09 (dd, J δ = 8.0, 4.5Hz, 1H), 2.56 (dd, J δ = 10.8, 4.5 Hz, 1H), 1.11 (s, 9H), 0.36 (s, 3H), 0.34(s, 3H) ppm. 13 C NMR (75 MHz, CDCl3) δ 137.4, 136.9, 135.0, 134.2, 131.5,130.1, 129.1, 128.5, 127.8, 127.5, 126.5, 116.0, 58.4, 55.1, 41.5, 22.0, –3.9, – 4.8 ppm, as Figure 15 and Figure 16 shown.

[0046] Example 9:

[0047] Take a 10 mL clean Schlenk tube and a magnetic stir bar, weigh copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %), tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %), and mix to obtain a mixture. After purging with argon three times, add a mixed solution prepared by dissolving (S,E)-N-benzylidene-2-methylpropane-2-sulfinamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butanol (29.6 mg, 0.4 mmol, 2.0 equiv) in tetrahydrofuran (0.8 mL) slowly to the above mixture, and stir for 10 min (the mixture turns into a green solution at the end of stirring). Then add phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv), and the reaction solution turns yellow. Then, stir the reaction system at room temperature for 16 h. After the reaction is completed, slowly add saturated NH4F methanol solution (0.5 mL) to quench the reaction (Note: gas is generated). After stirring the mixture for another 30 min, transfer it to a 50 mL round-bottom flask, and remove the solvent by rotary evaporation under reduced pressure. The crude product is separated by column chromatography to obtain the target product. The weight of the obtained target product is 115.7 mg, the yield is 60%, the diastereoselectivity d.r. = 10:1, and the product is a colorless oil; 11H NMR (300 MHz, CDCl3) δ 7.60 – 7.55 (m, 2H), 7.49 – 7.46 (m, 3H), 7.38 – 7.33 (m, 3H), 7.27 – 7.21 (m, 2H), 5.95 – 5.82 (dt, J J = 16.9, 10.1 Hz, 1H), 5.18 (d, J J = 10.1 Hz, 1H), 5.07 (d, J J = 16.9 Hz, 1H), 4.71 – 4.64 (m, 1H), 3.60 (d, J J = 3.1 Hz, 1H), 2.86 – 2.81 (m, 1H), 1.22 (s, 9H), 0.14 (s, 3H), 0.09 (s, 3H) ppm. 13 13C NMR (75 MHz, CDCl3) δ 141.0, 137.4, 134.0, 133.8, 129.2, 128.3, 128.1, 128.0, 127.8, 117.3, 58.7, 55.8, 41.1, 22.7, – 2.8, – 5.4 ppm, as Figure 17 and Figure 18 shown.

[0048] Example 10:

[0049] Take a 10 mL clean Schlenk tube and a magnetic stir bar, weigh copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %), tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %), and mix to obtain a mixture. After displacing with argon three times, dissolve the mixed solution of (S,E)-2-methyl-N-(4-methylbenzylidene)propane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butanol (29.6 mg, 0.4 mmol, 2.0 equiv) in tetrahydrofuran (0.8 mL), and slowly add the mixed solution to the above mixture. Stir for 10 min (at the end of stirring, a green solution is formed). Then add phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv), and the reaction solution turns yellow. Then, stir the reaction system at room temperature for 16 h. After the reaction is completed, slowly add a saturated NH4F methanol solution (0.5 mL) to quench the reaction (Note: gas is generated). After stirring the mixture for another 30 min, transfer it to a 50 mL round-bottom flask, and remove the solvent by rotary evaporation under reduced pressure. The crude product is separated by column chromatography to obtain the target product. The weight of the obtained target product is 155.9 mg, the yield is 78%, the diastereoselectivity d.r. = 9:1, and the product is a colorless oil; 1 H NMR (300 MHz, Acetone- d 6) δ 7.78 – 7.73 (m,2H), 7.61 – 7.57 (m, 3H), 7.28 (s, 4H), 5.96 (dt, J = 16.9, 10.5 Hz, 1H),5.19 (dd, J = 10.2, 2.3 Hz, 1H), 5.12 (dd, J = 16.9, 2.3 Hz, 1H), 4.71 – 4.67(m, 1H), 2.97 (dd, J = 10.8, 5.6 Hz, 1H), 2.49 (s, 3H), 1.25 (s, 9H), 0.29(s, 3H), 0.28 (s, 3H) ppm. 13 C NMR (75 MHz, Acetone- d6) δ 139.1, 137.8, 136.7, 134.9, 134.0, 129.1, 128.4, 128.2, 127.9, 116.1, 59.0, 55.2, 41.9, 22.0, 20.2, –3.2, –5.4 ppm, such as Figure 19 and Figure 20 shown

[0050] Example 11:

[0051] Take a 10 mL clean Schlenk tube and a magnetic stir bar, weigh copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %), tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %), and mix to obtain a mixture. After purging with argon three times, add a mixed solution prepared by dissolving (S,E)-N-(4-fluorobenzylidene)-2-methylpropane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butanol (29.6 mg, 0.4 mmol, 2.0 equiv) in tetrahydrofuran (0.8 mL) slowly to the above mixture, and stir for 10 min (at the end of stirring, a green solution is formed). Then add phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv), and the reaction solution turns yellow. Then, stir the reaction system at room temperature for 16 h. After the reaction is completed, slowly add saturated NH4F methanol solution (0.5 mL) to quench the reaction (note: gas is generated). After stirring the mixture for another 30 min, transfer it to a 50 mL round-bottom flask, and remove the solvent by rotary evaporation under reduced pressure. The crude product is separated by column chromatography to obtain the target product. The weight of the obtained target product is 135.2 mg, the yield is 67%, the diastereoselectivity d.r. = 9:1, and the product is a colorless oil; 1 1H NMR (300 MHz, CDCl3) δ 7.47 – 7.44 (m, 2H), 7.39 – 7.36 (m, 3H), 7.07 (t, J J = 7.0 Hz, 2H), 6.94 (t, J J = 8.5 Hz, 2H), 5.73 (dt, J J = 16.0, 10.5 Hz, 1H), 5.09 (d, J J = 10.2 Hz, 1H), 4.98 (d, J J = 16.8 Hz, 1H), 4.51 (t,J = 5.5 Hz, 1H), 3.45 (d, J = 5.7 Hz, 1H), 2.68 (dd, J = 10.9, 5.0 Hz, 1H), 1.10 (s, 9H), 0.07 (s, 3H), 0.01 (s, 3H) ppm. 13 C NMR (75 MHz, CDCl3) δ 162.2 (d, 1 J = 246.4 Hz), 136.9 (d, 4 J = 3.2 Hz), 134.0, 133.7, 129.9(d, 3 J = 8.0 Hz), 129.4, 128.1, 117.6, 115.0 (d, 2 J = 21.3 Hz), 58.4, 55.9, 41.4, 22.6, – 2.7, – 5.3 ppm. 19 F NMR (282 MHz, CDCl3) δ – 114.43 ppm, such as Figure 21 、 Figure 22 and Figure 23 shown.

[0052] Example 12:

[0053] Take a 10 mL clean Schlenk tube and a magnetic stir bar, weigh copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %), tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %), and mix them to obtain a mixture. After purging with argon three times, add a mixed solution prepared by dissolving (S,E)-N-(4-methoxybenzylidene)-2-methylpropane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butanol (29.6 mg, 0.4 mmol, 2.0 equiv) in tetrahydrofuran (0.8 mL) slowly into the above mixture, and stir for 10 min (after stirring, a green solution is formed). Then add phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv), and the reaction solution turns yellow. Then, stir the reaction system at room temperature for 16 h. After the reaction is completed, slowly add saturated NH4F methanol solution (0.5 mL) to quench the reaction (Note: gas is generated). After stirring the mixture for another 30 min, transfer it to a 50 mL round-bottom flask, and remove the solvent by rotary evaporation under reduced pressure. The crude product is separated by column chromatography to obtain the target product. The weight of the obtained target product is 137.2 mg, the yield is 66%, the diastereoselectivity d.r. = 7:1, and the product is a colorless oil; 1 H NMR (300 MHz, Acetone- d 6) δ 7.79 – 7.72(m, 2H), 7.61 – 7.56 (m, 3H), 7.33 – 7.28 (m, 2H), 7.04 – 6.98 (m, 2H), 5.96(dt, J = 16.9, 10.5 Hz, 1H), 5.19 (dd, J = 10.2, 2.3 Hz, 1H), 5.12 (dd, J =16.9, 2.2 Hz, 1H), 4.68 (t, J = 6.1 Hz, 1H), 3.96 (s, 3H), 2.96 (dd, J =10.8, 5.5 Hz, 1H), 1.25 (s, 9H), 0.30 (s, 3H), 0.28 (s, 3H) ppm. 13 C NMR (75MHz, Acetone- d6) δ 159.6, 138.3, 135.5, 134.6, 129.9, 129.6, 128.4, 116.6, 113.6, 59.3, 55.6, 55.1, 42.5, 22.6, –2.7, –4.8 ppm, as Figure 24 and Figure 25 shown

[0054] Example 13:

[0055] Take a 10 mL clean Schlenk tube and a magnetic stir bar, weigh copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %), tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %), and mix to obtain a mixture. After purging with argon three times, add a mixed solution prepared by dissolving (S,E)-N-(3-methoxybenzylidene)-2-methylpropane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butanol (29.6 mg, 0.4 mmol, 2.0 equiv) in tetrahydrofuran (0.8 mL) slowly to the above mixture, and stir for 10 min (the stirring ends, and a green solution is formed). Then add phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv), and the reaction solution turns yellow. Then, stir the reaction system at room temperature for 16 h. After the reaction is completed, slowly add saturated NH4F methanol solution (0.5 mL) to quench the reaction (Note: gas is generated). After stirring the mixture for another 30 min, transfer it to a 50 mL round-bottom flask, and remove the solvent by rotary evaporation under reduced pressure. The crude product is separated by column chromatography to obtain the target product. The weight of the obtained target product is 99.8 mg, the yield is 48%, the diastereoselectivity d.r. = 13:1, and the product is a colorless oil; 1 1H NMR (300 MHz, CDCl3) δ 7.49 – 7.45 (m, 2H), 7.38 – 7.35 (m, 3H), 7.18 (t, J J = 7.9 Hz, 1H), 6.76 (dd, J J = 14.1, 8.0 Hz, 2H), 6.65 (s, 1H), 5.79 (dt, J J = 16.6, 10.4 Hz, 1H), 5.08 (d, J J = 10.1 Hz, 1H), 4.96 (d, J= 16.9 Hz, 1H), 4.53 (t, J = 4.6 Hz, 1H), 3.74 (s, 3H), 3.47 (d, J = 5.0 Hz, 1H), 2.72 (dd, J = 10.7, 4.6 Hz, 1H), 1.65 (s, 1H), 1.12 (s, 9H), 0.06 (s, 3H), 0.00 (s, 3H) ppm. 13 C NMR (75 MHz, CDCl3) δ 159.3, 142.6, 137.5, 134.1, 133.9, 129.3, 129.2, 128.1, 120.7, 117.4, 114.3, 113.2, 58.6, 55.9, 55.3, 41.1, 22.8, –2.6, –5.2 ppm, as Figure 26 and Figure 27 shown.

[0056] Example 14:

[0057] Take a 10 mL clean Schlenk tube and a magnetic stir bar, weigh copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %), tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %), and mix to obtain a mixture. After purging with argon three times, add a mixed solution prepared by dissolving (S,E)-N-(3-chlorobenzylidene)-2-methylpropane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butanol (29.6 mg, 0.4 mmol, 2.0 equiv) in tetrahydrofuran (0.8 mL) slowly to the above mixture, and stir for 10 min (at the end of stirring, a green solution is formed). Then add phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv), and the reaction solution turns yellow. Then, stir the reaction system at room temperature for 16 h. After the reaction is completed, slowly add saturated NH4F methanol solution (0.5 mL) to quench the reaction (Note: gas is generated). After stirring the mixture for another 30 min, transfer it to a 50 mL round-bottom flask, remove the solvent by rotary evaporation under reduced pressure, and separate the crude product by column chromatography to obtain the target product. The weight of the obtained target product is 136.5 mg, the yield is 65%, the diastereoselectivity d.r. = 14:1, and the product is a colorless oil; 11H NMR (300 MHz, Acetone- d 6) δ 7.62 – 7.57(m, 2H), 7.45 – 7.35 (m, 3H), 7.28 – 7.18 (m, 4H), 5.67 (dt, J J = 16.7, 10.5Hz, 1H), 4.97 – 4.86 (m, 2H), 4.54 – 4.47 (m, 1H), 2.80 (dd, J J = 11.0, 6.7Hz, 1H), 1.04 (s, 9H), 0.19 (s, 3H), 0.18 (s, 3H) ppm. 13 13C NMR (75 MHz, Acetone- d 6) δ 145.1, 137.8, 134.9, 134.0, 133.2, 129.5, 129.2, 128.1, 127.9, 127.1, 126.8, 116.1, 59.9, 55.5, 41.7, 22.0, – 3.0, – 5.1 ppm, as Figure 28 and Figure 29 shown.

[0058] Example 15:

[0059] Take a 10 mL clean Schlenk tube and a magnetic stir bar. Weigh copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %), tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %), and mix them to obtain a mixture. After purging with argon three times, add a mixed solution prepared by dissolving (S,E)-N-(2-fluorobenzylidene)-2-methylpropane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butanol (29.6 mg, 0.4 mmol, 2.0 equiv) in tetrahydrofuran (0.8 mL) slowly into the above mixture, and stir for 10 min (after stirring ends, a green solution is formed). Then add phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv), and the reaction solution turns yellow. Then, stir the reaction system at room temperature for 16 h. After the reaction is completed, slowly add saturated NH4F methanol solution (0.5 mL) to quench the reaction (Note: gas is generated). After stirring the mixture for another 30 min, transfer it to a 50 mL round-bottom flask, and remove the solvent by rotary evaporation under reduced pressure. The crude product is separated by column chromatography to obtain the target product. The weight of the obtained target product is 60.5 mg, the yield is 30%, the diastereoselectivity d.r. = 10:1, and the product is a colorless oil; 1 H NMR (300 MHz, CDCl3) δ 7.54 – 7.49 (m, 2H),7.38 – 7.34 (m, 3H), 7.24 – 7.10 (m, 2H), 7.08 – 6.94 (m, 2H), 5.63 (dt, J J =16.8, 10.3 Hz, 1H), 4.93 (dd, J J = 10.1, 1.8 Hz, 1H), 4.84 (dd, J J = 16.9, 1.8Hz, 1H), 4.60 (t, J J = 9.1 Hz, 1H), 3.60 (d, J J = 9.9 Hz, 1H), 2.66 (dd, J J =10.6, 8.2 Hz, 1H), 0.96 (s, 9H), 0.31 (s, 3H), 0.14 (s, 3H) ppm. 13 C NMR (75MHz, CDCl3) δ 160.6 (d, 1 J= 244.7 Hz), 138.3, 135.2, 133.7, 129.8 (d, 2 J =12.6 Hz), 129.6 (d, 3 J = 5.0 Hz), 129.3, 129.2 (d, 3 J = 8.7 Hz), 129.1, 128.1,123.9 (d, 4 J = 3.4 Hz), 115.7 (d, 2 J = 22.4 Hz), 57.6, 56.0, 41.7, 22.4, –2.0, – 4.8 ppm. 19 19F NMR (282 MHz, CDCl3) δ – 116.21 ppm, such as Figure 30 、 Figure 31 and Figure 32 shown.

[0060] Example 16:

[0061] Take a 10 mL clean Schlenk tube and a magnetic stir bar, weigh copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %), tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %), and mix to obtain a mixture. After purging with argon three times, add a mixed solution prepared by dissolving (S,E)-N-(furan-2-ylmethylene)-2-methylpropane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butanol (29.6 mg, 0.4 mmol, 2.0 equiv) in tetrahydrofuran (0.8 mL) slowly to the above mixture, and stir for 10 min (at the end of stirring, a green solution is formed). Then add phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv), and the reaction solution turns yellow. Then, stir the reaction system at room temperature for 16 h. After the reaction is completed, slowly add saturated NH4F methanol solution (0.5 mL) to quench the reaction (Note: gas is generated). After stirring the mixture for another 30 min, transfer it to a 50 mL round-bottom flask, and remove the solvent by rotary evaporation under reduced pressure. The crude product is separated by column chromatography to obtain the target product. The weight of the obtained target product is 138.9 mg, the yield is 74%, the diastereoselectivity d.r. > 20:1, and the product is a colorless oil;1 1H NMR (300 MHz, CDCl3) δ 7.56 – 7.51 (m, 2H), 7.49 – 7.48 (m, 1H), 7.41 – 7.36 (m, 3H), 6.36 – 6.34 (m, 1H), 6.21 (dt, J J = 3.3, 0.7 Hz, 1H), 5.97 (dt, J J = 17.0, 10.4 Hz, 1H), 5.05 (dd, J J = 10.2, 2.2 Hz, 1H), 4.96 (ddd, J J = 17.0, 2.2, 0.8 Hz, 1H), 4.54 – 4.50 (m, 1H), 3.95 (d, J J = 8.1 Hz, 1H), 2.66 (dd, J J = 10.7, 4.9 Hz, 1H), 1.07 (s, 9H), 0.18 (s, 3H), 0.13 (s, 3H) ppm. 13 13C NMR (75 MHz, CDCl3) δ 154.3, 141.8, 137.0, 134.7, 133.9, 129.2, 127.7, 117.2, 110.2, 108.2, 56.0, 53.5, 41.4, 22.5, –4.0, –5.2 ppm, as Figure 33 and Figure 34 shown.

[0062] Example 17:

[0063] Take a 10 mL clean Schlenk tube and a magnetic stir bar. Weigh copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %), tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %), and mix them to obtain a mixture. After purging with argon three times, add a mixed solution prepared by dissolving (S,E)-2-methyl-N-(3-methylbut-1-en-2-yl)propane-2-sulfonamide, dimethyl(benzyl)(prop-1,2-dien-1-yl)silane, and tert-butanol (29.6 mg, 0.4 mmol, 2.0 equiv) in tetrahydrofuran (0.8 mL) slowly into the above mixture, and stir for 10 min (after stirring, a green solution is formed). Then add phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv), and the reaction solution turns yellow. Then, stir the reaction system at room temperature for 16 h. After the reaction is completed, slowly add saturated NH4F methanol solution (0.5 mL) to quench the reaction (Note: gas is generated). After continuing to stir the mixture for 30 min, transfer it to a 50 mL round-bottom flask, and remove the solvent by rotary evaporation under reduced pressure. The crude product is separated by column chromatography to obtain the target product. The weight of the obtained target product is 123.4 mg, the yield is 65%, the diastereoselectivity d.r. > 20:1, and the product is a white solid; 1 1H NMR (300 MHz, CDCl3) δ 7.44 – 7.39 (m, 2H),7.30 – 7.25 (m, 1H), 7.21 – 7.18 (m, 2H), 5.97 (dt, J J = 17.1, 10.6 Hz, 1H),5.28 (d, J J = 10.1 Hz, 1H), 5.15 (d, J J = 16.8 Hz, 1H), 3.80 – 3.71 (m, 1H),3.35 (d, J J = 6.4 Hz, 1H), 2.33 (s, 2H), 2.29 – 2.24 (m, 1H), 2.15 – 2.01 (m,1H), 1.79 – 1.69 (m, 1H), 1.50 – 1.43 (m, 1H), 1.38 (s, 9H), 1.17 – 1.13 (m,6H), 0.23 (s, 3H), 0.20 (s, 3H) ppm. 13 13C NMR (75 MHz, CDCl3) δ 139.4, 134.6, 128.31, 128.28, 124.3, 116.9, 55.8, 54.9, 43.5, 42.3, 24.5, 24.3, 24.1, 22.7, 21.2, –3.88, –3.91 ppm, such as Figure 35 and Figure 36 shown

[0064] Example 18:

[0065] Take a 10 mL clean Schlenk tube and a magnetic stir bar, weigh copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %), tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %), and mix to obtain a mixture. After purging with argon three times, add a mixed solution prepared by dissolving (S,E)-2-methyl-N-(3-methylbut-1-en-1-yl)propane-2-sulfonamide, methyl(diphenyl)(prop-1,2-dien-1-yl)silane, and tert-butanol (29.6 mg, 0.4 mmol, 2.0 equiv) in tetrahydrofuran (0.8 mL) slowly into the above mixture, and stir for 10 min (the mixture becomes a green solution at the end of stirring). Then add phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv), and the reaction solution turns yellow. Then, stir the reaction system at room temperature for 16 h. After the reaction is completed, slowly add saturated NH4F methanol solution (0.5 mL) to quench the reaction (note: gas is generated). After stirring the mixture for another 30 min, transfer it to a 50 mL round-bottom flask, and remove the solvent by rotary evaporation under reduced pressure. The crude product is separated by column chromatography to obtain the target product. The weight of the obtained target product is 162.5 mg, the yield is 76%, the diastereoselectivity d.r. > 20:1, and the product is a white solid; 1 1H NMR (300 MHz, Acetone- d 6) δ 7.65 – 7.61 (m, 4H), 7.42 – 7.35 (m, 6H), 5.91 (dt, J J = 16.9, 10.4 Hz, 1H), 5.01 (dd, J J = 10.1, 2.3 Hz, 1H), 4.91 (d, J J = 2.1 Hz, 1H), 4.85 (d, J J = 2.2 Hz, 1H), 3.64 – 3.56 (m, 1H), 2.78 (dd,J = 10.7, 3.4 Hz, 1H), 1.86 – 1.71 (m, 1H), 1.57 –1.48 (m, 1H), 1.19 – 1.10 (m, 10H), 0.76 (d, J = 6.7 Hz, 3H), 0.68 (s, 3Hz),0.54 (d, J = 6.5 Hz, 3H) ppm. 13 C NMR (75 MHz, Acetone- d 6) δ 136.0, 135.6,134.89, 134.87, 134.8, 129.5, 129.3, 128.0, 127.8, 116.6, 55.3, 55.2, 42.6,41.7, 23.9, 23.3, 22.2, 20.2, – 5.3 ppm, as Figure 37 and Figure 38 shown.

[0066] Example 19:

[0067] mol %), tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %), and mixed to obtain a mixture. After purging with argon three times, a mixed solution of (S,E)-2-methyl-N-(3-methylbut-1-en-2-yl)propane-2-sulfonamide, triphenyl(prop-1,2-dien-1-yl)silane, and tert-butanol (29.6 mg, 0.4 mmol, 2.0 equiv) dissolved in tetrahydrofuran (0.8 mL) was slowly added to the above mixture, and the mixture was stirred for 10 min (at the end of stirring, a green solution was formed). Then phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv) was added, and the reaction solution turned yellow. Then, the reaction system was stirred at room temperature for 16 h. After the reaction was completed, a saturated NH4F methanol solution (0.5 mL) was slowly added to quench the reaction (Note: gas was generated). After the mixture was stirred for an additional 30 min, it was transferred to a 50 mL round-bottom flask, and the solvent was removed by rotary evaporation under reduced pressure. The crude product was separated by column chromatography to obtain the target product. The weight of the target product obtained was 176.3 mg, the yield was 72%, the diastereoselectivity d.r. > 20:1, and the product was a colorless oil; 1 H NMR (300 MHz, Acetone- d6) δ 7.70 – 7.60 (m, 6H), 7.47 – 7.36 (m, 9H), 5.94 (ddd, J J = 17.5, 10.8, 9.4 Hz, 1H), 5.10 – 5.04 (m, 2H), 3.89 – 3.83 (m, 1H), 3.15 – 3.09 (m, 1H), 1.85 – 1.72 (m, 1H), 1.51 – 1.41 (m, 1H), 1.16 – 1.05 (m, 10H), 0.69 (d, J J = 6.7 Hz, 3H), 0.50 (d, J J = 6.5 Hz, 3H) ppm. 13 C NMR (75 MHz, Acetone- d 6) δ 136.2, 134.5, 134.0, 129.7, 128.0, 117.8, 55.2, 54.9, 42.3, 41.3, 23.8, 23.3, 22.3, 20.1 ppm, as Figure 39 and Figure 40 shown.

[0068] Obviously, the above embodiments are merely examples given for clear illustration and not limitations on the implementation manners. For those of ordinary skill in the art, other different forms of changes or variations can be made based on the above description. It is not necessary and impossible to enumerate all the implementation manners here. And the obvious changes or variations derived therefrom are still within the protection scope of the present invention.

Claims

1. A method for synthesizing chiral homoallylic amine compounds, characterized in that, It includes the following steps: Under the protection of inert gas, dissolve a copper salt catalyst, a phosphine ligand, an imine, an allenylsilane and tert-butanol in tetrahydrofuran, and stir and mix them; Add phenylsilane and react at 20 - 30 °C for 12 - 20 hours; After the reaction is completed, add a saturated ammonium fluoride methanol solution to quench the reaction; Continue to stir the mixture, remove the solvent by rotary evaporation under reduced pressure, and separate the crude product by column chromatography to obtain the target product; The structure of the imine is shown in Formula (1): The structure of the allenylsilane is shown in Formula (2): The structure of the target product is shown in Formula (3): In Formulas (1) to (3), R is isobutyl, n-butyl, n-pentyl, cyclopropyl, 5-chloropentyl, benzyl, 2-phenylethyl, 2-phenylethenyl, phenyl, 4-methylphenyl, 4-fluorophenyl, 4-methoxyphenyl, 3-methoxyphenyl, 3-chlorophenyl, 2-fluorophenyl, 2-furyl, and [Si] is dimethylbenzylsilicon, diphenylmethylsilicon, triphenylsilicon.

2. The synthetic method of the chiral homoallylamine compound according to claim 1, wherein: The copper salt catalyst is copper acetate, and its dosage is 5 mol% of the molar amount of the reaction substrate.

3. The synthesis method of the chiral homoallylamine compound according to claim 1, wherein: The phosphine ligand is tricyclohexylphosphine, and its dosage is 12 mol% of the molar amount of the reaction substrate.

4. The method for synthesizing chiral homoallylic amine compounds according to claim 1, wherein: The imine is one of (S,E)-2-methyl-N-(3-methylbut-2-en-1-yl)propane-2-sulfonamide, (S,E)-N-butyl-2-methylpropane-2-sulfonamide, (S,E)-N-hexylidene-2-methylpropane-2-sulfonamide, (S,E)-N-(cyclopropylmethylene)-2-methylpropane-2-sulfonamide, (S,E)-N-(5-chloropent-2-en-1-yl)-2-methylpropane-2-sulfonamide, (S,E)-2-methyl-N-(2-phenylethylidene)propane-2-sulfonamide, (S,E)-2-methyl-N-(3-phenylpropylidene)propane-2-sulfonamide, (S)-2-methyl-N-((1E,2E)-3-phenylallylidene)propane-2-sulfonamide, (S,E)-N-benzylidene-2-methylpropane-2-sulfinamide, (S,E)-2-methyl-N-(4-methylbenzylidene)propane-2-sulfonamide, (S,E)-N-(4-fluorobenzylidene)-2-methylpropane-2-sulfonamide, (S,E)-N-(4-methoxybenzylidene)-2-methylpropane-2-sulfonamide, (S,E)-N-(3-methoxybenzylidene)-2-methylpropane-2-sulfonamide, (S,E)-N-(3-chlorobenzylidene)-2-methylpropane-2-sulfonamide, (S,E)-N-(2-fluorobenzylidene)-2-methylpropane-2-sulfonamide and (S,E)-N-(furan-2-ylmethylene)-2-methylpropane-2-sulfonamide.

5. The synthesis method of the chiral homoallylic amine compound according to claim 1, characterized in that: The allenylsilane is one of dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, dimethyl(benzyl)(prop-1,2-dien-1-yl)silane, methyl(diphenyl)(prop-1,2-dien-1-yl)silane and triphenyl(prop-1,2-dien-1-yl)silane.

6. The synthesis method of the chiral homoallylamine compound according to claim 1, wherein: The dosage of tert-butanol is 1.5 - 3.0 equivalents of the molar amount of the reaction substrate.

7. The synthesis method of the chiral homoallylic amine compound according to claim 1, wherein: The dosage of phenylsilane is 3 - 8 equivalents of the molar amount of the reaction substrate.

8. The synthesis method of a chiral homoallylamine compound according to claim 1, characterized in that: The column chromatography uses 200 - 300 mesh column chromatography silica gel, and the eluent is petroleum ether with a boiling range of 60 - 90 °C.

9. Use of a chiral homoallylamine compound according to any one of claims 1 - 8 in the preparation of an HIV protease inhibitor, an adrenergic receptor blocker or an anticancer drug.

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