A synthesis method of chiral homoallylamine compounds and its application

Abstract

The invention discloses a synthetic method and application of a chiral homoallylamine compound, belongs to the field of pharmaceutical intermediate synthesis technology, comprising the following steps: under inert gas protection, a copper salt catalyst, a phosphine ligand, an imine, a allenylsilane and tert-butyl alcohol are dissolved in tetrahydrofuran, and stirring is mixed; phenylsilane is added and reacted at 20 30 DEG C for 12 20 hours; after the reaction is completed, a saturated methanol solution of ammonium fluoride is added to quench the reaction; the mixture is continued to be stirred, the solvent is removed by vacuum rotary evaporation, and the crude product is separated and obtained by column chromatography to obtain the target product. The present invention uses THF as a solvent, and when copper acetate is used as a catalyst, a chiral homoallylamine compound can be obtained at room temperature with a yield of up to 78%, with a diastereoselectivity greater than 20: 1.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical intermediate synthesis, and in particular to a synthesis method and application of a chiral homoallylamine compound. Background Art

[0002] The synthesis of chiral homoallylamines has long been a key area of ​​research for organic and medicinal chemists. Homoallylamine structural fragments are widely found in natural products and pharmaceutical molecules, such as the HIV protease inhibitor amprenavir, the adrenergic receptor blocker manzocin C, the anticancer cryptotoxin 337, and the natural product hilarix. Furthermore, this structure plays an important role in asymmetric organic small molecule catalysis and is widely present in chiral organic small molecule catalysts and ligand structures.

[0003]

[0004] Furthermore, chiral homoallylamines, as important building blocks in medicinal chemistry and organic chemistry, play a pivotal role in natural product total synthesis and new drug development. For example, using chiral homoallylamines as key intermediates has enabled the total synthesis of the alkaloids chloranil and (+)-disoprofen, as well as the broad-spectrum antibiotic vancomycin.

[0005]

[0006] In addition to the above two points, chiral homoallylamine compounds can 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 aminodienes through olefin metathesis reaction.

[0007]

[0008] Chiral amine compounds are an important and widely used class of organic compounds that play a vital role in the fields of materials and medicinal chemistry. Among the numerous chiral amine compounds, chiral homoallylamine compounds are highly favored by chemists because they possess allyl groups and can be easily and efficiently derivatized into other functional groups. Currently, the common method for preparing homoallylamines is the nucleophilic addition of allyl metal reagents to imine compounds. However, the complex structure of allyl metal reagents is difficult to prepare, which to some extent limits the widespread application of this synthetic strategy. Therefore, it is urgent to develop new, simple and efficient methods for synthesizing chiral homoallylamine compounds with a wide range of substrates. Summary of the Invention

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

[0010] To solve the above technical problems, on the one hand, the present invention provides a method for synthesizing chiral homoallylamine compounds, comprising the following steps:

[0011] Under the protection of inert gas, the copper salt catalyst, phosphine ligand, imine, allenylsilane and tert-butyl alcohol are dissolved in tetrahydrofuran and stirred to mix;

[0012] Add phenylsilane and react at 20-30°C for 12-20 hours;

[0013] After the reaction was completed, saturated ammonium fluoride methanol solution was added to quench the reaction;

[0014] The mixture was stirred continuously, the solvent was removed by rotary evaporation under reduced pressure, and the crude product was separated by column chromatography to obtain the target product;

[0015] The structure of the imine is shown in formula (1):

[0016]

[0017] The structure of the allenylsilane is shown in formula (2):

[0018]

[0019] The structure of the target product is shown in formula (3):

[0020]

[0021] In formulas (1) to (3), R is isobutyl, n-butyl, n-pentyl, cyclopropyl, 5-chloropentyl, benzyl, 2-phenylethyl, 2-phenylvinyl, phenyl, 4-methylphenyl, 4-fluorophenyl, 4-methoxyphenyl, 3-methoxyphenyl, 3-chlorophenyl, 2-fluorophenyl, or 2-furyl, and [Si] is dimethylbenzylsilyl, diphenylmethylsilyl, or triphenylsilyl.

[0022] Preferably, the copper salt catalyst is copper acetate, and its amount is 5 mol % of the molar amount of the reaction substrate.

[0023] Preferably, the phosphine ligand is tricyclohexylphosphine, and its amount is 12 mol % of the molar amount of the reaction substrate.

[0024] Preferably, the imine is (S,E)-2-methyl-N-(3-methylbutylidene)propane-2-sulfonamide, (S,E)-N-butyl-2-methylpropane-2-sulfonamide, (S,E)-N-hexylene-2-methylpropane-2-sulfonamide, (S,E)-N-(cyclopropylmethylene)-2-methylpropane-2-sulfonamide, (S,E)-N-(5-chloropentylene)-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-sulfonamide, (S,E)-2-methyl-N-(4-methylbenzylidene)propane-2-sulfonamide, (S,E)-N-(4-fluorobenzylidene)-2-methylpropane-2-sulfonamide, (S,E)-N-(4-methoxybenzylidene)- One of 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.

[0025] Preferably, 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.

[0026] Preferably, the amount of tert-butanol used is 2.0 equivalents of the molar amount of the reaction substrate.

[0027] Preferably, the amount of phenylsilane used is 5.0 equivalents based on the molar amount of the reaction substrate.

[0028] Preferably, the column chromatography uses 200-300 mesh column chromatography silica gel, the eluent is petroleum ether, and the boiling range of petroleum ether is 60-90°C.

[0029] On the other hand, the present invention provides a use of a chiral homoallylamine compound in the preparation of HIV protease inhibitors, adrenaline receptor blockers or anticancer drugs.

[0030] The technical solution of the present invention has the following advantages:

[0031] This invention provides a method for synthesizing chiral homoallylamine compounds and their application. Under copper-catalyzed conditions, allene silane reacts with N-tert-butylsulfenyl imine to produce a set of diastereoisomers. When using tetrahydrofuran as a solvent and copper acetate as a catalyst, the chiral homoallylamine compounds can be obtained at room temperature with a yield of up to 78% and a diastereoselectivity greater than 20:1. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 The compound prepared in Example 1 1 H spectrum;

[0033] Figure 2 The compound prepared in Example 1 13 C spectrum;

[0034] Figure 3 The compound prepared in Example 2 1 H spectrum;

[0035] Figure 4 The compound prepared in Example 2 13 C spectrum;

[0036] Figure 5 The compound prepared in Example 3 1 H spectrum;

[0037] Figure 6 The compound prepared in Example 3 13 C spectrum;

[0038] Figure 7 The compound prepared in Example 4 1 H spectrum;

[0039] Figure 8 The compound prepared in Example 4 13 C spectrum;

[0040] Figure 9 The compound prepared in Example 5 1 H spectrum;

[0041] Figure 10 The compound prepared in Example 5 13 C spectrum;

[0042] Figure 11 The compound prepared in Example 6 1 H spectrum;

[0043] Figure 12 The compound prepared in Example 6 13 C spectrum;

[0044] Figure 13The compound prepared in Example 7 1 H spectrum;

[0045] Figure 14 The compound prepared in Example 7 13 C spectrum;

[0046] Figure 15 The compound prepared in Example 8 1 H spectrum;

[0047] Figure 16 The compound prepared in Example 8 13 C spectrum;

[0048] Figure 17 The compound prepared in Example 9 1 H spectrum;

[0049] Figure 18 The compound prepared in Example 9 13 C spectrum;

[0050] Figure 19 The compound prepared in Example 10 1 H spectrum;

[0051] Figure 20 The compound prepared in Example 10 13 C spectrum;

[0052] Figure 21 The compound prepared in Example 11 1 H spectrum;

[0053] Figure 22 The compound prepared in Example 11 13 C spectrum;

[0054] Figure 23 The compound prepared in Example 11 19 F spectrum;

[0055] Figure 24 The compound prepared in Example 12 1 H spectrum;

[0056] Figure 25 The compound prepared in Example 12 13 C spectrum;

[0057] Figure 26 The compound prepared in Example 13 1 H spectrum;

[0058] Figure 27 The compound prepared in Example 13 13 C spectrum;

[0059] Figure 28 The compound prepared in Example 14 1 H spectrum;

[0060] Figure 29 The compound prepared in Example 14 13 C spectrum;

[0061] Figure 30 The compound prepared in Example 15 1 H spectrum;

[0062] Figure 31 The compound prepared in Example 15 13 C spectrum;

[0063] Figure 32 The compound prepared in Example 15 19 F spectrum;

[0064] Figure 33 The compound prepared in Example 16 1 H spectrum;

[0065] Figure 34 The compound prepared in Example 16 13 C spectrum;

[0066] Figure 35 The compound prepared in Example 17 1 H spectrum;

[0067] Figure 36 The compound prepared in Example 17 13 C spectrum;

[0068] Figure 37 The compound prepared in Example 18 1 H spectrum;

[0069] Figure 38 The compound prepared in Example 18 13 C spectrum;

[0070] Figure 39 The compound prepared in Example 19 1 H spectrum;

[0071] Figure 40 The compound prepared in Example 19 13 C spectrum. DETAILED DESCRIPTION

[0072] The following examples are provided for a better understanding of the present invention and are not intended to limit the best mode of implementation. They do not limit the content and scope of protection of the present invention. Any product identical or similar to the present invention obtained by anyone under the guidance of the present invention or by combining the features of the present invention with other prior arts shall fall within the scope of protection of the present invention.

[0073] If no specific experimental steps or conditions are specified in the examples, the conventional experimental steps or conditions described in the literature in this field can be used. If the manufacturer of the reagents or instruments is not specified, they are all commercially available conventional reagents.

[0074] Detection methods:

[0075] Melting points were determined using a MEL-TEMP II or XT-4 binocular micromelting point apparatus, and the thermometer was uncalibrated. Nuclear magnetic resonance spectroscopy was performed using a BRUKER-ACF-300 or BRUKER-ACF-400 instrument, with TMS as the internal standard. High-resolution mass spectrometry (HRMS) was performed using an Agilent Q-TOF 6520 mass spectrometer, using either an electrospray ionization (ESI) source or an electron impact (EI) source. 1 H NMR data are chemical shifts (δ) in ppm and are expressed as CDCl3, CD3OD, DMSO- d 6, Or Acetone- d 6 is the solvent. The split peak type (s is singlet, d is doublet, t is triplet, dd is two doublets, brs is broad singlet, m is multiplet) and the coupling constant is in Hz. 13 The chemical shifts of C NMR are also in ppm and are based on the solvents CDCl3: δ = 77.16 ppm; CD3OD: δ = 48.80 ppm; DMSO- d 6: 39.52 ppm; Acetone- d 6: 206.26 ppm is the internal standard.

[0076] Thin layer chromatography (TLC) plates were directly purchased thin layer chromatography silica gel prefabricated plates GF 254 (Yantai Chemical Industry Research Institute), UV or potassium permanganate colorimetric developer; column chromatography used 200-300 mesh column chromatography silica gel (Qingdao Ocean Chemical Plant), dry packed column. Column chromatography solvent ratio is volume ratio ( v / v ), petroleum ether boiling range 60-90 °C. Unless otherwise specified, all reagents were commercially available chemically pure or analytically pure products.

[0077] General synthesis method of this application:

[0078]

[0079] Take a 10 mL clean Shrek tube and a magnetic particle, 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 %) was added and mixed to obtain a mixture. After three argon replacements, a mixture of imine (1, 0.5 mmol, 1.0 equiv), allenylsilane (2, 1.0 mmol, 2.0 equiv), and tert-butanol (29.6 mg, 0.4 mmol, 2.0 equiv) dissolved in tetrahydrofuran (0.8 mL) was slowly added to the mixture and stirred for 10 min (a green solution formed upon completion of stirring). Phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv) was then added, causing the reaction solution to turn yellow. The reaction system was then stirred at room temperature for 16 h. After completion of the reaction, saturated NH4F methanol solution (0.5 mL) was slowly added to quench the reaction (caution: gas evolution). The mixture was stirred for 30 min and then transferred to a 50 mL round-bottom flask. The solvent was removed by rotary evaporation under reduced pressure, and the crude product was separated by column chromatography to obtain the target product 3.

[0080] Example 1:

[0081]

[0082] In a clean 10 mL Shrek tube with a magnetic bar, copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %) and tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %) were weighed and mixed to obtain a mixture. After three argon replacements, a solution of (S,E)-2-methyl-N-(3-methylbutylidene)propane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butyl alcohol (29.6 mg, 0.4 mmol, 2.0 equiv) dissolved in tetrahydrofuran (0.8 mL) was slowly added to the mixture and stirred for 10 minutes (a green solution formed upon completion of stirring). Phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv) was then added, causing the reaction solution to turn yellow. The reaction system was then stirred at room temperature for 16 hours. After the reaction was complete, saturated NH4F methanol solution (0.5 mL) was slowly added to quench the reaction (caution: gas generation). The mixture was stirred for 30 min and then transferred to a 50 mL round-bottom flask. The solvent was removed by rotary evaporation under reduced pressure. The crude product was separated by column chromatography to obtain the desired product. The weight of the desired product was 133.5 mg, with a yield of 73% and diastereoselectivity. d.r. > 20:1, the product is a white solid; melting point 62-63 °C; 1 H NMR (300 MHz, CDCl3) δ 7.52 –7.48 (m, 2H), 7.37 – 7.35 (m, 3H), 5.76 (dt, J = 16.9, 10.4 Hz, 1H), 5.04 (d, J = 9.7 Hz, 1H), 4.90 (d, J = 16.7 Hz, 1H), 3.50 – 3.42 (m, 1H), 3.03 (d, J =6.7 Hz, 1H), 2.20 (dd, 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 = 6.5 Hz, 3H), 0.73(d, J = 6.4 Hz, 3H), 0.34 (s, 6H) ppm. 13C 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.

[0083] Example 2:

[0084]

[0085] In a clean 10 mL Shrek tube with a magnetic bar, copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %) and tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %) were weighed and mixed to obtain a mixture. After three argon replacements, a solution of (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) dissolved in tetrahydrofuran (0.8 mL) was slowly added to the mixture and stirred for 10 minutes (a green solution formed upon completion of stirring). Phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv) was then added, causing the reaction solution to turn yellow. The reaction system was then stirred at room temperature for 16 hours. After the reaction is complete, saturated NH4F methanol solution (0.5 mL) is slowly added to quench the reaction (caution: gas evolution). The mixture is stirred for another 30 minutes, then transferred to a 50 mL round-bottom flask. The solvent is removed by rotary evaporation under reduced pressure, and the crude product is isolated by column chromatography to obtain the desired product. The weight of the desired product is 131.9 mg, with a yield of 75% and a diastereoselectivity of >20:1. The product is a colorless oil. 1 H NMR (300 MHz, CDCl3) δ 7.51 – 7.48 (m, 2H), 7.38 –7.35 (m, 3H), 5.74 (dt, J = 16.7, 10.5 Hz, 1H), 5.04 (d, J = 10.1 Hz, 1H),4.91 (d, J = 17.0 Hz, 1H), 3.39 – 3.32 (m, 1H), 3.04 (d, 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 CNMR (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.

[0086] Example 3:

[0087]

[0088] In a clean 10 mL Shrek tube with a magnetic bar, copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %) and tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %) were weighed and mixed to obtain a mixture. After three argon replacements, a solution of (S,E)-N-hexylidene-2-methylpropane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butyl alcohol (29.6 mg, 0.4 mmol, 2.0 equiv) dissolved in tetrahydrofuran (0.8 mL) was slowly added to the mixture and stirred for 10 minutes (a green solution formed upon completion of stirring). Phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv) was then added, causing the reaction solution to turn yellow. The reaction system was then stirred at room temperature for 16 hours. After the reaction is complete, saturated NH4F methanol solution (0.5 mL) is slowly added to quench the reaction (caution: gas evolution). The mixture is stirred for another 30 minutes, then transferred to a 50 mL round-bottom flask. The solvent is removed by rotary evaporation under reduced pressure, and the crude product is isolated by column chromatography to obtain the desired product. The weight of the desired product is 115.8 mg, with a yield of 61% and a diastereoselectivity of >20:1. The product is a colorless oil. 1 H 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, e.g. Figure 5 and Figure 6 shown.

[0089] Example 4:

[0090]

[0091] In a clean 10 mL Shrek tube with a magnetic bar, copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %) and tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %) were weighed and mixed to obtain a mixture. After three argon replacements, a solution of (S,E)-N-(cyclopropylmethylene)-2-methylpropane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butyl alcohol (29.6 mg, 0.4 mmol, 2.0 equiv) dissolved in tetrahydrofuran (0.8 mL) was slowly added to the mixture and stirred for 10 minutes (a green solution formed upon completion of stirring). Phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv) was then added, causing the reaction solution to turn yellow. The reaction system was then stirred at room temperature for 16 hours. After the reaction is complete, saturated NH4F methanol solution (0.5 mL) is slowly added to quench the reaction (caution: gas evolution). The mixture is stirred for another 30 min, then transferred to a 50 mL round-bottom flask. The solvent is removed by rotary evaporation under reduced pressure, and the crude product is isolated by column chromatography to obtain the desired product. The weight of the desired product is 118.8 mg, the yield is 82%, and the diastereoselectivity dr > 20:1. The product is a colorless oil. 1 H NMR (300 MHz, CDCl3) δ 7.56 – 7.48 (m, 2H),7.38 – 7.33 (m, 3H), 5.93 (dt, J = 16.9, 10.4 Hz, 1H), 5.06 (dd, J = 10.1,2.1 Hz, 1H), 4.90 (dd, J = 16.9, 1.6 Hz, 1H), 3.21 (d, J = 5.8 Hz, 1H), 2.65(ddd, J = 9.4, 5.8, 3.6 Hz, 1H), 2.39 (dd, 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. 13C 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.

[0092] Example 5:

[0093]

[0094] In a clean 10 mL Shrek tube with a magnetic bar, copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %) and tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %) were weighed and mixed to obtain a mixture. After three argon replacements, a solution of (S,E)-N-(5-chloropentylidene)-2-methylpropane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butyl alcohol (29.6 mg, 0.4 mmol, 2.0 equiv) dissolved in tetrahydrofuran (0.8 mL) was slowly added to the above mixture and stirred for 10 minutes (a green solution formed upon completion of stirring). Phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv) was then added, causing the reaction solution to turn yellow. The reaction system was then stirred at room temperature for 16 hours. After the reaction is complete, saturated NH4F methanol solution (0.5 mL) is slowly added to quench the reaction (caution: gas evolution). The mixture is stirred for another 30 min, then transferred to a 50 mL round-bottom flask. The solvent is removed by rotary evaporation under reduced pressure, and the crude product is isolated by column chromatography to obtain the desired product. The weight of the desired product is 144.0 mg, the yield is 72%, and the diastereoselectivity dr > 20:1. The product is a colorless oil. 1 H NMR (300 MHz, Acetone- d 6) δ 7.60 – 7.57 (m,2H), 7.41 – 7.37 (m, 3H), 5.83 (dt, J = 16.8, 10.5 Hz, 1H), 5.02 (dd, J =10.1, 2.3 Hz, 1H), 4.94 (dd, J = 16.9, 2.1 Hz, 1H), 3.50 (td, J= 6.7, 1.4Hz, 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.

[0095] Example 6:

[0096]

[0097] In a clean 10 mL Shrek tube with a magnetic bar, copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %) and tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %) were weighed and mixed to obtain a mixture. After three argon replacements, a solution of (S,E)-2-methyl-N-(2-phenylethylidene)propane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butyl alcohol (29.6 mg, 0.4 mmol, 2.0 equiv) dissolved in tetrahydrofuran (0.8 mL) was slowly added to the mixture and stirred for 10 minutes (a green solution formed upon completion of stirring). Phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv) was then added, causing the reaction solution to turn yellow. The reaction system was then stirred at room temperature for 16 hours. After the reaction is complete, saturated NH4F methanol solution (0.5 mL) is slowly added to quench the reaction (caution: gas evolution). The mixture is stirred for another 30 min, then transferred to a 50 mL round-bottom flask. The solvent is removed by rotary evaporation under reduced pressure, and the crude product is isolated by column chromatography to obtain the desired product. The weight of the desired product is 111.9 mg, with a yield of 56% and a diastereoselectivity of dr = 11:1. The product is a colorless oil. 1H 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 = 17.0, 10.3 Hz, 1H),5.10 (dd, J = 10.2, 2.0 Hz, 1H), 4.96 (dd, J = 17.1, 2.0 Hz, 1H), 3.75 – 3.65(m, 1H), 3.10 (d, J = 5.0 Hz, 1H), 2.96 (dd, J = 13.5, 3.7 Hz, 1H), 2.68 (dd, J = 13.5, 9.3 Hz, 1H), 2.58 (dd, J = 10.4, 4.9 Hz, 1H), 0.98 (s, 9H), 0.39 (s, 3H), 0.35 (s, 3H) ppm. 13 C 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, e.g. Figure 11 and Figure 12 shown.

[0098] Example 7:

[0099]

[0100] In a clean 10 mL Shrek tube with a magnetic bar, copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %) and tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %) were weighed and mixed to obtain a mixture. After three argon replacements, a solution of (S,E)-2-methyl-N-(3-phenylpropylidene)propane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butyl alcohol (29.6 mg, 0.4 mmol, 2.0 equiv) dissolved in tetrahydrofuran (0.8 mL) was slowly added to the mixture and stirred for 10 minutes (a green solution formed upon completion of stirring). Phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv) was then added, causing the reaction solution to turn yellow. The reaction system was then stirred at room temperature for 16 hours. After the reaction is complete, saturated NH4F methanol solution (0.5 mL) is slowly added to quench the reaction (caution: gas evolution). The mixture is stirred for another 30 min, then transferred to a 50 mL round-bottom flask. The solvent is removed by rotary evaporation under reduced pressure, and the crude product is isolated by column chromatography to obtain the desired product. The weight of the desired product is 109.6 mg, with a yield of 53% and a diastereoselectivity of dr = 11:1. The product is a colorless oil. 1 H 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 =16.8, 10.5 Hz, 1H), 5.05 (dd, J = 10.0, 2.1 Hz, 1H), 4.93 (dd, J = 16.7, 2.1Hz, 1H), 3.44 – 3.36 (m, 1H), 3.15 (d, J = 7.7 Hz, 1H), 2.82 – 2.75 (m, 1H), 2.65 – 2.55 (m, 1H), 2.16 (dd, 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 C 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.

[0101] Example 8:

[0102]

[0103] In a clean 10 mL Shrek tube with a magnetic bar, copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %) and tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %) were weighed and mixed to obtain a mixture. After three argon replacements, a solution of (S)-2-methyl-N-((1E,2E)-3-phenylallylidene)propane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butyl alcohol (29.6 mg, 0.4 mmol, 2.0 equiv) dissolved in tetrahydrofuran (0.8 mL) was slowly added to the above mixture and stirred for 10 minutes (a green solution formed upon completion of stirring). Phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv) was then added, causing the reaction solution to turn yellow. The reaction system was then stirred at room temperature for 16 hours. After completion, saturated NH4F methanol solution (0.5 mL) was slowly added to quench the reaction (caution: gas evolution). The mixture was stirred for another 30 minutes before being transferred to a 50 mL round-bottom flask. The solvent was removed by rotary evaporation under reduced pressure, and the crude product was isolated by column chromatography to obtain the desired product. The weight of the desired product was 129.6 mg, with a yield of 63% and a diastereoselectivity of dr = 2:1. The product was obtained as a colorless oil. 1 H NMR (300 MHz, Acetone- d 6) δ 7.59– 7.56 (m, 2H), 7.41 – 7.32 (m, 8H), 6.46 (dd, J = 15.8, 0.8 Hz, 1H), 6.30(dd, J = 15.8, 7.9 Hz, 1H), 5.92 (dt, J = 16.9, 10.5 Hz, 1H), 5.09 (dd, J=10.2, 2.2 Hz, 1H), 5.01 (dd, J = 16.9, 2.2 Hz, 1H), 4.09 (dd, J = 8.0, 4.5Hz, 1H), 2.56 (dd, J = 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, e.g. Figure 15 and Figure 16 shown.

[0104] Example 9:

[0105]

[0106] In a clean 10 mL Shrek tube with a magnetic bar, copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %) and tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %) were weighed and mixed to obtain a mixture. After three argon replacements, a solution of (S,E)-N-benzylidene-2-methylpropane-2-sulfenamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butyl alcohol (29.6 mg, 0.4 mmol, 2.0 equiv) dissolved in tetrahydrofuran (0.8 mL) was slowly added to the mixture and stirred for 10 minutes (a green solution formed upon completion of stirring). Phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv) was then added, causing the reaction solution to turn yellow. The reaction system was then stirred at room temperature for 16 hours. After the reaction is complete, saturated NH4F methanol solution (0.5 mL) is slowly added to quench the reaction (caution: gas evolution). The mixture is stirred for another 30 min, then transferred to a 50 mL round-bottom flask. The solvent is removed by rotary evaporation under reduced pressure, and the crude product is isolated by column chromatography to obtain the desired product. The yield of the desired product is 115.7 mg, with a diastereoselectivity of 10:1 and a diastereoselectivity of 10:1. The product is obtained as a colorless oil. 1H 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 = 16.9, 10.1 Hz, 1H), 5.18 (d, J = 10.1 Hz, 1H), 5.07 (d, J = 16.9 Hz,1H), 4.71 – 4.64 (m, 1H), 3.60 (d, 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 C 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.

[0107] Example 10:

[0108]

[0109] In a clean 10 mL Shrek tube with a magnetic bar, copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %) and tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %) were weighed and mixed to obtain a mixture. After three argon replacements, a solution of (S,E)-2-methyl-N-(4-methylbenzylidene)propane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butyl alcohol (29.6 mg, 0.4 mmol, 2.0 equiv) dissolved in tetrahydrofuran (0.8 mL) was slowly added to the mixture and stirred for 10 minutes (a green solution formed upon completion of stirring). Phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv) was then added, causing the reaction solution to turn yellow. The reaction system was then stirred at room temperature for 16 hours. After the reaction is complete, saturated NH4F methanol solution (0.5 mL) is slowly added to quench the reaction (caution: gas evolution). The mixture is stirred for another 30 minutes, then transferred to a 50 mL round-bottom flask. The solvent is removed by rotary evaporation under reduced pressure, and the crude product is isolated by column chromatography to obtain the desired product. The yield of the desired product is 155.9 mg, with a diastereoselectivity of 9:1 and a diastereoselectivity of 9:1. The product is obtained as 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.

[0110] Example 11:

[0111]

[0112] In a clean 10 mL Shrek tube with a magnetic bar, copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %) and tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %) were weighed and mixed to obtain a mixture. After three argon replacements, a solution of (S,E)-N-(4-fluorobenzylidene)-2-methylpropane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butyl alcohol (29.6 mg, 0.4 mmol, 2.0 equiv) dissolved in tetrahydrofuran (0.8 mL) was slowly added to the mixture and stirred for 10 minutes (a green solution formed upon completion of stirring). Phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv) was then added, causing the reaction solution to turn yellow. The reaction system was then stirred at room temperature for 16 hours. After the reaction is complete, saturated NH4F methanol solution (0.5 mL) is slowly added to quench the reaction (caution: gas evolution). The mixture is stirred for another 30 minutes, then transferred to a 50 mL round-bottom flask. The solvent is removed by rotary evaporation under reduced pressure, and the crude product is isolated by column chromatography to obtain the desired product. The desired product weighs 135.2 mg, with a yield of 67% and a diastereoselectivity of 9:1. The product is obtained as a colorless oil. 1 H NMR (300 MHz, CDCl3) δ 7.47 – 7.44 (m, 2H),7.39 – 7.36 (m, 3H), 7.07 (t, J = 7.0 Hz, 2H), 6.94 (t, J = 8.5 Hz, 2H), 5.73(dt, J = 16.0, 10.5 Hz, 1H), 5.09 (d, J = 10.2 Hz, 1H), 4.98 (d, 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, as Figure 21 、 Figure 22 and Figure 23 shown.

[0113] Example 12:

[0114]

[0115] In a clean 10 mL Shrek tube with a magnetic bar, copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %) and tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %) were weighed and mixed to obtain a mixture. After three argon replacements, a solution of (S,E)-N-(4-methoxybenzylidene)-2-methylpropane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butyl alcohol (29.6 mg, 0.4 mmol, 2.0 equiv) dissolved in tetrahydrofuran (0.8 mL) was slowly added to the above mixture and stirred for 10 minutes (a green solution formed upon completion of stirring). Phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv) was then added, causing the reaction solution to turn yellow. The reaction system was then stirred at room temperature for 16 hours. After the reaction is complete, saturated NH4F methanol solution (0.5 mL) is slowly added to quench the reaction (caution: gas evolution). The mixture is stirred for another 30 minutes, then transferred to a 50 mL round-bottom flask. The solvent is removed by rotary evaporation under reduced pressure, and the crude product is isolated by column chromatography to obtain the desired product. The weight of the desired product is 137.2 mg, with a yield of 66% and a diastereoselectivity of 7:1. The product is obtained as 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.

[0116] Example 13:

[0117]

[0118] In a clean 10 mL Shrek tube with a magnetic bar, copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %) and tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %) were weighed and mixed to obtain a mixture. After three argon replacements, a solution of (S,E)-N-(3-methoxybenzylidene)-2-methylpropane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butyl alcohol (29.6 mg, 0.4 mmol, 2.0 equiv) dissolved in tetrahydrofuran (0.8 mL) was slowly added to the mixture and stirred for 10 minutes (a green solution formed upon completion of stirring). Phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv) was then added, causing the reaction solution to turn yellow. The reaction system was then stirred at room temperature for 16 hours. After the reaction is complete, saturated NH4F methanol solution (0.5 mL) is slowly added to quench the reaction (caution: gas evolution). The mixture is stirred for another 30 minutes, then transferred to a 50 mL round-bottom flask. The solvent is removed by rotary evaporation under reduced pressure, and the crude product is isolated by column chromatography to obtain the desired product. The weight of the desired product is 99.8 mg, with a yield of 48% and a diastereoselectivity of dr = 13:1. The product is a colorless oil. 1 H NMR (300 MHz, CDCl3) δ 7.49 – 7.45 (m,2H), 7.38 – 7.35 (m, 3H), 7.18 (t, J = 7.9 Hz, 1H), 6.76 (dd, J = 14.1, 8.0Hz, 2H), 6.65 (s, 1H), 5.79 (dt, J = 16.6, 10.4 Hz, 1H), 5.08 (d, J = 10.1Hz, 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, e.g. Figure 26 and Figure 27 shown.

[0119] Example 14:

[0120]

[0121] In a clean 10 mL Shrek tube with a magnetic bar, copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %) and tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %) were weighed and mixed to obtain a mixture. After three argon replacements, a solution of (S,E)-N-(3-chlorobenzylidene)-2-methylpropane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butyl alcohol (29.6 mg, 0.4 mmol, 2.0 equiv) dissolved in tetrahydrofuran (0.8 mL) was slowly added to the mixture and stirred for 10 minutes (a green solution formed upon completion of stirring). Phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv) was then added, causing the reaction solution to turn yellow. The reaction system was then stirred at room temperature for 16 hours. After the reaction is complete, saturated NH4F methanol solution (0.5 mL) is slowly added to quench the reaction (caution: gas evolution). The mixture is stirred for another 30 minutes, then transferred to a 50 mL round-bottom flask. The solvent is removed by rotary evaporation under reduced pressure, and the crude product is isolated by column chromatography to obtain the desired product. The desired product weighs 136.5 mg, with a yield of 65% and a diastereoselectivity of dr = 14:1. The product is a colorless oil. 1H 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 = 16.7, 10.5Hz, 1H), 4.97 – 4.86 (m, 2H), 4.54 – 4.47 (m, 1H), 2.80 (dd, J = 11.0, 6.7Hz, 1H), 1.04 (s, 9H), 0.19 (s, 3H), 0.18 (s, 3H) ppm. 13 C 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, e.g. Figure 28 and Figure 29 shown.

[0122] Example 15:

[0123]

[0124] In a clean 10 mL Shrek tube with a magnetic bar, copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %) and tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %) were weighed and mixed to obtain a mixture. After three argon replacements, a solution of (S,E)-N-(2-fluorobenzylidene)-2-methylpropane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butyl alcohol (29.6 mg, 0.4 mmol, 2.0 equiv) dissolved in tetrahydrofuran (0.8 mL) was slowly added to the above mixture and stirred for 10 minutes (a green solution formed upon completion of stirring). Phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv) was then added, causing the reaction solution to turn yellow. The reaction system was then stirred at room temperature for 16 hours. After the reaction is complete, saturated NH4F methanol solution (0.5 mL) is slowly added to quench the reaction (caution: gas evolution). The mixture is stirred for another 30 min, then transferred to a 50 mL round-bottom flask. The solvent is removed by rotary evaporation under reduced pressure, and the crude product is isolated by column chromatography to obtain the desired product. The desired product weighs 60.5 mg, with a yield of 30% and a diastereoselectivity of dr = 10:1. 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 =16.8, 10.3 Hz, 1H), 4.93 (dd, J = 10.1, 1.8 Hz, 1H), 4.84 (dd, J = 16.9, 1.8Hz, 1H), 4.60 (t, J = 9.1 Hz, 1H), 3.60 (d, J = 9.9 Hz, 1H), 2.66 (dd, 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 F NMR (282 MHz, CDCl3) δ – 116.21 ppm, as Figure 30 、 Figure 31 and Figure 32 shown.

[0125] Example 16:

[0126]

[0127] In a clean 10 mL Shrek tube with a magnetic bar, copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %) and tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %) were weighed and mixed to obtain a mixture. After three argon replacements, a solution of (S,E)-N-(furan-2-ylmethylene)-2-methylpropane-2-sulfonamide, dimethyl(phenyl)(prop-1,2-dien-1-yl)silane, and tert-butyl alcohol (29.6 mg, 0.4 mmol, 2.0 equiv) dissolved in tetrahydrofuran (0.8 mL) was slowly added to the mixture and stirred for 10 minutes (a green solution formed upon completion of stirring). Phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv) was then added, causing the reaction solution to turn yellow. The reaction system was then stirred at room temperature for 16 hours. After the reaction is complete, saturated NH4F methanol solution (0.5 mL) is slowly added to quench the reaction (caution: gas evolution). The mixture is stirred for another 30 minutes, then transferred to a 50 mL round-bottom flask. The solvent is removed by rotary evaporation under reduced pressure, and the crude product is isolated by column chromatography to obtain the desired product. The weight of the desired product is 138.9 mg, with a yield of 74% and a diastereoselectivity of > 20:1. The product is a colorless oil. 1 H 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 = 3.3, 0.7 Hz, 1H), 5.97 (dt, J = 17.0, 10.4 Hz, 1H), 5.05 (dd, J =10.2, 2.2 Hz, 1H), 4.96 (ddd, J = 17.0, 2.2, 0.8 Hz, 1H), 4.54 – 4.50 (m,1H), 3.95 (d, J = 8.1 Hz, 1H), 2.66 (dd, J = 10.7, 4.9 Hz, 1H), 1.07 (s, 9H), 0.18 (s, 3H), 0.13 (s, 3H) ppm. 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, e.g. Figure 33 and Figure 34 shown.

[0128] Example 17:

[0129]

[0130] In a clean 10 mL Shrek tube with a magnetic bar, copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %) and tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %) were weighed and mixed to obtain a mixture. After three argon replacements, a solution of (S,E)-2-methyl-N-(3-methylbutylidene)propane-2-sulfonamide, dimethyl(benzyl)(prop-1,2-dien-1-yl)silane, and tert-butyl alcohol (29.6 mg, 0.4 mmol, 2.0 equiv) dissolved in tetrahydrofuran (0.8 mL) was slowly added to the mixture and stirred for 10 minutes (a green solution formed upon completion of stirring). Phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv) was then added, causing the reaction solution to turn yellow. The reaction system was then stirred at room temperature for 16 hours. After the reaction is complete, saturated NH4F methanol solution (0.5 mL) is slowly added to quench the reaction (caution: gas evolution). The mixture is stirred for another 30 minutes, then transferred to a 50 mL round-bottom flask. The solvent is removed by rotary evaporation under reduced pressure, and the crude product is isolated by column chromatography to obtain the desired product. The desired product weighs 123.4 mg, with a yield of 65% and a diastereoselectivity of > 20:1. The product is obtained as a white solid. 1 H 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 = 17.1, 10.6 Hz, 1H),5.28 (d, J = 10.1 Hz, 1H), 5.15 (d, J = 16.8 Hz, 1H), 3.80 – 3.71 (m, 1H), 3.35 (d, 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 C 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, as Figure 35 and Figure 36 shown.

[0131] Example 18:

[0132]

[0133] In a clean 10 mL Shrek tube with a magnetic bar, copper acetate (2.0 mg, 0.01 mmol, 5.0 mol %) and tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %) were weighed and mixed to obtain a mixture. After three argon replacements, a solution of (S,E)-2-methyl-N-(3-methylbutylidene)propane-2-sulfonamide, methyl(diphenyl)(prop-1,2-dien-1-yl)silane, and tert-butyl alcohol (29.6 mg, 0.4 mmol, 2.0 equiv) dissolved in tetrahydrofuran (0.8 mL) was slowly added to the mixture and stirred for 10 minutes (a green solution formed upon completion of stirring). Phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv) was then added, causing the reaction solution to turn yellow. The reaction system was then stirred at room temperature for 16 hours. After the reaction, saturated NH4F methanol solution (0.5 mL) was slowly added to quench the reaction (caution: gas evolution). The mixture was stirred for another 30 min, then transferred to a 50 mL round-bottom flask. The solvent was removed by rotary evaporation under reduced pressure, and the crude product was isolated by column chromatography to obtain the desired product. The weight of the desired product was 162.5 mg, with a yield of 76% and a diastereoselectivity of > 20:1. The product was obtained as a white solid. 1 H NMR (300 MHz, Acetone- d6) δ 7.65 – 7.61 (m,4H), 7.42 – 7.35 (m, 6H), 5.91 (dt, J = 16.9, 10.4 Hz, 1H), 5.01 (dd, J =10.1, 2.3 Hz, 1H), 4.91 (d, J = 2.1 Hz, 1H), 4.85 (d, 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, e.g. Figure 37 and Figure 38 shown.

[0134] Example 19:

[0135]

[0136] mol %), tricyclohexylphosphine (6.7 mg, 0.012 mmol, 12 mol %), and mixed to obtain a mixture. After purging the atmosphere with argon three times, a solution of (S,E)-2-methyl-N-(3-methylbutylidene)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 stirred for 10 min (a green solution formed upon completion of stirring). Phenylsilane (PhSiH3, 78 mL, 1.0 mmol, 5.0 equiv) was then added, causing the reaction solution to turn yellow. The reaction system was then stirred at room temperature for 16 h. After completion of the reaction, saturated NH4F methanol solution (0.5 mL) was slowly added to quench the reaction (caution: gas evolution). The mixture was stirred for another 30 minutes and then transferred to a 50 mL round-bottom flask. The solvent was removed by rotary evaporation under reduced pressure. The crude product was isolated by column chromatography to obtain the desired product. The yield was 72% (176.3 mg) with a diastereoselectivity of > 20:1. The product was obtained as a colorless oil. 1 H NMR (300 MHz, Acetone- d 6) δ 7.70 – 7.60(m, 6H), 7.47 – 7.36 (m, 9H), 5.94 (ddd, 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 = 6.7 Hz, 3H), 0.50 (d, 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, such as Figure 39 and Figure 40 shown.

[0137] Obviously, the above embodiments are merely examples for clarity of explanation and are not intended to limit the implementation methods. Those skilled in the art will readily appreciate that other variations or modifications based on the above descriptions are possible. It is not necessary and impossible to enumerate all implementation methods here. Obvious variations or modifications arising therefrom remain within the scope of protection of the present invention.

Claims

1. A method for synthesizing chiral homoallylamine compounds, characterized in that: The following steps are involved: Under the protection of inert gas, the copper salt catalyst, phosphine ligand, imine, allenylsilane and tert-butyl alcohol are dissolved in tetrahydrofuran and stirred to mix; Add phenylsilane and react at 20-30°C for 12-20 hours; After the reaction was completed, saturated ammonium fluoride methanol solution was added to quench the reaction; The mixture was stirred continuously, the solvent was removed by rotary evaporation under reduced pressure, and the crude product was separated 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-pentyl, cyclopropyl, 2-phenylethyl, phenyl, 4-fluorophenyl, 2-fluorophenyl, or 2-furyl, and [Si] is dimethylbenzylsilyl or diphenylmethylsilyl; The copper salt catalyst is copper acetate, and its amount is 5 mol% of the molar amount of the reaction substrate; The phosphine ligand is tricyclohexylphosphine, and its usage is 12 mol% of the molar amount of the reaction substrate.

2. The method for synthesizing chiral homoallylamine compounds according to claim 1, wherein: The imine is one of (S,E)-2-methyl-N-(3-methylbutylidene)propane-2-sulfenamide, (S,E)-N-hexylene-2-methylpropane-2-sulfenamide, (S,E)-N-(cyclopropylmethylene)-2-methylpropane-2-sulfenamide, (S,E)-2-methyl-N-(3-phenylpropylidene)propane-2-sulfenamide, (S,E)-N-benzylidene-2-methylpropane-2-sulfenamide, (S,E)-N-(4-fluorobenzylidene)-2-methylpropane-2-sulfenamide, (S,E)-N-(2-fluorobenzylidene)-2-methylpropane-2-sulfenamide and (S,E)-N-(furan-2-ylmethylene)-2-methylpropane-2-sulfenamide.

3. The method for synthesizing chiral homoallylamine compounds according to claim 1, wherein: The amount of tert-butanol used is 1.5-3.0 equivalents of the molar amount of the reaction substrate.

4. The method for synthesizing chiral homoallylamine compounds according to claim 1, wherein: The amount of the phenylsilane used is 3-8 equivalents of the molar amount of the reaction substrate.

5. The method for synthesizing a chiral homoallylamine compound according to claim 1, wherein: The column chromatography adopts 200-300 mesh column chromatography silica gel, and the eluent is petroleum ether, and the boiling range of petroleum ether is 60-90°C.

Images