Silicon-containing three-dimensional center silacyclohexylenone skeleton borane as well as preparation method and application thereof

Abstract

The invention relates to silicon-containing three-dimensional center silacyclohexenone skeleton borane as well as a preparation method and application thereof, the silicon-containing three-dimensional center silacyclohexenone skeleton borane has a structural formula as shown in a formula (I), and substituent groups R1 and R2 are respectively aryl or alkyl. According to the synthesis method of the compound, metal copper is used as a catalyst, and under the combined action of a chiral phosphine ligand and alkali, silacyclohexenone and a diborane compound are subjected to a hydroboration reaction to synthesize the compound. The synthesis method provided by the invention is simple to operate, mild in reaction condition, high in substrate universality, high in product yield and high in enantioselectivity. The synthesized compound is an important silicon-containing stereo center heterocyclic compound and can be widely applied to various fields of organic synthesis, medicine, material chemistry and fine chemical engineering.

Description

Technical Field

[0001] This invention relates to the field of catalytic chemistry, specifically to a silicon-containing stereocenter siloxane-hexene ketone skeleton borane, its preparation method, and its applications. Background Technology

[0002] Organosilicon compounds containing silicon stereocenters have attracted widespread attention due to their unique structure, physicochemical properties, and biological characteristics, and have been applied in numerous fields, such as bioactive molecules, advanced materials, mechanism probes, chiral auxiliaries, and chiral ligands. In recent years, researchers have developed an increasing number of transition metal-catalyzed and organocatalytic methods to construct silicon stereocenters, such as asymmetric hydrosilylation, asymmetric ring-opening of silanes, desymmetric arylation, and carbene-catalyzed desymmetric benzoin reaction of silydinium. However, these methods often require extreme conditions such as high temperature, high pressure, strong acids, and strong bases, which are not only complex to operate but also prone to side reactions, reducing the yield and purity of the target product. Furthermore, due to the lack of effective stereocontrol methods, the enantioselectivity of the synthesized products is low, making it difficult to meet the demand for high-purity chiral compounds in fine chemical and pharmaceutical synthesis fields.

[0003] Furthermore, most existing synthetic methods rely on specific substrates or complex synthetic routes, making large-scale production difficult. This significantly limits the widespread adoption and use of silicon-steric-center siloxane skeleton boranes in practical applications.

[0004] Currently, there are no reported synthetic methods for synthesizing silicon-stereocentric siloxane skeleton boranes via transition metal-catalyzed asymmetric hydroboration reactions. Developing a simple, efficient, mild, and highly enantioselective method for synthesizing silicon-stereocentric siloxane skeleton boranes is of great significance for promoting the development of organic synthesis, pharmaceutical research and development, and fine chemicals. Summary of the Invention

[0005] The purpose of this invention is to address the current lack of synthetic methods for synthesizing silicon-stereocentric siloxane skeleton boranes via transition metal catalysis. This invention provides a silicon-stereocentric siloxane skeleton borane, its preparation method, and its applications. The preparation method involves a transition metal-catalyzed asymmetric hydroboration reaction, which is simple, mild, and exhibits good yield and extremely high enantioselectivity. The obtained derivative contains multiple functional groups and multiple chiral centers, possessing potential biological activity. It can be widely used as a fine chemical intermediate in various organic reactions and drug synthesis, demonstrating considerable application value.

[0006] This invention is achieved through the following technical solution: In a first aspect, the present invention provides a silicon-containing stereocentric siloxane-hexenone skeleton borane having the structural formula shown in (I): In the formula, R 1 R 2 Each aryl group is independently selected from alkyl, aryl, or substituted aryl groups; the substitution is selected from alkyl, alkoxy, halogen, aryl, or heteroaryl groups.

[0007] Secondly, the present invention provides a method for preparing the above-mentioned silicon-stereocentric siloxane-containing skeletal borane, wherein the preparation method synthesizes the silicon-stereocentric siloxane-containing skeletal borane through a hydroboration reaction of siloxane and a diborane compound, as shown in the following reaction formula: The specific reaction steps are as follows: Under inert gas protection, siloxane, diborane compounds, transition metal catalysts, chiral phosphine ligands, and additives are mixed in a reaction medium and reacted. After the reaction is completed, extraction is performed, the organic phase is dried, and the solvent is removed by rotary evaporation. The crude product is purified by silica gel column chromatography to obtain the silicon-containing stereocenter siloxane skeleton borane.

[0008] The molar ratio of siloxane to diborane compounds is 1:1.2-1:1.5. Preferably, the concentration of the reactants siloxane and diborane compounds is 0.1-1.0 mol / L solution. Using siloxane and diborane compounds as raw materials, the reaction is easy to synthesize, simple to operate, convenient to post-process, and yields good yields and enantioselective products.

[0009] The transition metal catalyst is selected from one of copper tetraacetonitrile hexafluorophosphate, copper tetraacetonitrile tetrafluoroborate, cuprous chloride, copper acetate, and copper trifluoromethanesulfonate, and the amount used is 1%-10% of the molar amount of the silanecyclohexenone compound.

[0010] The chiral phosphine ligand is selected from one of the compounds with the structural formula shown in (II), and is used in an amount of 2-11% of the molar amount of siloxane. Using the complex formed in situ with the chiral phosphine ligand via a transition metal catalyst as a catalytic precursor is simple, the catalyst can be recycled, and the catalytic efficiency is high. It can synthesize silicon-stereocentric siloxane skeletal borane compounds with high yield and high enantioselectivity at room temperature. The additive is selected from one of potassium carbonate, potassium bicarbonate, sodium carbonate, sodium tert-butoxide, sodium tetraarylborate, cesium carbonate, triethylamine, N,N-diisopropylethylamine (DIPEA), and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The additive can control the stereoconfiguration of the product to obtain the target product with high enantioselectivity. The amount used is 10%-15% of the molar amount of silanecyclohexenone.

[0011] The reaction medium is selected from one of tetrahydrofuran, dichloromethane, toluene, and dioxane.

[0012] Preferably, the reaction temperature is 0-30 ℃ and the reaction time is 12-20 h.

[0013] Thirdly, the present invention provides the application of the above-mentioned silicon-containing stereocenter siloxane skeleton borane in drug synthesis, which can be used as an intermediate for silicon-containing drugs.

[0014] Compared with the prior art, the beneficial effects of the present invention are: This invention utilizes readily synthesizable siloxanes and diborane compounds as raw materials to efficiently synthesize a series of silicon-steric-center siloxane skeletal boranes via a transition metal-catalyzed asymmetric hydroboration reaction. The in-situ complex formed between the metal catalyst and a chiral phosphine ligand serves as the catalytic precursor. Additives are used to control the product's stereoconfiguration. The operation is simple, requiring only stirring at room temperature. The crude product is purified by rapid column chromatography followed by vacuum concentration to obtain a pure product. Post-processing is convenient, yielding a series of silicon-steric-center siloxanes with high yields and high enantioselectivity. This synthetic method is novel, simple to operate, and operates under mild reaction conditions, yielding target products with good yields and extremely high enantioselectivity. The obtained products can be widely used in various organic synthesis, pharmaceutical, materials chemistry, and fine chemical fields. For example, they are widely used as fine chemical intermediates in various organic reactions and drug synthesis, demonstrating considerable application value. Detailed Implementation

[0015] The present invention will be further described in detail below with reference to the embodiments. The raw materials used in the embodiments can be commercially available or prepared by conventional methods.

[0016] Example 1: Under a nitrogen atmosphere, phosphine ligands were added to a test tube. S,SPh-BPE (3.7 mg, 0.006 mmol), metal catalyst Cu(CH3CN)4PF6 (1.8 mg, 0.005 mmol), and 2.0 mL of dioxane solvent were added. After pre-stirring at room temperature for 30 min, diborane compound 5a (0.11 mmol), sodium tert-butoxide (0.04 mmol), and silanone compound 4a (0.1 mmol) were added sequentially. The reaction was stirred at room temperature for 17 h. After the reaction was completed by TLC, the mixture was extracted with ethyl acetate. The organic phase was dried and the solvent was removed by rotary evaporation. The crude product was purified by silica gel column chromatography to obtain 29.1 mg of white solid 6a, with a yield of 89% and 99%. ee . The physicochemical properties of this product are as follows: 1 H NMR (400 MHz, CDCl3): δ 7.58–7.56 (m, 2H), 7.41–7.36 (m, 3H), 7.07 (d, J = 14.4, 1H), 6.76 (d, J = 14.4, 1H), 2.84–2.71 (m,2H), 1.25–1.23 (m, 1H), 1.21 (d, J = 4.4, 12H), 0.51 (s, 3H); 13 C NMR (101MHz, CDCl3): δ 202.4, 146.8, 146.7, 135.0, 134.3, 130.0, 128.2, 83.6, 37.2,25.2, 24.8, -4.9; HRMS (ESI+) m / z : calcd for C 18 H 25 BO3Si [M+Na] + 350.1595,found: 350.1594; HPLC (Chiralpak OX, hexane / i -PrOH = 99.5 / 0.5 (v / v), flowrate = 0.5 mL / min, l = 254 nm, >99% ee ): t R = 54.532 min (major), 63.993 min (minor). Example 2: Under a nitrogen atmosphere, phosphine ligands were added to a test tube. S,S Ph-BPE (3.7 mg, 0.006 mmol), a metal catalyst Cu(CH3CN)4PF6 (1.8 mg, 0.005 mmol), and 2.0 mL of dioxane solvent were added. After pre-stirring at room temperature for 30 min, diborane compound 5a (0.11 mmol), sodium tert-butoxide (0.04 mmol), and silanone compound 4b (0.1 mmol) were added sequentially. The reaction was stirred at room temperature for 17 h. After the reaction was completed by TLC, the mixture was extracted with ethyl acetate. The organic phase was dried and the solvent was removed by rotary evaporation. The crude product was purified by silica gel column chromatography to obtain 29.4 mg of white solid 6b, with a yield of 86% and 99%. ee . The physicochemical properties of this product are as follows: 1 H NMR (400 MHz, CDCl3): δ 7.47 (d, J = 8.0, 2H), 7.21 (d, J = 7.6, 2H), 7.07 (d, J = 14.4, 1H), 6.74 (d, J = 14.0, 1H), 2.84–2.71 (m, 2H), 2.36 (s, 3H), 1.27–1.24 (m, 1H), 1.21 (d, J = 3.6, 12H), 0.50(s, 3H); 13 C NMR (101 MHz, CDCl3): δ 202.4, 147.0, 146.4, 139.9, 134.2, 131.2,129.0, 83.4, 37.2, 25.1, 24.7, 21.6, -5.0; HRMS (ESI+) m / z : calcd forC 19 H 27 BO3Si [M+Na] + 364.1751, found: 364.1758; HPLC (Chiralpak OX, hexane / i -PrOH = 99.5 / 0.5 (v / v), flow rate = 0.5 mL / min, l = 254 nm, 99% ee ): t R=57.198 min (major), 75.293 min (minor). Example 3: Under a nitrogen atmosphere, phosphine ligands were added to a test tube. S,S Ph-BPE (3.7 mg, 0.006 mmol), a metal catalyst Cu(CH3CN)4PF6 (1.8 mg, 0.005 mmol), and 2.0 mL of tetrahydrofuran solvent were added sequentially after pre-stirring at room temperature for 30 min. Then, a diborane compound 5a (0.11 mmol), sodium tert-butoxide (0.04 mmol), and a silanone compound 4c (0.1 mmol) were added. The reaction was stirred at room temperature for 17 h. After the reaction was completed as monitored by TLC, the mixture was extracted with ethyl acetate. The organic phase was dried, and the solvent was removed by rotary evaporation. The crude product was purified by silica gel column chromatography to obtain 31.5 mg of a white solid 6c, with yields of 88% and 99%. ee . The physicochemical properties of this product are as follows: 1 H NMR (400 MHz, CDCl3): 7.49 (d, J = 8.4, 2H), 7.05(d, J = 14.4, 1H), 6.93 (d, J = 8.4, 2H), 6.73 (d, J = 14.4, 1H), 3.82 (s,3H), 2.83–2.71 (m, 2H), 1.26–1.25 (m, 1H), 1.20 (d, J = 4.8, 12H), 0.48 (s, 3H); 13 C NMR (101 MHz, CDCl3): δ 202.6, 161.2, 147.3, 146.4, 135.8, 125.6,114.0, 83.5, 55.2, 37.3, 25.2, 24.8, -4.8; HRMS (ESI+) m / z : calcd forC 19 H 27 BO4Si [M+Na] + 380.1700, found: 380.1699; HPLC (Chiralpak OX, hexane / i-PrOH = 95 / 5 (v / v), flow rate = 0.5 mL / min, l = 214 nm, 99% ee ): t R = 26.395min (major), 28.615min (minor). Example 4: Under a nitrogen atmosphere, phosphine ligands were added to a test tube. S,S Ph-BPE (3.7 mg, 0.006 mmol), Cu(CH3CN)4PF6 (1.8 mg, 0.005 mmol) metal catalyst, and 2.0 mL dichloromethane solvent were added. After pre-stirring at room temperature for 30 min, diborane compound 5a (0.11 mmol), sodium tert-butoxide (0.04 mmol), and silanolone compound 4d (0.1 mmol) were added sequentially. The reaction was stirred at room temperature for 17 h. After the reaction was completed by TLC monitoring, the mixture was extracted with ethyl acetate. The organic phase was dried and the solvent was removed by rotary evaporation. The crude product was purified by silica gel column chromatography to obtain 25.0 mg of white solid 6d, with a yield of 65% and 99%. ee . The physicochemical properties of this product are as follows: 1 H NMR (400 MHz, CDCl3): δ 7.51 (d, J = 8.4, 2H), 7.41 (d, J = 8.4, 2H), 7.08 (d, J = 14.4, 1H), 6.74 (d, J = 14.0, 1H), 2.84–2.71 (m, 2H), 1.32 (s, 9H), 1.24–1.22 (m, 1H), 1.22 (d, J = 3.2, 12H), 0.49(s, 3H); 13 C NMR (101 MHz, CDCl3): δ 202.6, 153.1, 147.1, 146.6, 134.2, 131.4,125.2, 83.6, 37.3, 34.9, 31.3, 29.9, 25.2, 24.8, -4.7; HRMS (ESI+) m / z : calcdfor C 22 H 33 BO3Si [M+Na] +406.2221, found: 406.2224; HPLC (Chiralpak OX, hexane / i -PrOH = 95 / 5 (v / v), flow rate = 0.5 mL / min, l = 230 nm, >99% ee ): t R =22.315 min (major), 24.864 min (minor). Example 5: Under a nitrogen atmosphere, phosphine ligands were added to a test tube. S,S Ph-BPE (3.7 mg, 0.006 mmol), Cu(CH3CN)4PF6 (1.8 mg, 0.005 mmol) metal catalyst, and 2.0 mL dichloromethane solvent were added. After pre-stirring at room temperature for 30 min, diborane compound 5a (0.11 mmol), sodium tert-butoxide (0.04 mmol), and silanone compound 4e (0.1 mmol) were added sequentially. The reaction was stirred at room temperature for 17 h. After the reaction was completed by TLC monitoring, the mixture was extracted with ethyl acetate. The organic phase was dried and the solvent was removed by rotary evaporation. The crude product was purified by silica gel column chromatography to obtain 30.8 mg of white solid 6e, with a yield of 89% and 99%. ee . The physicochemical properties of this product are as follows: 1 H NMR (400 MHz, CDCl3): δ 7.55 (dd, J = 8.4, 6.0, 2H), 7.09 (d, J = 8.8, 1H), 7.04 (d, J = 14.8, 2H), 6.75 (d, J = 14.4, 1H),2.83–2.71 (m, 2H), 1.21–1.18 (m, 1H), 1.20 (d, J = 5.2, 12H), 0.50 (s, 3H); 13 C NMR (101 MHz, CDCl3): δ 202.3, 165.6, 163.1, 146.9, 146.4, 136.34, 136.26,130.52, 130.49, 115.6, 115.4, 83.6, 37.2, 25.2, 24.8, -4.9; 19F NMR (471 MHz, CDCl3): δ -110.40 (s); HRMS (ESI+) m / z : calcd for C 18 H 25 BFO3Si [M+Na] + 368.1500, found: 368.1504; HPLC (Chiralpak OX, hexane / i -PrOH = 99 / 1 (v / v), flow rate = 0.4 mL / min, l = 210 nm, >99% ee ): t R = 95.909 min. Example 6: Under a nitrogen atmosphere, phosphine ligands were added to a test tube. S,S Ph-BPE (3.7 mg, 0.006 mmol), Cu(CH3CN)4PF6 (1.8 mg, 0.005 mmol) metal catalyst, and 2.0 mL dichloromethane solvent were added. After pre-stirring at room temperature for 30 min, diborane compound 5a (0.11 mmol), sodium tert-butoxide (0.04 mmol), and silanone compound 4f (0.1 mmol) were added sequentially. The reaction was stirred at room temperature for 17 h. After the reaction was completed by TLC monitoring, the mixture was extracted with ethyl acetate. The organic phase was dried and the solvent was removed by rotary evaporation. The crude product was purified by silica gel column chromatography to obtain 23.9 mg of white solid 6f, with a yield of 66% and 99%. ee . The physicochemical properties of this product are as follows: 1 H NMR (400 MHz, CDCl3): δ 7.50 (d, J = 8.0, 2H), 7.36 (d, J = 8.4, 2H), 7.03 (d, J = 14.4, 1H), 6.75 (d, J = 14.0, 1H), 2.83–2.71 (m, 2H), 1.21 (d, J = 4.4, 12H), 1.21–1.18 (m, 1H), 0.50 (s, 3H); 13C NMR (101 MHz, CDCl3): δ 202.2, 147.0, 146.1, 136.5, 135.6, 133.3, 128.5, 83.7,37.1, 25.2, 24.8, -5.0; HRMS (ESI+) m / z : calcd for C 18 H 24 BClO3Si [M+Na] + 384.1205, found: 384.1213; HPLC (Chiralpak OX, hexane / i -PrOH = 99.5 / 0.5 (v / v), flow rate = 0.5 mL / min, l = 254 nm, >99% ee ): t R = 71.908 min. Example 7: Under a nitrogen atmosphere, phosphine ligands were added to a test tube. S,S Ph-BPE (3.7 mg, 0.006 mmol), Cu(CH3CN)4PF6 (1.8 mg, 0.005 mmol) metal catalyst, and 2.0 mL of dioxane solvent were added. After pre-stirring at room temperature for 30 min, diborane compound 5a (0.11 mmol), sodium tert-butoxide (0.04 mmol), and silanone compound 4 g (0.1 mmol) were added sequentially. The reaction was stirred at room temperature for 17 h. After the reaction was completed by TLC monitoring, the mixture was extracted with ethyl acetate. The organic phase was dried and the solvent was removed by rotary evaporation. The crude product was purified by silica gel column chromatography to obtain 6 g of 22.6 mg white solid, with a yield of 66% and 99%. ee . The physicochemical properties of this product are as follows: 1 H NMR (400 MHz, CDCl3): δ 7.50 (d, J = 7.2, 1H), 7.32 (t, J = 7.6, 1H), 7.19–7.18 (m, 2H), 7.16 (d, J = 14.4, 1H), 6.72 (d, J = 14.4, 1H), 2.84–2.66 (m, 2H), 2.48 (s, 3H), 1.38 (dd, J= 9.6, 4.0, 1H), 1.19 (d, J = 6.8, 12H), 0.55 (s, 3H); 13 C NMR (101 MHz, CDCl3): δ 202.3,148.0, 146.0, 144.0, 135.6, 133.1, 130.31, 130.26, 125.3, 83.5, 37.5, 25.1,24.8, 23.5, -3.6; HRMS (ESI+) m / z : calcd for C 19 H 27 BO3Si [M+K] + 380.1490,found: 380.1484; HPLC (Chiralpak OX, hexane / i -PrOH = 95 / 5 (v / v), flow rate =0.5 mL / min, l = 210 nm, >99% ee ): t R = 38.475 min (major), 40.378 min(minor). Example 8: Under a nitrogen atmosphere, phosphine ligands were added to a test tube. S,S Ph-BPE (3.7 mg, 0.006 mmol), Cu(CH3CN)4PF6 (1.8 mg, 0.005 mmol) metal catalyst, and 2.0 mL of dioxane solvent were added. After pre-stirring at room temperature for 30 min, diborane compound 5a (0.11 mmol), sodium tert-butoxide (0.04 mmol), and silanoxane compound 4h (0.1 mmol) were added sequentially. The reaction was stirred at room temperature for 17 h. After the reaction was completed by TLC, the mixture was extracted with ethyl acetate. The organic phase was dried and the solvent was removed by rotary evaporation. The crude product was purified by silica gel column chromatography to obtain 28.1 mg of white solid for 6 h, with a yield of 82% and 96%. ee . The physicochemical properties of this product are as follows: 1 H NMR (400 MHz, CDCl3): δ 7.38–7.36 (m, 2H), 7.30–7.22 (m, 2H), 7.08 (d, J = 14.4, 1H), 6.76 (d, J= 14.4, 1H), 2.84–2.71 (m,2H), 2.35 (s, 3H), 1.25–1.24 (m, 1H), 1.21 (d, J = 2.8 (12H), 0.50 (s, 3H); 13 C NMR (101 MHz, CDCl3): δ 202.5, 146.9, 146.6, 137.6, 134.9, 134.8, 131.3,130.8, 128.1, 83.5, 37.3, 25.2, 24.8, 21.6, -4.8; HRMS (ESI+) m / z : calcd forC 19 H 27 BO3Si [M+Na] + 364.1751, found: 364.1748; HPLC (Chiralpak OX, hexane / i -PrOH = 95 / 5 (v / v), flow rate = 0.5 mL / min, l = 230 nm, 96% ee ): t R = 15.217min (major), 16.315min (minor). Example 9: Under a nitrogen atmosphere, phosphine ligands were added to a test tube. S,S Ph-BPE (3.7 mg, 0.006 mmol), Cu(CH3CN)4PF6 (1.8 mg, 0.005 mmol) metal catalyst, and tetrahydrofuran solvent (2.0 mL) were added sequentially. After pre-stirring at room temperature for 30 min, diborane compound 5a (0.11 mmol), sodium tert-butoxide (0.04 mmol), and silanone compound 4i (0.1 mmol) were added. The reaction was stirred at room temperature for 17 h. After the reaction was completed by TLC monitoring, the mixture was extracted with ethyl acetate. The organic phase was dried and the solvent was removed by rotary evaporation. The crude product was purified by silica gel column chromatography to obtain 28.7 mg of colorless liquid 6i, with a yield of 80% and 99%. ee . The physicochemical properties of this product are as follows: 1 H NMR (400 MHz, CDCl3): δ 7.48 (d, J = 7.6, 1H), 7.39 (t, J= 8.0, 1H), 7.18 (d, J = 14.0, 1H), 6.97 (t, J = 7.2, 1H), 6.85(d, J = 8.4, 1H), 6.66 (d, J = 14.0, 1H), 3.82 (s, 3H), 2.84–2.68 (m, 2H), 1.42 (dd, J = 9.6, 4.0, 1H), 1.20 (d, J = 8.0, 12H), 0.47 (s, 3H); 13 C NMR (101 MHz, CDCl3): δ 202.8, 164.5, 148.7, 145.4, 136.0, 131.9, 122.7, 120.9,109.8, 83.4, 55.2, 37.5, 25.1, 24.8, -4.3; HRMS (ESI+) m / z : calcd forC 19 H 27 BO4Si [M+Na] + 380.1700, found: 380.1695; HPLC (Chiralpak OX, hexane / i -PrOH = 95 / 5 (v / v), flow rate = 0.5 mL / min, l = 210 nm, >99% ee ): t R = 17.890min (minor), 18.986min (major). Example 10: Under a nitrogen atmosphere, phosphine ligands were added to a test tube. S,SPh-BPE (3.7 mg, 0.006 mmol), Cu(CH3CN)4PF6 (1.8 mg, 0.005 mmol) metal catalyst, and tetrahydrofuran solvent (2.0 mL) were added sequentially. After pre-stirring at room temperature for 30 min, diborane compound 5a (0.11 mmol), sodium tert-butoxide (0.04 mmol), and silanone compound 4j (0.1 mmol) were added. The reaction was stirred at room temperature for 17 h. After the reaction was completed by TLC monitoring, the mixture was extracted with ethyl acetate. The organic phase was dried and the solvent was removed by rotary evaporation. The crude product was purified by silica gel column chromatography to obtain 30.4 mg of colorless liquid 6j, with yields of 85% and 96%. ee . The physicochemical properties of this product are as follows: 1 H NMR (400 MHz, CDCl3): δ 7.48 (dd, J = 7.2, 1.6,1H), 7.42–7.37 (m, 1H), 7.18 (d, J = 14.4, 1H), 6.97 (t, J = 7.2, 1H), 6.85(d, J = 8.0, 1H), 6.66 (d, J = 14.4, 1H), 3.82 (s, 3H), 2.84–2.68 (m, 2H), 1.42 (dd, J = 9.6, 4.0, 1H), 1.20 (d, J = 8.4, 12H), 0.47 (s, 3H); 13 C NMR (101 MHz, CDCl3): δ 202.8, 164.5, 148.7, 145.4, 136.1, 131.9, 122.7, 120.9,83.4, 55.3, 37.5, 25.1, 24.8, -4.3; HRMS (ESI+) m / z : calcd for C 19 H 27 BO4Si [M+Na] + 380.1700, found: 380.1703; HPLC (Chiralpak OX, hexane / i-PrOH = 95 / 5 (v / v), flow rate = 0.3 mL / min, l = 230 nm, 96% ee ): t R = 38.043 min (major), 42.537 min (minor). Example 11: Under a nitrogen atmosphere, phosphine ligands were added to a test tube. S,S Ph-BPE (3.7 mg, 0.006 mmol), Cu(CH3CN)4PF6 (1.8 mg, 0.005 mmol) metal catalyst, and 2.0 mL toluene solvent were added. After pre-stirring at room temperature for 30 min, diborane compound 5a (0.11 mmol), sodium tert-butoxide (0.04 mmol), and silanoxane compound 4k (0.1 mmol) were added sequentially. The reaction was stirred at room temperature for 17 h. After the reaction was completed by TLC monitoring, the mixture was extracted with ethyl acetate. The organic phase was dried and the solvent was removed by rotary evaporation. The crude product was purified by silica gel column chromatography to obtain 31.5 mg of colorless liquid 6k, with a yield of 78% and 99%. ee . The physicochemical properties of this product are as follows: 1 H NMR (400 MHz, CDCl3): δ 7.67–7.60 (m, 6H), 7.46(t, J = 7.2, 2H), 7.37 (t, J = 7.2, 1H), 7.11 (d, J = 14.4, 1H), 6.78 (d, J =14.4, 1H), 2.87–2.75 (m, 2H), 1.29–1.28 (m, 1H), 1.23 (d, J = 2.0, 12H), 0.55(s, 3H); 13 C NMR (101 MHz, CDCl3): δ 202.5, 146.7, 142.8, 140.9, 134.8, 133.6,129.0, 127.2, 127.3, 126.9, 83.6, 37.3, 25.2, 24.8, -4.9; HRMS (ESI+) m / z :calcd for C 24 H 29 BO3Si [M+Na]+ 427.1877, found: 427.1880; HPLC (Chiralpak OX,hexane / i -PrOH = 95 / 5 (v / v), flow rate = 0.5 mL / min, l = 250 nm, >99% ee ): t R = 23.815min (minor), 25.775min (major). Example 12: Under a nitrogen atmosphere, phosphine ligands were added to a test tube. S , S Ph-BPE (3.7 mg, 0.006 mmol), a metal catalyst Cu(MeCN)4BF4 (1.5 mg, 0.005 mmol), and 2.0 mL of dioxane solvent were added. After pre-stirring at room temperature for 30 min, a diborane compound 5a (0.11 mmol), a base sodium tert-butoxide (0.04 mmol), and a silanone compound 4l (0.1 mmol) were added sequentially. The reaction was stirred at room temperature for 17 h. After the reaction was completed by TLC monitoring, the mixture was extracted with ethyl acetate. The organic phase was dried and the solvent was removed by rotary evaporation. The crude product was purified by silica gel column chromatography to obtain 26.1 mg of colorless liquid (6l), with a yield of 68% and 99%. ee . The physicochemical properties of this product are as follows: 1 H NMR (400 MHz, CDCl3): δ 8.05 (s, 1H), 7.92 (d, J =8.0, 1H), 7.51 (d, J = 8.0, 1H), 7.92 (d, J = 8.0, 1H), 7.45 (d, J = 5.6,1H), 7.35 (d, J = 5.6, 1H), 7.12 (d, J = 14.4, 1H), 6.79 (d, J = 14.0, 1H),2.87–2.74 (m, 2H), 1.29 (dd, J = 8.8, 4.8, 1H), 1.21 (d, J = 2.8 (12H), 0.57 (s, 3H); 13C NMR (101 MHz, CDCl3): δ 202.4, 146.8, 146.6, 141.5, 139.4, 130.0,129.0, 126.5, 123.8, 122.4, 83.5, 37.2, 25.1, 24.7, -4.8; HRMS (ESI+) m / z :calcd for C 20 H 25 BO3SSi [M+K] + 422.1055, found: 422.1061; HPLC (Chiralpak OX,hexane / i -PrOH = 95 / 5 (v / v), flow rate = 0.5 mL / min, l = 210 nm, 99% ee ): t R =23.879 min (major), 25.048 min (minor). Example 13: Under a nitrogen atmosphere, phosphine ligands were added to a test tube. S , S Ph-BPE (3.7 mg, 0.006 mmol), a metal catalyst Cu(MeCN)₄BF₄ (1.5 mg, 0.005 mmol), and 2.0 mL of dioxane solvent were added. After pre-stirring at room temperature for 30 min, a diborane compound 5a (0.11 mmol), a base sodium tert-butoxide (0.04 mmol), and a silanone compound 4m (0.1 mmol) were added sequentially. The reaction was stirred at room temperature for 17 h. After the reaction was completed by TLC monitoring, the mixture was extracted with ethyl acetate. The organic phase was dried and the solvent was removed by rotary evaporation. The crude product was purified by silica gel column chromatography to obtain 24.7 mg of colorless liquid 6m, with a yield of 67% and 99%. ee . The physicochemical properties of this product are as follows: 1 H NMR (400 MHz, CDCl3): δ 7.83 (s, 1H), 7.63 (d, J =2.0, 1H), 7.51 (dd, J = 22.4, 8.0, 1H), 7.11 (d, J = 14.4, 1H), 6.773 (d, J =1.2, 2H), 6.771 (d,J = 14.4, 1H), 2.86–2.73 (m, 2H), 1.28–1.27 (m, 1H), 1.21(d, J = 4.0, 12H), 0.55 (s, 3H); 13 C NMR (101 MHz, CDCl3): δ 202.5, 156.2,147.1, 146.6, 145.2, 129.9, 128.4, 127.8, 127.7. 111.6, 106.5, 83.6, 37.3,25.2, 24.8, -4.6; HRMS (ESI+) m / z : calcd for C 20 H 25 BO4Si [M+K] + 406.1283,found: 406.1281; HPLC (Chiralpak OX, hexane / i -PrOH = 97 / 3 (v / v), flow rate =0.5 mL / min, l = 230 nm, >99% ee ): t R = 73.257 min. Example 14: Under a nitrogen atmosphere, phosphine ligands were added to a test tube. S , S Ph-BPE (3.7 mg, 0.006 mmol), Cu(MeCN)4BF4 (1.5 mg, 0.005 mmol) metal catalyst, and 2.0 mL of dioxane solvent were added. After pre-stirring at room temperature for 30 min, diborane compound 5a (0.11 mmol), sodium tert-butoxide (0.04 mmol), and silanone compound 4n (0.1 mmol) were added sequentially. The reaction was stirred at room temperature for 17 h. After the reaction was completed by TLC monitoring, the mixture was extracted with ethyl acetate. The organic phase was dried and the solvent was removed by rotary evaporation. The crude product was purified by silica gel column chromatography to obtain 36.9 mg of colorless liquid 6n, with a yield of 99% and 98%. ee . The physicochemical properties of this product are as follows: 1 H NMR (400 MHz, CDCl3): δ 7.04–7.01 (m, 3H), 6.85(d, J = 7.6, 1H), 6.73 (d,J = 14.4, 1H), 5.95 (s, 2H), 2.82–2.70 (m, 2H), 1.26–1.16 (m, 1H), 1.21 (d, J = 3.2, 12H), 0.471 (s, 3H); 13 C NMR (101 MHz, CDCl3): δ 202.4, 149.3, 147.8, 146.8, 146.6, 128.6, 127.7, 113.5, 109.0, 100.9, 83.6, 37.2, 25.2, 24.8, -4.8; HRMS (ESI+) m / z : calcd for C 19 H 25 BO5Si [M+K] + 410.1232, found: 410.1229; HPLC (Chiralpak OX*2, hexane / i -PrOH = 90 / 10(v / v), flow rate = 0.5 mL / min, l = 250 nm, 98% ee ): t R = 51.922 min (major),54.354 min (minor). Example 15: Under a nitrogen atmosphere, phosphine ligands were added to a test tube. S , S Ph-BPE (3.7 mg, 0.006 mmol), CuCl (0.5 mg, 0.005 mmol) as a metal catalyst, and 2.0 mL of dioxane solvent were added. After pre-stirring at room temperature for 30 min, diborane compound 5a (0.11 mmol), sodium tert-butoxide (0.04 mmol), and silanoxane compound 4o (0.1 mmol) were added sequentially. The reaction was stirred at room temperature for 17 h. After the reaction was completed by TLC monitoring, the mixture was extracted with ethyl acetate. The organic phase was dried and the solvent was removed by rotary evaporation. The crude product was purified by silica gel column chromatography to obtain 20.8 mg of colorless liquid 6o, with a yield of 55% and 99%. ee . The physicochemical properties of this product are as follows: 1H NMR (400 MHz, CDCl3): δ 8.08 (s, 1H), 7.86–7.83 (m, 3H), 7.62 (d, J = 8.4, 1H), 7.52–7.50 (m, 2H), 7.15 (d, J = 14.4, 1H), 6.81 (d, J = 14.4, 1H), 2.88–2.75 (m, 2H), 1.34–1.30 (m, 1H), 1.22 (d, J =2.0, 12H), 0.59 (s, 3H); 13 C NMR (101 MHz, CDCl3): δ 202.5, 146.9, 146.7,135.5, 134.2, 133.0, 132.4, 130.0, 128.3, 127.9, 127.5, 127.0, 126.3, 83.6,37.3, 25.2, 24.8, -4.8; HRMS (ESI+) m / z : calcd for C 22 H 27 BO3Si [M+K] + 416.1490,found: 416.1495; HPLC (Chiralpak OX*2, hexane / i -PrOH = 95 / 5 (v / v), flow rate= 0.5 mL / min, l = 230 nm, 99% ee ): t R = 47.173 min (minor), 49.736 min (major). Example 16: Under a nitrogen atmosphere, phosphine ligands were added to a test tube. S , SPh-BPE (3.7 mg, 0.006 mmol), Cu(CH3CN)4PF6 (1.8 mg, 0.005 mmol) metal catalyst, and 2.0 mL of dioxane solvent were added. After pre-stirring at room temperature for 30 min, diborane compound 5a (0.11 mmol), sodium tert-butoxide (0.04 mmol), and silanone compound 4p (0.1 mmol) were added sequentially. The reaction was stirred at room temperature for 17 h. After the reaction was completed by TLC monitoring, the mixture was extracted with ethyl acetate. The organic phase was dried and the solvent was removed by rotary evaporation. The crude product was purified by silica gel column chromatography to obtain 22.2 mg of colorless liquid 6p, with a yield of 65% and 99%. ee . The physicochemical properties of this product are as follows: 1 H NMR (400 MHz, CDCl3): δ 7.58 (dd, J = 8.0, 6.4,2H), 7.41–7.37 (m, 3H), 7.15 (d, J = 14.4, 1H), 6.81 (d, J = 14.4, 1H), 2.85–2.70 (m, 2H), 1.25–1.21 (m, 1H), 1.23 (s, 12H), 1.09–1.04 (m, 5H); 13 C NMR (101 MHz, CDCl3): δ 202.6, 147.4, 145.7, 134.5, 129.9, 128.2, 83.6, 37.6,25.2, 24.8, 7.7, 4.7; HRMS (ESI+) m / z : calcd for C 19 H 27 BO3Si [M+K] + 380.1490,found: 380.1485; HPLC (Chiralpak OX, hexane / i -PrOH = 99.5 / 0.5 (v / v), flowrate = 0.5 mL / min, l = 254 nm, >99% ee ): t R = 54.532 min (major), 63.993 min (minor). Example 17: Under a nitrogen atmosphere, phosphine ligands were added to a test tube.S , S Ph-BPE (3.7 mg, 0.006 mmol), Cu(CH3CN)4PF6 (1.8 mg, 0.005 mmol) metal catalyst, and 2.0 mL of dioxane solvent were added. After pre-stirring at room temperature for 30 min, diborane compound 5a (0.11 mmol), sodium tert-butoxide (0.04 mmol), and silanone compound 4q (0.1 mmol) were added sequentially. The reaction was stirred at room temperature for 17 h. After the reaction was completed by TLC monitoring, the mixture was extracted with ethyl acetate. The organic phase was dried and the solvent was removed by rotary evaporation. The crude product was purified by silica gel column chromatography to obtain 20.3 mg of colorless liquid 6q, with a yield of 57% and 99%. ee . The physicochemical properties of this product are as follows: 1 H NMR (400 MHz, CDCl3): δ 7.58 (dd, J = 7.2, 6.0,2H), 7.41–7.35 (m, 3H), 7.15 (d, J = 14.4, 1H), 6.79 (d, J = 14.4, 1H), 2.85–2.70 (m, 2H), 1.52–1.45 (m, 2H), 1.23 (s, 12H), 1.06–1.01 (m, 2H), 0.97 (t, J = 7.2, 3H); 13 C NMR (101 MHz, CDCl3): δ 202.6, 147.1, 146.0, 134.6, 134.5,129.9, 128.2, 83.6, 37.6, 25.2, 24.9, 18.4, 17.7, 15.4; HRMS (ESI+) m / z :calcd for C 20 H 29 BO3Si [M+K] + 394.1647, found: 394.1646; HPLC (Chiralpak OX,hexane / i -PrOH = 95 / 5 (v / v), flow rate = 0.5 mL / min, l = 210 nm, >99% ee ): t R = 35.555 min (major). The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any changes or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in the present invention should be included within the scope of protection of the present invention.

Claims

1. A silicon-containing stereocenters silacyclohexenone backbone borane, characterized by, The structural formula is shown as (I): wherein R 1 , R 2 are each independently selected from alkyl, aryl or substituted aryl; the substitution is selected from one of alkyl, alkoxy, halogen, aryl or heteroaryl.

2. A process for the preparation of a silicon-containing stereocentersilacyclohexenone skeleton borane as claimed in claim 1, characterized by, The preparation method comprises the following steps: Under the protection of inert gas, the silacyclohexenone, the diborane compound, the transition metal catalyst, the chiral phosphine ligand and the additive are mixed in a reaction medium to react, after the reaction is completed, extraction is carried out, the organic phase is dried, and then the solvent is removed by rotary evaporation, the crude product is separated and purified by silica gel column chromatography, and the silacyclohexenone skeleton borane with a silicon stereocenter is obtained. The synthesis route is shown as follows: 。 3. The preparation method according to claim 2, characterized in that, The molar ratio of the silacyclohexenone and the diborane compound is 1:1.2-1:1.

5.

4. The production method according to claim 3, characterized by, The concentration of the silacyclohexenone and the diborane compound is 0.1-1.0 mol / L.

5. The preparation method according to claim 2, characterized in that, The transition metal catalyst is selected from one of the following: tetraethyl copper hexafluorophosphate, tetraethyl copper tetrafluoroborate, cuprous chloride, copper acetate and copper triflate, and the use amount is 1%-10% of the molar amount of the silacyclohexenone compound.

6. The preparation method according to claim 2, characterized in that, The chiral phosphine ligand is selected from one of the compounds with the structural formula shown as (II), and the use amount is 2%-11% of the molar amount of the silacyclohexenone: 。 7. The preparation method according to claim 2, characterized in that, The additive is selected from one of the following: potassium carbonate, potassium bicarbonate, sodium carbonate, sodium tert-butoxide, sodium tetraarylborate, cesium carbonate, triethylamine, N,N-diisopropyl ethylamine and 1,8-diazabicyclo[5.4.0]undec-7-ene.

8. The preparation method according to claim 2, characterized in that, The reaction medium is selected from one of the following: tetrahydrofuran, dichloromethane, toluene and dioxane.

9. The preparation method according to claim 2, characterized in that, The reaction temperature is 0-30 DEG C, and the reaction time is 12-20 h.

10. The silacyclohexenone skeleton borane with a silicon stereocenter according to claim 1 is applied in the synthesis of a drug.

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