Multi-chiral-center non-biaryl organic silicon atropisomer as well as preparation method and application thereof

Abstract

The invention provides a multi-chiral-center non-biaryl organosilicone atropisomer and a preparation method and application thereof, and the structural formula of the multi-chiral-center non-biaryl organosilicone atropisomer is as shown in formula (I), the synthesis method of the multi-chiral-center non-biaryl organosilicone atropisomer specifically comprises the following steps: in the presence of a phosphine ligand, a nickel catalyst and a reaction medium, carrying out silicon-carbon bond activation on non-biaryl aldehyde and benzo silacyclobutane to carry out ring expansion reaction. According to the present invention, the reaction condition is mild, the operation is simple, the substrate universality is strong, the crude product is subjected to rapid column chromatography impurity removal, vacuum concentration is performed to obtain the pure product, the post-treatment is convenient, the finally obtained product has high stereoselectivity, and the non-biaryl organosilicon atropisomer contains a plurality of functional groups and a plurality of chiral centers, has potential biological activity, and can be used for the preparation of the non-biaryl organosilicon atropisomer. The compound can be used as a fine chemical intermediate to be widely applied to various organic reactions and drug synthesis, and has considerable application value.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, specifically relating to a multi-chiral center non-biaryl organosilicon transisomer, its preparation method, and its application. Background Technology

[0002] Axially chiral compounds with C–C and C–N bonds play unique roles in synthetic chemistry, medicinal chemistry, functional materials, and natural products. Unlike traditional centrally chiral compounds, their stereoconfigurations can interconvert at high temperatures without the breaking of chemical bonds. Furthermore, studies have shown that introducing other chiral centers into axially chiral compounds greatly enhances their applications as chiral ligands, catalysts, and bioactive molecules. For example, drug molecules such as vancomycin, korupensamin, and steganacin possess both axial and point chirality. The axially chiral 1,1'-binaphthyl-2,2'-bis(diphenylphosphine) skeleton can effectively catalyze reactions such as asymmetric cross-coupling. While substantial progress has been made in the synthesis of axially chiral compounds in recent years, the synthesis of compounds possessing both point and axial chirality remains challenging. Moreover, transition metal-catalyzed Si-C bond activation is one of the important strategies for synthesizing organosilicon compounds. However, due to the difficulty in introducing silicon atoms into compounds, this method has rarely been reported in constructing transisomers with multiple chiral centers.

[0003] Due to the unique structure and biological activity of trans-restricted isomers, scientists have developed various strategies to synthesize compounds with chiral axes. Among these, the (dynamic) kinetic resolution strategy for selective functionalization of racemic non-biaryl compounds with chiral axes is one of the important methods. Furthermore, transition metal-catalyzed Si-C bond activation allows for ring expansion of benzo[a]silane heterocyclic butanes, thereby introducing point chirality. Therefore, researchers have applied this strategy to the one-step construction of both point and axial chirality.

[0004] Therefore, it is essential to design and develop multidimensional strategies to synthesize carbon-chiral and axially chiral biaromatic compounds. Summary of the Invention

[0005] The first objective of this invention is to address the shortcomings of the prior art by providing a multi-chiral, non-biaryl organosilicon transisomer.

[0006] To achieve the above objectives, the present invention adopts the following technical solution: A multichiral, non-biaryl organosilicon transisomer has the following general formula (I): In the formula, R1 The substituents are hydrogen, substituted or unsubstituted alkyl, alkoxy, halogen, substituted or unsubstituted aryl, wherein the substituents in substituted alkyl groups are heteroatoms, and the substituents in substituted aryl groups are alkyl, alkoxy, haloalkyl, or halogen at different positions; R 2 R 3 Each group is independently selected from alkyl, alkoxy, or aryl groups; R 4 It is hydrogen, alkyl, alkoxy, halogen, aryl, or substituted aryl; when R 2 With R 3 At different times, it forms a trichiral center containing carbon chirality, axial chirality, and silicon chirality; when R 2 With R 3 At the same time, it constitutes a bipolar center containing carbon chirality and axial chirality.

[0007] As a preferred option, R 1 It is hydrogen, a C1-C6 substituted or unsubstituted alkyl group, or a C1-C4 alkoxy group; R 2 R 3 Each group is independently selected from C1-C6 alkyl, C1-C4 alkoxy, phenyl, substituted aryl, or naphthyl groups; R 4 It can be hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen, phenyl, substituted aryl or naphthyl.

[0008] Preferably, the compound represented by structural formula (I) is selected from one of the compounds represented by formulas (Ia) to (Io): * represents a chiral atom.

[0009] A second objective of this invention is to provide a method for preparing the compounds described above, exploring different strategies for Si–C bond activation reactions in a Ni-catalyzed system, coupling the construction of chiral silicon heterocycles with the formation of axial chirality, and establishing a new strategy for achieving one-step construction of both axial and point chirality. The key to the success of this reaction lies in the precise control of stereoselectivity.

[0010] Specifically, a method for preparing a multi-chiral, non-biaryl organosilicon transisomer includes the following steps: In the presence of phosphine ligands, nickel catalysts, and reaction media, non-biaryl phosphine-containing monoaldehydes are reacted with benzo[a]silane heterocyclic butane via a ring-expansion reaction activated by silicon-carbon bonds to synthesize non-biaryl oxasilane organosilicon transisomers with carbon chirality and axial chirality, or non-biaryl oxasilane transisomers with carbon chirality, axial chirality, and silicon chirality. Preferably, the nickel catalyst is bis(1,5-cyclooctadiene) nickel; Preferably, the phosphine ligand is any one of the compounds shown in formulas L1 to L27: Preferably, the molar ratio of non-biaryl phosphine monoaldehyde, benzosilane, phosphine ligand, and nickel catalyst is 1:(1-3):(0.12-0.4):(0.1-0.2). Preferably, the reaction medium is selected from at least one of diethyl ether, tetrahydrofuran, toluene, 1,4-dioxane, acetonitrile, or ethyl acetate.

[0011] Preferably, the reaction time is at least 15 hours, more preferably 15-20 hours; Preferably, the reaction temperature is 0~60 ℃.

[0012] A third objective of this invention is to provide the application of the above-mentioned multi-chiral non-biaryl organosilicon transisomers as chiral ligands or catalysts.

[0013] A fourth objective of this invention is to provide the application of the above-mentioned multi-chiral center non-biaryl organosilicon transisomers in the synthesis of chiral drugs.

[0014] Compared with the prior art, the present invention has the following beneficial effects: This invention synthesizes a multi-chiral non-biaryl organosilicon transisomer using a multidimensional strategy. This transisomer possesses at least carbon chirality and axial chirality, and may also possess silicon chirality. The synthesis method of the aforementioned multi-chiral non-biaryl organosilicon transisomer provided by this invention allows for reaction completion at relatively low temperatures with stirring. The reaction conditions are mild, the operation is simple, and the substrate is highly universal. The crude product can be purified by rapid column chromatography followed by vacuum concentration to obtain a pure product, making post-processing convenient. The final product exhibits high stereoselectivity. Furthermore, this non-biaryl organosilicon transisomer 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. Attached Figure Description

[0015] Figure 1 The crystal structure of compound Ia obtained in Example 3 is shown. Detailed Implementation

[0016] The present invention will be further described below with reference to specific embodiments, but the present invention is not limited to the following embodiments. Unless otherwise specified, the raw materials used in the embodiments can be commercially available or prepared by conventional methods.

[0017] In this invention, R in each compound 1 R 2 R 3 R 4 All of the above are as defined in this invention.

[0018] Unless otherwise specified, all reactions were carried out under nitrogen protection and magnetic stirring. Catalytic reactions were conducted in 25 mL Schlenk reaction tubes under nitrogen protection. Anhydrous solvents were obtained using an inert solvent purification system (Et₂O, CH₂Cl₂, THF, and toluene). All reagents were purchased from commercial suppliers and were ready for use without further purification. Column chromatography was performed on silica gel (200-300 mesh) using petroleum ether (bp: 60-90℃) and ethyl acetate as eluents. TLC was performed using F-254 pre-coated silica gel plates, with fluorescence quenching (…). max = 254 nm) for chromatographic development. Nuclear magnetic resonance spectra were recorded on a Bruker Avance spectrometer (400 MHz or 500 MHz) using CDCl3 as solvent. Chemical shift ( The NMR standard is expressed in ppm, and the coupling constant (J) is expressed in Hertz (Hz). 1 (H NMR) CDCl3 = 7.26 ppm; 13 (C NMR) CDCl3 = 77.16 ppm; 1 H NMR data recording.

[0019] as follows: Chemical shift is indicated by s for singlet, d for doublet, dd for doublet, t for triplet, q for quartet, m for multiplet, and br for broad peak. The coupling constant is in Hz. (ppm) records 13 CNMR. High-resolution mass spectrometry (HRMS) analysis was performed using Waters Micromass (ESI-TOF). HPLC was performed on an Agilent 1260 Infinity instrument or a Waters Alliance e2695 instrument.

[0020] Example 1: General method for preparing the compound shown in formula (II) Under nitrogen protection, N,N-diisopropylbenzamide (10.3 g, 50 mmol, 1.0 equivalent) and anhydrous tetrahydrofuran (100.0 mL) were added to a flame-dried flask equipped with a magnetic stir bar. Then, n-butyllithium (2.5 M hexane solution, 22 mL, 55 mmol, 1.1 equivalent) was added dropwise, and the reaction mixture was stirred at -78 °C for 15 min. After stirring for another 30 min, dichlorophenylphosphine (10.8 mL, 60 mmol, 1.2 equivalent) was added dropwise at the same temperature. The reaction mixture was stirred at -78 °C for 1 hour, and the reaction was confirmed to be complete by thin-layer chromatography. The mixture was then allowed to cool naturally to room temperature while maintaining continuous stirring. Finally, the reaction was quenched with saturated ethyl acetate solution and extracted with ethyl acetate (3 × 30 mL). The organic phase was washed successively with water and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The product S2 was purified by column chromatography.

[0021] S2 (10.1 g, 26 mmol, 1.0 equivalent) was dissolved in 52 mL of tetrahydrofuran, and then 13.5 mL of n-butyllithium (2.5 M n-butyllithium hexane solution, 33.8 mmol, 1.3 equivalent) was added dropwise under nitrogen protection at -78 °C. The resulting mixture was stirred at -78 °C for 1 hour, and then 2.4 mL of N,N-dimethylformamide (31.2 mmol, 1.2 equivalent) was added. After 15 minutes, the reaction mixture was allowed to warm naturally to room temperature, and stirring was continued for 2–3 hours. The reaction progress was observed by pouring the mixture into water, and the mixture was extracted with ethyl acetate (3 × 30 mL). The organic phase was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. Product II (a non-biaryl phosphine monoaldehyde) was purified by column chromatography.

[0022] Example 2: General method for preparing the compound shown in formula (I) A non-biaryl phosphine monoaldehyde (0.2 mmol) and BINAP-derived phosphoridamide ligand L27 (10 mol%) were added to a 25 mL Schlenk reaction tube after anhydrous and oxygen-free conditions. The tube was then transferred to an argon-atmospheric glove box. Ni(cod)₂ (10 mol%) was then weighed into the reaction tube and transferred outside the glove box. Ethyl acetate (2 mL) and benzo[a]silane heterocyclic butane were subsequently added to the reaction tube, and the reaction was carried out at room temperature for 20 h. After the reaction, the mixture was filtered through diatomaceous earth, the solvent was removed under vacuum, and the product was purified by silica gel column chromatography to obtain the multichiral non-biaryl organosilicon transisomer.

[0023] Example 3 (Ia) Preparation of compound Ia: Ia was prepared by a method substantially the same as that in Example 2. The crude product was purified by column chromatography: n-hexane / ethyl acetate = 20:1. A white solid with a melting point of 86-88°C was given. 54.3 mg, yield 48%.

[0024] [α]25 D = -51.5 (c = 0.81, CHCl3). The compound with structure Ia was analyzed using Waters 2695 high-performance liquid chromatography (HPLC). The column was a Chiralcel-OD column, the mobile phase was n-hexane / isopropanol = 99:1, the flow rate was 1 mL / min, and the wavelength was 254 nm. The retention time of the major enantiomer was t. r =23.166 min, minor enantiomer retention time t r =33.423 min. The results show that the corresponding selection excess value of the compound shown in structure Ia is ( er The ratio is 97:3. 1 H NMR (400 MHz, CDCl3) d 7.41 (dd, J = 7.8, 1.2 Hz, 1H), 7.35-7.24 (m, 10H), 7.22-7.16 (m, 1H), 7.14-7.10 (m, 1H), 7.09 (d, J = 4.3 Hz, 2H), 6.99-6.91 (m, 1H), 6.53 (d, J = 7.7 Hz,1H), 5.98 (s, 1H), 3.93-3.89 (m, 1H), 3.53-3.48 (m, 1H), 2.24 (d, J = 15.6 Hz, 1H), 2.07 (d, J = 15.4 Hz, 1H), 1.58 (d, J = 6.7 Hz, 3H), 1.44 (d, J = 6.7 Hz, 3H), 1.20 (d, J = 6.5 Hz, 3H), 1.14 (d, J = 6.6 Hz, 3H), 0.24 (s, 3H), 0.10 (s, 3H). 13 CNMR (100 MHz, CDCl3) d168.4, 144.0, 143.7, 141.2, 140.1, 140.0, 137.9, 137.8, 137.3, 137.2, 135.2, 134.6, 134.5, 133.7, 133.5, 133.3, 130.6, 130.2, 128.7, 128.6, 128.5, 128.4, 128.3, 127.5, 125.5, 73.7, 73.6, 51.3, 46.2, 21.0, 20.8, 20.7, 20.6, 20.5, 20.2, -0.1, -0.4. 31 p NMR (162 MHz, CDCl3) d -14.41, -14.56.HRMS (ESI) m / z: [M+H] + Calculated for C 35 H 41 NO2PSi: 566.2639; found 566.2642. The absolute configuration of compound Ia was determined using X-ray single-crystal diffraction.

[0025] Compound Ia precipitated in a culture system of dichloromethane and n-hexane. The X-ray crystal structure data is stored in the Cambridge Crystallography Data Centre, catalog number CCDC 2452057. The crystal structure is as follows: Figure 1 As shown in Table 1 below, detailed information is available.

[0026] Table 1 Crystal information of compound Ia Example 4 (Ib) Preparation of compound Ib: Ib was prepared by a method substantially the same as that in Example 2. The crude product was purified by column chromatography: n-hexane / ethyl acetate = 15:1. A white solid with a melting point of 81-83°C was given. 73.1 mg, yield 53%.

[0027] [α]25 D = 4.8 (c = 2.29, CHCl3). The compound with structure Ib was analyzed using Waters 2695 high-performance liquid chromatography (HPLC). The column was a Chiralcel-OD column, the mobile phase was n-hexane / isopropanol = 97:3, the flow rate was 1 mL / min, and the wavelength was 254 nm. The retention time of the major enantiomer was t. r =5.180 min, minor enantiomer retention time t r=13.506 min. The results show that the corresponding selection excess value of the compound with the Ib structure is ( er The ratio is 98:2. 1 H NMR (400 MHz, CDCl3) d 7.55-7.51(m, 2H), 7.50-7.45 (m, 1H), 7.36-7.34 (m, 1H), 7.34-7.30 (m, 3H), 7.30-7.26(m, 3H), 7.26-7.24 (m, 4H), 7.24-7.20 (m, 6H), 7.19 (s, 1H), 7.17 (s, 1H), 7.09-7.04 (m, 2H), 7.04-7.00 (m, 1H), 6.92 (td, J = 7.5, 1.7 Hz, 1H), 6.60 (d, J = 7.7 Hz, 1H), 6.13 (s, 1H), 3.82-3.75 (m, 1H), 3.41-3.34 (m, 1H), 2.62 (d, J =4.2 Hz, 2H), 1.49 (d, J = 6.8 Hz, 3H), 1.31 (d, J = 6.8 Hz, 3H), 1.06 (d, J = 6.6Hz, 3H), 0.84 (d, J = 6.6 Hz, 3H). 13 C NMR (100 MHz, CDCl3) d 168.3, 143.8, 143.5, 141.4, 140.0, 137.9, 137.8, 137.1, 137.0, 134.9, 134.8, 134.7, 134.5, 134.3, 133.9, 133.8, 133.7, 133.6, 133.5, 133.4, 133.3, 131.0, 130.3, 130.2, 130.1, 128.6, 128.5, 128.4, 128.0, 127.9, 127.7, 125.8, 74.4, 51.2, 46.1, 20.8, 20.7, 20.4, 20.1, 18.1. 31 p NMR (162 MHz, CDCl3) d -14.24, -14.84.HRMS (ESI) m / z:[M+H]+ Calculated for C 45 H 45 NO2PSi: 690.2952; found 690.2960. Example 5 (Ic) Preparation of compound Ic: Ic was prepared using a method substantially the same as that described in Example 2. The crude product was purified by column chromatography: hexane / ethyl acetate = 20:1. A colorless oily liquid was obtained. 60.6 mg, yield 51%.

[0028] [α]25 D = -39.0 (c = 0.68, CHCl3). The compound with structure Ic was analyzed using Waters 2695 high-performance liquid chromatography (HPLC). The column was a Chiralcel-OD column, the mobile phase was n-hexane / isopropanol = 99:1, the flow rate was 1 mL / min, and the wavelength was 254 nm. The retention time of the major enantiomer was t. r =9.530 min, minor enantiomer retention time t r =19.403 min. The results show that the corresponding selection excess value of the compound shown in the Ic structure is ( er The ratio is 97:3. 1 H NMR (400 MHz, CDCl3) d 7.35(d, J = 7.7 Hz, 1H), 7.32-7.17 (m, 11H), 7.15-7.08 (m, 1H), 7.06-6.99 (m, 2H), 6.94-6.84 (m, 1H), 6.50 (d, J = 7.7 Hz, 1H), 5.94 (s, 1H), 3.88-3.82 (m, 1H), 3.49-3.42 (m, 1H), 2.19 (d, J = 15.6 Hz, 1H), 2.00 (d, J = 15.5 Hz, 1H), 1.52(d, J = 6.8 Hz, 3H), 1.38 (d, J = 6.7 Hz, 3H), 1.14 (d, J = 6.6 Hz, 3H), 1.10 (d, J =6.8 Hz, 3H), 0.90 (t, J = 7.9 Hz, 3H), 0.77 (t, J= 7.8 Hz, 3H), 0.62 (q, J = 8.1Hz, 2H), 0.50 (q, J = 7.8 Hz, 2H). 13 C NMR (100 MHz, CDCl3) d 168.3, 143.7, 143.3,141.1, 140.5, 140.4, 138.1, 137.8, 137.7, 137.1, 137.0, 135.0, 134.2, 133.6,133.4, 133.2, 130.5, 129.9, 128.5, 128.4, 128.3, 128.2, 127.3, 125.3, 73.9,73.8, 51.1, 46.1, 20.8, 20.7, 20.6, 20.4, 20.0, 17.0, 6.7, 6.6, 6.3, 6.1. 31 PNMR (162 MHz, CDCl3) d -14.32, -14.80.HRMS (ESI) m / z: [M+H] + Calculated for C 37 H 45 NO2PSi: 594.2952; found 594.2952. Example 6 (Id) Preparation of compound Id: Id was prepared using a method substantially the same as that described in Example 2. The crude product was purified by column chromatography: hexane / ethyl acetate = 20:1. A colorless oily liquid was obtained. 24.4 mg, yield 21%.

[0029] [α]25 D = -7.9 (c = 0.73, CHCl3). The compound with structure Id was analyzed using Waters 2695 high-performance liquid chromatography (HPLC). The column was a Chiralcel-OD column, the mobile phase was n-hexane / isopropanol = 95:5, the flow rate was 1 mL / min, and the wavelength was 254 nm. The retention time of the major enantiomer was t. r =4.093 min, minor enantiomer retention time t r =6.138 min. The results show that the corresponding selection excess value of the compound with structure Id is ( er The ratio is 95.5:4.5. 1 H NMR (400 MHz, CDCl3) d7.68 (d, J = 7.8 Hz, 1H), 7.28 (d, J = 7.7 Hz, 1H), 7.24 (d, J = 5.3 Hz, 7H), 7.21-7.12 (m, 3H), 7.09 (d, J = 7.6 Hz, 1H), 7.04 (dd, J = 7.3, 3.2 Hz, 1H), 6.95 (d, J = 7.6 Hz, 1H), 6.87 (d, J = 7.6 Hz, 1H), 5.13 (dd, J = 11.0, 2.0 Hz, 1H), 3.77-3.70 (m, 1H), 3.42-3.35 (m, 1H), 3.05 (dd, J = 16.2, 2.1 Hz, 1H), 2.84 (dd, J =16.1, 11.0 Hz, 1H), 2.32 (s, 3H), 1.51 (d, J = 6.7 Hz, 3H), 1.28 (d, J = 6.8 Hz,3H), 1.01 (d, J = 6.6 Hz, 6H), 0.43 (s, 3H), 0.36 (s, 3H). 13 C NMR (100 MHz,CDCl3) d 168.5, 145.9, 142.2, 141.1, 141.0, 137.9, 137.8, 137.2, 137.1, 134.2,133.7, 133.6, 133.3, 133.1, 132.3, 129.8, 128.7, 128.6, 128.5, 128.3, 127.8,127.5, 126.6, 71.8, 71.7, 51.2, 46.1, 44.1, 23.0, 21.0, 20.7, 20.6, 20.5,20.2, 1.5, 0.6. 31 P NMR (162 MHz, CDCl3) d -14.80, -14.85.HRMS (ESI) m / z: [M+H] + calculated for C 36 H43 NO2PSi: 580.2795; found 580.2801. Example 7 (Ie) Preparation of compound Ie: Ie was prepared using a method substantially the same as that described in Example 2. The crude product was purified by column chromatography: hexane / ethyl acetate = 20:1. A colorless oily liquid was obtained. 56.8 mg, yield 49%.

[0030] [α]25 D = -5.0 (c = 2.32, CHCl3). The compound with the structure shown in the figure was analyzed using Waters 2695 high-performance liquid chromatography (HPLC). The column was a Chiralcel-OD column, the mobile phase was n-hexane / isopropanol = 99:1, the flow rate was 1 mL / min, and the wavelength was 254 nm. The retention time of the major enantiomer was t. r =12.040 min, minor enantiomer retention time t r =24.458 min. The results show that the corresponding selection excess value of the compound with the Ie structure is ( er The ratio is 98.5:1.5. 1 H NMR (400 MHz, CDCl3) d 7.41 (dd, J = 7.8, 1.2 Hz, 1H), 7.34-7.31 (m, 4H), 7.31-7.26 (m, 7H), 7.11-7.08 (m, 1H), 6.98 (d, J = 7.7 Hz, 1H), 6.91 (d, J = 7.7 Hz, 1H), 6.29 (s, 1H), 5.94 (s, 1H), 3.93-3.87 (m, 1H), 3.56-3.49 (m, 1H), 2.21 (d, J = 5.0 Hz, 1H), 2.13 (s, 3H), 2.02 (d, J = 15.5 Hz, 1H), 1.58 (d, J = 6.8 Hz, 3H), 1.45 (d, J = 6.8Hz, 3H), 1.20 (dd, J = 6.6, 2.0 Hz, 6H), 0.24 (s, 3H), 0.10 (s, 3H). 13 C NMR (100MHz, CDCl3) d 168.3, 143.7, 143.4, 142.4, 141.0, 140.1, 140.0, 137.9, 137.7, 137.3, 137.1, 134.6, 134.1, 133.6, 133.5, 133.4, 131.9, 130.4, 130.0, 128.9, 128.7, 128.6, 128.4, 128.3, 127.5, 73.6, 51.2, 46.1, 21.4, 20.9, 20.8, 20.7, 20.5, 20.1, 19.8, -0.2, -0.5. 31 p NMR (162 MHz, CDCl3) d -14.06, -14.43.HRMS(ESI) m / z: [M+Na] + Calculated for C 36 H 42 NO2PSiNa: 602.2615; found 602.2606. Example 8 (If) Preparation of compound If: If was prepared using a method substantially the same as that in Example 2. The crude product was purified by column chromatography: n-hexane / ethyl acetate = 20:1. A colorless oily liquid was obtained. 38.5 mg, yield 33%.

[0031] [α]25 D = -13.5 (c = 0.16, CHCl3). The compound with the If structure was analyzed using Waters 2695 high-performance liquid chromatography (HPLC). The column was a Chiralcel-OD column, the mobile phase was n-hexane / isopropanol = 99.5:0.5, the flow rate was 1 mL / min, and the wavelength was 254 nm. The retention time of the major enantiomer was t. r =22.821 min, minor enantiomer retention time t r =26.216 min. The results show that the corresponding selection excess value of the compound with the If structure is ( er The ratio is 80:20. 1 H NMR (400MHz, CDCl3) d 7.46 (d, J = 7.7 Hz, 1H), 7.39-7.32 (m, 6H), 7.28 (d, J = 12.2 Hz, 5H), 7.13 (dd, J= 7.7, 3.5 Hz, 1H), 7.06 (dd, J = 8.3, 5.7 Hz, 1H), 6.82 (td, J =8.4, 2.7 Hz, 1H), 6.21 (dd, J = 10.1, 2.7 Hz, 1H), 5.92 (s, 1H), 3.93-3.87 (m,1H), 3.57-3.50 (m, 1H), 2.22 (d, J = 15.5 Hz, 1H), 2.04 (d, J = 15.5 Hz, 1H),1.58 (d, J = 6.7 Hz, 3H), 1.45 (d, J = 6.7 Hz, 3H), 1.20 (d, J = 6.8 Hz, 6H), 0.29(s, 3H), 0.11 (s, 3H). 13 C NMR (100 MHz, CDCl3) d 168.2, 168.1, 161.9, 159.5,143.7, 143.4, 143.2, 143.1, 139.1, 139.0, 137.6, 137.4, 136.9, 136.8, 134.5,134.5, 133.6, 133.6, 133.4, 131.4, 131.3, 130.9, 129.9, 128.8, 128.7, 128.6,128.5, 128.4, 128.3, 127.4, 115.4, 115.1, 114.5, 114.3, 73.0, 51.2, 46.1,21.0, 20.7, 20.6, 20.5, 20.1, 19.6, -0.2, -0.7. 31 P NMR (162 MHz, CDCl3) d -14.14, -14.60. 19 F NMR (376 MHz, CDCl3) d -117.04, -117.22.HRMS (ESI) m / z: [M+Na] + calculated for C 35 H 39 FNO2PSiNa: 606.2364; found 606.2364. Example 9 (Ig) Preparation of compound Ig: Ig was prepared using a method substantially the same as that in Example 2. The crude product was purified by column chromatography: hexane / ethyl acetate = 20:1. A colorless oily liquid was obtained. 42.0 mg, yield 36%.

[0032] [α]25 D = -7.3 (c = 0.06, CHCl3). The compound with the structure shown in Ig was analyzed using Waters 2695 high-performance liquid chromatography (HPLC). The column was a Chiralcel-OD column, the mobile phase was n-hexane / isopropanol = 99.5:0.5, the flow rate was 1 mL / min, and the wavelength was 254 nm. The retention time of the major enantiomer was t. r =10.639 min, minor enantiomer retention time t r =41.729 min. The results show that the corresponding selection excess value of the compound shown in the Ig structure is ( er The ratio is 92.5:7.5. 1 H NMR (400MHz, CDCl3) d 7.41 (d, J = 7.6 Hz, 1H), 7.34-7.25 (m, 8H), 7.24 (d, J = 10.3 Hz,3H), 7.14-7.11 (m, 1H), 6.79 (dd, J = 9.3, 2.4 Hz, 1H), 6.67-6.57 (m, 1H), 6.42(dd, J = 8.5, 6.0 Hz, 1H), 5.90 (s, 1H), 3.90-3.84 (m, 1H), 3.53-3.46 (m, 1H), 2.20 (d, J = 15.5 Hz, 1H), 2.05 (d, J = 15.5 Hz, 1H), 1.55 (d, J = 6.8 Hz, 3H), 1.41 (d, J = 6.8 Hz, 3H), 1.17 (d, J = 6.6 Hz, 3H), 1.12 (d, J = 6.7 Hz, 3H), 0.24(s, 3H), 0.09 (s, 3H). 13 C NMR (100 MHz, CDCl3) d 168.3, 168.2, 163.3, 160.9, 143.8, 143.5, 139.6, 139.5, 137.9, 137.8, 137.7, 137.6, 137.1, 137.0, 134.6, 133.7, 133.5, 133.4, 133.2, 129.9, 129.8, 128.7, 128.6, 128.5, 128.4, 116.8, 116.6, 112.2, 112.0, 73.0, 51.2, 46.2, 20.9, 20.8, 20.7, 20.6, 20.5, 20.1, -0.2, -0.6. 31 p NMR (162 MHz, CDCl3) d -30.08, -29.51. 19 F NMR (376 MHz, CDCl3) d -115.07, -116.28.HRMS (ESI) m / z: [M+Na] + Calculated for C 35 H 39 FNO2PSiNa:606.2364; found 606.2372. Example 10 (Ih) Preparation of compound Ih: Ih was prepared using a method substantially the same as that in Example 2. The crude product was purified by column chromatography: hexane / ethyl acetate = 15:1. A colorless oily liquid was obtained. 59.6 mg, yield 50%.

[0033] [α]25 D = -11.2 (c = 0.30, CHCl3). The compound with the structure shown in Ih was analyzed using Waters 2695 high-performance liquid chromatography (HPLC). The column was a Chiralcel-IA column, the mobile phase was n-hexane / isopropanol = 99.8:0.2, the flow rate was 0.4 mL / min, and the wavelength was 254 nm. The retention time of the major enantiomer was t. r =36.781 min, minor enantiomer retention time t r =43.369 min. The results show that the corresponding selection excess value of the compound with the Ih structure is ( er The ratio is 91:9. 1 H NMR (400 MHz, CDCl3) d7.38 - 7.24 (m, 8H), 7.24 - 7.21 (m, 2H), 7.11 - 7.04 (m, 2H), 6.90 (d, J J = 2.5 Hz, 2H), 6.62 - 6.52 (m, 2H), 5.92 (s, 1H), 3.95 - 3.88 (m, 1H), 3.58 (s, 3H), 3.51 - 3.44 (m, 1H), 2.21 (d, J J = 15.5 Hz, 1H), 2.04 (d, J J = 15.5 Hz, 1H), 1.53 (d, J J = 6.9 Hz, 3H), 1.39 (d, J J = 6.3 Hz, 3H), 1.17 (d, J J = 6.6 Hz, 3H), 1.13 (d, J J = 6.8 Hz, 3H), 0.22 (s, 3H), 0.09 (s, 3H). 13 13C NMR (100 MHz, CDCl3) d 170.1, 159.2, 135.7, 135.6, 135.1, 133.7, 133.6, 133.5, 133.4, 131.6, 130.5, 128.7, 128.6, 128.5, 128.4, 128.2, 127.7, 127.5, 126.2, 125.5, 120.4, 114.5, 73.6, 55.2, 51.2, 46.1, 21.1, 21.0, 20.8, 20.7, 20.5, 20.4, 20.1, -0.2, -0.5. 31 31P NMR (162 MHz, CDCl3) d -13.59, -13.93. HRMS (ESI) m / z: [M + Na] + calculated for C 36 H 42 NO3PSiNa: 618.2564; found 618.2568. Example 11 (Ii) Preparation of compound Ii: Ii was prepared by a method substantially the same as that in Example 2. The crude product was purified by column chromatography: n-hexane / ethyl acetate = 20:1. A colorless oily liquid was obtained. 47.5 mg, yield 41%.

[0034] [α]25 D = -32.7 (c = 0.33, CHCl3). The compound with structure Ii was analyzed using Waters 2695 high-performance liquid chromatography (HPLC). The column was a Chiralcel-OD column, the mobile phase was n-hexane / isopropanol = 99:1, the flow rate was 1 mL / min, and the wavelength was 254 nm. The retention time of the major enantiomer was t. r =22.774 min, minor enantiomer retention time t r =31.942 min. The results show that the corresponding selection excess value of the compound with structure Ii is ( er The ratio is 92:8. 1 H NMR (400 MHz, CDCl3) d 7.36-7.26 (m, 7H), 7.25-7.22 (m, 3H), 7.20-7.16 (m, 1H), 7.11-7.05 (m, 2H), 6.98-6.89 (m, 2H), 6.51 (d, J = 7.7 Hz, 1H), 5.93 (s, 1H), 3.94-3.87 (m, 1H), 3.51-3.44 (m, 1H), 2.22 (d, J = 13.6 Hz, 1H), 2.18 (s, 3H), 2.05 (d, J = 15.5 Hz, 1H), 1.54 (d, J = 6.8 Hz, 3H), 1.40 (d, J = 6.9 Hz, 3H), 1.17 (d, J = 6.7 Hz, 3H), 1.09 (d, J = 6.7 Hz, 3H), 0.23 (s, 3H), 0.10 (s, 3H). 13 C NMR (100 MHz, CDCl3) d168.6, 141.6, 141.2, 139.8, 139.7, 138.3, 137.9, 137.8, 137.4, 137.3, 135.2, 135.1, 133.7, 133.5, 133.4, 133.2, 130.7, 130.4, 128.6, 128.5, 128.4, 128.3, 127.4, 125.4, 73.5, 51.2, 46.1, 21.6, 20.9, 20.7, 20.6, 20.5, 20.4, 20.1, -0.2, -0.5. 31 p NMR (162 MHz, CDCl3) d -14.30, -14.48.HRMS (ESI) m / z: [M+Na] + Calculated for C 36 H 42 NO2PSiNa: 602.2615; found 602.2615. Example 12 (Ij) Preparation of compound Ij: Ij was prepared using a method substantially the same as that described in Example 2. The crude product was purified by column chromatography: hexane / ethyl acetate = 20:1. A colorless oily liquid was obtained. 59.6 mg, yield 47%.

[0035] [α]25 D = -61.5 (c = 0.03, CHCl3). The compound with structure Ij was analyzed using Waters 2695 high-performance liquid chromatography (HPLC). The column was a Chiralcel-OD column, the mobile phase was n-hexane / isopropanol = 99:1, the flow rate was 1 mL / min, and the wavelength was 254 nm. The retention time of the major enantiomer was t. r =21.239 min, minor enantiomer retention time t r =29.522 min. The results show that the corresponding selection excess value of the compound with structure Ij is ( er The ratio is 91.5:8.5. 1 H NMR (400 MHz, CDCl3) d 7.63 (s, 1H), 7.34-7.26 (m, 8H), 7.25-7.17 (m, 3H), 7.11-7.07 (m, 2H), 6.98-6.92 (m, 1H), 6.41 (d, J= 7.7 Hz, 1H), 5.97 (s, 1H), 3.83 - 3.76 (m, 1H), 3.525 - 3.48 (m, 1H), 2.23 (d, J = 15.6 Hz, 1H), 2.05 (d, J = 15.6 Hz, 1H), 1.54 (d, J = 6.7 Hz, 3H), 1.40 (d, J = 6.8 Hz, 3H), 1.19 (d, J = 6.6 Hz, 6H), 0.22 (s, 3H), 0.10 (s, 3H). 13 C NMR (100 MHz, CDCl3) d 167.2, 146.7, 146.3, 141.1, 141.0, 140.4, 137.9, 136.7, 136.6, 136.0, 135.8, 135.7, 135.6, 135.1, 133.9, 133.7, 133.5, 133.4, 133.2, 130.9, 130.7, 130.5, 129.1, 128.9, 128.8, 128.7, 128.6, 128.4, 127.9, 127.8, 127.2, 127.1, 127.0, 126.3, 125.7, 125.2, 124.9, 122.5, 77.5, 73.2, 51.3, 46.3, 20.9, 20.8, 20.7, 20.4, 20.0, -0.3, -0.6. 31 P NMR (162 MHz, CDCl3) d -14.06, -14.45. 19 F NMR (376 MHz, CDCl3) d -62.45, -62.52. HRMS (ESI) m / z: [M + Na] + calculated for C 36 H 39 F3NO2PSiNa: 656.2332; found 656.2335. Example 13 <[ (Ij) Preparation of compound Ik: Ik was prepared using a method substantially the same as that described in Example 2. The crude product was purified by column chromatography: hexane / ethyl acetate = 20:1. A yellow oily liquid was obtained. 45.1 mg, yield 38%.

[0036] [α]25 D = -4.7 (c = 0.73, CHCl3). The compound with the structure shown in Ik was analyzed using Waters 2695 high-performance liquid chromatography (HPLC). The column was a Chiralcel-OD column, the mobile phase was n-hexane / isopropanol = 99:1, the flow rate was 1 mL / min, and the wavelength was 254 nm. The retention time of the major enantiomer was t. r =25.109 min, minor enantiomer retention time t r =32.703 min. The results show that the corresponding selection excess value of the compound with the Ik structure is ( er The ratio is 98.5:1.5. 1 H NMR (400 MHz, CDCl3) d 7.24-7.17 (m, 6H), 7.17-7.13 (m, 3H), 7.13-7.08 (m, 2H), 7.05-6.96 (m, 2H), 6.91-6.82 (m, 2H), 6.41 (d, J = 7.7 Hz, 1H), 5.84 (s, 1H), 3.85-3.78 (m, 1H), 3.42-3.35 (m, 1H), 2.39 (q, J = 7.6 Hz, 2H), 2.12 (d, J = 15.5 Hz, 1H), 1.96 (d, J = 15.5 Hz, 1H), 1.45 (d, J = 6.8 Hz, 3H), 1.31 (d, J = 6.7 Hz, 3H), 1.08 (d, J =6.6 Hz, 3H), 1.00 (d, J = 6.9 Hz, 3H), 0.95 (t, J = 7.6 Hz, 3H), 0.14 (s, 3H), 0.00 (s, 3H). 13 C NMR (100 MHz, CDCl3) d168.7, 144.3, 141.9, 141.8, 141.3, 139.7, 139.6, 138.1, 138.0, 137.5, 137.4, 135.2, 134.0, 133.7, 133.5, 133.4, 133.2, 130.4, 129.5, 128.5, 128.4, 128.2, 127.4, 125.4, 73.6, 51.2, 46.1, 28.6, 21.0, 20.7, 20.5, 20.2, 20.1, 15.0, -0.1, -0.5. 31 p NMR (162 MHz, CDCl3) d -13.96, -14.15.HRMS (ESI) m / z: [M+Na] + Calculated for C 37 H 44 NO2PSiNa: 616.2771;found 616.2762. Example 14 (Il) Preparation of compound 1l: 1l was prepared by a method substantially the same as that in Example 2. The crude product was purified by column chromatography: n-hexane / ethyl acetate = 20:1. A white solid with a melting point of 87-89°C was given. 45.5 mg, yield 35%.

[0037] [α]25 D = -9.5 (c = 1.77, CHCl3). The compound with structure Il was analyzed using Waters 2695 high-performance liquid chromatography (HPLC). The column was a Chiralcel-AD column, the mobile phase was n-hexane / isopropanol = 99.6:0.4, the flow rate was 0.2 mL / min, and the wavelength was 254 nm. The retention time of the major enantiomer was t. r =29.068 min, minor enantiomer retention time t r =37.637 min. The results show that the corresponding selection excess value of the compound shown in structure Il is ( er The ratio is 97:3. 1 H NMR (400 MHz, CDCl3) d 7.35 (d, J = 7.7 Hz, 3H), 7.29-7.16 (m, 9H), 7.16-6.99 (m, 3H), 6.89(dq, J = 8.2, 4.3 Hz, 1H), 6.48 (d,J = 7.7 Hz, 1H), 5.91 (s, 1H), 3.88-3.81 (m,1H), 3.49-3.43 (m, 1H), 2.18 (d, J = 15.5 Hz, 1H), 2.01 (d, J = 15.5 Hz, 1H).1.60-1.48 (m, 8H), 1.38 (d, J = 6.7 Hz, 3H), 1.25 (d, J = 6.8 Hz, 3H), 1.12 (dd, J = 13.4, 6.6 Hz, 6H), 0.82-0.70 (m, 6H), 0.68-0.17 (m, 4H). 13 C NMR (100 MHz, CDCl3) d 168.4, 168.3, 144.0, 143.6, 141.1, 140.1, 140.0, 137.9, 137.8, 137.2, 137.1, 135.1, 134.5, 133.7, 133.5, 133.4, 133.2, 130.5, 130.1, 128.7, 128.6, 128.5, 128.4, 128.3, 128.2, 127.4, 125.5, 73.6, 51.2, 46.2, 21.1, 21.0, 20.9, 20.8, 20.7, 20.5, 20.4, 20.1, 20.0, -0.2, -0.5. 31 p NMR (162 MHz, CDCl3) d -14.38, -14.53.HRMS (ESI) m / z: [M+H] + Calculated for C 41 H 53 NO2PSi: 650.3578; found 650.3577. Example 15 (Im) Preparation of compound Im: Im was prepared using a method substantially the same as that described in Example 2. The crude product was purified by column chromatography: hexane / ethyl acetate = 20:1. A colorless oily liquid was obtained. 69.1 mg, yield 55%.

[0038] [α]25 D = -3.4 (c = 0.62, CHCl3). The compound with the structure shown in Im was analyzed using Waters 2695 high-performance liquid chromatography (HPLC). The column was a Chiralcel-IB column, the mobile phase was n-hexane / isopropanol = 99:1, the flow rate was 1 mL / min, and the wavelength was 254 nm. The retention time of the major enantiomer was t. r =16.797 min, minor enantiomer retention time t r =8.753, 13.592 min. The results show that the corresponding selection excess values ​​of the major enantiomers of the compound shown in the Im structure are ( er The ratio is >99:1. 1 HNMR (400 MHz, CDCl3) d 7.53-7.46 (m, 1H), 7.39 (dd, J = 11.8, 7.8 Hz, 1H), 7.31-7.27 (m, 2H), 7.24-7.12 (m, 13H), 7.09-7.00 (m, 3H), 6.94-6.83 (m, 1H), 6.58(d, J = 7.8 Hz, 1H), 6.06 (s, 1H), 3.89-3.82 (m, 1H), 3.50-3.43 (m, 1H), 2.39(d, J = 13.4 Hz, 1H), 2.19 (d, J = 15.5 Hz, 1H), 1.52 (d, J = 6.8 Hz, 3H), 1.40 (d, J = 6.6 Hz, 3H), 1.15 (d, J = 6.6 Hz, 3H), 1.05 (d, J = 6.6 Hz, 3H), 0.45 (s, 3H). 13 C NMR (100 MHz, CDCl3) d168.4, 168.3, 143.9, 143.8, 143.6, 143.5, 141.4, 141.1, 140.4, 140.3, 139.8, 139.7, 137.9, 137.8, 137.7, 137.2, 137.1, 137.0, 136.7, 136.6, 134.7, 134.4, 134.4, 134.2, 133.8, 133.7, 133.5, 133.4, 133.3, 133.2, 131.0, 130.6, 130.1, 130.0, 128.6, 128.5, 128.4, 128.3, 128.2, 128.1, 128.0, 127.9, 127.7, 127.6, 127.5, 125.7, 125.6, 74.4, 74.3, 73.9, 73.8, 51.2, 51.1, 46.2, 46.1, 21.0, 20.8, 20.7, 20.7, 20.7, 20.5, 20.4, 20.1, 20.1, 20.0, 18.7, -1.8, -1.9. 31 p NMR (162 MHz, CDCl3) d -14.27, -14.54, -14.73.HRMS(ESI) m / z: [M+H] + Calculated for C 40 H 43 NO2PSi: 628.2795; found 628.2795. Example 16 (In) Preparation of compound In: In was prepared by a method substantially the same as that in Example 2. The crude product was purified by column chromatography: n-hexane / ethyl acetate = 20:1. A colorless oily liquid was obtained. 74.4 mg, yield 58%.

[0039] [α]25 D = -10.0 (c = 1.76, CHCl3). The compound with the In structure was analyzed using Waters 2695 high-performance liquid chromatography (HPLC). The column was a Chiralcel-IB column, the mobile phase was n-hexane / isopropanol = 99:1, the flow rate was 1 mL / min, and the wavelength was 254 nm. The retention time of the major enantiomer was t. r =18.370, 20.568 min, minor enantiomer retention time t r=9.683, 15.360 min. The results show that the corresponding selection excess values ​​of the major enantiomers of the compound shown in the In structure ( er The ratio is >99:1. 1 H NMR (400 MHz, CDCl3) d 7.64–7.46 (m, 1H), 7.39 (dd, J = 11.8, 7.8 Hz, 1H),7.32-7.13 (m, 16H), 7.09-6.98 (m, 3H), 6.94-6.86 (m, 1H), 6.58 (d, J = 7.8 Hz,1H), 6.06 (s, 1H), 3.91-3.84 (m, 1H), 3.48-3.41 (m, 1H), 2.39 (d, J = 15.5 Hz, 1H), 2.23 (d, J = 13.5 Hz, 1H), 2.12 (s, 3H), 1.52 (d, J = 6.8 Hz, 3H), 1.40 (d, J = 6.6 Hz, 3H), 1.15 (d, J = 6.6 Hz, 3H), 1.05 (d, J = 6.6 Hz, 3H), 0.45 (s, 3H). 13 C NMR (100 MHz, CDCl3) d 168.7, 168.6, 141.5, 141.2, 138.3, 135.0, 134.8, 134.3, 134.1, 133.8, 133.7, 133.5, 133.4, 133.3, 133.2, 131.0, 130.7, 130.6, 130.2, 130.1, 128.6, 128.5, 128.4, 128.3, 128.2, 128.0, 127.9, 127.6, 127.5, 125.8, 125.6, 74.3, 73.9, 51.2, 46.2, 21.7, 21.0, 20.9, 20.7, 20.6, 20.4, 20.2, 20.1, 19.9, 18.7, -1.7, -1.9. 31 p NMR (162 MHz, CDCl3) d-14.19, -14.48, -17.70.HRMS (ESI) m / z: [M+H] + Calculated for C 41 H 45 NO2PSi: 642.2952; found642.2961. Example 17 (Io) Preparation of compound Io: Io was prepared using a method substantially the same as that described in Example 2. The crude product was purified by column chromatography: hexane / ethyl acetate = 20:1. A colorless oily liquid was obtained. 66.8 mg, yield 52%.

[0040] [α]25 D = -4.8 (c = 0.46, CHCl3). The compound with structure Io was analyzed using Waters 2695 high-performance liquid chromatography (HPLC). The column was a Chiralcel-IB column, the mobile phase was n-hexane / isopropanol = 99:1, the flow rate was 1 mL / min, and the wavelength was 254 nm. The retention time of the major enantiomer was t. r =18.778, 20.765 min, minor enantiomer retention time t r =9.485, 15.456 min. The results show that the corresponding selection excess values ​​of the major enantiomers of the compound shown in the Io structure ( er The ratio is 92.5:7.5. 1 H NMR (400 MHz, CDCl3) d 7.62-7.48 (m, 1H), 7.45-7.28 (m, 3H), 7.28-7.14 (m, 12H), 7.13-6.83 (m, 4H), 6.58 (d, J = 7.8 Hz, 1H), 6.04 (s, 1H), 3.91-3.84 (m, 1H), 3.48-3.41 (m, 1H), 2.41 (t, J = 6.9 Hz, 1H), 2.38 (d, J = 4.9 Hz, 1H), 2.23 (d, J = 9.9 Hz, 1H), 1.51 (d, J = 6.8 Hz, 3H), 1.39 (d, J = 6.7 Hz, 3H), 1.14 (d, J = 6.6 Hz, 3H), 0.97 (d,J = 1.8 Hz, 3H), 0.88 (d, J = 6.6 Hz, 3H), 0.45(s, 3H). 13 C NMR (100 MHz, CDCl3) d 168.7, 168.6, 144.2, 141.5, 141.4, 141.2, 140.1, 140.0, 139.6, 139.5, 138.1, 138.0, 137.9, 137.6, 137.4, 137.3, 136.8, 136.6, 134.7, 134.3, 133.7, 133.6, 133.5, 133.4, 133.2, 133.1, 130.9, 130.6, 130.1, 123.0, 129.5, 129.3, 128.4, 128.3, 128.2, 128.0, 127.8, 127.7, 127.6, 127.4, 125.7, 125.6, 74.4, 74.0, 51.1, 46.1, 46.0, 28.6, 21.0, 20.9, 20.7, 20.6, 20.4, 20.1, 20.0, 18.7, 15.0, 14.9, -1.7, -1.9. 31 p NMR (162 MHz, CDCl3) d -13.85, -14.13, -14.35.HRMS (ESI) m / z: [M+H] + Calculated for C 42 H 47 NO2PSi:656.3108; found 656.3106. Application Example 1: Application of product Ia as a chiral ligand The compounds of this invention can be used as chiral ligands and / or catalysts in the synthesis of chiral drugs. This embodiment uses compound Ia as an example for illustration. Since the compounds provided by this invention all have multiple chiral centers, it is obvious that their chirality can be utilized to synthesize chiral drugs. Tris(dibenzylacetone)dipalladium-chloroform adduct (Pd2(dba)3·CHCl3) (4.1 mg, 0.004 mmol, 2 mol%) and Ia (9.1 mg, 0.016 mmol, 8 mol%) were dissolved in cyclohexane (2 mL, 0.1 M) and placed in a flame-dried Shrek tube. The mixture was stirred at room temperature for 30 minutes under nitrogen protection. Then, diphenylalkyne (35.6 mg, 0.2 mmol, 1 equivalent) and phenyl(1,3,5-trimethylphenyl)dihydrosilane (45.3 mg, 0.2 mmol, 1 equivalent) were added sequentially. The reaction tube was cooled to 0°C and stirred for 72 hours. After the reaction was complete, the product was purified by short-column diatomaceous earth chromatography using ethyl acetate (EtOAc) as solvent. The crude product was concentrated under reduced pressure and purified by silica gel column chromatography using petroleum ether (PE) as eluent to finally obtain the target product (III).

[0041] Preparation of Compound III: Prepared according to the method in Example 18. The crude product was purified by column chromatography: n-hexane / ethyl acetate = 80:1. A yellow oily liquid was given. 38.5 mg, yield 46%.

[0042] The compound with structure III was analyzed using Waters 2695 high-performance liquid chromatography (HPLC). The column was a Chiralcel-OD column, the mobile phase was n-hexane / isopropanol = 99.9:0.1, the flow rate was 1 mL / min, and the wavelength was 254 nm. The retention time of the major enantiomer was determined. r =5.341 min, minor enantiomer retention time t r =6.991 min. The results show that the corresponding selection excess value of the major enantiomer of the compound shown in structure III is ( er The ratio is 66.5:33.5. 1 HNMR (400 MHz, CDCl3): δ 7.42 (d, J = 6.8 Hz, 2H), 7.17-7.11 (m, 3H), 7.06-6.95 (m, 5H), 6.91-6.90 (m, 6H), 6.70(s, 2H), 5.49 (s, 1H), 2.21 (s, 6H), 2.12 (s, 3H). The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. A multi-chiral, non-biaryl organosilicon transisomer, characterized in that, The structural formula of the multi-chiral non-biaryl organosilicon transisomer is shown in formula (I) below: In the formula, R 1 It is hydrogen, substituted or unsubstituted alkyl, alkoxy, halogen, substituted or unsubstituted aryl, the substituent in the substituted alkyl is a heteroatom, and the substituent in the substituted aryl is an alkyl, alkoxy, haloalkyl, or halogen at different positions; R 2 R 3 Each is independently selected from alkyl, alkoxy, or aryl groups; R 4 It can be hydrogen, alkyl, alkoxy, halogen, aryl, or substituted aryl.

2. The multi-chiral center non-biaryl organosilicon transisomer according to claim 1, characterized in that, R 1 It is hydrogen, C1-C6 substituted or unsubstituted alkyl or C1-C4 alkoxy; R 2 R 3 Each group is independently selected from C1-C6 alkyl, C1-C4 alkoxy, phenyl, substituted aryl, or naphthyl groups; R 4 It can be hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen, phenyl, substituted aryl or naphthyl.

3. The multi-chiral center non-biaryl organosilicon transisomer according to claim 2, characterized in that, The compound represented by formula (I) is selected from one of the compounds represented by formulas (Ia) to (Io):

4. A method for preparing the multi-chiral central non-biaryl organosilicon transisomer as described in any one of claims 1-3, characterized in that, The preparation method includes the following steps: In the presence of phosphine ligands, nickel catalysts and reaction media, non-biaryl phosphine monoaldehydes are reacted with benzo[a]silane heterocyclic butane via silicon-carbon bond activation to undergo ring expansion reaction, thereby synthesizing the multi-chiral non-biaryl organosilicon transisomer. The synthesis route is shown below:

5. The preparation method according to claim 4, characterized in that, The nickel catalyst is bis(1,5-cyclooctadiene) nickel.

6. The preparation method according to claim 4, characterized in that, The phosphine ligand is any one of the compounds shown in formulas L1 to L27 below:

7. The preparation method according to claim 4, characterized in that, The molar ratio of non-biaryl phosphine monoaldehyde, benzosilane, phosphine ligand, and nickel catalyst is 1:(1-3):(0.12-0.4):(0.1-0.2).

8. The preparation method according to claim 4, characterized in that, The reaction time is at least 15 hours, and the reaction temperature is 0–60℃.

9. The use of the multi-chiral non-biaryl organosilicon transisomer as described in any one of claims 1-3 as a chiral ligand or catalyst.

10. The use of the multi-chiral center non-biaryl organosilicon transisomer as described in any one of claims 1-3 in the synthesis of chiral drugs.

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