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

Abstract

The invention provides a multi-chiral-center biaryl organosilicone atropisomer as well as a preparation method and application thereof, and provides a multi-chiral-center biaryl organosilicone atropisomer with a structural formula as shown in a formula (I), and a synthesis method for synthesizing the multi-chiral-center biaryl organosilicone atropisomer. In the presence of a phosphine ligand, a nickel catalyst and a reaction medium, biaryl dialdehyde and benzosilacyclobutane are subjected to silicon-carbon bond activation and a desymmetry reaction. The method is mild in reaction condition, simple to operate and high in substrate universality, a crude product can be subjected to vacuum concentration after being subjected to rapid column chromatography impurity removal to obtain a pure product, post-treatment is convenient, the finally obtained product is high in stereoselectivity, in addition, the biaryl skeleton can be used as a chiral synthesis precursor to be widely applied to various organic reactions and drug synthesis, and the method is suitable for industrial production. And the method has considerable application value. # imgabs0 #

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and specifically relates to a multi-chiral center biaryl organosilicon atropisomer and a preparation method and application thereof. Background Art

[0002] Axial chiral compounds with C–C and C–N bonds play a unique role in synthetic chemistry, medicinal chemistry, functional materials and natural products. Axial chiral compounds are different from traditional central chiral compounds in that their stereo configurations can be mutually converted at high temperatures without the need for chemical bond breaking. In addition, studies have shown that the introduction of other chiral centers into axial chiral compounds has great application value in the fields of chiral ligands, catalysts and bioactive molecules. For example, vancomycin, korupensamin, steganacin, etc. all contain both axial chirality and central chirality. In recent years, substantial progress has been made in the synthesis of axial chiral compounds, but the synthesis of compounds with both central chirality and axial chirality is still challenging. In addition, transition metal-catalyzed Si-C bond activation is one of the important strategies for the synthesis of organosilicon compounds. However, due to the difficulty in introducing silicon atoms into compounds, this method has rarely been reported in the construction of atropisomers of chiral centers.

[0003] Due to the unique structure and biological activity of atropisomers, scientists have developed a variety of strategies to synthesize compounds with chiral axes, among which the atropselective functionalization of racemic biaryl compounds through the strategy of (dynamic) kinetic resolution is one of the important methods for synthesizing compounds with chiral axes. In addition, studies have shown that the desymmetrization reaction of potential chiral compounds or mesomorphs has become one of the important and efficient strategies in asymmetric synthesis, and it has attracted much attention because it can simultaneously construct multiple chiral centers at the reaction site and potential chiral center. Therefore, researchers have applied this strategy to the one-step construction of central chirality and axial chirality.

[0004] Therefore, it is very necessary to design and develop multidimensional strategies to achieve the synthesis of carbon-chiral and axial-chiral biaryl compounds. Summary of the invention

[0005] The first purpose of the present invention is to provide a multi-chiral central biaryl organosilicon atropisomer in view of the deficiencies of the prior art, explore the Si-C bond activation reaction using different strategies under the Ni catalytic system, couple the construction of chiral silicon heterocycles with the formation of axial chirality, and establish a new strategy that can achieve the one-step construction of axial chirality and central chirality. The key to the success of this reaction lies in the precise control of stereoselectivity.

[0006] A multi-chiral center biaryl organosilicon atropisomer, the general structure of which is shown in the following formula (I):

[0007]

[0008] In the formula, * represents a chiral carbon atom, R 1 is alkyl, alkoxy, halogen, heteroatom-substituted alkyl, aryl or substituted aryl, wherein the substituents in the substituted aryl are alkyl, alkoxy, halogenated alkyl or halogen at different positions; R 2 is hydrogen, alkyl, alkoxy, or aryl; R 5 is hydrogen, alkoxy or halogen; R 6 is an alkyl group, an aldehyde group, an alkoxy group, a halogen group, an aryl group or a substituted aryl group; R 7 is hydrogen, alkyl, alkoxy, aryl; R is selected from the following structures:

[0009]

[0010] Among them, R 3 is alkyl, alkoxy, halogen, or aryl; R 4 is an alkyl group or a phenyl group, R 8 is an alkyl group, an aryl group or a substituted aryl group; Indicates the site where R is connected to the mother nucleus; when R 8 With R 4 When R 8 With R 4 When the two atoms are the same, they form a chiral center containing carbon chirality and axial chirality.

[0011] Preferably, R1 is C1-C6 alkyl, C1-C4 alkoxy or methylthio; R2 is hydrogen, C1-C6 alkyl, C1-C4 alkoxy, naphthyl or quinoline; R 3 is methyl, methoxy, halogen or naphthyl; R 4 It is a C1-C4 alkyl group or an unsubstituted phenyl group.

[0012] The second object of the present invention is to provide a method for preparing the compound as described above, wherein R 6 is an aldehyde group, R 7 When R is hydrogen and R is of formula (I-II), the method comprises the following steps: in the presence of a phosphine ligand, a nickel catalyst and a reaction medium, a biaryl dialdehyde and a benzosilacyclobutane are subjected to a silicon-carbon bond activation / desymmetrization reaction to synthesize a biaryl oxysilyl atrophisomer having carbon chirality and axial chirality, or a biaryl oxysilyl atrophisomer having carbon chirality, axial chirality and silicon chirality:

[0013]

[0014] When R 5When R is hydrogen and R is of formula (II), the method comprises the following steps: in the presence of a phosphine ligand, a nickel catalyst and a reaction medium, reacting a biaryl aldehyde with benzosilacyclobutane through a silicon-carbon bond activation / desymmetrization reaction, and performing post-treatment with tetrabutylammonium fluoride (TBAF) to synthesize a biaryl secondary alcohol compound having carbon chirality and axial chirality;

[0015]

[0016] Preferably, the nickel catalyst is bis(1,5-cyclooctadiene)nickel;

[0017] Preferably, the phosphine ligand is any one of the compounds represented by the following formulae L1 to L21:

[0018]

[0019] Preferably, the molar ratio of biaryl dialdehyde or biaryl aldehyde, benzosilacyclobutane, phosphine ligand, and nickel catalyst is 1: (1-3): (0.12-0.4): (0.1-0.2);

[0020] The reaction medium is selected from at least one of diethyl ether, tetrahydrofuran, toluene, 1,4-dioxane or ethyl acetate;

[0021] The reaction time is at least 1h;

[0022] The reaction temperature is 10-60°C.

[0023] The third object of the present invention is to provide the use of the above-mentioned multi-chiral center biaryl organosilicon atropisomer as a chiral ligand and a catalyst.

[0024] The fourth object of the present invention is to provide the use of the above-mentioned multi-chiral center biaryl organosilicon atropisomer in the synthesis of chiral drugs.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] The present invention synthesizes a multi-chiral center biaryl organosilicon atropisomer through a multi-dimensional strategy, which has at least carbon chirality and axial chirality, and may also have silicon chirality; the synthesis method of the above-mentioned multi-chiral center biaryl organosilicon atropisomer provided by the present invention can complete the reaction by stirring at a relatively low temperature, and the reaction conditions are mild, the operation is simple, and the substrate universality is strong. The crude product can be subjected to rapid column chromatography to remove impurities and then concentrated under reduced pressure to obtain a pure product, and the post-processing is convenient. The final product has high stereoselectivity. In addition, the biaryl skeleton can be used as a chiral synthesis precursor and is widely used in various organic reactions and drug synthesis, and has considerable application value. DETAILED DESCRIPTION

[0027] The present invention is further described below with reference to the embodiments.

[0028] Unless otherwise stated, all reactions were carried out under nitrogen protection and magnetic stirring. The catalytic reaction was carried out in a 25 mL Schlenk reaction tube under nitrogen protection. Anhydrous solvents were obtained by an inert solvent purification system (Et2O, CH2Cl2, THF and toluene. All reagents were purchased from commercial suppliers and used directly without further purification. Silica gel (200-300 mesh) was subjected to column chromatography using petroleum ether (bp: 60-90°C) and ethyl acetate as eluents. TLC thin layer chromatography was performed using F-254 pre-coated silica gel plates, and fluorescence quenching (λ max =254 nm) to develop the chromatogram. The nuclear magnetic resonance spectra were recorded on a Bruker Avance (400 MHz or 500 MHz) spectrometer using CDCl3 as solvent. Chemical shifts (δ) are expressed in ppm and coupling constants (J) are expressed in Hertz (Hz). NMR standards are as follows: ( 1 H NMR)CDCl3=7.26ppm;( 13 C NMR) CDCl3 = 77.16 ppm; 1 HNMR data recording.

[0029] As follows: δ represents chemical shift, s represents singlet, d represents doublet, dd represents doublet, t represents triplet, q represents quartet, m represents multiplet, br represents broad peak, and coupling constant is in Hz. It is recorded as chemical shift (δ, ppm) 13 CNMR. High resolution mass spectrometry (HRMS) analysis was performed using Waters Micromass (ESI-TOF). HPLC was performed on an Agilent 1260infinity instrument or a Waters Alliance e2695 instrument.

[0030] In the embodiments of the present invention, the following general synthesis method is adopted:

[0031]

[0032]

[0033] Add biaryl aldehyde or biaryl dialdehyde (0.2mmol), TADDOL-derived phosphoramidite ligand (12mol%) to a 25mL Schlenk reaction tube that has been operated in anhydrous and oxygen-free conditions and transfer it to a glove box in an argon atmosphere, then weigh Ni(cod)2 (10mol%) into the reaction tube and transfer it outside the glove box. Then, add 1,4-dioxane (2mL) and benzo-containing silicon-containing four-membered ring to the above reaction tube in sequence, and the reaction is carried out at room temperature for 20h. After the reaction is completed, filter with diatomaceous earth, remove the solvent in vacuo, and purify by silica gel column chromatography to obtain a multi-chiral center biaryl organosilicon atropisomer.

[0034] Example 1

[0035]

[0036] The crude product was purified by column chromatography to obtain a colorless oily product: 67.5 mg, 78% yield.

[0037] [α]25D=-254.1(c=0.61,CHCl3).

[0038] 1 H NMR(400MHz, CDCl3)δ9.61(s,1H),7.85-7.75(m,2H),7.51-7.41(m,3H),7.22-7.15(m,8H),7.11-7.00(m,2H) ,6.55(d,J=7.6Hz,1H),5.69(s,1H),2.14(d,J=15.2Hz,1H),1.97(d,J=15.6Hz,1H),0.21(s,3H),0.04(s,3H).

[0039] 13 C NMR (100MHz, CDCl3) δ192.2,143.2,142.02,141.95,141.8,140.4,137.2,134.7,133.6,133.5,131.0, 130.3,130.10,129.4,128.9,128.4,128.3,128.0,127.1,127.0,126.8,124.8,72.4,20.8,-0.4,-0.7.

[0040] HRMS(ESI)m / z:[M+Na] + calculated for C 29 H 26 NaO2Si,457.1594; found457.1599.

[0041] HPLC analysis was performed using a Chiralpak OX column: (n-hexane:isopropanol=98:2, 1.0 ml / min, 254 nm); t R =7.049min,>99.9%ee.

[0042] Example 2

[0043]

[0044] The crude product was purified by column chromatography to obtain a colorless oily product: 53.9 mg, 56% yield.

[0045] [α]25D=-331.6(c=0.61,CHCl3).

[0046] 1 H NMR (500MHz, CDCl3) δ9.68 (s, 1H), 7.84-7.77 (m, 2H), 7.76-7.70 (m, 3H), 7.66 (d, J = 8.5 Hz,1H),7.59(d,J=7.5Hz,1H),7.51-7.45(m,2H),7.45-7.39(m,2H),7.32(d,J=8.5Hz, 1H),7.28-7.21(m,2H),7.21-7.14(m,2H),7.07(t,J=7.5Hz,1H),6.63(d,J=7.5Hz,1H) ,5.84(s,1H),2.17(d,J=16.5Hz,1H),2.03(d,J=15.5Hz,1H),0.22(s,3H),0.08(s,3H).

[0047] 13 C NMR (100MHz, CDCl3) δ192.1,143.1,142.2,141.9,141.8,137.9,137.2,134.8,133.8,133.5,133.3,132.2,131.0,130.4,130. 4,128.9,128.6,128.4,128.2,128.0,127.8,127.6,127.2,127.2,127.1,126.9,126.2,126.1,124.8,72.4,20.8,-0.5,-0.7.

[0048] HRMS(ESI)m / z:[M+Na] + calculated for C 33 H 28 NaO2Si,507.1751; found507.1750.

[0049] HPLC analysis was performed using a Chiralpak OD column: (n-hexane:isopropanol=99:1, 0.8 ml / min, 254 nm); t R =7.017min,>99.9%ee.

[0050] Example 3

[0051]

[0052] The crude product was purified by column chromatography to obtain a white solid product: mp 105-106°C. 75.0 mg, 94% yield.

[0053] [α]25D=-138.2 (c=0.79, CHCl3).

[0054] 1 H NMR (500MHz, CDCl3) δ9.65(d,J=1.0Hz,1H),8.07(dd,J=7.5,1.5Hz,1H),7.84(dd,J=8.0,1.5Hz,1H),7.63(t,J=8 .0Hz,1H),7.43(dd,J=8.0,1.5Hz,1H),7.35(ddd,J=15,7.5,1.5Hz,1H),7.16(t,J=7.5Hz,1H),7.12(d,J=7.5Hz, 1H),7.06-6.97(m,2H),6.93(dd,J=7.5,1.5Hz,1H),6.44(d,J=8.0Hz,1H),5.50(s,1H),2.82-2.75(m,1H),2.12( d,J=15.0Hz,1H),1.92(d,J=15.5Hz,1H),1.23(d,J=7.0Hz,3H),1.07(d,J=7.0Hz,3H),0.22(s,3H),0.06(s,3H).

[0055] 13 C NMR (100MHz, CDCl3) δ192.5,147.1,143.4,142.3,141.5,136.8,134.8,134.1,133.4,130.3,130.2, 129.0,128.6,127.9,127.1,126.8,125.61,125.55,124.8,72.3,30.3,23.9,23.8,20.7,-0.2,-0.7.

[0056] HRMS(ESI)m / z:[M+Na] + calculated for C26 H 28 NaO2Si,423.1751; found423.1754.

[0057] HPLC analysis was performed using a Chiralpak OD column: (n-hexane:isopropanol=99.4:0.6, 0.8 ml / min, 254 nm); t R =6.525min,>99.9%ee.

[0058] Example 4

[0059]

[0060] The crude product was purified by column chromatography to obtain a colorless oily product: 55.3 mg, 74% yield.

[0061] [α]25D=-120.8(c=0.51,CHCl3).

[0062] 1 H NMR(400MHz, CDCl3)δ9.60(s,1H),8.05(dd,J=7.6,1.2Hz,1H),7.82(dd,J=8.0,1.6Hz,1H),7.61(t,J=7.6Hz,1H),7.35-7.23(m,2H),7.20-7 .04(m,3H),7.03-6.88(m,2H),6.46(d,J=7.6Hz,1H),5.45(s,1H),2.10(d,J=14.8Hz,4H),1.90(d,J=15.6Hz,1H),0.20(s,3H),0.07(s,3H).

[0063] 13 C NMR (100MHz, CDCl3) δ192.6,143.7,141.9,141.5,136.9,136.5,134.9,133.8,130.6,130. 3,130.0,128.6,128.5,127.8,126.99,126.97,125.9,124.8,72.3,20.5,20.4,-0.5,-0.7.

[0064] HRMS(ESI)m / z:[M+Na] + calculated for C 24 H 24 NaO2Si,395.1438; found395.1436.

[0065] HPLC analysis was performed using a Chiralpak OD column: (n-hexane:isopropanol=99.3:0.7, 1.2 ml / min, 254 nm); t R =4.543min,>99.9%ee.

[0066] Example 5

[0067]

[0068] The crude product was purified by column chromatography to obtain a colorless oily product: 37.7 mg, 42% yield.

[0069] [α]25D=-249.4(c=0.75,CHCl3).

[0070] 1 HNMR (400MHz, CDCl3) δ9.64(s,1H),7.83(d,J=7.6Hz,1H),7.77(d,J=8.0Hz,1H),7.51(t,J=7.6Hz,1H),7.41(s,2H),7.24-7.09(m,8H ),7.04(t,J=7.6Hz,1H),6.50(d,J=8.0Hz,1H),5.66(s,1H),2.16(d,J=15.2Hz,1H),2.01(d,J=15.2Hz,1H),0.21(s,3H),0.04(s,3H).

[0071] 13 C NMR (100MHz, CDCl3) δ191.7,142.07,141.5,141.2,140.4,139.2,137.0,135.4,134.7,133.5,133.1,131 .4,130.8,130.5,129.2,129.1,128.9,128.4,128.1,127.5,127.3,126.8,124.9,72.4,20.7,-0.3,-0.7.

[0072] HRMS(ESI)m / z:[M+Na] + calculated for C 29 H 25 ClNaO2Si,491.1205; found491.1203.

[0074] HPLC analysis was performed using a Chiralpak INB column: (n-hexane:isopropanol=99:1, 0.5 ml / min, 254 nm, ratio 86.8:1.4:3.5:8.2); major diastereomers t R =6.833,7.382minor,97%ee; minordiastereomers t R =8.481,9.145min.

[0075] Example 6

[0076]

[0077] The crude product was purified by column chromatography to obtain a colorless oily product: 67.2 mg, 87% yield.

[0078] [α]25D=-104.8(c=0.66,CHCl3).

[0079] 1 H NMR (400MHz, CDCl3) δ9.60 (d, J=0.8Hz, 1H), 8.05 (dd, J=7.6, 1.2Hz, 1H), 7.82 ( dd,J=7.6,1.6Hz,1H),7.61(t,J=7.6Hz,1H),7.22-7.09(m,3H),7.04-6.92(m,2 H),6.89-6.82(m,1H),6.49(d,J=7.6Hz,1H),5.50(s,1H),2.36(s,3H),2.11(d ,J=15.6Hz,1H),2.03(s,3H),1.93(d,J=15.6Hz,1H),0.21(s,3H),0.09(s,3H).

[0080] 13 C NMR (100MHz, CDCl3) δ192.7,144.5,141.9,141.5,137.1,136.8,135.1,134.8,133.9,130.6, 130.0,128.4,128.2,127.8,127.0,126.8,125.3,124.8,72.3,20.7,20.4,17.0,-0.5,-0.7.

[0081] HRMS(ESI)m / z:[M+Na] + calculated for C 27 H 24NaO2Si,431.1438; found431.1436.

[0082] HPLC analysis was performed using a Chiralpak OD column: (n-hexane:isopropanol = 99.5:0.5, 0.6 ml / min, 254 nm); major diastereomers t R =8.532min,>99.9%ee; minor diastereomers t R =9.783min.

[0083] Example 7

[0084]

[0085] The crude product was purified by column chromatography to obtain a yellow oily product: 57.2 mg, 74% yield.

[0086] [α]25D=-133.7(c=0.70,CHCl3).

[0087] 1 H NMR (400MHz, CDCl3) δ9.63(s,1H),8.05(dd,J=7.6,1.2Hz,1H),7.83(dd,J=7.6,1.2Hz,1H),7.61(t,J=8.0Hz,1H),7.21-7.08(m,3H),7.00(t,J=7 .6Hz,1H),6.88(s,2H),6.48(d,J=7.6Hz,1H),5.51(s,1H),2.33(s,3H), 2.10(d,J=16.4Hz,4H),1.95(d,J=15.6Hz,1H),0.24(s,3H),0.09(s,3H).

[0088] 13 C NMR (100MHz, CDCl3) δ192.8,143.9,142.1,141.6,138.1,136.9,136.2,134.8,133.9,131.8,130 .8,130.5,130.2,128.5,127.8,127.0,126.9,126.7,124.8,72.3,21.3,20.5,20.3,-0.5,-0.7.

[0089] HRMS(ESI)m / z:[M+Na] + calculated for C 25 H 26NaO2Si,409.1605; found409.1603.

[0090] HPLC analysis was performed using a Chiralpak OD column: (n-hexane:isopropanol=99.3:0.7, 1 ml / min, 254 nm); major diastereomers t R =4.893min,>99.9%ee; minor diastereomers t R =5.597min.

[0091] Example 8

[0092]

[0093] The crude product was purified by column chromatography to obtain a white solid product: mp 109-111°C. 52.5 mg, 64% yield. [α]25D = -134.4 (c = 0.63, CHCl3).

[0094] 1 H NMR(400MHz, CDCl3) δ9.44(d,J=0.8Hz,1H),8.96(dd,J=4.4,1.4Hz),8.18-8.09(m,2H),7.90(dd,J=8.01.6 Hz,1H),7.85(d,J=8.4Hz,1H),7.73(t,J=8.0Hz,1H),7.61(dd,J=8.8,7.2Hz,1H),7.37(dd,J=8.4,4.0Hz,1H ),7.32(dd,J=7.2,1.2Hz,1H),7.15(td,J=7.6,1.2Hz,1H),7.07(d,J=6.4Hz,1H),7.01(t,J=7.2Hz,1H),6. 51(d,J=7.6Hz,1H),5.28(s,1H),1.98(d,J=15.6Hz,1H),1.68(d,J=15.6Hz,1H),0.01(s,3H),-0.08(s,3H).

[0095] 13 C NMR (100MHz, CDCl3) δ191.7,150.9,147.9,142.9,141.1,140.5,136.9,134.9,134.3,133.2,1 30.6,130.1,129.4,129.0,128.8,128.0,127.4,126.8,124.8,121.9,72.3,20.2,-0.8,-0.8.

[0096] HRMS(ESI)m / z:[M+Na] + calculated for C 26 H 23 NNaO2Si,432.1390; found432.1385.

[0097] HPLC analysis was performed using a Chiralpak OX column: (n-hexane:isopropanol=80:20, 1 ml / min, 254 nm, ratio 7.4:2.4:84.3:5.9); major diastereomers t R =13.982,18.085min,84%ee; minor diastereomers t R =15.796,24.819min.

[0098] Example 9

[0099]

[0100] The crude product was purified by column chromatography to obtain a colorless oily product: 63.1 mg, 77% yield.

[0101] [α]25D=-151.9 (c=0.48, CHCl3).

[0102] 1 HNMR (500MHz, CDCl3) δ9.44(s,1H),8.13(d,J=8.5Hz,1H),7.92(t,J=8.5Hz,2H),7.86(d,J=8.0Hz ,1H),7.72(t,J=8.0Hz,1H),7.55-7.48(m,2H),7.44(t,J=7.5Hz,1H),7.35(t,J=7.5Hz,1H),7.21 (d,J=6.5Hz,1H),7.15(t,J=7.5Hz,1H),7.06(d,J=7.5Hz,1H),7.01(t,J=7.5Hz,1H),6.52(d,J=8 .0Hz,1H),5.33(s,1H),1.97(d,J=15.5Hz,1H),1.65(d,J=15.5Hz,1H),0.02(s,3H),-0.09(s,3H).

[0103] 13C NMR (125MHz, CDCl3) δ192.4,142.8,142.3,141.8,137.1,134.9,134.8,133.3,132.7,130.4,12 9.0,128.8,128.4,127.9,127.03,126.99,126.8,126.5,126.2,125.1,124.8,72.2,20.3,-0.8.

[0104] HRMS(ESI)m / z:[M+Na] + calculated for C 27 H 24 NaO2Si,431.1438; found431.1436.

[0105] HPLC analysis was performed using a Chiralpak OD column: (n-hexane:isopropanol=99.2:0.8, 0.9 ml / min, 254 nm); t R =7.084min,>99.9%ee.

[0106] Example 10

[0107]

[0108] The crude product was purified by column chromatography to obtain a white solid product: mp 132-135°C. 70.8 mg, 82% yield.

[0109] [α]25D=-164.3(c=0.28,CHCl3).

[0110] 1 HNMR (400MHz, CDCl3) δ9.58 (s, 1H), 7.55 (d, J = 3.2Hz, 1H), 7.43-7.36 (m, 2H), 7.32 (td, J = 7.6, 1.6 Hz,1H),7.15(td,J=7.2,1.6Hz,1H),7.09(d,J=7.2Hz,1H),7.04-6.95(m,2H),6.91(dd,J=7.6,1. 6Hz,1H),6.47(d,J=7.6Hz,1H),5.45(s,1H),3.91(s,3H),2.98-2.59(m,1H),2.10(d,J=15.2Hz,1 H),1.89(d,J=15.2Hz,1H),1.21(d,J=6.8Hz,3H),1.04(d,J=6.8Hz,3H),0.21(s,3H),0.03(s,3H).

[0111] 13 C NMR (100MHz, CDCl3) δ192.4,159.6,147.6,144.0,141.3,136.7,136.5,135.2,133.2,130.8,130.3,12 8.9,127.8,127.1,125.6,125.5,124.8,121.5,110.1,72.2,55.6,30.2,23.9,23.8,20.6,-0.2,-0.7.

[0112] HRMS(ESI)m / z:[M+Na] + calculated for C 27 H 30 NaO3Si,453.1856; found453.1858.

[0113] HPLC analysis was performed using a Chiralpak OX column: (n-hexane:isopropanol=99:1, 1 ml / min, 254 nm, ratio 7.4:2.4:84.3:5.9); t R =7.438min,>99.9%ee.

[0114] Embodiment 11

[0115]

[0116] The crude product was purified by column chromatography to obtain a colorless oily product: 69.7 mg, 81% yield. [α]25D = -120.3 (c = 0.64, CHCl3).

[0117] 1HNMR(500MHz, CDCl3)δ9.64(s,1H),8.07(dd,J=8.0,1.5Hz,1H),7.87(dd,J=8.0,1.5Hz,1H),7.62(t,J=8.0Hz,1H),7 .42(dd,J=8.0,1.0Hz,1H),7.34(td,J=7.5,1.5Hz,1H),7.20-7.11(m,2H),7.06-6.96(m,2H),6.93(dd,J=7.5,1.0Hz, 1H),6.42(d,J=8.0Hz,1H),5.51(s,1H),2.76-2.83(m,1H),2.14(d,J=15.5Hz,1H),1.93(d,J=15.5Hz,1H),1.22(d,J= 7.0Hz,3H),1.07(d,J=7.0Hz,3H),0.95(t,J=8.0Hz,3H),0.78(t,J=8.0Hz,3H),0.73-0.64(m,2H),0.58-0.47(m,2H).

[0118] 13 C NMR (100MHz, CDCl3) δ192.7,147.1,143.3,142.6,141.7,137.1,134.8,134.1,133.4,130.3,130.2, 129.0,128.6,127.9,127.1,126.7,125.6,125.5,124.7,30.3,24.0,23.8,17.5,6.7,6.6,6.4,6.1.

[0119] HRMS(ESI)m / z:[M+Na] + calculated for C 28 H 32 NaO2Si,451.2064; found451.2060.

[0120] HPLC analysis was performed using a Chiralpak OX column: (n-hexane:isopropanol=99:1, 0.6 ml / min, 254 nm); t R =8.755,9.183min,>99%ee.

[0121] Example 12

[0122]

[0123] The crude product was purified by column chromatography to obtain a colorless oily product: 44.7 mg, 49% yield.

[0124] [α]25D=-186.0(c=0.78,CHCl3).

[0125] 1 HNMR (400MHz, CDCl3) δ7.84 (dd, J=16.8, 8.8Hz, 2H), 7.59 (d, J=8.8Hz, 1H), 7.53 (dd, J=8.0, 1. 6Hz,1H),7.49-7.37(m,3H),7.33(ddd,J=8.0,6.4,1.2Hz,1H),7.29-7.22(m,1H),7.21-7.18( m,2H),7.17-7.10(m,3H),7.09-7.03(m,3H),6.96(ddd,J=9.6,7.6,2.0Hz,1H),6.53(d,J=7.6 Hz,1H),5.76(s,1H),2.13(d,J=15.2Hz,1H),2.00(d,J=15.2Hz,1H),0.23(s,3H),0.06(s,3H).

[0126] 13 C NMR (100MHz, CDCl3) δ142.0,141.9,141.1,137.5,137.2,136.9,136.4,133.0,132.6,131.6,130.2,130.2,129.0,1 28.3,128.1,128.0,127.8,127.6,127.3,127.2,127.0,126.8,126.0,125.9,125.6,124.6,73.6,20.9,-0.2,-0.6.

[0127] HRMS(ESI)m / z:[M+Na] + calculated for C 32 H 28 NaOSi,479.1802; found479.1809.

[0128] The product was analyzed by HPLC using a Chiralpak OD column: (n-hexane:isopropanol, 99.2:0.8, 0.9 ml / min, 254 nm, ratio 2.5:4.2:0:93.3); major diastereomers t R =5.238min,6.693min,95%ee; minor diastereomers t R =5.69min.

[0129] The recovered raw material was analyzed by HPLC using a Chiralpak OX column: 27.9 mg, 44% yield. (n-hexane:isopropanol=98:2, 1 ml / min, 254 nm); t R =9.256min,11.477min,97%ee.

[0130] Embodiment 13

[0131]

[0132] The crude product was purified by column chromatography to obtain a colorless oily product: 36.3 mg, 43% yield.

[0133] [α]25D=-4.2 (c=0.59, CHCl3).

[0134] 1 H NMR (500MHz, CDCl3) δ7.97(d,J=8.5Hz,1H),7.92(dd,J=8.0,1.0Hz,1H),7.65(d,J=9.0Hz,1H),7.50(ddd,J =8.0,6.5,1.5Hz,2H),7.43-7.34(m,2H),7.34-7.29(m,1H),7.19-7.12(m,2H),7.09(ddd,J=9.0,7.5,1.5H z,1H),6.96(ddd,J=9.0,7.5,1.5Hz,2H),6.53(d,J=8.0Hz,1H),5.63(s,1H),2.78-2.62(m,1H),2.14(d,J= 15.5Hz,1H),1.97(d,J=15.0Hz,1H),1.19(d,J=7.0Hz,3H),1.03(d,J=6.5Hz,3H),0.23(s,3H),0.10(s,3H).

[0135] 13 C NMR (100MHz, CDCl3) δ147.6,141.8,137.6,137.1,137.0,136.3,133.2,132.8,130.4,130.3,128.4,128.3,128 .0,127.59,127.55,127.0,126.2,126.0,125.9,125.6,125.6,124.7,73.7,30.3,24.4,24.0,20.8,-0.1,-0.6.

[0136] HRMS(ESI)m / z:[M+Na] + calculated for C29 H 30 NaOSi,445.1958; found445.1953.

[0137] The product was analyzed by HPLC using a Chiralpak OD column: (n-hexane:isopropanol, 100:0, 1 ml / min, 254 nm, ratio 198.3:0:1.7:0); major diastereomers t R =5.288min,6.838min,97%ee.

[0138] The recovered raw material was analyzed by HPLC using a Chiralpak OX column: 28.0 mg, 51% yield. (n-hexane:isopropanol=98:2, 1 ml / min, 254 nm); t R =6.573min,>99.9%ee.

[0139] Embodiment 14

[0140]

[0141] The crude product was purified by column chromatography to obtain a colorless oily product: 38.9 mg, 55% yield.

[0142] [α]25D=-73.0 (c=0.67, CHCl3).

[0143] 1 H NMR (400MHz, CDCl3) δ7.72-7.78(m,2H),7.65(d,J=8.8Hz,1H),7.34-7.38(m,1H),7.27-7.18(m,4H),7.15-7.08(m,2H),7. 06-7.01(m,2H),6.99-6.97(m,1H),6.95-6.91(m,1H),6.56(dd,J=7.2,1.2Hz,1H),5.72(s,1H),1.92(s,3H),1.78(s,3H).

[0144] 13 C NMR (100MHz, CDCl3) δ141.6,138.2,137.7,137.6,137.5,137.0,136.1,133.1,132.5,130.6,130.3,130. 1,128.1,127.9,127.8,127.5,127.3,126.3,126.2,126.1,126.0,125.9,125.7,124.5,70.7,20.0,19.1.

[0145] HRMS(ESI)m / z:[M+Na] + calculated for C 25 H 22 NaO,361.1563; found 361.1563.

[0146] The product was analyzed by HPLC using a Chiralpak OX column: (n-hexane:isopropanol, 95:5, 1 ml / min, 254 nm); major diastereomers t R =9.09,10.393min,96%ee.

[0147] The recovered raw material was analyzed by HPLC using a Chiralpak Phen column: 30.4 mg, 49% yield. (n-hexane:isopropanol=98:2, 1 ml / min, 254 nm); t R =7.422,7.969min,98%ee.

[0148] Embodiment 15

[0149]

[0150] The crude product was purified by column chromatography to obtain a colorless oily product: 31.5 mg, 43% yield.

[0151] [α]25D=-163.0 (c=0.69, CHCl3).

[0152] 1 H NMR (400MHz, CDCl3) δ7.72-7.68(m,2H),7.64(dd,J=8.0,1.6Hz,1H),7.39-7.30(m,2H),7.28-7.19(m,3 H),7.16-7.10(m,3H),7.07-6.97(m,2H),6.89(d,J=7.2Hz,1H),5.64(s,1H),2.21(s,3H),1.74(s,3H).

[0153] 13C NMR (100MHz, CDCl3) δ140.9,138.4,138.0,136.3,135.5,135.0,133.2,132.5,130.9,130.2,129. 2,128.9,128.2,127.1,126.5,126.3,126.2,126.0,125.9,125.1,124.8,124.2,70.9,19.8,14.8.

[0154] HRMS(ESI)m / z:[M+Na] + calculated for C 25 H 22 NaOS,393.1284; found 393.1283.

[0155] The product was analyzed by HPLC using a Chiralpak OX column: (n-hexane:isopropanol, 80:20, 1 ml / min, 254 nm); major diastereomers t R =6.019,7.283min,95%ee,minor diastereomers t R =9.046,9.958min.

[0156] The recovered raw material was analyzed by HPLC using a Chiralpak OX column: 30.4 mg, 49% yield. (n-hexane:isopropanol=98:2, 1 ml / min, 254 nm); t R =15.402,17.175min,64%ee.

[0157] Example 16

[0158]

[0159] The crude product was purified by column chromatography to obtain a colorless oily product: 29.7 mg, 34% yield.

[0160] [α]25D=7.1 (c=0.59, CHCl3).

[0161] 1H NMR (400MHz, CDCl3) δ7.77(dd,J=7.6,1.6Hz,1H),7.69(d,J=8.8Hz,1H),7.53(dd,J=8.0,1.6Hz,1H),7.50-7.48(m, 1H),7.45-7.37(m,3H),7.35-7.28(m,2H),7.11-6.96(m,8H),6.91(dd,J=6.8,1.6Hz,1H),5.49(s,1H),1.74(s,3H).

[0162] 13 C NMR (100MHz, CDCl3) δ140.7,140.1,139.5,138.1,137.5,135.31,135.26,133.3,133.2,132.9,132.6,131. 6,130.3,129.0,128.8,128.6,128.4,127.9,127.4,126.8,126.6,126.5,126.1,125.9,125.1,70.3,19.5.

[0163] HRMS(ESI)m / z:[M+Na] + calculated for C 30 H 23 ClNaO,457.1330; found 457.1329.

[0164] The product was analyzed by HPLC using a Chiralpak OX column: (n-hexane:isopropanol, 95:5, 1 ml / min, 254 nm); major diastereomers t R =9.549,10.615min,91%ee.

[0165] The recovered raw material was analyzed by HPLC using a Chiralpak OX column: 30.4 mg, 49% yield. (n-hexane:isopropanol=98:2, 1 ml / min, 254 nm); t R =10.364,11.372min,35%ee.

[0166] Embodiment 17

[0167]

[0168] The crude product was purified by column chromatography to obtain a colorless oily product: 36.9 mg, 55% yield.

[0169] [α]25D=-81.1(c=0.76,CHCl3).

[0170] 1 H NMR (400MHz, CDCl3) δ7.80-7.76(m,2H),7.56(d,J=8.8Hz,1H),7.37-3.7(m,1H),7.28-7.19(m,2H),7.16-7.1 0(m,3H),7.04(dd,J=6.0,3.6Hz,2H),6.97-6.87(m,2H),5.73(s,1H),2.29(s,3H),1.81(s,3H),1.79(s,3H).

[0171] 13 C NMR (100MHz, CDCl3) δ141.5,138.3,137.6,137.5,137.2,136.7,136.3,135.9,135.6,133.0,132.8,130.3,1 29.3,128.3,128.0,127.7,127.4,127.1,126.5,126.2,126.0,125.9,125.4,124.6,70.9,20.7,19.2,16.8.

[0172] HRMS(ESI)m / z:[M+Na] + calculated for C 26 H 24 NaO,375.1719; found 375.1717.

[0173] The product was analyzed by HPLC using a Chiralpak OX column: (n-hexane:isopropanol, 95:5, 1 ml / min, 254 nm); major diastereomers t R =8.508,10.208min,98%ee.

[0174] The recovered raw material was analyzed by HPLC using a Chiralpak OX column: 30.4 mg, 49% yield. (n-hexane:isopropanol=98:2, 1 ml / min, 254 nm); t R =7.261,7.663min,86%ee.

[0175] Embodiment 18

[0176]

[0177] The crude product was purified by column chromatography to obtain a colorless oily product: 35.3 mg, 52% yield.

[0178] [α]25D=-109.8(c=0.79,CHCl3).

[0179] 1 H NMR (400MHz, CDCl3) δ7.84-7.71(m,2H),7.57(d,J=8.4Hz,1H),7.36-7.31(m,1H),7.26-7.19(m,2H),7.18-7.13(m,1H),7 .09(s,1H),7.06-6.99(m,2H),7.00-6.87(m,2H),6.85-6.80(m,1H),5.73(s,1H),2.30(s,3H),1.88(s,3H),1.79(s,3H).

[0180] 13 C NMR (100MHz, CDCl3) δ141.7,137.8,137.7,137.4,136.9,136.0,134.5,133.1,132.7,130.9,130.3 4,130.29,128.1,127.5,127.2,126.5,126.3,126.2,126.0,125.8,124.6,70.8,21.4,12.0,19.2.

[0181] HRMS(ESI)m / z:[M+Na] + calculated for C 26 H 24 NaO,375.1719; found 375.1718.

[0182] The product was analyzed by HPLC using a Chiralpak OX column: (n-hexane:isopropanol, 95:5, 1 ml / min, 254 nm); major diastereomers t R =9.011,10.602min,96%ee.

[0183] The recovered raw material was analyzed by HPLC using a Chiralpak OX column: 30.4 mg, 49% yield. (n-hexane:isopropanol=98:2, 1 ml / min, 254 nm); t R =6.998,7.465min,>99%ee.

[0184] Embodiment 19

[0185]

[0186] The crude product was purified by column chromatography to obtain a colorless oily product: 41.9 mg, 56% yield.

[0187] [α]25D=-136.1(c=0.75,CHCl3).

[0188] 1 H NMR (400MHz, CDCl3) δ7.87-7.75(m,4H),7.63(d,J=8.8Hz,1H),7.39-7.27(m,3H),7.26-7.21(m,1H),7.19-7.15(m,2H ),7.12-7.06(m,1H),7.05-7.01(m,1H),7.01-6.97(m,2H),6.90-6.82(m,2H),5.53(s,1H),1.75(s,1H),1.58(s,3H).

[0189] 13 C NMR (100MHz, CDCl3) δ141.5,139.1,135.9,135.7,135.6,133.8,133.3,133.1,132.9,130.3,128.6,12 8.4,128.1,128.0,127.5,127.0,126.8,126.7,126.3,126.2,126.0,125.7,125.5,124.7,70.7,19.1.

[0190] HRMS(ESI)m / z:[M+Na] + calculated for C 28 H 22 NaO,397.1563; found 397.1562.

[0191] The product was analyzed by HPLC using a Chiralpak OX column: (n-hexane:isopropanol, 90:10, 1 ml / min, 254 nm); major diastereomers t R =7.104,8.885min,94%ee.

[0192] The recovered raw material was analyzed by HPLC using a Chiralpak AD column: 30.4 mg, 49% yield. (n-hexane:isopropanol=98:2, 1 ml / min, 254 nm); t R =8.950min,>99.9%ee.

[0193] Embodiment 20

[0194]

[0195] The crude product was purified by column chromatography to obtain a colorless oily product: 40.1 mg, 48% yield.

[0196] [α]25D=-22.5(c=0.68,CHCl3).

[0197] 1 H NMR (400MHz, CDCl3) δ7.75(dd,J=8.0,1.2Hz,1H),7.65(d,J=8.4Hz,1H),7.56(dd,J=7.6,1.2Hz,2H),7.46(ddd,J=8.8,7.2,1.2Hz,1H),7.40(ddd,J=8.4, 6.8,1.6Hz,1H),7.38-7.30(m,2H),7.27-7.20(m,2H),7.09-6.98(m,6H),6.8 2-6.79(m,1H),6.74(d,J=7.6Hz,1H),5.47(s,1H),2.18(s,3H),1.61(s,3H).

[0198] 13 C NMR (100MHz, CDCl3) δ141.5,140.6,140.6,137.2,136.8,136.3,135.1,133.8,133.0,132.9,132.1,130.3,130.0 ,129.2,128.6,128.5,128.4,128.2,127.7,127.6,127.2,127.1,126.8,126.5,125.94,125.4,70.2,21.3,19.3.

[0199] HRMS(ESI)m / z:[M+Na] + calculated for C 31 H 26 NaO,437.1876; found 437.1873.

[0200] The product was analyzed by HPLC using a Chiralpak OX column: (n-hexane:isopropanol, 80:20, 1 ml / min, 254 nm); major diastereomers t R =4.235,5.011min,97%ee.

[0201] The recovered raw material was analyzed by HPLC using a Chiralpak OX column: 30.4 mg, 49% yield. (n-hexane:isopropanol=98:2, 1 ml / min, 254 nm); t R =10.079,12.847min,90%ee.

[0202] Embodiment 21

[0203]

[0204] The crude product was purified by column chromatography to obtain a colorless oily product: 52.5 mg, 71% yield.

[0205] [α]25D=-257.7(c=0.68,CHCl3).

[0206] 1 H NMR (400MHz, CDCl3) δ7.88-7.80 (m, 3H), 7.64 (dd, J = 8.4, 1.2Hz, 1H), 7.54-7.4 9(m,1H),7.48-7.41(m,1H),7.38(d,J=8.4Hz,1H),7.32(ddd,J=8.8,7.6,1.2Hz ,1H),7.20(ddd,J=8.8,7.6,1.6Hz,1H),7.08-6.97(m,3H),6.80(dd,J=7.2,2.0 Hz,1H),6.03(d,J=1.2Hz,1H),5.94(s,1H),5.90(d,J=1.6Hz,1H),1.82(s,3H).

[0207] 13 C NMR (100MHz, CDCl3) δ147.4,145.7,140.8,138.9,135.0,133.3,132.4,131.6,130.3,129.2,128.2 ,127.2,126.5,126.4,126.2,125.9,125.8,125.1,124.8,122.2,119.8,108.6,100.8,71.1,19.4.

[0208] HRMS(ESI)m / z:[M+Na] + calculated for C 25 H 20 NaO3,391.1305; found 391.1301.

[0209] HPLC analysis was performed using a Chiralpak OD column: (n-hexane:isopropanol, 96:4, 0.8 ml / min, 254 nm); major diastereomers t R =17.908,19.687min,98%ee.

[0210] Embodiment 22

[0211]

[0212] The crude product was purified by column chromatography to obtain a colorless oily product: 56.2 mg, 74% yield. [α]25D = -219.4 (c = 0.88, CHCl3).

[0213] 1 H NMR (400MHz, CDCl3) δ7.92-7.79(m,2H),7.71-7.60(m,2H),7.55-7.48(m,1H),7.47-7.40(m,2H),7.07-6.98(m,3H),6.95(d,J =7.2Hz,1H),6.82(dd,J=7.2,1.6Hz,1H),6.02(d,J=1.2Hz,1H),5.93(s,1H),5.90(d,J=1.2Hz,1H),2.43(s,3H),1.78(s,3H).

[0214] 13 C NMR (100MHz, CDCl3) δ147.4,145.7,140.5,138.9,135.2,133.3,132.4,131.8,131.6,130.2,129. 2,128.2,127.8,126.5,126.4,126.2,125.2,124.8,122.2,119.8,108.5,100.8,71.1,21.4,19.0.

[0215] HRMS(ESI)m / z:[M+Na] + calculated for C 26 H 22 NaO3,405.1461; found405.1457.

[0216] HPLC analysis was performed using a Chiralpak OD column: (n-hexane:isopropanol=95:5, 1 ml / min, 230 nm); t R =9.674,12.631min,98%ee.

[0217] Embodiment 23

[0218]

[0219] The crude product was purified by column chromatography to obtain a colorless oily product: 23.0 mg, 26% yield.

[0220] [α]25D=3.3 (c=0.90, CHCl3).

[0221] 1 H NMR (400MHz, CDCl3) δ9.58(s,1H),8.02(dd,J=7.6,1.6Hz,1H),7.84(dd,J=7.6,1.2Hz,1H),7.56(t,J=7.6Hz,1H),7.36-7.18(m,7H),7.14-7.08(m,1H ),7.08-7.02(m,2H),7.01-6.94(m,2H),6.49(d,J=7.6Hz,1H),5.56(s,1H) ,2.28(d,J=15.6Hz,1H),2.10(s,3H),2.05(d,J=15.6Hz,1H),0.46(s,3H).

[0222] 13 C NMR (100MHz, CDCl3) δ192.6,143.7,141.7,141.7,136.5,136.5,136.5,135.0,134.9,133.8,133.7,130. 7,130.4,130.1,130.1,128.6,128.6,128.0,127.9,127.0,127.0,125.9,125.0,72.6,20.5,20.1,-2.2.

[0223] HRMS(ESI)m / z:[M+Na] + calculated for C 29 H 26 NaO2Si,457.1594; found457.1592.

[0224] HPLC analysis was performed using a Chiralpak AD column: (n-hexane:isopropanol=99.8:0.2, 0.6 ml / min, 254 nm); t R =29.257min,>99.9%ee.

[0225] The compound obtained by the invention has obvious chirality and can be used as a chiral ligand and catalyst and applied to the synthesis of chiral drugs.

[0226] The above is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed by the present invention should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention should be based on the protection scope of the claims.

Claims

1. A multi-chiral center biaryl organosilicon atropisomer, characterized in that: The structural formula is shown in formula (I): In the formula, * represents a chiral carbon atom; R 1 is alkyl, alkoxy, halogen, heteroatom-substituted alkyl, aryl or substituted aryl, wherein the substituents in the substituted aryl are alkyl, alkoxy, halogenated alkyl or halogen at different positions; R 2 is hydrogen, alkyl, alkoxy, or aryl; R 5 is hydrogen, alkoxy or halogen; R 6 is an alkyl group, an aldehyde group, an alkoxy group, a halogen group, an aryl group or a substituted aryl group; R 7 is hydrogen, alkyl, alkoxy, aryl; R is selected from the following structural fragments: Among them, R 3 is alkyl, alkoxy, halogen, or aryl; R 4 is an alkyl group or a phenyl group, R 8 is an alkyl group, an aryl group or a substituted aryl group.

2. The multi-chiral center biaryl organosilicon atropisomer according to claim 1, characterized in that: R1 is C1-C6 alkyl, C1-C4 alkoxy or methylthio; R2 is hydrogen, C1-C6 alkyl, C1-C4 alkoxy, naphthyl or quinoline; R 3 is methyl, methoxy, halogen or naphthyl; R 4 It is a C1-C4 alkyl group or an unsubstituted phenyl group.

3. A method for preparing a multi-chiral biaryl organosilicon atropisomer according to any one of claims 1 to 2, characterized in that: When R 6 is an aldehyde group, R 7 When R is hydrogen and R is of formula (I-II), the preparation method comprises the following steps: in the presence of a phosphine ligand, a nickel catalyst and a reaction medium, a biaryl dialdehyde and a benzosilacyclobutane are reacted through silicon-carbon bond activation and desymmetrization reaction to synthesize the multi-chiral center biaryl organosilicon atropisomer: When R 5 When R is hydrogen and R is of formula (II), the preparation method comprises the following steps: in the presence of a phosphine ligand, a nickel catalyst and a reaction medium, a biaryl aldehyde and a benzosilacyclobutane are subjected to silicon-carbon bond activation and desymmetrization reaction, and post-treated with tetrabutylammonium fluoride TBAF to synthesize the multi-chiral center biaryl organosilicon atropisomer; 4. The preparation method according to claim 3, characterized in that: The nickel catalyst is bis(1,5-cyclooctadiene)nickel.

5. The preparation method according to claim 3, characterized in that: The phosphine ligand is any one of the compounds represented by the following formulas L1 to L21:

6. The preparation method according to claim 3, characterized in that: The molar ratio of the biaryl dialdehyde or biaryl aldehyde, benzosilacyclobutane, phosphine ligand and nickel catalyst is 1:(1-3):(0.12-0.4):(0.1-0.2).

7. The preparation method according to claim 3, characterized in that: The reaction medium is selected from at least one of diethyl ether, tetrahydrofuran, toluene, 1,4-dioxane or ethyl acetate.

8. The preparation method according to claim 3, characterized in that: The reaction time is at least 1 hour, and the reaction temperature is 10-60°C.

9. Use of the multi-chiral center biaryl organosilicon atropisomer according to any one of claims 1 to 2 as a chiral ligand or catalyst.

10. Use of the multi-chiral center biaryl organosilicon atropisomer according to any one of claims 1 to 2 in the synthesis of chiral drugs.

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