A method for preparing a chiral silicon-containing stereocenter tetrasubstituted silane compound

Abstract

The invention discloses a method for preparing a chiral silicon-containing stereocenter tetrasubstituted silane compound, which mainly comprises the following steps: adding silicon-containing dialdehyde, alcohol or phenol, chiral nitrogen heterocyclic carbene catalyst, organic base and oxidant to an organic solvent, heating to 30-50°C for reaction, and after the reaction is complete, post-processing to obtain the chiral silicon-containing stereocenter tetrasubstituted silane compound. The preparation method can be carried out under mild conditions, has good stereoselectivity, is easy to operate, and has simple post-processing, avoiding the use of heavy metal catalysts that may remain in the product; the reaction raw materials are cheap and easy to obtain, the substrate functional group has good compatibility, can be easily enlarged, has strong practicality, and can be designed and synthesized according to actual needs. A variety of chiral silicon-containing stereocenter tetrasubstituted silane compounds can be designed and synthesized, which is easy to operate and broadens the applicability of this method.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and in particular relates to a method for preparing a chiral silicon-containing stereocenter tetrasubstituted silane compound. Background Art

[0002] Organosilicon compounds are important reagents and synthetic building blocks in synthetic chemistry, medicinal chemistry and materials science. In recent years, silane compounds with optically active chiral centers on silicon atoms have attracted more and more attention due to their excellent performance. For example: Compound 1 can be used as a chiral reagent for the kinetic resolution of secondary alcohols (Angew.Chem.Int.Ed.2005,44,7620-7624.); Compound 2 shows higher antidepressant activity than its carbon analogs (Org.Chem.Front.2021,8,5941-5947.); and Compound 3 has a very high fluorescence quantum efficiency and exhibits a significant circularly polarized light effect (J.Am.Chem.Soc.2021,143,5301-5307.):

[0003]

[0004] The methods for obtaining chiral silicon-containing stereocenter silane compounds reported in the literature today mainly include:

[0005] 1) Use chiral high performance liquid chromatography (HPLC) to directly perform optical resolution on racemic silane compounds: This method is limited by the separation capacity of the chromatographic column and can generally only produce a small amount of optically pure silane compounds (Organometallics 2003, 22, 4343–4346.).

[0006] 2) Copper-catalyzed kinetic resolution reaction of monohydrosilane and chiral alcohol: This reaction requires an equivalent amount of chiral alcohol as a reaction reagent, and the yield and enantioselectivity of the obtained product are not high (Adv. Synth. Catal. 2006, 348, 1171-1182).

[0007] 3) Chiral Box ligand-induced nucleophilic addition reaction of lithium reagent to silyl ether: This method requires the use of 3 equivalents of chiral Box ligand as a coordination reagent, and the reaction needs to be carried out at low temperature (-78°C) (J.Am.Chem.Soc.2008,130,16132-16133.).

[0008] 4) Rhodium-catalyzed desymmetric coupling reaction of dihydrosilane and heterocycle: This reaction requires the use of expensive, toxic and residual heavy metal catalysts, which is relatively costly (Angew. Chem. Int. Ed. 2022, 61, e202117820.).

[0009] In summary, although chiral silicon-containing stereogenic silane compounds are a class of compounds with great application prospects, most of the methods currently developed have limitations such as low separation efficiency, the need to use toxic heavy metal catalysts that are easy to remain, harsh reaction conditions, narrow substrate applicability, or poor stereoselectivity. Based on this, we have developed a method for the high stereoselective synthesis of chiral silicon-containing stereogenic tetrasubstituted silane compounds under relatively mild conditions. Summary of the invention

[0010] The present invention provides a method for synthesizing a chiral tetrasubstituted silane compound containing a silicon stereocenter under relatively mild conditions. The preparation method has good stereoselectivity, is easy to operate, has wide substrate applicability, does not require the use of heavy metal catalysts that may remain in the product, and is convenient for post-treatment. In addition, the method can be further scaled up, providing the possibility for large-scale industrial production and application.

[0011] A method for preparing a chiral silicon-containing stereo-center tetrasubstituted silane compound mainly comprises the following steps: adding silicon-containing dialdehyde, alcohol or phenol, a chiral nitrogen heterocyclic carbene catalyst, an organic base and an oxidant to an organic solvent, heating to 30-50° C. for reaction, and after the reaction is complete, post-treating to obtain the chiral silicon-containing stereo-center tetrasubstituted silane compound;

[0012] The structure of the silicon-containing dialdehyde is shown in formula (II):

[0013]

[0014] The structure of the alcohol or phenol is as shown in formula (III):

[0015] R 4 -OH (III);

[0016] The structure of the chiral nitrogen heterocyclic carbene catalyst is shown in formula (IV):

[0017]

[0018] The structure of the organic base is shown in formula (V):

[0019]

[0020] The structure of the oxidant is shown in formula (VI):

[0021]

[0022] The structure of the chiral silicon-containing stereocenter tetrasubstituted silane compound is shown in formula (I):

[0023]

[0024] In formulas (I) to (III), R 1 is a substituted or unsubstituted phenyl, naphthyl or heterocyclic group, wherein the substituent on the phenyl group is selected from C1-C4 alkyl, C1-C4 alkoxy, trifluoromethyl or halogen, and the substitution position is any position on the benzene ring;

[0025] R 2 is a C1-C4 alkyl group;

[0026] R 3 is H, C1-C4 alkyl, C1-C4 alkoxy, trifluoromethyl or halogen, and the substitution position is any position on the benzene ring;

[0027] R 4 It is C1-C4 alkyl, allyl, benzyl, substituted or unsubstituted phenyl, the substituent on the phenyl is selected from C1-C4 alkyl, C1-C4 alkoxy or halogen, and the substitution position is any position on the benzene ring.

[0028] The alkyl group is a substituent formed by removing a hydrogen atom from an alkane molecule, and is more preferably a straight-chain alkyl group.

[0029] The silicon-containing dialdehyde: alcohol or phenol: chiral nitrogen heterocyclic carbene catalyst: organic base: oxidant = 1: 1.2: 0.2: 1.2: 1.2;

[0030] The reaction formula is as follows:

[0031]

[0032] In the reaction, the chiral nitrogen heterocyclic carbene catalyst (IV) may first remove a molecule of fluoroboric acid under the action of the organic base DMAP (V) to generate a free nitrogen heterocyclic carbene catalyst, and the catalyst then combines with one of the aldehyde groups in the silicon-containing dialdehyde (II) to generate a Breslow intermediate, and then the Breslow intermediate is oxidized by the oxidant (VI) to generate an acylazole ion intermediate, and finally the acylazole ion intermediate reacts with alcohol or phenol (III) to generate a chiral silicon-containing stereocenter tetrasubstituted silane compound (I).

[0033] In the present invention, the optional post-treatment process includes: filtration, silica gel mixing, and finally column chromatography purification to obtain the corresponding chiral silicon-containing stereocenter tetrasubstituted silane compound. Column chromatography purification is a commonly used technical means in the art.

[0034] As a preference, R 1 is substituted or unsubstituted phenyl, 1-naphthyl, 2-naphthyl or 2-thienyl;

[0035] The substituent on the phenyl group is p-methoxy, p-trifluoromethyl, p-fluorine, p-chlorine, p-methyl, m-methyl or o-methyl. In this case, the silicon-containing dialdehyde is easy to obtain, the reaction yield is high, and the stereoselectivity is good. The numbering order of the substituents is determined according to the IUPAC nomenclature.

[0036] As a preference, R 2 In this case, the silicon-containing dialdehyde is easy to obtain, the reaction yield is high, and the stereoselectivity is good.

[0037] As a preference, R 3 is p-methoxy, p-fluorine, m-methyl, m-trifluoromethyl, m-fluorine or m-chlorine. In this case, the silicon-containing dialdehyde is easy to obtain, and the reaction yield is high and the stereoselectivity is good. The numbering order of the substituents is determined according to the IUPAC nomenclature.

[0038] As a preference, R 4 The alcohol or phenol is easy to obtain, and the reaction yield is high and the stereoselectivity is good.

[0039] The alcohol or phenol is cheap and readily available, and is used in excess relative to the silicon-containing dialdehyde. To ensure that the reaction proceeds more completely, the organic base and the oxidant are also used in excess relative to the silicon-containing dialdehyde. Preferably, on a molar basis, the ratio of silicon-containing dialdehyde: alcohol or phenol: chiral nitrogen heterocyclic carbene catalyst: organic base: oxidant is 1:1.2:0.2:1.2:1.2.

[0040] Preferably, the reaction temperature is 40° C. Too high a reaction temperature will increase the reaction cost, and conversely it will be difficult to ensure the completeness of the reaction.

[0041] Preferably, the reaction time is 72 hours. Too long a reaction time will increase the reaction cost, and conversely it will be difficult to ensure the completeness of the reaction.

[0042] In the present invention, any organic solvent that can fully dissolve the raw materials can cause the reaction to occur, but the reaction efficiency varies greatly. Preferably, an aprotic solvent is used, which can effectively promote the reaction. Preferably, the aprotic organic solvent is dichloromethane or toluene. More preferably, the organic solvent is dichloromethane. In this case, various raw materials can be converted into products at a higher conversion rate.

[0043] The amount of the organic solvent used is sufficient to dissolve the raw materials well. The amount of the organic solvent used for 0.1 mmol of silicon-containing dialdehyde is about 0.5 mL.

[0044] As a further preference, the chiral silicon-containing stereocenter tetrasubstituted silane compound is one of the compounds represented by formula (I-1) to formula (I-10):

[0045]

[0046]

[0047]

[0048] For example, formula (I-1) and (I-8) are known compounds, and the rest are unknown compounds.

[0049] In the above preparation method, the alcohol or phenol, chiral nitrogen heterocyclic carbene catalyst, organic base and oxidant are commercially available products, which can be easily obtained from the market. The silicon-containing dialdehyde amine can be synthesized simply and quickly from the corresponding dichlorosilane, o-bromobenzaldehyde and ethylene glycol.

[0050] Compared with the prior art, the beneficial effects of the present invention are embodied in that: the preparation method can be carried out under mild conditions, has good stereoselectivity, is easy to operate, and has simple post-treatment, avoiding the use of heavy metal catalysts that may remain in the product; the reaction raw materials are cheap and easy to obtain, the substrate functional group compatibility is good, and a variety of chiral silicon-containing stereocenter tetrasubstituted silane compounds can be designed and synthesized according to actual needs, and the practicability is strong. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] Figure 1 is the H NMR spectrum of the product (I-1) obtained in Example 1;

[0052] Figure 2 The NMR carbon spectrum of the product (I-1) obtained in Example 1;

[0053] Figure 3 The lower figure is a high performance liquid chromatogram of the product (I-1) obtained in Example 1, and the upper figure is a corresponding achiral product obtained by the method of Example 1 but using an achiral catalyst.

[0054] Figure 4 This is a high-resolution mass spectrum of the product (I-1) obtained in Example 1. DETAILED DESCRIPTION

[0055] The present invention is further described below in conjunction with specific embodiments, but it should be emphasized that the present invention is by no means limited to the contents represented by these embodiments.

[0056] Examples 1 to 17

[0057] According to the raw material ratio in Table 1, silicon-containing dialdehyde (II), alcohol or phenol (III), chiral nitrogen heterocyclic carbene catalyst (IV), organic base (V), oxidant (VI) and organic solvent are added in sequence to a 10 ml Schlenk tube (or a 100 ml Schlenk tube), mixed and stirred evenly, and after the reaction is completed according to the reaction conditions in Table 2, filtered, mixed with silica gel, and purified by column chromatography to obtain the corresponding chiral silicon-containing stereocenter tetrasubstituted silane (I). The reaction process is shown in the following formula:

[0058]

[0059] Table 1

[0060]

[0061]

[0062] Table 2

[0063]

[0064] In Table 1 and Table 2, T is the reaction temperature, Ph is a phenyl group, Bn is a benzyl group, Naphthyl is a naphthyl group, Thienyl is a thienyl group, Me is a methyl group, Allyl is an allyl group, and ee is the enantiomeric excess.

[0065] The structural confirmation data of some compounds prepared in Examples 1 to 17 are as follows:

[0066] The NMR of the chiral silicon-containing stereocenter tetrasubstituted silane compound (I-1) prepared in Example 1 is ( 1 HNMR and 13 C NMR), high resolution mass spectrometry (HRMS) and high performance liquid chromatography (HPLC) detection data are:

[0067]

[0068] 1 H NMR (400MHz, CDCl3) δ9.98 (s, 1H), 8.10 (d, J = 7.2Hz, 1H), 7.94 (d, J = 7.6Hz, 1H), 7.54-7.28 (m, 14H), 7.22-7.20 (m, 2H), 5.03 (s, 2H), 0.94 (s, 3H); 13 C{ 1H}NMR (100MHz, CDCl3) δ193.0,167.6,141.4,140.8,139.5,138.1,137.6,137.4,135.8,135.6,135.1,132.8, 131.7,130.6,130.3,129.4,129.3,128.9,128.4,128.2,128.1,127.8,66.7,-0.3.HRMS(ESI-TOF)m / z:[M+Na] + calcd.for C 28 H 24 NaO3Si + 459.1387, found 459.1385. HPLC analysis: 95%ee, [CHIRALPAK IC column; 1.0mL / min; solvent system: i-PrOH / hexane=10 / 90; retention times: 6.5min (minor), 7.4min (major)].

[0069] The NMR of the chiral silicon-containing stereocenter tetrasubstituted silane compound (I-2) prepared in Example 8 is ( 1 HNMR and 13 C NMR), high resolution mass spectrometry (HRMS) and high performance liquid chromatography (HPLC) detection data are:

[0070]

[0071] 1 H NMR (400MHz, CDCl3) δ9.93(s,1H),8.13(d,J=7.6Hz,1H),7.93(d,J=7.2Hz,1H),7.59-7.40(m ,8H),7.37(d,J=7.2Hz,1H),7.31-7.28(m,4H),7.23-7.20(m,2H),5.07(s,2H),0.94(s,3H); 13 C{ 1 H}NMR(100MHz,CDCl3)δ192.9,167.6,143.7,140.8,139.5(d,J C-F =105.7Hz),137.6,137.4,135.6,135.5,135.2,133.1,132.3,131.9,130.6(q,J C-F =40.8Hz),130.3,129.6,128.5,128.3,128.2,124.3(q,JC-F =270.2Hz),124.2(d,J C-F =3.6Hz),66.8,-0.6.HRMS(ESI-TOF)m / z:[M+Na] + calcd.for C 29 H 23 F3NaO3Si + 527.1261, found527.1262. HPLC analysis: 92%ee, [CHIRALPAK IC column; 1.0mL / min; solvent system: i-PrOH / hexane=10 / 90; retention times: 5.1min (minor), 5.7min (major)].

[0072] The NMR of the chiral silicon-containing stereocenter tetrasubstituted silane compound (I-3) prepared in Example 9 is ( 1 HNMR and 13 C NMR), high resolution mass spectrometry (HRMS) and high performance liquid chromatography (HPLC) detection data are:

[0073]

[0074] 1 H NMR (400MHz, CDCl3) δ9.99 (s, 1H), 8.10 (d, J = 7.6Hz, 1H), 7.95 (d, J = 7.2Hz, 1H), 7.54-7.29 (m,9H),7.24-7.16(m,6H),5.03(dd,J1=13.6Hz,J2=12.4Hz,2H),2.29(s,3H),0.93(s,3H); 13 C{ 1 H}NMR (100MHz, CDCl3) δ193.1,167.6,141.7,140.8,139.5,137.8,137.7,137.4,137.0,135.8,135.6,132.8,132.2, 131.8,130.4,130.3,129.8,129.4,129.2,128.4,128.3,128.1,127.7,66.7,21.6,-0.2.HRMS(ESI-TOF)m / z:[M+Na] + calcd.for C 29 H 26 NaO3Si +473.1543, found 473.1544. HPLC analysis: 94%ee, [CHIRALPAKIC column; 1.0mL / min; solvent system: i-PrOH / hexane=10 / 90; retention times: 6.5min (minor), 7.3min (major)].

[0075] The NMR of the chiral silicon-containing stereocenter tetrasubstituted silane compound (I-4) prepared in Example 10 is ( 1 H NMR and 13 C NMR), high resolution mass spectrometry (HRMS) and high performance liquid chromatography (HPLC) detection data are:

[0076]

[0077] 1 H NMR (400MHz, CDCl3) δ10.05(s,1H),8.15(d,J=7.6Hz,1H),8.01(d,J=8.0Hz,1H),7.88(d,J=8.0Hz,2H),7.74 (d,J=8.4Hz,1H),7.56-7.26(m,13H),7.19-7.17(m,2H),5.05(dd,J1=18.8Hz,J2=12.4Hz,2H),1.07(s,3H); 13 C{ 1 H}NMR (100MHz, CDCl3) δ193.1,167.6,141.6,140.1,139.2,138.2,138.0,136.8,136.3,136.1,136.0,135.5,133.6,132.9,131.8, 130.4,130.3,130.2,129.6,129.5,129.1,129.0,128.4,128.3,128.1,125.5,125.2,125.1,66.8,2.4.HRMS(ESI-TOF)m / z:[M+Na] + calcd.for C 32 H 26 NaO3Si +509.1543, found 509.1552. HPLC analysis: 92%ee, [CHIRALPAK AS-H column; 1.0mL / min; solvent system: i-PrOH / hexane=10 / 90; retention times: 6.6min (major), 7.4min (minor)].

[0078] The NMR of the chiral silicon-containing stereocenter tetrasubstituted silane compound (I-5) prepared in Example 11 is ( 1 H NMR and 13 C NMR), high resolution mass spectrometry (HRMS) and high performance liquid chromatography (HPLC) detection data are:

[0079]

[0080] 1 H NMR (400MHz, CDCl3) δ9.99 (s, 1H), 8.11-8.09 (m, 1H), 7.93 (d, J = 8.4Hz, 1H), 7.63 (d, J = 4.4 Hz,1H),7.56-7.45(m,6H),7.31-7.29(m,3H),7.23-7.18(m,4H),5.06(s,2H),1.01(s,3H); 13 C{ 1 H}NMR (100MHz, CDCl3) δ192.9,167.6,141.3,140.5,139.8,138.3,137.1,136.8,136.7,135.6,135.1,13 2.9,132.1,131.6,130.6,130.1,129.6,129.3,128.5,128.2,128.1,66.8,0.9.HRMS(ESI-TOF)m / z:[M+H] + calcd.for C 26 H 23 O3SSi + 443.1132, found 443.1136. HPLC analysis: 96%ee, [CHIRALPAK IC column; 1.0mL / min; solvent system: i-PrOH / hexane=10 / 90; retention times: 6.8min (minor), 7.3min (major)].

[0081] The NMR of the chiral silicon-containing stereocenter tetrasubstituted silane compound (I-6) prepared in Example 12 is ( 1 H NMR and 13 C NMR), high resolution mass spectrometry (HRMS) and high performance liquid chromatography (HPLC) detection data are:

[0082]

[0083] 1 H NMR(400MHz, CDCl3)δ9.99(s,1H),7.64(d,J=2.0Hz,1H),7.49(d,J=2.0Hz,1H),7.40-7.24(m,10H),7.19(s,2H),7 .02-7.00(m,1H),6.96-6.93(m,1H),5.04(dd,J1=18.0Hz,J2=12.4Hz,2H),3.86(s,3H),3.82(s,3H),0.89(s,3H); 13 C{ 1 H}NMR (100MHz, CDCl3) δ192.8,167.4,160.6,160.5,142.5,139.3,138.8,138.6,137.6,135.5,135.1,133.2,129.8 ,128.9,128.4,128.3,128.2,127.8,119.6,117.2,116.3,113.2,66.8,55.3,55.3,0.2.HRMS(ESI-TOF)m / z:[M+Na] + calcd.for C 30 H 28 NaO5Si + 519.1598, found 519.1611. HPLC analysis: 95%ee, [CHIRALPAK IC column; 1.0mL / min; solvent system: i-PrOH / hexane=10 / 90; retention times: 12.0min (minor), 16.2min (major)].

[0084] The NMR of the chiral silicon-containing stereocenter tetrasubstituted silane compound (I-7) prepared in Example 13 is ( 1 H NMR and 13 C NMR), high resolution mass spectrometry (HRMS) and high performance liquid chromatography (HPLC) detection data are:

[0085]

[0086] 1 H NMR (400MHz, CDCl3) δ9.89 (s, 1H), 8.05 (d, J = 8.4Hz, 1H), 7.85 (d, J = 8.0Hz, 1H), 7.52-7.49 (m, 1H), 7.44 -7.30(m,10H),7.27-7.26(m,1H),7.23-7.20(m,2H),5.07(dd,J1=16.4Hz,J2=12.4Hz,2H),0.92(s,3H); 13 C{ 1 H}NMR (100MHz, CDCl3) δ191.5,166.8,143.2,142.1,140.0,139.0,138.8,137.2,137.1,136.5,135.4,135 .0,133.7,132.8,131.8,129.7,129.6,129.4,128.5,128.3,128.0,67.0,-0.6.HRMS(ESI-TOF)m / z:[M+Na] + calcd.for C 28 H 22 Cl2NaO3Si + 527.0607, found 527.0597. HPLC analysis: 91%ee, [CHIRALPAK IC column; 1.0mL / min; solvent system: i-PrOH / hexane=10 / 90; retention times: 5.3min (minor), 5.8min (major)].

[0087] The NMR of the chiral silicon-containing stereocenter tetrasubstituted silane compound (I-8) prepared in Example 14 is ( 1 H NMR and 13 C NMR), high resolution mass spectrometry (HRMS) and high performance liquid chromatography (HPLC) detection data are:

[0088]

[0089] 1H NMR (400MHz, CDCl3) δ10.02(s,1H),8.09(d,J=7.6Hz,1H),7.98(d,J=7.2Hz,1H),7.91(s,1H),7.8 3-7.74(m,3H),7.57-7.53(m,1H),7.50-7.45(m,6H),7.40-7.35(m,2H),3.52(s,3H),1.03(s,3H); 13 C{ 1 H}NMR (100MHz, CDCl3) δ193.0,168.2,141.3,140.9,139.1,137.7,137.5,135.9,135.8,135.7,133.6,132.9,131 .7,131.3,131.0,130.3,129.5,129.4,128.2,127.7,127.0,126.4,125.8,51.8,-0.3.HRMS(ESI-TOF)m / z:[M+Na] + calcd.for C 26 H 22 NaO3Si + 433.1230, found 433.1240. HPLC analysis: 91%ee, [CHIRALPAKIC column; 1.0mL / min; solvent system: i-PrOH / hexane=10 / 90; retention times: 8.3min (minor), 11.9min (major)].

[0090] The NMR of the chiral silicon-containing stereocenter tetrasubstituted silane compound (I-9) prepared in Example 15 is ( 1 H NMR and 13 C NMR), high resolution mass spectrometry (HRMS) and high performance liquid chromatography (HPLC) detection data are:

[0091]

[0092] 1 H NMR (400MHz, CDCl3) δ10.02(s,1H),8.13(d,J=7.6Hz,1H),7.97(d,J=7.6Hz,1H),7.91(s,1H),7.83-7. 73(m,3H),7.57-7.35(m,9H),5.75-5.65(m,1H),5.21-5.09(m,2H),4.47(d,J=5.6Hz,2H),1.04(s,3H);13 C{ 1 H}NMR (100MHz, CDCl3) δ193.0,167.5,141.3,140.9,139.3,137.7,137.6,135.9,135.8,135.7,133.6,132.9,132.8,131 .8,131.3,130.9,130.2,129.5,129.4,128.2,127.7,126.9,126.4,125.8,118.4,65.7,-0.2.HRMS(ESI-TOF)m / z:[M+Na] + calcd.for C 28 H 24 NaO3Si + 459.1387, found 459.1378.[α] 24 D =+31.0 (c=0.5in CHCl3). HPLC analysis: 86%ee, [CHIRALPAK IC column; 1.0mL / min; solventsystem: i-PrOH / hexane=10 / 90; retention times: 6.7min (minor), 9.7min (major)].

[0093] The NMR of the chiral silicon-containing stereocenter tetrasubstituted silane compound (I-10) prepared in Example 16 is ( 1 H NMR and 13 C NMR), high resolution mass spectrometry (HRMS) and high performance liquid chromatography (HPLC) detection data are:

[0094]

[0095] 1 H NMR (400MHz, CDCl3) δ10.01(s,1H),8.29(d,J=7.6Hz,1H),7.96(d,J=7.6Hz,1H),7.91(s,1H),7 .84-7.73(m,3H),7.58-7.44(m,9H),7.15(d,J=8.8Hz,2H),6.61(d,J=8.4Hz,2H),1.04(s,3H); 13 C{ 1H}NMR(100MHz,CDCl3)δ193.0,166.1,148.9,141.0,140.6,140.3,138.0,137.8,135.9,135.3,134.8,133.7,133.0,132.9,132.4,131.7,131.3,131.1,130.9,129.6,129.5,129.3,128.2,127.7,127.0,126.5,125.9,122.8,-0.4.HRMS(ESI-TOF)m / z:[M+Na] + calcd.for C 31 H 23 ClNaO3Si + 529.0997,found 529.1008.HPLCanalysis:98%ee,[CHIRALPAK IC column;1.0mL / min;solvent system:i-PrOH / hexane=10 / 90;retention times:7.2min(minor),14.2min(major)]。

Claims

1. A method for preparing a chiral silicon-containing stereocenter tetrasubstituted silane compound, characterized in that: The method comprises the following steps: adding silicon-containing dialdehyde, alcohol or phenol, chiral nitrogen heterocyclic carbene catalyst, organic base and oxidant into an organic solvent, heating to 30-50° C. for reaction, and after the reaction is complete, post-treating to obtain the chiral silicon-containing stereocenter tetrasubstituted silane compound; The structure of the silicon-containing dialdehyde is shown in formula (II): The structure of the alcohol or phenol is as shown in formula (III): R 4 -OH(III)? The structure of the chiral nitrogen heterocyclic carbene catalyst is shown in formula (IV): The structure of the organic base is shown in formula (V): The structure of the oxidant is shown in formula (VI): The structure of the chiral silicon-containing stereocenter tetrasubstituted silane compound is shown in formula (I): In formulas (I) to (III), R 1 is substituted or unsubstituted phenyl, 1-naphthyl, 2-naphthyl or 2-thienyl; The substituent on the phenyl group is p-methoxy, p-trifluoromethyl, p-fluorine, p-chlorine, p-methyl, m-methyl or o-methyl; R 2 is a C1-C4 alkyl group; R 3 is H, C1-C4 alkyl, C1-C4 alkoxy, trifluoromethyl or halogen; R 4 is C1-C4 alkyl, allyl, benzyl, substituted or unsubstituted phenyl, wherein the substituent on the phenyl is selected from C1-C4 alkyl, C1-C4 alkoxy or halogen; The organic solvent is dichloromethane.

2. The method for preparing a chiral silicon-containing stereocenter tetrasubstituted silane compound according to claim 1, characterized in that: R 2 It is methyl or ethyl.

3. The method for preparing a chiral silicon-containing stereocenter tetrasubstituted silane compound according to claim 1, characterized in that: R 3 It is p-methoxy, p-fluoro, m-methyl, m-trifluoromethyl, m-fluoro or m-chloro.

4. The method for preparing a chiral silicon-containing stereocenter tetrasubstituted silane compound according to claim 1, characterized in that: R 4 It is methyl, allyl, benzyl or p-chlorophenyl.

5. The method for preparing a chiral silicon-containing stereocenter tetrasubstituted silane compound according to claim 1, characterized in that: In terms of molar amount, silicon-containing dialdehyde: alcohol or phenol: chiral nitrogen heterocyclic carbene catalyst: organic base: oxidant = 1: 1.1-1.2: 0.1-0.2: 1.1-1.2: 1.1-1.

2.

6. The method for preparing a chiral silicon-containing stereocenter tetrasubstituted silane compound according to claim 1, characterized in that: The reaction temperature was 40°C.

7. The method for preparing a chiral silicon-containing stereocenter tetrasubstituted silane compound according to claim 1, characterized in that: The reaction time is 60 to 80 hours.

8. The method for preparing a chiral silicon-containing stereocenter tetrasubstituted silane compound according to claim 1, characterized in that: The chiral silicon-containing stereocenter tetrasubstituted silane compound is one of the compounds represented by formula (I-1) to formula (I-10):

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