Quaternary carbon type chiral allyl gem-silicon-boron compound, synthetic method thereof and application of quaternary carbon type chiral allyl gem-silicon-boron compound in allyl boronation reaction

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to a quaternary carbon type chiral allyl gem-silicon-boron compound as well as a synthesis method and application thereof, the structural formula of the quaternary carbon type chiral allyl gem-silicon-boron compound is # imgabs0 #, and the quaternary carbon type chiral allyl gem-silicon-boron compound can be used as a novel allyl bimetallic reagent to be subjected to an allyl boronation reaction to obtain the quaternary carbon type chiral allyl gem-silicon-boron compound. An E-anti homoallylic alcohol structural framework is obtained through complete double-bond selectivity and excellent diastereoselectivity, and compared with an existing synthesis method of a trisubstituted olefin-containing homoallylic alcohol structural building block, the method has the advantages of simple steps, high synthesis efficiency, wide application range and remarkable stereochemical control advantage; the building block has a wide application prospect for natural products or drug intermediates with the building block with the structure. When the quaternary carbon type chiral allyl gem-silicon boron compound is applied to allyl boronation reaction, the quaternary carbon type chiral allyl gem-silicon boron compound has the advantages of high synthesis efficiency, wide substrate applicability, excellent selectivity, high yield and low synthesis cost.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a quaternary carbon chiral allyl geminal silicon boron compound, a synthesis method thereof and an application of synthesizing a chiral high-propylene alcohol compound through an allyl borylation reaction. Background Art

[0002] 3,5-Dimethyl chiral homoallyl alcohol compounds containing trisubstituted olefins are common and key acyclic systems widely found in polyene or macrolide polyketone compounds (as shown below). At present, many research groups have developed several good methods to construct this building block, including direct construction using Kobayashi's vinylene silicon-based N,O-acetal through the vinylogous Mukaiyama Aldol reaction. In this method, the N,O-acetal needs to be prepared in advance, and there are differences in the diastereoselectivity of the reaction for different aldehydes; other methods require at least two steps to complete the construction, including Marshall–Tamaru propargylation to obtain chiral homoallyl alcohols, and then Trost's ene / yne coupling or hydrozirconium / iodination to complete the construction; or asymmetric butylation using α,α-disubstituted butyl borate, asymmetric hydroformylation of dienes, and Wittig olefination of aldehyde precursors. Despite these advances, there are very limited methods that can directly and stereoselectively obtain trisubstituted olefin-containing homoallyl alcohol building blocks that can be transformed in a variety of ways. (The structure is as follows).

[0003]

[0004] Active molecules containing 3,5-dimethyl chiral homopropylene alcohol compounds

[0005] Allyl metal (such as boron or silicon) reagents have been widely used in organic chemical synthesis due to their unique metalloid chemical properties and good accessibility. Since the late 1970s, the research focus has gradually shifted to controlling the stereochemistry of CC bond formation in the reaction of allyl metals with aldehydes or ketones, which has further promoted the widespread application of allyl organometallic compounds in stereocontrolled organic synthesis. However, these studies mainly focused on allyl monometallic reagents. It was not until Matteson reported the first allyl 1,1-borosilicate reagent that the research on allyl dimetallic reagents began to be gradually valued. Scientists such as Hiyama, Shimizhu, Hall, Roush, Chen Ming and Cho developed a series of allyl 1,1-borosilicate reagents, which made outstanding contributions to the stereochemical control of their reactions with aldehydes, ketones and even imines, achieving high enantioselectivity and high regioselectivity.

[0006] The allyl 1,1-geminal borosilicate reagents currently developed are still limited to non-quaternary borosilicate compounds. Their bifunctionalization with electrophilic reagents can only generate 1,2-disubstituted olefins, in which the CH bond at the 1-position is difficult to further transform or introduce other groups. In contrast, 1,1-geminal borosilicate compounds containing quaternary carbon centers can increase the complexity and diversity of the structure. However, due to the poor accessibility of this type of structure, there are currently no other reports and applications except for the work of this group.

[0007]

[0008] At present, the reaction of allyl silicon boron reagents with aldehydes

[0009] At present, there are few studies on the allyl boronation reaction of allyl geminal silicon boron compounds with aldehydes. According to existing reports (as above), only Z-selective compounds can be obtained after reaction with aldehydes, and E-selective compounds cannot be obtained, thereby limiting the application of allyl silicon boron reagents in the efficient synthesis of structures of different double bond types. The method of the present invention can obtain the E-anti high allyl alcohol structure skeleton with complete double bond selectivity and excellent diastereoselectivity. Combined with the quaternary carbon geminal silicon boron reagent substituted with formate previously developed by the applicant, two double bond types of structures can be efficiently synthesized as needed. Summary of the invention

[0010] The purpose of the present invention is to overcome the deficiencies of the prior art and provide a quaternary carbon chiral allyl geminal silicon boron compound, a synthesis method thereof and an application thereof in synthesizing chiral high allyl alcohol compounds.

[0011] The object of the present invention is achieved through the following technical scheme: a quaternary carbon chiral allyl geminal silicon boron compound, as shown in the following structural formula I:

[0012]

[0013] In the formula, R is one of C1-C6 normal alkyl, C3-C6 cycloalkyl, C2-C5 alkenyl, phenyl, chlorine atom substituted phenyl, fluorine atom substituted phenyl, methyl substituted phenyl, methoxy substituted phenyl; Si is one of dimethyl tert-butylsilyl, dimethylphenylsilyl, dimethylbenzylsilyl and trimethylsilyl. Bpin is pinacol borate, i.e. 4,4,5,5-tetramethyl-1,3,2-dioxaborolane.

[0014] Preferably, R is methyl, ethyl, cyclopropyl, vinyl, propenyl or phenyl.

[0015] The present invention also provides a method for synthesizing the above-mentioned quaternary carbon chiral allyl geminal silicon boron compound, comprising the following steps:

[0016] The quaternary carbon chiral allyl geminal silicon boron compound is synthesized by using an alkenyl silicon boron compound and a Grignard reagent RMgX as substrates through a vinylogous Matteson reaction in a solvent, and the reaction formula is as follows:

[0017]

[0018] In the formula, LG is acetyl (Ac), pivaloyl (Piv), N,N-diisopropylcarbamate (Cb), tert-butyloxycarbonyl (Boc) or phosphate (OPO (OR 1 )), said R 1 is Me, Et or iPr; the counter ion X of the Grignard reagent is one of Cl, Br and I.

[0019] Furthermore, the molar ratio of the alkenyl silicon boron compound to the Grignard reagent RMgX is in the range of 1:1 to 3;

[0020] And / or, the temperature range of the vinylogous Matteson reaction is -40°C to 25°C;

[0021] And / or, the vinylogous Matteson reaction time is 10min to 4h;

[0022] And / or, the solvent of the vinylogous Matteson reaction is toluene, tetrahydrofuran, ether, dichloromethane or dichloroethane.

[0023] The present invention also provides an application of the quaternary carbon chiral allyl geminal silicon boron compound for synthesizing chiral high-propylene alcohol compounds.

[0024] Furthermore, the quaternary carbon chiral allyl geminal silicon boron compound is used as an allyl bimetallic reagent to synthesize the chiral homoallyl alcohol compound through an allyl borylation reaction.

[0025] Furthermore, the chiral homoallyl alcohol compound includes a trisubstituted olefin E-anti homoallyl alcohol compound, and the synthesis method includes the following steps:

[0026] The quaternary carbon chiral allyl geminal silicon boron compound and aldehyde are used as substrates, and the trisubstituted olefin E-anti homoallyl alcohol compound is obtained by allylic borylation reaction in a fluorine-containing solvent. The reaction formula is as follows:

[0027]

[0028] In the formula, R 2It is one of C1-C8 alkyl, C1-C8 alkyl substituted with O, N heteroatom or phenyl, C3-C8 alkenyl, C3-C8 alkenyl substituted with oxygen atom, phenylpropargyl, trimethylsilyl substituted alkynyl, C3-C8 alkynyl substituted with oxygen atom, phenyl, furyl, thienyl, quinolyl, indolyl, benzothiazolyl, phenyl substituted with nitro, trifluoromethyl, chlorine atom, cyano, ethynyl, methyl and methoxy.

[0029] Preferably, the R 2 It is ethyl, isobutyl, phenylpropyl, benzyloxy, 2-methyl-1,3-dioxolanyl, N-methyl-N-toluenesulfonyl-3-amino, trimethylsilyl, ethyl acrylate, p-nitrophenyl, and benzothiazolyl.

[0030] Further, the fluorinated solvent in the allyl borylation reaction includes one of trifluoroethanol (TFE), hexafluoroisopropanol (HFIP), trifluoroisopropanol, and 3,3,3-trifluoro-1-propanol;

[0031] And / or, in the allyl borylation reaction, the molar ratio of the quaternary carbon chiral allyl geminal silicon boron compound to the aldehyde is in the range of 1:1 to 3 or 1 to 3:1;

[0032] and / or, the temperature range of the allyl borylation reaction is 25° C. to 80° C.;

[0033] And / or, the allyl borylation reaction time is 0.5h to 24h.

[0034] The present invention also provides the E-anti chiral high allylic alcohol compound synthesized by the above application.

[0035] The beneficial effects of the present invention are:

[0036] 1. The present invention provides a quaternary carbon chiral allyl geminal silicon boron compound, which can be used as a novel allyl bimetallic reagent to obtain an E-anti homoallyl alcohol structural skeleton through an allylic borylation reaction with complete double bond selectivity and excellent diastereoselectivity. Compared with the existing synthesis method of this structure containing a trisubstituted olefin homoallyl alcohol structural building block, the present invention has simple steps, efficient synthesis, wide application range and significant stereochemical control advantages, and has broad application prospects for natural products or drug intermediates having this structural building block.

[0037] 2. The present invention also provides a method for preparing the above-mentioned quaternary carbon-type chiral allyl geminal silicon boron compound, which solves the problem of accessibility of the preparation of quaternary carbon-type allyl geminal silicon boron compounds, and can diversify the synthesis of differently substituted quaternary carbon-type allyl geminal silicon boron compounds. The present invention uses alkenyl silicon boron compounds and Grignard reagents as substrates, does not require additional catalysts, and has mild conditions. The Grignard reagent is a commercially available cheap reagent. Therefore, the method developed by the present invention breaks the synthesis barrier of quaternary carbon-type allyl silicon boron reagents, and has the significant advantages of low price and efficient synthesis in terms of substrate preparation.

[0038] 3. When the quaternary carbon-type chiral allyl geminal silicon-boron compound of the present invention is applied to the allylic borylation reaction, no additional catalyst is required, and the fluorinated solvent used is also a commercially available cheap reagent. At the same time, the corresponding chiral high-allyl alcohol compound can be prepared on a large scale, in high yield and with high selectivity by this method. Compared with previous work, the method can effectively control the double bond selectivity of the reaction only by solvent control, and is different from the catalysis using Lewis acid, protic acid and strong base, and has obvious innovation in mechanism. Therefore, the quaternary carbon-type geminal silicon-boron compound and the corresponding chiral high-allyl alcohol compound synthesis method provided by the present invention have the advantages of high synthesis efficiency, wide substrate applicability, excellent selectivity, high yield and low synthesis cost on the basis of innovation. DETAILED DESCRIPTION

[0039] The technical solution of the present invention is further described in detail below, but the protection scope of the present invention is not limited to the following.

[0040] The allyl quaternary carbon geminal silicon boron reagent previously synthesized by the inventor of the present application can react with various aldehydes and can obtain highly allyl alcohol products with extremely high enantioselectivity in excellent yield. Later, when considering obtaining chiral allyl quaternary carbon geminal silicon boron reagents with more diverse structures and different substitutions in the R group, the present invention was proposed.

[0041] The present invention starts from the key intermediate alkenyl geminal silicon boron compound, prepares the hydroxyl group as the leaving group, utilizes the electron-deficient property of boron to coordinate with the nucleophilic reagent first, then undergoes a 1,2-migration reaction, and then the alkenyl double bond isomerizes, and utilizes the Matteson reaction of vinylogous olefin to successfully prepare quaternary carbon-type allyl geminal silicon boron reagents substituted with different groups.

[0042] After confirming the reaction conditions of the migration reaction, we synthesized a series of allylic geminal boron reagents with different R group substitutions through the vinylogous Matteson reaction of different Grignard reagents with allyl ester compounds with leaving groups.

[0043]

[0044] Reaction conditions: rac-6 (0.1 mmol, 1.0 equiv.), RMgBr (0.12 mmol, 1.2 equiv.), DCM (1 mL).

[0045] When we obtained chiral compound 6 from chiral propargyl alcohol, under the above conditions, the ee value of the obtained quaternary carbon geminal boron silane reagent was 88%, and the optical purity was lost during the chiral transfer process. Therefore, for the chiral substrate, we screened the leaving group and reaction solvent. As shown in Table 1, when the leaving group was OPiv, the solvent was dichloroethane, and the methyl Grignard reagent was an ether solution of magnesium bromide, a chiral geminal boron silane reagent with good optical purity was obtained with an ee value of 97%.

[0046]

[0047] Table 1 Condition screening of chiral substrate migration reaction

[0048]

[0049] After obtaining several chiral geminal silicon boron compounds with high ee values ​​substituted by different silicon groups, we applied them to the allylic borylation reaction with aldehydes. As shown in Table 2, alkyl aldehydes, which are more common in natural products, were used as template substrates. When phenyldimethyl silicon boron reagent 5b was selected, a pair of double bond isomers with an almost 1:1 ratio was obtained. The use of proton acid or Lewis acid catalysis commonly used in this type of reaction did not significantly improve the double bond selectivity. When a proton solvent was used, the selectivity increased significantly. When carried out in a fluorinated solvent, the reaction rate was accelerated, and the yield was significantly improved at the same time. At the same time, the double bond selectivity was significantly improved. In hexafluoroisopropanol, a complete E-anti product can be obtained. Applying this condition to dimethylphenylsilane or other silicon-substituted allyl silicon boron reagents with poor initial selectivity can also achieve excellent double bond selectivity.

[0050] Table 2 Screening of optimal conditions for the reaction of allyl silicon boron reagents with aldehydes

[0051]

[0052] Based on the results of the condition screening, the application scope of the allylic borylation reaction with aldehydes was investigated using the dimethyl tert-butyl substituted silicon boron reagent 5a, and the results are shown below. According to previous studies, the reactivity of alkyl aldehydes with quaternary carbon-type allyl borate esters is generally low. Under the conditions of HFIP, high-allylic alcohol compounds 10a-10i can still be obtained with excellent anti-selectivity and enantioselectivity in high yields. It has good tolerance for various functional groups, including ethers, sulfonamides, ketals, and alkynyl groups, and the presence of these functional groups will be beneficial to subsequent derivatization reactions. The reagent also reacts well with enals and acetylenes, and all can be carried out at room temperature to obtain 10n-10q in good yields. Aromatic aldehydes substituted with electron-donating or electron-withdrawing groups can also smoothly obtain 10j-10m. The aromatic Bpin in the aldehyde does not interfere with the allylation reaction, which allows the Suzuki-Miyaura cross-coupling reaction to be applied to later modifications; the Lewis basic nitrogen in the aromatic heterocyclic substituted aldehyde does not interfere with the Lewis acidity of the pinacol borate ester, indicating the potential utility of this method in drug discovery. The obtained compound 10b can be directly applied to the synthesis of the natural product Calyculin C, the compound 10h can be applied to the synthesis of Amphidinolide X, and the compound 10n can be applied to the synthesis of Apoptolidin C1-C11 fragment.

[0053]

[0054] Application scope of the reaction of allyl silicon boron reagents with aldehydes

[0055] The specific operation methods and data are as follows:

[0056] Example 1 Preparation of allyl quaternary carbon type chiral geminal silicon boron reagent

[0057]

[0058] Starting with (R) / (S)-3-butyn-2-ol chiral raw material, under the action of n-butyl lithium, the C-terminal is selectively siliconized, and then TBS is used to protect the hydroxyl group to obtain alkynyl silicon compound 2. Subsequently, under the action of lithium triethylborohydride and zinc trifluoromethanesulfonate, a selective cis-hydroboration reaction is carried out, and the silicon protection is removed under the action of CSA or catalytic amount of bismuth trifluoromethanesulfonate to obtain alkenyl silicon boron compound 3. Next, under the action of pivalic anhydride, the easily leaving Piv protecting group is given to the alcoholic hydroxyl group, and then the vinylogous Matteson reaction occurs under the action of methylmagnesium bromide, and finally the allyl quaternary carbon geminal silicon boron reagent 5 with an ee value of 97% is obtained on a 10g scale. Through the investigation of solvents and hydroxyl protecting groups, when the hydroxyl group is protected by a Piv group and dichloroethane is used as the solvent, this step has good chiral transfer. In this route to compound 3, there have been related operations reported by this group before. This article describes the synthesis steps in detail starting from alkenyl geminal silicon boron compound 3, and the focus of the synthesis is the last vinylogous Matteson reaction.

[0059] Synthesis of compound 4:

[0060] In a 100 mL round-bottom flask, anhydrous magnesium bromide (10.4 mmol) was added to a 40 mL DCM solution of pivalic anhydride (10.4 mmol), stirred at room temperature for 30 minutes, then triethylamine (12 mmol) was added, stirred at room temperature for 15 minutes, a DCM solution of compound 3 (8 mmol) was added, and then reacted for 6 hours. After quenching with water, the aqueous phase was extracted three times with EtOAc (40 mL x 3), the organic layers were combined and washed with saturated NaCl, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel flash column chromatography (petroleum ether / EtOAc=100 / 1) to obtain 3.1 g of colorless oily product 4 in 93% yield.

[0061] Vinyl Matteson reaction operation steps:

[0062] The reaction bottle (100 mL) previously dried in an oven for 30 minutes was ventilated three times under an oil pump. Under argon protection, 4 (5 mmol) was added to a reaction bottle containing 40 mL of DCE solution, cooled at 0 ° C, and then 1.67 mL of 3 M methyl magnesium bromide ether solution was slowly added, stirred for 30 minutes, quenched with 15 mL of saturated ammonium chloride solution, and then the aqueous phase was extracted three times with DCM (20 mL × 3), the organic layers were combined and washed with saturated NaCl, then dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel flash column chromatography (petroleum ether / EtOAc=200 / 1) to obtain 1.15 g of colorless oily product 5 in 74% yield. Using Piv protected substrate 4 and under the optimal reaction conditions, good chiral transfer (ee=96-98%) can be obtained.

[0063]

[0064] R f =0.45 (ethyl acetate: petroleum ether = 1:50); [α] D 25 = +14.3 (c = 1.06 in chloroform); 1 H NMR (400MHz,

[0065] CDCl3)δ5.82(dq,J=15.2,1.6Hz,1H),5.07(dq,J=15.2,6.4Hz,1H),1.68(dd,J=6.4,1.6Hz,

[0066] 3H),1.21(s,12H),1.16(s,9H),0.90(s,9H),-0.01(s,3H),-0.01(s,3H); 13 C NMR(100MHz, CDCl3)δ135.0,117.7,82.8,28.1,25.0,24.9,19.4,18.4,15.7,-6.6,-6.7; HRMS(ESI-TOF,m / z)calcd for C 17 H 35 BO2SiNa[M+Na] + :333.2392, found 333.2399.

[0067]

[0068] R f =0.45 (ethyl acetate: petroleum ether = 1:30); [α] D 25 = +3.2 (c = 0.89 in chloroform); 1 H NMR (600MHz, CDCl3) δ7.55–7.43(m,2H),7.39–7.27(m,3H),5.77(dq,J=15.4,1.6Hz,1H),4.96(dq,J=15.4 ,6.4Hz,1H),1.68(dd,J=6.4,1.6Hz,3H),1.17(s,6H),1.16(s,6H),1.09(s,3H),0.33(s,3H),0.30(s,3H); 13C NMR(150MHz, CDCl3)δ137.4,134.8,133.6,128.8,127.1,119.1,82.9,25.0,24.8,18.4,14.8,-4.6,-4.7; HRMS(ESI-TOF,m / z)calcd forC 19 H 31 BO2SiNa[M+Na] + :353.2079,found353.2076.

[0069]

[0070] R f =0.45 (ethyl acetate: petroleum ether = 1:30); [α] D 25 = -13.1 (c = 1.18 in chloroform); 1 H NMR (600MHz, CDCl3) δ7.22–7.15(m,2H),7.05(td,J=7.4,1.2Hz,1H),7.01–6.93(m,2H),5.79(dq,J=15.4,1.6Hz,1H),5.13(dq,J=15.4,6. 4Hz,1H),2.21–2.09(ABq,J=13.2Hz,2H),1.71(dd,J=6.4,1.6Hz,3H),1.25(s,6H),1.25(s,6H),1.17(s,3H),-0.07(s,3H),-0.10(s,3H); 13 C NMR(150MHz, CDCl3)δ140.5,133.5,128.4,128.0,123.8,118.7,83.0,25.1,24.9,23.2,18.5,14.4,-5.6,-5.7; HRMS(ESI-TOF,m / z)calcd for C 20 H 33 BO2SiNa[M+Na] + :367.2236, found 367.2240.

[0071] Example 2 Quaternary carbon-type allyl silicon boron reagents with different substitutions

[0072]

[0073] Experimental operation: Under argon protection, the reaction tube (10 mL) previously dried in an oven for 30 minutes was ventilated three times under an oil pump. 6 (37.5 mg, 0.1 mmol) was added to a reaction tube containing 1 mL of DCM solution, 0.15 mL of 1 M methylmagnesium bromide reagent was added at 0°C, stirred for 10 minutes, quenched with 1 mL of saturated ammonium chloride solution, and then the aqueous phase was extracted three times with EtOAc (1 mL×3), the organic layers were combined and washed with saturated NaCl, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel flash column chromatography (petroleum ether / EtOAc=200 / 1) to obtain 14.5 mg of colorless oily product 7a with a yield of 70%.

[0074] 1 H NMR (400MHz, CDCl3) δ7.49(m,2H),7.42(m,3H),5.78(dt,J=15.5,1.7Hz,1H),4.98(m,1H) ,1.69(dd,J=6.3,1.7Hz,3H),1.17(d,J=5.1Hz,12H),1.10(s,3H),0.33(d,J=13.2Hz,6H); 13 C NMR (100MHz, CDCl3) δ136.3,133.7,132.5,127.7,126.7,118.6,81.8,23.9,23.8,17.4,13.8,-5.6,-5.6; IR(neat)cm -1 2967,1332 1135,856,812,709,478; HRMS(ESI-TOF,m / z)calcd for C 19 H 11 Si[M+K] + :242.0893,found 242.0895.

[0075]

[0076] 7b: The operation method is the same as 7a: 6 (37.5 mg, 0.1 mmol.), EtMgBr (0.15 mL, 0.15 mmol.), 1 mL DCM, react for 10 min to obtain 16.7 mg of colorless oily product 7b with a yield of 75%.

[0077] 1H NMR (400MHz, CDCl3) δ7.49(m,2H),7.32(td,J=6.0,2.8Hz,3H),5.48(dd,J=15.9,1.9Hz,1H),5.05(dd,J=15.8,6.4Hz,1H),1.79(dt ,J=14.3,7.1Hz,1H),1.70(dd,J=6.4,1.6Hz,3H),1.45(m,1H),1.21(d,J=8.4Hz,12H),0.85(t,J=7.1Hz,3H),0.32(d,J=8.0Hz,6H); 13 C NMR (100MHz, CDCl3) δ137.3,135.4,130.7,128.8,127.1,121.2,82.8,25.4,24.7,22.5,18.6,11.8,-4.1,-4.4; IR(neat)cm -1 2972,2923,1332 1135,856,812,709,478; HRMS(ESI-TOF,m / z)calcd for C 14 H 21 Si[M+K] + :256.1050,found 256.1053.

[0078]

[0079] 7c: The operation method is the same as 7a: 6 (37.5 mg, 0.1 mmol.), i-PrMgBr (0.15 mL, 0.15 mmol.), 1 mL DCM, react for 10 min to obtain 17.8 mg of colorless oily product 7c with a yield of 77%.

[0080] 1 H NMR (400MHz, CDCl3) δ7.54(m,2H),7.30(m,3H),5.42(m,2H),1.99(m,J=6.8Hz,1H),1.74(d,J=4.9H z, 3H), 1.20 (d, J = 25.3Hz, 12H), 1.03 (d, J = 6.9Hz, 3H), 0.92 (d, J = 6.8Hz, 3H), 0.37 (d, J = 9.3Hz, 6H); 13 C NMR (100MHz, CDCl3) δ140.8,136.9,133.5,130.3,128.8,124.6,84.4,32.4,27.2,26.6,24.1,22.7,20.8,0.1,-0.2; IR(neat)cm -12965,2932,1334,1137,852,815,705,485; HRMS(ESI-TOF,m / z)calcd for C 15 H 23 Si[M+Na] + :254.1467,found 254.1471.

[0081]

[0082] 7d: The operation method is the same as 7a: 6 (37.5 mg, 0.1 mmol), cyclopropylmagnesium bromide (0.15 mL, 0.15 mmol), 1 mL DCM, react for 10 min to obtain 17.9 mg of colorless oily product 7d in 78% yield.

[0083] 1 H NMR (400MHz, CDCl3) δ7.58(m,2H),7.35(m,3H),5.63(dt,J=15.5,1.6Hz,1H),5.29(dq,J=15.5,6.4Hz,1H),1.72( dd,J=6.4,1.6Hz,3H),1.14(d,J=21.0Hz,12H),0.75(m,1H),0.66(m,1H),0.40(m,7H),0.38(s,1H),0.09(m,1H); 13 C NMR (100MHz, CDCl3) δ137.9,134.9,132.6,128.6,126.9,120.8,82.5,25.1,24.5,18.7,12.0,3.9,3.5,-3.5,-4.0; IR(neat)cm -1 2935,2912,1325,1131,842,825,711,479; HRMS(ESI-TOF,m / z)calcdfor C 15 H 21 Si[M+Na] + :252.1310,found 254.1309.

[0084]

[0085] 7e: The operation method is the same as 7a: 6 (37.5 mg, 0.1 mmol), cyclopentylmagnesium bromide (0.15 mL, 0.15 mmol), 1 mL DCM, react for 10 min to obtain 25.2 mg of colorless oily product 7e with a yield of 98%.

[0086] 1H NMR (400MHz, CDCl3) δ7.5(m,2H),7.32(m,3H),5.45(dd,J=15.9,1.6Hz,1H),5.34(m,1H),2.1(m,1H),1.72(dd,J=6.1,1 .3Hz,3H),1.66(m,2H),1.54(m,3H),1.40(m,2H),1.25(d,J=5.9Hz,1H),1.20(d,J=20.5Hz,12H),0.36(d,J=8.6Hz,6H); 13 C NMR (100MHz, CDCl3) δ141.7,137.3,134.2,130.7,129.2,124.8,84.8,44.3,33.1,33.0,28.1,27.8,27.5,27.4,21.3,-0.0,-0.3; IR(neat)cm -1 2945,2928,1328,1134,845,824,715,473; HRMS(ESI-TOF,m / z)calcd for C 17 H 25 Si[M+Na] + :296.1363,found 296.1365.

[0087]

[0088] 7f: The operation method is the same as 7a: 6 (37.5 mg, 0.1 mmol), phenylmagnesium bromide (0.15 mL, 0.15 mmol), 1 mL DCM, react for 10 min to obtain 25.2 mg of colorless oily product 7f with a yield of 95%.

[0089] 1 H NMR(400MHz CDCl3)δ7.21(m,3H),7.14(m,2H),7.06(m,2H),6.95(m,3H),5.79(dd,J=15.8,2.1Hz,1H),5.33(d q,J=15.9,6.4Hz,1H),1.68(dd,J=6.4,1.7Hz,3H),1.14(d,J=6.3Hz,12H),0.26(d,J=19.1Hz,6H); 13 C NMR (100MHz, CDCl3) δ142.0,136.8,134.2,130.2,127.6,127.4,126.4,125.8,124.3,123.0,82.2,23.9,23.7,17.9,-4.0,-4.7; IR(neat)cm-1 2962,1345,1328,1267,1139,842,827,711,478; HRMS(ESI-TOF,m / z)calcd forC 18 H 21 Si[M+K] + :304.1052, found 304.1050.

[0090]

[0091] 7g: The operation method is the same as 7a: 6 (37.5 mg, 0.1 mmol), 4-fluorophenylmagnesium bromide (0.15 mL, 0.15 mmol), 1 mL DCM, react for 10 minutes, and 26.3 mg of colorless oily product 7g is obtained with a yield of 93%.

[0092] 1 H NMR (400MHz, CDCl3) δ7.2(m,5H),6.86(m,2H),6.75(m,2H),5.75(dd,J=15.7,1.7Hz,1H),5.36(dq ,J=15.7,6.4Hz,1H),1.68(dd,J=6.4,1.6Hz,3H),1.15(d,J=7.6Hz,12H),0.25(d,J=27.1Hz,6H); 13 C NMR (100MHz, CDCl3) δ160.3(d,J=161Hz),138.6(d,J=2.1Hz),137.5,135.2,131.2,129.7(d,J=4 .8Hz),128.8,126.9,125.7,114.1(d,J=13.8Hz),83.3,24.9,24.7,18.9,-3.0,-3.8; IR(neat)cm -1 2958,1362,1347,1272,1159,847,821,717,475; HRMS(ESI-TOF,m / z)calcd for C 18 H 20 Si[M+Na] + :306.1214,found306.1216.

[0093]

[0094] 7h: The operation method is the same as 7a: 6 (37.5 mg, 0.1 mmol), 4-methoxyphenylmagnesium bromide (0.15 mL, 0.15 mmol), 1 mL DCM, react for 10 minutes, and 27.2 mg of colorless oily product 7h is obtained at 92%.

[0095] 1 H NMR (400MHz, CDCl3) δ7.31(m,3H),7.23(m,2H),6.94(d,J=8.7Hz,2H),6.71(d,J=8.9Hz,2H),5.83(dd,J=15.7,1.7Hz,1H ),5.39(dt,J=15.7,6.4Hz,1H),3.76(s,3H),1.74(dd,J=6.4,1.6Hz,3H),1.22(d,J=4.0Hz,12H),0.33(d,J=19.3Hz,6H); 13 C NMR (100MHz, CDCl3) δ156.5,138.1,135.3,134.9,131.7,129.5,128.7,126.9,125.1,113.0,83.2,55.2,24.9,24.7,-2.9,-3.6; IR(neat)cm -1 3127,2948,1352,1341,1278,1157,841,829,715,473; HRMS(ESI-TOF,m / z)calcd for C 19 H 23 Si[M+Na] + :318.1416, found 318.1413.

[0096]

[0097] 7i: The operation method is the same as 7a: 6 (37.5 mg, 0.1 mmol), vinyl magnesium bromide (0.15 mL, 0.15 mmol), 1 mL DCM, react for 10 min to obtain 20.1 mg of colorless oily product 7i with a yield of 95%.

[0098] 1 H NMR (400MHz, CDCl3) δ7.44(m,2H),7.23(m,3H),5.89(dd,J=17.4,10.8Hz,1H),5.47(m,1H),5.36 (m,1H),4.85(m,2H),1.63(dd,J=6.2,1.4Hz,3H),1.11(d,J=3.8Hz,12H),0.28(d,J=3.9Hz,6H);13 C NMR (100MHz, CDCl3) δ138.0,136.1,134.0,128.8,127.9,126.0,122.5,110.4,82.0,23.9,23.8,17.8,-5.4,-5.4; IR(neat)cm -1 3115,2967,1621,1364,1281,1171,851,819,724,458; HRMS(ESI-TOF,m / z)calcd for C 14 H 19 Si[M+Na] + :238.1154, found 238.1152.

[0099]

[0100] 7j: The operation method is the same as 7a: 6 (37.5 mg, 0.1 mmol), isopropenylmagnesium bromide (0.15 mL, 0.15 mmol), 1 mL DCM, react for 10 min to obtain 21.8 mg of colorless oily product 7j with a yield of 95%.

[0101] 1 H NMR (400MHz, CDCl3) δ7.62(m,2H),7.34(m,3H),5.71(d,J=15.8Hz,1H),5.29(m,1H),4.88(s,1H) ,4.69(s,1H),1.79(d,J=6.3Hz,3H),1.68(s,3H),1.28(d,J=2.1Hz,12H),0.44(d,J=13.6Hz,6H); 13 C NMR (100MHz, CDCl3) δ146.3,138.7,135.2,131.3,128.6,127.0,123.9,111.1,83.2,24.9,24.9,24.5,18.7,-2.7,-3.2; IR(neat)cm -1 2954,2936,1632,1367,1279,1156,853,814,727,458; HRMS(ESI-TOF,m / z)calcd for C 15 H 21 Si[M+Na] + :252.1310,found252.1311.

[0102] Example 4 Application of Quaternary Carbon-Type Geminal Silicon Boron Reagent in Allyl Boration Reaction

[0103]

[0104] Under argon protection, allyl geminalosilicate reagent 5a (62 mg, 0.2 mmol) was dissolved in 1 mL of hexafluoroisopropanol solution and added to a 10 mL reaction tube, followed by the addition of phenylpropanaldehyde (32 mg, 0.24 mmol) using a microsyringe. The mixture was stirred in an oil bath at 60 °C for 10 h (other aldehydes were monitored by TLC until the silicic acid reagent 5a was completely consumed, usually 3-12 h). The reaction liquid was cooled to room temperature and the solvent was removed under reduced pressure. The crude product was purified by silica gel flash column chromatography (petroleum ether / EtOAc=30 / 1) to obtain 54 mg of homoallyl alcohol compound 10a.

[0105] R f =0.35 (ethyl acetate: petroleum ether = 1:10); [α] D 25 = +11.8 (c = 1.02 in chloroform); ee = 97%. HPLC (OD-H, n-hexane / isopropanol = 97 / 3, flow rate = 0.8 mL / min, λ = 230 nm, T = 25 ° C): t R =8.68min(major),10.83min(minor); 1 H NMR (400MHz, CDCl3) δ7.34-7.23(m,2H),7.24-7.13(m,3H),5.57(d,J=9.2Hz,1H),3.45-3.33(m,1H),2.92-2.79(m,1H),2.75- 2.59(m,2H),1.92-1.79(m,1H),1.74(s,3H),1.75-1.65(m,1H),1.64(s,OH),0.95(d,J=6.8Hz,3H),0.87(s,9H),0.05(s,6H); 13 C NMR(100MHz, CDCl3)δ142.9,142.4,136.7,128.5,128.3,125.7,74.6,38.9,36.0,32.2,26.9,17.1,16.6,-6.3; HRMS(ESI-TOF,m / z)calcd forC 20 H 34 OSiNa[M+Na] + :341.2272,found341.2271.

[0106]

[0107] 10b: The operation method is the same as 10a: 5a (62 mg, 0.2 mmol), propionaldehyde (18 mg, 0.3 mmol), 1 mL hexafluoroisopropanol, react at room temperature for 8 hours to obtain 45 mg of colorless oily product 10b with a yield of 92%.

[0108] R f =0.5 (ethyl acetate: petroleum ether = 1:10); [α] D 25 = +32.6 (c = 0.81 in chloroform); ee = 99%. HPLC (OD-H, n-hexane / isopropanol = 100 / 0, flow rate = 0.5 mL / min, λ = 220 nm, T = 10°C): t R =39.47min(minor),48.88min(major); 1 H NMR (400MHz, CDCl3) δ5.58 (dq, J=9.2Hz, 1.6Hz, 1H), 3.31 (ddd, J=8.2Hz, 6.6Hz, 3.6Hz, 1H), 2.72-2.58 (m, 1H), 1.73 (d, J= 1.6Hz,3H),1.65-1.56(m,1H),1.46-1.32(m,1H),0.97(t,J=7.2Hz,3H),0.96(d,J=6.8Hz,3H),0.86(s,9H),0.05(s,6H); 13 C NMR(100MHz, CDCl3)δ143.1,136.3,76.7,38.4,27.0,26.9,17.1,16.7,16.5,10.1,-6.3; HRMS(ESI-TOF,m / z)calcd for C 14 H 30 OSiNa[M+Na] + :265.1959,found 265.1956.

[0109]

[0110] 10c: The operation method is the same as 10a: 5a (62 mg, 0.2 mmol), isovaleraldehyde (21 mg, 0.24 mmol), 1 mL hexafluoroisopropanol, react at room temperature for 10 hours to obtain 47 mg of colorless oily product 10c with a yield of 87%.

[0111] R f =0.5 (ethyl acetate: petroleum ether = 1:10); [α] D 25= +8.8 (c = 1.02 in chloroform); ee = 97% (10 c-OAc, measured after acetylation). HPLC (OD-H, n-hexane / isopropanol = 100 / 0, flow rate = 0.4 mL / min, λ = 220 nm, T = 10°C): t R =15.03min(minor),15.88min(major); 1 H NMR (400MHz, CDCl3) δ5.57 (dq, J=9.6Hz, 1.6Hz, 1H), 3.45 (ddd, J=9.6Hz, 6.2Hz, 3.2Hz, 1H), 2.70-2.52 (m, 1H), 1.91-1.74 (m, 1H), 1. 73(d,J=1.6Hz,3H),1.41-1.19(m,2H),0.96(d,J=6.8Hz,3H),0.93(d,J=6.8Hz,3H),0.90(d,J=6.4Hz,3H),0.86(s,9H),0.05(s,6H); 13 CNMR(100MHz, CDCl3)δ143.1,136.4,73.2,43.5,39.3,26.9,24.6,23.9,21.7,17.1,16.6,16.5,-6.3; HRMS(ESI-TOF,m / z)calcd for C 16 H 34 OSiNa[M+Na] + :293.2272,found293.2275.

[0112]

[0113] 10d: The operation method is the same as 10a: 5a (62 mg, 0.2 mmol), benzyloxyacetaldehyde (33 mg, 0.24 mmol), 1 mL hexafluoroisopropanol, react at 60 ° C for 8 hours to obtain 61 mg of colorless oily product 10d with a yield of 91%.

[0114] R f =0.3 (ethyl acetate: petroleum ether = 1:10); [α] D 25 = +18.7 (c = 0.63 in chloroform); ee = 97%. HPLC (OD-H, n-hexane / isopropanol = 98 / 2, flow rate = 1.0 mL / min, λ = 230 nm, T = 25 ° C): t R =7.59min(minor),11.66min(major); 1H NMR (400MHz, CDCl3) δ7.39-7.27(m,5H),5.64(dq,J=9.2Hz,1.6Hz,1H),4.55(dd,J=16.8Hz,12.0Hz,2H),2.75-2.65(m,1H),3.51(dd,J=9.6Hz,3.2Hz ,1H),3.41(dd,J=9.6Hz,7.6Hz,1H),2.85-2.72(m,1H),2.18(d,J=2.4Hz,O H),1.71(d,J=1.6Hz,3H),0.99(d,J=6.8Hz,3H),0.85(s,9H),0.03(s,6H); 13 C NMR(100MHz, CDCl3)δ142.5,138.1,135.3,128.4,127.7,74.0,73.4,72.6,35.2,26.9,17.1,16.6,16.3,-6.3,-6.3; HRMS(ESI-TOF,m / z)calcd for C 20 H 34 O2SiNa[M+Na] + :357.2221, found 357.2220.

[0115]

[0116] 10e: The operation method is the same as 10a: 5a (62 mg, 0.2 mmol), p-methoxybenzyloxypropanal (46 mg, 0.24 mmol), 1 mL hexafluoroisopropanol, react at 60 °C for 6 hours to obtain 70 mg of colorless oily product 10e with a yield of 93%.

[0117] R f =0.3 (ethyl acetate: petroleum ether = 1:10); [α] D 25 = +11.3 (c = 0.46 in chloroform); ee = 98%. HPLC (OD-H, n-hexane / isopropanol = 98 / 2, flow rate = 0.6 mL / min, λ = 250 nm, T = 25°C): t R =14.69min(minor),15.75min(major); 1H NMR (400MHz, CDCl3) δ7.28-7.22(m,2H),6.90-6.83(m,2H),5.63(dq,J=9.2Hz,1.6Hz,1H),4.45(s,2H),3.80(s,3H),3.73- 3.56(m,3H),2.73-2.60(m,1H),1.77-1.66(m,2H),1.71(d,J=1.6Hz,3H),0.98(d,J=6.8Hz,3H),0.86(s,9H),0.04(s,6H); 13 C NMR (100MHz, CDCl3) δ159.2,143.1,135.3,130.2,129.3,113.8,74.4,72.9,68.8, 55.3,38.6,33.8,26.9,17.1,16.4,16.4,-6.3,-6.3; HRMS(ESI-TOF,m / z)calcdfor C 22 H 38 O3SiNa[M+Na] + :401.2483,found 401.2480.

[0118]

[0119] 10f: The operation method is the same as 10a: 5a (62 mg, 0.2 mmol), benzyloxyvaleraldehyde (46 mg, 0.24 mmol), 1 mL hexafluoroisopropanol, react at 60 ° C for 6 hours to obtain 62 mg of colorless oily product 10f with a yield of 83%.

[0120] R f =0.4 (ethyl acetate: petroleum ether = 1:10); [α] D 25 = +13.1 (c = 1.22 in chloroform); ee = 98%. HPLC (OD-H, n-hexane / isopropanol = 99 / 1, flow rate = 0.8 mL / min, λ = 250 nm, T = 25°C): t R =29.78min(major),32.91min(minor); 1H NMR (400MHz, CDCl3) δ7.38-7.23(m,5H),5.57(dq,J=9.6Hz,2.0Hz,1H),4.50(s,2H),3.48(d,J=6.4Hz,2H),3.41-3.33(m,1H),2 .71-2.57(m,1H),1.72(d,J=1.6Hz,3H),1.71-1.50(m,4H),1.50-1.34(m,2H),0.95(d,J=6.8Hz,3H),0.87(s,9H),0.05(s,6H); 13 C NMR (100MHz, CDCl3) δ143.0,138.6,136.4,128.3,127.6,127.5,75.2,72.9,70.4 ,38.8,33.9,29.8,26.9,22.4,17.1,16.6,16.5,-6.3; HRMS(ESI-TOF,m / z)calcd for C 23 H 40 O2SiNa[M+Na] + :399.2690, found 399.2691.

[0121]

[0122] 10g: The operation method is the same as 10a: 5a (62 mg, 0.2 mmol), N-methyl-N-toluenesulfonyl propionaldehyde (58 mg, 0.24 mmol), 1 mL of hexafluoroisopropanol, react at 60 ° C for 10 hours to obtain 49 mg of colorless oily product 10g with a yield of 58%.

[0123] R f =0.5 (ethyl acetate: petroleum ether = 1:3); [α] D 25 = +4.3 (c = 0.74 in chloroform); ee = 98%. HPLC (OD-H, n-hexane / isopropanol = 97 / 3, flow rate = 0.8 mL / min, λ = 230 nm, T = 25 ° C): t R =14.46min(major),18.10min(minor); 1H NMR (400MHz, CDCl3) δ7.67(d,J=8.0Hz,2H),7.31(d,J=8.4Hz,2H),5.60(dq,J=9.6Hz,1.6Hz,1H) ,3.59(td,J=6.4Hz,2.8Hz,1H),3.39(ddd,J=13.5Hz,8.8Hz,6.7Hz,1H),2.87(ddd,J=13.5Hz,7. 1Hz,4.3Hz,1H),2.73(s,3H),2.71-2.61(m,1H),2.42(s,3H),2.19(d,J=3.5Hz,OH),1.80-1.64( m,1H),1.72(d,J=1.6Hz,3H),1.58-1.47(m,1H),0.99(d,J=6.8Hz,3H),0.86(s,9H),0.04(s,6H); 13 C NMR (100MHz, CDCl3) δ143.3,142.8,136.1,134.4,129.7,127.4,71.9,47.3,3 8.5,35.1,32.1,26.9,21.5,17.1,16.6,16.4,-6.3; HRMS(ESI-TOF,m / z)calcd for C 22 H 39 NO3SSiNa[M+Na] + :448.2313, found 448.2307.

[0124]

[0125] 10h: The operation method is the same as 10a: 5a (62 mg, 0.2 mmol), 2-methyl-1,3-dioxolane-2-acetaldehyde (31 mg, 0.24 mmol), 1 mL of hexafluoroisopropanol, react at 60 °C for 10 hours to obtain 58 mg of colorless oily product 10h with a yield of 92%.

[0126] R f =0.3 (ethyl acetate: petroleum ether = 1:10); [α] D 25 =-1.2 (c = 1.04 in chloroform); ee = 97%. HPLC (OD-H, n-hexane / isopropanol = 99.5 / 0.5, flow rate = 0.6 mL / min, λ = 220 nm, T = 25 ° C): t R =13.12min(minor),14.22min(major); 1H NMR (400MHz, CDCl3) δ5.68 (dq, J=9.2Hz, 1.8Hz, 1H), 4.04-3.91 (m, 4H), 3.81 (dt, J=8.0Hz, 4.4Hz, 1H), 3.34 (s, 1H), 2.7 3-2.58(m,1H),1.82-1.72(m,2H),1.71(d,J=1.6Hz,3H),1.36(s,3H),1.00(d,J=6.8Hz,3H),0.86(s,9H),0.04(s,6H); 13 C NMR(100MHz, CDCl3)δ143.0,134.4,110.5,71.3,64.7,64.2,42.1,38.1,26.9,24.0,17.2,16.2,16.2,-6.3,-6.3; HRMS(ESI-TOF,m / z)calcd for C 17 H 34 O3SiNa[M+Na] + :337.2170,found337.2167.

[0127]

[0128] 10i: The operation method is the same as 10a: 5a (62 mg, 0.2 mmol), 5-trimethylsilyl-3-ynylpropanal (34 mg, 0.24 mmol), 1 mL hexafluoroisopropanol, react at 60 ° C for 8 hours to obtain 42 mg of colorless oily product 10i with a yield of 62%. f =0.3 (ethyl acetate: petroleum ether = 1:10); [α] D 25 = +9.7 (c = 0.31 in chloroform); ee = 96%. HPLC (OD-H, n-hexane / isopropanol = 100 / 0, flow rate = 0.5 mL / min, λ = 220 nm, T = 25 ° C): t R =29.66min(minor),34.40min(major); 1 H NMR (400MHz, CDCl3) δ5.57 (dq, J=9.4Hz, 1.7Hz, 1H), 3.50 (t, J=7.2Hz, 1H), 2.75-2.60 (m, 1H), 2.48-2.27 (m, 2H), 1.83 -1.67(m,2H),1.73(d,J=1.7Hz,3H),1.65-1.51(m,1H),0.98(d,J=6.7Hz,3H),0.86(s,9H),0.14(s,9H),0.04(s,6H);13 C NMR(100MHz, CDCl3)δ142.8,136.5,107.4,84.8,74.3,38.6,33.1,26.9,17.1,16.5,16.5,0.1,-6.3; HRMS(ESI-TOF,m / z)calcd for C 19 H 39 OSi2[M+H] + :339.2534, found 339.2530.

[0129]

[0130] 10j: The operation method is the same as 10a: 5a (62 mg, 0.2 mmol), 4-formylphenylboronic acid pinacol ester (56 mg, 0.24 mmol), 1 mL hexafluoroisopropanol, react at 60°C for 8 hours to obtain 70 mg of colorless oily product 10j with a yield of 84%. f =0.35 (ethyl acetate: petroleum ether = 1:10); [α] D 25 =+55.0 (c=1.29 in chloroform); ee=98%.HPLC (OD-H, n-hexane / isopropanol=98 / 2, flow rate=0.5 mL / min, λ=240 nm, T=25°C): t R =16.36min(major),20.06min(minor); 1 H NMR (400MHz, CDCl3) δ7.78(d,J=8.8Hz,2H),7.35(d,J=8.0Hz,2H),5.61(dq,J=9.6Hz,2.0Hz,1H),4.36(d,J=8.0Hz,1H) ,2.99-2.84(m,1H),2.09(s,OH),1.75(d,J=2.0Hz,3H),1.35(s,12H),0.87(s,9H),0.79(d,J=6.8Hz,3H),0.06(s,6H); 13 C NMR(100MHz, CDCl3)δ145.6,143.0,137.6,134.6,126.4,83.7,78.5,41.0,26.9,24.9,24.8,17.1,16.6,16.6,-6.3,-6.3; HRMS(ESI-TOF,m / z)calcd for C 24 H 41 BO3SiNa[M+Na] +:439.2811, found 439.2811.

[0131]

[0132] 10k: The operation method is the same as 10a: 5a (62 mg, 0.2 mmol), benzothiazole-2-carboxaldehyde (39 mg, 0.24 mmol), 1 mL hexafluoroisopropanol, react at 60 ° C for 5 hours, and 60 mg of colorless or light yellow oily product 10k is obtained with a yield of 86%. f =0.55 (ethyl acetate: petroleum ether = 1:3); [α] D 25 =+59.8 (c=0.85 in chloroform); ee=99%.HPLC (AD-H, n-hexane / isopropanol=96 / 4, flow rate=0.8 mL / min, λ=240 nm, T=25°C): t R =10.17min(minor),11.73min(major); 1 H NMR (400MHz, CDCl3) δ7.98(d,J=8.4Hz,1H),7.88(d,J=8.0Hz,1H),7.46(ddd,J =8.4Hz,7.2Hz,1.2Hz,1H),7.37(ddd,J=8.4Hz,7.2Hz,1.2Hz,1H),5.70(dq,J=9 .2Hz,1.6Hz,1H),4.93(dd,J=5.6Hz,1H),3.27-3.13(m,1H),2.09(s,OH),1.62 (d,J=2.0Hz,3H),1.22(d,J=6.8Hz,3H),0.76(s,9H),0.03(s,3H),0.01(s,3H); 13 C NMR (100MHz, CDCl3) δ174.1,152.4,140.3,138.2,135.0,125.9,124.9,122.9,12 1.7,76.0,40.2,26.7,17.0,16.6,16.6,-6.3,-6.4; HRMS(ESI-TOF,m / z)calcdfor C 19 H 30 NOSSi[M+H] + :348.1812,found348.1810.

[0133]

[0134] 101: The operation method is the same as 10a: 5a (62 mg, 0.2 mmol), p-nitrobenzaldehyde (36 mg, 0.24 mmol), 1 mL of hexafluoroisopropanol, react at 60 °C for 5 hours to obtain 66 mg of yellow oily product 101 with a yield of 86%.

[0135] R f =0.35 (ethyl acetate: petroleum ether = 1:10); [α] D 25 = +60.2 (c = 0.83 in chloroform); ee = 96%. HPLC (OD-H, n-hexane / isopropanol = 97 / 3, flow rate = 1.0 mL / min, λ = 250 nm, T = 25°C): t R =12.42min(minor),13.54min(major); 1 H NMR (400MHz, CDCl3) δ8.20(d,J=8.8Hz,2H),7.52(d,J=8.8Hz,2H),5.58(dq,J=9.6Hz,2.0Hz,1H),4.50(dd,J=7.2Hz,2.0 Hz,1H),2.96-2.82(m,1H),2.24(d,J=2.0Hz,OH),1.70(d,J=1.6Hz,3H),0.87(d,J=6.8Hz,3H),0.85(s,9H),0.06(s,6H); 13 C NMR(100MHz, CDCl3)δ150.0,147.4,141.4,138.9,127.7,123.3,77.5,41.0,26.8,17.1,16.7,16.6,-6.3,-6.3; HRMS(ESI-TOF,m / z)calcd for C 18 H 30 NO3Si[M+H] + :336.1990,found336.1991.

[0136]

[0137] 10m: The operation method is the same as 10a: 5a (62 mg, 0.2 mmol), 2,5-dimethoxy-3-nitrobenzaldehyde (51 mg, 0.24 mmol), 1 mL hexafluoroisopropanol, react at 60 ° C for 8 hours to obtain 73 mg of yellow oily product 10m with a yield of 92%.

[0138] R f =0.4 (ethyl acetate: petroleum ether = 1:10); [α] D25 =+77.5 (c=0.96 in chloroform); ee=98%.HPLC (AD-H, n-hexane / isopropanol=98 / 2, flow rate=1.0 mL / min, λ=250 nm, T=25°C): t R =13.46min(major),16.61min(minor); 1 H NMR (600MHz, CDCl3) δ7.30-7.24(m,2H),5.65(dq,J=9.0,1.8Hz,1H),4.78(d,J=7.5Hz,1H),3.89(s,3H),3.83( s,3H),3.01-2.92(m,1H),1.65(d,J=1.8Hz,3H),0.89(d,J=6.8Hz,3H),0.86(s,9H),0.07(s,3H),0.06(s,3H); 13 CNMR (150MHz, CDCl3) δ155.2,145.1,143.5,141.7,140.1,138.6,119.3,108.6,72 .0,63.2,55.9,40.4,26.9,17.1,17.1,16.5,-6.2,-6.4; HRMS(ESI-TOF,m / z)calcd forC 20 H 33 NO5SiNa[M+H] + :418.2021, found 418.2016.

[0139]

[0140] 10n: The operation method is the same as 10a: 5a (62 mg, 0.2 mmol), 3-trimethylsilyl propioaldehyde (30 mg, 0.24 mmol), 1 mL trifluoroethanol (TFE), react at room temperature for 3 hours to obtain 60 mg of colorless oily product 10n with a yield of 97%. f =0.5 (ethyl acetate: petroleum ether = 1:10); [α] D 25 =-12.0 (c = 0.97 in chloroform); ee = 96%. HPLC (OD-H, n-hexane / isopropanol = 99 / 1, flow rate = 0.8 mL / min, λ = 220 nm, T = 25°C): t R =7.82min(minor),8.65min(major); 1H NMR (600MHz, CDCl3) δ5.54 (dq, J=9.6Hz, 1.8Hz, 1H), 4.18 (d, J=6.0Hz, 1H), 2.94-2.84 (m, 1H),1.75(d,J=1.8Hz,3H),1.07(d,J=6.6Hz,3H),0.86(s,9H),0.17(s,9H),0.04(s,6H); 13 C NMR(150MHz, CDCl3)δ141.9,136.7,105.1,90.2,66.7,39.0,26.9,17.2,16.5,15.5,-0.2,-6.4,-6.4; HRMS(ESI-TOF,m / z)calcd for C 17 H 34 OSi2Na[M+Na] + :333.2041, found 333.2040.

[0141]

[0142] 10o: The operation method is the same as 10a: 5a (62 mg, 0.2 mmol), 4-dimethyl-tert-butylsilyloxy-2-butynal (48 mg, 0.24 mmol), 1 mL of hexafluoroisopropanol, react at room temperature for 8 hours to obtain 75 mg of colorless oily product 10o with a yield of 98%.

[0143] R f =0.65 (ethyl acetate: petroleum ether = 1:10); [α] D 25 = +2.9 (c = 0.63 in chloroform); ee = 98%. HPLC (OD-H, n-hexane / isopropanol = 98 / 2, flow rate = 0.7 mL / min, λ = 220 nm, T = 25 ° C): t R =6.89min(major),8.15min(minor); 1 H NMR (400MHz, CDCl3) δ5.54 (dq, J=9.2Hz, 1.7Hz, 1H), 4.35 (d, J=1.7Hz, 2H), 4.25-4.14 (m, 1H), 2.96-2.82 (m, 1H), 1.8 2(d,J=4.6Hz,OH),1.75(d,J=1.7Hz,3H),1.07(d,J=6.7Hz,3H),0.91(s,9H),0.86(s,9H),0.12(s,6H),0.04(s,6H); 13C NMR(100MHz, CDCl3)δ141.9,136.9,84.3,84.2,66.5,51.7,39.2,26.8,25.8,18.3,17.1,16.5,15.7,-5.1,-6.4,-6.4; HRMS(ESI-TOF,m / z)calcd for C 21 H 42 O2Si2Na[M+Na] + :405.2616,found 405.2619.

[0144]

[0145] 10p: The operation method is the same as 10a: 5a (62 mg, 0.2 mmol), trans-4-oxy-2-butenoic acid ethyl ester (31 mg, 0.24 mmol), 1 mL hexafluoroisopropanol, react at room temperature for 8 hours to obtain 57 mg of colorless oily product 10p with a yield of 92%.

[0146] R f =0.35 (ethyl acetate: petroleum ether = 1:10); [α] D 25 = +19.3 (c = 0.54 in chloroform); ee = 97%. HPLC (AS-H, n-hexane / isopropanol = 97 / 3, flow rate = 0.8 mL / min, λ = 230 nm, T = 25 ° C): t R =7.54min(major),8.64min(minor); 1 H NMR (400MHz, CDCl3) δ6.94(dd,J=15.6Hz,5.6Hz,1H),6.05(dd,J=15.6Hz,1.6Hz,1H),5.53(dq,J=9.2Hz,1.8Hz,1H),4.20(q,J=7.2Hz,2H),4.0 9-4.02(m,1H),2.86-2.71(m,1H),1.82(brs,OH),1.74(d,J=1.8Hz,3H) ,1.29(t,J=7.2Hz,3H),1.00(d,J=6.4Hz,3H),0.86(s,9H),0.05(s,6H); 13 C NMR(100MHz, CDCl3)δ166.4,147.9,141.5,138.0,121.6,74.8,60.4,38.9,26.8,17.1,16.6,16.3,14.2,-6.3,-6.4; HRMS(ESI-TOF, m / z)calcd for C17 H 32 O3SiNa[M+Na] + :335.2013, found 335.2006.

[0147]

[0148] 10q: The operation method is the same as 10a: 5a (62 mg, 0.2 mmol), 4-benzyloxy-2-butenal (42 mg, 0.24 mmol), 1 mL hexafluoroisopropanol, react at room temperature for 8 hours to obtain 51 mg of colorless oily product 10q with a yield of 71%.

[0149] R f =0.4 (ethyl acetate: petroleum ether = 1:10); [α] D 25 = +15.7 (c = 0.37 in chloroform); ee = 99%. HPLC (AD-H, n-hexane / isopropanol = 97 / 3, flow rate = 0.5 mL / min, λ = 230 nm, T = 25 ° C): t R =17.02min(major),18.71min(minor); 1 H NMR (600MHz, CDCl3) δ7.42–7.26(m,5H),5.83(dt,J=15.6,5.6Hz,1H),5.75(ddt,J=15.6,6.8,1.2Hz,1H),5.55(dq,J=9.4,1.6Hz,1H),4.52(s ,2H),4.05(d,J=5.4Hz,2H),3.88(t,J=7.0Hz,1H),2.77–2.69(m,1H),1.75(d,J=1.6Hz,3H),0.95(d,J=6.8Hz,3H),0.86(s,9H),0.05(s,6H); 13 C NMR (150MHz, CDCl3) δ142.7,138.3,137.0,133.5,128.9,128.4,127.7,127.6, 76.1,72.1,70.1,39.0,26.9,17.1,16.5,16.3,-6.3; HRMS(ESI-TOF,m / z)calcd for C 22 H 36 O2SiNa[M+Na] + :383.2377, found 383.2375.

[0150] The above is only a preferred embodiment of the present invention. It should be understood that the present invention is not limited to the form disclosed herein, and should not be regarded as excluding other embodiments, but can be used in various other combinations, modifications and environments, and can be modified within the scope of the concept described herein through the above teachings or the technology or knowledge of the relevant field. The changes and modifications made by those skilled in the art shall not deviate from the spirit and scope of the present invention, and shall be within the scope of protection of the claims attached to the present invention.

Claims

1. A quaternary carbon chiral allyl geminal silicon boron compound, characterized in that: As shown in the following structural formula I: In the formula, R is one of C1-C6 n-alkyl, C3-C6 cycloalkyl, C2-C5 alkenyl, phenyl, chlorine atom substituted phenyl, fluorine atom substituted phenyl, methyl substituted phenyl, methoxy substituted phenyl; Si is one of dimethyl tert-butylsilyl, dimethylphenylsilyl, dimethylbenzylsilyl and trimethylsilyl.

2. The quaternary carbon chiral allyl geminal silicon boron compound according to claim 1, characterized in that: The R is methyl, ethyl, cyclopropyl, vinyl, propenyl or phenyl.

3. The method for synthesizing the quaternary carbon chiral allyl geminal silicon boron compound according to claim 1 or 2, characterized in that: The following steps are involved: The quaternary carbon chiral allyl geminal silicon boron compound is synthesized by using an alkenyl silicon boron compound and a Grignard reagent RMgX as substrates through a vinylogous Matteson reaction in a solvent, and the reaction formula is as follows: In the formula, LG is acetyl, pivaloyl, N,N-diisopropylcarbamate, tert-butoxycarbonyl or OPO (OR 1 ), the R 1 is Me, Et or iPr; the counter ion X of the Grignard reagent is one of Cl, Br and I.

4. The synthesis method according to claim 3, characterized in that The molar ratio of the alkenyl silicon boron compound to the Grignard reagent RMgX is in the range of 1:1 to 3; And / or, the temperature range of the vinylogous Matteson reaction is -40°C to 25°C; And / or, the vinylogous Matteson reaction time is 10min to 4h; And / or, the solvent of the vinylogous Matteson reaction is toluene, tetrahydrofuran, ether, dichloromethane or dichloroethane.

5. Use of the quaternary carbon chiral allyl geminal silicon boron compound according to claim 1 for synthesizing chiral high-propylene alcohol compounds.

6. The use according to claim 5, characterized in that: The quaternary carbon chiral allyl geminal silicon boron compound is used as an allyl bimetallic reagent to synthesize the chiral homoallyl alcohol compound through an allyl borylation reaction.

7. The use according to claim 6, characterized in that: The chiral homoallyl alcohol compound comprises a trisubstituted olefin E-anti homoallyl alcohol compound, and the synthesis method comprises the following steps: The quaternary carbon chiral allyl geminal silicon boron compound and aldehyde are used as substrates, and the trisubstituted olefin E-anti homoallyl alcohol compound is obtained by allylic borylation reaction in a fluorine-containing solvent. The reaction formula is as follows: In the formula, R 2 It is one of C1-C8 alkyl, C1-C8 alkyl substituted with O, N heteroatom or phenyl, C3-C8 alkenyl, C3-C8 alkenyl substituted with oxygen atom, phenylpropargyl, trimethylsilyl substituted alkynyl, C3-C8 alkynyl substituted with oxygen atom, phenyl, furyl, thienyl, quinolyl, indolyl, benzothiazolyl, phenyl substituted with nitro, trifluoromethyl, chlorine atom, cyano, ethynyl, methyl and methoxy.

8. The use according to claim 7, characterized in that: The R 2 It is ethyl, isobutyl, phenylpropyl, benzyloxy, 2-methyl-1,3-dioxolanyl, N-methyl-N-p-toluenesulfonyl-3-amino, trimethylsilyl, ethyl acrylate, p-nitrophenyl or benzothiazolyl.

9. The use according to claim 7, characterized in that: The fluorine-containing solvent in the allyl borylation reaction includes one of trifluoroethanol, hexafluoroisopropanol, trifluoroisopropanol, and 3,3,3-trifluoro-1-propanol; And / or, in the allyl borylation reaction, the molar ratio of the quaternary carbon chiral allyl geminal silicon boron compound to the aldehyde is in the range of 1:1 to 3 or 1 to 3:1; and / or, the temperature range of the allyl borylation reaction is 25° C. to 80° C.; And / or, the allyl borylation reaction time is 0.5h to 24h.

10. The E-anti chiral high propylene alcohol compound synthesized by the application of any one of claims 5 to 9.

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