Chiral silacyclopentane with silicon-containing stereo center and preparation method of chiral silacyclopentane

Abstract

The invention belongs to the technical field of organic synthesis, and particularly discloses a preparation method of a chiral silacyclopentane derivative with a silicon-containing stereocenter. Under the action of a chiral catalyst, 2-mercaptobenzothiazole is used for carrying out ring-opening desymmetry on a prochiral 3-silacyclopentene epoxy compound, and the reaction has good yield and enantiomer selectivity. The method overcomes the defects in the aspect of synthesis of chiral silacyclopentane reported in previous literatures: a stoichiometric chiral lithium amide reagent is needed under anhydrous and anaerobic conditions, and a greatly excessive nucleophilic reagent is needed due to relatively low reaction activity. The method is mild in reaction condition, free of metal and high in reaction activity, and the structure comprises a silicon three-dimensional center.

Description

Technical Field

[0001] The invention relates to a chiral silaalkane and a preparation method thereof. The obtained chiral silaalkane can be used as an organic synthesis building block for preparing bioactive molecules, and specifically relates to a chiral silacyclopentane containing a silicon stereocenter and a preparation method thereof. Background Art

[0002] Chiral organosilicon compounds containing silicon stereocenters are currently at the forefront of asymmetric catalysis research (Chin. J. Org. Chem. 2023, 43, 3388). Silicon atoms and carbon atoms belong to the same main group, but because the radius of silicon atoms is larger than that of carbon atoms, it generally brings challenges to stereoselective control during the reaction process. In addition, after the introduction of silicon atoms into drug or material molecules, the lipid solubility of the original molecules will be greatly improved, as well as the activity and metabolic process of drug molecules. Therefore, organosilicon chemistry has attracted great attention from synthetic chemists in organic synthesis.

[0003] The construction of chiral organosilicon compounds containing silicon stereocenters using asymmetric catalysis is still difficult, specifically in the following two aspects: (1) The large atomic radius of silicon makes it impossible for the catalyst to effectively transfer chiral information to the reaction intermediates in the enantioselective determination step, often resulting in products with low enantioselectivity; (2) Silicon-containing (prochiral) substrates are difficult to synthesize.

[0004] In 2016, Tomooka's group reported a method for synthesizing silanol derivatives containing a silicon stereocenter (Angew.Chem.Int.Ed.2016,55,5814), but this method requires the use of a large excess of chiral lithium amide (3 equivalents) and strict dehydration reaction conditions to obtain products with ideal yields and enantioselectivity. The one-pot desymmetrization-ring-opening reaction of prochiral 3-silacyclopentene epoxides with acid-catalyzed organic carboxylic acids not only requires a long reaction time (120 h) but also requires expensive Martin reagents. In particular, only the trans isomer I is suitable for the reaction.

[0005] Directly through chirality There are currently no relevant literature reports on the synthesis of chiral silacyclopentane derivatives containing silicon stereocenters by acid-catalyzed desymmetric reactions of prochiral 3-silacyclopentene epoxides (especially their cis-isomers). Summary of the invention

[0006] The object of the present invention is to provide a chiral silacyclopentane containing a silicon stereocenter and a preparation method thereof.

[0007] The structure of the chiral silacyclopentane containing a silicon stereocenter is shown in Formula I:

[0008]

[0009] Where R 1 Selected from:

[0010] Any of the following:

[0011] R 2 Selected from:

[0012] Any of methyl (Me) and tert-butyl (tBu);

[0013] R 3 Selected from: any one of H, Me, F, Br, Cl, tBu.

[0014] The preparation method comprises the following steps:

[0015] Chirality Under the action of an acid catalyst, a prochiral 3-silacyclopentene epoxy compound and a 2-mercaptobenzothiazole compound undergo a desymmetric reaction in an organic solvent to generate a product I, wherein the 2-mercaptobenzothiazole acts as a nucleophilic reagent. Prochiral 3-silacyclopentene oxide was desymmetrized under acid catalyst.

[0016] The structural formula of the prochiral 3-silacyclopentene epoxy compound is

[0017] Preferably, the prochiral 3-silacyclopentene epoxy compound is

[0018] and

[0019] The structure of the 2-mercaptobenzothiazole compound is:

[0020] Preferably, the 2-mercaptobenzothiazole compound is (MBT).

[0021] Preferably, the organic solvent is selected from toluene, benzene, xylene, trifluorotoluene, and chlorobenzene.

[0022] Preferably, the chirality The acid catalyst is selected from the group consisting of Formula A, B or C or their corresponding enantiomers:

[0023]

[0024] Wherein R is independently selected from anthracenyl, 3,5-diphenylphenyl, 4-tert-butylphenyl:

[0025] Preferably, the chirality The acid catalyst is a catalyst having the following formula CPA-1 or its enantiomer:

[0026]

[0027] Any variant catalyst obtained by structural modification of the preferred catalyst and its application in the desymmetrization reaction of prochiral silacyclopentene epoxide by 2-mercaptobenzothiazole are logical extensions of the content of the present invention.

[0028] Furthermore, the preparation method comprises the following steps: cooling the system to which the prochiral 3-silacyclopentene epoxy compound, 2-mercaptobenzothiazole and an organic solvent are added to -30°C to 0°C; maintaining the temperature and continuously stirring, adding the chiral Acid catalyst, then continue to maintain temperature and stir until the reaction is complete.

[0029] More preferably, the temperature is -15°C;

[0030] More preferably, the molar ratio of the prochiral 3-silacyclopentene epoxy compound to the nucleophilic reagent 2-mercaptobenzothiazole is 1:1.0; The molar ratio of the acid catalyst is 1000:1.

[0031] Furthermore, the 2-mercaptobenzothiazole of the present invention is synthesized by the following steps:

[0032]

[0033] The above reaction steps are summarized as follows:

[0034] (1) Salicylic acid and diphenylphosphoryl azide (DPPA) undergo Curtius rearrangement reaction in an organic solvent, and the intermediate is hydrolyzed to obtain compound 1.

[0035] Preferably, the reaction temperature of step (1) is 100-150°C, more preferably 115°C;

[0036] Preferably, the molar ratio of salicylic acid to diphenylphosphoryl azide is 1:1.0 to 2.0, more preferably 1:1.5.

[0037] The reaction solvent is selected from toluene, dichloromethane, benzene, preferably toluene.

[0038] (2) Compound 1 is reacted with an amino protecting agent to protect the amino group of Compound 1 to obtain Compound 2.

[0039] Preferably, the amino protecting agent is selected from: di-tert-butyl dicarbonate (Boc2O), benzoic anhydride (Bz2O), acetic anhydride (Ac2O), benzyl chloroformate (CbzCl).

[0040] Preferably, the ratio of compound 1 to the amino protecting agent is 1:1.0 to 2.0, more preferably 1:1.1.

[0041] (3) Compound 2 is reacted with a trifluoromethanesulfonylating agent to convert the hydroxyl group in Compound 2 into trifluoromethanesulfonate. The obtained crude product is directly subjected to amino deprotection reaction with a reagent for deamino protecting group to obtain Compound 3.

[0042] Preferably, compound 2 is reacted with a trifluoromethanesulfonylating agent in the presence of triethylamine.

[0043] Preferably, the trifluoromethanesulfonylating agent is selected from: trifluoromethanesulfonyl chloride or trifluoromethanesulfonic anhydride. The reaction temperature is -78°C to 0°C, preferably -50°C; and the reaction solvent is preferably dichloromethane.

[0044] Preferably, the ratio of the compound 2 to the trifluoromethanesulfonylating agent is 1:1.0 to 2.0, preferably 1:1.1.

[0045] The obtained trifluoromethanesulfonyl intermediate needs to be deprotected from the amino protecting group after simple purification. The reagent for deprotecting the amino protecting group is selected from: trifluoroacetic acid or hydrogen chloride, preferably hydrogen chloride. The ratio of the intermediate to hydrogen chloride is 1:1.0 to 10.0, preferably 1:5.0.

[0046] (4) Compound 3 reacts with ethyl xanthate to obtain 2-mercaptobenzothiazole (MBT).

[0047] Preferably, the above reaction is carried out in a solvent at 100-160° C., and the solvent is selected from formamide or N-methylpyrrolidone, preferably formamide.

[0048] Preferably, the ethyl xanthate is selected from halide salts, preferably potassium salts and sodium salts.

[0049] Preferably, the ratio of compound 3 to ethyl xanthate is 1:1.0 to 10.0, preferably 1:1.2; the reaction temperature is preferably 120°C or 150°C.

[0050] The present invention has the following advantages:

[0051] 1. Under the action of a chiral catalyst, 2-mercaptobenzothiazole is used to perform ring-opening desymmetrization on a prochiral 3-silacyclopentene epoxy compound, and the reaction has good yield and enantiomeric selectivity. The shortcomings of the prior art in the synthesis of chiral silacyclopentanes are overcome: the need for stoichiometric chiral lithium amide reagents under anhydrous and oxygen-free conditions, and the need for a large excess of nucleophilic reagents due to low reaction activity. The present invention has mild reaction conditions, does not require metal, has high reaction activity, and contains a silicon stereo center in the structure.

[0052] 2. The chiral product obtained by the present invention has great application value in the synthesis of ligands and bioactive compounds. DETAILED DESCRIPTION

[0053] Example 1, synthesis of compound 1:

[0054]

[0055] Under nitrogen atmosphere, salicylic acid (2.8 g, 20 mmol, 1.0 equiv) and 50 mL of anhydrous toluene were placed in a 250 mL two-necked bottle. Under magnetic stirring, triethylamine (5.6 mL, 40 mmol, 2.0 equiv) and diphenylphosphoryl azide (DPPA, 8.3 g, 30 mmol, 1.5 equiv) were added to the reaction system in sequence by syringe. The obtained reaction solution was reacted at 115 ° C for 24 h. After the reaction was completed, the reaction solution was cooled to room temperature and then 50 mL of water was added. The obtained two-phase mixed solution was stirred at 50 ° C for 1 hour, and all low-boiling solvents were removed by rotary evaporation. The residue was separated by column chromatography (developing solvent: petroleum ether / ethyl acetate = 20:1) to obtain the target product.

[0056] The product characterization data are as follows:

[0057] Pale yellow oil (1.7 g, 79% yield).

[0058] 1 H NMR (400MHz, DMSO-d6): δ8.90(s,1H),6.65-6.63(m,1H),6.50-6.57(m,2H),6.34-6.42(m,1H),4.46(s,2H).

[0059] 13 C NMR(100MHz,DMSO-d6):144.4,136.8,119.9,116.9,114.9,114.8.

[0060] Example 2, synthesis of compound 2:

[0061]

[0062] Under nitrogen atmosphere, o-aminophenol 1 (1.1 g, 10 mmol, 1.0 equiv) and 20 mL of ultra-dry dichloromethane were placed in a 100 mL round-bottom single-necked flask. After the reaction system was cooled to 0 ° C, di-tert-butyl dicarbonate (Boc2O, 2.4 g, 11 mmol, 1.1 equiv) was added to the reaction system with a syringe under magnetic stirring. The obtained reaction solution was reacted at room temperature for 12 h. After the reaction was completed, all low-boiling solvents were removed by rotary evaporation. The residue was separated by column chromatography (developing solvent: petroleum ether / ethyl acetate = 20:1) to obtain the target product.

[0063] White solid (1.9 g, 90% yield).

[0064] 1 H NMR (400MHz, CDCl3)8.15(br,1H),7.00-7.12(m,2H),6.95-6.99(m,1H),6.80-6.89(m,1H),6.69(br,1H),1.55(s,9H)ppm.

[0065] 13 C NMR (75MHz, CDCl3)147.5,125.6,125.5,121.4,120.7,118.9,82.1,28.2ppm.

[0066] Example 3, synthesis of compound 3:

[0067]

[0068] Under nitrogen protection, a 100 mL round-bottom flask containing compound 2 (2.1 g, 10 mmol, 1.0 equiv) and ultra-dry dichloromethane (50 mL) was cooled to -78 °C. Triethylamine (2.1 mL, 15 mmol, 1.5 equiv) was added to the reaction system at once through a syringe, and the reaction was stirred for 30 minutes. At the same reaction temperature, trifluoromethanesulfonic anhydride (1.6 mL, 11 mmol, 1.1 equiv) was slowly added through a syringe. After the addition was completed, the reaction system was slowly heated to -50 °C and reacted for 5 h. After the reaction was completed, 10 mL of dilute hydrochloric acid (1 M) was added to the reaction system to quench the reaction, and the reaction was extracted with dichloromethane (20 mL × 3), dried over anhydrous sodium sulfate, and filtered. The residue was purified by column chromatography (petroleum ether / ethyl acetate = 10:1) to obtain the intermediate.

[0069] Under nitrogen protection, the intermediate was dissolved in a solution of hydrogen chloride in 1,4-dioxane (12.5 mL, 4 M in 1,4-dioxane, 5.0 equiv), and the obtained reaction system was reacted at room temperature for 10 h. After the reaction, the reaction solution was spin-dried and directly purified by column chromatography (petroleum ether / ethyl acetate = 10:1 to 1:1) to obtain the hydrochloride of product 3.

[0070] Note: The product is unstable and should not be left for a long time. The present invention directly proceeds to the subsequent synthesis.

[0071] Example 4, Synthesis of MBT:

[0072]

[0073] Under nitrogen atmosphere, compound 3 (2.4 g, 10 mmol, 1.0 equiv), potassium ethyl xanthate (1.9 g, 12 mmol, 1.2 equiv) and ultra-dry formamide (20 mL) were placed in a 100 mL round-bottom flask, and the obtained reaction solution was heated to 120°C in an oil bath and stirred at the same reaction temperature for 24 hours. After the reaction was completed, formamide was removed by vacuum distillation, 100 mL of deionized water was added to the residue, and dichloromethane was extracted (50 mL×3), the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the solvent was removed by rotary evaporation. The obtained residue was purified by column chromatography (petroleum ether / ethyl acetate = 5:1 to 2:1) to obtain the target product MBT.

[0074] Pale yellow solid (669 mg, 40% yield, total yield for two steps).

[0075] 1 H NMR (500MHz, DMSO-d6,) δ13.77(s,1H),7.69(d,J=7.5Hz,1H),7.40(t,J=7.5Hz,1H),7.24-7.30(m,2H)ppm.

[0076] 13 C NMR (125MHz, DMSO-d6) δ190.6,141.5,129.7,127.6,124.5,122.6,112.5ppm.

[0077] Example 5: Synthesis of Chiral Silane I-3a

[0078] In a 4 ml vial equipped with a magnetic stirrer, add the epoxy compound II-syn-1a (0.2 mmol, 1.0 equiv), 2-mercaptobenzothiazole compound 2a (0.2 mmol, 1.0 equiv) and xylene (1.0 mL). The vial was carefully sealed with a pierceable screw cap and electrical tape, and then cooled to -15 ° C. Stir at the same temperature for 5 minutes, and add 50 μL of a xylene solution of the chiral catalyst CPA-1 (code CPA-1, 0.2 mg, 0.0002 mmol, 0.1 mol%). Then, stir at the same temperature and monitor the reaction process by thin layer chromatography (TLC). After the reaction is completed, silica gel column chromatography (eluent: n-hexane / ethyl acetate = 10:1) is directly performed to obtain the desired product I-3a. The synthetic route is shown below.

[0079]

[0080] The product was a colorless oil (72 mg, 91% yield, 72% ee).

[0081] The characterization data are as follows:

[0082] HPLC analysis of the product:Daicel IC column; 10% i-PrOHin n-hexane; 1.0mL / min; λ = 254nm, retention times: 16.1min (major), 21.3min (minor).

[0083] 1 H NMR(400MHz, CDCl3)δ7.78(d,J=8.0Hz,1H),7.70(d,J=8.0Hz,1H),7.56–7.53(m,2H),7.42–7.35(m,4H),7.29–7.25(m,1H),5 .63(br,1H),4.25–4.17(m,1H),3.83–3.75(m,1H),1.84–1.79(m,1H),1.73–1.68(m,1H),1.23–1.11(m,2H),0.95(s,9H)ppm.

[0084] 13 C NMR (100MHz, CDCl3) δ168.0,152.3,135.4,134.7,134.5,129.6,127.9,126.3,124.7,121.4,121.0,79.8,55.5,26.4,19.3,16.8,14.8ppm.

[0085] HRMS(ESI+)Calcd for C 21 H 26 NOS2Si[M+H] + :400.1225,found:400.1206. Example 6: Synthesis of Chiral Silane I-3b:

[0086] According to the steps of Example 5, the starting material epoxy compound II-syn-1a was replaced by II-anti-1a, and the synthesis route is as follows:

[0087]

[0088] The product I-3b was a colorless oil (76 mg, 96% yield, 79% ee).

[0089] The characterization data are as follows:

[0090] HPLC analysis of the product:Daicel IC column; 15% i-PrOHin n-hexane; 1.0mL / min; λ = 254nm, retention times: 10.3min (major), 23.6min (minor).

[0091] 1 H NMR (400MHz, CDCl3) δ7.86–7.83(m,1H),7.75–7.72(m,1H),7.54–7.51(m,2H),7.43–7.36(m,4H),7.33–7.29(m,1H ),5.72(d,J=4Hz,1H),4.13–4.06(m,1H),3.94–3.86(m,1H),1.86–1.74(m,2H),1.22–1.10(m,2H),0.99(s,9H)ppm.

[0092] 13 C NMR (100MHz, CDCl3) δ168.0,152.4,135.5,134.7,134.6,129.6,127.9,126.3,124.7,121.5,121.0,79.0,56.2,26.4,18.7,16.9,15.7ppm.

[0093] HRMS(ESI+)Calcd for C 21 H 26 NOS2Si[M+H]+ :400.1225,found:400.1214. Example 7: Synthesis of Chiral Silane I-3c

[0094] According to the steps of Example 5, the starting material epoxy compound II-syn-1a was replaced by II-syn-1b, and the synthesis route is as follows:

[0095]

[0096] The product I-3c was a colorless oil (78 mg, 94% yield, 68% ee).

[0097] The characterization data are as follows:

[0098] HPLC analysis of the product:Daicel IC column; 10% i-PrOHin n-hexane; 1.0mL / min; λ = 210nm, retention times: 13.7min (major), 19.0min (minor).

[0099] 1 H NMR (400MHz, CDCl3) δ7.80(d,J=8.0Hz,1H),7.73(d,J=8.0Hz,1H),7.54–7.51(m,2H),7.42–7.37(m,1H),7.32–7.26(m,1H),7.11–7.07(m, 2H),5.63(d,J=1.0Hz,1H),4.25–4.17(m,1H),3.82–3.74(m,1H),1.84–1.79(m,1H),1.70–1.66(m,1H),1.22–1.15(m,2H),0.95(s,9H)ppm.

[0100] 13 C NMR(100MHz,CDCl3)δ167.8,164.0(d, 1 J C-F =241Hz),152.3,136.6(d, 3 J C-F =7Hz),135.4,130.0(d, 4 J C-F =4Hz),126.3,124.7,121.4,121.0,115.2(d, 2 J C-F=20Hz),79.8,55.3,26.3,19.4,16.8,14.9ppm.

[0101] 19 F NMR (375MHz, CDCl3) δ-110.8ppm.

[0102] HRMS(ESI+)Calcd for C 21 H 25 FNOS2Si[M+H] + :418.1131,found:418.1120. Example 8: Synthesis of Chiral Silane I-3d

[0103] According to the steps of Example 5, the starting material epoxy compound II-syn-1a was replaced by I-3c. The synthesis route is as follows:

[0104]

[0105] The product I-3d was a colorless oil (74 mg, 89% yield, 72% ee).

[0106] The characterization data are as follows:

[0107] HPLC analysis of the product:Daicel IC column; 10% i-PrOHin n-hexane; 1.0mL / min; λ = 254nm, retention times: 13.3min (major), 17.9min (minor).

[0108] 1 H NMR(400MHz, CDCl3)δ7.80(d,J=8.0Hz,1H),7.72(d,J=8.0Hz,1H),7.42–7.34(m,2H),7.32–7.22(m,3H),7.11–7.06(m,1H), 5.63(s,1H),4.25–4.17(m,1H),3.82–3.74(m,1H),1.85–1.79(m,1H),1.72–1.68(m,1H),1.23–1.16(m,2H),0.96(s,9H)ppm.

[0109] 13 C NMR(100MHz,CDCl3)δ167.8,162.5(d, 1 J C-F=251Hz),152.3,137.6(d, 4 J C-F =4Hz),135.4,130.3(d, 3 J C-F =3Hz),129.7(d, 3 J C-F =7Hz),127.8,126.3,124.7,121.4,121.03,120.98(d, 2 J C-F =19Hz),116.6(d, 2 J C-F =21Hz),79.7,55.2,26.3,19.3,16.8,14.7ppm.

[0110] 19 F NMR (375MHz, CDCl3) δ-113.1ppm.

[0111] HRMS(ESI+)Calcd for C 21 H 25 FNOS2Si[M+H] + :418.1131,found:418.1112. Example 9: Synthesis of Chiral Silane I-3e

[0112] According to the steps of Example 5, the starting material epoxy compound II-syn-1a was replaced by II-syn-1d, and the synthesis route is as follows:

[0113]

[0114] The product I-3e was a colorless oil (84 mg, 96% yield, 72% ee).

[0115] The characterization data are as follows:

[0116] HPLC analysis of the product:Daicel IC column; 10% i-PrOHin n-hexane; 1.0mL / min; λ = 254nm, retention times: 10.8min (major), 14.2min (minor).

[0117] 1H NMR(400MHz,CDCl3)δ7.81(d,J=8.0Hz,1H),7.71(d,J=8.0Hz,1H),7.42–7.38(m,1H),7.32–7.26(m,1H),7.05–7.03(m,2H),6.87–6.81(m,1H),5.61(br,1H),4.25–4.17(m,1H),3.80–3.73(m,1H),1.85–1.79(m,1H),1.71–1.67(m,1H),1.21–1.13(m,2H),0.97(s,9H)ppm.

[0118] 13 C NMR(100MHz,CDCl3)δ167.6,162.8(d, 1 J C-F =252Hz),162.7(d, 1 J C-F =252Hz),152.3,139.43(d, 4 J C-F =5Hz),139.38(d, 4 J C-F =5Hz),135.4,126.8,124.8,121.4,121.1,116.79(d, 2 J C-F =22Hz),116.78(d, 3 J C-F =11Hz),105.2(d, 2 J C-F =25Hz),105.0(d, 2 J C-F =25Hz),79.5,55.1,26.3,19.1,16.8,14.7ppm.

[0119] Note:the two fluorine atoms become non-equivalent based on theresults on 13 C NMR.

[0120] 19 F NMR(375MHz,CDCl3)δ-109.6ppm.

[0121] HRMS(ESI+)Calcd for C 21 H 24 F2NOS2Si[M+H] +:436.1037,found:436.1022. Example 10: Synthesis of Chiral Silane I-3f

[0122] According to the steps of Example 5, the starting material epoxy compound II-syn-1a was replaced by II-syn-1e, and the synthesis route is as follows:

[0123]

[0124] The product I-3f was a colorless oil (76 mg, 91% yield, 69% ee).

[0125] The characterization data are as follows:

[0126] HPLC analysis of the product:Daicel IC column; 10% i-PrOHin n-hexane; 1.0mL / min; λ = 254nm, retention times: 14.4min (major), 19.7min (minor).

[0127] 1 H NMR (600MHz, CDCl3) δ7.83–7.81(m,1H),7.75–7.73(m,1H),7.48–7.47(m, 2H),7.43–7.40(m,1H),7.33–7.30(m,1H),7.23(d,J=6.0Hz,2H),5.59(br, 1H),4.25–4.21(m,1H),3.85–3.80(m,1H),2.39(s,3H),1.85–1.81(m,1H) ,1.73–1.69(m,1H),1,26–1,22(m,1H),1.19–1.14(m,1H),0.98(s,9H)ppm.

[0128] 13 C NMR (150MHz, CDCl3) δ168.0,152.3,139.6,135.4,134.7,130.8,128.7,126.3,124.7,121.4,121.0,79.8,55.6,26.4,21.5,19.4,16.8,14.9ppm.

[0129] HRMS(ESI+)Calcd for C 22 H 28 NOS2Si[M+H] +:414.1382,found:411.1369. Example 11: Synthesis of Chiral Silane I-3g

[0130] According to the steps of Example 5, the starting material epoxy compound II-syn-1a was replaced with II-syn-1f, and the synthesis route is as follows:

[0131]

[0132] The product I-3g is a colorless oil (80 mg, 92% yield, 70% ee).

[0133] The characterization data are as follows:

[0134] HPLC analysis of the product:Daicel IC column; 10% i-PrOHin n-hexane; 1.0mL / min; λ = 230nm, retention times: 20.6min (major), 30.1min (minor).

[0135] 1 H NMR (400MHz, CDCl3) δ7.80(d,J=8.0Hz,1H),7.72(d,J=8.0Hz,1H),7.47(d,J=8.0Hz,2H),7.41–7.37(m,1H),7.31–7.26(m,1H),6.93(d,J= 8.0Hz,2H),5.59(br,1H),4.23–4.16(m,1H),3.83–3.75(m,4H),1.82–1.77(m,1H),1.69–1.63(m,1H),1.20–1.08(m,2H),0.95(s,9H)ppm.

[0136] 13 C NMR (100MHz, CDCl3) δ168.0,160.8,152.3,136.1,135.4,126.3,125.1,124.7,121.4,121.0,113.7,80.0,55.5,55.1,26.3,19.4,16.9,15.0ppm.

[0137] HRMS(ESI+)Calcd for C 22 H 28 NO2S2Si[M+H] + :430.1331,found:430.1319. Example 12: Synthesis of Chiral Silane I-3h

[0138] According to the steps of Example 5, the starting material epoxy compound II-syn-1a was replaced by II-syn-1g, and the 2-mercaptobenzothiazole compound 2a was replaced by 2b. The synthesis route is as follows:

[0139]

[0140] The product I-3h was a colorless oil (82 mg, 96% yield, 71% ee).

[0141] The characterization data are as follows:

[0142] HPLC analysis of the product:Daicel IC column; 10% i-PrOHin n-hexane; 1.0mL / min; λ = 230nm, retention times: 16.7min (major), 32.1min (minor).

[0143] 1 H NMR (600MHz, CDCl3) δ7.70–7.69(m,1H),7.53(s,1H),7.48–7.46(m,2H),7.24–7.21(m,3H),5.72(br,1H),4.24–4.19(m,1H),3.81– 3.75(m,1H),2.46(s,3H),2.38(s,3H),1.84–1.80(m,1H),1.71–1.68(m,1H),1.25–1.21(m,1H),1.17–1.12(m,1H),0.98(s,9H)ppm.

[0144] 13 C NMR (150MHz, CDCl3) δ166.5,150.4,139.5,135.6,134.8,134.7,130.8,128.7,127.7, 120.9,120.8,79.9,55.5,26.4,21.52,21.45,19.4,16.8,14.9ppm.HRMS(ESI+)Calcd for C 23 H 30 NOS2Si[M+H] + :428.1538,found:428.1523. Example 13: Synthesis of Chiral Silane I-3i

[0145] According to the steps of Example 12, the starting material 2-mercaptobenzothiazole compound 2a was replaced by 2c. The synthesis route is as follows:

[0146]

[0147] The product I-3i was a colorless oil (90 mg, 91% yield, 84% ee).

[0148] The characterization data are as follows:

[0149] HPLC analysis of the product:Daicel IC column; 10% i-PrOHin n-hexane; 1.0mL / min; λ = 230nm, retention times: 11.2min (major), 14.3min (minor).

[0150] 1 H NMR (600MHz, CDCl3) δ7.97(s,1H),7.59(d,J=6.0Hz,1H),7.47(d,J=12.0Hz,2H),7.43–7.42(m,1H),7.24(d,J=12.0Hz,2H),4.23–4. 19(m,1H),3.87–3.82(m,1H),2.39(s,3H),1.84–1.80(m,1H),1.73–1.70(m,1H),1.24–1.14(m,2H),0.98(s,9H)ppm.Note:theproton of OH is not displayed.

[0151] 13 C NMR (150MHz, CDCl3) δ170.2,153.4,139.6,134.7,134.1,130.6,128.8,127.7,124.2,122.0,119.9,79.7,55.7,26.3,21.5,19.3,16.8,14.9ppm.

[0152] HRMS(ESI+)Calcd for C 22 H 27 BrNOS2Si[M+H] + :492.0487,found:492.0474. Example 14: Synthesis of Chiral Silane I-3j

[0153] According to the steps of Example 12, the starting material 2-mercaptobenzothiazole compound 2a was replaced by 2d. The synthesis route is as follows:

[0154]

[0155] The product I-3j was a colorless oil (96 mg, 97% yield, 72% ee).

[0156] The characterization data are as follows:

[0157] HPLC analysis of the product:Daicel IC column; 10% i-PrOHin n-hexane; 1.0mL / min; λ = 230nm, retention times: 7.6min (major), 9.4min (minor).

[0158] 1 H NMR (600MHz, CDCl3) δ8.09–8.07(m,1H),7.87–7.83(m,1H),7.58–7.47(m,3H),7.30–7.24(m,2H),5.03(br,1 H),4.29–4.22(m,1H),3.95–3.87(m,1H),2.39(s,3H),1.86–1.73(m,2H),1.26–1.19(m,2H),0.98(s,9H)ppm. 19 F NMR (565MHz, CDCl3) δ-61.8ppm.

[0159] HRMS(ESI+)Calcd for C 23 H 27 F3NOS2Si[M+H] + :482.1255,found:482.1245.

Claims

1. A chiral silacyclopentane containing a silicon stereocenter, characterized in that: The structure of the chiral silacyclopentane containing a silicon stereocenter is shown in Formula I: Where R 1 Selected from: Any of the following; R 2 Selected from: Any of methyl and tert-butyl; R 3 Selected from: any one of H, Me, F, Br, Cl, tBu.

2. The method for preparing chiral silacyclopentane according to claim 1, characterized in that: The steps include: Chirality Under the action of an acid catalyst, a prochiral 3-silacyclopentene epoxy compound and a 2-mercaptobenzothiazole compound undergo a desymmetric reaction in an organic solvent to generate product I. The structural formula of the prochiral 3-silacyclopentene epoxy compound is The structure of the 2-mercaptobenzothiazole compound is:

3. The preparation method according to claim 2, characterized in that: The prochiral 3-silacyclopentene epoxy compound is 4. The preparation method according to claim 2, characterized in that: The 2-mercaptobenzothiazole compound is 5. The preparation method according to claim 2, characterized in that: The organic solvent is selected from toluene, benzene, xylene, trifluorotoluene or chlorobenzene.

6. The preparation method according to claim 2, characterized in that: The chirality The acid catalyst is selected from the group consisting of Formula A, B or C or their corresponding enantiomers: Wherein R is independently selected from anthracenyl, 3,5-diphenylphenyl, and 4-tert-butylphenyl.

7. The preparation method according to claim 2, characterized in that: The chirality The acid catalyst is a catalyst having the following formula CPA-1 or its enantiomer:

8. The preparation method according to claim 2, characterized in that: The preparation method comprises the following steps: cooling a system to which a prochiral 3-silacyclopentene epoxy compound, 2-mercaptobenzothiazole and an organic solvent are added to a temperature between -30°C and 0°C; maintaining the temperature and continuously stirring, adding a chiral Acid catalyst, then continue to maintain temperature and stir until the reaction is complete.

9. The preparation method according to claim 8, characterized in that: The molar ratio of the prochiral 3-silacyclopentene epoxy compound to 2-mercaptobenzothiazole is 1:1.0; the prochiral silacyclopentene oxide and the chiral The molar ratio of the acid catalyst is 1000:

1.

10. The preparation method according to claim 4, characterized in that: The 2-mercaptobenzothiazole is synthesized by the following steps: (1) Salicylic acid and diphenylphosphoryl azide (DPPA) undergo Curtius rearrangement reaction in an organic solvent, and the intermediate is hydrolyzed to obtain compound 1: (2) Compound 1 is reacted with an amino protecting agent, di-tert-butyl dicarbonate, to protect the amino group of Compound 1, to obtain Compound 2: (3) Compound 2 reacts with a trifluoromethanesulfonylating agent to convert the hydroxyl group in Compound 2 into trifluoromethanesulfonate. The obtained crude product is directly subjected to amino deprotection reaction with a reagent for deamino protecting group to obtain Compound 3: (4) Compound 3 reacts with ethyl xanthate to obtain 2-mercaptobenzothiazole.

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