Method for synthesizing optically active organosilicon compounds by asymmetric conjugate addition

Abstract

The invention discloses a method for synthesizing optically active organosilicon compounds by asymmetric conjugate addition, and belongs to the field of organic chemistry. With β-silyl α,β-unsaturated ketone 1 and organic boronic acid 2 as raw materials, an optically active organosilicon compound 3 is obtained by asymmetric conjugate addition reaction in an organic solvent in the presence of a chiral binaphthol or tetrabenzocyclooctatetraene catalyst and a molecular sieve. The reaction raw materials of the method are easy to obtain, no metal catalyst is required, the catalytic efficiency is high, the reaction conditions are mild, and the product can reach up to 98%ee.

Description

Technical Field

[0001] The invention belongs to the technical field of asymmetric synthesis in organic chemistry, and specifically relates to a method for synthesizing optically active organosilicon compounds through asymmetric conjugated addition. Background Art

[0002] Organosilicon compounds have a very important position in the field of organic chemistry due to their unique properties and wide range of uses. In recent years, pharmacologists have become increasingly interested in the biological properties of organosilicon compounds. Silicon replaces carbon, providing an innovative approach to drug discovery. Since silicon has no inherent toxicity, the introduction of silicon provides a broader space for drug design.

[0003] Organosilicon compounds are used in various fields, and the synthesis, transformation and performance research of chiral organosilicon compounds are also receiving more and more attention. One of the main methods to obtain such compounds is to convert potentially chiral silicon-containing substrates into chiral organosilicon products using asymmetric catalysis. The enantioselective conjugate addition of nucleophiles to β-silyl α, β-unsaturated ketones can be used to simply construct optically active organosilicon compounds. Great progress has been made in the asymmetric conjugate addition reaction of organic boronic acids and their derivatives with β-silyl α,β-unsaturated ketones catalyzed by transition metals Rh and Cu (Org. Lett. 2005, 21, 4757–4759; Org. Lett. 2007, 22, 4643–4645; Org. Lett. 2007, 16, 3187–3190; Chem. Eur. J. 2014, 20, 16764–16772). In recent years, the asymmetric conjugate addition reaction of organic boronic acids and α,β-unsaturated carbonyl compounds catalyzed by organic small molecules has become an important synthetic method for constructing CC bonds (Molecules 2018, 23, 2317–2353). This method has many advantages, such as low catalyst toxicity, easy preparation, and good stability; the organic boron compounds (boronic acids, organic boric esters, and organic boric acid salts) used are low in toxicity, cheap and readily available, and have good functional group tolerance; the reaction operation is simple and there is no metal residue after the reaction, which plays an important role in modern organic synthesis.

[0004] Therefore, it is very necessary to develop a catalytic system that does not require transition metal participation, has good reaction activity, and is simple to operate, so as to realize the asymmetric conjugate addition reaction of organic boronic acid and β-silyl α, β-unsaturated ketone and obtain a series of optically active organic silicon compounds. Summary of the invention

[0005] In order to overcome the above technical defects, the present invention provides a method for synthesizing optically active organosilicon compounds by asymmetric conjugate addition. The method uses organic boronic acid and β-silyl α, β-unsaturated ketone as raw materials, chiral binaphthol compounds or tetrabenzocyclooctatetraene compounds as catalysts, and molecular sieves as additives to undergo an asymmetric conjugate addition reaction to synthesize optically active organosilicon compounds in a one-step process with high yield and high enantioselectivity.

[0006] The method for synthesizing optically active organosilicon compounds by asymmetric conjugate addition of the present invention comprises the following steps: using β-silyl α,β-unsaturated ketone 1 and organic boronic acid 2 as raw materials, reacting in an organic solvent in the presence of a chiral binaphthol or chiral tetrabenzocyclooctatetraene catalyst and a molecular sieve to obtain an optically active organosilicon compound 3. The reaction equation is as follows:

[0007]

[0008] Wherein: SiR3 is selected from trimethylsilicon, dimethylphenylsilicon or methyldiphenylsilicon; R 1 is selected from substituted phenyl, naphthyl, furanyl, thienyl, C1-C6 alkyl or cyclohexyl, wherein the substituent in the substituted phenyl is hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen, trifluoromethyl, C1-C4 alkoxycarbonyl or nitro; R 2 Selected from substituted styryl, β-naphthylene, phenylpropane, p-methoxyphenyl, wherein the substituent in the substituted benzene is hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen, trifluoromethyl, C1-C4 alkoxycarbonyl or nitro.

[0009] Furthermore, in the above technical solution, R 1 is substituted phenyl, 3-furyl, 2-furyl, 1-naphthyl, 2-naphthyl, phenethyl or cyclohexyl; R 2 It is styryl, p-methylstyryl, m-methylstyryl, o-methylstyryl, p-methoxystyryl, p-fluorostyryl, m-fluorostyryl, p-chlorostyryl, p-bromostyryl, p-trifluoromethylstyryl, 2-naphthylstyryl, 2-benzofuranyl or p-methoxyphenyl.

[0010] Further, in the above technical solution, the chiral binaphthol catalyst is R=H, F, Cl, Br, I, Ph, 3,5-Me2C6H4, 3,5-(MeO)2C6H4, 3,5-(CF3)2C6H4; under the preferred conditions, the chiral binaphthol catalysts are the following three:

[0011]

[0012] Furthermore, in the above technical solution, the chiral tetrabenzocyclooctatetraenol catalyst is R=H, F, Cl, Br, I, Ph, 3,5-Me2C6H4, 3,5-(MeO)2C6H4, 3,5-(CF3)2C6H4; under the preferred conditions, the chiral tetrabenzocyclooctatetraenol catalyst is the following two:

[0013]

[0014] Furthermore, in the above technical solution, the molar ratio of the β-silyl α,β-unsaturated ketone 1, the organic boronic acid 2 and the catalyst is 1:2-4:0.05-0.20.

[0015] Furthermore, in the above technical solution, the organic solvent is selected from toluene, dichloromethane, tetrahydrofuran, trifluorotoluene, o-xylene, m-xylene, chlorobenzene, 1,2-dichloroethane, ethyl ether, methyl tert-butyl ether, acetonitrile or 1,4-dioxane.

[0016] Furthermore, in the above technical solution, the reaction temperature is 0 to 40°C, preferably 25°C.

[0017] Further, in the above technical solution, the molecular screening or Molecular sieve.

[0018] Furthermore, in the above technical solution, the entire reaction process is carried out under nitrogen or argon, preferably nitrogen.

[0019] Beneficial effects of the invention:

[0020] The reaction raw materials of the invention are easily available, the reaction conditions are mild, the post-treatment is simple, no metal catalyst is required, the chiral binaphthol or chiral tetrabenzocyclooctatetraene catalyst can be recycled and reused, and the product yield and enantioselectivity are good to excellent. DETAILED DESCRIPTION

[0021] Example 1 Condition Optimization Experiment

[0022]

[0023]

[0024]

[0025] a β-Silyl α,β-unsaturated ketone 1a (0.1 mmol), trans-2-phenylvinylboronic acid 2a (0.2 mmol), catalyst (0.01 mmol, 10 mol%), Molecular sieves (100 mg), 1.0 mL anhydrous solvent, nitrogen atmosphere; b Isolated yield; c ee was analyzed by HPLC chiral column; d No molecular sieve; e Molecular sieves (100 mg); f Molecular sieves (100 mg); g 0℃; h 40℃; i trans-2-phenylvinylboronic acid 2a (0.15 mmol); j Cat 5 (0.005 mmol, 5 mol%); k (S)-3,3'-(CF3)2C6H3-BINOL (0.01mmol, 10mol%).

[0026] During the reaction condition screening process, the effects of different chiral catalysts on the reaction were investigated (labels 1-11), and Cat 2, 3, 5 and Cat 9, 10 were determined to be the best catalysts. Then the effects of different solvents on the reaction were investigated (labels 11-17), and toluene was finally selected as the solvent. At the same time, the effects of molecular sieves, temperature, catalyst dosage and raw material ratio on the reaction were investigated (labels 18-24), and the reaction temperature was finally selected to be 25°C and the catalyst dosage was 10 mol%. The typical operation of the reaction conditions is as follows (taking label 5 as an example):

[0027] Under nitrogen protection, 100 mg of Molecular sieves, catalyst Cat 5 (7.1 mg, 0.01 mmol), β-silyl α, β-unsaturated ketone 1a (20.4 mg, 0.1 mmol) and organic boronic acid 2a (29.6 mg, 0.2 mmol, evacuated 3 times, then added toluene (1.0 mL), stirred at 25 ° C for 48 h. TLC showed that compound 1a disappeared. After the solvent was removed under reduced pressure, rapid silica gel column chromatography (ether / petroleum ether 1 / 40-1 / 50) was used for separation and purification to obtain 27.8 mg of colorless solid 3aa, with a yield of 90%. mp 55-56 ° C; HPLC (Daicel Chiralcel OD-H, n-hexane / isopropanol = 95:5, flow rate 1.0 mL / min, λ = 254 nm) t R (major)=4.5min,t R (minor)=5.3min,99.1:0.9er,98%ee; [α] D 21 = +25.0 (c 1.0, CHCl3); 1H NMR (400MHz, CDCl3) δ7.95-7.92(m,2H),7.57-7.53(m,1H),7.47-7.44(m,2H),7.26-7.21(m,4H),7.15-7.11(m,1 H),6.22-6.12(m,2H),3.19(dd,1H,J=16.4,9.6Hz),3.12(dd,1H,J=16.4,4.8Hz),2.48-2.43(m,1H),0.09(s,9H); 13 C{1H}NMR(100MHz, CDCl3)δ199.8,138.3,137.4,133.0,131.4,128.7,128.5,128.2,128.0,126.6,125.9,38.3,29.7,-2.8; HRMS(ESI)m / z:[M+Na] + Calcd for C 20 H 24 SiONa 331.1489; Found 331.1488.

[0028] Under the same operating conditions, the reaction was further treated with Mg(O t Bu)2 (0.01mmol, 10mol%), to give 24.3mg colorless solid 3aa, yield 79%, 97%ee;

[0029] Example 2

[0030]

[0031] Under nitrogen protection, 100 mg of Molecular sieve, catalyst Cat 5 (7.1 mg, 0.01 mmol), β-silyl α, β-unsaturated ketone 1b (21.8 mg, 0.1 mmol) and organic boronic acid 2a (29.6 mg, 0.2 mmol, 2.0 eq), evacuate 3 times, add toluene (1.0 mL), and stir at 25 ° C for 48 h. TLC shows that compound 1b disappears. After removing the solvent under reduced pressure, rapid silica gel column chromatography (ether / petroleum ether 1 / 40-1 / 50) is used for separation and purification to obtain 30.0 mg of colorless solid 3ba, with a yield of 93%. mp 43–45 ° C; HPLC (Daicel Chiralcel OD-H, n-hexane / isopropanol = 95:5, flow rate 1.0 mL / min, λ = 254 nm) t R (major)=4.4min,t R (minor)=6.0min,98.5:1.5er,97%ee;[α]D 22 = +22.8 (c 1.0, CHCl3); 1 H NMR (600MHz, CDCl3) δ7.84 (d, 2H, J = 8.4Hz), 7.26-7.22 (m, 6H), 7.15-7.12 (m, 1H), 6.20-6.14 (m, 2H), 3 .15(dd,1H,J=16.2,9.6Hz),3.09(dd,1H,J=16.2,4.8Hz),2.46-2.43(m,1H),2.41(s,3H),0.08(s,9H); 13 C{1H}NMR(150MHz,CDCl3)δ199.4,143.7,138.3,134.8,131.5,129.4,128.5 ,128.4,127.8,126.5,125.9,38.2,29.7,21.8,-2.8; HRMS(ESI)m / z:[M+Na] + Calcd for C 21 H 26 SiONa 345.1645; Found 345.1644.

[0032] Example 3

[0033]

[0034] Under nitrogen protection, 100 mg of Molecular sieves, catalyst Cat 5 (7.1 mg, 0.01 mmol), β-silyl α, β-unsaturated ketone 1e (23.4 mg, 0.1 mmol) and organic boronic acid 2a (29.6 mg, 0.2 mmol, evacuated 3 times, then added toluene (1.0 mL), stirred at 25 ° C for 48 h. TLC showed that 1e disappeared. After the solvent was removed under reduced pressure, rapid silica gel column chromatography (ether / petroleum ether 1 / 20-1 / 50) was used for separation and purification to obtain 31.8 mg of light yellow liquid 3ea, with a yield of 94%. HPLC (Daicel Chiralcel OD-H, n-hexane / isopropanol = 95:5, flow rate 1.0 mL / min, λ = 254 nm) t R (major) = 6.4min,t R (minor)=14.0min,98.5:1.5er,97%ee;[α] D 22 = +24.9 (c 1.0, CHCl3); 1H NMR (600MHz, CDCl3) δ7.94-7.92(m,2H),7.28-7.22(m,4H),7.15-7.12(m,1H),6.94-6.92(m,2H),6.21-6.14( m,2H),3.86(m,3H)3.13(dd,1H,J=16.2,9.6Hz),3.06(dd,1H,J=16.2,4.2Hz),2.46-2.43(m,1H),0.08(s,9H); 13 C{ 1 H}NMR(150MHz, CDCl3)δ198.3,163.5,138.3,131.5,130.5,130.4,128.5,127.8,126.5,125.9,113.9,55.6,37.9,29.8,-2.8; HRMS(ESI)m / z:[M+Na] + Calcd for C 21 H 26 SiO2Na 361.1594; Found 361.1594.

[0035] Example 4

[0036]

[0037] Under nitrogen protection, 100 mg of Molecular sieve, catalyst Cat 5 (7.1 mg, 0.01 mmol), β-silyl α, β-unsaturated ketone 1f (22.2 mg, 0.1 mmol) and organic boronic acid 2a (29.6 mg, 0.2 mmol), evacuate 3 times, add toluene (1.0 mL), and stir at 25 ° C for 48 h. TLC shows that 1f disappears. After removing the solvent under reduced pressure, rapid silica gel column chromatography (ether / petroleum ether 1 / 30-1 / 50) is used for separation and purification to obtain 31.7 mg of light yellow liquid 3fa, with a yield of 97%. HPLC (Daicel Chiralcel AD-H, n-hexane / isopropanol = 95:5, flow rate 1.0 mL / min, λ = 254 nm) t R (major) = 4.3min, t R (minor)=5.2min,98.7:1.3er,97%ee;[α] D 22 = +20.7 (c 1.0, CHCl3); 1H NMR (600MHz, CDCl3) δ7.98-7.95(m,2H),7.26-7.23(m,4H),7.16-7.11(m,3H),6.20-6.12(m,2 H),3.17(dd,1H,J=16.2,9.6Hz),3.09(dd,1H,J=16.2,4.2Hz),2.47-2.43(m,1H),0.09(s,9H); 13 C{ 1 H}NMR(150MHz, CDCl3)δ198.2,165.8(d,J=253.5Hz),138.1,133.7(d,J=3.0Hz),131.1, 130.8(d,J=9.0Hz),128.5,128.0,126.6,125.9,115.8(d,J=21.0Hz),38.2,29.7,-2.8; 19 F{ 1 H}NMR(564MHz, CDCl3)δ–105.7; HRMS(ESI)m / z:[M+Na] + Calcd for C 20 H 23 SiOFNa 349.1394; Found349.1393.

[0038] Example 5

[0039]

[0040] Under nitrogen protection, 100 mg of Molecular sieve, catalyst Cat 5 (7.1 mg, 0.01 mmol), β-silyl α, β-unsaturated ketone 1g (23.9 mg, 0.1 mmol) and organic boronic acid 2a (29.6 mg, 0.2 mmol), evacuate 3 times, add toluene (1.0 mL), and stir at 25°C for 48 h. TLC shows that 1g disappears. After removing the solvent under reduced pressure, rapid silica gel column chromatography (ether / petroleum ether 1 / 40-1 / 50) is used for separation and purification to obtain 33.9 mg of colorless liquid 3ga, with a yield of 99%. mp 50-51°C; HPLC (Daicel Chiralcel AD-H, n-hexane / isopropanol = 95:5, flow rate 1.0 mL / min, λ = 254 nm) t R (major)=5.0min,t R (minor)=6.2min,98.5:1.5er,97%ee;[α] D 22= +23.3 (c 1.0, CHCl3); 1 H NMR (600MHz, CDCl3) δ7.87 (d, 2H, J = 8.4Hz), 7.43 (d, 2H, J = 8.4Hz), 7.25-7.23 (m, 4H), 7.15-7.13 (m, 1H), 6. 19-6.11(m,2H),3.14(dd,1H,J=16.2,9.6Hz),3.08(dd,1H,J=16.2,4.2Hz),2.44-2.40(m,1H),0.09(s,9H); 13 C{ 1 H}NMR(150MHz, CDCl3)δ198.6,139.4,138.1,135.6,134.0,129.7,129.0,128.5,128.1,126.7,125.9,38.3,29.7,-2.8; HRMS(ESI)m / z:[M+Na] + Calcd for C 20 H 23 SiOClNa 365.1099; Found 365.1083.

[0041] Example 6

[0042]

[0043] Under nitrogen protection, 100 mg of Molecular sieve, catalyst Cat 5 (7.1 mg, 0.01 mmol), β-silyl α, β-unsaturated ketone 1i (27.3 mg, 0.1 mmol) and organic boronic acid 2a (29.6 mg, 0.2 mmol), evacuate 3 times, add toluene (1.0 mL), and stir at 40 ° C for 48 h. TLC shows that 1i almost disappears. After removing the solvent under reduced pressure, rapid silica gel column chromatography (ether / petroleum ether 1 / 40-1 / 60) is used for separation and purification to obtain 34.1 mg of light yellow liquid 3ia, with a yield of 90%. HPLC (Daicel Chiralcel AD-H, n-hexane / isopropanol = 95:5, flow rate 1.0 mL / min, λ = 254 nm) t R (major) = 4.3min, t R (minor)=4.6min,97.0:3.0er,94%ee;[α] D 16 = +11.6 (c 1.0, CHCl3); 1H NMR (600MHz, CDCl3) δ8.00(d,1H,J=1.8Hz),7.75(dd,1H,J=10.8,2.4Hz),7.54(d,1H,J=8.4Hz),7.26-7.25(m,4H),7.17-7.14(m,1H),6.19 (d,1H,J=15.6Hz),6.12(dd,1H,J=16.2,9.0Hz),3.13(dd,1H,J=16.2,9.0Hz),3.06(dd,1H,J=16.2,4.2Hz),2.42-2.39(m,1H),0.09(s,9H); 13 C{ 1 H}NMR(150MHz,CDCl3)δ197.5,138.0,137.6,136.8,133.4,130.9,130.8,13 0.3,128.6,128.3,127.3,126.8,125.9,38.4,29.6,-2.8; HRMS(EI)m / z:[M] + Calcd for C 20 H 22 OCl2Si 376.0811; Found 376.0818.

[0044] Example 7

[0045]

[0046] Under nitrogen protection, 100 mg of Molecular sieve, catalyst Cat 5 (7.1 mg, 0.01 mmol), β-silyl α, β-unsaturated ketone 1k (25.4 mg, 0.1 mmol) and organic boronic acid 2a (29.6 mg, 0.2 mmol, 2.0 eq), evacuate 3 times, add toluene (1.0 mL), stir at 40 ° C for 48 h. TLC shows that 1k disappears, and the solvent is removed under reduced pressure and then separated and purified by rapid silica gel column chromatography (ether / petroleum ether 1 / 40-1 / 50) to obtain 32.3 mg of colorless solid 3ka, with a yield of 90%. mp95-97 ° C; HPLC (Daicel Chiralcel AD-H, n-hexane / isopropanol = 95:5, flow rate 1.0 mL / min, λ = 254 nm) t R (major)=7.2min,t R (minor)=8.1min,98.6:1.4er,97%ee;[α] D 22 = +14.3 (c1.0, CHCl3);1 H NMR (400MHz, CDCl3) δ8.46(s,1H),8.02-7.95(m,2H),7.90-7.87(m,2H),7.62-7.54(m,2H),7.27-7. 21(m,4H),7.15-7.11(m,1H),6.25-6.16(m,2H),3.35-3.23(m,2H),2.55-2.49(m,1H),0.12(s,9H); 13 C{ 1 H}NMR (100MHz, CDCl3) δ199.8,138.3,135.7,134.7,132.7,131.4,129.69,129.67,128.6,128. 53,128.49,128.1,127.9,126.9,126.6,125.9,124.3,38.5,29.9,-2.7; HRMS(ESI)m / z:[M+Na] + Calcd for C 24 H 26 SiONa 381.1645; Found 381.1632.

[0047] Example 8

[0048]

[0049] Under nitrogen protection, 100 mg of Molecular sieve, catalyst Cat 5 (7.1 mg, 0.01 mmol), β-silyl α, β-unsaturated ketone 1n (19.4 mg, 0.1 mmol) and organic boronic acid 2a (29.6 mg, 0.2 mmol, 3.0 eq), evacuate 3 times, add toluene (1.0 mL), stir at 40 ° C for 48 h. TLC shows that 1n disappears, and the solvent is removed under reduced pressure and then separated and purified by rapid silica gel column chromatography (ether / petroleum ether 1 / 40-1 / 50) to obtain 32.8 mg of colorless solid 3na, with a yield of 91%. mp66-67 ° C; HPLC (Daicel Chiralcel AS-H, n-hexane / isopropanol = 95:5, flow rate 1.0 mL / min, λ = 254 nm) t R (major)=8.2min,t R (minor)=10.3min,98.0:2.0er,96%ee;[α] D 22 = +7.1 (c1.0, CHCl3); 1H NMR (600MHz, CDCl3) δ7.54-7.52(m,3H),7.39-7.36(m,3H),7.25-7.20(m, 4H),7.15-7.13(m,1H),7.05(d,1H,J=3.6Hz),6.47-6.46(m,1H),6.19(d,1 H, J=16.2Hz), 6.10 (dd, 1H, J=15.6, 8.4Hz), 3.02 (dd, 1H, J=15.6, 10.8Hz), 2.86(dd,1H,J=16.2,3.6Hz),2.70-2.66(m,1H),0.38(s,3H),0.37(s,3H); 13 C{ 1 H}NMR (150MHz, CDCl3) δ189.0,153.0,146.2,138.1,136.8,134.2,130.5,129.5,128.6, 128.5,128.0,126.6,125.9,116.9,112.3,38.1,29.3,-4.1,-4.9; HRMS(ESI)m / z:[M+Na] + Calcd for C 23 H 24 SiO2Na383.1438; Found 383.1436.

[0050] Example 9

[0051] Under nitrogen protection, 100 mg of Molecular sieves, catalyst Cat 5 (7.1 mg, 0.01 mmol), β-silyl α, β-unsaturated ketone 1p (29.4 mg, 0.1 mmol) and organic boronic acid 2a (29.6 mg, 0.2 mmol, 2.0 eq), evacuated 3 times, and then added dry toluene (1.0 mL), stirred at 40 ° C for 48 h. TLC showed that 1p remained, and the solvent was removed under reduced pressure and then separated and purified by rapid silica gel column chromatography (ether / petroleum ether 1 / 40-1 / 50) to obtain 18.3 mg of light yellow liquid 3pa, with a yield of 46%.

[0052]

[0053] HPLC (Daicel Chiralcel OD-H, n-hexane / isopropanol = 95:5, flow rate 1.0 mL / min, λ = 254 nm) R (major)=6.6min,t R(minor)=10.5min,98.4:1.6er,97%ee;[α] D 22 = +1.6 (c1.0, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.49-7.46(m,2H),7.39-7.33(m,3H),7.30-7.12(m,8H),7.10-7.08(m,2H),6.17(d,1H,J =16.0Hz),6.04(dd,1H,J=16.0,8.4Hz),2.81-2.77(m,2H),2.66-2.62(m,2H),2.55-2.40(m,3H),0.32(s,6H); 13 C{ 1 H}NMR (150MHz, CDCl3) δ209.5,141.3,138.0,136.7,134.2,130.7,129.5,128.59,128.55,128.5 2,128.4,128.0,126.8,126.1,125.9,44.4,42.8,29.7,29.1,-4.2,-5.0; HRMS(ESI)m / z:[M+Na] + Calcd for C 27 H 30 SiONa 421.1958; Found 421.1953.

[0054] Example 10

[0055]

[0056] Under nitrogen protection, 100 mg of Molecular sieve, catalyst Cat 5 (7.1 mg, 0.01 mmol), β-silyl α, β-unsaturated ketone 1q (27.2 mg, 0.1 mmol) and organic boronic acid 2a (29.6 mg, 0.2 mmol, 2.0 eq), evacuate 3 times, add toluene (1.0 mL), and stir at 60 ° C for 48 h. TLC shows that 1q remains. After removing the solvent under reduced pressure, rapid silica gel column chromatography (ether / petroleum ether 1 / 40-1 / 50) is used for separation and purification to obtain 21.8 mg of light yellow liquid 3qa, with a yield of 58%. HPLC (Daicel Chiralcel AS-H, n-hexane / isopropanol = 95:5, flow rate 1.0 mL / min, λ = 254 nm) t R (major)=4.0min,t R(minor)=4.6min,98.8:1.2er,98%ee;[α] D 22 = +5.2 (c 1.0, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.51-7.48(m,2H),7.39-7.34(m,3H),7.28-7.22(m,4H),7.17-7.14(m,1H),6.17(d,1H,J=15.6Hz),6.06 (dd,1H,J=16.0,8.4Hz),2.67-2.45(m,3H),2.29-2.24(m,1H),1.73-1.56(m,6H),1.26-1.21(m,4H),0.33(s,3H),0.32(s,3H); 13 C{ 1 H}NMR(100MHz,CDCl3)δ213.2,138.2,137.0,134.2,131.2,129.4,128.6,128.2,128.0,1 26.6,125.9,50.8,40.5,28.6,28.4,26.0,25.9,25.7,-4.1,-4.8; HRMS(ESI)m / z:[M+Na] + Calcd for C 25 H 32 SiONa 399.2115; Found 399.2113.

[0057] Embodiment 11

[0058] According to the reaction conditions of Example 10, (E)-1-phenyl-3-(trimethylsilyl)prop-2-en-1-one 1a and different organic boronic acid compounds 2 were used, and the reaction results were as follows:

[0059]

[0060] b React at 40℃ for 48h. c React at 145℃ for 48h.

[0061] Example 12

[0062]

[0063] Under nitrogen protection, 100 mg of Molecular sieves, catalyst Cat 5 (7.1 mg, 0.01 mmol), (E)-1-phenyl-3-(trimethylsilyl)prop-2-en-1-one 1a (20.4 mg, 0.1 mmol) and organic boronic acid 2b (32.4 mg, 0.2 mmol), evacuate the air three times, add toluene (1.0 mL), and stir at 25°C for 48 h. TLC shows that 1a disappears. After removing the solvent under reduced pressure, rapid silica gel column chromatography (ether / petroleum ether 1 / 40-1 / 50) is used for separation and purification to obtain 31.6 mg of colorless solid 3ab, with a yield of 98%. mp 79-81°C; HPLC (Daicel Chiralcel AS-H, n-hexane / isopropanol = 95:5, flow rate 1.0 mL / min, λ = 254 nm) t R (major)=4.2min,t R (minor)=4.9min,99.0:1.0er,98%ee;[α] D 23 = +26.2 (c 1.0, CHCl3); 1 H NMR (600MHz, CDCl3) δ7.94-7.92(m,2H),7.56-7.53(m,1H),7.45(t,2H,J=7.8Hz),7.15(d,2H,J=7.8Hz),7.05(d,2H,J=7.8Hz),6.16(d,1H,J=1 6.2Hz), 6.10 (dd, 1H, J = 16.2, 9.0Hz), 3.17 (dd, 1H, J = 16.2, 9.6Hz), 3.11 (dd, 1H, J = 16.2, 4.8Hz), 2.45-2.41 (m, 1H), 2.29 (s, 3H), 0.08 (s, 9H); 13 C{ 1 H}NMR(150MHz, CDCl3)δ200.0,137.4,136.3,135.4,133.0,130.2,129.2,128.7,128.2,127.8,125.8,38.4,29.6,21.2,-2.8; HRMS(ESI)m / z:[M+Na] + Calcd for C 21 H 26 SiONa 345.1645; Found 345.1645.

[0064] Example 13

[0065]

[0066] Under nitrogen protection, 100 mg of Molecular sieves, catalyst Cat 5 (7.1 mg, 0.01 mmol), (E)-1-phenyl-3-(trimethylsilyl)prop-2-en-1-one 1a (20.4 mg, 0.1 mmol) and organic boronic acid 2e (35.6 mg, 0.2 mmol), evacuate the air three times, add toluene (1.0 mL), and stir at 40°C for 48 h. TLC showed that 1a disappeared. After removing the solvent under reduced pressure, rapid silica gel column chromatography (ether / petroleum ether 1 / 40-1 / 50) was used for separation and purification to obtain 6.1 mg of light yellow liquid 3ae, with a yield of 18%. HPLC (Daicel Chiralcel AS-H, n-hexane / isopropanol = 95:5, flow rate 1.0 mL / min, λ = 254 nm) t R (major) = 6.1min, t R (minor)=7.5min,96.3:3.7er,93%ee;[α] D 19 = +11.4 (c0.25, CHCl3); 1 H NMR (600MHz, CDCl3) δ7.93 (d, 2H, J = 7.8Hz), 7.55 (t, 1H, J = 7.2Hz), 7.46 (t, 2H, J = 7.8Hz), 7.18 (d, 2H, J = 6.0Hz), 6.79 (d, 2H, J = 9.0Hz), 6.13 (d, 1H, J=15.6Hz),6.00(dd,1H,J=16.2,9.6Hz),3.78(s,3H),3.16(dd,1H,J=16.2,9.6Hz),3.11(dd,1H,J=16.2,4.2Hz),2.43-2.39(m,1H),0.08(s,9H); 13 C{ 1 H}NMR(150MHz, CDCl3)δ200.0,158.6,137.4,133.0,131.2,129.1,128.7,128.2,127.4,126.9,114.0,55.5,38.4,29.5,-2.8; HRMS(ESI)m / z:[M+Na] + Calcd for C 21 H 26 SiO2Na 361.1594; Found 361.1595.

[0067] Embodiment 14

[0068]

[0069] Under nitrogen protection, 100 mg of Molecular sieves, catalyst Cat 5 (7.1 mg, 0.01 mmol), (E)-1-phenyl-3-(trimethylsilyl)prop-2-en-1-one 1a (20.4 mg, 0.1 mmol) and organic boronic acid 2f (33.2 mg, 0.2 mmol), evacuate 3 times, add toluene (1.0 mL), and stir at 25 ° C for 48 h. TLC shows that 1a disappears. After removing the solvent under reduced pressure, rapid silica gel column chromatography (ether / petroleum ether 1 / 40-1 / 50) is used for separation and purification to obtain 30.4 mg of light yellow liquid 3af, with a yield of 93%. HPLC (Daicel Chiralcel AS-H, n-hexane / isopropanol = 95:5, flow rate 1.0 mL / min, λ = 254 nm) t R (major)=4.5min,t R (minor)=5.1min,98.2:1.8er,96%ee;[α] D 18 = +19.8 (c 1.0, CHCl3); 1 H NMR (600MHz, CDCl3) δ7.94-7.93(m,2H),7.57-7.54(m,1H),7.47-7.45(m,2H),7.21-7.18(m,2H),6.94-6.91(m,2H),6.15(d,1H,J= 16.2Hz), 6.06 (dd, 1H, J = 16.2, 9.0Hz), 3.17 (dd, 1H, J = 16.8, 9.6Hz), 3.12 (dd, 1H, J = 16.2, 4.2Hz), 2.45-2.41 (m, 1H), 0.09 (s, 9H); 13 C{ 1 H}NMR(150MHz, CDCl3)δ199.8,161.8(d,J=243.0Hz),137.3,134.4(d,J=4.5Hz),133.1,131.1 (d,J=1.5Hz),128.7,128.2,127.2(d,J=7.5Hz),126.8,115.3(d,J=21.0Hz),38.3,29.6,-2.8; 19 F{ 1 H}NMR(564MHz, CDCl3)δ–116.3; HRMS(ESI)m / z:[M+Na] + Calcd for C 20 H 23SiOFNa 349.1394; Found 349.1394.

[0070] Embodiment 15

[0071]

[0072] Under nitrogen protection, 100 mg of Molecular sieves, catalyst Cat 5 (7.1 mg, 0.01 mmol), (E)-1-phenyl-3-(trimethylsilyl)prop-2-en-1-one 1a (20.4 mg, 0.1 mmol) and organic boronic acid 2h (36.4 mg, 0.2 mmol), evacuate the air three times, add toluene (1.0 mL), and stir at 25°C for 48 h. TLC showed that 1a disappeared. After the solvent was removed under reduced pressure, rapid silica gel column chromatography (ether / petroleum ether 1 / 40-1 / 50) was used for separation and purification to obtain 33.3 mg of white solid 3ah, with a yield of 97%. mp 85-86°C; HPLC (Daicel Chiralcel AD-H, n-hexane / isopropanol = 95:5, flow rate 1.0 mL / min, λ = 254 nm) t R (major)=5.3min,t R (minor)=6.1min,98.6:1.4er,97%ee;[α] D 23 = +26.8 (c 1.0, CHCl3); 1 H NMR (600MHz, CDCl3) δ7.94-7.93(m,2H),7.55(t,1H,J=7.2Hz),7.46(t,2H,J=7.8Hz),7.20-7.15(m,4H),6. 16-6.11(m,2H),3.17(dd,1H,J=16.2,9.6Hz),3.12(dd,1H,J=16.8,4.8Hz),2.46-2.43(m,1H),0.09(s,9H); 13 C{ 1 H}NMR(150MHz, CDCl3)δ199.7,137.2,136.7,133.1,132.2,132.0,128.8,128.6,128.2,127.0,126.7,38.2,29.7,-2.8; HRMS(ESI)m / z:[M+Na] + Calcd for C 20 H 23 SiOClNa 365.1099; Found 365.1083.

[0073] Example 16

[0074]

[0075] Under nitrogen protection, 100 mg of Molecular sieves, catalyst Cat 5 (7.1 mg, 0.01 mmol), (E)-1-phenyl-3-(trimethylsilyl)prop-2-en-1-one 1a (20.4 mg, 0.1 mmol) and organic boronic acid 2i (45.4 mg, 0.2 mmol), evacuate the air three times, add toluene (1.0 mL), and stir at 25°C for 48 h. TLC shows that 1a disappears. After removing the solvent under reduced pressure, rapid silica gel column chromatography (ether / petroleum ether volume ratio 1 / 40-1 / 50) is used for separation and purification to obtain 32.5 mg of white solid 3ai, with a yield of 84%. mp 94-96°C; HPLC (Daicel Chiralcel AD-H, n-hexane / isopropanol = 95:5, flow rate 1.0 mL / min, λ = 254 nm) t R (major)=5.6min,t R (minor)=6.4min,98.5:1.5er,97%ee;[α] D 23 = +25.8 (c 1.0, CHCl3); 1 H NMR (600MHz, CDCl3) δ7.94 (d, 2H, J = 7.2Hz), 7.56 (t, 1H, J = 7.2Hz), 7.47 (t, 2H, J = 7.8Hz), 7.35 (d, 2H, J = 9.0Hz), 7.11 (d, 2H ,J=8.4Hz),6.18-6.10(m,2H),3.18(dd,1H,J=16.2,9.6Hz),3.12(dd,1H,J=16.8,4.8Hz),2.46-2.42(m,1H),0.09(s,9H); 13 C{ 1 H}NMR(150MHz, CDCl3)δ199.7,137.2,137.1,133.1,132.3,131.6,128.8,128.2,127.4,126.7,120.1,38.1,29.7,-2.8; HRMS(ESI)m / z:[M+Na] + Calcdfor C 20 H 23 SiOBrNa 409.0594; Found 409.0582.

[0076] Embodiment 17

[0077]

[0078] Under nitrogen protection, 100 mg of Molecular sieves, catalyst Cat 5 (7.1 mg, 0.01 mmol), (E)-1-phenyl-3-(trimethylsilyl)prop-2-en-1-one 1a (20.4 mg, 0.1 mmol) and organic boronic acid 2g (43.2 mg, 0.2 mmol), evacuate the air three times, add toluene (1.0 mL), and stir at 25°C for 48 h. TLC showed that 1a disappeared. After removing the solvent under reduced pressure, rapid silica gel column chromatography (ether / petroleum ether 1 / 40-1 / 50) was performed to separate and purify 29.4 mg of colorless solid 3aj, with a yield of 78%. mp 65-66°C; HPLC (Daicel Chiralcel AD-H, n-hexane / isopropanol = 95:5, flow rate 1.0 mL / min, λ = 254 nm) t R (major)=5.1min,t R (minor)=5.9min,97.6:2.4er,95%ee;[α] D 23 = +19.4 (c 1.0, CHCl3); 1 H NMR (600MHz, CDCl3) δ7.96-7.95(m,2H),7.58(t,1H,J=7.2Hz),7.50-7.47(m,4H),7.34(d,2H,J=7.8Hz),6.30(dd,1H,J=16.2 ,9.0Hz),6.23(d,1H,J=16.2Hz),3.22(dd,1H,J=16.2,9.6Hz),3.16(dd,1H,J=16.2,4.2Hz),2.53-2.49(m,1H),0.12(s,9H); 13 C{ 1 H}NMR(150MHz, CDCl3)δ199.6,141.6,137.2,134.5,133.2,128.8,128.4(q,J=33.0H z),128.2,126.6,125.9,125.5(q,J=3.0Hz),124.5(q,J=270.0Hz),38.1,29.9,-2.8; 19 F{ 1 H}NMR(564MHz, CDCl3)δ–62.3; HRMS(ESI)m / z:[M+Na] + Calcd for C 21H 23 Si OF3Na 399.1362; Found 399.1362.

[0079] Embodiment 18

[0080]

[0081] Under nitrogen protection, 100 mg of Molecular sieves, catalyst Cat 5 (7.1 mg, 0.01 mmol), (E)-1-phenyl-3-(trimethylsilyl)prop-2-en-1-one 1a (20.4 mg, 0.1 mmol) and organic boronic acid 2k (39.6 mg, 0.2 mmol), evacuate the air three times, add toluene (1.0 mL), and stir at 25°C for 48 h. TLC shows that 1a disappears. After removing the solvent under reduced pressure, rapid silica gel column chromatography (ether / petroleum ether 1 / 40-1 / 50) is used for separation and purification to obtain 28.3 mg of colorless solid 3ak, with a yield of 79%. mp 93-97°C; HPLC (Daicel Chiralpak IF, n-hexane / isopropanol = 95:5, flow rate 1.0 mL / min, λ = 254 nm) t R (major)=6.3min,t R (minor)=7.3min,98.9:1.1er,98%ee;[α] D 18 = +26.6 (c 1.0, CHCl3); 1 H NMR (600MHz, CDCl3) δ7.96-7.95(m,2H),7.74-7.70(m,3H),7.57-7.55(m,2H),7.50-7.45(m,3H),7.42-7.36(m,2H),6.36(d,1H,J= 16.2Hz), 6.29 (dd, 1H, J = 15.6, 8.4Hz), 3.23 (dd, 1H, J = 16.2, 10.2Hz), 3.16 (dd, 1H, J = 16.2, 4.2Hz), 2.53-2.49 (m, 1H), 0.12 (s, 9H); 13 C{ 1 H}NMR (150MHz, CDCl3) δ199.9,137.4,135.7,133.9,133.1,132.6,131.9,128.8,128.3,1 28.1,127.9,127.7,126.2,125.4,125.1,123.7,38.4,29.9,-2.7; HRMS(ESI)m / z:[M+Na] +Calcd for C 24 H 26 SiONa 381.1645; Found 381.1647.

[0082] Embodiment 19

[0083]

[0084] Under nitrogen protection, 100 mg of Molecular sieves, catalyst Cat 5 (7.1 mg, 0.01 mmol), (E)-1-phenyl-3-(trimethylsilyl)prop-2-en-1-one 1a (20.4 mg, 0.1 mmol) and p-methoxyphenylboronic acid 2l (30.4 mg, 0.2 mmol), evacuate the air three times, add dry toluene (1.0 mL), and stir at 145°C for 48 h. TLC showed that 1a disappeared. After removing the solvent under reduced pressure, rapid silica gel column chromatography (ether / petroleum ether 1 / 40-1 / 50) was used for separation and purification to obtain 5.6 mg of yellow liquid 3al, with a yield of 18%. HPLC (Daicel Chiralcel AS-H, n-hexane / isopropanol = 95:5, flow rate 1.0 mL / min, λ = 254 nm) t R (major)=5.4min,t R (minor)=6.3min,95.6:4.4er,91%ee;[α] D 19 = -2.4 (c 0.25, CHCl3); 1 H NMR (600MHz, CDCl3) δ7.90-7.89(m,2H),7.54-7.52(m,1H),7.44-7.42(m,2H),6.98-6.96(m,2H),6.77-6.75(m, 2H),3.75(s,3H),3.47(dd,1H,J=16.8,10.2Hz),3.25(dd,1H,J=16.8,4.8Hz),2.81-2.79(m,1H),-0.01(s,9H); 13 C{ 1 H}NMR(150MHz, CDCl3)δ199.7,157.0,137.4,135.2,132.9,128.7,128.4,128.2,113.8,55.3,39.4,30.5,-2.7; HRMS(ESI)m / z:[M+Na] + Calcd for C 19 H 24SiO2Na 335.1438; Found335.1437.

[0085] The above embodiments describe the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited by the above embodiments, and the above embodiments and descriptions are only for explaining the principles of the present invention. Without departing from the scope of the principles of the present invention, the present invention may have various changes and improvements, and these changes and improvements all fall within the scope of protection of the present invention.

Claims

1. A method for synthesizing an optically active organosilicon compound by asymmetric conjugated addition, characterized in that: The method comprises the following steps: using β-silyl α,β-unsaturated ketone 1 and organic boronic acid 2 as raw materials, reacting in an organic solvent in the presence of a chiral binaphthol catalyst and a molecular sieve to obtain an optically active organic silicon compound 3; the reaction equation is as follows: Wherein: SiR3 is selected from trimethylsilicon, dimethylphenylsilicon or methyldiphenylsilicon; R 1 is selected from substituted phenyl, naphthyl, furanyl, thienyl, C1-C6 alkyl or cyclohexyl, wherein the substituent in the substituted phenyl is hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen, trifluoromethyl, C1-C4 alkoxycarbonyl or nitro; R 2 is selected from substituted styryl, β-naphthylene, benzofuranyl, p-methoxyphenyl, wherein the substituent in the substituted styryl is hydrogen, C1-C4 alkyl, C1-C4 alkoxy, halogen, trifluoromethyl, C1-C4 alkoxycarbonyl or nitro; the chiral binaphthol catalyst is The organic solvent is selected from toluene, dichloromethane, trifluorotoluene, o-xylene, m-xylene or 1,2-dichloroethane.

2. The method for synthesizing optically active organosilicon compounds by asymmetric conjugated addition according to claim 1, characterized in that: The molar ratio of the β-silyl α,β-unsaturated ketone 1, the organic boronic acid 2 and the catalyst is 1:2-4:0.05-0.

20.

3. The method for synthesizing optically active organosilicon compounds by asymmetric conjugated addition according to claim 1, characterized in that: The reaction temperature is 0-40°C.

4. The method for synthesizing optically active organosilicon compounds by asymmetric conjugated addition according to claim 1, characterized in that: Molecular screening or Molecular sieve.

5. The method for synthesizing optically active organosilicon compounds by asymmetric conjugated addition according to any one of claims 1 to 4, characterized in that: The entire reaction process was carried out under nitrogen or argon.

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