Study Onasymmetric Syntheses Of Opticallyactive α-(2-methyl-3-furylthio) Ketones

The preparation of optically activeα-(2-methyl-3-furylthio) ketones was investigated by Shi's asymmetric epoxidation in this thesis.Two different synthetic routes of racemicα-(2-methyl-3-furylthio) ketones were studied first. In the first method,α-(2-methyl-3-furylthio) ketones were synthesized by four-step reactions, the Grignard reaction, the Swern oxidation,α-bromination and SN2 nucleophilic substitution starting from bromoalkanes. Bromoalkanes reacted with ethyl formate by the Grignard reaction to give alcohols in about 85% yield; the alcohols obtained were oxidized by the Swern oxidation to produce the corresponding ketones in about 75% yield;α-bromoketones were prepared by the reactions of ketones with bromine in about 70% yield;α-bromoketones reacted with 2-methyl-3-furyl thiol in the presence of K₂CO₃ to giveα-(2-methyl-3-furylthio) ketones in about 65% yield. The final products were characterized by ¹HNMR,¹³CNMR and MS. The overall yield was about 30%. Compared with the method of reactingα-chloro ketones with 2-methyl-3-mercapto furan catalyzed by sodium methoxide in literature, this route gave the products in higher yields with advantage of convenient operation.In the second method, the products were obtained through enolization, oxidation and nucleophilic substitution starting from ketones. The silyl enol ethers were formed by the reactions of ketones with chlorotrimethyl silane catalyzed by base, 4-(3-heptenyl) trimethylsilyl ether and 5-(4-nonenyl) trimethylsilyl ether in over 80% yields and 2, 6-dimethyl-4-(3-heptenyl) trimethyl silyl ether in about 70% yield. The oxidation of silyl enol ethers by MCPBA gaveα-hydroxy ketones in >85% yields.α-Hydroxy ketones reacted with MsCl to give msylates in >90% yields. The mesylates reacted with 2-methyl-3-mercapto furan catalyzed by base to giveα-(2-methyl-3-furylthio) ketones in 82-85% yields. Compared with the method in literature, no polysubstitution occurred from silyl enol ethers toα-hydroxy ketones, and the mesylates are more reactive thanα-haloketones since mesyl group is a better leaving group. This method is unknown so far in literature and has some advantages of convenient operation, high yield and less by-products.The ketones were transformed to silyl enol ethers and the optically activeα-hydroxy ketones werer obtained by the following Shi's asymmetric epoxidation. The effects of substitution groups on silane, the amount of catalyst and reaction temperature on the Shi's asymmetric epoxidation were studied. The amount of catalyst and reaction temperature made slight effects on chemical yields and enantilselectivity, while the substitution groups on double bond and silane played the key role in the Shi's asymmetric epoxidation. Big bulky groups favored high chemical yield and ee value. The highest yield of 3-hydroxy-4-heptanone was about 75% with 61% ee, 4-hydroxy-5-nonanone in about 80% yield with about 50% ee, 2, 6-dimethyl-3-hydroxy-4-heptanone in about 80% yield with about 84% ee. The absolute configuration of the products was confirmed to be R compared with the product of the Sharpless AD according to literature. The obtained optically activeα-hydroxy ketones were transformed to mesylates then followed by a SN2 nucleophilic substitution to form the optically active final products,3-(2-methyl-3-furylthio)-4-heptanone, 4-(2-methyl-3-furylthio)-5-nonanone and 2, 6-dimethyl-3- (2-methyl-3-furylthio)-4-heptanone. The ee values were 55.8%,44.6%,77.6% respectively. The ee values of the final products were very close to those ofα-hydroxy ketones, which indicated that no racemization occurred in the substitution.