Bis-guanidinium salts catalyzed enantioselective phase-transfer alkylations of cyclic ketones and silyl enol ethers

• Main Author: Chen, Wenchao
• Other Authors: Tan Choon Hong
• Format: Theses and Dissertations
• Language: English
• Published: 2016
• Subjects: DRNTU::Science
• Online Access: http://hdl.handle.net/10356/68853
• Institution: Nanyang Technological University

The aim of this project is to further develop the application of BSA and its analogues in asymmetric phase-transfer catalyzed alkylation reactions. In conclusion, we have developed the first highly enantioselective bis-guanidinium salt catalyzed phase-transfer alkylation reactions of cyclic ketones and silyl enol ethers by the using of BAS and its analogues. And we found that, for the alkylation reactions of cyclic ketones, the enantioselectivity can be improved a lot by tuning the structure of non-chiral BSA analogues, which opened a new way to achieve high enantioselectivity. In this catalysis system, the catalyst, fluorine source, BSA analogues, all the three parts are tunable to improve the enantionselectivity. Furthermore, as for the alkylation reactions of silyl enol ethers, we found that by the adding of catalytic amount of BSA, the yield was greatly improved with even better enantioselectivity, which provide a new strategy to solve the low yield problem of Mukaiyama type reactions. These results surely indicate the great potential of application of BAS and it’s analogues in asymmetric phase-transfer catalysis, which provides a new powerful strategy to active high pKa substrates and solve the low yield problem of Mukaiyama type reactions in asymmetric version. Firstly, a series of BSA analogues were synthesized. Then, we applied BAS and it’s analogues in bis-guanidinium salts catalyzed alkylation reactions. As for the alkylation reactions of cyclic ketones up to 99% ee was obtained, and for most of the substrates, the yield was excellent. As for the alkylation reactions of silyl enol ethers , up to 91% ee was obtained. At last, suggestions to further improvement were proposed and detailed experimental procedures were provided.