Cinchona Urea-Catalyzed Asymmetric Sulfa-Michael Reactions: The Brønsted Acid−Hydrogen Bonding Model

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• 作者：Matthew N. Grayson ; K. N. Houk
• 刊名：Journal of the American Chemical Society
• 出版年：2016
• 出版时间：July 27, 2016
• 年：2016
• 卷：138
• 期：29
• 页码：9041-9044
• 全文大小：331K
• 年卷期：0
• ISSN：1520-5126

文摘

The cinchona alkaloid-derived urea-catalyzed asymmetric conjugate addition of aromatic thiols to cycloalkenones was studied using density functional theory (DFT). Deprotonation of the thiol gives a protonated amine that activates the electrophile by Brønsted acid catalysis, while the urea group binds the nucleophilic thiolate by hydrogen bonding. These results demonstrate the generality of the Brønsted acid−hydrogen bonding transition state (TS) model for cinchona alkaloid catalysis that we recently showed to be favored over Wynberg’s widely accepted ion pair−hydrogen bonding model and represent the first detailed mechanistic study of a cinchona urea-catalyzed reaction. The conformation of the catalyst methoxy group has a strong effect on the TS, an effect overlooked in previous mechanistic studies of reactions catalyzed by cinchona alkaloids.