Diastereoselective Trifluoroacetylation of Highly Substituted Pyrrolidines by a Dakin−West Process

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• 作者：Marcus Baumann ; Ian R. Baxendale
• 刊名：Journal of Organic Chemistry
• 出版年：2016
• 出版时间：December 2, 2016
• 年：2016
• 卷：81
• 期：23
• 页码：11898-11908
• 全文大小：543K
• ISSN：1520-6904

文摘

A robust approach allowing for the efficient trifluoroacetylation of a series of highly substituted pyrrolidines in a diastereoselective manner is reported. The transformation is based on a Dakin–West reaction of advanced pyrrolidine 2-carboxylic acid derivatives that can be assembled stereoselectively in four synthetic steps. Importantly, this work demonstrates how the introduction of lateral substituents on the pyrrolidine scaffold enables the generation of the desired trifluoroacetylation products, which was not possible previously due to the exclusive formation of trifluoromethylated oxazoles (vide infra). In the course of this work we succeeded for the first time in isolating and characterizing (HRMS, IR, ¹H, ¹³C and ¹⁹F NMR, X-ray) different intermediates of the Dakin–West reaction allowing us to probe its mechanism.