Construction of Stereogenic α,α-Disubstituted Cycloalkanones via 1° Amine Thiourea Dual Catalysis: Experimental Scope and Computational Analyses
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- 作者：Jun Yong Kang ; Ryne C. Johnston ; Kevin M. Snyder ; Paul Ha-Yeon Cheong ; Rich G. Carter
- 刊名：Journal of Organic Chemistry
- 出版年：2016
- 出版时间：May 6, 2016
- 年：2016
- 卷：81
- 期：9
- 页码：3629-3637
- 全文大小：739K
- 年卷期：0
- ISSN：1520-6904
文摘
The mechanistic exploration and an expanded experimental discussion of the organocatalyzed, asymmetric Pfau–d’Angelo reaction by exploiting a bifunctional 1° amine thiourea catalyst system is disclosed. Notable breadth in substrate scope has been demonstrated on both the cyclic ketone moiety and the α,β-unsaturated electrophile. Exploration into the matched and mismatched selectivity of this process with a ketone containing pre-existing stereocenters has been demonstrated. Computational analyses of the reaction mechanism are reported. In concert with kinetic isotope effect (KIE) experiments, these computational results provide a detailed understanding of the likely mechanism, including the aspects of the organocatalyst scaffold that are critical for stereoselectivity.