Department of Chemistry and The Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005 (P.R. China).
Key Laboratory of Synthetic Chemistry of Natural Substances, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences (P.R. China).
Angew Chem Int Ed Engl. 2015 Nov 9;54(46):13739-42. doi: 10.1002/anie.201506907. Epub 2015 Sep 25.
An umpolung Mannich-type reaction of secondary amides, aliphatic aldehydes, and electrophilic alkenes has been disclosed. This reaction features the one-pot formation of C-N and C-C bonds by a titanocene-catalyzed radical coupling of the condensation products, from secondary amides and aldehydes, with electrophilic alkenes. N-substituted γ-amido-acid derivatives and γ-amido ketones can be efficiently prepared by the current method. Extension to the reaction between ketoamides and electrophilic alkenes allows rapid assembly of piperidine skeletons with α-amino quaternary carbon centers. Its synthetic utility has been demonstrated by a facile construction of the tricyclic core of marine alkaloids such as cylindricine C and polycitorol A.
本文首次报道了仲酰胺、脂肪醛和缺电子烯烃的极性反转 Mannich 型反应。该反应通过茂钛催化的缩合产物（仲酰胺和醛）与亲电烯烃的自由基偶联一锅法形成 C-N 和 C-C 键。该方法可以高效制备 N-取代的γ-酰胺基酸衍生物和γ-酰胺酮。酮酰胺和缺电子烯烃之间的扩展反应允许快速构建具有α-氨基季碳中心的哌啶骨架。该方法的合成实用性已通过海洋生物碱如圆柱菌素 C 和多西他醇 A 的三环核心的简便构建得到证明。
