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Efficient Synthesis of All-Carbon Quaternary Centers via the Conjugate Addition of Functionalized Monoorganozinc Bromides
Published on: May 26, 2019
Synthesis of Mannich-type derivatives from amides activated by hydrogen bonding with ZnCl2
Zhiyu Hu1, Zongbo Xie1, Zhiqiang Zhu1
1Jiangxi Province Key Laboratory of Synthetic Chemistry, East China University of Technology, Nanchang 330013, Jiangxi, China. zbxie@ecut.edu.cn zhgle@ecut.edu.cn and School of Chemistry, Biology and Material Science, East China University of Technology, Nanchang 330013, Jiangxi, China. zbxie@ecut.edu.cn zhgle@ecut.edu.cn.
Abstract:
The amide group has one of the most significant functionalities found in many natural products. Herein, low-nucleophilic amides are used in a Mannich-type reaction to synthesize N-acyl-protected amine derivatives. A highly efficient synthetic method utilizing simple aldehydes, N-substituted anilines, and amides as substrates was established through a one-pot amide pathway activated by hydrogen bonding between the ZnCl2 and amide under solvent-free conditions. This strategy can be broadly applied to medicinal chemistry. More importantly, compared with the previous Lewis acid catalyzed reaction, we proposed a new application of zinc chloride.
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