铜催化苯甲酰胺与烷基偶氮试剂环化合成含α-取代季碳中心异喹啉二酮

doi:10.11944/j.issn.1000-0518.2017.03.160220

摘要/Abstract

摘要：

发展了一种苯甲酰胺自由基自由基环化制备α-官能化叔烷基取代的异喹啉二酮的新反应。此环化反应以偶氮试剂为α-取代叔烷基自由基源物质,利用碘化亚铜/空气体系催化N-烷基-N-甲基丙烯酰基苯甲酰胺发生环化,经过串联自由基加成/环化/碳-碳键形成过程,一步构建了三重碳-碳键,以41%~71%的产率合成了一系列异喹啉二酮及其衍生物。特别值得提出得是,此研究发展了一种新型α-官能叔烷基自由基源物质,发现了一种同时引入两个α-官能叔烷基片段的串联新反应。反应底物适应范围广,反应高效,催化体系廉价实用,为具有潜在药用价值的含α-取代季碳中心的异喹啉二酮及衍生物的合成提供了一条廉价、简单、快捷的新途径。

关键词: 异喹啉二酮, 苯甲酰胺, 串联环化, 铜催化, 烷基偶氮试剂

Abstract:

A radical cyclization reaction of benzamides toward isoquinolinedione bearing α-substituted quaternary carbon was developed. Using alkyl azo compounds as tertiary radical sources, N-alkyl-N-methacryloylbenzamides underwent cascade radical addition/cyclization/C—C bond formation in the presence of Cu catalyst and air, and constructed triple-fold carbon-carbon bonds in a single step, leading to a series of isoquinolinediones in 41% to 71% yield. Notably, this work discovered a new type of radical precursor to α-functional tertiary radical and a protocol to incorporate two α-functional tertiary alkyl moieties. The broad substrate scope and high efficiency allow this method a cheap, simple and rapid catalytic synthetic entry to pharmaceutically interesting isoquinolindiones.

Key words: isoquinolindione, benzamide, cascade cyclization, copper catalysis, alkyl azo compounds

邓佑林, 唐石, 袁莉, 李增增, 王良能, 李立洋, 黄桂秀, 刘盈盈, 吴伊婷, 付丽. 铜催化苯甲酰胺与烷基偶氮试剂环化合成含α-取代季碳中心异喹啉二酮[J]. 应用化学, 2017, 34(3): 330-337.

DENG Youlin, TANG Shi, YUAN Li, LI Zengzeng, WANG Liangneng, LI Liyang, HUANG Guixiu, LIU Yingying, WU Yiting, FU Li. Copper-catalyzed Cyclization of Benamides and Alkyl Azo Compounds Leading to Isoquinolinediones Bearing α-Substituted Quaternary Carbon[J]. Chinese Journal of Applied Chemistry, 2017, 34(3): 330-337.

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