文献类型：期刊文献

英文题名：Lewis Acid-Catalyzed Asymmetric [2σ+2π] Cycloaddition Reactions of Bicyclo[1.1.0]butanes and Vinyl Azido/Diazo Compounds

作者：Ren, Haosong[1,2];Lin, Zhongren[1,2];Li, Tianxiang[1,2];Li, Zhenyue[1,2];Yu, Xinhong[1,2];Zheng, Jun[1,2]

机构：[1]Minist Educ, Engn Res Ctr Pharmaceut Proc Chem, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China

年份：2025

卷号：15

期号：6

起止页码：4634

外文期刊名：ACS CATALYSIS

收录：;EI(收录号：20251018008801);WOS:【SCI-EXPANDED(收录号:WOS:001437911200001)】；

基金：We are grateful for the financial support from the National Natural Science Foundation of China (22301075), Shanghai Scientific and Technological Innovation Projects (23ZR1417400), East China University of Science and Technology for startup funding, the Program of Introducing Talents of Discipline to Universities, and the 111 Project (BP0719034).

语种：英文

外文关键词：asymmetric Lewis acid-catalysis; cycloaddition reaction; bridged bicyclic scaffolds; vinyl azides; vinyldiazo compounds

摘要：The [2 sigma + 2 pi] cycloaddition reaction of bicyclo[1.1.0]butanes (BCBs) and alkenes is a powerful method to construct pharmaceutically valuable bicyclo[2.1.1]hexane (BCH) frameworks. Asymmetric strategies developed have enabled [2 sigma + 2 pi] cycloaddition reactions of electron-deficient alkenes. However, an effective approach for electron-rich alkenes remains to be realized. Here we report asymmetric [2 sigma + 2 pi] cycloaddition reactions of BCBs and electron-rich alkene moieties of vinyl azido and diazo compounds. The chiral Lewis acid-activated BCB ketone complexes are crucial for achieving the reactivity and enantioselectivity. This protocol allows for the synthesis of chiral BCHs featuring two to three quaternary carbon centers and alpha-chiral tertiary azido or diazo functionalities in up to 98% yield, >19:1 dr, and >99% ee. Broad substrate scope, gram-scale synthesis, and good functional group compatibility demonstrate the practicality for synthesizing complex bicyclic structures. Mechanistic studies reveal that the nucleophilic attack of electron-rich alkenes on the cyclobutyl cation intermediate is the rate-limiting step.