Tang Lei, Xiao Yuanjiu, Wu Feng, Zhou Jin-Lan, Xu Tong-Tong, Feng Jian-Jun
State Key Laboratory of Chemo/Biosensing and Chemometrics, Advanced Catalytic Engineering Research Center of the Ministry of Education, College of Chemistry and Chemical Engineering, Hunan University Changsha, Hunan, 410082, P. R. China.
Angew Chem Int Ed Engl. 2023 Nov 27;62(48):e202310066. doi: 10.1002/anie.202310066. Epub 2023 Oct 25.
Bicyclo[2.1.1]hexanes (BCHs) are becoming ever more important in drug design and development as bridged scaffolds that provide underexplored chemical space, but are difficult to access. Here a silver-catalyzed dearomative [2π+2σ] cycloaddition strategy for the synthesis of indoline fused BCHs from N-unprotected indoles and bicyclobutane precursors is described. The strain-release dearomative cycloaddition operates under mild conditions, tolerating a wide range of functional groups. It is capable of forming BCHs with up to four contiguous quaternary carbon centers, achieving yields of up to 99 %. In addition, a scale-up experiment and the synthetic transformations of the cycloadducts further highlighted the synthetic utility.
双环[2.1.1]己烷（BCHs）作为一种提供未被充分探索的化学空间的桥连骨架，在药物设计与开发中变得越来越重要，但难以获得。本文描述了一种银催化的脱芳构化[2π+2σ]环加成策略，用于从N-未保护的吲哚和双环丁烷前体合成吲哚并双环[2.1.1]己烷。应变释放脱芳构化环加成反应在温和条件下进行，能耐受多种官能团。它能够形成含有多达四个相邻季碳中心的双环[2.1.1]己烷，产率高达99%。此外，放大实验和环加成产物的合成转化进一步突出了其合成实用性。
