Li Xingguang, Duan Meng, Yu Peiyuan, Houk K N, Sun Jianwei
Department of Chemistry, the Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China.
The Hong Kong Branch of Chinese National Engineering Research Centre for Tissue Restoration & Reconstruction, Clear Water Bay, Kowloon, Hong Kong SAR, China.
Nat Commun. 2021 Aug 12;12(1):4881. doi: 10.1038/s41467-021-25165-7.
Catalytic asymmetric dearomatization (CADA) is a powerful tool for the rapid construction of diverse chiral cyclic molecules from cheap and easily available arenes. This work reports an organocatalytic enantioselective dearomatization of substituted thiophenes in the context of a rare remote asymmetric 1,10-conjugate addition. By suitable stabilization of the thiophenyl carbocation with an indole motif in the form of indole imine methide, excellent remote chemo-, regio-, and stereocontrol in the nucleophilic addition can be achieved with chiral phosphoric acid catalysis under mild conditions. This protocol can be successfully extended to the asymmetric dearomatization of other heteroarenes including selenophenes and furans. Control experiments and DFT calculations demonstrate a possible pathway in which hydrogen bonding plays an important role in selectivity control.
催化不对称去芳构化（CADA）是一种从廉价且易于获得的芳烃快速构建多种手性环状分子的强大工具。本文报道了在罕见的远程不对称1,10-共轭加成背景下，对取代噻吩进行有机催化对映选择性去芳构化反应。通过以吲哚亚胺甲基化物形式的吲哚基序对噻吩基碳正离子进行适当稳定，在手性磷酸催化下，在温和条件下亲核加成反应中可实现出色的远程化学、区域和立体控制。该方案可成功扩展至包括硒吩和呋喃在内的其他杂芳烃的不对称去芳构化反应。对照实验和密度泛函理论计算表明了一种可能的途径，其中氢键在选择性控制中起着重要作用。
