Carbene-catalyzed activation of remote nitrogen atoms of (Benz)imidazole-derived aldimines for enantioselective synthesis of heterocycles

• Main Authors: Yang, Xing, Xie, Yongtao, Xu, Jun, Ren, Shichao, Mondal, Bivas, Zhou, Liejin, Tian, Weiyi, Zhang, Xinglong, Hao, Lin, Jin, Zhichao, Chi, Robin Yonggui
• Other Authors: School of Physical and Mathematical Sciences
• Format: Article
• Language: English
• Published: 2021
• Subjects: Science; Heterocycles; Imines
• Online Access: https://hdl.handle.net/10356/148222
• Institution: Nanyang Technological University

A new mode of carbene-catalyzed heteroatom activation and asymmetric reactions is disclosed. The reaction starts with addition of a carbene catalyst to a (benz)imidazole-derived aldimine substrate. Subsequent oxidation and proton transfer lead to the formation of a catalyst-bound triaza-diene as the key intermediate, in which the nitrogen atom at a site remote to the catalyst-substrate bond is activated. This unusual triaza-diene intermediate then undergoes highly enantioselective reactions with activated ketones through a concerted asynchronous pathway, as supported by mechanistic studies and preliminary density function theory calculation.