Transition-metal-catalyzed switchable divergent cycloaddition of para-quinone methides and vinylethylene carbonates: Access to different sized medium-sized heterocycles

Divergent synthesis of medium-sized rings with controllable ring sizes represents a longstanding challenge in organic synthesis. Herein, we developed a transition-metal-catalyzed switchable divergent cycloaddition of para-quinone methides and vinylethylene carbonates by controlling the steric hindrance of substituent. Different from reported alkoxide-triggered annulations, this process undergoes a regiodivergent allylation of para-quinone methides followed by 1,6-addition reaction, providing a new route to selectively synthesize seven- to ten-membered nitrogen-containing heterocycles in high yields with excellent regioselectivities. This protocol features a broad substrate scope, wide functional group tolerance as well as operational simplicity. The reaction mechanism was investigated by conducting a series of control experiments as well as DFT calculations and the origins of the regioselectivities of the cycloaddition process were rationalized. (C) 2022 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.