Highly Chemoselective and Enantioselective Synthesis of 3,4-2<i>H</i>-Pyrindin-2-ones by an NHC-Catalyzed [3 + 3] Cyclization
Jun Yan, Zhaoxin Song, Chengtao Zhao, Kuangxi Shi, Limin Yang, Guofu Zhong
Abstract
A highly chemoselective and enantioselective cyclization of γ-chloroenals and ketimines has been developed to synthesize enantiopure 3,4-2H-pyrindin-2-ones as major products. It is proposed that the intermediate enone IV reacted with an enamine to proceed with a [3 + 3] cyclization, thereby affording 3,4-2H-pyrindin-2-ones as major products. Interestingly, the addition of LiCl promoted the formation of the enamine and accelerated the [3 + 3] cyclization. In contrast, the [4 + 2] cycloaddition reaction between the intermediate vinyl enolate VIII and an imine offered 5,6-2H-pyrindin-2-ones as minor products. This protocol represents the exceptional potential of N-heterocyclic carbene (NHC) catalytic reactions in accessing biologically active 3,4-2H-pyrindin-2-one derivatives in good yield with high chemoselectivities and excellent enantiomeric purities.