Asymmetric synthesis of N-N axially chiral compoundsviaorganocatalytic atroposelectiveN-acylation

Abstract

Compared with the well-developed C-C and C-N axial chirality, the asymmetric synthesis of N-N axial chirality remains elusive and challenging. Herein we report the first atroposelectiveN-acylation reaction of quinazolinone type benzamides with cinnamic anhydrides for the direct catalytic synthesis of optically active atropisomeric quinazolinone derivatives. This reaction features mild conditions and a broad substrate scope and produces N-N axially chiral compounds with high yields and very good enantioselectivities. Besides, the synthetic utility of the protocol was proved by a large scale reaction, transformation of the product and the utilization of the product as an acylation kinetic resolution reagent. Moreover, DFT calculations provide convincing evidence for the interpretation of stereoselection.