Asymmetric synthesis of N-N axially chiral compounds via organocatalytic atroposelective N-acylation

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 atroposelective N-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.

Automated summary

This study reported the first atroposelective N-acylation reaction for the direct catalytic synthesis of optically active atropisomeric quinazolinone derivatives. The reaction features mild conditions, broad substrate scope, high yields, and very good enantioselectivities. The synthetic utility of the protocol was supported by a large scale reaction, transformation of the product, and the utilization of the product as an acylation kinetic resolution reagent, with DFT calculations providing convincing evidence for stereoselection interpretation.