Asymmetric synthesis of N–N axially chiral compounds via organocatalytic atroposelective N-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 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.

Graphical abstract: Asymmetric synthesis of N–N axially chiral compounds via organocatalytic atroposelective N-acylation

Supplementary files

Article information

Article type
Edge Article
Submitted
29 Sep 2021
Accepted
10 Nov 2021
First published
24 Nov 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2022, Advance Article

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

W. Lin, Q. Zhao, Y. Li, M. Pan, C. Yang, G. Yang and X. Li, Chem. Sci., 2022, Advance Article , DOI: 10.1039/D1SC05360D

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