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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.

SUBMITTER: Lin W

PROVIDER: S-EPMC8694391 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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

Lin Wei W Zhao Qun Q Li Yao Y Pan Ming M Yang Chen C Yang Guo-Hui GH Li Xin X

Chemical science 20211124 1

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 ve ...[more]

PMID: 35059162

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