Asymmetric Synthesis of Chiral Aliphatic α-Tertiary Aminonitriles via Organocatalytic Isomerization of Cyanoketimines

Abstract

Comprehensive Summary:Chiral α-tertiary aminonitriles are valuable synthetic intermediates. They are also found in various structures of biologically active molecules. Therefore, numerous reports of catalytic asymmetric synthesis of chiral α-aminonitriles continuously emerged during the past few decades. Great strides have been made for the synthesis of chiral α-aryl and α-branched alkyl aminonitriles. However, efficient methods for catalytic asymmetric synthesis of chiral α-linear alkyl aminonitriles remain limited. We herein report a new synthetic approach to chiral α-tertiary alkyl aminonitriles via catalytic asymmetric isomerization of cyanoketimines. The synthetic value of this method was illustrated by application to a concise catalytic asymmetric synthesis of vildagliptin.

Keywords

Isomerization / Aminonitriles / Cyanoketimine / Protonation / Organocatalysis / Enantioselectivity

RIGHTS & PERMISSIONS

2024 SIOC, CAS, Shanghai, & WILEY-VCH GmbH