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

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. The study presents a new synthetic approach to chiral α‐tertiary alkyl aminonitriles via catalytic asymmetric isomerization of cyanoketimines. It features a complementary method to the catalytic asymmetric Strecker reaction and umpolung addition of cyanoketimine. The utility of this method was illustrated by the development of a concise enantioselective synthesis of vildagliptin.