Titanocene(III)‐Catalyzed Three‐Component Reaction of Secondary Amides, Aldehydes, and Electrophilic Alkenes

Abstract

Abstract An umpolung Mannich‐type reaction of secondary amides, aliphatic aldehydes, and electrophilic alkenes has been disclosed. This reaction features the one‐pot formation of CN and CC bonds by a titanocene‐catalyzed radical coupling of the condensation products, from secondary amides and aldehydes, with electrophilic alkenes. N‐substituted γ‐amido‐acid derivatives and γ‐amido ketones can be efficiently prepared by the current method. Extension to the reaction between ketoamides and electrophilic alkenes allows rapid assembly of piperidine skeletons with α‐amino quaternary carbon centers. Its synthetic utility has been demonstrated by a facile construction of the tricyclic core of marine alkaloids such as cylindricine C and polycitorol A.