The Aza‐Cope/Mannich Reaction

Abstract Because of their ability to rapidly build molecular complexity, reactions that construct several carbon‐carbon bonds are of special value in organic synthesis. Among these transformations, cascade reactions form several bonds by an orchestrated sequence in which the first bond‐forming step reveals functionality that allows subsequent bond forming transformations. In 1979 such a sequence for the synthesis of 3‐acylpyrrolidines and azacyclic structures that contain this unit was reported. This reaction is now commonly called the aza‐Cope/Mannich reaction, a [3,3]‐sigmatropic rearrangement of an unsaturated iminium cation generates the iminium ion and enol that are participants in a subsequent intramolecular Mannich reaction. The aza‐Cope/Mannich reaction has not been the subject of comprehensive review. This chapter covers the common version of the transformation discussed above along with the formation of 3‐acylpyrrolidines by a related base‐promoted cascade sequence.