Recent Advances in Piperazine Synthesis

Abstract

Piperazine ranks as the third most common N-heterocycle appearing in small-molecule pharmaceuticals. This review highlights recent advances in methods development for the construction of the piperazine­ ring system with particular emphasis on preparing carbon-substituted piperazines.1 Introduction2 Reduction of (Di)ketopiperazine3 N-Alkylation4 Transition-Metal-Catalyzed/Mediated Piperazine Synthesis4.1 The SnAP and SLAP Methods4.2 Palladium-Catalyzed Cyclization4.3 Gold-Catalyzed Cyclization4.4 Other Metal-Catalyzed/Mediated Cyclization4.5 Borrowing Hydrogen Strategy4.6 Imine Reductive Cyclization5 Reduction of Pyrazines6 Miscellaneous7 Conclusion