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 Introduction

2 Reduction of (Di)ketopiperazine

3 N-Alkylation

4 Transition-Metal-Catalyzed/Mediated Piperazine Synthesis

4.1 The SnAP and SLAP Methods

4.2 Palladium-Catalyzed Cyclization

4.3 Gold-Catalyzed Cyclization

4.4 Other Metal-Catalyzed/Mediated Cyclization

4.5 Borrowing Hydrogen Strategy

4.6 Imine Reductive Cyclization

5 Reduction of Pyrazines

6 Miscellaneous

7 Conclusion

Keywords

piperazine - heterocycle - synthesis - cyclization - catalysis

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