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
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