Opportunities and challenges for direct C-H functionalization of piperazines
Zhishi Ye1, Kristen E Gettys1, Mingji Dai1
1Department of Chemistry and Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907, United States.
Abstract:
Piperazine ranks within the top three most utilized N-heterocyclic moieties in FDA-approved small-molecule pharmaceuticals. Herein we summarize the current synthetic methods available to perform C-H functionalization on piperazines in order to lend structural diversity to this privileged drug scaffold. Multiple approaches such as those involving α-lithiation trapping, transition-metal-catalyzed α-C-H functionalizations, and photoredox catalysis are discussed. We also highlight the difficulties experienced when successful methods for α-C-H functionalization of acyclic amines and saturated mono-nitrogen heterocyclic compounds (such as piperidines and pyrrolidines) were applied to piperazine substrates.
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