title: Opportunities and challenges for direct C-H functionalization of piperazines.
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.
authors.affiliation: Department of Chemistry and Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907, United States.
authors.forename: Zhishi
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Department of Chemistry and Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907, United States.
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Gettys
authors.affiliation: Department of Chemistry and Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907, United States.
authors.forename: Mingji
authors.initials: M
authors.lastname: Dai
keywords: C–H functionalization; heterocycle; photoredox catalysis; piperazine; α-lithiation