Background: Substituted piperazine heterocycles are among the most significant structural components
of pharmaceuticals. N1/N4 substituted piperazine containing drugs and biological targets are ranked 3rd
in the top most frequent nitrogen heterocycles in U.S. FDA approved drugs. The high demand of N1/N4 substituted
piperazine containing biologically active compounds and U.S. FDA approved drugs, has prompted the
development of Pd catalyzed C-N bond formation reactions for their synthesis. Buchwald-Hartwig reaction is
the key tool for the synthesis of these compounds.
Objective: This review provides strategies for Pd catalyzed C-N bond formation at N1/N4 of piperazine in the
synthesis of drugs and biological targets with diverse use of catalyst-ligand system and reaction parameters.
Conclusion: It is clear from the review that a vast amount of work has been done in the synthesis of N1/N4
substituted piperazine containing targets under the Pd catalyzed Buchwald-Hartwig amination of aryl halides
by using different catalyst-ligand systems. These methods have become increasingly versatile as a result of innovation
in catalyst design and improvements in reaction conditions. This review gives an overview of recent
utilization of Buchwald-Hartwig amination reaction in drug/target synthesis.