Potassium Carbonate Catalyzed Intramolecular Post-Ugi Hydroamination Reaction Leading to N-Aryl Piperazine Derivatives

Abstract N-Arylpiperazines are prominent structures found in natural products and synthetic chemical entities, including therapeutic agents. In this work, we introduce a novel strategy for the effective synthesis of distinctive piperazine compounds through a post-Ugi cyclization under transition-metal-free conditions. This method involves the formation of a four-component Ugi adduct by combining an aldehyde, an isocyanide, a primary propargylamine, and an oxamic acid. Subsequently, an intramolecular alkyne hydroamination reaction occurs, leading to the formation of a piperazine derivative through carbon–nitrogen bond formation. The products have been characterized by 1H and 13C NMR spectroscopy.