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.

Key words

piperazines - hydroamination - post-Ugi modification - catalyst-free reaction - multicomponent reaction

Publication History

Received: 07 December 2024

Accepted after revision: 10 January 2025

Article published online:
14 April 2025

• References and Notes

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• 13 Ugi Adducts 5; General Procedure A mixture of the appropriate propargylamine 1 (2.0 mmol), aldehyde 2 (2.0 mmol), isocyanide 3 (2.0 mmol), and acid 4 (2.0 mmol) in MeOH (2.0 mL) was stirred at r.t. for 24 h. When the starting materials were completely consumed (TLC), the product was precipitated and recrystallized from EtOH.
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