Recent Advances in Homogeneous and Heterogeneous Catalysis for A3-Coupling Reactions: Synthesis of Propargylamines and Their Derivatives.

Abstract

A3 coupling, a three-component reaction involving an aldehyde, an amine, and a terminal alkyne, has emerged as a powerful and atom-economical strategy for the synthesis of propargylamines, which are valuable intermediates in organic and medicinal chemistry. Owing to its operational simplicity, high efficiency, and ability to form C─C and C─N bonds in a single step, A3 coupling has attracted significant attention over the past two decades. This review provides a comprehensive overview of recent advancements in A3 coupling, with particular emphasis on catalytic systems developed between 2021 and 2025. The discussion is systematically divided into homogeneous and heterogeneous catalytic approaches. In addition, emerging metal-free methodologies and alternative activation strategies, such as microwave-assisted, photo-assisted, and ionic liquid-mediated A3 coupling, are also summarized. Special attention is given to the role of catalyst design in improving efficiency, selectivity, and environmental compatibility. Overall, this review aims to consolidate recent developments, compare different catalytic strategies, and provide insights into current challenges and future directions in A3 coupling.

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