Recent Advances in Solvent-Free Sonogashira Coupling.

The Sonogashira coupling reaction holds an irreplaceable position in fields such as drug synthesis, natural product preparation, and functional material development. Through the integration of technical means such as mechanochemistry and microwave irradiation with efficient catalytic systems, the greening and high efficiency of the Sonogashira reaction process are achieved. This paper systematically reviews the research progress of solvent-free Sonogashira coupling reactions, focusing on classifying and elaborating on the design principles, catalytic performance, and reaction mechanisms of palladium-catalyzed, copper-catalyzed, palladium-copper co-catalyzed, and other novel catalytic systems. Both standard Sonogashira (Ar-X) and acyl-Sonogashira (Ar-COCl coupling) reactions are involved. It also analyzes the advantages and limitations of each system in terms of substrate compatibility, catalytic activity, and cyclic stability, providing a reference for the theoretical research and practical application of solvent-free Sonogashira coupling reactions.