Scratching Beneath the Surface: Catalyst Evolution and Reusability in the Direct Mechanocatalytic Sonogashira Reaction

Abstract

We present a solvent-free Sonogashira coupling of various para-substituted aryl halides with trimethylsilyl acetylene or phenylacetylene using a palladium catalyst and copper (0) co-catalyst under mechanochemical conditions. This study investigates the critical components required for C–C bond formation and explores the in situ generation of an active catalyst from individual precursors traditionally used in solution-phase chemistry. We demonstrate the role of Pd (0) in different metal forms (powder and foil) within a copper milling jar, highlighting the importance of thermal activation and ligand presence in generating a reactive catalytic species. Notably, Pd was found to embed into the copper surface, enabling multiple reaction cycles without additional Pd, as confirmed by surface analysis. Furthermore, thermal control of the reaction allows for chemoselective activation of one halide over another. Our findings provide insights into the development of catalytic systems during mechanochemical reactions from individual components, offering a cost-effective and sustainable approach to solvent-free organic transformations. This study underscores the potential of mechanochemical methods for designing reusable catalytic systems with enhanced efficiency and selectivity.