Water-Soluble Au-NHC Complexes for Aqueous A³ Coupling: Ligand Architecture, Catalyst Speciation, and Reuse

The development of water-soluble gold catalysts for reactions in water remains challenging because catalyst speciation and oxidation-state changes can strongly influence activity and stability. Herein, two water-soluble Au-(III)-NHC complexes (2a-b)-selected for their distinct structural features-were synthesized and evaluated in the A³-coupling reaction in aqueous media, together with their corresponding Au-(I) precursor. Among the Au-(III)-NHC precatalysts 2a and 2b, complex 2b displayed superior activity compared to 2a, affording quantitative yields at 1 mol % and maintaining significant conversion even at 0.2 mol % loading. Steric analysis based on %V_Bur calculations showed that, upon Au-Cl bond cleavage, the sulfonate side chain in 2b cyclized and coordinates to the metal center, leading to a significant increase in buried volume. Recycling experiments showed progressive deactivation of both Au-(III) precatalysts, while NMR monitoring in the presence of phenylacetylene provided evidence for changes in Au-(III)/Au-(I) speciation, including formation of Au-(I) species. Addition of catalytic amounts of CuCl₂ improved the recycling of 2b, although catalyst reuse remained limited to three cycles. These results establish a correlation between ligand-controlled steric modulation, oxidation-state stability, and catalytic performance in aqueous Au-(III)-NHC systems for the multicomponent A³-coupling reaction.