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 %VBur 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.