Computational Mechanistic Elucidation of C–N Cross-Coupling Reactions via Ligand-Enabled Au(I)/Au(III) Catalysis: Insights into Y‑Arylation of Y–H Bonds (Y = N, C, O, S) Under Base-Free Conditions

Arylation of Y–H bonds (Y = N, C, O, S) catalyzed by transition metal complexes typically requires an external base to deprotonate the Y–H bonds, thereby preparing the system for Y-aryl coupling. However, designing catalytic reactions that operate without external bases is preferred due to benefits such as simplicity, cost savings, and reduced environmental impact. In this study, we demonstrate that substrates with Y–H bonds can undergo Y-arylation under base-free conditions if their coordination to the metal center renders them sufficiently acidic for deprotonation by the solvent. We identified several reports in the literature that meet this criterion, including the arylation of anilines and 1,3,5-trimethoxybenzene using hemilabile ligand-enabled Au(I)/Au(III) catalysis in methanol. Our density functional theory (DFT) calculations reveal that the key intermediate in such catalysis is an Au(III)-substrate adduct. The success of the catalysis under base-free conditions depends on the acidity (pKa) of this adduct, which is significantly influenced by the substrate substituents. For example, our calculations indicate that the pKa values for Au(III)-coordinated p-nitroaniline and 1,3,5-trimethoxybenzene in methanol are 2.1 and 4.6, respectively. These adducts are thus sufficiently acidic to be easily deprotonated by the solvent, enabling arylation under base-free conditions.