Mechanism of Gold-Catalyzed Arylation-Lactonization: A Density Functional Theory Study on the Role of the (MIC^N)AuCl Complex in Au(I)/Au(III) Catalysis

Gold-catalyzed redox transformations via Au(I)/Au(III) cycles offer efficient oxidative addition and reductive elimination under mild, oxidant-free conditions. Recent studies highlight the role of hemilabile mesoionic carbene (MIC) ligands in stabilizing key intermediates. Using DFT, we investigated the mechanism of the arylation-lactonization of γ-alkenoic acids, revealing two viable pathways, <i>cis</i> and <i>trans</i>, each with distinct rate-determining steps. While the <i>trans</i> pathway avoids decomposition of the catalyst, its lactonization step is hindered by a high barrier. In contrast, the <i>cis</i> pathway features competing productive and decomposition routes. By correlating computed activation barriers with experimental yields, we built statistically significant multivariable models (<i>R</i>² = 0.919), enabling the prediction of product yields across various substituted aryl iodides. These models revealed clear electronic and steric trends. Additionally, ligand modifications suggest that <i>trans</i>-selective oxidative addition can be improved through steric tuning with the <i>trans</i> effect also influencing selectivity. Overall, this study provides valuable design principles for future gold-catalyzed redox processes.