Computational analysis of sulfoxonium ylide's dual role in ruthenium-catalyzed dehydrogenative annulations

Abstract

Transition metal-catalyzed dehydrogenative annulation reactions utilizing α-carbonyl sulfoxonium ylides constitute an efficient strategy for ring skeleton construction. These versatile ylide reagents can function as both C–H activation substrates and carbene precursors. Herein, we employ density functional theory calculations to systematically investigate the mechanism of ruthenium-catalyzed dehydrogenative annulation between α-carbonyl sulfoxonium ylide 1 and maleimide 2, with special focus on the dual role of sulfoxonium ylides. The C–H activation step is identified as rate-determining, wherein both the nucleophilic carbon and the carbonyl oxygen may serve as the coordination center for the directing group in 1. Computational analyses reveal that the nucleophilic carbon-directed pathway exhibits both kinetic and thermodynamic advantages, establishing it as the predominant coordination mode. The subsequent steps proceed sequentially with relatively lower barriers: Ru–carbene formation, followed by migratory insertion, and concluding with reductive elimination. We also investigate how Ru–carbene formation at different stages affects catalytic activity. Ru–carbene formation before C–H activation makes C–H activation kinetically unfeasible, while its occurrence after migratory insertion increases the barrier of migratory insertion, making this pathway uncompetitive. This work can provide fundamental insights into the bifunctional reactivity of sulfoxonium ylides in organometallic chemistry.