Exploring the Generality of Post-Transition State Bifurcations for Metal-Catalyzed C–H Insertion Reactions that Form 4-Membered Rings

Abstract

Post-transition state bifurcations (PTSBs) previously have been identified in dirhodium-catalyzed C–H insertion reactions that form β-lactones, where a single transition structure provides direct access to both insertion and fragmentation products. Here, we investigate whether this behavior is a general feature of metal-catalyzed C–H insertion reactions by extending the analysis to iridium- and ruthenium-based catalysts, amide (lactam-forming) substrates, and metal-free carbene reactions. Using quantum chemical calculations, ab initio molecular dynamics (AIMD) simulations, and principal component analysis (PCA)-based potential energy surface (PES) construction, we demonstrate that PTSBs are present across all types of metal-catalyzed systems examined. Catalyst identity influences PES topography and product selectivity, with iridium-based systems showing greater selectivity for lactone formation than ruthenium-based systems. For amide substrates, fragmentation proceeds via a two-step pathway through a discrete intermediate not observed in the ester series. Collectively, these results establish PTSBs as a general feature of the reaction landscape for metal-catalyzed C–H insertion reactions that form 4-membered rings.