Ambimodal (2 + 1)/(4 + 1) Pseudopericyclic Transition States in Reactions between Dihalocarbenes and Olefins

We report the first example of ambimodal (2 + 1)/(4 + 1) pseudopericyclic transition states (TSs) in reactions between dihalocarbenes and olefins. Quasi-classical molecular dynamics simulations of the model reaction between dibromocarbene and 1,2-bis(methylene)cycloheptane reveal a single ambimodal TS that bifurcates to the experimentally observed (2 + 1) and (4 + 1) products. Intrinsic bond orbital (IBO) and principal interacting orbital (PIO) analyses attribute this ambimodality to the amphiphilicity of dibromocarbene: its empty p-type orbital engages the diene HOMO, while its σ-lone pair interacts with both the C2 and C4 lobes of the diene LUMO. The resulting ambimodal transition structure displays a large disparity in competing bond lengths─an outlier relative to established correlations between bond length differences and ambimodal selectivity. Entropic path sampling reveals a pronounced entropic trap along the (2 + 1) pathway, giving rise to a post-transition-state dynamical intermediate that promotes extensive roaming rather than immediate product formation. This dynamic window allows the weaker (4 + 1) interaction to develop and compete, thereby enabling ambimodality despite the substantial bond length difference. An analogous ambimodal (2 + 1)/(4 + 1) cycloaddition is identified between nucleophilic dimethoxycarbene and alkenyl aldehyde relevant to natural product synthesis, underscoring the generality and synthetic utility of this manifold. Together, these findings reveal how structure, orbital interactions, and post-transition-state dynamics cooperatively govern ambimodal selectivity in this previously unrecognized carbene reaction manifold and provide a foundation for developing new strategies to tune reaction selectivity.