Resolving Entangled Reactivity Modes through External Electric Fields and Substitution: Application to E2/SN2 Reactions.

In this study, we explore strategies to resolve entangled reactivity modes. More specifically, we consider the competition between SN2 and E2 reaction pathways for alkyl halides and nucleophiles/bases. We first demonstrate that the emergence of an E2-preference is associated with an enhancement of the magnitude of the resonance stabilization in the transition-state (TS) region, resulting from the improved mixing of electrostatically stabilized valence bond structures into the TS wavefunction. Subsequently, we show that the TS resonance energy can be tuned selectively and rationally either through the application of an oriented external electric field directed along the C-C axis of the alkyl halide or through a regular substitution approach of the C-C moiety. We end our study by demonstrating that the insights gained from our analysis enable one to rationalize the main reactivity trends emerging from a recently published large database of competing SN2 and E2 reaction pathways.