Nucleophilic Substitution (S_N2): Dependence on Nucleophile, Leaving Group, Central Atom, Substituents, and Solvent

Abstract

The reaction potential energy surface (PES), and thus the mechanism of bimolecular nucleophilic substitution (SN2), depends profoundly on the nature of the nucleophile and leaving group, but also on the central, electrophilic atom, its substituents, as well as on the medium in which the reaction takes place. Here, we provide an overview of recent studies and demonstrate how changes in any one of the aforementioned factors affect the SN2 mechanism. One of the most striking effects is the transition from a double‐well to a single‐well PES when the central atom is changed from a second‐period (e. g. carbon) to a higher‐period element (e.g, silicon, germanium). Variations in nucleophilicity, leaving group ability, and bulky substituents around a second‐row element central atom can then be exploited to change the single‐well PES back into a double‐well. Reversely, these variations can also be used to produce a single‐well PES for second‐period elements, for example, a stable pentavalent carbon species.

Nucleophilic Influences and Origin of the SN2 Allylic Effect

“…Nonetheless, we also carried out computations that simulated the bulk effect for several typical solvents to test how the kinetic parameters change from the gas to solution phase. To gain deeper understanding of the factors that influence reactivities, we performed activation strain analyses . We also evaluated a number of theoretical quantities that characterize the properties of the nucleophiles as well as the corresponding transition states.…”

“…To gain deeper understanding of the factors that influence reactivities, we performed activation strain analyses. [12][13][14][15] We also evaluated an umber of theoretical quantities that characterize the properties of the nucleophiles as well as the corresponding transition states.…”

Ambident Nucleophilic Substitution: Understanding Non‐HSAB Behavior through Activation Strain and Conceptual DFT Analyses

“…The change from the typical double‐well PES (Figure a) to the single‐well PES (Figure b) associated with S N 2@Si reactions is in line with previous reports . The studied S N 2@Si reactions proceed from the reactants to a stable central transition complex (TC) via a barrierless process and then finally to the products.…”

Silicon‐Free SuFEx Reactions of Sulfonimidoyl Fluorides: Scope, Enantioselectivity, and Mechanism

“…Further mechanism investigations were made possible by utilizing the chirality of sulfur atom in the sulfonimidoyl fluoride 1 and its SuFEx products. Previous mechanism‐oriented reports have typically focused on substitution reactions on disulfides, yielding addition–elimination and S N 2 as the most widely accepted mechanisms, with the detailed mechanism being sensitive to the strain, counter cations, leaving groups, substituents on sulfur atom, nucleophiles, solvents,– and so on (see for an overview). Analogously, we considered as the three most likely mechanisms those summarized in Figure .…”