Electrostatic Switching between SN1 and SN2 Pathways.

Abstract

A test set 264 nucleophilic substitution reactions was studied via accurate quantum chemical reactions to establish the relative preferences for SN1 versus SN2 mechanisms. In low polar solvents, reactions involving anionic nucleophiles and leaving groups favored SN2 pathways. In contrast, SN1 is preferred for those reactions involving neutral nucleophiles and leaving groups except where the carbocation intermediates are exceptionally unstable. For neutral nucleophiles and anionic leaving groups, SN2 is generally preferred over SN1 except for exceptionally stable carbocation intermediates. On the basis of these studies, candidate reactions for which distinct SN1 or SN2 preferences could be reversed by electric fields were selected. As proof of concept, the SN1/SN2 preferences for the reaction of tBu-triflate with pyridine (SN2 to SN1) and with piperidine (SN1 to SN2) were switched by both charged functional groups and point charges (i.e., electric fields) along the reaction axis, with a positive charge on the nucleophile side favoring SN1 and a negative charge favoring SN2 for these reactions.