Hydrogen bonding induces a mechanistic change in nucleophilic aromatic substitution with amine nucleophiles and aryl fluorides

Abstract

Nucleophilic aromatic substitution (S_NAr) reactions are known to proceed through both stepwise and concerted pathways, dictated largely by electrophile structure. In this paper, we show that the mechanism of S_NAr is influenced by intramolecular hydrogen bonding to the leaving group. We propose that this corresponds to a mechanistic transition from a stepwise/borderline mechanism to a concerted mechanism, as a result of stabilization of the elimination transition state. Our conclusions are supported by kinetic analysis examining the effects of the H-bond donor, the electrophile, and the nucleophile.