Post-Transition State Bifurcation in Iron-Catalyzed Arene Aminations

Abstract

Recently, an iron-catalyzed meta-selective arene amination strategy was reported to show excellent regiocontrol, operational simplicity, and high atom and cost efficiencies. In this work, density functional theory (DFT) calculations and quasiclassical molecular dynamics (MD) simulations were carried out to study the mechanism of this reaction. Our computations revealed an unreported ambimodal attack of arene by hydroxylamine-O-sulfate, which forms not only σ-complex via electrophilic addition but also an aziridinium intermediate through energetically concerted electrophilic–nucleophilic additions. Quasiclassical trajectories suggest the orientation of the attacking NH2+ group with respect to arene control: (a) site selectivity of the post-transition state nucleophilic attack and (b) σ-complex/aziridinium selectivity on the bifurcating surface. The final amination products can be favorably generated via the ring opening of aziridinium intermediates, rearrangement of σ-complexes, and deprotonation of the resultant carbocations. Overall, our study illustrates a novel pathway in which an ambimodal reaction is incorporated into the standard SEAr mechanism.