Post-Transition State Bifurcation in Iron-Catalyzed Arene Aminations

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 quasi-classical 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 sigma-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) sigma-complex/aziridinium selectivity on the bifurcating surface. The final amination products can be favorably generated via the ring opening of aziridinium intermediates, rearrangement of sigma-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.

Automated summary

A recent study has demonstrated the effectiveness of an iron-catalyzed meta-selective arene amination strategy in terms of regiocontrol, operational simplicity, and atom efficiency. Density functional theory calculations and quasi-classical molecular dynamics simulations were used to investigate the mechanism of this reaction, revealing an unreported ambimodal attack of arene by hydroxylamine-O-sulfate. The study illustrates a novel pathway where an ambimodal reaction is incorporated into the standard SEAr mechanism.