Fe-Catalyzed Aziridination Is Governed by the Electron Affinity of the Active Imido-Iron Species

Aziridination has very recently been found to be catalyzed by heme and nonheme Fe enzymes, opening the way to biotechnological developments. However, its mechanism is not fully understood owing to the contrasting behaviors exhibited by several Fe catalysts. Indeed, whereas a few Fe catalysts exhibit an activity dominated by inductive effects, the activity of others reveal significant and even dominant radical delocalization. Therefore, no clear and general rationale of aziridination has yet emerged. Elaborating on our previous studies, we anticipated that replacing two pyridines of a pentanitrogen ligand by two quinolines would enhance the electron affinity of the corresponding imido FeIV active species and hence its aziridination activity. This proved to be the case, and Hammett correlations indicate an electrophilic active species and dominant inductive effects. The calculated reaction profile points to a two-step mechanism with the formation of the first C-N bond being rate-determining and involving a strong charge transfer in the transition state. The aziridine ring closure in the second step is almost barrierless. A clear correlation of aziridination yields with calculated EA for Fe-catalysts indicate that the dependence of aziridination efficacy on EA of active species is a quite general feature. To generalize this analysis, we reinvestigated a catalyst exhibiting a radical delocalization dominance. Indeed, a similar two-step mechanism was found, which involves a partial charge transfer in the C-N bond formation as all other cases. The interesting point is that owing to the strong steric hindrance of the catalyst substitution, the aziridine ring closure of the intermediate benzylic radical (second step) becomes rate-determining, thus explaining the dominance of the radical delocalization effect. Eventually, a general aziridination two-step mechanism has been rationalized, and EA thus appears as the key descriptor for Fe-based catalytic aziridination that can be used in a predictable way.