Catalyst-Enabled Chemoselective Metalloradical Activation for Molecular Rearrangement via Ester Migration and Allylic C(sp3)–H Amination

Abstract

An iron-based metalloradical activation concept is developed for an intramolecular molecular rearrangement via ester migration and an allylic C(sp3)–H amination using tetrazole as a nitrene precursor. It has been shown that an appropriate choice of catalyst can switch the chemoselectivity of a particular substrate from molecular rearrangement toward allylic C(sp3)–H amination. The scope of the reactions has been demonstrated by the use of a wide number of tetrazoles and aryl azides. Preliminary mechanistic studies revealed that while molecular rearrangement proceeds via an electrophilic nitrene transfer mechanism, C(sp3)–H amination follows a distinctive metalloradical activation mechanism controlled by the electronic properties of the iron–porphyrin catalysts. Collectively, this discovery highlights the advancement of chemoselective metalloradical catalysis, which should find wide application in medicinal chemistry and drug discovery.