Catalyst-Enabled Chemoselective Metalloradical Activation for Molecular Rearrangement via Ester Migration and Allylic C(sp

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.