Benzylic C(sp3)−H Azidation: Copper vs Iron Catalysis

The generation of benzylic radicals through hydrogen atom abstraction (HAT) has been a recent research focus and various C(sp³)−H bond functionalization protocols have been developed relying on this elementary step. We report herein copper- and iron-catalyzed C(sp³)−H benzylic azidation reactions using mCPBA and NFSI as oxidant, respectively, and TMSN₃ as azide source. The reaction is thought to be initiated via intermolecular abstraction of benzylic hydrogen by the in situ generated heteroatom-centered radicals. The Fe(OTf)₃-catalyzed azidation protocol displays good chemoselectivity as it takes place preferentially at the secondary and tertiary benzylic C(sp³)−H bonds over the primary benzylic and tertiary aliphatic carbons. Efforts on the development of catalytic enantioselective processes are also documented.