Iron-Catalyzed Primary Amination of C(sp3)–H Bonds

Primary amines are privileged molecules in drug development. Yet, there is a noticeable scarcity of methods for directly introducing a primary amine group into the ubiquitous C(sp3)–H bonds within organic compounds. Here, we report an iron-based catalytic system that enables direct primary amination of C(sp3)–H bonds under aqueous conditions and air. Various types of C(sp3)–H bonds, including benzylic, allylic, and aliphatic ones, can be readily functionalized with high selectivity and efficiency. The broad utility of this method has been further verified by late-stage amination of 11 complex bioactive molecules. Mechanistic studies unveil a protonated iron-nitrene complex as the key intermediate for the C–H bond activation. This work extends the toolbox for direct C(sp3)–H functionalizations, opening up new opportunities for late-stage modifications of organic molecules.