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.