Asymmetric C–H Amination via Fe(III)-Metalloradical Catalysis Featuring α-Fe(IV)-Aminyl Radicals as Key Intermediates

Metalloradical catalysis (MRC) offers a general mechanistic platform for controlling the reactivity and selectivity of homolytic radical reactions. While Co(II)-based d⁷-metalloradical catalysts have dominated the field, we introduce here an Fe(III)-based d⁵-metalloradical system that is highly effective for asymmetric C-H amination. In particular, we reveal that five-coordinate Fe(III) complexes of porphyrins with an axial ligand, a family of stable 15e-metalloradicals, are potent metalloradical catalysts for 1,5-C(sp³)-H amination of aryl azides. Leveraging a specially designed <i>D</i>₂-symmetric chiral amidoporphyrin ligand, this Fe(III)-based metalloradical system enables the homolytic activation of various aryl azides for the intramolecular amination of diverse C(sp³)-H bonds, allowing for the high-yielding construction of chiral indolines with excellent enantioselective control. Notably, this process operates without light or additional additives and generates N₂ as the sole byproduct. Through comprehensive experimental investigations and detailed computational studies, we provide compelling evidence in support of the underlying stepwise radical mechanism. The catalytic pathway involves key steps of hydrogen atom abstraction (HAA) and radical substitution (RS), mediated by the initially generated α-Fe(IV)-aminyl radicals and the subsequently formed ε-Fe(IV)-alkyl radicals, respectively.