Manganese-catalyzed benzylic C(sp(3))–H amination for late-stage functionalization

Reactions that directly install nitrogen into C–H bonds of complex molecules are significant because of their potential to change the chemical and biological properties of a given compound. Although selective intramolecular C–H amination reactions are known, achieving high levels of reactivity, while maintaining excellent site-selectivity and functional-group tolerance, remains a challenge for intermolecular C–H amination. Herein, we report a manganese perchlorophthalocyanine catalyst [Mn(III)(ClPc)] for intermolecular benzylic C–H amination of bioactive molecules and natural products that proceeds with unprecedented levels of reactivity and site-selectivity. In the presence of Brønsted or Lewis acid, the [Mn(III)(ClPc)]-catalyzed C–H amination demonstrates unique tolerance for tertiary amine, pyridine and benzimidazole functionalities. Mechanistic studies suggest that C–H amination likely proceeds through an electrophilic metallonitrene intermediate via a stepwise pathway where C–H cleavage is the rate-determining step of the reaction. Collectively these mechanistic features contrast previous base-metal catalyzed C–H aminations and provide new opportunities for tunable selectivities.