Site- and Enantioselective Manganese-Catalyzed Benzylic C–H Azidation of Indolines

A manganese-catalyzed highly site- and enantioselective benzylic C–H azidation of indolines has been described. The practical method is applicable for azidation of a tertiary benzylic C–H bond with good functional group tolerance, allowing facile access to structurally diverse tertiary azide-containing indolines in high efficiency with excellent site-, chemo-, and enantioselectivity. The generality of the method was further demonstrated by site- and enantioselective azidation of the secondary benzylic C–H bond for a range of secondary azide-containing indolines. The benzylic C–H azidation method allows to straightforwardly and enantioselectively install a variety of nitrogen-based functional groups and diverse bioactive molecules at the C3 position of indoline frameworks through post-azidation manipulations. Gram-scale synthesis was also demonstrated, further highlighting the synthetic potential of the method. Mechanistic studies by combined experiments and computations elucidated the reaction mechanism and origins of stereoselectivity.