Electrochemically driven nickel catalysis for formal C–H amination

Abstract

The C–H amination of arenes represents a streamlined approach to arylamines, yet most existing methods rely on preactivated nitrogen reagents or directing groups, limiting practicality and substrate scope. Herein, we report a nickel-catalyzed electroreductive formal C–H amination of aryl bromides with secondary amines, enabling efficient access to 4-bromomorpholinobenzene derivatives. This halogen-enabled strategy allows formal C–H amination through transient bromine removal and reinstallation. The reaction employs electricity as a traceless redox reagent, proceeds under mild conditions without stoichiometric chemical oxidants, and exhibits broad functional group tolerance. Mechanistic studies suggest that the transformation involves electrochemically generated Ni(0) species and nitrogen-centered radicals, followed by nickel-mediated C–N bond formation and subsequent bromination. The synthetic utility of this protocol is demonstrated by gram-scale reactions, diverse downstream transformations, and a concise synthesis of the pharmaceutically relevant scaffold Entospletinib.