Transition-Metal-Mediated Direct C–H Amination of Hydrocarbons with Amine Reactants: The Most Desirable but Challenging C–N Bond-Formation Approach

Abstract

Cross-dehydrogenative couplings (CDCs) have become one of the most straightforward protocols in the C–H bond functionalizations, showing step- and atom-efficiency without need of prefunctionalization of substrates and reactants. However, catalytic C–H amination procedures based on the CDC strategy by employing amine reactants are considered to be challenging mainly due to the highly nucleophilic character of parent amines to inhibit the catalytic turnovers and the difficulty in optimizing proper oxidative conditions. In spite of these concerns, recent efforts have led to notable advances in the C–H amination procedures, particularly in the intermolecular reaction system. In this Perspective, we address the recent achievements in the transition-metal-mediated CDC amination reactions with two types of hydrocarbon substrates: (i) direct amination of acidic C–H bonds with parent amines and (ii) chelation-assisted CDC amination/amidation of nonacidic C–H bonds. Mechanistic aspects are also briefly delineated in representative amination reactions to provide insights for the future development of highly practical and more environmentally benign processes.