Copper-Catalyzed sp³ C–H Amination

Abstract

Among the transition metals, copper-based catalyst systems enable the widest range of N-containing reagents in C–H amination to allow for the direct incorporation of versatile N-based functionalities via ubiquitous C–H bonds. In addition to nitrene-based approaches involving sulfonyliminoiodinanes (PhI═NSO2R), diverse non-nitrene protocols have been developed that allow for the direct use of organic amides, nitrosoarenes, and hydroxylamines, strained heterocycles such as oxaziridines, acetonitrile, secondary sulfonylamines, and even alkylamines and arylamines. Synthetic, mechanistic, and theoretical studies reveal discrete copper nitrenes [Cu]═NR and copper amides [Cu]–NHR to be key reactive intermediates in C–H amination. Copper-catalyzed sp3 C–H amination is reviewed, connecting catalytic reactivity patterns with likely copper intermediates wherever possible, with the goal to stimulate the further development of C–H functionalization reactions with copper which possess significant sustainability advantages over other contemporary approaches involving noble metals.