Nitrogen-Centered Radicals in Functionalization of sp² Systems: Generation, Reactivity, and Applications in Synthesis

The chemistry of nitrogen-centered radicals (NCRs) has plentiful applications in organic synthesis, and they continue to expand as our understanding of these reactive species increases. The utility of these reactive intermediates is demonstrated in the recent advances in C-H amination and the (di)amination of alkenes. Synthesis of previously challenging structures can be achieved by efficient functionalization of sp² moieties without prefunctionalization, allowing for faster and more streamlined synthesis. This Review addresses the generation, reactivity, and application of NCRs, including, but not limited to, iminyl, aminyl, amidyl, and aminium species. Contributions from early discovery up to the most recent examples have been highlighted, covering radical initiation, thermolysis, photolysis, and, more recently, photoredox catalysis. Radical-mediated intermolecular amination of (hetero)arenes can occur with a variety of complex amine precursors, generating aniline derivatives, an important class of structures for drug discovery and development. Functionalization of olefins is achievable in high anti-Markovnikov regioselectivity and allows access to difunctionalized structures when the intermediate carbon radicals are trapped. Additionally, the reactivity of NCRs can be harnessed for the rapid construction of N-heterocycles such as pyrrolidines, phenanthridines, quinoxalines, and quinazolinones.