Radical approaches for C(sp3)–N bond cleavage in deaminative transformations

Abstract

Amines are versatile and widely available functional groups that serve as key building blocks in organic synthesis, particularly in pharmaceutical development. The deaminative functionalization of amines, where the C–N bond of amine is cleaved to function as a carbon source of the reaction, could be very useful for building the carbon framework of organic molecules. Conventional methods for C(sp³)–N bond cleavage often rely on two-electron ionic pathways or transition metal catalysis, which typically require activated amines or toxic reagents, limiting their broad applicability. In contrast, radical-based approaches provide a promising alternative, utilizing homolytic C–N bond cleavage to generate carbon-centered radicals that can participate in a range of transformations. These methods offer complementary substrate scopes and unique reactivity profiles, expanding the synthetic utility of amines. This review summarizes recent advancements in radical-mediated deaminative transformations, focusing on the mechanisms, substrate compatibility, and emerging applications in synthetic organic chemistry.