Advances in net-1,2-hydrogen atom transfer of oxygen- and nitrogen-centered radicals: mechanisms and applications in...

The selective activation of C(sp³)-H bonds in a molecule possessing multiple inequivalent hydrogens remains a critical challenge in organic synthesis. One method to achieve such activation is via well-explored 1,5-hydrogen atom transfer (HAT) processes of heteroatom-centered radicals. In contrast to 1,5-HAT, the emerging field of heteroatom-centered radical-mediated 1,2-HAT offers a complementary strategy for the selective activation of C-H bonds positioned α to heteroatoms (mostly N and O). In this review, we systematically outline recent progress in O- and N-centered radical net-1,2-HAT pathways, covering mechanisms and synthetic applications under transition-metal catalysis, photoredox, electrochemical, and super-electron-donor (SED) promoted conditions. The core mechanism, involving the translocation of a radical site from a heteroatom to an α-carbon atom, enables subsequent coupling reactions or can be used to initiate cascade reactions. The utility of this strategy is highlighted by its mild conditions, excellent functional group compatibility, and applicability to complex substrates, establishing it as a robust method for heteroatom-directed α-C-H functionalization. The scope, limitations, gaps in the literature and possible future directions are discussed.