Visible-light-induced glycosyl radicals from diverse precursors for C-glycosylation

C-Glycosides are crucial structural motifs in drug discovery and biology due to their enhanced metabolic stability and resistance to enzymatic hydrolysis compared to their O-glycoside counterparts. The synthesis of these molecules often relies on the generation of glycosyl radicals as key intermediates for forging C-C bonds at the anomeric center. In this context, visible-light photoredox catalysis has emerged as a transformative platform, enabling the mild, selective, and sustainable generation of glycosyl radicals from a diverse array of bench-stable precursors. This review provides a comprehensive, precursor-centric overview of this rapidly evolving area. Distinct from prior reviews that are conducted based on the reaction type or product class, we systematically categorize and critically evaluate glycosyl radical precursors according to their activation mechanisms: (1) reductively activated precursors (glycosyl halides, glycosyl NHPI redox-active esters and TFPy thioglycosides), (2) oxidatively activated precursors (glycosyl carboxylic acids, 1,4-dihydropyridine (DHP) derivatives, glycosyl sulfonates and trifluoroborates), and (3) precursors activated via electron donor-acceptor (EDA) complexes or energy transfer (glycosyl sulfides, sulfoxides, and sulfones). For each class, we discuss the mechanistic pathways, critically assess their respective advantages and limitations in terms of stability, accessibility, functional group tolerance, and stereoselectivity, and highlight innovative applications in constructing complex C-glycosides.