Stereoselective Synthesis of (Hetero)aryl C-Nucleosides via Mild Decarboxylative Reductive Cross-Electrophile Coupling

C-nucleosides represent an important yet synthetically challenging class of targets in drug discovery. Herein, we report a mild synthesis of (hetero)aryl C-nucleosides via decarboxylative reductive cross-electrophile coupling of ribosyl N-hydroxyphthalimide esters with widely abundant and structurally diverse aryl bromides. This modular approach operates under homogeneous, room temperature conditions, exhibiting broad substrate scope and functional group compatibility across a variety of furanosides and pyranosides. Notably, we demonstrated this methodology in a Parallel Medicinal Chemistry (PMC) workflow to deliver a library of diverse (hetero)aryl C-nucleosides.