Synthesis of C-Heteroaryl Nucleosides via Deoxygenative Arylation

C-Aryl nucleosides are medicinally valuable due to their enhanced metabolic stability achieved by replacing a labile C-N bond with a C-C bond to nucleobases. Herein, a direct metallaphotoredox deoxygenative arylation to access heteroaryl C-nucleosides is described. Leveraging high-throughput experimentation, a pyridine-carboxamidine nickel precatalyst was identified as being optimal for cross-coupling with various heteroaryl bromides. Additionally, a range of modified ribose and glucose derivatives were evaluated, demonstrating the broad applicability of this transformation for the rapid synthesis of structurally diverse C-nucleosides.