Synthesis of C6-Substituted Purine Nucleoside Analogues via Late-Stage Photoredox/Nickel Dual Catalytic Cross-Coupling

Nucleoside analogues have been and continue to be extremely important compounds in drug discovery. Despite the significant effort dedicated to their synthesis, medicinal chemistry campaigns around these structures are often hampered by synthetic challenges. We describe a strategy for the functionalization of purine nucleosides via photoredox and nickel-catalyzed sp²-sp³ cross-coupling. The conditions described herein allow for coupling of unprotected nucleosides with readily available alkyl bromides, providing opportunities for their application to parallel medicinal chemistry.