Electrochemical Site-Specific Dehydrogenative Hydroxyalkylation of Purine Nucleosides with Alcohols.

An electrochemical protocol for C6-selective hydroxyalkylation of purine nucleosides with alcohols via direct C(sp2)-C(sp3) cross-coupling was established. The protocol employed N-Hydroxyphthalimide (NHPI) as a hydrogen atom transfer mediator, yielding C6-hydroxyalkyl purine nucleosides in moderate to excellent yields. This electrochemical method is distinguished by its mild oxidant-free conditions, good regioselectivity, readily available raw materials, and validity for the late-stage modification of bioactive molecules. Mechanistic studies suggested that the reaction proceeded via an electro-generated α-hydroxyalkyl radical.