Light, metal-free regioselective C6-H alkylation of purines and purine nucleosides with alcohols

A metal-, light-free radical alkylation reaction of purines and nucleosides has been achieved with readily available alcohols (1 degrees, 2 degrees, 3 degrees) as the alkyl radical sources enabled by oxalates, which does not need any catalysts, N-2 protection, and protecting groups. Although there are three potential active C(sp(2))-H bonds and four interferential nitrogen atoms in the purine motif, the reaction still shows excellent regioselectivity at C-6-H position and does not face multialkylation problem. Besides, this approach shows broad functional groups tolerance and is scalable to the gram level, which can be applied to late-stage C-H alkylation of purine to synthesize 6-cyclopentyl nebularine with anti-CEM activity, thus demonstrating its utility.

Automated summary

Researchers have achieved metal- and light-free radical alkylation reactions of purines and nucleosides using readily available alcohols and oxalates as alkyl radical sources. The reaction shows excellent regioselectivity and avoids multialkylation problems. It also demonstrates broad functional group tolerance and scalability to gram levels, making it useful for synthesizing 6-cyclopentyl nebularine with anti-CEM activity.