Metal-Free, Light-Mediated, Site-Specific, Radical C6-H Alkylation of Purines with Alcohols Intervened by Oxalates without Catalysts

Herein, we report the development of a radical deoxy-functionalization strategy for the direct C-H alkylation of purines and purine nucleosides with alcohols (1 degrees, 2 degrees, 3 degrees) intervened by oxalates under 12 W blue LED irradiation. The reaction shows high regioselectivity at C6-H position of purine and is suitable for N9-, N7-substitued purines. The process accommodates purines and alcohols to deliver a wide range of products (31 examples) in 41-91 % yields, which avoids transition metal catalysts and organometallic reagents, and is not sensitive to moisture and air. Besides, the mild protocol displays broad functional groups tolerance and is easily up scalable to gram scale and can be used for late-stage C-H alkylation of purine to synthesize pharmaceutical 6-cyclopentyl nebularine with anti-CEM activity or natural d-menthol modification.

Automated summary

We developed a radical deoxy-functionalization strategy for direct C-H alkylation of purines and purine nucleosides with alcohols under blue LED irradiation. The reaction exhibited high regioselectivity and broad functional group tolerance. It provided a wide range of products in good yields, avoiding the use of transition metal catalysts and organometallic reagents.