A highly site-selective and Markovnikov-type radical C6-H alkylation of purines with alkenes is achieved, allowing fast construction of the C(sp2)-C(sp3) bond at the C-6-position of purines and purine nucleosides using O2 as a green oxidant and alkenes as cheap alkylation reagents. The route was also a radical route to synthesize C6-alkyl-N7-substituted purines with potential steric hindrance between C6-alkyl groups and N7-substituted groups. This reaction is easily scaled up and has excellent functional group compatibility and broad substrate scopes. Moreover, the unstable intermediate was also separated, which was the key evidence for the reaction mechanism.