Metal-free, direct acylation of purines to access C6-acylated purine derivatives induced by TBHP via Minisci-type reaction

Abstract

A metal-free C–H functionalization of purines with aldehydes was developed to access C⁶-acylated purines via green radical reactions. Theoretically, there are many competitive reactions due to the three C–H bonds (C²–H, C⁶–H, C⁸–H) in the purine, and the acylation only happens at the purinyl C⁶-position. This method avoids a metal catalyst and provides a green approach to construct C–C (sp²) bonds at the purinyl C⁶-position, while maintaining excellent compatibility with various functional groups. Moreover, the protocol features broad substrate scope and easy scale-up. The transformation of the product demonstrates the significant practical value of the method. The primary mechanism was proposed based on controlled experiments.