In recent years, there has been a resurgence of interest in the synthesis of purine derivatives due to the discovery of purine-derived ligands for a variety of nucleotide dependent enzymes. The majority of chemistry has focused on substitution of the purine core structure by alkylation at N9 and nucleophilic-aromatic substitution reactions at C2 and C6. Here we report the syntheses of aryl, N-aryl, O-aryl substituted purine libraries by the palladium-mediated coupling of boronic acids, anilines or phenols at the C2 position, and copper(II)-mediated N-arylation with boronic acids at the N9 position. The chemistry described here greatly expands our ability to introduce different functionality and create new purine scaffolds. © 2001 Published by Elsevier Science Ltd.