Catalyst-controlled regioselective Sonogashira coupling of 9-substituted-6-chloro-2,8-diiodopurines

Abstract

An efficient methodology for the regioselective Sonogashira cross-coupling of 9-substituted 2,8-diiodopurines has been developed. Regioselectivity is governed by the nature of the ligand in the palladium catalyst. In general, when catalysts like Pd(PPh₃)₄ containing a monodentate ligand were used, Sonogashira alkynylation was preferred at the C2-I bond (C2-selective product). In contrast, the preferred coupling site was switched from the C2-position to the C8-position by employing catalysts such as Pd₂(dba)₃·CHCl₃ or palladium catalysts having bidentate or electron-rich monodentate phosphine ligands.