Synthesis Of N~9-(ortho-halogenatedaryl) Purines By N~3-directed Palladium-Catalyzed C-H Activation

The N9-(ortho-substituentedaryl)purine derivatives have attracted extensive attention from medicinal chemists due to the broad bioactivities.Therefore,it's very important to research the synthesis of N9-(ortho-substituentedaryl)purine derivatives:In this papper,a palladium-catalyzed directed halogenation of N9-arylpurines on the ortho-position of the benzene ring was developed byusing purinyl N3 atom as the directing group and NXS(X = B,C)as the halogenation reagents and the oxidant.Finally,23 compounds of N9-(ortho-monohalogenatedaryl)purines were synthesized with moderate to excellent yields.This reaction have an ample substrate scope and high levels of regio-and stereoselectivities.The substrates containing meta-substituents were selectively halogenated at the less encumbered position,however,we did not observe products in cases of ortho-substituents in the phenyl ring as ortho-substituents hindered the formation of the metallacycle.Meanwhile,various dialkylamino groups at the C-6 position were used to block N1 site for catalyst coordination.At last,the control experiment suggested that N3 atom is the main active site for the C-H functionalization of the halogenation in N9-arylpurines.