Palladium-catalyzed C–N and C–C cross-couplings as versatile, new avenues for modifications of purine 2′-deoxynucleosides

Methods involving palladium-catalysis can be efficiently applied to the relatively labile purine 2′-deoxynucleosidic systems. The net result is the remarkably ready access to new and unusual 2′-deoxyribonucleoside analogs bearing subsitutents on the purine moiety. C–N cross-coupling reactions are particularly attractive for the synthesis of N6 and N2 substituted 2′-deoxyadenosines and 2′-deoxyguanosines, respectively, as well as C-8 modified 2′-deoxyguanosines. CC bond-formation on the other hand, provides access to nucleosides containing hydrophobic hydrocarbon entities. Although the common theme for C–N and C–C cross-coupling is catalysis by Pd, there are substantial differences between the two classes of reactions. Furthermore, there are pronounced differences in reactivity trends at the C-6 position compared to those at the C-2. Optimized reaction conditions for both varieties of transformations can be found whereby novel purine 2′-deoxynucleosides can be readily obtained.