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 N-6 and N-2 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. (C) 2002 Elsevier Science B.V. All rights reserved.