Suzuki-Miyaura cross-coupling of haloaromatic compounds with arylboronic acids provides a simple entry to biaryl systems. Despite its ease, to date, there are no detailed investigations of this procedure for deoxynucleoside modification. As shown in this study, a wide variety of C-6 arylpurine 2'-deoxyriboside (C-6 aryl 2'-deoxynebularine analogues) and C-2 aryl 2'-deoxyinosine analogues can be conveniently prepared via the Pd-mediated cross-coupling of arylboronic acids with the C-6 halonucleosides, 6-bromo- or 6-chloro-9[2-deoxy-3,5-bis-O-(tert-butyldimethylsilyl)-beta-D-erythro-pentofuranosyl]purine (1 and 2), and the C-2 halonucleoside, 2-bromo-O(6)-benzyl-3',5'-bis-O-(tert-butyldimethylsilyl)-2'-deoxyinosine (3). Although bromonucleoside 1 proved to be a good substrate for the Pd-catalyzed Suzuki-Miyaura cross-couplings, we have noted that for several C-6 arylations, the chloronucleoside 2 provides superior coupling yields. Also described in this study is a detailed evaluation of catalytic systems that led to optimal product recoveries. Finally, a comparison of the C-C and C-N bond-forming reactions of deoxynucleosides is also reported. On the basis of this comparison, we provide evidence that C-N bond formation at the C-6 position, leading to N-aryl 2'-deoxyadenosine analogues, is more sensitive to the ligand used, whereas C-C bond-forming reactions at the same position are not. In contrast to the ligand dependency exhibited in C-N bond formation at the C-6 position, comparable reactions at the C-2 position of purine deoxynucleosides proceed with less sensitivity to the ligand used.