Phosphorylation of ddC and 3TC was efficiently performed on soluble poly(ethylene glycol) support. The corresponding 5' -monophosphate derivatives were obtained by oxidation of the support bound 5' -H-phosphonate intermediates. Then, di- and triphosphorylations were carried out using a carbonyldiimidazole activation step followed by nucleophilic substitution with suitable phosphate salts. Trivalent phosphorus chemistry appeared as a good alternative for monophosphate synthesis of acid-sensitive 2',3' -dideoxynucleosides.