Two-step conversion of uridine and cytidine to variously C5-C functionalized analogs

C5-substituted pyrimidine nucleosides are an important class of molecules that have practical use as biological probes and pharmaceuticals. Herein we report an operationally simple protocol for C5-functionalization of uridine and cytidine via transformation of underexploited 5-trifluoromethyluridine or 5-trifluoromethylcytidine, respectively. The unique reactivity of the CF 3 group in the aromatic ring allowed the direct incorporation of several distinct C5-C "carbon substituents": carboxyl, nitrile, ester, amide, and amidine. 5-CF 3 -pyrimidine ribo nucleosides offer rapid, efficient and scalable C5 heteronucleobase functionality with carboxyl, nitrile, ester, amide and amidine groups.