A nucleoside carrying a perfluorinated tert-butyl group (4) was prepared by a Sonogashira coupling of 5-iodo-2′-deoxyuridine with 4,4,4-trifluoro-3,3-is(trifluoromethyl)-1-butyne in nearly quantitative yield and subsequently incorporated into DNA oligomers. Thermal denaturation studies showed that 4 had a negligible effect on duplex stabilty when compared to thymidine. Transition from single strand to duplex was monitored by 19 F NMR spectroscopy at micromolar concentrations of oligomers, demonstrating the sensitivity of 4 as an NMR reporter nucleoside.Fluorine has many advantages as a probe for NMR spectroscopy of nucleic acids and other biopolymers.