A simple and efficient method for synthesis of 5-substituted 2'-deoxyuridine nucleosides using metal-halogen exchange reaction of 5-iodo-2'-deoxyuridine sodium salt.

Treatment of the sodium salt of 2'-deoxy-3', 5'-bis-O-(tert-butyldimethylsilyl)-5-iodouridine (3) with n-BuLi effected regioselective lithiation at the 5-position and the following reaction with various electrophiles afforded 5-substituted 2'-deoxyuridines including 1b, the precursor of stable spin-labeled 1a, in good yields.