Syntheses of C-6 Aryl- and Alkynyl-Substituted Thymidines from Thymidine trans-5,6-Bromohydrins

C-6-substituted thymidines are biochemically important compounds. The thymidine (6-4) photoproduct [i.e., 5-hydroxy- 6-(thymidine-4-yl) dihydrothymidine], in particular, is a DNA lesion that is triggered by the UV irradiation of sunlight. Herein, we report a metal-free cis-diastereoselective ring opening of thymidine 5,6-epoxides by using mildly nucleophilic organofluoroborates in the presence of BF3 center dot Et2O to provide facile access to (6-4) photoproduct analogues. A broad range of aryl and alkynylfluoroborates are compatible with the reaction conditions, which also tolerate various protecting groups. Furthermore, the epoxide addition products can undergo a thionyl chloride/pyridine promoted dehydration process to give the respective pharmaceutically attractive C-6-substituted thymidines in high yields, thus providing a new and straightforward method for their synthesis.