Solvent-controlled regioselective protection of 5′-O-protected thymidine

This paper describes an efficient procedure for selective 3′-O- or 3-N-protection of 5′-O-tert-butyldimethylsilylthymidine, depending on the use of aprotic polar solvents with low or high dielectric constant, respectively. These syntheses were activated by either ultrasound or microwaves. Several alkyl bromides offer a convenient route to prepare 3′-O- or 3-N-protected and functionalized thymidine derivatives.