Regioselective O- and N-Alkylation of Pyrimidine Nucleosides via the Mitsunobu Reaction

Significance

The influence of the N3-substituent on the N1- versus O²- ambident alkylation regio­selectivity of thymines 1 via the Mitsunobu reaction is reported. When N3-3,5-dinitrobenzoyl thymine was used as a nucleophile, alkylation proceeded with high N1-regioselectivity but in moderate chemical yield; alternatively, the N3-benzyl­oxymethyl group provides the product with good N1-regio­selectivity in high yield. For O²-alkylation, the N3-2,6-dimethylbenzoyl group affords the O²-isomer exclusively in good yield.