Selective alkylation of pyrimidyl dianions II: synthesis, characterization, and comparative reactivity of 3′, 5′-o-bis- tetrahydropyranyl, trimethylsilyl and tert-butyldimethylsilyl derivatives of 5-bromo-2′-deoxyuridine

Three compounds which can be used as precursors for thymidine synthesis via methylation at the 5 position, including 3′, 5′-o-bis(tetrahydropyranyl)-5-bromo-2′-deoxyuridine 1a, 3′, 5′-o-bis-(trimethylsily)-5-bromo-2′-deoxyuridine 1b, and 3′, 5′-o-bis-(t-butyldimethylsilyl)-5-bromo-2′-deoxyuridine 1c, were prepared, isolated and characterized by spectroscopic methods. Alkylation with methyl iodide using an organo-lithium reagent at low temperature produced 72%, 41% and 74% of thymidine 6, respectively. Tetrahydropyranyl and t-butyldimethylsilyl ethers are found to be better precursors for introduction of a methyl group at the 5 position.