Synthesis of 2,4-disubstituted pyrimidin-5-yl C-2′- deoxyribonucleosides by sequential regioselective reactions of 2,4-dichloropyrimidine nucleosides

Article abstract of DOI:10.1002/ejoc.201000164

A new modular synthesis of diverse 2,4-disubstituted pyrimidin-5-yl C-2′-deoxyribonucleosides by sequential regioselective reactions of 2f6-dichloropyrimidm-5-yl C-nucleosides was developed. The intermediate was prepared by the Heck coupling of 2,6-dichloro-5-iodopyrimidine with glycal followed by desilylation and reduction. Its mild nucleophilic substitutions or Fe-catalyzed cross-coupling with MeMgCl proceeded regioselectively at position 4, whereas at elevated temperatures or with excess of MeMgCl, double substitution occurred. The 2-chloro-4-substituted intermediates undergo another substitution or coupling to afford 2,4-disubstituted derivatives.