Synthesis of 2,4-Disubstituted Pyrimidin-5-yl C-2'-Deoxyribonucleosides by Sequential Regioselective Reactions of 2,4-Dichloropyrimidine Nucleosides

0350066 - ÚOCHB 2011 RIV DE eng J - Journal Article
Kubelka, Tomáš - Slavětínská, Lenka - Klepetářová, Blanka - Hocek, Michal
Synthesis of 2,4-Disubstituted Pyrimidin-5-yl C-2'-Deoxyribonucleosides by Sequential Regioselective Reactions of 2,4-Dichloropyrimidine Nucleosides.
European Journal of Organic Chemistry. -, č. 14 (2010), s. 2666-2669. ISSN 1434-193X. E-ISSN 1099-0690
R&D Projects: GA MŠMT LC512; GA AV ČR IAA400550902
Institutional research plan: CEZ:AV0Z40550506
Keywords : C-nucleosides * pyrimidines * cross-coupling
Subject RIV: CC - Organic Chemistry
Impact factor: 3.206, year: 2010

A new modular synthesis of diverse 2,4-disubstituted pyrimidin-5-yl C-2'-deoxyribonucleosides by sequential regioselective reactions of 2,6-dichloropyrimidin-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.
Permanent Link: http://hdl.handle.net/11104/0190161