Unusual Radical 6-endo Cyclization to the Carbocyclic-ENA and Elucidation of its Solution Conformation by 600 MHz NMR and ab initio Calculations
2008 (English)In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 6, no 24, 4627-4633 p.Article in journal (Refereed) Published
In our previous paper (J. Am. Chem. Soc., 2007, 129, 8362), we reported the synthesis of 7'-Me-Carba-LNA and 8'-Me-Carba-ENA thymidine through 5-hexenyl or 6-heptenyl radical cyclization. Both 5-hexenyl and 6-heptenyl radical cyclized exclusively in the exo form, giving unwanted exocyclic C7'-methyl group. In the present study, we showed that the regioselectivity of the 5-hexenyl radical cyclization could be favorably tuned by introduction of a hydroxyl group beta to the olefinic double bond, yielding about 9% of the 6-endo cyclization product. Possible pathways to give 6-endo cyclization product 9 compared to the intermediates responsible to give the 5-exo cyclization product 5 has been discussed. Based on this unique 6-endo cyclization strategy, a carbocyclic ENA modified thymidine (carba-ENA) has been successfully synthesized, which also enabled us to perform its full solution conformation analysis by using NMR (H-1 at 600 MHz) observables for the first time
Place, publisher, year, edition, pages
2008. Vol. 6, no 24, 4627-4633 p.
IdentifiersURN: urn:nbn:se:uu:diva-106716DOI: 10.1039/b813870bISI: 000261744900021OAI: oai:DiVA.org:uu-106716DiVA: diva2:225923