Nucleosides and nucleotides .156. Chelation-controlled and nonchelation-controlled diastereofacial selective thiophenol addition reactions at the 2'-position of 2'-[(alkoxycarbonyl)methylene]-2'-deoxyuridines: Conversion of (Z)-2'-[(alkoxycarbonyl)methylene]-2'-deoxyuridines into their (E)-isomers

The Wittig reaction of 1-[3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-beta-D-erythro-pentofuranos-2-ulosyl]uracil (4) with Ph(3)P=CHCO(2)R (R = ethyl or tert-butyl) exclusively gave (Z)-2'-[(alkoxycarbonyl)methylene] derivatives 5 and 13, respectively, in high yields. An unusual beta-facial selectivity of thiophenol addition to the 2'-[(alkoxycarbonyl)methylene] moiety of 5 and 13 was observed, and this facial selectivity was found to be influenced by both the thiolate counter cation and the bulkiness of the alkoxy moiety. Treatment of 2'-[(ethoxycarbonyl)methylene] derivative 5 with LiSPh (1.5 equiv) in the presence of PhSH in THF selectively gave 2'beta-(phenylthio) derivative 11 in high yield along with a trace of 2'alpha-(phenylthio) derivative 10. On the other hand, when 2'-[(tert-butoxycarbonyl)methylene] derivative 13 was treated with KSPh in the presence of PhSH in dioxane/DMF, the facial selectivity was reversed to selectively give the 2'alpha-(phenylthio) adduct 14 (alpha:beta, 77:23) in 90% yield. Oxidation of 14 with m-chloroperbenzoic acid in CH2Cl2 and subsequent pyrolysis of the resulting sulfoxides exclusively gave the (Z)-isomer 13 in 92% yield. The oxidative syn-elimination of the (2'R)-2'-[(tert-butoxycarbonyl)methyl]-2'-deoxy-2'-thiophenoxy-5'-(triiso-propylsilyl)uridine (17), which was obtained from 14 in two steps, exclusively gave the desired (E)-[(tert-butoxycarbonyl)methylene] derivatives 18 in 90% yield. Deprotection of 18 gave the (E)-(carboxymethylene)-2'-deoxyuridine (3). The (Z)-(carboxymethylene)-2'-deoxyuridine (2) was synthesized from 13 in a similar manner.