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 -diyl)-beta-D-erythro-pentofuranos-2-ulosyl]ura cil (4) with Ph(3)P=CHCO(2)R (R = ethyl or tert-butyl) exclusively gav e (Z)-2'-[(alkoxycarbonyl)methylene] derivatives 5 and 13, respectivel y, in high yields. An unusual beta-facial selectivity of thiophenol ad dition to the 2'-[(alkoxycarbonyl)methylene] moiety of 5 and 13 was ob served, and this facial selectivity was found to be influenced by both the thiolate counter cation and the bulkiness of the alkoxy moiety. T reatment of 2'-[(ethoxycarbonyl)methylene] derivative 5 with LiSPh (1. 5 equiv) in the presence of PhSH in THF selectively gave 2'beta-(pheny lthio) derivative 11 in high yield along with a trace of 2'alpha-(phen ylthio) derivative 10. On the other hand, when 2'-[(tert-butoxycarbony l)methylene] derivative 13 was treated with KSPh in the presence of Ph SH in dioxane/DMF, the facial selectivity was reversed to selectively give the 2'alpha-(phenylthio) adduct 14 (alpha:beta, 77:23) in 90% yie ld. Oxidation of 14 with m-chloroperbenzoic acid in CH2Cl2 and subsequ ent pyrolysis of the resulting sulfoxides exclusively gave the (Z)-iso mer 13 in 92% yield. The oxidative syn-elimination of the eoxy-2'-thio phenoxy-5'-(triiso-propylsilyl)uridine (17), which was obtained from 1 4 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.