NUCLEOSIDES AND NUCLEOTIDES .151. CONVERSION OF (Z)-2'-(CYANOMETHYLENE)-2'-DEOXYURIDINES INTO THEIR (E)-ISOMERS VIA ADDITION OF THIOPHENOL TO THE CYANOMETHYLENE MOIETY FOLLOWED BY OXIDATIVE SYN-ELIMINATION REACTIONS

The Wittig reaction of -diyl)-beta-D-erythro-pentofuranos-2-ulosyl]ura cil (6) with Ph(3)P=CHCN afforded (Z)-2'-cyanomethylene derivative 7 e xclusively. The (E)-isomer was accessed from its (Z)-isomer through a sequence of addition of thiophenol to the 2'-cyanomethylene moiety of the (Z)-isomer from the alpha-face, selectively, and stereoselective o xidative syn-elimination of the resulting adduct. The diastereofacial selectivity of the benzenethiolate addition to the cyanomethylene moie ty was found to be influenced by participation of the 2-carbonyl group at the base moiety and steric hindrance of the sugar protecting group s. Although nucleophilic addition reactions at the 2'-position of 6 ha ve been well-known to occur from the alpha-face selectively, treatment of 7 with LiSPh in THF unexpectedly afforded a mixture of alpha- and beta-phenylthio derivatives 8 and 9 in almost equal ratio. Furthermore , an unusual beta-facial selective addition was observed on treatments of 7 with PhSAlMe(2) in CH2Cl2 or wit LiSPh in the presence of Mg(ClO 4)(2) in THF. On the other hand, when (Z)-2'-(cyanomethylene)-5'-O-tri isopropylsilyl derivative 10 was treated with LiSPh, the alpha-phenylt hio derivative 13 was obtained predominantly (89:11). Oxidation of 8 w ith m-chloroperbenzoic acid (m-CPBA) in CH2Cl2 and pyrolysis of the re sulting sulfoxides afforded the (Z)-isomer 7 exclusively. Treatment of 13 with m-CPBA under the same conditions afforded the desired (E)-cya nomethylene derivatives 18 as a major product (E:Z = 14:1) in good yie ld. Deprotection of 18 by the standard procedures furnished (E)-2'-(cy anomethylene)-2'-deoxyuridine (5).