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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(1)

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(1)

Abdalla E. A. Hassan, Naozumi Nishizono, Noriaki Minakawa, Satoshi Shuto, Akira Matsuda

J Org Chem. 1996 Sep 6;61(18):6261-6267.

PMID: 11667465

Abstract:

The Wittig reaction of 1-[3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-beta-D-erythro-pentofuranos-2-ulosyl]uracil (6) with Ph(3)P=CHCN afforded (Z)-2'-cyanomethylene derivative 7 exclusively. 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 oxidative syn-elimination of the resulting adduct. The diastereofacial selectivity of the benzenethiolate addition to the cyanomethylene moiety was found to be influenced by participation of the 2-carbonyl group at the base moiety and steric hindrance of the sugar protecting groups. Although nucleophilic addition reactions at the 2'-position of 6 have 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 CH(2)Cl(2) or with LiSPh in the presence of Mg(ClO(4))(2) in THF. On the other hand, when (Z)-2'-(cyanomethylene)-5'-O-triisopropylsilyl derivative 10 was treated with LiSPh, the alpha-phenylthio derivative 13 was obtained predominantly (89:11). Oxidation of 8 with m-chloroperbenzoic acid (m-CPBA) in CH(2)Cl(2) and pyrolysis of the resulting sulfoxides afforded the (Z)-isomer 7 exclusively. Treatment of 13 with m-CPBA under the same conditions afforded the desired (E)-cyanomethylene derivatives 18 as a major product (E:Z = 14:1) in good yield. Deprotection of 18 by the standard procedures furnished (E)-2'-(cyanomethylene)-2'-deoxyuridine (5).

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
LS7931178	1-(triisopropylsilyl)pyrrole-3-boronic acid			Price

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