Stereoselective synthesis and conformational analysis of aromatic C-thionucleosides

Tetrahydrothiophene derivatives 2a–2d, which are useful intermediates in the synthesis of C-thionucleosides, were obtained by a tandem strategy that involves the base-catalyzed conjugate addition of ethyl 2-mercaptoacetate to trans-cinnamaldehyde followed by cyclization. The solvent and the nature of the amine used as Lewis base influence the stereo- selectivity of the reaction. The reduction of each isolated derivative 2a–2d was performed with LiAlH4 to afford C-thionucleosides 3a–3d. The configuration and conformation of each diastereomer 2a–2d and 3a–3d was assigned by means of the analysis of vicinal proton–proton coupling constants. The X-ray structure of 2d, 3a, and 3b confirmed the configuration assigned to each isomeric tetrahydrothiophenes. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:289–298, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20205