Stereoselective synthesis and conformational analysis of aromatic C‐thionucleosides

Abstract

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

Synthetic Routes to Chiral Nonracemic and Racemic Dihydro- And Tetrahydrothiophenes

“…A tandem annulation strategy featuring the use of both carbon–sulfur and carbon–carbon bond ring-forming reactions was deployed to the synthesis of polysubstituted thiophanes. Thus, a one-pot, base-catalyzed thia-Michael/cyclization sequence between ethyl 2-mercaptoacetate 503 and trans -cinnamaldehyde 280 provided the four diastereomeric racemates 504 – 507 (Scheme ) …”