Synthesis of the Cyclopentyl Nucleoside (−)-Neplanocin A from D-Glucose via Zirconocene-Mediated Ring Contraction

✍ Scribed by Leo A. Paquette; Zhenjiao Tian; Christopher K. Seekamp; Tony Wang

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: German
• Weight: 288 KB
• Volume: 88
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.200590099

✦ Synopsis

Abstract

Two approaches for the conversion of d‐glucose to (−)‐neplanocin A (2), both based on the zirconocene‐promoted ring contraction of a vinyl‐substituted pyranoside, are herein evaluated (Scheme 1). In the first pathway (Scheme 2), the substrate possesses the α‐d‐allo configuration (see 6) such that ultimate introduction of the nucleobase would require only an inversion of configuration. However, this precursor proved unresponsive to Cp~2~Zr (=[ZrCl~2~(Cp)~2~]), an end result believed to be a consequence of substantive nonbonded steric effects operating in a key intermediate (Scheme 5). In contrast, the C(2) epimer (see 7) experienced the desired metal‐promoted conversion to an enantiomerically pure polyfunctional cyclopentane (see 5 in Scheme 3). The substituents in this product are arrayed in a manner such that conversion to the target nucleoside can be conveniently achieved by a double‐inversion sequence (Scheme 4). Recourse to palladium(0)‐catalyzed allylic alkylation did not provide an alternate means of generating 2.