Revision of absolute configuration of enantiomeric (methylenecyclopropyl)carbinols obtained from (R)-(-)- and (S)-(+)-epichlorohydrin and methylenetriphenylphosphorane. Implications for reaction mechanism and improved synthesis of antiviral methylenecyclopropane analogues of nucleosides

J Org Chem. 2002 Jan 11;67(1):286-9. doi: 10.1021/jo010511j.

Abstract

Absolute configurations of enantiomeric methylenecyclopropanecarbinols obtained by reaction of (R)- and (S)-epichlorohydrin 5 with methylenetriphenylphosphorane or resolution of the corresponding oxaphospholane 6 via a salt with L-(+)-tartaric acid and subsequent Wittig transformation with formaldehyde were revised. The (-)-oxaphospholane 6 has the S,S and (-)-(methylenecyclopropyl)carbinol (4) the R configuration. The configurations of (+)-6 and (+)-4 are then R,R and S, respectively. These assignments are in accord with an initial attack of phosphorane at the oxirane ring of epichlorohydrin. An improved preparation of key enantiomeric intermediates (R)-1a and (S)-1a, important for synthesis of antiviral purine methylenecyclopropane analogues of nucleosides, is also described.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenine / analogs & derivatives*
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Cyclopropanes / chemistry*
  • Epichlorohydrin / chemistry
  • Methanol / analogs & derivatives*
  • Methanol / chemistry*
  • Molecular Structure
  • Nucleosides / chemistry
  • Phosphoranes / chemistry
  • Stereoisomerism

Substances

  • Antiviral Agents
  • Cyclopropanes
  • Nucleosides
  • Phosphoranes
  • Epichlorohydrin
  • Adenine
  • Methanol