First stereospecific synthesis of (E)- or (Z)-alpha-fluoroenones via a kinetically controlled Negishi coupling reaction

J Org Chem. 2006 May 26;71(11):4316-9. doi: 10.1021/jo0604787.

Abstract

A highly stereospecific synthesis of (E)- or (Z)-alpha-fluoro-alpha,beta-unsaturated ketones 4, via a kinetically controlled Negishi palladium-catalyzed coupling reaction, was developed, providing an easy and general access to valuable fluorinated intermediates (pharmaceutical, peptide mimic, and so on). The synthesis involved a reaction between E/Z gem-bromofluoroolefins 2 and alkoxyvinylzinc species 6 under controlled reaction temperature. At 10 degrees C, (Z)-4 (70 to 99% yields) was obtained along with unreacted (Z)-2 (66 to 99% yields). At THF reflux, the recovered olefin was transformed into (E)-4 (up to 98% yield).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fluorine / chemistry*
  • Hydrocarbons / chemistry*
  • Kinetics
  • Molecular Structure

Substances

  • Hydrocarbons
  • Fluorine