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

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 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).