Synthesis of Racemic Frenolicin via Organochromium and Organopalladium Intermediates

A synthesis of the natural quinone antibiotic frenolicin has been completed. Crucial steps include nucleophilic addition/oxidation with an arene-chromium complex to produce a 2,3-disubstituted anisóle derivative and intramolecular alkoxy-carbonylation of an alkene to form the substituted pyran ring. The palladium-catalyzed alkoxy-carbonylation procedure is shown in models to be effective with disubstituted double bonds, giving stereochemical control in formation of adjacent chiral centers. While the pyran synthesis in this case produces the unnatural cis arrangement of substituents, a deprotection and equilibration procedure with boron tribromide generates the natural trans configuration.