Synthesis of the isocoumarin portion of the rubromycins

A synthesis of the isocoumarin found in the rubromycin class of natural products is reported. The isocoumarin ring system is formed via Heck coupling of a pyruvate synthon with a terephthalic acid derivative followed by an intramolecular acid-catalyzed cyclization. The requisite terephthalic acid precursor is generated by carboxylation of catechol and then desymmetrization of the aromatic ring by halogenation. The isocoumarin derivative that has been produced is an appropriate precursor for the synthesis of γ-rubromycin, purpuromycin, and heliquinomycin.