An efficient synthesis of peri-hydroxy aromatic compounds via a strong-base-induced [4+2] cycloaddition of homophthalic anhydrides with enolizable enones

An efficient synthesis of peri-hydroxy aromatic compounds has been accompli shed via a strong-base-induced [4+2] cycloaddition of homophthalic anhydrid es with a-sulfinyl-substituted derivatives of enolizable enones. The unsubs tituted enones did not undergo an efficient [4+2] cycloaddition reaction wi th homophthalic anhydrides, presumably due to their enolization under the b asic reaction conditions. The sulfinyl group not only promotes the cycloadd ition reaction but also undergoes in situ elimination under the reaction co nditions to afford the peri-hydroxy aromatic compounds ina single step. The application of this methodology for the synthesis of a key intermediate of antitumor antibiotic fredericamycin A is described. PM3 calculations of va rious 2-substituted cyclopentenones as well as the mechanism of the cycload dition are also discussed.