An Efficient Synthesis of peri-Hydroxy Aromatic Compounds via a Strong-Base-Induced [4+2] Cycloaddition of Homophthalic Anhydrides with Enolizable Enones

Abstract

An efficient synthesis of peri-hydroxy aromatic compounds has been accomplished via a strong-base-induced [4+2] cycloaddition of homophthalic anhydrides with alpha-sulfinyl-substituted derivatives of enolizable enones. The unsubstituted enones did not undergo an efficient [4+2] cycloaddition reaction with homophthalic anhydrides, presumably due to their enolization under the basic reaction conditions. The sulfinyl group not only promotes the cycloaddition reaction but also undergoes in situ elimination under the reaction conditions to afford the peri-hydroxy aromatic compounds in a single step. The application of this methodology for the synthesis of a key intermediate of antitumor antibiotic fredericamycin A is described. PM3 calculations of various 2-substituted cyclopentenones as well as the mechanism of the cycloaddition are also discussed.