A simple and efficient synthesis of isocoumarins and alkylidenephthalides from 3-(1-hydroxycarbethoxy/alkyl)phthalides with a DEAD/PPh3/TBHP system

A facile and novel approach to the synthesis of 3-carbethoxy-isocoumarins and 3-alkylidenephthalides is described. The methodology employs DEAD/PPh3/TBHP as the reagent system proceeding through unprecedented 1,2-shift intramolecular ring expansion or simple elimination depending upon substituents present on 3-substituted phthalides, with broader substrate scope. This strategy is amply demonstrated in the short synthesis of bioactive molecules such as cytogenin and (Z)-3-butylidene-7-hydroxy-5-methoxyphthalide.