Oxidative generation of isobenzofurans from phthalans: application to the formal synthesis of (±)-morphine†‡

Abstract

Treatment of phthalan derivatives with p-chloranil in dodecane in the presence of molecular sieves at 160–200 °C allowed the generation of unstabilized isobenzofurans, which underwent intramolecular Diels–Alder reaction to give endo cycloadducts exclusively. The cycloaddition turned out to be reversible, providing an equilibrium mixture of endo adducts when heating a substrate with a stereocenter on the tether. We also demonstrated the regioselective allylation of an oxygen-bridged cycloadduct upon exposure to EtAlCl₂ in the presence of allyltrimethylsilane, and the conversion to Rice's intermediate completed a formal synthesis of (±)-morphine.