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 having 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.