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

Treatment of phthalan derivatives with -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 EtAlCl in the presence of allyltrimethylsilane, and the conversion to Rice's intermediate completed a formal synthesis of (±)-morphine.