A Concise Synthesis of Pleurotin Enabled by a Nontraditional C–H Epimerization

Abstract

An 8-step synthesis of a known pentacyclic intermediate towards the natural product pleurotin (1) is described. Pleurotin and related benzoquinone natural products are of great interest for their powerful anticancer and antibiotic activities. The route features a regio- and diastereoselective intermolecular Diels-Alder cycloaddition and an alkoxy-radical-induced HAT-mediated C–H epimerization to construct pleurotin’s carbon framework with appropriate relative stereochemical relationships. The synthesis concludes with a ring-forming benzylic C–H oxidation to deliver oxepane 19.