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

Abstract

An 8-step synthesis of a known pentacyclic intermediate toward the natural product pleurotin (<b>1</b>) 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 photoenolization/Diels-Alder cycloaddition and an alkoxy-radical-induced hydrogen atom transfer-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 <b>19</b>.