Synthesis of Plakortolides E and I Enabled by Base Metal Catalysis

A protecting-group-free synthesis of two endoperoxide natural products, plakortolide E and plakortolide I, is reported. Key-steps feature the use of earth-abundant transition metals, consisting of a vanadium-mediated epoxidation, an iron-catalyzed allylic substitution, and a cobalt-induced endoperoxide formation. Our approach combines redox-economy, chemoselective bond-forming reactions, and telescoping into one-pot operations to forge an overall efficient synthesis.