Total Synthesis of Astellatol.

Abstract: A nearly‐30‐year‐old unanswered synthetic puzzle, astellatol, has been solved in an enantiospecific manner. The highly congested pentacyclic skeleton of this rare sesterterpenoid, which possesses a unique bicyclo[4.1.1]octane motif, ten stereocenters, a cyclobutane that contains two quaternary centers, an <italic>exo</italic>‐methylene group, and a sterically encumbered isopropyl <italic>trans</italic>‐hydrindane motif, makes astellatol arguably one of the most challenging targets for sesterterpenoid synthesis. An intramolecular Pauson–Khand reaction was exploited to construct the right‐hand side scaffold of this sesterterpenoid. An unprecedented reductive radical 1,6‐addition, mediated by SmI₂, forged the cyclobutane motif. Last, a strategic oxidation/reduction step provided not only the decisive solution for the remarkably challenging late‐stage transformations, but also a highly valuable unravelling of the notorious issue of <italic>trans</italic>‐hydrindane synthesis. Importantly, the synthesis of astellatol showcases a rapid, scalable strategy to access diverse complex isopropyl <italic>trans</italic>‐hydrindane sesterterpenoids. [ABSTRACT FROM AUTHOR]