Concise Total Synthesis of the Cage-Like Sesquiterpenoid (+)-Daphnepapytone A

ABSTRACT: We report the first total synthesis of (+)-daphnepapytone A, an unprecedented member of the guaiane-derived sesquiterpenoids, and several related guaiane-derived natural products including diarthroncha C, daphnenicillata W, and oleodaphnone. Our first-generation strategy was thwarted by an unsuccessful late-stage biomimetic [2+2] cycloaddition, however our second-generation de novo approach provided expedient access to the tetracyclic core of daphnepapytone A through an intramolecular allenyl thermal [2+2] cycloaddition and a cage-like Pauson–Khand reaction with a labile cyclobu-tane.