Achmatowicz rearrangement-enabled unified total syntheses of (+)-passifetilactones A–C

In this manuscript, we report the enantio- and diastereoselective total synthesis of three cytotoxic 2-pyrone-derived natural products passifetilactones A-C. Our strategy leverages a unified synthetic approach that originates from simple furan-based building blocks. Key transformations include the Corey-Bakshi-Shibata (CBS) reduction to access chiral furan-derived alcohol, NBS-mediated Achmatowicz rearrangement to construct the α-hydroxy-<i>δ</i>-pyrone core, followed by a highly stereoselective, iridium-catalyzed dynamic kinetic intramolecular redox isomerization to access the <i>δ</i>-hydroxy-α-pyrone framework. This streamlined route enables efficient access to passifetilactones A, B, and C in 13, 5, and 8 steps, with overall yields of 12%, 54%, and 37%, respectively.