Four-Step Synthesis of (±)-Nanolobatolide via Site-Selective Functionalization

Herein, we report a streamlined four-step synthesis of (±)-nanolobatolide, a neuroprotective tetracyclic diterpenoid (5/5/5/7 system), from guaiazulene <i>via</i> dearomatization and precise site-selective functionalization. The sequence features a regioselective Diels-Alder reaction within a polyene framework, followed by selective epoxidation coupled with <i>in situ</i> lactonization. A late-stage, site-selective hydrogenation enabled by cooperative hydrogen atom transfer (cHAT) catalysis further highlights the importance of precise olefin functionalization in achieving structural complexity.