Expanding Terpenoid Chemical Space Through Radical‐Mediated Remodeling of the 4‐nor‐(3 <i>Z</i> ,7 <i>E</i> )‐Neodolabellane Framework

We report the bioinspired divergent syntheses of sp³-rich polycyclic frameworks from a structurally modified neodolabellane precursor. The designed bicyclo[9.3.0]tetradeca-3,7-diene intermediate differs from natural neodolabellane in that it possesses a (3Z,7E) moiety and lacks a C4 methyl substituent, yet retains the core architecture necessary for transannular cyclization. This unnatural 4-nor (3Z,7E)-neodolabellane-type scaffold was synthesized via a photocatalytic tandem Ueno-Stork cyclization/intermolecular Giese-addition sequence that establishes a cyclopentane ring bearing four contiguous stereocenters, followed by ring-closing metathesis that constructs the rigid 11-membered ring. Radical-mediated transannular reactions proved to be highly effective. A low-valent-titanium-mediated reductive epoxide ring-opening reaction provided the neo-fusicoccane-type 5/8/5 skeleton, whereas iron-hydride-mediated reductive olefin coupling afforded the non-natural 5/8/5 skeleton in high yield. This study demonstrated that subtly structurally modified terpenoid frameworks enable divergent skeletal remodeling, theeby expanding the chemical space accessible from biosynthetically relevant scaffolds.