Terpenoid Synthesis via Convergent Radical Annulation

The development of a convergent radical annulation strategy for the synthesis of complex terpenoids from sclareolide is disclosed. This approach employs a 1,3-diradical synthon to enable rapid C-ring annulation through inter- and intramolecular radical couplings, exemplified in the concise syntheses of serratene and cyclodammarane scaffolds from a common intermediate. Key features include a rapid alternating polarity (rAP) Kolbe electrolysis for onoceradiene assembly, a Co-electrocatalytic metal-catalyzed hydrogen atom transfer (MHAT) 7-endo-trig cycloisomerization─the first of its kind─to form the serratene core, and a tandem Fe-mediated reductive olefin coupling/enolate alkylation cascade─also unprecedented─to forge the [4.3.1] propellane motif of cyclodammaranes with complete diastereocontrol over three contiguous quaternary centers. These routes, completed in 5–9 steps, maximize skeletal bond-forming efficiency, feature unique radical cascades, and highlight the advantages of radical-based disconnections in terpenoid synthesis.