Concise Syntheses of Harziane Diterpenoids by Merging Local Desymmetrization and Radical Retrosynthesis

Harziane diterpenoids possess a highly caged 6/5/7/4 core framework and four contiguous stereocenters, including two quaternary ones, and present significant challenges to chemical synthesis. Herein, we report an efficient strategy to rapidly access harziane diterpenoids by merging local desymmetrization and radical retrosynthesis. The strained bicyclo[5.2.0]nonene motif was installed using a local desymmetrizing intramolecular aldol reaction with high diastereotopic group selectivity, while the bridged [3.2.1] ring system and three contiguous stereocenters were rapidly forged by means of three strategic radical fragment couplings, i.e., Baran reductive olefin coupling, photocatalytic deoxygenative alkylation, and acyl radical cyclization.