Total Synthesis of (+/-)-Cephanolides B and C via a Palladium-Catalyzed Cascade Cyclization and Late-Stage sp(3) C-H Bond Oxidation

Herein, we report the first total syntheses of complex cephalotaxus diterpenoids cephanolide B and C from commercially available 5-bromo-2-methylanisole. Key to the success of this synthetic route is a palladium-catalyzed cascade cyclization reaction, which allowed us to efficiently forge the 6-5-6 cis-fused tricyclic ring systems found in the entire family of cephalotaxus diterpenoids. Additionally, site-selective late-stage sp(3) C-H bond oxidation served as a key strategic element in the chemical synthesis of cephanolide C.