Facile Synthesis of the Tricyclic Core of Daphniphyllum Alkaloid Daphnilongeranin B via Oxidative Nazarov Reaction

ABSTRACT Daphniphyllum alkaloid daphnilongeranin B presents synthetic challenges due to its congested hexacyclic skeleton, seven stereogenic centers, and two vicinal quaternary centers. Recently, we discovered a series of TEMPO + BF 4 − ‐promoted Nazarov reactions and demonstrated their value in the synthesis of five‐membered ring‐containing small molecules and structurally complex natural products. Herein, we report a concise synthesis of its [7‐5‐5] tricyclic core via a 7‐step approach, using commercially available, inexpensive cycloheptenone as the starting material. Key transformations include a Babler‐Dauben rearrangement, an intramolecular aldol condensation, and a pivotal TEMPO⁺BF4 − ‐mediated oxidative Nazarov reaction via an easily synthesized, unfunctionalized tertiary divinyl carbinol (TDC). These results showcase the utility of our mild Nazarov methodology and lay the foundation for the total synthesis of daphnilongeranin B.