Total Synthesis of Isodaphlongamine H by Iridium‐Catalyzed Reductive [3+2] Cycloaddition of N‐Hydroxylactam

The total synthesis of isodaphlongamine H based on a lactam strategy, which enables quick access to complex cyclic amines, is described. The strategy begins with alkylation of a chiral lactam and subsequent N‐oxidation via an imino ether to afford the N‐hydroxylactam. For the key transformation to functionalize the amide carbonyl, an iridium‐catalyzed reductive [3+2] cycloaddition of the N‐hydroxylactam provides a tricyclic isoxazolidine in a one‐pot process. After the coupling reaction with an allylic silane fragment, the total synthesis is accomplished through intramolecular Hosomi‐Sakurai allylation to construct a pentacyclic core. The deoxygenated pentacyclic intermediate shows higher cytotoxicity against HeLa and U937 cell lines than isodaphlongamine H, and might become a lead compound for further biological study.