Total Synthesis of Longeracinphyllin A.

The first and asymmetric total synthesis of longeracinphyllin A, a hexacyclic Daphniphyllum alkaloid, has been accomplished. A tetracyclic intermediate was prepared through silver-catalyzed alkyne cyclization and Luche radical cyclization. A phosphine-promoted [3 + 2] cycloaddition reaction was exploited to construct the sterically congested E ring bearing vicinal tertiary and quaternary centers. The cyclopentenone motif was assembled by using intramolecular Horner-Wadsworth-Emmons olefination. Raney Ni reduction delivered the tertiary amine from a thioamide precursor at a late stage.