Anion cascade reactions III: Synthesis of 3-isoquinuclidone bridged polycyclic lactams

Abstract

Bridged polycyclic lactams are important structural units in organic functional materials, natural products, and pharmaceuticals. A flexible and efficient anion cascade reaction was developed for the preparation of bridged polycyclic lactams from readily available malonamides and 1,4‑dien-3-ones. Various highly substituted bridged polycyclic lactams were synthesized in good to excellent yields by tandem nucleophilic sequences in the presence of tBuOK in commercially available EtOH solvent at 60 °C. Notably, the simple reactions can be run on a gram scale. Mechanistically, bis-Michael addition reaction and hemiaminalization reactions are involved in the tandem transformation.