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

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 degrees 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.(c) 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.