Amide-Based Polyene Cyclization: Stereoselective Construction of <i>cis</i> - or <i>trans</i> -Octahydrobenzo[ <i>f</i> ]isoquinolines

An amide-based polyene cyclization has been developed for the stereoselective synthesis of octahydrobenzo[f]isoquinolines. This reaction employs E-olefins as substrates and features a wide substrate scope, affording products in good yields with high diastereoselectivity. Notably, the stereochemical outcome is precisely controlled by the reaction temperature, representing a novel activation mode in polyene chemistry. Importantly, the synthesized octahydrobenzo[f]isoquinolines exhibit selective agonism for the δ-opioid receptor, providing valuable insights for developing more effective δ-opioid receptor agonists.