An amide-based polyene cyclization has been developed for the stereoselective synthesis of octahydrobenzofisoquinolines. 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 octahydrobenzofisoquinolines exhibit selective agonism for the δ-opioid receptor, providing valuable insights for developing more effective δ-opioid receptor agonists.
Cao et al. (Sat,) studied this question.