Synthesis of ent‐Ketorfanol via a C–H Alkenylation/Torquoselective 6π Electrocyclization Cascade

The asymmetric synthesis of ent‐ketorfanol from simple and commercially available precursors is reported. A Rh^I‐catalyzed intramolecular C? H alkenylation/torquoselective 6π electrocyclization cascade provides a fused bicyclic 1,2‐dihydropyridine as a key intermediate. Computational studies were performed to understand the high torquoselectivity of the key 6π electrocyclization. The computational results demonstrate that a conformational effect is responsible for the observed selectivity. The ketone functionality and final ring are introduced in a single step by a redox‐neutral acid‐catalyzed rearrangement of a vicinal diol to give the requisite carbonyl, followed by intramolecular Friedel–Crafts alkylation.