Total Synthesis of the Congested Propellane Alkaloid (−)‐Acutumine

The enantioselective total synthesis of (−)‐acutumine is described. The synthetic strategy was inspired by the premise that the cyclohexenone ring could be derived from an aromatic precursor. After successful construction of a propellane model system, an initial attempt to prepare the spirocyclic subunit was thwarted by incorrect regioselectivity in a radical cyclization. A second‐generation approach involving a radical–polar crossover reaction was successful, and the chemistry developed in the aforementioned model system was then applied to synthesize the natural product. Key reactions included a phenolic oxidation, a diastereoselective ketone allylation utilizing Nakamura's chiral allylzinc reagent, an anionic oxy‐ C ope rearrangement, an acid‐promoted cyclization of a secondary amine onto an α,β‐unsaturated ketal, and a regioselective methyl enol etherification of a 1,3‐diketone.