An Improved Practical Route to （±）-Epibatidine through L-Proline Catalyzed Intramolecular Michael Addition

This paper describes a rapid and practical synthetic route involving six-step reactions towards the diastereose- lectively synthesis of （±）-endo-Epibatidine, starting from 6-chloro-3-pyridinecarboxaldehye. The effective Henry reaction gave precursor （E）-6-（6-chloropyridin-3-yl）-5-nitrohex-5-en-2-one （3a） which could be used in the next step. Various benzoic acid derivatives were used to optimize intramolecular Michael addition of ketone to pyridinylnitroolefins to provide the key intermediate 3-（6-chloropyridin-3-yl）-4-nitrocyclohexanone （±）-7a） with high yield.