Enantioselective Intramolecular Desymmetric α-Addition of Cyclohexanone to Propiolamide Catalyzed by Sodium L-Prolinate

.Summary of main observation and conclusion An enantioselective desymmetric nucleophilic alpha-addition of cyclohexanone to propiolamide has been developed through a 6-exo-dig cyclization reaction. By employing simple and readily available L-proline sodium salt as a bifunctional catalyst, a series of chiral 6,6-bicyclic bridged products bearing morphan scaffold have been isolated in good yields and excellent enantioselectivities. Density functional theory (DFT) calculations elucidated the origins of the enantioselectivity and regioselectivity of this transformation. A salt bridge that links the amide carbonyl group with proline carboxylate in the transition state was proven to be the driving force for the induction of excellent enantioselectivity.