Enantioselective Michael Reactions Catalyzed By Chiral Primary Amine And Applications In Total Synthesis

With this paper, new methods for asymmetric Michael addition of sulfones and 2-hydroxy-1,4-naphthoquinone to enones have been developed, respectively, by primary amine organocatalysts.The asymmetric Michael reactions of bis(phenylsulfonyl)methane and enones were investigated for the first time, employing bifunctional organocatalyst 9-amino-(9-deoxy)-epicinchona alkaloid. Many factors on the Michael addition including catalysts, solvent, additives and temperature in the reaction system were investigated. Under the optimum reaction conditions, a series of aliphatic enones were found to be good reactants in the system, affording the 1,4-adducts in excellent yields (up to 96%) with high enantioselectivities (up to 98%). Moreover, desulfonation of the adducts offered the optical 3-methyl-ketone compounds and the methodology has been successfully demonstrated its synthetic utility in the chiral synthesis of R-muscone and S-celery ketone.The enantioselective Michael reactions of 2-hydroxy-1,4-naphthoquinone and enones were investigated for the first time. Chiral primary amine 9-amino-(9-deoxy)-epicinchona alkaloid were also found to be an excellent catalyst, offering the adducts with up to 96% enantioselectivities. Both of the aliphatic and aromatic enones had high reactivities these novel transformations.