Organocatalytic Asymmetric Conjugate Addition of 3-Alkyl-Substituted Oxindoles to Vinyl Ketones

摘要

Oxindole structures are widely present in a large number of natural and biologically active molecules. Particularly, oxindole scaffolds bearing a quaternary stereocenter at the 3-position are a versatile common motif found in a variety of biologically and pharmaceutically active natural products and utilized as building blocks for indole alkaloid synthesis. Several methods for their asymmetric formation and transformation are of considerable interest. Among the established strategies for the synthesis of chiral 3,3-disubstituted oxindoles, a transition metal-catalyzed asymmetric reaction has been intensively studied. Recently, organocatalytic enantio-selective conjugate addition reactions of oxindoles with enals, nitroalkenes, and vinyl sulfones have been reported. Several groups have reported an enantioselective conjugate addition reaction of 3-aryloxindoles to vinyl ketones catalyzed by organocatalysts, phase-transfer catalyst, and chiral calcium phosphate. Although there have been reports for the catalytic enantioselective conjugate addition reaction of 3-aryl-sub-stituted oxindoles to vinyl ketones, a few examples for the catalytic enantioselective conjugate addition reaction of 3-alkyl-substituted oxindoles to cyclic enones were reported using chiral primary or secondary amine catalysts. Therefore, the development of alternative catalysts for the catalytic enantioselective conjugate addition reaction of 3-alkyl-sub-stituted oxindoles to vinyl ketones would be highly desirable.