A Modular Strategy for the Direct Catalytic Asymmetric α-Amination of Carbonyl Compounds

Abstract

Summary Direct catalytic methods for the stereoselective introduction of various non-protected amines at the carbon atom adjacent to a carbonyl group remain elusive in synthetic chemistry, even though they offer the most straightforward entry to chiral α-aminocarbonyl compounds. Here, we demonstrate that the in situ activation of hydroxylamines with trichloroacetonitrile enables direct transfer of their amine moieties to the C-3 position of oxindoles with rigorous enantiocontrol under the catalysis of chiral 1,2,3-triazolium salts. This protocol provides a powerful and practical means of accessing optically active 3-aminooxindoles with a wide array of alkyl and aryl substituents on nitrogen. Other carbonyl compounds, such as β-ketoesters and α-cyanoesters, can also be directly transformed into the corresponding α-aminocarbonyls with high enantioselectivity.