α-Carbonylimine to α-Carbonylamide: An Efficient Oxidative Amidation Approach.

Our interest in generating amide bonds by employing the activated C=N system has led to the development of an efficient oxidative amidation reaction between 2-oxoaldehyde and weak nucleophilic amines (anilines, benzamides and sulfonamides). Mechanistic studies support the involvement of α-carbonylimine (–CO–C=N–) based compounds or intermediates as a central feature of the reaction, in which an adjacent CO moiety enhances the electrophilicity of the C=N system, which favors attack of the oxidant (TBHP or SeO2), thereby resulting in the generation of the desired products in good yields. The direct oxidative coupling of 2-oxoaldehydes and weak nucleophilic amines has been accomplished through either MgSO4–TBHP–pyridine/CuBr, or SeO2·pyridine promoted methods. In the current study, SeO2·pyridine emerged as a versatile reagent with which to promote initial α-carbonylimine formation between 2-oxoaldehyde and weak nucleophilic amine, and subsequent oxidation to the corresponding α-carbonylamide. The reported methodology constitutes one of the few reports of the synthesis of α-ketoamides from anilines, perhaps the second report for the generation of α-ketoimides, and the first report of the generation of 2-oxoamides with sulfonamides.