Transition Metal-Catalyzed Addition of Amines to Acrylic Acid Derivatives. A High-Throughput Method for Evaluating Hydroamination of Primary and Secondary Alkylamines

Several new classes of transition metal-catalyzed reactions of amines with the CC bond of acrylic acid derivatives were discovered using a high-throughput colorimetric assay. This assay is general for the reactions of primary and secondary alkylamines with acrylic acid derivatives, and the screening of potential catalysts using this assay revealed a number of different metal/ligand combinations that promote these hydroaminations. The colorimetric assay revealed catalysts for the addition of piperidine to methacrylonitrile, crotononitrile, ethyl crotonate, and ethyl methacrylate, as well as catalysts for reactions of butylamine and aniline with methacrylonitrile. A catalyst for the addition of aniline to crotononitrile at 100 °C was also discovered. The products of these reactions are basic building blocks for the synthesis of β-amino acids, amino alcohols, and diamines. These reactions may ultimately produce an enantioselective route to optically active difunctional materials from commodity reagents.