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 C=C bond of acrylic acid derivatives were discovered using a high-throu ghput colorimetric assay. This assay is general for the reactions of primar y and secondary alkylamines with acrylic acid derivatives, and the screenin g of potential catalysts using this assay revealed a number of different me tal/ligand combinations that promote these hydroaminations. The colorimetri c assay revealed catalysts for the addition of piperidine to methacrylonitr ile, crotononitrile, ethyl crotonate, and ethyl methacrylate, as well as ca talysts for reactions of butylamine and aniline with methacrylonitrile. A c atalyst for the addition of aniline to crotononitrile at 100 degreesC was a lso discovered. The products of these reactions are basic building blocks f or the synthesis of beta -amino acids, amino alcohols, and diamines. These reactions may ultimately produce an enantioselective route to optically act ive difunctional materials from commodity reagents.