Polymer-Supported α-Acylamino Ketones: Preparation and Application in Syntheses of 1,2,4-Trisubstituted-1H-imidazoles

Polymer-supported alpha-acylamino ketones were prepared from resin-bound amines, bromoketones, and carboxylic acids. Selective monoalkylation of amines by bromoketones was carried out via 4-nitrobenzenesulfonamides. There was a striking difference in the reaction outcome between 2-Nos and 4-Nos derivatives. Alpha-acylamino ketones were converted to imidazoles. The cyclization was performed on resin, allowing further polymer-supported elaboration of imidazoles including synthesis of bis-heterocyclic compounds. A small combinatorial array of imidazoles was synthesized. Target compounds were prepared under mild conditions using commercially available building blocks for the introduction of three points of diversity.