Multicomponent Synthesis of Uracil Analogues Promoted by Pd-Catalyzed Carbonylation of α-Chloroketones in the Presence of Isocyanates and Amines

A short and efficient one-pot synthesis of uracil derivatives with a high structural variability is described. The process is a multicomponent reaction based on a palladium-catalyzed carbonylation of alpha-chloroketones in the presence of primary amines and isocyanates. In most cases, when the formation of unsymmetrical N,N'-disubstituted uracil derivatives can occur, the methodology demonstrates to be highly regioselective. A mechanistic hypothesis involving beta-dicarbonyl palladium intermediates and urea derivatives, generated in situ, has been discussed.