Pyrrolidinodiones in Enol-Ugi, Enol-Passerini, and Anomalous Enol-Passerini Condensations ^†

In continuation of our recent research on the development of novel multicomponent reactions with isocyanides, we have used, for the first time, enols as the acid components in Ugi- and Passerini-type reactions. Thus, electron-poor pyrrolidinodiones react with aldehydes, amines, and isocyanides to give the enaminic four-component adducts. Conversely, in the absence of the amine component, careful control of the reaction conditions allows the involvement of one or two molecules of isocyanide to afford, selectively, either Passerini-type or pseudo-enol-Ugi-type products. These unprecedented condensations of isocyanides, aldehydes, amines, and 4-substituted pyrrolidine-2,3-diones constitute an excellent strategy for the preparation of new biologically relevant pyrrolidinones having peptidic or pseudo-peptidic groups on carbon 3.