Pyrrolidinodiones in Enol-Ugi, Enol-Passerini and anomalous enol-Passerini condensations

In continuation with our recent research in 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, enols 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.