UC San Diego

Isocyanide based multicomponent reactions, including the Ugi four-component and Passerini three-component reactions, offer chemists a powerful tool for quickly constructing complex molecules. A particular form of the Ugi reaction, in which two of the four reacting components are introduced into a single molecule, is useful for synthesizing cyclic products. Using a newly developed convertible isocyanide, known as indole isocyanide, in the Ugi reaction allowed for the mild synthesis of various pyroglutamic acids. This effort led first to a racemic total synthesis of the natural product dysibetaine. A project to achieve the stereoselective synthesis of the same natural product led to the discovery of a unique Ugi reaction. Usually a carboxylic acid is one of the four reacting components in this reaction, however in this unusual case an ester acts as the carboxylic acid component. In addition to the natural product syntheses, a detailed explanation of the scope and mechanism of the new convertible indole isocyanide is presented. Finally, we reveal a new stereoselective, Brønsted-acid catalyzed Passerini-type reaction