Off the Beaten Track: The Use of Secondary Amines in the Ugi Reaction

Although the Ugi multicomponent reaction is more than 40 years old, there is still room for its application to the discovery of new multicomponent transformations, even within the constraints of its classic four‐reactant menu (aldehyde, amine, carboxylic acid, and isocyanide). Replacement of a primary amine with a secondary one thus allows the Mumm‐like rearrangement step to be avoided, freezing the reaction course at the stage of an imino‐anhydride intermediate susceptible to alternative nucleophilic trapping. Mainstream post‐transformation strategies can then add a further level of complexity. The potential of this approach to expedite access to molecular scaffolds of biological relevance and to create unprecedented chemical diversity is outlined.