Ugi–Smiles Couplings of 4-Substituted Pyridine Derivatives: A Fast Access to Chloroquine Analogues

4-Hydroxy and mercapto pyridines were successfully tested in Ugi–Smiles couplings. Such multicomponent reactions applied to quinoline derivatives afford a very convenient and short synthesis of antimalarial analogues

Substituent Effects in Ugi–Smiles Reactions

In a recent communication, we described the mechanism of the well-known Ugi-type reactions with a model system (J. Org. Chem. 2012, 77, 1361−1366). Herein, focusing on the Ugi–Smiles coupling, we study the effects of each of the four reactants on the energy profile to further explain the experimental results. The variations observed with different carbonyl compounds rely on their influence on the formation of the aryl-imidate, whereas the variations on the amine preferentially affect the Smiles rearrangement. The effect of substituents on the phenol derivative is seen upon both aryl-imidate formation and the rearrangement. The effect of the isocyanide substituents is less pronounced

Challenging 50 Years of Established Views on Ugi Reaction: A Theoretical Approach

The Ugi reaction is one of the most famous multicomponent couplings, and its efficiency is still explained by the original mechanism suggested by Ugi in the 60s. This article aims to present a thorough theoretical study of this reaction. It describes how the imine is activated and how the new stereogenic center is formed. Our calculations strongly suggest alternatives to some commonly accepted features, such as the reversibility of the intermediate steps, and temper the nature of the driving force of the reaction