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

Taming Nickel-Catalyzed Suzuki-Miyaura Coupling: A Mechanistic Focus on Boron-to-Nickel Transmetalation

The mechanism of boron-to-nickel transmetalation, the key step of the nickel-catalyzed Suzuki-Miyaura (S-M) coupling, was examined both experimentally and theoretically. Dinuclear μ-hydroxo-bridged complexes formed by reaction of <i>trans</i>-[ArNi­(PR₃)₂X] with hydroxide are not directly involved in transmetalation, but they rather act as a resting state for the catalyst. The base/boronic acid ratio is the crucial parameter, as it modulates the extent of formation of these dinuclear species and thus tunes the catalytic activity. These findings explain some limitations encountered in practical applications of nickel-catalyzed S-M couplings and suggest how to tailor the experimental conditions in order to overcome these difficulties

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

Labeling of Hyaluronic Acids with a Rhenium-tricarbonyl Tag and Percutaneous Penetration Studied by Multimodal Imaging

Hyaluronic acids were labeled with a rhenium-tricarbonyl used as single core multimodal probe for imaging and their penetration into human skin biopsies was studied using IR microscopy and fluorescence imaging (labeled SCoMPI). The penetration was shown to be dependent on the molecular weight of the molecule and limited to the upper layer of the skin