Systematic Expansion of an Ugi-Based Multicomponent Synthesis of Tetrasubstituted Imidazoles

Résumé fourni par la source

Highly substituted imidazoles are privileged scaffoldsin medicinal and synthetic chemistry; however, general andmodular access to densely substituted variants remains limited.Although Ugi-derived imidazole formation has been reported inisolated cases, its broader applicability has not been systematicallyexplored. Herein, we present a comprehensive expansion andoptimization of an Ugi-based one-pot synthesis enabling thepreparation of tetrasubstituted imidazoles from readily accessibleglyoxal derivatives. In contrast to earlier studies largely restricted toaryl glyoxals, this protocol demonstrates broad compatibility withaliphatic and aromatic glyoxals, as well as diverse amines,carboxylic acids, and isocyanides, providing full substitution controlover all four positions of the imidazole ring. Key parameters governing chemoselectivity and ammonium-induced cyclization wereidentified, affording the target imidazoles in moderate to excellent yields. This study establishes the Ugi−imidazole transformation asa robust and diversity-oriented synthetic platform suitable for the rapid generation of medicinally relevant imidazole scaffolds.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.