p‐TSA‐Mediated Four‐Component Reaction: One‐Step Access to Mesoionic 1H‐Imidazol‐3‐ium‐4‐olates, Direct NHC Precursors

Abstract

p‐TSA‐mediated four‐component condensation is described. The reaction of an isocyanide, amine, aldehyde, and amide catalyzed by p‐TSA afforded diversely substituted mesoionic 1H‐imidazol‐3‐ium‐4‐olates in one step. These products were obtained in good to excellent HPLC purity under mild reaction conditions. This formation of mesoionic compounds, structurally related to sydnones and münchnones, represent attractive intermediates and direct precursors for anionic N‐heterocyclic carbenes. Atom economy, time efficiency, and commercially available starting materials make this one‐pot synthesis user‐friendly.

p-Toluenesulfonic acid-promoted organic transformations for the generation of molecular complexity

“…Tetrasubstituted mesoionic imidazole-derived heterocycles are synthetically very important as these are used as direct precursors of N-heterocyclic carbenes. Recently, Prof. Cankařová 27 reported the synthesis of substituted mesoionic 1 H -imidazol-3-ium-4-olates by p -TSA-mediated four-component condensation reactions of amine, aldehyde, isocyanide, and amide (Scheme 18). These mesoionic compounds are structurally affiliated with sydnones and münchnones, comprise promising intermediates and prime precursors for anionic N-heterocyclic carbenes, and were produced under mild reaction conditions with good to high HPLC purity.…”