Modular Synthesis of 3,4-Disubstituted Pyrroles Through Three-Component Van Leusen Reaction of Propargylamines with Tosylmethyl Isocyanide and Water

A novel three-component van Leusen strategy has been developed for the efficient and straightforward synthesis of valuable 3,4-disubstituted pyrroles from easily available propargylamines, tosylmethyl isocyanide, and water. This transformation advances through the formation of a pyrrole framework via [3 + 2] cycloaddition with tosylmethyl isocyanide and a sequential nucleophilic substitution, ring-opening, and deprotonation/protonation cascade process. This reaction provides a convenient modular access to pyrrole derivatives with aryl and benzoyl groups through the formation of three new bonds and one heterocycle from readily available acyclic precursors in a single step.