Micellar Palladium-Catalyzed Aqueous Sonogashira Coupling with Amphiphilic Polymer PEG–PVEG

Abstract An efficient, copper-free, palladium-catalyzed aqueous Sonogashira reaction has been developed, enabled by the self-assembly of the amphiphilic copolymer polyethylene glycol-polyvinylethylene glycol (PEG–PVEG). Using 0.02 mol % of CataCXium A Pd G3 as the catalyst under mild conditions, this aqueous micellar system accommodates a broad range of (hetero)aryl bromides and chlorides, affording the corresponding substituted alkynes in high efficiency with excellent functional group tolerance. The synthetic utility of this system was demonstrated by the successful preparation of pharmaceutical intermediates and indole derivatives. Notably, this protocol exhibited high in-flask recyclability with the reaction medium remaining effective for at least four consecutive runs.