Modular Synthesis of Furans with Four Nonidentical Substituents by Aqueous Defluorinative Reaction of Trifluoromethyl Enones with Two Nucleophiles

A three-component reaction of trifluoromethyl enones, phosphine oxides, and alcohols in water solution is developed. This defluorinative reaction occurs through a cascade process involving defluorophosphorylation, defluoroalkyloxylation, and defluoroheteroannulation, enabling the modular synthesis of furans with four distinct substituents: C2-alkyloxy, C3-trifluoromethyl, C4-phosphoryl, and C5-(hetero)aryl groups. Moreover, apart from alcohol substrates, the scope of nucleophiles could be further extended to phenols, azacycles, or sulfonamide.