Modular Synthesis\nof Furans with Four Nonidentical\nSubstituents by Aqueous Defluorinative Reaction of Trifluoromethyl\nEnones with Two Nucleophiles

A three-component reaction of trifluoromethyl enones,\nphosphine\noxides, and alcohols in water solution is developed. This defluorinative\nreaction occurs through a cascade process involving defluorophosphorylation,\ndefluoroalkyloxylation, and defluoroheteroannulation, enabling the\nmodular synthesis of furans with four distinct substituents: <i>C</i>2-alkyloxy, <i>C</i>3-trifluoromethyl, <i>C</i>4-phosphoryl, and <i>C</i>5-(hetero)aryl groups.\nMoreover, apart from alcohol substrates, the scope of nucleophiles\ncould be further extended to phenols, azacycles, or sulfonamide.