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: <i>C</i>2-alkyloxy, <i>C</i>3-trifluoromethyl, <i>C</i>4-phosphoryl, and <i>C</i>5-(hetero)aryl groups. Moreover, apart from alcohol substrates, the scope of nucleophiles could be further extended to phenols, azacycles, or sulfonamide.