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