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

Xueying Huang, Shu‐Ji Gao, Danhua Ge, Mengtao Ma, Zhi‐Liang Shen, Xue‐Qiang Chu

2024Organic Letters24 citationsDOI

Abstract

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

Topics & Concepts

ChemistryNucleophileTrifluoromethylArylPhosphinePhenolsAlcoholOrganic chemistrySulfonamideAqueous solutionCombinatorial chemistryMedicinal chemistryCatalysisAlkylFluorine in Organic ChemistryCatalytic C–H Functionalization MethodsOxidative Organic Chemistry Reactions
Modular Synthesis of Furans with Four Nonidentical Substituents by Aqueous Defluorinative Reaction of Trifluoromethyl Enones with Two Nucleophiles | Litcius