Three-Component Sulfonylation and Heteroannulation Enabled by 3-Fold Defluorofunctionalization of Trifluoromethyl Enones

Trifluoromethyl enone emerges as a versatile and multifaceted building block in organic synthesis. A defluorinative heterocyclization reaction of readily available β,β-ditrifluoromethylated enones and biocompatible sodium sulfinates has been developed for the modular synthesis of densely functionalized furans with regio-defined <i>C</i>2,4-bissulfonyl and <i>C</i>3-trifluoromethyl substitutions. This three-component method proceeds through a sequential sulfonylation and intramolecular <i>O</i>-cyclization, enabling the assembly of one furan ring, the formation of C-SO₂/C-O bonds, and the cleavage of three C(sp³)-F bonds in a one-pot manner under transition metal-free conditions. Moreover, the obtained furan product can further react with a benzyne precursor to generate 1,4-epoxynaphthalene through a Diels-Alder cycloaddition. The reaction is also distinguished by its broad substrate scope, excellent functional group tolerance, and scalability.