Selective defluorohydroxylation, defluoroetherification, and defluorodifluoromethoxylation of polyfluoro(hetero)arenes

Abstract

Site-selective defluorofunctionalization of polyfluoro(hetero)aromatic compounds, which can harness the feature of the polyfluoro(hetero)aromatic core while simultaneously introducing valuable functionalities, represents a promising strategy for the synthesis of privileged organofluorides. Herein, we report a tunable platform for the selective defluorohydroxylation, defluoroetherification, and defluorodifluoromethoxylation of readily available polyfluoro(hetero)arenes under transition-metal-free conditions. First, a variety of polyfluorophenols were synthesized in moderate to good yields with good functional group tolerance when the reaction was carried out in the presence of NaOH as the nucleophilic aromatic substitution (S_NAr) hydroxylating agent at room temperature. Moreover, an intermolecular multicomponent approach for the defluoroetherification of polyfluoro(hetero)arenes through a sequence involving selective C(sp²)–F bond activation, insertion of an oxygen-atom as a connecting bridge, and ensuing coupling with simple alkyl/benzyl/allylic/propargylic electrophiles was developed for the one-pot assembly of polyfluoroaromatic ether products. Additionally, when difluorocarbene precursors, such as BrCF₂CO₂Na and BrCF₂CO₂H, were employed in place of electrophiles, defluorodifluoromethoxylation of polyfluoroarenes was achieved, facilitating the streamlined synthesis of valuable polyfluoroaryl difluoromethyl ethers.