| Given the importance of polyfluorinated diaryl ethers in pharmaceutically active compounds and as effective liquid crystal dopants, the development of a practical catalyst system that can be used to synthesize these molecules with broad functional group compatibility and tolerance is desired. To date, polyfluorinated diaryl ethers or alkyl aryl ethers have been synthesized via nucleophilic aromatic substitution processes. However, early works showed that this method resulted mostly in low to medium yield of products and usually required longer reaction time, and the substrate scope was limited.we have developed an efficient, ligand-free palladium-catalyzed method for the cross coupling reaction of pentafluorobenzene with phenols. Our catalysis system proceeds with high chemo-and regioselectivity for the C-F bond activation in the para-position with respect to the hydrogen substituent. A wide variety of phenols can be employed in this coupling reaction to afford the corresponding polyfluorinated aryl ethers in moderate to good yields.Our study commenced by examining the coupling reaction of phenol with pentafluorobenzene using Pd(OAc)2 as the catalyst, AgNO3 as the additive and K2CO3 as the base. The desired polyfluorinated diaryl ether product was obtained in excellentisolated yield when the reaction was carried out in DMF at 120℃. The isolated yield of polyfluorinated diaryl ether product was up to 94%. Compounds was characterized by mass spectroscopy,1H,13C and 19F NMR spectroscopy.A plausible mechanism for this reaction is depicted,the initiated SN2 attack of palladium species (A) on the pentafluorobenzene (at 3-position of C6HF5) leads to the formation of intermediate B, which undergoes C-F bond cleavage and fluoride abstraction by AgNO3, and phenolate coordination to afford intermediate C. Subsequent reductive elimination from C would produce the polyfluorinated aryl ether, as well as the palladium(0) species A, and complete the catalytic cycle. |
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