Catalytic SNAr Hydroxylation and Alkoxylation of Aryl Fluorides

Nucleophilic aromatic substitution (SNAr) is a powerful strategy for incorporating a heteroatom into an aromatic ring by displacement of a leaving group with a nucleophile, but this method is limited to electron-deficient arenes. We have now established a reliable method for accessing phenols and phenyl alkyl ethers via catalytic SNAr reactions. The method is applicable to a broad array of electron-rich and neutral aryl fluorides, which are inert under classical SNAr conditions. Although the mechanism of SNAr reactions involving metal arene complexes is hypothesized to involve a stepwise pathway (addition followed by elimination), experimental data that support this hypothesis is still under exploration. Mechanistic studies and DFT calculations suggest either a stepwise or stepwise-like energy profile. Notably, we isolated a rhodium eta(5)-cyclohexadienyl complex intermediate with an sp(3)-hybridized carbon bearing both a nucleophile and a leaving group.

Automated summary

A reliable method for accessing phenols and phenyl alkyl ethers via catalytic SNAr reactions has been established in this study, applicable to a broad array of electron-rich and neutral aryl fluorides. Experimental data supporting the mechanism of SNAr reactions are still under exploration, with mechanistic studies and DFT calculations suggesting a stepwise or stepwise-like energy profile. Notably, a rhodium eta(5)-cyclohexadienyl complex intermediate has been isolated with an sp(3)-hybridized carbon bearing both a nucleophile and a leaving group.