Catalytic C-Demethylation of Phenols and Anilines Enabled by a Removable Mono-Directing Group

The activation of inert carbon–carbon (C–C) bonds remains a major challenge in organic synthesis, particularly for unstrained and nonpolar systems such as aryl–methyl (Ar–Me) bonds. Existing strategies predominantly rely on bidentate chelating directing groups, limiting their applicability. Herein, we report a ruthenium-catalyzed activation of Ar–Me bonds enabled by a removable mono-directing group, phosphinite, which is easily installed and cleaved. This approach offers broad substrate scope, tolerating various functional groups including halides, ethers, boronates, and heterocycles. Mechanistic studies suggest that a Ru–hydride species generated in situ is responsible for C–Me bond activation, with methane identified as a byproduct. The method also demonstrates remarkable selectivity for Ar–Me bonds over other aryl–alkyl linkages and is applicable to both phenol and aniline derivatives. This strategy potentially provides a general and practical platform for C–C bond cleavage, expanding the toolbox for molecular editing.