Ruthenium-Catalyzed <i>meta</i>-Alkylationof (Hetero)aromatic Acids with Pyridinium Salts Utilizing UbiquitousAmines as Substrates

Carboxylic acids and amines are structurally diverse, abundant, and widely available building blocks, and new coupling models between carboxylic acids and amines will greatly expand the chemical space. Herein, we report a ruthenium-catalyzed <i>meta</i>-alkylation of (hetero)aromatic carboxylic acids with pyridinium salts utilizing ubiquitous amines as substrates. Key to this advance is the 5,5′-dimethyl bipyridine-ligated cycloruthenium complex that facilitates the single-electron-reduction of pyridinium salts and LiCl as the Lewis acid additive in a protic and acidic solvent (^<i>t</i>BuOH/HFIP) promoting the protodemetalation and regenerating the catalyst. Broad substrate scope (67 examples, up to 91% yield) with excellent functional group tolerance and a late-stage <i>meta</i>-alkylation with drug moieties demonstrates its potential applications in drug synthesis.