Ligand-enabled ruthenium-catalyzed meta-C-H alkylation of (hetero)aromatic carboxylic acids.

ABSTRACT

Carboxylates are ideal directing groups because they are widely available, readily cleavable and excellent linchpins for diverse follow-up reactions. However, their use in meta-selective C-H functionalizations remains a substantial unmet catalytic challenge. Herein, we report the ruthenium-catalyzed meta-C-H alkylation of aromatic carboxylic acids with various functionalized alkyl halides. A bidentate N-ligand increases the electron density at the metal center of ortho-benzoate ruthenacycles to the extent that single-electron reductions of alkyl halides can take place. The subsequent addition of alkyl radicals is exclusively directed to the position para to the CAr-Ru bond, i.e., meta to the carboxylate group. The resulting catalytic meta-C-H alkylation extends to a wide range of (hetero)aromatic carboxylic acids including benzofused five-membered ring heteroarenes but no pyridine derivatives in combination with secondary/tertiary alkyl halides, including fluorinated derivatives. It also allows site-selective C5-H alkylation of 1-naphthoic acids. The products are shown to be synthetic hubs en route to meta-alkylated aryl ketones, nitriles, amides, esters and other functionalized products.