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.