Introduction of the Trifluoropropionate Moiety into Aromatic Rings via Rhodium-Catalyzed Coupling of Arylboronic Acids with Diazoesters

A catalytic method for the introduction of pharmaceutically meaningful fluorinated propionic acid side chains into aromatic compounds is presented. In the presence of rhodium catalyst [RhCp*Cl₂]₂, various arylboronic acids are efficiently coupled with an easy-to-access diazoester reagent to give perfluorinated derivatives of phenylpropionic acids, including top-selling profen drugs. The key advantage of this approach is that the pharmacophore is introduced as a whole and is compatible with various functionalities and drug discovery.