Formal C-H Carboxylation of Unactivated Arenes

Abstract

A formal C-H carboxylation of unactivated arenes using CO₂ in green solvents is described. The present strategy combines a sterically controlled Ir-catalyzed C-H borylation followed by a Cu-catalyzed carboxylation of the in situ generated organoboronates. The reaction is highly regioselective for the C-H carboxylation of 1,3-disubstituted and 1,2,3-trisubstituted benzenes, 1,2- or 1,4-symmetrically substituted benzenes, fluorinated benzenes and different heterocycles. The developed methodology was applied to the late-stage C-H carboxylation of commercial drugs and ligands.

Keywords: C−H activation; carbon dioxide; carboxylation; green solvent; late-stage functionalization.