Palladium-Catalyzed Ortho C–H Arylation of Unprotected Anilines: Chemo- and Regioselectivity Enabled by the Cooperating Ligand [2,2′-Bipyridin]-6(1H)-one

Abstract

Metal-catalyzed C−H functionalizations on the aryl ring of anilines usually need cumbersome N-protection−deprotection strategies to ensure chemoselectivity. We describe here the Pd-catalyzed direct C−H arylation of unprotected anilines with no competition of the N-arylation product. The ligand [2,2′-bipyridin]-6(1H)-one drives the chemoselectivity by kinetic differentiation in the product-forming step, while playing a cooperating role in the C−H cleavage step. The latter is favored in an anionic intermediate where the NH moiety is deprotonated, driving the regioselectivity of the reaction toward ortho substitution.