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.