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

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