Primary Amide Directed Regioselective <i>ortho</i>-C–H-Arylation of (Aryl)Acetamides

Abstract

An efficient and regioselective palladium(II)-catalyzed primary acetamide assisted ortho arylation of arylacetamide has been discovered. This is the first report where functionalizable primary acetamide (-CH₂CONH₂) is used as a directing group for C(sp²)-H activation/cross-coupling reactions, circumventing the extra steps of installation and subsequent removal of the directing groups. The synthetic utility of this transformation is demonstrated through the scale-up synthesis. In addition, the primary acetamide can be manipulated into synthetically important derivatives such as nitriles and carboxylic acids.