Pd(II)-Catalyzed Chemoselective Acetoxylation of C(sp2)–H and C(sp3)–H Bonds in Tertiary Amides

Palladium-catalyzed chemoselective C­(sp2)–H and C­(sp3)–H acetoxylation of synthetically useful tertiary amides is reported under relatively mild reaction conditions. This protocol proceeds through the assistance of a weakly coordinated directing group (CO) and requires low catalyst (1.0 mol %) loading. Diverse functionalities, such as C­(sp2)–Cl, C­(sp3)–Cl, −CF3, −COOEt, and −NO2 groups, including morpholinyl, piperazinyl, and pyrrolidinyl heterocycles, are compatible under the reaction conditions. Further functionalization of this protocol is demonstrated by hydrolysis to alcohols, alcohol–acids, as well as reduction to tertiary amines. A preliminary kinetic isotope effect study supported the rate-limiting C–H bond activation process.