Pd(II)-Catalyzed Chemoselective Acetoxylation of C(sp)-H and C(sp)-H Bonds in Tertiary Amides.

Palladium-catalyzed chemoselective C(sp)-H and C(sp)-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(sp)-Cl, C(sp)-Cl, -CF, -COOEt, and -NO 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.