Multiple remote C(sp³)–H functionalizations of aliphatic ketones via bimetallic Cu–Pd catalyzed successive dehydrogenation

The dehydrogenation-triggered multiple C(sp3)-H functionalizations at remote positions γ, δ or ε, ζ to carbonyl groups of aliphatic ketones with aryl/alkenyl carboxylic acids as coupling partners have been achieved using a bimetallic Cu-Pd catalyst system. This reaction allows access to alkenylated isocoumarins and their derivatives in generally good yields with high functional group tolerance. The identification of bimetallic Cu-Pd synergistic catalysis for efficient successive dehydrogenation of aliphatic ketones, which overcomes the long-standing challenge posed by the successive dehydrogenation desaturation of terminally unsubstituted alkyl chains in aliphatic ketones, is essential to achieving this bimetallic Cu-Pd catalyzed dehydrogenation coupling reaction.