Copper-catalyzed dehydrogenative γ-C(sp3)-H amination of saturated ketones for synthesis of polysubstituted anilines

Metal-catalyzed beta-C-H functionalization of saturated carbonyls via dehydrogenative desaturation proved to be a powerful tool for simplifying synthesis of valuable beta-substituted carbonyls. Here, we report a copper-catalyzed dehydrogenative gamma-C(sp(3))-H amination of saturated ketones that initiates the three-component coupling of saturated ketones, amines and N-substituted maleimides to construct polysubstituted anilines. The protocol presented herein enables both linear and alpha-branched butanones to couple a wide spectrum of amines and various N-substituted maleimides to produce diverse tetra- or penta-substituted anilines in fair-to-excellent yields with good functional group tolerance. The mechanism studies support that this ketone dehydrogenative gamma-C(sp(3))-H amination was triggered by the ketone alpha,beta-dehydrogenation desaturation that activates the adjacent gamma-C(sp(3))-H bond towards functionalization. This alpha,beta-dehydrogenation desaturation-triggered cascade sequence opens up a new avenue to the remote C(sp(3))-H functionalization of saturated ketones and has the potential to enable the rapid syntheses of complex compounds from simple starting materials.