Deacylative Transformations of Ketones via Aromatization-Promoted C−C Bond Activation

Carbon−hydrogen (C−H) and carbon−carbon (C−C) bonds are the main constituents of organic matter. The recent advancement of C−H functionalization technology has vastly expanded our toolbox for organic synthesis(1). In contrast, C−C activation methods that allow for editing the molecular skeleton remain limited(2–7). To date, a number of methods have appeared for catalytic C−C activation, particularly with ketone substrates, which are typically promoted either by ring-strain release as a thermodynamic driving force(4,6) or using directing groups(5,7) (DGs) to control the reaction outcome. While effective, these strategies require highly strained ketone substrates or those containing a preinstalled DG, or are limited to more specialist substrate classes(5). Here, we report a general C−C activation mode driven by aromatization of an in situ-formed pre-aromatic intermediate. This reaction suitable for various ketone substrates, is catalyzed by an iridium/phosphine combination, and is promoted by a hydrazine reagent and 1,3-dienes. Specifically, the acyl group is removed from the ketone, transformed to a pyrazole, and the resulting alkyl fragment undergoes various transformations. These include the deacetylation of methyl ketones, carbenoid-free formal homologation of aliphatic linear ketones, and deconstructive pyrazole synthesis from cyclic ketones. Given that ketones are prevalent in feedstock chemicals, natural products and pharmaceuticals, these transformations could offer new strategic bond disconnections in the synthesis of complex bioactive molecules.