Intermolecular Cyclization of Alkyl Chains of Ketones for Constructing <i>ortho</i> -Diacylbenzenes

<i>ortho</i>-Diacylbenzenes serve as versatile precursors for pharmaceutical synthesis, other biological applications, and organic synthesis. The intermolecular cyclization between the alkyl chains of two ketone substrates for the synthesis of <i>ortho</i>-diacylbenzenes offers atom-economical access to <i>ortho</i>-diacylbenzenes. However, intermolecular cyclization between the alkyl chains of two ketone substrates is a challenging chemical transformation. Here, we report that the copper-catalyzed reaction between ketone substrates containing alkyl chains in the presence of TEMPO as the oxidant undergoes dehydrogenation-initiated intermolecular [4 + 2] cyclization between the alkyl chains of two ketone substrates to regioselectively produce the <i>ortho</i>-diacylbenzene with high functional group tolerance. This copper-catalyzed intermolecular cyclization between the alkyl chains of two ketone substrates enables ketone substrates containing diverse molecular scaffolds to serve as efficient substrates for the synthesis of <i>ortho</i>-diacylbenzenes, although butyl-phenyl-ketones containing substituents at the δ-positions of the butyl chains regioselectively produce <i>meta</i>-diacylbenzene products. Consequently, structurally complex ketones generated from natural products or bioactive compounds undergo targeted transformation to efficiently produce <i>ortho</i>-diacylbenzenes. Interestingly, this copper-catalyzed intermolecular cyclization between the alkyl chains of two ketone substrates proceeds through the electrophilic TEMPO-catalyzed unknown [4 + 2] cycloaddition of two electron-poor alkenyl ketone intermediates, which overcomes the general requirement of the Diels-Alder cycloaddition reactions.