Intermolecular Cyclization of Alkyl Chains of Ketones for Constructing ortho-Diacylbenzenes.

ortho-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 ortho-diacylbenzenes offers atom-economical access to ortho-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 ortho-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 ortho-diacylbenzenes, although butyl-phenyl-ketones containing substituents at the δ-positions of the butyl chains regioselectively produce meta-diacylbenzene products. Consequently, structurally complex ketones generated from natural products or bioactive compounds undergo targeted transformation to efficiently produce ortho-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.