Transition metal-catalyzed C-C bond activation is currently a developing area and it has dramatically expanded the chemist’s toolbox for the synthesis of complex organic scaffolds. The oxidative addition of the C-C bond to the metal can generate two C-M bonds, which enables direct functionalization of two individual C-center.  Among the various approaches of C-C bond activation, targeting a strained organic molecule brought tremendous success for the synthetic community. Though, a three-membered strained system like cyclopropane derivatives has been extensively used, more strained smallest Huckel aromatic molecule cyclopropenone was less investigated. By taking advantage of the inherent strain of cyclopropenone, we have generated four-membered palladacyclobutenone. The intermediate palladacyclobutenone can discharge and arrest one molecule of carbon monoxide to generate palladacyclopentendione. The following intermediate can be further functionalized in presence of structurally diverse anilines to deliver maleimide derivatives with the release of hydrogen gas (detected in GC). Herein, for the first time, cyclopropenone was used as a green carbon monoxide source. In another case, palladacyclobutenone underwent σ-bond metathesis in presence of phenols and anilines to give <i>α,β</i>- unsaturated esters and amides. The vinylic hydrogen in the product is coming from phenol/aniline, which was proved by deuterium exchange studies. The bulky <i>N</i>-heterocycle ligand is providing the necessary steric requirement to the reaction, playing a pivotal role. Further, the proposed mechanism was supported by detailed mechanistic studies. The generality and the scope of the reaction were extended through late-stage functionalization of bioactive molecules and drugs such as umbelliferon, estrone, and procaine.

Palladium catalyzed C-C bond activation: Harnessing the strain of cyclopropenone

ACS Fall 2021

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