Expedient assembly of densely functionalized indanones via nickel-catalyzed alkene hydroacylation with methyl esters

Abstract

Given the chemical feedstock availability but intrinsic chemical inertness, the development of applicable cross-coupling with methyl esters as acyl electrophiles remains highly desirable and particularly challenging. Herein, we report a novel and concise nickel-catalyzed intramolecular alkene hydroacylation protocol, resulting in the expeditious generation of a wide range of medicinally active indanone and indazolone derivatives in good efficiency. This straightforward approach features good functional group tolerance, easy post-synthetic modification, total synthesis and LSF of some representative clinical drugs. A preliminary in vitro antioxidant evaluation reveals that 2-(4-dimethylaminophenyl)-1-indanone and 2-aryl-3-indazolone derivatives exhibit excellent free radical scavenging activities.