Chemo- and Regioselective Construction of Functionalized Isocoumarin, Flavone, and Isoquinolinedione via a One-pot Reaction of o-Quinol Acetate and Soft Nucleophiles

A one-pot strategy for the synthesis of substituted isocoumarin, flavone, and isoquinolinedione derivatives through a switchable C-arylation/lactonization or SNAr reaction from a wide range of soft nucleophiles and o-quinol acetates has been developed. This base-mediated protocol proceeds under transition-metal-free conditions and selectively affords various heteroarenes in 13-98% yields from readily prepared or commercially available 1,3-dicarbonyl and alpha-EWG-substituted carbonyl compounds. The synthetic utility is further demonstrated in the synthesis of potential anti-HIV and anti-coronavirus derivatives and COX-2 inhibitors. In addition, detailed experimental and computational studies are performed to provide an intensive understanding and strong support of the reaction mechanism.

Automated summary

A one-pot synthesis of substituted isocoumarin, flavone, and isoquinolinedione derivatives has been developed using a switchable C-arylation/lactonization or SNAr reaction. This base-mediated protocol proceeds under transition-metal-free conditions and selectively affords various heteroarenes in good yields. The synthetic utility of this method is demonstrated in the synthesis of potential anti-HIV and anti-coronavirus derivatives and COX-2 inhibitors. Detailed experimental and computational studies provide a comprehensive understanding of the reaction mechanism.