Quinazolinone-to-Isoquinoline Metamorphosis by Ruthenium-Catalyzed [4+2] Annulation with Sulfoxonium Ylides

Abstract

Molecular editing of quinazolinones to isoquinolines by a novel ruthenium-catalyzed [4+2] annulation with sulfoxonium ylides has been developed. The method permits the precise and rapid assembly of multisubstituted aminoisoquinolines, a class of heterocycles that play a privileged role in organic synthesis and pharmaceutical development. This new catalytic process exhibits novel programmability, including directed C−H acetylation, nucleophilic cyclization, and alcoholysis. Remarkably, various 2-arylquinazolinones and sulfoxonium ylides could be employed in excellent yields with broad functional group tolerance. This heterocycle-to-heterocycle protocol is compatible with green chemistry using an EtOH solvent and releasing H 2 O and dimethyl sulfoxide as byproducts.