Synthesis of C6-Substituted Isoquinolino[1,2-<i>b</i>]quinazolines via Rh(III)-Catalyzed C–H Annulation with Sulfoxonium Ylides

Abstract

We report the synthesis of C6-substituted isoquinolino[1,2-<i>b</i>]quinazolinones via rhodium(III)-catalyzed C-H annulation with sulfoxonium ylides and evaluation of the cytotoxic activity of the scaffold. This C-H activation approach enables the most straightforward and convergent synthesis of C6-substituted isoquinolino[1,2-<i>b</i>]quinazolines reported to date. This operationally simple method is compatible with a wide variety of the sulfoxonium ylide and arene C-H activation coupling partners, permitting access to diverse isoquinolino[1,2-<i>b</i>]quinazolines. This method shows a high atom economy, generating H₂O and dimethyl sulfoxide (DMSO) as by-products. This method is scalable and operates with exquisite N-lactam cyclization selectivity, thus enabling expedient access to new heterocyclic analogues featuring promising cytotoxic properties.