Diverse Isoquinoline Scaffolds by Ugi/Pomeranz-Fritsch and Ugi/Schlittler-Müller Reactions

Abstract

The Pomeranz-Fritsch reaction and its Schlittler-Müller modification were successfully applied in the Ugi postcyclization strategy by using orthogonally protected aminoacetaldehyde diethyl acetal and complementary electron rich building blocks. Several scaffolds, including isoquinolines, carboline, alkaloid-like tetrazole-fused tetracyclic compounds, and benzo[d]azepinone scaffolds, were synthesized in generally moderate to good yield. All our syntheses provide a short MCR-based sequence to novel or otherwise difficult to access scaffolds. Hence, we foresee multiple applications of these synthesis technologies.