Exceedingly Fast, Direct Access to Dihydroisoquinolino[1,2- b]quinazolinones through a Ruthenium(II)-Catalyzed Redox-Neutral C-H Allylation/Hydroamination Cascade.

Abstract

A ruthenium(II)-catalyzed redox-neutral synthesis of dihydroisoquinoline-fused quinazolinone derivatives has been accomplished through the merger of C-H activation and alkene difunctionalization using quinazolinone as an inherent directing group. This intermolecular reaction proceeds rapidly and is complete within 10 min, providing the annulation product in high yields without any stoichiometric metal oxidant. Mechanistically, this tandem reaction proceeds through directed ortho C-H allylation followed by hydroamination with the proximal -CONH group, to furnish 6-methyl-5,6-dihydro-8 H-isoquinolino[1,2- b]quinazolin-8-ones in a single operation. The carboxylic acid additive has a dual role in the formation of active catalyst and protodemetalation.