An efficient method for the synthesis of isoquinolino[1,2-b]quinazolin-8-one derivatives and 12-methyl-12H-isoindolo[1,2-b]quinazoline-10-one derivatives is described herein. With rhodium catalysis, the desired products are obtained through a sequence reaction of C–H activation-based alkenylation and intramolecular aza-Heck-type cyclization. The developed method has a wide range of substrate tolerance under mild conditions and provides an alternative for the structural elaboration of quinazoline compounds.