The first Ru(II)-catalyzed C-H activation/[4 + 2] annulation of aryl imidates with heteroaromatic iodonium ylides is reported. Our approach features the utilization of a commercially available ruthenium catalyst, providing a one-step construction of phelligridin analogues from easily available and nonpreactivated starting materials. The developed methodology is successfully employed for the total synthesis of phelligridin A, significantly streamlining previous multistep synthesis. The potential of this approach is further demonstrated through a modular synthesis of the core structure of phelligridin C/D.