Abstract: Indenoisoquinolinediones, as exemplified by lead compounds indotecan and indimitecan, are a class of non-camptothecin topoisomerase I poisons that display marked cytotoxic properties and for some of them antitumor activities in xenograft models. We have developed two alternative and dramatically different synthetic approaches to a variety of highly fused and diversely substituted models that differ from the elaboration of key precursors, i.e. arylated 2,3-dihydroisoquinolones. The first one is based upon a Suzuki-Miyaura cross-coupling reaction involving enol phosphates combined with a ring-closing metathesis (RCM) reaction to ensure the creation of the six-membered lactam unit. The second approach hinges upon the photoinduced electrocyclization of the 6π electron aromatic enamides. The presence of phenolic methoxy groups precluded an additional mandatory and problematic oxidation step to generate the unsaturated lactam ring. Intramolecular carbocationic annulation reaction and ultimate oxidation of the latent hydroxyl functionality completed the synthesis of the targeted title compounds.