Transannular Approach to 2,3-Dihydropyrrolo[1,2‑b]isoquinolin-5(1H)‑ones through Brønsted Acid-Catalyzed Amidohalogenation

A transannular approach has been developed for the construction of pyrrolo­[1,2-b]­isoquinolinones starting from benzo-fused nine-membered enelactams. This process takes place in the presence of a halogenating agent and under Brønsted acid catalysis and proceeds via a transannular amidohalogenation, followed by elimination. The reaction has been found to be wide in scope, enabling the formation of a variety of tricyclic products in good overall yield, regardless of the substitution pattern in the initial lactam substrate. The reaction has also been applied to the total synthesis of a reported topoisomerase I inhibitor and to the formal synthesis of rosettacin. Further extension of this methodology allows the preparation of 10-iodopyrrolo­[1,2-b]­isoquinolinones by using an excess of halogenating agent and these compounds can be further manipulated through standard Suzuki coupling chemistry into a variety of 10-aryl-substituted pyrrolo­[1,2-b]­isoquinolinones.