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

A transannular approach has been developed for the construction of pyrrolo[1,2-b]isoquinolinones starting from benzofused nine-membered enelactams. This process takes place in the presence of a halogenating agent and under Bronsted 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.

Automated summary

A transannular approach has been developed for the construction of pyrrolo[1,2-b]isoquinolinones starting from benzofused nine-membered enelactams. The reaction has a wide scope and can produce a variety of tricyclic products in good overall yield regardless of the substitution pattern in the initial lactam substrate. Furthermore, this method can be used for the total synthesis of certain biologically active compounds.