Divergent synthesis of indenoisoquinolines and indenoisochromenes by rhodium-catalysed cyclocondensation of N-substituted benzamides with 2-diazoindenediones

Abstract

An atom-and step-economical method for the synthesis of indenoisoquinolines as a scaffold of topoisomerase I inhibitors was developed using rhodium-catalysed cyclocondensation of N-monosubstituted benzamides with 2-diazoindenedione, where the unexpected indenoisochromenes were obtained in high yields with high selectivity through rhodium-catalysed cyclocondensation of N-tert-butylbenzamides with 2-diazoindenediones (2). These results indicated that the kinds of substituents on a nitrogen atom of the starting benzamides controlled which product—indenoisoquinolines or indenoisochromenes—could be obtained selectively by the tuning of rhodium catalyst systems under optimal reaction conditions. Namely, indeno[1,2-c]isoquinolin-5,11-diones (3 and 5) were formed directly from 1,3-dicarbonyl intermediates by intramolecular nucleophilic attack of an amide nitrogen atom on a carbonyl group in 1,3-dicarbonyl intermediates, followed by dehydration, whereas indeno[1,2-c]isochromene-5,11-diones (7) were obtained from enol tautomers of 1,3-dicarbonyl intermediates by intramolecular nucleophilic attack of a hydroxyl group on an amide carbonyl group together with liberation of an amine.