Sequential Copper-Catalyzed Sonogashira Coupling, Hydroamination and Palladium-Catalyzed Intramolecular Direct Arylation: Synthesis of Azepino-Fused Isoindolinones

A sequential copper-catalyzed Sonogashira coupling followed by an intramolecular hydroamination and palladium-catalyzed intramolecular direct arylation reaction was developed to provide a convenient and modular approach for the synthesis of useful azepino-fused isoindolinones. Nineteen azepino-fused isoindolinones were prepared in moderate to high (22–90 %) yields. The developed protocol tolerated various functional groups and involved the formation of one carbon–nitrogen and two carbon–carbon bonds in a one-pot fashion. The palladium-catalyzed intramolecular direct arylation step involved formation of an unusual eight-membered palladacycle.