Regioselective Insertion of Diazo Compounds Into 3‐Hydroxyisoindolinones for the Synthesis of Isoquinolones

Both 3‐hydroxyisoindolinones and isoquinolones are structural motifs found in many natural alkaloids, and their derivatives exhibit a wide range of therapeutic applications. Herein, we report the direct conversion of 3‐hydroxyisoindolinones into isoquinolones via a diazo ester insertion reaction. This transformation involves the nucleophilic addition of diazo esters to iminium ions, which are generated in situ from the dehydration of 3‐hydroxyisoindolinones. The resulting diazonium intermediates undergo ring expansion through exclusive 1,2‐nitrogen migration to give isoquinolones in the presence of a bulky triarylborane Lewis acid catalyst. In contrast, when the nitrogen atom and the 3‐aryl group of the starting material are tethered by an alkyl bridge, protoberberine alkaloid derivatives are formed via regiospecific 1,2‐aryl migration.