Synthesis of Isoindole N-Oxides by Palladium-Catalyzed C-H Functionalization of Aldonitrones

A palladium-catalyzed strategy for isoindole N-oxide ring construction by C-H functionalization of aldonitrones is described. Our protocol is of general character, providing isoindole N-oxides with a variety of functional groups, including very sterically congested products. Further transformations into spirocyclic isoindolines, isoindoles, or a polycyclic isoquinolinium salt have been demonstrated as well. A mechanistic study suggests that the catalytic process proceeds via a Heck-type addition to the double C=N bond.

Automated summary

A palladium-catalyzed strategy for constructing isoindole N-oxide ring by C-H functionalization of aldonitrones is presented. The protocol is versatile and allows for the introduction of various functional groups, even in sterically congested products. Transformations into spirocyclic isoindolines, isoindoles, and polycyclic isoquinolinium salt have also been demonstrated. Mechanistic studies suggest a Heck-type addition to the double C=N bond as the catalytic process.