Asymmetric Brønsted Acid Catalyzed Isoindoline Synthesis: Enhancement of Enantiomeric Ratio by Stereoablative Kinetic Resolution

Improving with time : The first catalytic asymmetric synthesis of chiral 1,3‐disubstituted isoindolines is based on a Brønsted acid catalyzed one‐pot reaction consisting of a Friedel–Crafts reaction and a base‐catalyzed aza‐Michael addition (see scheme). The enantiomeric ratio of the product significantly increases with reaction time as a result of a Brønsted acid catalyzed stereoablative kinetic resolution, which occurs in tandem to the first step.