Catalytic Asymmetric Isoindoline Synthesis

Significance

The authors present a catalytic asymmetric one-pot, two-step protocol to substituted isoindolines. The first step of this cascade is an aza-Friedel-Crafts reaction of indole 1 and N-tosyliminoenoate 2, catalyzed by Brønsted acid 3. The mono-addition product 5 was subsequently cyclized in a DBU-promoted Michael reaction to afford chiral isoindolines 4. The increasing formation of byproduct 6 with longer reaction times coming along with increased enantiomeric ratios of 4 denoted a stereoablative kinetic resolution taking place during the acid-catalyzed step. This assumption was confirmed in further experiments.