Chiral Brønsted Acid-Catalyzed Intramolecular Asymmetric Dearomatization Reaction of Indoles with Cyclobutanones via Cascade Friedel–Crafts/Semipinacol Rearrangement

Abstract

The highly efficient synthesis of chiral indolines fused with an azabicyclo[2.2.1]heptanone moiety is achieved by an asymmetric dearomatization reaction of indoles with cyclobutanones. A new chiral imidodiphosphorimidate (IDPi) catalyst is synthesized and exhibits extraordinary activity in promoting a cascade Friedel-Crafts/semipinacol rearrangement. Target molecules are prepared in good yields (up to 95%) with excellent enantioselectivity (up to 98% ee) with operational convenience. Combined experimental and computational studies provide detailed mechanistic insights into the energy landscape and origin of the stereochemical induction of the reaction.