Regio- and Enantioselective N-Heterocyclic Carbene-Catalyzed Annulation of Aminoindoles Initiated by Friedel-Crafts Alkylation

Chiral annulated indoles are unique molecules with numerous examples of this structural motif in natural and medicinally relevant compounds. However, accessing these enantioenriched molecules, particularly indoles annulated on the benzene ring, has been limited and often overlooked. This study presents a highly efficient organocatalytic protocol for synthesizing chiral annulated indoles. The efficiency of the developed methodology is demonstrated by its broad substrate scope, excellent functional group tolerance, and the use of only 1 mol% of a chiral conjugated acid of catalyst. Additionally, the study of the observed regioselectivity, gram-scale reaction, and various follow-up transformations underscore the potential of this method.