Brønsted Acid Catalyzed Friedel-Crafts Reaction

Significance

An organocatalytic asymmetric Friedel-Crafts reaction of indoles 2 with α-aryl enamides 1 catalyzed by the chiral phosphoric acid TRIP, which was previously introduced by the List and Akiyama groups, is described. Chiral amines 3 bearing quaternary carbon atoms were obtained in high yields and enantioselectivities. Enamides 1 are in equilibrium with their corresponding ketimines, which can subsequently be protonated by phosphoric acid 4. Additionally, a hydrogen bond is assumed to be formed between the N-H of indole 2 and phosphoric acid 4. This hypothesis is supported by the fact that both N-methylated enamides 1 and indoles 2 are poor substrates.