Enantioselective Aza-Friedel–Crafts Reaction of Indoles with Ketimines Catalyzed by Chiral Potassium Binaphthyldisulfonates

Abstract

The enantioselective aza-Friedel–Crafts reaction of indoles with low-reactive ketimines has been developed in the presence of a chiral monopotassium binaphthyldisulfonate as a strong Brønsted acid catalyst. A broad substrate scope was achieved, and the corresponding 3-indolylmethanamines with a chiral quaternary carbon center were obtained in high yields with high enantioselectivities. The addition of a catalytic amount of acetic acid considerably promoted the reaction, and a gram-scale reaction could be achieved with reduced catalyst loading.

Direct Asymmetric Arylation of Imines

“…However, the reaction proceeds in the presence of a potassium salt of chiral strong Brønsted acid catalyst, bis‐potassium binaphthyldisulfonate. A broad substrate scope was observed, and the corresponding 3‐indolylmethanamines with a quaternary chiral carbon center were obtained in high yields and with high enantioselectivities (Scheme ) . Notably, 4‐OMe‐substituted indole gave the product with 90% ee but in low yield (20% within 20 h), probably due to the steric hindrance.…”

Catalytic C3 aza-alkylation of indoles

“…This approach could also be applied to aliphatic ketimines, even though with lower yields and stereoselectivities. 14 Thioureas. Thioureas are common bifunctional chiral organocatalysts, able to promote asymmetric reactions through the formation of a network of hydrogen bonding interactions with the reacting nucleophiles and electrophiles.…”

“…12,13 If a chiral catalyst is employed, a control over the reaction stereochemistry could be exerted. 14 The mechanism, depicted in Scheme 1, can occur in one-pot, through the in-situ generation of the iminium intermediate, or the imine could be pre-formed and isolated. The catalyst plays a fundamental role also in the stabilization of the iminium moiety and during indole alkylation at C3 position, favouring the re-aromatization process accordingly to the Friedel-Crafts model (Scheme 1).…”

Urea derivative organocatalyzed enantioselective Friedel–Crafts alkylation of α‐naphthols with isatins

“…[26][27][28][29][30][31][32][33] Despite the great achievements in such reactions, the main focus has been on the use of reactive heteroarenes-indoles, pyrroles, and furan as nucleophiles. [34][35][36][37][38][39][40][41][42][43] The application of hydroxylarenes is rare because of their reduced nucleophilicity. [44][45][46][47][48][49][50][51][52][53][54][55] In 2014, Wu et al 56 disclosed the first enantioselective F-C reaction of α-naphthols with isatins employing cinchona derivatives to provide 3-aryl-3-hydroxy-2-oxindoles with 26%-94%ees.…”