Asymmetric Friedel–Crafts addition of indoles to N-sulfonyl aldimines catalyzed by Cu(ii) chiral amino alcohol based Schiff base complexes

Abstract

Recyclable copper(II) chiral amino alcohol based Schiff base complexes smoothly catalysed the Friedel-Crafts alkylation of indole with aryl aldimine in good yields (98%) and with enantioselectivities up to 97%. The effects of ligand structure, solvent, metal source and temperature on the reaction were also studied. The catalytic system worked very well several times retaining its performance. To understand the mechanism of the catalytic Friedel-Crafts addition reaction, a kinetic investigation was carried out with different concentrations of the catalyst Cu(II)-L 2 , indole and N-(3-nitrobenzylidene)-4-methylbenzene sulfonamide as a model substrate. The Friedel-Crafts alkylation reaction of N-(3-nitrobenzylidene)-4-methylbenzene sulfonamide was first order with respect to the concentration of the catalyst and the nucleophile but did not depend on the initial concentration of the substrate (aryl aldimine). An appropriate mechanism of the Friedel-Crafts alkylation reaction is proposed.

Direct Asymmetric Arylation of Imines

“…The reaction afforded the corresponding products in good to excellent yields (up to 98%) with moderate to high enantioselectivities (up to 97%) (Scheme 13). [27] Here also, the N-Me-indole did not react under the reaction conditions.…”

“…applied dinuclear copper catalyst based on ligand 7 for the asymmetric alkylation of indoles with N ‐sulfonylaldimines to produce 3‐indolyl methanamine derivatives. The reaction afforded the corresponding products in good to excellent yields (up to 98%) with moderate to high enantioselectivities (up to 97%) (Scheme ) . Here also, the N ‐Me‐indole did not react under the reaction conditions.…”

The Future of Catalysis by Chiral Lewis Acids

“…Because of their nucleophilic reactivity, indoles have been the featured substrates in the vast majority of applications, and a wide variety of chiral catalysts have been used to activate an α,β-unsaturated nitro compound [181][182][183], α,β-unsaturated ester [184][185][186], trifluoropyruvate [187,188], or imine [189] for electrophilic substitution. Applications to phenols [190] have been more limited (Scheme 40).…”

Catalytic C3 aza-alkylation of indoles

“…Finally, dinuclear copper-based chiral complexes (4 in Figure 1) were reported by Bajaj and co-workers. 66 The required chiral Shiff base ligands were easily accessed reacting aromatic bis-aldehydes with different enantiopure amino alcohols, and were exploited in combination with Cu(OTf) 2 . This catalyst efficiently promoted the reaction between indoles and N-sulfonyl aldimines, with excellent yields and modest to high enantioselectivity.…”