Highly enantioselective Friedel-Crafts alkylation of indoles with α,β-unsaturated ketones with simple Cu(II)-oxazoline-imidazoline catalysts

Abstract

A series of novel chiral ligands L1-L4 with an imidazoline-oxazoline framework have been developed as new type of non-symmetric N,N-bidentate ligands. All the chiral ligands were prepared from 2,2-diethylmalonic acid and enantiomerically pure (S)-2-amino-3-methyl-1-butanol in four steps with excellent optical purity. These newly developed ligands efficiently affect the copper-catalyzed enantioselective addition of indole to α,β- unsaturated ketones, yielding the corresponding adducts in good yield and high enantiomeric excess. The fine-tuning capability of these ligands plays a significant role in achieving high enantioselectivity in the asymmetric alkylation (up to 99% ee). The higher enantioselectivity of the reaction could be due to the activation and asymmetric induction of chiral Lewis acid metal complex coordinated by enones through a concerted mechanism of 1,4-metal bonding model. © 2013 Elsevier Ltd. All rights reserved.