An Efficient Enantioselective Method for Asymmetric Friedel-Crafts Alkylation of Indoles with α,β-Unsaturated Aldehydes

The Lewis base-Lewis base bifunctional catalytic system has been developed and successfully applied to the asymmetric Friedel-Crafts alkylation of indoles with alpha,beta-unsaturated aldehydes. The reactions are promoted by chiral diphenylprolinol trimethylsilyl ether in the presence of triethylamine. By this protocol, optically active 3-substituted indoles can be obtained in an organocatalytic process that is free of Lewis or protic acid in high yields with up to 98% ee. Besides, this reaction could be carried out on a gram scale without any loss in the enantioselectivity.