Asymmetric Friedel-Crafts Reaction of Indoles with Ethyl Trifluoropyruvate Using a Copper(I)-Bisoxazolidine Catalyst

Bisoxazolidine 1 is an effective ligand in the copper(I)-catalyzed Friedel-Crafts reaction of alkyl trifluoropyruvates and indoles. A range of ethyl 2-(3'-indolyl)-3,3,3-trifluoro-2-hydroxypropanoates was produced in up to 99% yield and 94% ee within 30 min to 4 h. The effect of temperature on conversion and enantioselectivity proved to be substrate specific and was optimized individually. Of particular interest is that this method tolerates the presence of substituents in various positions in the indole ring. Yields ranging from 90-97% and ee values between 90 and 94% were obtained at optimized temperatures with substrates carrying substituents in position 1 or 7.