Catalytic, highly enantioselective Friedel-crafts reactions of aromatic and heteroaromatic compounds to trifluoropyruvate. A simple approach for the formation of optically active aromatic and heteroaromatic hydroxy trifluoromethyl esters

A new catalytic enantioselective synthetic method for the formation of opti cally active aromatic and heteroaromatic hydroxy-trifluoromethyl ethyl este rs is presented. This catalytic enantioselective Friedel-Crafts reaction of trifluoromethyl pyruvate with aromatic and heteroaromatic compounds is cat alyzed by a chiral bisoxazoline copper(II) complex and proceeds in good yie ld and with high enantiomeric excess. For a series of substituted indoles, the corresponding 3-substituted hydroxytrifluoromethyl ethyl esters are for med in up to 93% yield and 94% ee. Pyrrole and 2-substituted pyrroles also react with trifluoromethyl pyruvate in a highly enantioselective aromatic e lectrophilic reaction and up to 93% ee and good yields are obtained. Furane s and thiophenes give the corresponding 2-hydroxy-trifluoromethyl ethyl est ers in high enantiomeric excess; however, the yields of the products are on ly moderate. Various types of aromatic compounds react in this catalytic re action with trifluoromethyl pyruvate to give the aromatic electrophilic add ition product in good yield. To obtain high enantiomeric excess (>80% eel i t is necessary that aromatic amines are protected with sterically demanding protecting groups such as benzyl or allyl. This prevents coordination of t he amine nitrogen atom to the catalyst, as aromatic amines having a N,N-dim ethyl group probably coordinate to the catalyst, leading to a significant r eduction of the enantioselective properties of the catalyst. On the basis o f the experimental results and the absolute configuration of the formed chi ral center, the mechanism for the catalytic enantioselective Friedel-Crafts reaction is discussed.