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Direct Catalytic Asymmetric Synthesis of Trifluoromethylated γ-Amino Esters/Lactones via Umpolung Strategy

Hu, Bin, Deng, Li
Journal of organic chemistry 2018 v.84 no.2 pp. 994-1005
Lewis acids, Lewis bases, acrylates, carbon, catalysts, chemical bonding, chemical reactions, chemical structure, diastereoselectivity, enantioselectivity, esters, imines, lactones, organic chemistry, quinine
Enabled by the discovery of new cinchonium salts and coadditives, a direct and efficient asymmetric access to trifluoromethylated γ-amino esters/lactones has been realized through the enantioselective and diastereoselective umpolung reaction of trifluoromethyl imines with acrylates or α,β-unsaturated lactones as carbon electrophiles. At 0.5–5.0 mol % catalyst loadings, the newly developed catalytic system activates a variety of imine substrates as unconventional nucleophiles to mediate highly chemo-, regio-, diastereo-, and enantioselective C–C bond forming reactions. The developed synthetic protocol represents an excellent strategy to target a series of versatile and enantiomerically enriched γ-amino esters/lactones in good to excellent yields from the readily available starting materials. Additionally, we found that the epi-vinyl catalysts based on cinchonidine and quinine promote a similarly high enantioselective reaction generating the opposite configuration of chiral products in a highly efficient manner, which allows convenient access to either the R- or S-enantiomer of the chiral amine products in high yields and excellent enantioselectivities.