Enantioselective synthesis of trifluoromethyl substituted cyclohexanones via an organocatalytic cascade Michael/aldol reaction

An enantioselective (92-99% ee) Michael/aldol cascade reaction between 4,4,4-trifluoroacetoacetates and alpha,beta-unsaturated enones was established in the presence of cinchona alkaloid-based primary amines. Various beta-CF3-cyclohexanones were constructed in high yields (81-99%) as a couple of separable diastereomers. This tandem reaction was sensitive to acidic co-catalysts, with a Michael/aldol condensation process favorably occurring to generate beta-CF3-cyclohexenones (42-69% yield, 84-96% ee) in the presence of trifluoroacetic acid.