Organocatalytic Asymmetric Michael Addition of Pyrazol-5-ones to β-Trifluoromethyl-α,β-unsaturated ketones: Stereocontrolled Construction of Vicinal Quaternary and Tertiary Stereocenters

An efficient organocatalytic asymmetric Michael addition of 4-substituted-pyrazol-5-ones to β-trifluoromethyl-α,β-unsaturated ketones was developed. In the presence of a dipeptide-base urea-amide-tertiary amine catalyst, an array of chiral products containing pyrazolone and trifluoromethyl moieties bearing vicinal quaternary and tertiary stereocenters were obtained in good yields with good to excellent enantio- and diastereoselectivities (up to 95% yields, up to 97% ee and >20:1 d.r.). Moreover, the reaction was compatible with 4-substituted-pyrazol-5-ones containing either aryl or alkyl group at the C3 position.