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

Abstract

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-based 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 enantioselectivity and diastereoselectivity (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.