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-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.