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.

本研究开发了一种高效的有机催化不对称迈克尔加成（Michael addition）反应，实现4-取代吡唑-5-酮与β-三氟甲基-α,β-不饱和酮之间的不对称加成。在基于二肽的脲-酰胺型叔胺催化剂作用下，可得到一系列兼具吡唑啉酮与三氟甲基官能团的手性产物，此类产物分子中含有相邻的季碳和叔碳立体中心；目标产物收率良好，对映选择性与非对映选择性均处于良好至优异水平，最高收率可达95%，最高对映体过量值（enantiomeric excess, ee）为97%，非对映体比率（diastereomeric ratio, d.r.）大于20:1。此外，该反应对C3位带有芳基或烷基的4-取代吡唑-5-酮底物均具有良好的兼容性。