Organocatalyzed Asymmetric Michael Addition of 4‐Monosubstituted‐pyrazol‐5‐ones to Enones: Construction of Vicinal Quaternary and Tertiary Stereocenters

Abstract

Pyrazolone moiety bearing an all‐carbon quaternary stereogenic center is frequent in biologically active products and pharmaceuticals. The catalytic route for the construction of a quaternary carbon center possesses challenges. In this report, catalytic asymmetric Michael addition of 4‐monosubstituted‐pyrazol‐5‐ones to simple enones catalysed by primary amine‐Brønsted acid composite has been developed. An array of pyrazolone derivatives bearing vicinal all carbon quaternary and tertiary stereocenters, were obtained in moderate to good diastereoselectivities (up to 92:8 dr) and good to excellent enantiomeric excess (up to 99% ee). In addition, antipode for enantiomers of the pyrazolone derivatives were also be realized in good to high stereoselectivities (up to 92:8 dr and up to 98% ee).