Direct Organocatalytic Asymmetric Michael Reaction of Fluorine Hemiaminal-Type Nucleophile to 4-Nitro-5-Styrylisoxazoles

Herein, we report a chiral bifunctional thiourea catalyzed asymmetric Michael addition reaction between 2-(trifluoromethyl)oxazol-5(2H)-one as a direct C-2-position nucleophile to 4-nitro-5-styrylisoxazoles for the first time. The reaction affords the corresponding products bearing adjacent CF3-substituted hetero-quaternary and tertiary stereocenters in moderate to high yields (up to 94% yield) with good to excellent enantioselectivities (up to 99% ee) and excellent diastereoselectivities (up to > 20:1 dr) under mild reaction conditions. Moreover, the selected compounds displayed good biological activities and further investigation is underway.