Water‐Enabled Catalytic Asymmetric Michael Reactions of Unreactive Nitroalkenes: One‐Pot Synthesis of Chiral GABA‐Analogs with All‐Carbon Quaternary Stereogenic Centers

Abstract

AbstractWater enables new catalytic reactions for otherwise unreactive substrate systems. Under the “on water” reaction conditions, extremely unreactive β,β‐disubstituted nitroalkenes smoothly underwent enantioselective Michael addition reactions with dithiomalonates using a chiral squaramide catalyst, affording both enantiomers of highly enantioenriched Michael adducts with all‐carbon‐substituted quaternary centers. The developed “on water” protocol was successfully applied for the scalable one‐pot syntheses of chiral GABA analogs with all‐carbon quaternary stereogenic centers at the β‐position, which might show highly interesting pharmaceutical properties.