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

Water enables new catalytic reactions for otherwise unreactive substrate systems. Under the on water reaction conditions, extremely unreactive beta,beta-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 beta-position, which might show highly interesting pharmaceutical properties.