Access to Chiral GABA Analogues Bearing a Trifluoromethylated All-Carbon Quaternary Stereogenic Center through Water-Promoted Organocatalytic Michael Reactions

摘要

Water enables the highly challenging enantioselective Michael addition of sterically congested beta-trifluoromethyl-beta-aryl- or -alkyl-substituted nitroolefins with dithiomalonates. Under on-water conditions, the reaction rates were remarkably accelerated as a result of enforced hydrophobic interactions between catalysts and reactants. Takemoto-type thiourea catalysts are very effective for this transformation, affording highly enantioenriched Michael adducts that provide simple access to chiral gamma-aminobutyric acid (GABA) analogues with a beta-trifluoromethylated quaternary stereocenter.