Enantioselective Organocatalytic Conjugate Addition of Malonates to β,β-Disubstituted β-Trifluoromethyl Enones under High Pressure

The first enantioselective Michael addition of malonates to acyclic β,β-disubstituted enones has been developed. Sterically hindered β-trifluoromethyl α,β-unsaturated 2-acyl thiazoles and benzothiazoles were found to be the most reactive groups of enones in the reaction catalyzed by bifunctional tertiary amine-thioureas (2-5 mol %). However, application of hyperbaric conditions (8-10 kbar) was required. The adducts containing quaternary stereogenic centers with a CF₃ group were obtained in high yields (vs <1% at 1 bar) with enantiomeric excesses up to 95%.