Bifunctional Primary Amino‐thiourea Asymmetric Catalysis: The Imine‐Iminium Ion Mechanism in the Michael Addition of Nitromethane to Enone

Abstract

AbstractPrimary‐amine thioureas are preeminent organocatalysts used in challenging asymmetric Michael‐type reactions, such as in the addition of nitromethane to enones. However, the complete reaction mechanism of this reaction has not yet been fully elucidated. Considering that the primary‐amine group could act via both base and iminium ion catalysis, both mechanisms were investigated in this work using theoretical methods. The calculations have indicated that the base catalysis is kinetically unfeasible, with very high overall ΔG≠. An imine‐iminium ion catalysis is a viable route. This mechanism requires the participation of an acid as a cocatalyst (additive) in several steps, including the formation of the imine. The rate‐determining step corresponds to the proton transfer from the nitromethane to the imine, forming the nitronate‐iminium ion‐pair intermediate. This complex reacts via nucleophilic attack of the nitronate ion to the electrophilic carbon of the iminium ion, forming a new C−C bond that determines the enantioselectivity of the reaction.