Bifunctional Transition Metal-Based Molecular Catalysts for Asymmetric C–C and C–N Bond Formation

This paper describes recent advances in the development of the asymmetric catalytic reactions promoted by conceptually new bifunctional molecular catalysts. These reactions include the enantioselective Michael addition of 1,3-dicarbonyl compounds to cyclic enones and nitroalkenes, and the enantioselective direct amination of α-cyanoacetates to diazoesters. The nature of the catalyst in each particular case was delicately tuned by adjusting the combination of the central metal together with the structures of the cooperating ligands, applied solvents, and the reaction conditions to achieve the utmost catalytic performance in terms of reactivity and selectivity. In the presence of the optimized catalyst the addition reactions proceeded smoothly with a 1:1 M ratio of the reagents to give the corresponding chiral adducts with excellent yields and ee’s. Preliminary mechanistic studies based on NMR spectroscopy and DFT analysis showed that the key step of the catalytic cycle is the interaction of the bifunctional catalyst with a pronucleophilic reagent that leads to stereoselective formation of C-, O-, or N-bound amino complexes. The resulting amino catalyst bearing metal-bound nucleophiles readily reacts with an electrophile that acquires the reactive conformation through the cooperative effect of the acidic NH protons. This results in the formation of a C–C or a C–N bond yielding the corresponding products in a highly stereoselective manner.