The Origins of the Stereoselectivity and Enantioswitch in the Rare-Earth-Catalyzed Michael Addition: A Computational Study

The general strategy for forming an opposite enantiomeric product from an asymmetric reaction involves using the opposite enantiomeric catalyst. For the Michael addition of 4-substituted-5-pyrazolones (1) to 1,4-dicarbonyl but-2-enes (2) catalyzed by rare earth with the chiral N,N′-dioxide derivative ligand (L), the product enantioselectivity was switched only by changing the rare earth from Sc to Y. To understand the mechanism, we investigated the reaction energy profile using the density functional theory combined with the automated reaction path search method. The enantioselectivity on 1 was determined by the coordination structure of the pre-reaction complex. The pre-reaction complex of the Sc system was ScL(OTf)1, where only the Si-face attack of 2 was blocked. Conversely, the pre-reaction complex of the Y system had one more triflate anion, (YL(OTf)₂1), which stabilized the different coordination structure, where only the Re-face attack of 2 was blocked. The origin of the diastereoselectivity was also investigated based on the transition states (TSs) of the C−C bond formation. The orientation of 2 at the TSs was fixed because of the proton transfer, which destabilized the TS affording the minor diastereomer.