Exploration of Dependence of Organo-Catalyzed Enantioselective Michael Addition on the Pore Size of Mesoporous Host

Confinement, an effective strategy to improve the enantioselectivity in metal-catalyzed asymmetric synthesis, is a great challenge to the heterogeneous organocatalysis via hydrogen-bonding activation in that hydrogen bonding is more sensitive to the complicated spatial or chemical microenvironment in confined spaces. Here, visible improvement of enantioselectivity has been experimentally achieved on heterogeneous 9-amino (9-deoxy) epiquinine and 9-thiourea epiquinine catalysts in the Michael addition by rationally modulating the pore size of the mesoporous host. The enantiomer excess for heterogeneous 9-thiourea epiquinine is level with the homogeneous counterpart when the support pore size is reduced to an optimized spatial dimension. Theoretical calculations revealed that the immobilization can switch the activation routes, and the hydrogen-bonding interaction between substrate and pore wall influences the energy gap between R/S transition states, well accounting for the dependence of enantioselectivity on the pore size experimentally observed in the heterogeneous organocatalytic Michael addition. The results not only demonstrate significant development in the comprehension of confinement in the heterogeneous asymmetric catalysis but also suggest an original strategy in designing efficient enantioselective heterogeneous catalysts.