Linker-Cluster Cooperativity in Confinement of Proline-Functionalized Zr-Based Metal-Organic Frameworks and its Effect on the Organocatalytic Aldol Reaction

Metal organic frameworks (MOFs) provide unique opportunities for molecular heterogeneous catalysis by mimicking the active sites of enzymes. However, understanding and controlling the interaction between the metal node and the organic linker carrying the catalytic unit and the resulting confinement effects remain challenging. Here, in a combined theoretical and experimental approach Zr-UiO-67-MOFs with ortho-N-acylproline-functionalized biphenyl-dicarboxylate linkers were prepared and compared with the corresponding MOFs with regioisomeric meta-linkers. As benchmark catalysis the organocatalytic aldol reaction of p-nitrobenzaldehyde and cyclohexanone was studied. Experimental results revealed that the ortho-linker accelerated the aldol reactions, whereas the regioisomeric meta-linker decreased the reaction rate, which was rationalized by pore blocking of the meta-linker via molecular dynamics simulations. Moreover, the acid modulator used in the MOF preparation also played a critical role in the formation of acetal byproducts through competing acid catalysis. Our study provides novel insights into the cooperative catalysis between the linker-attached organocatalyst and the MOF metal center.