De novo construction of amine-functionalized metal-organic cages as heterogenous catalysts for micro flow catalysis

Abstract Micro flow catalysis is a cutting-edge approach with the potential to significantly advance chemical synthesis and manufacturing in terms of control, safety, efficiency, and scalability. However, a notable challenge in this field is developing heterogeneous catalysts with high activity and stability for micro-flow catalysis. Here we showcase incorporating amine-containing metal-organic cages into automated microfluidic reactors through strong covalent bonds, enabling highly continuous flow catalysis. This facilitates the design and synthesis of two Fe4L4 tetrahedral cages with different cavity sizes, each containing four uncoordinated amines. Post-synthetic modifications of the amine groups with 3-isocyanatopropyltriethoxysilane introduce multiple silane chains into the cage, covalently immobilized on the inner walls of the automated microfluidic system. This streamlines the process of catalyst loading and substrate conversion into a singular, integrated system. The immobilized cages prove highly efficient for the reaction of sequential condensation and cyclization of anthranilamide with aldehydes, showing comparable reactivity and superior recyclability in relative to free cages. This superiority arises from the large cage cavity, facilitating substrate accommodation and conversion, a high mass transfer rate and stable covalent bonds between cage and microreactor. This study represents the first report on the growth of self-assembled cages in the microreactor for continuous flow catalysis. It exemplifies the synergy of cages with microreactor technology, highlighting the benefits of heterogenous cages and potentials for future automated synthesis processes.