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The development of flow processes for metal-ligand self-assembly and ring-closing metathesis has facilitated the efficient and scalable preparation of iron(II) pentafoil knot and Star of David [2]catenane. Use of a flow reactor also enables the formation of the otherwise inaccessible coordinatively labile zinc(II) pentameric helicate, leading to an efficient two-step synthesis of the zinc(II) pentafoil knot. As the first example of topology-synthesis in flow, our work demonstrates that the metal-ligand self-assembly can be readily adapted to flow techniques, even for labile complexes that are difficult to prepare in batches. The method is well-positioned for expansion to other topological complexes made from the metal template approach. Transitioning from laboratory batch synthesis to efficient large-scale production using continuous flow reactors not only paves the way for new applications of flow synthesis in chemical topology but also enhances the accessibility of these “hard-to-make” entangled moieties, thereby opening avenues for exploring their applications in various fields.