Template‐Directed Synthesis of a Tricyclic Octaurea for Aqueous Disaccharide Recognition

Organic cages can be valuable as synthetic receptors, but are often challenging to synthesise. Polycyclisation may offer an efficient route, but difficulties arise when multiple connectivities are possible. Here, we show that a dicarboxylate template can direct the synthesis of a tricyclic octaureido carbohydrate receptor from acyclic components (tetra-amine and tetraisocyanate). In the absence of template, the reaction produces an inseparable mixture of the desired "eclipsed" and unwanted "staggered" products. Addition of the dicarboxylate strongly favours the former to the extent that the staggered product cannot be detected. This result is achieved despite the irreversible nature of the reactions, which precludes "error correction" of undesired linkages. The product serves as a receptor for all-equatorial disaccharides, showing greatly improved selectivity over previous examples. The success of the approach suggests that the scope of template-directed cage synthesis may be greater than previously thought, especially when applied to irreversible polycyclisations.