Self-assembled resorcin[4]arene hexamer catalyzes the intramolecular hydroalkoxylation of unsaturated alcohols to the corresponding cyclic ethers under mild conditions. The mode of catalysis and encapsulation-based substrate selectivity of the host efficiently mimic the basic principle of operation observed in enzymes.

Molecular capsules have attracted interest as simple enzyme mimetics and several examples of catalytic transformations in water-soluble metal–ligand based systems have been reported. This is not the case for hydrogen-bond based molecular capsules, which in contrast can be employed in organic solvents. We describe herein our investigations of such a system: The resorcin[4]arene hexamer is one of the largest hydrogen bond-based self-assembled capsules and has been studied intensively due to its ready availability. We present evidence that the capsule acts as a reasonably strong Brønsted acid (pKa approximately 5.5–6). This finding explains the capsule’s high affinity toward tertiary amines that are protonated and therefore encounter cation-π interactions inside the cavity. We were able to translate this finding into a first synthetic application: A highly substrate-selective Wittig reaction. We also report that this property renders the capsule an efficient enzyme-like catalyst for substrate selective diethyl acetal hydrolysis.

Self-assembled resorcin[4]arene hexamer catalyzes the intramolecular hydroalkoxylation of unsaturated alcohols to the corresponding cyclic ethers under mild conditions. The mode of catalysis and encapsulation-based substrate selectivity of the host efficiently mimic the basic principle of operation observed in enzymes.