In this Account, we outline our investigation into the supramolecular resorcinarene capsule as a catalyst. Molecular capsules not only are of interest due to the similarities of their binding pockets with those of natural enzymes but also feature potential advantages for catalysis. Due to the restricted internal volume of the binding pockets, substrate selectivities are commonly observed. Substrates that are encapsulated more efficiently will be converted selectively in the presence of less suitable substrates. This size selectivity cannot be obtained in a regular solution experiment. In addition, because of the distinct chemical environment inside the capsule, different product selectivities may be observed. Furthermore, the encapsulation of reactive catalysts inside confined environments may improve catalyst compatibility for multicatalyst tandem reactions. Although the potential advantages of performing catalysis inside closed microenvironments are generally recognized, the number of known catalytically active supramolecular host systems is still very limited. There are several reasons, the most important of which is that it is very difficult to predict the catalytic potential of known supramolecular host systems. In several cases, even the encapsulation behavior of host systems is not completely understood or explored. Therefore, it is evident that further research is required to explore the potential of catalysis inside supramolecular capsules. Our initial research mainly focused on understanding the puzzling encapsulation behavior of the self-assembled resorcinarene capsule I and the closely related pyrogallolarene capsule II. After the elucidation of the decisive differences between these two systems, we explored the catalytic potential of capsule I. A variety of different reactions were successfully performed inside its cavity. The most important examples highlighted in this Account are iminium catalysis, the tail-to-head terpene cyclization, and the carbonyl-olefin metathesis. In the case of proline-mediated iminium catalysis, we were able to demonstrate that the enantioselectivity for the product formation was increased when the reaction was performed inside the cavity of capsule I. This is remarkable since the capsule is formed from achiral building blocks and, therefore, does not add chiral information to the reaction mixture. The tail-to-head terpene cyclization is the most complex reaction performed so far inside capsule I. The cyclic monoterpenes eucalyptol and α-terpinene were formed in useful yields. Interestingly, these products have not yet been synthetically accessible in solution directly from acyclic terpene precursors. Furthermore, we demonstrated that the cocatalytic system of capsule I and HCl is suitable for carbonyl-olefin metathesis. HCl was shown to be an inefficient catalyst for this reaction in solution experiments. This demonstrates that the different chemical environment inside the supramolecular container can lead to altered product selectivity. In general, we hope to demonstrate...

The tail-to-head terpene cyclization is arguably one of the most complex reactions found in nature. The hydrogen-bond-based resorcinarene capsule represents the first man-made enzyme-like catalyst that is capable of catalyzing this reaction. Based on noncovalent interactions between the capsule and the substrate, the product selectivity can be tuned by using different leaving groups. A detailed mechanistic investigation was performed to elucidate the reaction mechanism. For the cyclization of geranyl acetate, it was found that the cleavage of the leaving group is the rate-determining step. Furthermore, the studies revealed that trace amounts of acid are required as cocatalyst. A series of control experiments demonstrate that a synergistic interplay between the supramolecular capsule and the acid traces is required for catalytic activity.

long investigations into bent anthracene dimers as versatile building blocks for supramolecular capsules. The investigations initiated in 2008 with the design of an anthracene dimer with a meta-phenylene spacer bearing two substituents on the convex side. Using the bent polyaromatic building block, we began to develop novel supramolecular capsules from two different synthetic approaches. One is a coordination approach, which was pursued by converting the building block into a bent ligand with two pyridine units at the terminal positions. The ligands quantitatively assemble into an M 2 L 4 -type capsule through coordination bonding with metal ions. The other is a π-stacking approach, which was followed by utilizing the block as a bent amphiphilic molecule with two trimethylammonium groups at the spacer. In water, the amphiphiles spontaneously assemble into a micelle-type capsule through the hydrophobic effect and π-stacking interactions. Simple modification of the building block allowed us to prepare a wide variety of coordination capsules as well as π-stacking capsules, bearing different hydrophilic side-chains, terminal substitutions, connecting units, polyaromatic panels, or spacer units. The coordination capsule possesses a rigid cavity, with a diameter of ∼1 nm, surrounded by multiple anthracene panels. The spherical polyaromatic cavity binds various synthetic molecules (e.g., paracyclophanes, corannulene, BODIPY, and fullerene C 60 ) in aqueous solutions. With the aid of the polyaromatic shell, photochemically and thermally reactive radical initiators and oligosulfurs are greatly stabilized in the cavity. Biomolecules such as hydrophilic sucrose and oligo(lactic acid)s as well as hydrophobic androgenic hormones are bound by the capsule with high selectivity. In addition, long amphiphilic poly(ethylene oxide)s are threaded into the closed shell of the capsule(s) to generate unusual pseudorotaxane-shaped host−guest complexes in water. In contrast, the π-stacking capsule furnishes a flexible cavity, adaptable to the size and shape of guest molecules, encircled by multiple anthracene panels. In water, the capsule binds hydrophobic fluorescent dyes (e.g., Nile red and DCM) in the cavity. Simple grinding of the bent amphiphile with highly hydrophobic nanocarbons such as fullerenes, nanographenes, and carbon nanotubes (followed by sonication) as well as metal-complexes such as Cu(II)-phthalocyanines and Mn(III)tetraphenylporphyrins leads to the efficient formation of water-soluble host−guest complexes upon encapsulation. Red emission from otherwise water-deactivated Eu(III)-complexes is largely enhanced in water through encapsulation. Moreover, the incorporation of pH-and photoswitches into the amphiphile affords stimuli-responsive π-stacking capsules, capable of releasing bound guests by the addition of acid and light irradiation, respectively, in water. The host functions of the coordination and π-stacking capsules are complementary to each other, which enables selection of the capsule-type depending on the envis...

Carbonyl-olefin metathesis represents a powerful yet underdeveloped method for the formation of carbon-carbon bonds. So far, no Brønsted acid based method for the catalytic carbonyl-olefin metathesis has been described. Herein, a cocatalytic system based on a simple Brønsted acid (HCl) and a self-assembled supramolecular host is presented. The developed system compares well with the current benchmark catalyst for carbonyl-olefin metathesis in terms of substrate scope and yield of isolated product. Control experiments provide strong evidence that the reaction proceeds inside the cavity of the supramolecular host. A mechanistic probe indicates that a stepwise reaction mechanism is likely.