Enzymes achieve high substrate and product selectivities by orientating and activating the substrate(s) appropriately inside a confined and finely optimized binding pocket. Enzyme catalysis is generally regarded as the ultimate role model for chemical catalysis, and some basic aspects of enzymes have already been mimicked successfully with man-made catalysts. One fascinating facet of substrate activation inside enzyme pockets, which has not been mimicked with man-made catalysts so far, involves proton wires. A proton wire facilitates the dual activation of a nucleophile and an electrophile via a reciprocal proton transfer, enabling highly stereoselective reactions under mild conditions. Here we present evidence for such an activation mode inside the supramolecular resorcin[4]arene capsule and demonstrate that it enables catalytic and highly selective glycosylation reactions. Extensive control experiments provide very strong evidence that the reactions take place inside the molecular container. The communicating dual activation mode enabled by the proton wire is, to our knowledge, unknown in supramolecular and molecular catalysis so far.Enzymes have functioned as role models for chemists working in the broad field of catalysis. They enable conversions in an aqueous environment by binding the substrate(s) inside a hydrophobic binding pocket. The finely optimized environment of such binding pockets facilitates the highly selective conversion by orientating and activating the substrate(s) appropriately. Some aspects of enzymes, for instance, the binding pocket, have already been mimicked successfully with

Chiral pyrrolidine derivatives are important building blocks for natural product synthesis. Carbonyl olefin metathesis has recently emerged as a powerful tool for the construction of such building blocks from chiral amino acid derivatives. Here, we demonstrate that the supramolecular resorcinarene catalyst enables access to chiral 2,5-dihydropyrroles under Brønsted acid catalysis. Moreover, this catalytic system even tolerated Lewis-basic-protecting groups like mesylates that are not compatible with alternative catalysts. As expected for conversion inside a closed cavity, the product yield and selectivity depended on the size of the substrates.

<div>Carbohydrates are of central importance in biology. The selective chemical synthesis of carbohydrates, however, still poses a challenge; particularly, the selective formation of the</div><div>thermodynamically labile b-glycosidic bond is difficult and depends on the substrate’s substitution pattern. We here demonstrate that a molecular capsule catalyzes the highly</div><div>challenging selective formation of b-glycosides independent of the substrate’s substitution pattern and configuration. We demonstrate the versatility of the catalyst by synthesizing small to medium sized 1,2-cis, 2-deoxy, and 1,2-trans b-glycosides in very high selectivity and good yield. The confined space inside the molecular capsule naturally limits the scope concerning the size of reactants. Interestingly, the proposed mechanism involves the synchronized activation of the glycosyl donor and acceptor inside the supramolecular capsule via a relay involving seven hydrogen bonds. Such an activation is known for enzymes, however, to our knowledge, is unprecedented for man-made catalysts.</div>

In the version of this article initially published, in the penultimate sentence of the "Mechanistic investigations" paragraph, in the text now reading "Based on the SKIE and the first reaction order of methanol observed, " "first reaction order" originally appeared as "zero reaction order. " The text has been corrected in the HTML and PDF versions of the article.

<div>Carbohydrates are of central importance in biology. The selective chemical synthesis of carbohydrates, however, still poses a challenge; particularly, the selective formation of the</div><div>thermodynamically labile b-glycosidic bond is difficult and depends on the substrate’s substitution pattern. We here demonstrate that a molecular capsule catalyzes the highly</div><div>challenging selective formation of b-glycosides independent of the substrate’s substitution pattern and configuration. We demonstrate the versatility of the catalyst by synthesizing small to medium sized 1,2-cis, 2-deoxy, and 1,2-trans b-glycosides in very high selectivity and good yield. The confined space inside the molecular capsule naturally limits the scope concerning the size of reactants. Interestingly, the proposed mechanism involves the synchronized activation of the glycosyl donor and acceptor inside the supramolecular capsule via a relay involving seven hydrogen bonds. Such an activation is known for enzymes, however, to our knowledge, is unprecedented for man-made catalysts.</div>