The Cylindrical Molecular Capsule: Expansion and Application

This proposal deals with host-guest assemblies which are an important class of supramolecular structures. The cylindrical self-assembled capsule 1.1 features a closed cavitiy, selectively binds smaller guest molecules and temporarily isolates them from the solvent. These complexes self-assemble when, and only when, the spaces inside the capsules are appropriately filled. Molecules are held within the space of the capsule for lifetimes ranging from milliseconds to hours, and conventional NMR spectroscopy is used to report on the chemical and magnetic environment as well as the arrangement of molecules in the encapsulation complex. One special feature of this capsule is the capability to reversibly expand via insertion of glycoluril units 2. The incorporation of these spacer elements into the capsule (1.2 4 .1) results in an increase of the cavity`s volume and of its length. Accordingly, a variety of longer guests are encapsulated in the new assembly. An interesting application of capsules like 1.1 or 1.24 .1 is their use as "molecular flasks". In solution molecular encounters are short-lived and chaotic. On the other hand two encapsulated molecules are trapped together for approx. one second and the limited volume results in high (approx. 4 M) concentrations inside. Moreover, the restricted sliding and tumbling of coencapsulated molecules make for arrangements that feature specific intermolecular contacts, stabilize reactive intermediates, and lead to regioselective reactions. So far only two examples of reactions inside capsule 1.1 have been reported: a 1,3-dipolar cycloaddition and the reaction of a carboxylic acids with an isonitrile. We want to furnish the spacer units 2 with photo-isomerizable azobenzene substituents, to fully utilize the astonishing feature via controlled contraction and expansion of capsule 1.1. To identify suitably sized spacers, a variety of differently substituted units will be synthesized and tested. Herein we propose a six step synthetic plan with late product diversification for the synthesis of the glycoluril spacers 3. The azobenzene-substituted expanded capsule 1.34 .1 will be used to study the possibility to circumvent product inhibition and to study the gas behaviour inside such capsules. The second part of this application deals with the investigation of the - so far - unexplored Diels-Alder reaction inside these cylindrical capsules. The properties of the molecular flasks should enable the reaction at much lower temperature as compared to regular thermal Diels-Alder reactions in solution and probably with different ortho- /meta- and endo-/exo-selectivities. In addition we also want to explore the feasibility of an unprecedented unactivated, uncatalyzed intermolecular Diels-Alder reaction inside these molecular flasks.