Tetraloop compounds

Figure S.9 Approaches to tetraloop compounds with different size and structure of the loops via heterodimerization with tetra-tosylurea 4 followed by olefin metathesis and hydrogenation.

The structure of bis- to tetraloop compounds is clearly proved by their ESI mass spectra (which usually show the molecular ion with high abundance) and by their 1H NMR spectra in hydrogen bond breaking solvents, where they exist as monomeric species. Examples of symmetrical bis- and tetraloop compounds are shown in Figure 5.10b,c. They demonstrate simultaneously that the molecules are kept in the... 

Figure 5.10 Molecular conformation of a tetraloop calix[4]arene 9 (Y=Me,n=10) in the crystalline state (a). 1H NMR spectra (400 MHz) of a bisloop compound 8 (Y=Me,n—10) in DMSO-d6 (H20 peak is marked by asterisk) at 25 °C (b) and of a tetraloop compound...

A single-crystal X-ray structure for a tetraloop compound shows the molecules (not unexpectedly) in a pinched cone conformation (see Figure 5.10a), although the time-averaged conformation deduced from the1H NMR-spectra is C4v-symmetrical (Figure 5.10b). 

Tetraloop compounds 9 contain a huge macrocycle (formed by fourfold metathesis), which is covalently connected to the calix[4]arene skeleton via four urea linkages. Cleavage of these connections is easily possible in boiling acetic add (Scheme 5.13). Thus, flexible, macrocyclic molecules 11 are available in 50-75% yield [53], which would be difficult to obtain by non-templated macrocydization reactions under high-dilution conditions. 

The inability of bis-, tris-, or tetraloop compounds to form homodimers and the general tendency of tetra-urea calix[4]arenes to dimerize can be further exploited for the synthesis of mechanically interlocked molecules. A 1 1 mixture of tetra-ureas 5 or 6 with bis- or tetraloop compounds 8 or 9 (in practice the non-reactive loop component is added in a small excess) contains exclusively heterodimers (e.g., 5-8, 5-9, or 6-9), since this is the only possibility, to have all the urea functions involved in the favorable hydrogen-bonded belt.5 Again this is easily evidenced by the complete absence of peaks for the homodimer 5-5, or 6-6 in the H NMR spectra (for an example see Figure 5.11). 

Based on all experience, it is justified to predict, that the combination of trisloop compounds with bis- or tetraloop compounds to give the respective catenanes will also proceed selectively with high yield (Scheme 5.16), since only one heterodimer is possible in all these cases. Only the combination of a trisloop compound 10 with its alkenyl precursor 7 may lead to two regioisomeric dimers. 

The preorganization of functional groups attached to the urea residues could also be used for the synthesis of multiple rotaxanes. Schematically, this is shown for tetra[2] rotaxanes in Scheme 5.20. Bis[2]rotaxanes will be available analogously, using a bisloop compound 8 instead of the tetraloop compound 9. 

In practice it is reasonable to use the non-reactive compound in the heterodimer, the tetra-tosylurea 4, in a small excess, to exclude the undesired formation of homodimers 5-5 or 6-6. After metathesis, the dimer is decomposed by a hydrogen-bond breaking solvent (usually THF), and the crude product is usually hydrogenated directly, to avoid complications by cis-trans isomerism. The whole reaction sequence is schematically summarized in Scheme 5.12. Bis- and tetraloop calix[4]-arenes 8 and 9 were easily prepared in high yields (70-95%) [51,52] for residues Y = methyl, pentyl, and dodecyl, and loop sizes of n = 2 m + 2 = 8, 10, 14, and 20.4 Several aspects show the generality of this approach ... 

As shown in Section 5.5, bisloop or tetraloop tetra-ureas (8, 9) do not form homodimers, while monoloop compounds (e.g., 15) form selectively only one homodimer. These selectivities may be summarized as follows ... 

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