Synthesis rotaxane

Template effects have been used in rotaxane synthesis to direct threading of the axle through the wheel. Since macrocycHc compounds such as cyclodextrins, crown ethers, cyclophanes, and cucurbiturils form stable complexes with specific guest molecules, they have been widely used in the templated synthesis of rotax-anes as ring (wheel) components. Here, we briefly discuss macrocycles used in the synthesis of rotaxane dendrimers and their important features. 

Scheme 2. Rotaxane synthesis combining different meth- threading-followed-by-stopperingthen (2) slippage...

Hiibner GM, Reuter C, Seel C, Vogtle F (2000) Rotaxane synthesis via nucleophilic substitution reactions the trapping of electrophilic threads by organic anion-wheel complexes. Synthesis 1 103-108... 

After the synthesis of the first amide-linked [2]rotaxanes, Vogtle et al. set out to study the limits of molecular recognition, which in terms of Emil Fischer means to discover if the lock (macrocycle) is specific to a certain key, or if several keys (monoamide threads) fit. It turned out that - in contrast to catenane formation - rotaxane synthesis is very tolerant towards the variation of the building... 

The diacid dichlorides used so far in rotaxane synthesis all have arene building blocks in common. Nevertheless, the initial amide bond formed between the dichloride and one stopper molecule (cf. 54) is thought to be responsible for successful molecular recognition of the semi-axle and the macromonocycle. Consequently olefinic and aliphatic diacid dichlorides 59a-g were subjected to the threading procedure to test the need for arene units (Figure 25). 

The reaction of fumaryl dichloride (59a) with 52 in the presence of macro-ring 32 resulted indeed in 26% [2]rotaxane 60a and 26% of the pure thread 61a [19]. The remarkably high yield of 60a indicates that arene units are not needed for this nonionic template-assisted reaction. When, however, the 2,4-hexadiene diacid dichloride (59b) was used for rotaxane synthesis the [2]rotaxane 60b, even though detected by mass spectrometry, could not be isolated, either at room tem-... 

As mentioned above, H NMR measurements indicated a higher association constant for the monoamide-macrocycle complex than for the diacid dichloride-macrocycle complex. Further hints of a route to monoamide intermediates like 54 were supplied when diisocyanates 69 and 70 were subjected to rotaxane synthesis (Figure 28) [45]. 

Depending on the functionality of the stopper (amine 52 or phenol 71), the reaction affords rotaxanes with urea bonding pattern 72-74 or with carbamate units 75. In each instance the temperature had to be raised to 40°C to ensure rotaxane formation and, interestingly, the free axle 76 was the only one to be isolated. This indicates that the low solubility of the reactants and the dumbbells can be the limiting factor in rotaxane synthesis when diisocyanates are incorporated. Molecular recognition is still effective, and again the decisive pattern for molecular aggregation seems to be the initial amide bond. Furthermore the macrocycle confers solubility on the thread. 

This seems to be the first rotaxane synthesis based on an anionic template and latest results indicate that this new strategy can be extended to ester- and acetal-based axles [70]. Hence the anionic procedure represents a powerful alternative to the rotaxane synthesis assisted by a neutral template. 

To overcome the low yields encountered in statistical methods, Schill and coworkers imaginatively introduced the chemical conversion method [4, 5, 16]. As illustrated in Figure 2, this method requires very careful design (i) the cavity of a cyclic species covalendy linked to a difunctional linear species should be penetrated by the linear species, structure 14 and (ii) both the cyclic and the linear moieties must be inert to the cleavage reaction of the covalent linkage Z between them. By this means, the yield for rotaxane synthesis was increased to about 40% in last step. The disadvantages of this method are its multiple steps and time-consuming nature. 

In the 1980s Ogino first applied this interaction in rotaxane synthesis, i.e., threading CD on to an a,co-diamine [38—40]. Almost at the same time, Yamanari et al. reported the preparation of very similar rotaxanes by the same approach [41,42]. Lawrence and coworkers prepared a stable rotaxane by threading / -CD... 

VIII. The Next Surprise Rotaxane Synthesis Mediated by a Template... 

Scheme 4 a rotaxane synthesis based on hydrophobic effects which lead to inclusion of an... 

Scheme 16 anion-templated rotaxane synthesis via a Michael addition reaction. 

Figure 10.55 Statistical rotaxane synthesis (a) product from solution and (b) analogue prepared in higher yield (6 %) on a solid support.

Schalley, C.A, Silva, G., Nising, C.F., Linnartz, P. Analysis and improvement of an anion-templated rotaxane synthesis, Helv. Chim. Acta, 85 (2002), 1578-1596. 

A very surprising and fruitful result was obtained when a control experiment related to an amide templated synthesis was made. Dibromo compound 19 utilized in the reaction looked similar to the axle centerpiece used in the amide template synthesis but lacked the amide in the middle which was crucial for this purpose. However, when the reaction was complete, it was found that rotaxane 24 was formed with 80-95% yield [12] (Figure 9). It seemed reasonable to assume that this time not the axle but the stopper coordinated to the macrocycle [27], This suggestion was supported by the high binding constant of the deprotonated stopper-wheel complex 21 18 (> 105 M"1) derived from H NMR titrations. In the rotaxane synthesis, this complex reacts with the semiaxle 23 producing a rotaxane. 

Figure 11. Anion-mediated rotaxane synthesis generating rotaxanes with functionalized axle center-pieces.

Scheme 6.5.3. Anion template effect for efficient rotaxane synthesis. 

Leigh and coworkers developed in parallel a Ni-catalyzed reductive homocoupling of alkyl halides 93 toward an efficient synthesis of rotaxanes (Fig. 22) [122]. In model studies 5-12 mol% of the Ni(II) precatalyst and terpy 8a or (/LA i-Ph-PyBOX 5g sufficed for the coupling of alkyl halides under normal conditions, under which 78-99% of dimers 94 were obtained. A macrocyclic Ni(PyBOX) complex, which has to be present stoichiometrically due to its function as the wheel, serves as the precatalyst in the rotaxane synthesis. Initial reduction of... 

IV. Transition-Metal-Controlled Threading A New Principle of Rotaxane Synthesis... 

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