Rotaxanes 3 , symmetrical

The successful synthesis of both symmetrical and unsymmetrical [3]rotaxanes revealed the strength of the threading approach - even though the neutral template responsible for the formation of the rotaxanes offers only weak interactions, two macrocycles can be mechanically bound to an elongated amide thread. 

Figure 27. Syntheses of symmetrical 67 and unsymmetrical 66 amide-linked [3]rotaxanes.

Rotaxanes made with two oriented macrocycles, but a symmetrical dumbbell will also display interesting stereochemical features. Depending on the mutual orientations of the two threaded rings, a pair of enantiomers and a meso form of the [3]-rotaxane are obtained, as shown schematically in... 

Threading of two cyclodextrins onto a symmetrical dumbbell can occur head-to-head, head-to-tail, or tail-to-tail, defining a new class of diastereoisomeric [3]-rotaxanes, as shown schematically in Figure 2.12d. Anderson and co-workers have shown that end-capping of 4,4,-bis(diazonio)azobenzene chloride 43 with 2,6-dimethylphenol 44 in the presence of a-CDX produced the [3]-rotaxane 45 in 12% yield, in addition to the [2]-rotaxane 46 in 9% yield, and free dumbbell 47 in trace amounts (Figure 2.18).42 The stereochemistry of the [3]-rotaxane species is remarkable because the two cyclodextrin beads have their smallest rims facing to each other. Therefore the threading reaction was stereoselective. The reasons for the exclusive formation of the tail-to-tail stereoisomer are not clearly established. 

As already pointed out in the case of rotaxanes, mechanical movements can also be induced in catenanes by chemical, electrochemical, and photochemical stimulation. Catenanes 164+ and 174+ (Fig. 19) are examples of systems in which the conformational motion can be controlled electrochemically [82, 83], They are made of a symmetric electron acceptor, tetracationic cyclophane, and a desymmetrized ring comprising two different electron donor units, namely a tetrathiafulvalene (TTF) and a dimethoxybenzene (DOB) (I64 1) or a dimethoxynaphthalene (DON) (174+) unit. Because the TTF moiety is a better electron donor than the dioxyarene units, as witnessed by the potentials values for their oxidation, the thermodynamically stable conformation of these catenanes is that in which the symmetric cyclophane encircles the TTF unit of the desymmetrized macrocycle (Fig. 19a, state 0). 

Despite the fact that none of the three non-symmetrical [2]-rotaxanes just described fully meet the goal of having the cyclophane tetracation solely occupying the 7i-electron-donor site with the lowest oxidation potential, in two cases this isomer is the preferred one - provided that an appropriate choice of solvent is used. The results of these studies are still of considerable value in a general sense since they serve to delineate some of the subtleties inherent in attempting to use this approach to obtain a controllable shuttle. ... 

Two higher homologues of the [2]-rotaxane are represented the [3]-rotaxane and the [4]-rotaxane. Whereas [3]-rotaxanes are relatively common [56-60], this is not the case for the linear [4]-rotaxane [61] and its branched or dendritic analogue [62]. Very important in the recent developments of rotaxane chemistry is the [2]-rotaxane whose dumbbell contains two separated sites for interaction of the threaded macrocycle. In this molecule, the macrocycle may be moved between two sites of the dumbbell, in a degenerate manner, if the sites are identical [63-65], or in a controlled manner, thanks to an external trigger, if the sites are different [28-31]. A chiral [2]-rotaxane, whose chirality arises from the mechanical bonding, is obtained if the macrocycle is oriented (by an appropriate substitution pattern) and the dumbbell made non-symmetrical, for example by attaching two different stoppers [66],... 

The best yield obtained for a [2]-rotaxane was 41%, in the case of a mixed sulphonamide/amide spacer [104], Combining this non-symmetrical spacer and a raacrocycle oriented by alternating sulphonamide and amide linkages, allowed the preparation of chiral rotaxanes, which could be resolved into the separated enantiomers by HPLC on optically active stationary phases [66]. 

Fig. 7. (a) Dethreading/rethreading of a [2]pseudorotaxane (b) switching of the ring component between the two stations of the dumbbell-shaped component of a [2]rotaxane (c) switching between the two structures in a [2]catenane containing a non-symmetrical macrocyclic component... 

For [3]rotaxanes, i.e., an axle with two wheels, even diastereomers exist, if both wheels have a directionality with respect to their atom sequence.Both wheels can then display the same clockwise atom sequence yielding a mirror symmetrical species that can be regarded as the supramolecular analogue of the meso form of tartaric acid. If the two wheels assemble on the axle with opposing directionality, diastereomers are formed. 

A rotaxane-based molecular shutde can have chirality regulated by the position of a macrocycle. Movement of the macrocycle between stations is restricted by the introduction of a bulky group. Asymmetric benzoylation of racemic rotaxane, which has two stations and one hydroxy group on the symmetric position of the shaft molecule, catalysed by a chiral nicotinamide derivative gives enantiomericaUy enriched rotaxane with a 67 33 distribution of enantiomers by trapping the macrocycle on one side (Scheme 5.49) [129]. 

Boroxine formation, through the cyclotrimerization of three boronic acid units, is another reversible reaction recently applied in dynamic covalent synthesis (Figure 1.3u). The forward reaction is entropicaUy driven by the release of water molecules upon condensation and is favored where electron-donating groups in the para position are used [42]. To date, this reaction has only been used in the designed thermodynamic synthesis of a Cj-symmetric [4]rotaxane 26, apparently under thermodynamic control (Scheme 1.12) [43]. However, it could be envisaged that... 

Scheme 1.12 Templated synthesis of a Cs-symmetric [4]rotaxane 26 generated through reversible boroxine formation [43].

The rotaxane-like orientations observed in the solid state for the centro-symmetrically-located guests in the middle of the [BBIPYBIXYCY]" " cavities conjure up a highly suggestive situation. The marriage of the molecular recognition features from these two host-guest systems, combined with further covalent modification, leads... 

---