Rotaxane clipping

Scheme 12a-d There are several general methods to prepare rotaxanes a threading followed by capping b clipping c slippage d snapping... 

Scheme 19 Stoddart has employed the clipping method to prepare [2]rotaxane 42. Reversible imine bonds are used to generate a dynamic mixture containing the threaded and un-threaded components...

The templated syntheses of amide-based rotaxanes discussed until now have made use of the threading-followed-by-capping method. However there are also examples in which the clipping approach has been employed. Leigh, for example, has used a five-component clipping method to prepare [2]rotaxanes. Isophthalamide and peptide-based threads were shown to template the formation of benzylic amide macrocycles about them in non-polar solvents [69, 70]. When the peptide-based threads (49) contain bulky stoppers at their ends, the [2]rotaxanes (50) can be prepared in high yields (see Scheme 24) [71]. 

Scheme 24 Templated synthesis of [2]rotaxane 50 by the clipping mechanism...

Clipping. The clipping method relies on the synthesis of the rotaxane by formation of the macrocycle (host) in the presence of a dumbbell shaped molecule. The partial macrocycle undergoes a ring closing reaction around the dumbbell shaped molecule, thereby forming the rotaxane. 

The clipping reaction used in [52, 53, 55] to synthesize tetralactam-based squaraine rotaxanes such as 14 and 15 afforded only moderate yields (ca. 28-35%) of the rotaxanes, possibly because of the unavoidable presence of nucleophiles that react with the chemically unstable squaraines during the reaction. The slippage approach [62] minimizes the squaraine dye s contact with nucleophiles during the rotaxane formation process and therefore can be used to efficiently encapsulate a squaraine dye such as 23 in a macrocycle such as 25 [63],... 

Figure 1. Threading (a and b) and slipping (c) approaches to [2]iotaxanes. Clipping (not shown) is another synthetic approach to rotaxanes. It involves the macrocyclization of the ring component around the preformed dumbbell-shaped component.

Figure 20. No rotaxane formation is detected when the building blocks 46, 47, and 3 are subjected to a clipping process.

The amide hydrogen-bonding motif has been shown to support the clipping, threading, and slipping approaches to the formation of rotaxanes. The wide scope of the neutral template synthesis is enriched by the promising possibilities of the non-template synthesis performed in the melt. Numerous rotaxanes were obtained on a preparative scale and are available for further chemistry. 

It is necessary to point out that while various types of polyrotaxane have been conceived (Table 1), to date, only polyrotaxanes of Types 4, 5, 6, 7, 9, 10 and 11 have been reported. Polyrotaxanes of Types 8 and 12 are worth study this might provide more interesting information about the relationship between properties and structure. In addition to those discussed so far, other potential preparation approaches have also been conceived but have not been applied. These methods are simply summarized and demonstrated via those for the side-chain polyrotaxanes of Type 10 (Figure 18). They are (i) chemical conversion, (ii) polymerization of rotaxane monomers, (iii) clipping (cyclization in the presence of preformed polymer), and (iv) grafting. The corresponding methods for other types of polyrotaxanes in Table 1 are analogous [6-8, 12]. 

For the preparation of rotaxanes, three different routes can be followed (Scheme 6.2A). In the threading procedure, the macrocycle will first encircle the thread to form a so-called pseudorotaxane. By end-capping the thread with bulky groups that prevent de-threading, a [2]rotaxane is formed. The clipping method that is used for the preparation of catenanes can also be applied for the synthesis of rotaxanes hence the macrocycle is assembled in the presence of the end-capped... 

However, preorganization by reversible interactions via hydrogen bonds does not necessarily need a further template such as an anion. Direct intermolecular hydrogen bonds between derivatives of isophthalic acid and 2,6-pyridine diacid were used to synthesize a series of new catenanes [17,18], rotaxanes [18c,19], and trefoil knots [20]. The interaction of dibenzylammonium cations and dibenzo[24]crown[8] [21] led to the preparation of rotaxanes by the attachment of stoppers to the thread ends (Scheme 5.5) [22], or similarly by clipping of the crown ether chain wrapped around the ammonium dumbbell [23]. Recently, several novel catenanes were synthesized via the macrocydic connection of three ammonium cations threaded through three crown ether rings attached to a triptycene core [24]. 

Scheme 5.20 Two possibilities to synthesize tetra[2]rotaxanes (schematic) (a) by stoppering (FC represents a suitable functional group) or (b) by clipping (ring closure by metathesis).

Multiple ring-closure reactions between adjacent urea functions of a suitably functionalized tetra-urea in a heterodimer with a second tetra-urea bearing bulky groups can also create the structural elements of a rotaxane. This strategy is usually called clipping (see Scheme 5.7). 

The synthesis of fourfold [2]rotaxanes by clipping requires the efficient formation of heterodimers between a tetra-urea substituted by bulky stopper groups and an octaalk-enyl urea 6. We initially hoped that the steric crowding in homodimers of a tetra-tritylphenylurea calix[4]arene would be sufficient to shift the equilibrium toward the heterodimers in a mixture with 6. However, the distribution of the dimers was close to the statistical ratio and the desired rotaxane could be obtained in only 5% yield [59]. 

Figure 10.1 Clipping strategies in macrocyclization reactions resulting in interlocked products such as [2]rotaxanes and [2]catenanes.

The macrocyclization reaction described above has been used to generate a great number of catenane (12) and rotaxane (13) architectures (Scheme 10.4) using both crown ethers [preformed macrocyclic components 14 (strategy A)] and hydroqui-none-based dumbbell-shaped polyethers [preformed acyclic components 15 ( clipping )] as templates [14b, 15]. These templates are also relatively robust with regard to the substitution of different groups into both the tetracationic cyclophane and the neutral frameworks. 

The application of this template to the clipping of acyclic dumbbell-shaped molecules to form rotaxanes [14] has received less intensive scrutiny but involves a similar synthetic scheme and conditions. A few representative examples of [2]rot-axanes synthesized in this manner (16-20) are shown in Figure 10.2 [15c, 18-21]. The use of a 1,5-dihydroxynaphthalene core in these cases usually results in higher yields of the desired interlocked products [18,21]. 

Figure 10.2 Representative examples of various clipped [2]rotaxanes synthesized by Stoddart and coworkers. 

Figure 2.9. Directed clipping. The directed synthesis of [2]-rotaxane 20 by cyclization of the key intermediate 16.

Figure 2.11. Templated clipping. H-bonding interactions control the preparation of [2]-rotaxane 30.

Not only does DNA form itself into catenated and knotted structures, it also rotaxanates itself with macrocyclic enzymes. A,-Exonuclease [30, 37] is an enzyme that participates in DNA replication and repair by fully encircling DNA as it sequentially hydrolyzes nucleotides - a biomolecular rotaxane The structure of the enzyme is shown in Fig. 3d. T4 DNA polymerase holoenzyme [38] is an analogous example its protein subunits clamp around a DNA strand to form a toroid in what chemists of the mechanical bond would call a clipping process. It should be noted that chemists have been able to mimic this concept of a topologically linked catalyst on a polymer [39] using traditional organic catalytic reactions. 

The first [2]-rotaxane prepared by the Stoddart group to act as a molecular shuttle, 19, is shown in Figure 4.11. Formation of this system involved the clipping... 

Figure 4.12 A homologous series of rotaxanes (n = 2-5), prepared by clipping ...

Rotaxane entities bearing other molecular architectures have also been synthe-sised. For example, the clipping mechanism has been employed to clip the linked reagent 20 around two dumb-bell-shaped components of type 21, giving rise to the bis-[2]-rotaxane 22 shown in Figure 4.13. 

A template-directed synthesis of [2]-rotaxanes, with a yield in one case of 72%, has been reported. The experiments employed dumb-bell-shaped components incorporating terminal triisopropylsilyl stoppers connected to a central 1,5-dioxynaph-thalene recognition site by [-CH2CH20-] spacers (n = 1-3). - These components were used as templates for the synthesis ( clipping reaction ) of the corresponding rotaxanes incorporating cyclobis(paraquat-p-phenylene) as the ring component. The... 

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