Covalent template synthesis

Scheme 10.2 Covalent template synthesis of an 18-membered macrocycle.

The technique is applied to link non-cyclic ligsons together to form macrocyclic systems. The ligson heteroatoms have weak donor properties, so that centres such as transition and rare earth element, alkali, and alkaline metal ions are not able to play a template role in synthesis from the relevant species. The metalloids are able to form covalent bonds to weak donors and are thus suitable for the realisation of the required reactions. Organo-element compounds of appropriate metals are used for covalent-template synthesis. These combine the coordination ability of metals and the substitution ability of organic moieties, and therefore facilitate the wide range of chemical conversions involved in template processes. The basic feature of the reactions considered here is the weakness of bonds between matrix and ligsons, so that the synthesis of the free macrocyclic compound may be completed by release of the template. 

Until now most covalent-template syntheses have been carried out to form macro-cyclic polylactones [1, 6-16]. The synthesis of tetralactones L1562-L1567 represented in Scheme 7-1 has been achieved in 30-85% yield [7, 10]. Other cyclic stannoxanes are also suitable for covalent-template synthesis of macrocyclic tetralactones, for example L1568 (Eq. 7.1) [10]. Tetralactones L1569 (Eq. 7.2) and L1570 (Eq. 7.3) are synthesised in an analogous way [10]. 

Organosilicon derivatives can be used for the covalent-template synthesis of macrocyclic polylactams [28, 29]. The method includes conversion of acyclic dia-... 

Production of materials in which the daughter polymer and the template together form a final product seems to be the most promising application of template polymerization because the template synthesis of polymers requiring further separation of the product from the template is not acceptable for industry at the present stage. Possible method of production of commonly known polymers by template polymerization can be based on a template covalently bonded to a support and used as a stationary phase in columns. Preparation of such columns with isotactic poly(methyl methacrylate) covalently bonded to the microparticulate silica was suggested by Schomaker. The template process can be applied in order to produce a set of new materials having ladder-type structure, properties of which are not yet well known. A similar method can be applied to synthesis of copolymers with unconventional structure. 

Cryptophane synthesis is accomplished by one of two methods. Initial procedures employed a covalent template effect in which one CTV-derived bowl preorganised the cyclisation of the second under high dilution conditions (Scheme 6.16a). More recently, a much more straightforward procedure has been developed in which cryptophanes are formed directly in a double trimerisation reaction (Scheme 6.16b). 

It was not only for the basic scientific knowledge but also for the new challenges in the synthesis and the beauty of the final structures that nearly half a century ago, chemists started to investigate intertwined macrocyclic supramolecules such as rotaxanes and catenanes [4], Earlier, when the syntheses of such structures were at their infancy, the routes to such systems were troublesome. The statistical methods [5] proved to be low-yield processes. Multistep procedures [6] involving a covalent junction which is formed between two parts that are needed to stay together until the structure is complete were not convenient as well. The use of non-covalent templates thus provided a more straightforward and high-yield approach to the problem. 

We have shown how templated synthesis approaches are currently revolutionizing the covalent chemistry of fullerenes. They provide elegant and imaginative protocols to produce highly selectively functionalized fullerene building blocks for three-dimensional molecular scaffolding. 

These results show unambiguously that templates are an attractive alternative to the tedious precursor synthesis commonly used for the preparation of shape-persistent macrocydes. They allow the preparation of symmetrically and even of nonsymmetrically functionalized PAMs in high yields. Moreover, the increased amount of the shape-persistent macrocyde in the crude product simplifies the purification procedure in most cases. However, both the supramolecular and the covalent template approach require the presence of appropriate functional groups that bind (are bound) to the template. 

Fig. 8 The two applied approaches to catenane synthesis prior to 1983. (a) The first statistical synthesis [58] relied upon the macrocyclization of a linear compound (7) in the presence of a deuterated cycloalkane (III) to achieve small amounts of the catenane V. (b) The first example [59] of directed synthesis by covalent templation was a catenane that formed after cleaving the covalent bonds around the aromatic core in compound 16. Reproduced with permission from [58] (copyright 1960 American Chemical Society), [59] (copyright 1964 Wiley-VCH)...

Fig. 26 Active template synthesis [185] (i) metal catalyst is bound in the cavity of a macrocycle, ( ) reagents (half-dumbbells in this example) coordinate the metal within the macrocycle, (Hi) a covalent bond is catalytically formed, resulting also in a mechanical bond, and (iv) catalyst is regenerated and the MIM is expelled...

The breakthrough in catenane synthesis occurred when the statistical and covalent template methods were abandoned in favor of approaches that relied... 

Schwartz and Shanzer have used silicon as a metaloid template for the one-step synthesis of biomimetric macrocycles (Lifson et al., 1987). Silicon functions as a covalent template by forming weak bonds to the heteroatoms and can be easily removed using mild cpnditions. Silicon tetraisocyanate was reacted with ethylene glycol followed by carbonyl diimidazole to give a polycyclic product that was desiliconated with water. 

This chapter will concentrate on examples of templated synthesis where the template takes the form of a temporary, covalent tether. The intermediate molecule containing both reacting species is in all cases isolable (or potentially so). This distinguishes this intra molecularization approach from substrate-directed stereoselective synthesis. In this case, the template, most frequently a metal, is used in a much more transient sense allowing the potential for developing catalytic systems, which is obviously not possible using a covalently bound template. 

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