Metal-ion template syntheses

The effect of metal ions in promoting certain cyclization reactions has been recognized for a very long time. Thus the first synthetic 

Apart from this one-reaction type, the routine use of metal template procedures for obtaining a wide range of macrocyclic systems stems from 1960 when Curtis discovered a template reaction for obtaining an isomeric pair of Ni(n) macrocyclic complexes (Curtis, 1960). Details of this reaction are discussed later in this chapter. The template synthesis of these complexes marked the beginning of renewed interest in macrocyclic ligand chemistry which continues to the present day. 

Two possible roles for the metal ion in a template reaction have been delineated (Thompson Busch, 1964). First, the metal ion may sequester the cyclic product from an equilibrium mixture such as, for example, between products and reactants. In this manner the formation of the macrocycle is promoted as its metal complex. The metal ion is thus instrumental in shifting the position of an equilibrium - such a process has been termed a thermodynamic template effect. Secondly, the metal ion may direct the steric course of a condensation such that formation of the required cyclic product is facilitated. This process has been called the kinetic template effect. 

Examples of the operation of both types of effect have been documented. Nevertheless, while these effects are useful concepts, as mentioned previously, very often the role of the metal ion in a given in situ reaction may be quite complex and, for instance, involve aspects of both effects. As well, the metal may play less obvious roles in such processes. For example, it may mask or activate individual functional groups or influence the reaction in other ways not directly related to the more readily defined steric influences inherent in both template effects. 

In view of the above, it is not surprising that a detailed understanding of the part played by the metal ion in many (perhaps the majority ) of published template reactions still remains to be elucidated. Nevertheless, in the following discussion an attempt has been made to illustrate a representative cross section of such in situ reactions even though, for many examples, little comment can be made concerning mechanistic details of the respective condensations. 

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The use of metal ions as kinetic synthetic templates is extremely widespread, and is an excellent way in which to bring about the organisation of a number of reacting components in order to direct the geometry of the product. Because some metal ions, such as the transition metals, often have preferred coordination geometries (e.g. tetrahedral, square planar, octahedral etc), changes in metal ion may have a profound effect on the nature of the templated product. Metal-ion-templated syntheses may be classified more generally as examples of self-assembly with covalent postmodification. For example, the synthesis of the artificial siderophore 10.2 is effected by the use of an octahedral Fe3+ template.8 In this case, the macrobicyclic product is obtained as the Fe3+ complex from which it is difficult to separate. 

A common disadvantage of many template reactions is that it is often difficult to remove the metal ion. Such syntheses are therefore in situ syntheses of metal complexes and can only occasionally be used for the synthesis of the metal-free ligands. 

The synthetic strategy used for the construction of concave pyridine bislactams 3 (Scheme 1) can also be applied to other concave bases. When instead of a pyridine-2,6-dialdehyde 4, l,10-phenanthroline-2,9-dicarbaldehyde (9) was used in a metal ion template directed synthesis of macrocyclic diimines, after reduction, also macrocyclic 1,10-phenanthroline diamines 10 could be obtained in good yields. Here too, the crude diamines 10 were used in the next reaction step. Bridging of 10 with diacyl dichlorides 8 gave concave 1,10-phenanthroline bislactams 11. Scheme 2 summarizes the synthesis and lists the synthesized bimacrocycles 11 [18]. 

The catenands are synthesized using the metal ion template effect, whereby a bis complex is formed from an a,a -disubstituted o-phenanthroline. This initial product is treated with a diiodoal-kane to effect the ring closures.34... 

Let us start the discussion with a metal ion template, which was introduced by Sauvage and his coworkers in the mid-1980s (Fig. 2, top left). A Cu(I) ion with its preferred tetrahedral coordination geometry is capable of binding two phenanthroline units. If one of the phenan-throlines is incorporated in a macrocycle, which later will become the wheel, the second ligand is drawn into the cavity by the copper ion and can be easily equipped with two stoppers. The rotaxane precursor can then be dernetallated by treatment with cyanide ions to yield the desired rotaxane. Similarly, catenanes and other mechanically bound molecules can be synthesized. Also, other transition metals were used, some of which had an octahedral coordination geometry and were reacted with terpyridine instead of phenanthroline units. 

Almost all metal template-based syntheses of catenanes use Cu" ", but there are a few instances of other metal ion templates, including Zn +, Pd, and Pt +. The relative substitution-lability of Pd + makes it suitable as a preparative template the substitution-inertness of Pt + has been used as the basis for a temperature-switchable catenane molecular lock [257]. This mode of switching is based on platinum-nitrogen bond dissociation at elevated temperatures. 

In most cases the symmetric boron-capped clathrochelates have been synthesized by template condensation on a metal ion matrix as, for instance, is shown in Scheme 68 <2005MI3>. 

Template contributions. Alkali metal ions have been documented to play a template role in a number of crown syntheses. Thus, for example, the presence of K+ has been shown to promote the formation of 18-crown-6 in syntheses such as [4.2] (Green, 1972) intermediates of type (174) are... 

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