Metal ions template-directed synthesis

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 use of metals for prearranging reaction centers as neighboring groups has a special value in the production of macrocycles (template effect). Although these ligands can be sometimes prepared directly, the addition of metal ion during the synthesis will often increase the yield, modify the stereochemical nature of the product, or even be essential in the buildup of the macrocycle. There have been few mechanistic studies of these processes. The alkali and alkaline-earth metal ions can promote the formation of benzo[18]crown-6 in methanol ... 

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. 

It has been known for decades that metal ions can affect the course of organic reactions [lb], A possible role of minerals in the molecular evolution process was critically reviewed by Lahav [2]. The hypothetical involution of minerals in this process encompasses a variety of reactions, from mere adsorption to template-directed synthesis (e. g., of amino acids and sugarlike molecules), stereoselective adsorption of organic molecules, and catalytic condensation of peptides. 

The template synthesis represents an elegant method that uses metal ions to direct reactions of ligands and provides a useful route to macrocyclic structures. Several books159-161 describe the template processes that involve reactions on matrices used to synthesize polyazamacrocyles, crown ethers, cryptands, rotaxanes, knots,159 clathrochelates,160 phthalocyanines,161 etc. which are applied, e.g., as molecular switches, in ion exchange, electron transfer or catalysis. An example of clathrochelate synthesis is given in Chapter 1.33... 

Van Roode JHG, Orgel LE Template-directed synthesis of oligoguanylates in the presence of metal-ions. J Mol Biol 1980, 144(4) 579—585. 

Scheme 3 Cooperative template-directed synthesis of MesoMOFs via self-assembly of metal ions and organic ligands (Reprinted with permission from Ref. 31. Copyright (2012) American Chemical Society.)...

Chelation itself is sometimes useful in directing the course of synthesis. This is called the template effect (37). The presence of a suitable metal ion facihtates the preparation of the crown ethers, porphyrins, and similar heteroatom macrocycHc compounds. Coordination of the heteroatoms about the metal orients the end groups of the reactants for ring closure. The product is the chelate from which the metal may be removed by a suitable method. In other catalytic effects, reactive centers may be brought into close proximity, charge or bond strain effects may be created, or electron transfers may be made possible. 

It should be noted that the basic reactions used to prepare phthalocyanine derivatives today are fundamentally those developed by Linstead and coworkers in the 1930s [52-54]. Due to the large number of substituted phthalocyanines described in the literature, space limitations mean that a detailed review of synthetic aspects cannot be provided here. The following discussion is concerned with the synthesis of lanthanide phthalocyanines via (i) template tetramerization of phthalonitrile with lanthanide salts, (ii) direct metalation of the metal-free ligands by the salts or (iii) metal exchange of a labile metal ion or ions for a lanthanide. 

Probably one of the commonest reactions encountered in the template synthesis of macrocycles is the formation of imine C=N bonds from amines and carbonyl compounds. We have seen in the preceding chapters that co-ordination to a metal ion may be used to control the reactivity of the amine, the carbonyl or the imine. If we now consider that the metal ion may also play a conformational role in arranging the reactants in the correct orientation for cyclisation, it is clear that a limitless range of ligands can be prepared by metal-directed reactions of dicarbonyls with diamines. The Tt-acceptor imine functionality is also attractive to the co-ordination chemist as it gives rise to strong-field ligands which may have novel properties. All of the above renders imine formation a particularly useful tool in the arsenal of preparative co-ordination chemists. Some typical examples of the templated formation of imine macrocycles are presented in Fig. 6-12. 

The nickel ) complex of 92 cannot be prepared directly via the template method, but can be prepared by a transmetallation procedure. Synthesis of the macrocycle in the presence of one of the metal ions known to be effective as a template is followed by a metal exchange process in solution to insert the nickel ) ion. This cation exhibits a strong preference for the square planar, square pyramidal, and octahedral geometries 79). Thus the failure of the nickel ) cation to behave as a template ion in the synthesis of 92 is probably due to the disinclination of the metal to accommodate the pentagonal array of donor nitrogen atoms necessary for reaction to occur. 

Condensation reactions between carbonyl compounds and primary amines have played a central role in the synthesis of new macrocyclic ligands [28-34]. Usually, though not in all cases, such reactions are conducted in the presence of metal ions which can serve to direct the condensation preferentially to cyclic rather than oligomeric/polymeric products and to stabilize the macrocycle once formed. The relative atomic radius of the templating ion has a considerable effect on the size of the macrocycle formed. For instance, in what is now classic work, cations such as Mg(Il) (r = 0.72 A) were found to stabilize the formation of macrocycles such as 60 from 1 1 condensations [35], while larger cations such as Sr(II)... 

At present, the known catenanes can be divided into two categories - those prepared by metal template synthesis and those synthesised in the absence of a metalion influence. A considerable number of catenanes of the first type have been prepared by Sauvage et al. as well as by a number of other workers. However, discussion on these important metal-ion-directed systems is deferred to the next chapter in which particular supramolecular assemblies produced by metal-ion-controlled procedures are discussed. 

In some cases, a free clathrochelate ligand has been isolated after its template construction on the metal ion and demetallation of the resultant complexes. In particular, this has made it possible to synthesize sarcophaginates of many metals incapable of forming clathrochelates via direct template synthesis they are formed from... 

Clathrochelate ribbed-functionalized tris-dioximates have attracted interest because they offer scope for the synthesis of polynuclear complexes with targeted structural parameters and physicochemical properties (see above). In most instances, it is not necessary to functionalize all a-dioximate fragments, and it appears to be sufficient to modify only one of the three ribs in the clathrochelate framework to alter the properties significantly. Several feasible synthetic routes to clathrochelate monoribbed-functionalized tris-dioximates have been proposed in Ref. 68. A direct template condensation of the mixture of a-dioximes with Lewis acids on a metal ion (Scheme 15, Route I) leads to the formation of a poorly separable mixture of nonsymmetric and symmetric products, in which the latter predominate. Halogenation of the initial clathrochelate... 

Binuclear clathrochelate iron(II) oximehydrazonates may be synthesized by the main methods used for the synthesis of macrobicycles of this type proposed for clathrochelate tris-dioximates by a direct template reaction on a metal ion the cross-linking of initial nonmacrocyclic complexes a cross-linking group exchange reaction and a ligand modification reaction. The template condensation of a mononuclear complex to a binuclear one followed by the encapsulation of another metal ion and capping reaction may be also used for the preparation of these compounds. The main methods for the synthesis of these complexes are shown in Scheme 88 [193]. 

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