Macrocycle template synthesis

Figure 4.24 Template synthesis of a gold(lll) macrocycle complex.

Template effects have been used in rotaxane synthesis to direct threading of the axle through the wheel. Since macrocycHc compounds such as cyclodextrins, crown ethers, cyclophanes, and cucurbiturils form stable complexes with specific guest molecules, they have been widely used in the templated synthesis of rotax-anes as ring (wheel) components. Here, we briefly discuss macrocycles used in the synthesis of rotaxane dendrimers and their important features. 

In this review, we tried to cover all the supramolecular species that maybe classified as rotaxane dendrimers. We classified them by their structures - where in dendrimer rotaxane-hke features are introduced. Several different types of macrocycles have been employed as a ring component in the templated synthesis of rotaxane dendrimers. While the synthesis of Type I and II rotaxanes dendrimers is relatively straightforward, that of well-defined Type III rotaxane dendrimers, particularly those of second and higher generations, is still challenging. 

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. 

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 ... 

Figure 51. Anionic template synthesis of rotaxane 118 with a bis(phenyl ether) axle. The mechanical bond is formed by reaction of the phenolate-macrocycle complex [32-115] (supramolecular nucleophile) with the semiaxle intermediate 117. 

N. V. Gerbeleu, V. B. An on, J. Burgess Template Synthesis of Macrocyclic Compounds 1999, ISBN 3-527-29559-3... 

The subject matter of this chapter will be subdivided into sections concerning template synthesis of the complexes structural and thermodynamic properties of the complexes with synthetic cyclic polyamines complexes with mixed-donor macrocycles reactivity of the complexes cryptates and complexes with phthalocyanines and porphyrins. 

The template synthesis has also been successfully employed for the preparation of macrocycles containing mixed donor atoms. Examples which refer to tetra- and bexa-dentate ligands are given in Schemes 42, 47 and 50.2649,2653 2654,2658 Apart from the template synthesis a number of nickel macrocycles have been prepared by direct combination of the appropriate nickel(II) salt with the preformed macrocyclic ligand in alcoholic medium, often MeOH (see also Tables 103, 106-108). 

Neutral nickel(II) complexes with a number of deprotonated porphyrins have been prepared in most cases by the direct reaction of a nickel salt, usually Ni(ac)2-4H20, with the preformed diacid macrocycle, using media such as DMF, MeC02H or PhCl at refluxing temperature. Recently, the template synthesis of the complex with tetraalkylporphyrins has been reported (Scheme 61).2883 On the other hand the condensation reaction of 1,3,4,7-tetraalkylisoindole and nickel acetate tetrahydrate gives the [Ni(omtbp)] complex (omtbp = octamethyltetrabenzoporphyrinate dianion), 2884... 

The macrocyclic complexes (97) and (98) have been prepared by template synthesis.624-626... 

Template syntheses of P macrocycles are a new area. In fact, a 1978 review93 of template synthesis made no mention of P macrocycles. Template syntheses have been developed by Stelzer and co-workers.94 Firstly, two molecules of the bidentate secondary phosphine are complexed with a nickel(II) or palladium(II) salt (Scheme 6) and the resultant secondary phosphine complex is then condensed with a diketone to form the macrocyclic metal complex. Unfortunately, these macrocycles are strong field ligands and no method has yet been devised to remove the metal from the ring. On the other hand, Cooper and co-workers95 have used a template synthesis to produce a [l4]aneP2N2 macrocycle (Scheme 7). 

Simple macrocyclic quadridentate complexes can be synthesized by template reactions from ethers derived from salicylaldehyde and diamines in the presence of appropriate metal ions such as nickel(II) (equation 3).35>36 However, these reactions can also be carried out quite effectively in the absence of metal ions to yield the free ligands, which can be obtained by hydrolysis of the complexes. An iron(II) macrocyclic quinquedentate chelate of this type has been produced by template synthesis (equation 4).37... 

Pyridine-2,6-dicarbaldehyde and 2,6-diacetylpyridine have been widely used in the template synthesis of imine chelates ranging in complexity from linear tridentates, such as (17),38 39 to macrocyclic structures with a range of ring sizes, such as (18).40-42 The in situ formation of macrocyclic ligands of this type depends upon the ring size and the strength of complexation of the triamine by the metal ion at the pH of the reaction. Related complexes with an additional donor atom attached to R2 have been synthesized also.43 44... 

Template reactions of dicarbonyl compounds and diamines have been extended recently to include the dialdehydes (3O)60>61 and (32)62-63 and a range of new diamines such as (31) and (33).64 Examples are shown in equations (6) and (7). The new diamines have also been used in the template synthesis of macrocyclic complexes based on 2,6-diacetylpyridine.60,65... 

Template reactions between malonaldehydes and diamines in the presence of copper(II), nickel(II) or cobalt(II) salts yield neutral macrocyclic complexes (equation 15).99-102 Both aliphatic102 and aromatic101 diamines can be used. In certain cases, non-macrocyclic intermediates can be isolated and subsequently converted into unsymmetrical macrocyclic complexes by reaction with a different diamine (Scheme ll).101 These methods are more versatile and more convenient than an earlier template reaction in which propynal replaces the malonaldehyde (equation 16).103 This latter method can also be used for the non-template synthesis of the macrocyclic ligand in relatively poor yield. A further variation on this reaction type allows the use of an enol ether (vinylogous ester), which provides more flexibility with respect to substituents (equation 17).104 The approach illustrated in equation (15), and Scheme 11 can be extended to include reactions of (3-diketones. The benzodiazepines, which result from reaction between 1,2-diaminobenzenes and (3-diketones, can also serve as precursors in the metal template reaction (Scheme 12).101 105 106 The macrocyclic complex product (46) in this sequence, being unsubstituted on the meso carbon atom, has been shown to undergo an electrochemical oxidative dimerization (equation 18).107... 

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