Synthesis of clathrochelates

Metal ion directed (template) syntheses of the macrobicyclic complexes are effected through cyclization of the preformed tris-complexes or semiclathrochelate as well as via interaction of metal ion bis-complexes with cross-linking agents. 

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 

A number of clathrochelate ligands (Sections 2.3 and 2.4) can be preliminarily synthesized by conventional organic chemistry procedures. However, the role of the template effect can not be discounted either. In the majority of cases, alkali metal ions (most common Na+ and Cs ions) presumably act as templates that are then readily extruded from the clathrochelate ligand cavity. 

For instance, this reaction pathway has been employed for the preparation of tin-capped iron(II) tris-dioximates by the treatment of hydroxy- and alkoxyboron-capped clathrochelate complexes with 

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The nonmacrocyclic iron(II) tris-complex (an intermediate product in the synthesis of clathrochelates, see Chapter 4) have readily reacted with two molecules of IGe(CF3)3 in aqueous solution. In this case IGe(CF3)3 formed dianionic octahedral capping groups. The ions released in the course of the reaction were neutralized by calcium carbonate. The resultant clathrochelate [FeNx3(Ge(CF3)3)2] dianion was isolated as a salt with a bulky organic (n.-C4H9)4hT cation [73]. 

The synthesis of clathrochelates resulting from capping with antimony(V) compounds was realized for the first time as described in Ref. 74. With antimony(V) halogenides, only polymeric complexes were isolated, but antimony(V) triorganyles, unlike tin(IV) triorganyles, readily form nioximate iron(II) clathrochelates by Reaction 19. 

Goedken and Peng s idea to employ the reaction between the amino groups, bound to the metal ion, and formaldehyde for the synthesis of clathrochelates proved to be beneficial. It has served as a basis for later studies of Sargeson and coworkers on the synthesis of sepulchrates and sarcophaginates. 

A considerable (approximately 300-500-fold) decrease in the synthesis rate constant for the FeGx3(BR)2 complexes was observed compared with those for nioximates and 4-methylnioximates. It correlates with the corresponding decrease in p , stability constant for the [Fe(H2Gx)3] + dication (Table 27) and indirectly confirms the fact that the synthesis of clathrochelate occur via formation of the protonated [Fe(H2D)3] + tris-complex. 

Nucleophilic displacement at centres other than carbon (for example, boron, silicon etc.) is an effective tool for producing new chelate rings via heteroatom-heteroatom bond formation. This procedure has been widely used for coupling oxime groups in the synthesis of clathrochelates and related monomacrocyclic oxime-based species. 

The BF4 anion in the clathrochelate [CoDma(BF)2](BF4) complex can readily be replaced by another large inorganic anion (e.g. PFe ) via an exchange reaction occurring in aqueous-acetonitrile solution in the presence of a great excess of the substituting anion salt [39]. The reduction of the [CoDma(BF)2](BF4) clathrochelate with Nal solution in acetone yielded a macrobicyclic cobalt(II) CoDma(BF)2 complex. The synthesis of the latter via a template condensation on the Co2+ ion was not yet successful. 

In the synthesis of the boron-capped cobalt(II) tris-dioximates, ferrocenylboronic acid was also used as a capping agent [43], Reaction of this Lewis acid with anhydrous C0CI2 and dioximes in oxygen-free methanol gave clathrochelate CoNx3(BFc)2 and CoDm3(BFc)2 complexes ... 

Synthesis of the clathrochelate with hydridoboron capping groups via template condensation in dry acetonitrile occurs by Reaction 12 FeBrj + 3H2NX + 2NaBH4 FeNx3(BH)2 + 2NaBr + 6H2 (12)... 

With the majority of alicyclic boron-capped iron(II) dioximates, neither template condensation nor recrystallization from organic solvents gave crystals suitable for X-ray analysis. A rate-controlled template condensation within several days yielded FeGx3(B0H)2 3H20 monocrystals, since the synthesis of this clathrochelate compound proceeds much more slowly than that of analogous complexes with nioxime and 4-methylnioxime [62, 63]. 

The cycloaddition reaction proceeds under more rigid conditions and takes more time than a direct template condensation on the iron(II) ion. This can be explained by the fact that the overall mechanism of clathrochelate synthesis involves an intermediate tris-complex formation step. It is evident that macrocyclic square-planar iron(II) bis-dioximates are relatively kinetically stable, and the... 

A direct synthesis of C2-nonsymmetric tris-dioximate iron (II) clathrochelates via the formation of semiclathrochelate complex 2 cannot be realized even with a great excess of complex 1, since compound 2 readily disproportionates to give 1 and 3 (Scheme 9). 

The synthesis of C2-nonsymmetric clathrochelate iron(II) dioximates was realized through a stepwise assembling on the sorbent surface (Scheme 11). 

The best results were obtained with aluminium hydroxide resulting from hydrolysis of aluminium(III) iso-propylate. A high sorption capacity (ca 10%) of compound 2, a high degree of desorption of complex 3, and the purity of the resulted clathrochelate 4 make aluminium(III) hydroxide the most suitable matrix for the synthesis of targeted compounds [64]. 

The introduction of lipophilic substituents is of interest for producing surface-active compounds (surfactants) and liquid-crystal systems. The complexes with allyl substituents at the apical boron atoms are precursors for the synthesis of linear and netlike polymeric clathrochelates. 

The most feasible Routes I-III for the synthesis of triribbed-functionalized a-dioximate clathrochelates (Scheme 12) were proposed in Ref. 65. The halogen-carbon bonds are reasonably active in nucleophilic substitution reactions, and the dihalogenoxime complexes are relatively stable (unlike dihalogenoximes, these complexes are available and undergo no intramolecular conversions... 

The use of Route III presented problems because the attempts to obtain hexahalogenide precursors from initial dihalogendioximes by the standard procedures of synthesis of such clathrochelates have not been successful. Nevertheless, the conditions under which the yield of these complexes was 60-90 % were selected in Ref. 65 nitromethane was as a solvent, and acetonitrile FeAN4Cl2 solvato-complex as a source of Fe + ions, and the water was removed from the reaction mixture. The three hexachloride precursors with phenylboronic, re-butylboronic, and fluoroboronic capping groups (Scheme 13) were obtained [65]. 

The reaction with an excess of methylmercaptan in the presence of potassium carbonate at room temperature led to the formation of partially substituted products only, mainly trisubstituted clathrochelates. Therefore, a more active potassium methylmercaptanate was used in the synthesis of the hexasubstituted product, and the reaction readily proceeded in a high yield [65]. 

The appropriate conditions for the synthesis of tris-azamacrocyclic clathrochelates containing dioximate fragments in polyazamacrocyclic rings were not selected. Attempts to use open-chain polyamines, as well as their complexes with transition metals, primarily Ni2+, gave no desired results. 

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... 

Dichloride FeBd2(C12Gm)(BF)2 precursor readily reacted with aliphatic primary amines of different natures in the DMF and THF to produce disubstituted clathrochelates (Scheme 22). The secondary amines react with dichloride precursor to substitute one of the two reactive chlorine atoms, and this permits one to obtain spacer-containing clathrochelate and bis-clathrochelate (Scheme 23). An alternative pathway for the synthesis of bis-clathrochelates uses... 

The synthesis of boron-capped clathrochelate iron(II) tris-dioximates has been realized for wide range of substituents at the boron atom. The attempts to obtain analogous trialkyl- and triaryl-tin-capped iron(II) compounds have not been successful. In the some cases, polymeric clathrochelate compounds have been formed, especially when reactions proceed under basic conditions. With tin(IV) iodide, the primarily formed soluble green complexes also readily transform into polymeric red compounds that are presumably associated with the detachment of iodide ions because of steric hindrance between substituents in dioxime fragments and the bulky iodide atoms of capping groups [70],... 

This free clathrochelate ligand has been employed for the synthesis of nonprotonated and tetraprotonated free cages using tetra-/i-butylammonium hydroxide and HCIO4, respectively, as well as chromium(III)-capped magnesium, manganese(II) and lithium clathrochelates (Scheme 32) [85],... 

A similar procedure was employed to obtain the [Co(diNOsar)]3" cation optically active isomers and salts of other anions [101]. A more rational approach to the synthesis of this clathrochelate was reported in Ref. 102. 

Cerium (III) or tin(II) ions were chosen as a reductant [5]. Application of redox processes is promising for the synthesis of novel sarcophaginates with higher stability and a small cavity size. The reactivity of sarcophaginate ligands may also be employed to prepare imine-, hydroxylamine-, and amide-containing systems not only with cyclohexanediamine derivatives, but with simpler clathrochelates as well. 

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