Coordination template effect

The kinetic template effect is observed in reactions in which the metal ion acts by coordinating the reactants. This effect has also been described as a coordination template effect. A more direct description of a kinetic template reaction is one which involves Combination of two Ligands Attached to the same. Metal ion. Such a description leads to the useful acronym CLAM reaction , which graphically portrays the key reaction step. The process can be generalized and compared with the non-template reaction in Scheme 30. 

A reaction is described as proceeding by a kinetic template effect if it provides a route to a product that would not be formed in the absence of the metal ion and where the metal ion acts by coordinating the reactants. An alternative description for this process is the coordination template effect that more aptly describes how the stereochemistry imposed by the metal ion, through coordination, promotes a series of controlled steps in a multistep reaction, e.g., Scheme 1 17, 136, 137). 

The template centre plays the key role in matrix reactions. If the steric course of macrocyclisation, or other multistep reaction, is directed and facilitated by the ligsons spatial structures, and their activation by coordination to the metal ion or another centre, then the process is controlled by the kinetic coordination template effect. If the metal ion (or another centre) sequesters one of the components from an equilibrium mixture (starting ligsons and oilier competing molecular species) and, as a consequence, shifts the position of the equihbriiun towards the formation of the desired product in the form of its metal complex, then the thennodynamic (or equilibrium) coordination template effect is considered to be operative for the reaction. 

Reactions with a pronounced kinetic coordination template effect are found, in particular, in cases of preparation of macrocycUc compounds by ring-closure of chelate precursors. For example, when the complex [Ni(L4)] is electrophilically alkylated with l,2-bis(bromomethyl)benzene, the macrocyclic product [Ni(L5)Br2] is isolated ( q. 1.1). 

In the above examples of the kinetic coordination template effect, the metal ion serves to transfer information to interacting compoimds, so the structure of the reaction product is predetermined. In such cases the strict geometry of the metal ion eoordination sphere [2, 11] may be considered as an information source. 

It should be noted that uncoordinated allylphosphine does not cyclise when treated with initiator, This gives evidence for the kinetic coordination template effect operating in this process. In conditions of kinetic control (enforced by spatial effects resulting from coordination to the metal), macrocyclic product formation by addition of P-H to the C=C double bond of a neighbouring coordinated allylphosphine proceeds contrary to Markovnikov s rule (phosphorus as a more electronegative element bonded to a less substituted carbon atom). This template process is notable for its exceptional regiospecific character in that the formation of Markovnikov addition products is not detected. 

The following reactions provide examples of the thermodynamic coordination template effect. 

Thus, when we say that, for instance, a kinetic coordination template effect is responsible for the production of some product, it does not mean that a possible contribution from the thermodynamic coordination template effect is ruled out. The role of the matrix does not depend on one or other of the two coordination template effects prevailing. It consists not only in the strict suppression of side effects, but also in directing the process to its most favourable pathway [2, 4]. 

The chelate [Ni(L4)] transformation into the macrocyclic product [Ni(L5)Br2] [36, 37] belongs to those coordinated ligand reactions which are also template transformations. The latter are realised as a result of the kinetic coordination template effect with formation of a new chelate ring, whereas the alkylation of [Ni( L4)] with methyl iodide or benzyl bromide is merely a reaction of a coordinated ligand. 

The discussion commences with examples illustrating the effectiveness of the first synthetic approach, where the manifestation of the coordination template effect of the metal template is evident. Thus, for instance, interaction of [M(en)2] " , where M = Ni, Cu or Pd, with an excess of formaldehyde and carbon acid nitroethane in basic solution gives the cyclam-substituted derivatives [M(L130)] " in high yield (Eq. 2.73) [160-162]. 

The product is kinetically rather stable, due to the lack of (or reduced) nucleophilic properties of the coordinated primary amine group. However, in basic media, it easily turns into [Cu(L15)](C104)2. The kinetic coordination template effect is presumably manifested at this key step of macroc clisation if one assumes that, in the presence of base, the nucleophilic amido ligand is generated in sufficient concentration to allow the ring-closure reaction to proceed at a reasonable rate. 

Thus, introduction of electron-withdrawing groups into the y position of y -diketonate residues results in considerable activation of the coordinated CO groups and creates conditions favourable for the kinetic coordination template effect to operate. Chelates [M(L6)] and [M(L228)], where M = Ni or Cu, also interact with 1,3-diaminopropane forming 15-membered macrocyclic systems [273, 285]. 

So, when assessing the possibility of achieving either template process, the reactivity of the interacting groups, the conditions for displaying kinetic (the possibility of coordination and activation of the ligsons participating in the reaction, by 1/2 data) and thermodynamic coordination template effects, as well as the factors enumerated earlier in Chapter 1, must all be taken into account. 

By heating a mixture of solutions of o-phda in dimethylformamide and propargyl aldehyde in methanol the Schiff base H2L3OI was obtained in 27% yield [336]. In the presence of Cu +, Co or Ni + ions, macrocyclic complexes are produced in about 70% yield, thanks mainly to the thermodynamic coordination template effect. 

Scheme 2-35. Illustration of the kinetic coordination template effect in the synthesis of phthalo-cyanines.

The coordination template effect is widely used for the preparation of various monomacrocyclic compounds synthesised in two-dimensional space, as exemplified by the material presented in the previous chapters. Examples of reactions between ligsons positioned around a matrix in three-dimensional space are much less common. This chapter illustrates the use of the template effect in elegant syntheses of three-dimensional polymacrocyclic systems. 

The synthesis of H6L1022 was carried out by the high dilution technique (yield 18%), as well as in nearly quantitative yield through a template reaction using a published [140] procedure. Iron(III) is bound even more strongly in [Fe(L1022)J than to EDTA or natural siderophores, as shown by competition experiments in water at pH 11.5 [142]. The effectiveness of these applications of the coordination template effect is attributed to a number of favourable factors ... 

Molecular Organization, Portal to Supramolecular Chemistry. Structural Analysis of the Factors Associated with Molecular Organization in Coordination and Inclusion Chemistry, including the Coordination Template Effect , D. H. Busch and N. A. Stephenson, Coord. Chem. Rev. (1990) 100, 119. 

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