Kinetic/thermodynamic templation

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. 

The ability of a chemical to act as a template is frequently attributed to a combination of thermodynamic and kinetic factors. As has been defined by Busch [3] a thermodynamic template binds more strongly to one of the products present in an equilibrium (i.e. a mixture under thermodynamic control) shifting the reaction towards the formation of this specific product which is then obtained in higher yields. In contrast, kinetic templates operate under irreversible conditions by stabilising the transition state leading to the final product. 

Further understanding of the kinetic of template polymerization needs consideration of the process entropy. Applying a well known lattice model, it is easy to see that entropy changes, AS, in free polymerization and the template polymerization, differs considerably. According to the principles of statistical thermodynamics, the entropy of mixing is given by the equation ... 

Many reactions in this section probably owe a thermodynamic template effect for part of their success, but it is the kinetic effect which is most clearly illustrated. Reactions have been chosen to display a range of geometrical features and also various types of bond formation. The coverage will be selective and many topics will be developed more fully in Chapter 61.1 The present section will be subdivided according to the involvement or otherwise of donor atoms. 

Busch classified templates as thermodynamic [13a, 27] or kinetic [ 13b, 28], A thermodynamic template shifts the position of equilibrium of a reversible reaction by preferentially binding one product. Kinetic templates operate on irreversible reactions by stabilizing the main transition states leading to the desired product. Kinetic templates almost invariably bind the product more strongly than the starting material, so they also favor the formation of the product thermodynamically. Conversely, thermodynamic templates are likely to accelerate formation of the product by transition state stabilization, so classification of the observed effect depends crucially on the reaction conditions and time scale. 

Most of the templates diseussed in this chapter are kinetic templates. Some of the early examples of metal cation templated macrocyclization studied by Curtis and Busch [7,9] (Schemes 1-1 and 1-2) are thought to operate under thermodynamie eontrol. The clearest evidence for a thermodynamic template effect comes when the template-free product is not stable under the reaction conditions. For example, treatment of 1,2-dicyanoben-zene 11 with boron trichloride or uranyl chloride results in the formation of subphthalo-... 

Another interesting example of a thermodynamic template is adamantanecarboxylate 21 in the reaction shown in Scheme 1-6, discovered by Fujita and co-workers [31]. Cage 24 is only formed in very low yield, as part of an intractable mixture of oligomeric products, when 22 and 23 are mixed. When four equivalents of the template 21 are added, the equilibrium shifts towards 24 and the 1 4 complex is the only species observable by H-NMR. The cage 24 remains intact after the templates have been removed by acidification and solvent extraction, and is kinetically stable at room temperature. 

Diels-Alder reactions have also been accelerated inside the cavities of cyclic porphyrin trimers [45]. For example, diene 52 and dienophile 53 react selectively to give the exo adduct 54 (Scheme 1-14) inside the cavity of 39 [45a,b], Cyclic porphyrin trimer 39 is an effective kinetic and thermodynamic template for this reversible Diels-Alder reaction, of which the stereochemical outcome may be reversed to give mainly the endo adduct if a smaller porphyrin trimer is used [45 c]. 

Different roles for the metal ion in a template reaction have been dehneated and termed thermodynamic template effect and kinetic template effect In the first case, the metal ion picks out the macrocyclic ligand from an equilibrating mixture of products, thus driving the reaction equilibrium... 

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]. 

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