Pericyclic reactions, reactivity rates

The way the substituents affect the rate of the reaction can be rationalised with the aid of the Frontier Molecular Orbital (FMO) theory. This theory was developed during a study of the role of orbital symmetry in pericyclic reactions by Woodward and Hoffinann and, independently, by Fukui Later, Houk contributed significantly to the understanding of the reactivity and selectivity of these processes. ... 

The structural requirements of the mesomeric betaines described in Section III endow these molecules with reactive -electron systems whose orbital symmetries are suitable for participation in a variety of pericyclic reactions. In particular, many betaines undergo 1,3-dipolar cycloaddition reactions giving stable adducts. Since these reactions are moderately exothermic, the transition state can be expected to occur early in the reaction and the magnitude of the frontier orbital interactions, as 1,3-dipole and 1,3-dipolarophile approach, can be expected to influence the energy of the transition state—and therefore the reaction rate and the structure of the product. This is the essence of frontier molecular orbital (EMO) theory, several accounts of which have been published. 16.317 application of the FMO method to the pericyclic reactions of mesomeric betaines has met with considerable success. The following section describes how the reactivity, electroselectivity, and regioselectivity of these molecules have been rationalized. 

Most pericyclic reactions, though of course not all, are little influenced by Coulombic forces for example, it is well known that the polarity of the solvent has little effect on the rate of Diels-Alder reactions. We can therefore expect that a major factor influencing reactivity will be the size of the frontier orbital interaction represented by the third term of equation 2-7, p. 27. This is why this chapter is much the largest in this book the most dramatic successes of frontier orbital theory have been the explanations it has given to an amazingly large number of observations in pericyclic chemistry. 

Nevertheless, frontier orbital theory, for all that it works, does not explain why the barrier to forbidden reactions is so high. Perturbation theory uses the sum of all filled-with-filled and filled-with-unfilled interactions (Chapter 3), with the frontier orbitals making only one contribution to this sum. Frontier orbital interactions cannot explain why, whenever it has been measured, the transition structure for the forbidden pathway is as much as 40 kJ mol 1 or more above that for the allowed pathway. Frontier orbital theory is much better at dealing with small differences in reactivity. We shall return later in this chapter to frontier orbital theory to explain the much weaker elements of selectivity, like the effect of substituents on the rates and regioselectivity, and the endo rule, but we must look for something better to explain why pericyclic reactions conform to the Woodward-Hoffmann rules with such dedication. 

In this case, Cucurbituril (53) reveals a number of enzymelike features The reaction exhibits saturation behaviour, it becomes independent of substrate concentration with sufficient amounts of 54 and 55, high concentrations of 54 retard the cycloaddition (substrate inhibition), and release of product 56 from its complex with Cucurbituril (53) is the rate determining step. NMR spectroscopic data suggest that both starting materials of the cycloaddition are hydrogen bonded to the carbonyl groups of 53 with their ammonium moiety and that the reactive substituents extend into the interior of Cucurbituril (53). In this cavity the pericyclic reaction takes place to form the 1,2,3-triazole 56. Kinetic data indicate that the formation of the ternary complex of Cucurbituril (53) with the two starting materials 54 and 55 is not strainless. Since the reaction is still accelerated very much it is assumed that the transition state of the reaction corresponds to the size of the cavity more closely than the substrates. This is a further indication that this case is a useful enzyme model. 

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