The Entropic Hypothesis

The preceding interpretations of the results are essentially based on enthalpy considerations. However, an entropic basis for the selectivity toward the Cy 5 radical in the 5-hexenyl case has also been advanced. Capon and Rees suggested that more conformations are available for CyS cyclization than for Cy6 cyclization. Although sometimes used, this way of rationalizing five-membered ring formation does not seem to have been tested. 

Recently, Tedder proposed that rotational entropy may be a very important factor which favors five-membered ring formation. The origin of this suggestion lies in his work in which he found small but regular variations of preexponential factors for the intermolecular addition of alkyl radicals to 

Recent calculations suggest that (Cy 5) radical formation can be accounted for on the basis of entropy alone. Since these theoretical results are not in agreement with the experimental data in both the Cy5/Cy6 and Cy6/Cy7 cases as discussed, for instance, in Table 3, they must be considered with caution. 

It seems clear that none of these rationalizations is completely satisfactory and probably are not mutually exclusive. Nevertheless, it will be seen in the following sections that these approaches may be useful as qualitative guides in irreversible cyclizations processes of radicals not only in the 5-hexenyl system but also in other cases. 

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The entropic hypothesis seems at first sight to gain strong support from experiments with model compounds of the type listed in Table 9.1. These compounds show a huge rate acceleration when the number of degrees of freedom (i.e., rotation around different bonds) is restricted. Such model compounds have been used repeatedly in attempts to estimate entropic effects in enzyme catalysis. Unfortunately, the information from the available model compounds is not directly transferable to the relevant enzymatic reaction since the observed changes in rate constant reflect interrelated factors (e.g., strain and entropy), which cannot be separated in a unique way by simple experiments. Apparently, model compounds do provide very useful means for verification and calibration of reaction-potential surfaces... 

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