Primary deuterium KIEs

Because of their dependence on mass, KIEs have been used in two ways to detect tunnelling. One is that primary deuterium KIEs are larger than predicted on the basis of zero-point energy alone when tunnelling makes a significant contribution to the KIE. For example, primary deuterium KIEs larger than 25 have been reported (Lewis and Funderburk, 1967 Wilson et al., 1973) for proton transfer reactions where tunnelling is important. 

Because unexpectedly large primary deuterium KIEs are observed in reactions where tunnelling is important, and unexpectedly large secondary deuterium KIEs have been observed in some hydron transfers in elimination and enzyme-catalysed hydride transfer reactions, Saunders (vide infra) wondered whether very large secondary deuterium KIEs were also indicative of tunnelling. 

Table 35 Calculated secondary a- and primary deuterium KIEs for the model hydride transfer reaction (45).°...

More experimental data where the secondary KIE was larger than the EIE were subsequently published by Subramanian and Saunders (1984). The 2-arylethyl system was employed in these studies because other relevant data, such as the primary deuterium KIE, were available for this reaction. Special techniques were developed to determine the primary and the secondary tritium KIEs for this system. Three isotopically distinct elimination reactions (49-51) are possible for a 2-arylethyl derivative tracer labelled with tritium at the 2-position. 

The results of these calculations have implications on the applicability of the rule of the geometric mean, which indicates that the KIE for a doubly labelled species should be the product of the KIEs for the corresponding singly labelled substrates. For instance, the KIE for the doubly labelled [17] should be the product of the secondary deuterium KIE, ]/ ]> associated with the nontransferring hydrogen and the primary deuterium KIE, / , produced by the transferring hydrogen (equation 58)). 

Another polarimetric method for the accurate determination of KIEs bears a strong resemblance to the isotopic quasi-racemate method, described above. In this method, Bach and co-workers (1991) utilized what they called isotopically engendered chirality to determine the primary deuterium KIE for an elimination reaction. In theory, the method can be used for any reaction where a substrate with a plane of symmetry yields, under normal conditions, a racemic mixture. For instance, if the plane of symmetry in the unlabelled... 

Deuterium nmr spectroscopy has been utilized for the last decade to determine large (primary deuterium) KIEs in reactions with isotopes present at the natural abundance level (Pascal et al., 1984,1986 Zhang, 1988). A great advantage of this approach is that labelled materials do not have to be synthesized. Neither is there any need for selective degradation procedures, which are often necessary to produce the molecules of low mass, e.g. C02, acceptable for isotope ratio mass spectrometry. Moreover, the KIEs for several positions can be determined from one sample. However, until quite recently the relatively low precision of the nmr integrations that are used for the quantitative assessment of the amount of deuterium at specific molecular sites has limited the applicability of this technique for determining small (secondary deuterium) KIEs. 

The experimental data in Table 37.1 indicate a primary deuterium KIE at C3 in all cases studied. This result definitively rules out the El mechanism, as the breakage of the C3-H bond does not occur during the rate-determining step. As we can see in the El transition state represented in Fig. 37.2, the C-F bond is being broken but the C3-H bond remains unaltered. A noticeable F KIE (F atom colored red) and a secondary D KIE at C4 (D colored blue) should be however expected in an El process. 

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