Hydrogen transfer isotope effects

The pyridine-catalysed lead tetraacetate oxidation of benzyl alcohols shows a first-order dependence in Pb(OAc)4, pyridine and benzyl alcohol concentration. An even larger primary hydrogen kinetic isotope effect of 5.26 and a Hammett p value of —1.7 led Baneijee and Shanker187 to propose that benzaldehyde is formed by the two concurrent pathways shown in Schemes 40 and 41. Scheme 40 describes the hydride transfer mechanism consistent with the negative p value. In the slow step of the reaction, labilization of the Pb—O bond resulting from the coordination of pyridine occurs as the Ca—H bond is broken. The loss of Pb(OAc)2 completes the reaction with transfer of +OAc to an anion. 

In view of the large hydrogen-deuterium isotope effect of 5.26, Baneijee and coworkers proposed that the proton transfer mechanism (Scheme 41) is also operating. In this mechanism, pyridine behaves as a base and abstracts a proton in the rate-determining step. 

HEAVY ATOM AND REMOTE HYDROGEN KINETIC ISOTOPE EFFECTS IN GLYCOSYL TRANSFER... 

Bell (14) has pointed out that a plot of hydrogen kinetic isotope effects for a variety of proton transfer reactions vs. the difference in pK between the two bases shows a central maiximum near fipK =0.0 and decreasing limbs for ApK <0 or > 0. An example of this is shown in figure 4 from Bell and Cox (14). 

More often, one sees simplifications of the equations designed to apply to particular models. The maximum hydrogen/deuterium isotope effect for a proton transfer,... 

Limbach, H. H. Miguel Lopez, J. Kohen, A. Arrhenius curves of hydrogen transfers Tunnel effects, isotope effects and effects of pre-equilibria. Phil. Trans. R. Soc. B 2006,361,1399-1415. 

As discussed below, studies of the multiple kinetic hydrogen/deuterium isotope effects show that the reactions of 16-19 exhibit only a single barrier, involving a concerted hydrogen bond compression followed by a concerted multiple proton transfer. The different behavior of these complexes as compared to the stepwise intramolecular multiple proton transfers will be discussed later. 

Wawzonek et al. first investigated the mechanism of the cyclization of A-haloamines and correctly proposed the free radical chain reaction pathway that was substantiated by experimental data. "" Subsequently, Corey and Hertler examined the stereochemistry, hydrogen isotope effect, initiation, catalysis, intermediates, and selectivity of hydrogen transfer. Their results pointed conclusively to a free radical chain mechanism involving intramolecular hydrogen transfer as one of the propagation steps. Accordingly, the... 

Stames el al.I7 have provided support for the above mechanism (Scheme 6.29) by determining the unsaturated chain ends (112) in low conversion PVAc by l3C NMR. They were able to distinguish (112) from chain ends that might have been formed if transfer involved abstraction of a vinylic hydrogen. The number of unsaturated chain ends (112) was found to equate with the number of -CH OAc ends suggesting that most chains arc formed by transfer to monomer. Stames et a . 13 also found an isotope effect k kD of 2.0 for the abstraction reaction with CTTpCHOiCCD as monomer. This result is consistent with the mechanism shown in Scheme 6.28 but is contrary to an earlier finding.174... 

For allyl acetate a significant deuterium isotope effect supports the hydrogen abstraction mechanism (Scheme 6,31).183 Allyl compounds with weaker CTT-X bonds (113 X=SR, S02R, Bi etc.) may also give chain transfer by an addition-fragmentation mechanism (Section 6.2.3). 

Transition state theory has been useful in providing a rationale for the so-called kinetic isotope effect. The kinetic isotope effect is used by enzy-mologists to probe various aspects of mechanism. Importantly, measured kinetic isotope effects have also been used to monitor if non-classical behaviour is a feature of enzyme-catalysed hydrogen transfer reactions. The kinetic isotope effect arises because of the differential reactivity of, for example, a C-H (protium), a C-D (deuterium) and a C-T (tritium) bond. 

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