Arene oxides kinetic deuterium isotope effect

The formation of the Wheland intermediate from the ion-radical pair as the critical reactive intermediate is common in both nitration and nitrosation processes. However, the contrasting reactivity trend in various nitrosation reactions with NO + (as well as the observation of substantial kinetic deuterium isotope effects) is ascribed to a rate-limiting deprotonation of the reversibly formed Wheland intermediate. In the case of aromatic nitration with NO, deprotonation is fast and occurs with no kinetic (deuterium) isotope effect. However, the nitrosoarenes (unlike their nitro counterparts) are excellent electron donors as judged by their low oxidation potentials as compared to parent arene.246 As a result, nitrosoarenes are also much better Bronsted bases249 than the corresponding nitro derivatives, and this marked distinction readily accounts for the large differentiation in the deprotonation rates of their respective conjugate acids (i.e., Wheland intermediates). 

The observations that the pH-independent reactions of deuterium-labeled 5-met-hoxyindene oxide and 6-methoxy-1,2,3,4-tetrahydronaphthalene-1,2-oxide show significant primary kinetic deuterium isotope effects for the ketone-forming reactions, whereas the pH-independent reactions of deuterium-labeled naphthalene oxide and benzene oxide do not, are quite puzzling. Clearly, more work needs to be done to fully understand why transition-state structures for rearrangement of arene oxides to phenols differ from those for rearrangement of benzylic epoxides to ketones. 

Perdenteration of the methylene hnker affords a relatively kinetically stable complex, which allows for the monitoring of exogenons snbstrate oxidations. When (7) is exposed to cold (-95 °C) acetone solntions of the lithium salts of para-substituted phenolates, clean conversion to the corresponding o-catechols is observed. Deuterium kinetic isotope effects (KIEs) for these hydroxylation reactions of 1.0 are observed, which is consistent with an electrophilic attack of the peroxo ligand on the arene ring. An electrophilic aromatic substitution is also consistent with the observation that lithium jo-methoxy-phenolate reacts substantially faster with (7) than lithium / -chloro-phenolate. Furthermore, a plot of observed reaction rates vs. / -chloro-phenolate concentration demonstrated that substrate coordination to the metal center is occurring prior to hydroxylation, and thus may be an important feature in these phenolate o-hydroxylation reactions. 

Investigation on secondary kinetic isotope effects with deuterium labeling on the arene suggests a reaction mechanism in which the C-H bond cleavage is the rate-determining step. This may explain the requirement for the methyl-substituted alkene in order to arrive at a more stabilized neopentyl-like palladium intermediate M. For 2-chlorophenyl as aryl substituent, the superiority of the present pathway was demonstrated over a potential sequence of oxidative insertion,... 

However, evidence contradictory to the arene oxide intermediate has been reported [128]. The kinetic isotope effects on the PAH-catalyzed oxygenation have been studied using three deuterium-labeled phenylalanines, [4- H]-, [3,5- H]-, and [2,3,4,5,6- H]phenylalanine. It is expected that the yield of tyrosine with [4- H]phenylalanine decreases relative to that with non-labeled substrate because of kinetic isotope effect, and that the decrease in the yield of tyrosine is balanced by a commensurate increase in the amounts of 3-hydroxyphenylalanine if the reaction occurs via an arene oxide intermediate. The kinetic isotope effects obtained from the experiments, however, are actually 1.22 for the formation of tyrosine and 1.01 for that of 3-hydroxyphenylalanine, indicating that the amount of 3-hydroxyphenylalanine is not affected by the deuteriumlabeling at 4-position of the aromatic ring and is independent of the consumption of tyrosine. The experiments with the other labeled substrates also supported the independent formation of tyrosine and 3-hydroxyphenylalanine. Thus, these results... 

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