Kinetic isotope effects a-deuterium

What concerns us here are three topics addressing the fates of bromonium ions in solution and details of the mechanism for the addition reaction. In what follows, we will discuss the x-ray structure of the world s only known stable bromonium ion, that of adamantylideneadamantane, (Ad-Ad, 1) and show that it is capable of an extremely rapid degenerate transfer of Br+ in solution to an acceptor olefin. Second, we will discuss the use of secondary a-deuterium kinetic isotope effects (DKie) in mechanistic studies of the addition of Br2 to various deuterated cyclohexenes 2,2. Finally, we will explore the possibility of whether a bromonium ion, generated in solution from the solvolysis of traAU -2-bromo-l-[(trifluoromethanesulfonyl)oxy]cyclohexane 4, can be captured by Br on the Br+ of the bromonium ion, thereby generating olefin and Br2. This process would be... 

According to Scheme 11, the isomeric ortho para) product ratios are established during the collapse of the radical pair in (64) (most probably at the positions of AN+- with the highest electron density). Furthermore, the absence of a measurable kinetic isotope effect in the decay of the deuterated analogue (C6D5OCH.v) in Table 3 is predicted from Scheme 11 since the proton loss occurs in a subsequent, rapid step (65). The absence of a deuterium kinetic isotope effect also indicates that the presence of pyridine in the triad in (63) does not lead to the nitroanisoles by an alternative... 

Secondary a-deuterium kinetic isotope effects (KIEs) have been widely used to determine the mechanism of SN reactions and to elucidate the structure of their transition states (Shiner, 1970a Westaway, 1987a). Some of the significant studies illustrating these principles are presented in this section. 

Direct evidence about the first step of activation of butane was obtained on a V-P oxide catalyst in the butane oxidation to maleic anhydride based on deuterium kinetic isotope effect (34). It was found that when a butane molecule was labeled with deuterium at the second and third carbon, a deuterium kinetic isotope effect of 2 was observed. No kinetic isotope effect was observed, however, if the deuterium label was at the first or fourth carbon. By comparing the observed and theoretical kinetic isotope effects, it was concluded that the first step of butane activation on this catalyst was the cleavage of a secondary C—H bond, and this step was the rate-limiting step. 

In this way four pairs of values of 0 and hydrogen based on a-deuterium kinetic isotope effects (which measure the degree of rehybridisation of the anomeric carbon atom), it was possible, using Allinger s (1977) MM2 molecular mechanics program, to calculate the conformation of the rest of the molecule. 

Since the N(5)-methylflavinium cation undergoes general-base-catalyzed dealkylation (Equation 36) (31) with a deuterium kinetic isotope effect (N(5)—CH3/N(5)—CD3) of greater than 10, we chose —CD3 and more simply —CH2CH3 as the N(5)-blocking groups. The compound 4a-FlEtOOH is prepared routinely in our laboratory in... 

This solvation rule for 5n2 reactions can be useful in predicting the influence of a change in solvent on the structure of activated complexes. It is in agreement with studies involving leaving group heavy atom and secondary a-deuterium kinetic isotope effects, as well as theoretical calculations of solvent effects on transition-state structures. Possible limitations of this solvation rule have been discussed see [498] and relevant references cited therein. 

A deuterium kinetic isotope effect of 2 has been found in the hydrogenation of 1,3-pentadiene using a Ziegler-Natta catalyst, cobalt(ll,lll) /r -oxostearate-AlEts, Co O(Ci7H35C02)6(H20)3 5H2O-AICI3. The reaction was found to be of a kinetic order of 0.3 in the diene, and first order in the hydrogen and the catalyst. The kinetics and the selectivity of the reaction has been studied at 253-293 K. 

D. Crich and N. S. Chandrasekera, Mechanism of 4,6-O-benzylidene-directed jS-mannosylation as determined by a-deuterium kinetic isotope effects, Angew. Chem. Int. Ed., 43 (2004) 5886-5889. 

The Northrop-Cleland nomenclature system for isotope effects greatly simplifies their discussion the non-abundant isotope and, in the case of secondary effects, site of substitution are written as superscripts to V or VjK in parentheses, so that °(F/A) refers to an a-deuterium kinetic isotope effect on kcatZ-Klm and (K) refers to an effect on kcat- The effects on individual rate and equilibrium constants are written as superscripts is the p-tritium effect on an equilibrium constant and " k+2 is the effect on the k+2 step. Although in principle potentially ambiguous (e.g. could in principle refer to or the relatively short-lived F), in practice any ambiguity is resolved from the context. 

Table 5.3 a-Deuterium kinetic isotope effects on the hydrolysis of the glycosyl-enzyme intermediates of retaining glcyosidases. 

The second-order rate constant of hydride transfer from AcrH2 to TolSQ with HiS 2H+ (ArF 111) increases linearly with [His-2H + ] (gray circles in Figure 2.10a).45 The rates of hydride transfer exhibit a deuterium kinetic isotope effect (/thh/ dh 1.7 0.1) when AcrH2 is replaced by the dideuterated compound AcrD2 (kDH denotes the rate constant of hydride transfer from AcrD2 to TolSQ with His-2H + ) (black circles in Figure 2.10b).49 In sharp contrast to this, no deuterium kinetic... 

An interesting and potentially useful observation in the mutational work is that the substitution of leucine for Hisl43o decreased the activity to 0.2% of wild type. This significant activity allowed the deuterium kinetic isotope effect for the reaction of [ 1- H2] propane-1,2-diol to be measured. The value obtained turned out to be 2 for ° cat, about one-fifth to one-sixth of that for wild-type enzyme. Substitution of alanine gave about 1.5% activity and a deuterium kinetic isotope effect of 5-6. It appears that the hydrogen transfer is not solely rate limiting in these variants. 

The reaction is analogous to that of DDH, with the substitution of NH3 + in place of OH at C2 of the substrate and the elimination ofNH4+ instead of H2O. Unlike DDH, the activity of EAL does not require K. Reaction of [l- H]ethanolamine proceeds with a deuterium kinetic isotope effect of 6.8, and deuterium transfer to C2 occurs without exchange with the medium. Oxygen at Cl of the substrate is retained in the product, and adenosyl-C5 of adenosylcobalamin mediates hydrogen transfer from Cl of the substrate to C2 of the product as in DDH. ... 

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