Kinetic isotope effects carbonyl carbon

In this study, benzaldehyde and benzaldehyde-methyllithium adduct were fully optimized at HF/6-31G and their vibrational frequencies were calculated. The authors used MeLi instead of lithium pinacolone enolate, since it was assumed that the equilibrium IBs are not much different for the MeLi addition and lithium enolate addition. Dehalogena-tion and enone-isomerization probe experiments detected no evidence of a single electron transfer to occur during the course of the reaction. The primary carbonyl carbon kinetic isotope effects and chemical probe experiments led them to conclude that the reaction of lithium pinacolone enolate with benzaldehyde proceeds via a polar mechanism. 

Distinction between PL and ET mechanisms is not straightforward. Various experimental methods have been used so far to demonstrate the ET process, including spectroscopic detection of radical intermediates detection of products indicative of radical intermediates " and measurement of secondary deuterium " and carbonyl carbon kinetic isotope effects (KlEs) "" . The combination of several experimental methods, including KIE, substituent effect and probe experiments, was shown to be useful in distinguishing the ET process from the PL process for the addition reactions of the Grignard and other organometallic reagents . 

The carbonyl-carbon kinetic isotope effect (KIE) and the substituent effects for the reaction of lithium pinacolone enolate (112) with benzaldehyde (equation 31) were analyzed by Yamataka, Mishima and coworkers ° and the results were compared with those for other lithium reagents such as MeLi, PhLi and AllLi. Ab initio (HF/6-31-I-G ) calculations were carried out to estimate the equilibrium isotope effect (EIE) on the addition to benzaldehyde. In general, a carbonyl addition reaction (equation 32) proceeds by way of either a direct one-step polar nucleophilic attack (PL) or a two-step process involving electron transfer (ET) and a radical ion intermediate. The carbonyl-carbon KIE was of primary nature for the PL or the radical coupling (RC) rate-determining ET mechanism, while it was considered to be less important for the ET rate-determining mechanism. The reaction of 112 with benzaldehyde gave a small positive KIE = 1.019),... 

A different view on the rate-determining step in this type of reactions was published 1 year later [57] after carbonyl carbon kinetic isotope effects and relative reactivities of ortho-, meta-, and para-substituted benzophenones were determined. Scheme 20 presents the reactions proposed by these authors (see also [49] and Schemes 12 and 13) ... 

In a recent publication [13] of the results of yet another study of carbonyl carbon kinetic isotope effects (KIE), such an effect was found however, for fert-butylmagnesium chloride, contrary to what had earlier been reported [57]. The author justified his work as follows... 

No carbonyl carbon kinetic isotope effect was found for the reaction of allylmagnesium bromide with benzophenone [13,57]. The rate of the homolytic mechanism—which could be predicted on the basis of the oxidation potential of allylmagnesium bromide [46]—is slower than the concerted six-center reaction. 

Proof for single-electron transfer in reactions of allyl- and crotylmagnesium bromide with benzophenone had been reported a few years before, in 1988, based on measurements of carbonyl carbon kinetic isotope effects (which were nonexistent) and substituent effect techniques [65]. Doubt about the correct interpretation of the observed phenomenon was discussed earlier in this chapter (see p. 237 [13]). 

The effect of ring substituents on the rate constants, deuterium kinetic isotope effects and Arrhenius parameters for ene-additions of acetone to 1,1-diphenylsilane have been explained in terms of a mechanism involving fast, reversible formation of a zwitterionic silene-ketone complex, followed by a rate-limiting proton transfer between the a-carbonyl and silenic carbon. A study of the thermal and Lewis acid-catalysed intramolecular ene reactions of allenylsilanes with a variety of... 

As assumed, the small and positive valne of H/D kinetic isotope effect may be used as a criterion for an electron-transfer pathway. For example, anion-radicals of a-benzoyl-co-haloalkanes can react in two routes (Kimura and Takamnkn 1994). The first ronte is the common one—an electron is transferred from the oxygen anion of the carbonyl gronp to a terminal halogen. The transfer provokes fission of the carbon-halogen bond. The second ronte is the S 2 reaction, leading to a cyclic product as shown in Scheme 2.37. 

The analysis and interpretation of kinetic isotope effects (KIE) from the carbonyl carbon has been used to postulate SET processes for the first step in the reactions between ketones and MeLi or Mc2CuLi however, the ratedetermining steps within the overall mechanistic scheme in Eq. (5) depend on the steric and electronic properties of the substrate [63]. 

Independent support for this suggestion has been obtained by Swain (1961) who found a kinetic isotope effect (N14)/ (N15)< 1 in the acid hydrolysis of benzamide. This is considered to be evidence that the C—N bond is shorter in the transition state than in the ground state and rules out a direct bimolecular displacement mechanism on carbonyl carbon. 

Carbonyl compounds as carbon acids have been reviewed from kinetic and thermodynamic perspectives. " Effects of high pressure on kinetic isotope effects have been interpreted using a new equation which permits a distinction between pressure-sensitive transition state phenomena (such as tunnelling) and the pressure-insensitive dependence on zero-point energy difference. " ... 

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