Equilibrium isotope effect , lithium

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),... 

Quantum mechanical calculations have recently led to the suggestion that in the presence of Lewis acidic BF3 the reductive elimination reactions of trialkyl-copper(III) species may proceed via the formation of a Lewis acid-[P-cuprio(III) enolate] complex. DFT calculations have been employed to probe the mechanism for the SN2-substitution reaction of methyl halides and epoxides with lithium organocuprates(I) operate, with solvent effects, BF3 effects and trans-diaxial epoxide opening taken into account. Calculations have lately been combined with mass spectrometric results to probe equilibrium isotope effects for the coordination of C2H4 and C2D4 to otherwise bare coinage metal cations. ... 

The lack of a substrate isotope effect suggests very extensive internal return and is readily explained in terms of the fact that conversion of the hydrocarbon to the anion would require very little structural reorganisation. Since koba = k 1k 2/(kLl+k 2) and k 2 is deduced as > k2, then kobs = Kk 2, the product of the equilibrium constant and the rate of diffusion away of a solvent molecule, neither of the steps having an appreciable isotope effect. If the diffusion rates are the same for reactions of each compound then the derived logarithms of partial rate factors (above) become pAT differences between benzene and fluorobenzene hydrogens in methanol. However, since the logarithms of the partial rate factors were similar to those obtained with lithium cyclohexylamide, a Bronsted cor-... 

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. 

In 1998, Hasanayn and Streitwieser reported the kinetics and isotope effects of the Aldol-Tishchenko reaction . They studied the reaction between lithium enolates of isobu-tyrophenone and two molecule of beuzaldehyde, which results iu the formation of a 1,3-diol monoester after protonation (Figure 28). They analyzed several aspects of this mechanism experimentally. Ab initio molecular orbital calculatious ou models are used to study the equilibrium and transition state structures. The spectroscopic properties of the lithium enolate of p-(phenylsulfonyl) isobutyrophenone (LiSIBP) have allowed kinetic study of the reaction. The computed equilibrium and transition state structures for the compounds in the sequence of reactions in Figure 28 are given along with the computed reaction barriers and energy in Figure 29 and Table 6. 

Aldol reactions have continued to attract attention.28-39 hi order to determine the mechanism of addition of lithium pinacolone enolate [CH2=C(OLi)C(Me)3] to benzaldehyde the carbonyl-carbon KIE (xlk/nk = 1.019) and the substituent effects (p = 1.16 0.31) have been compared with those for other lithium reagents.28,29 The small positive KIE, which is larger than the equilibrium IE (nK/nK = 1.006) determined by ab initio MO calculations (HF/6—31 + G ), is in contrast with nk/l4k = 1.000 for MeLi addition which proceeds by the rate-determining ET mechanism, characterized by a much smaller p value. Since probe experiments showed no evidence of single electron transfer, it has been concluded that the significant isotope effect for reaction of lithium pinacolone enolate is indicative of rate-determining polar attack (PL) rather than radical coupling (RC) (Scheme 2). 

TABLE 13. Computed reaction and activation energies (kcalmoD ) and corresponding kinetic (KIE) and equilibrium (ElE) isotope effects a reaction sequence between lithium acetaldehyde enolate (Lien) and formaldehyde... 

The counterion was found to be a significant factor in the equilibrium, with the more highly substituted enolate increasingly favored as the cation varied from sodium or potassium to lithium. Beutelman, H. P. Xie, L. Saunders, W. H., Jr. /. Org. Chem. 1989,54,1703 determined that the primary hydrogen kinetic isotope effect for proton removal from alkyl ketones by strong bases such as lithium diisopropylamide in THF or DME was kn/ko = 2.3 to 5.9 at 0°C. The results suggested a very early transition state. The reactions appeared to depend on more than one base reacting with each ketone, however. See also Xie, L. Saunders, W. H., Jr. /. Am. Chem. Soc. 1991, 113, 3123. 

The mechanism of addition of lithium pmacolone enolate, H2C=C(OLi)Bu. to benzaldehyde has been investigated by the determination of kinetic isotope effects69 (phenyl-ds and carbonyl-13C) C—C bond formation occurs in the rate-determining step (a result supported by MO calculations), in contrast to addition of MeLi or PhLi, which proceed via electron transfer. Further carbonyl-13 C isotopic studies on substituted benzaldehydes (including equilibrium effects) by the same authors confirmed these conclusions.70... 

A partial separation of lithium isotopes has been effected by the use of a zeolite (p. 248), and a complete one of from by means of a cationic resin. Spedding, Powell and Svec (1955) found an equilibrium between the ammonium form of Dowex 50X12 resin and ammonium hydroxide with the separation factor resin/ N resin x solution/ N solution) = 1.0257 ... 

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