Lithium pinacolone enolate, addition benzaldehyde

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. 

FIGURE 27. The polar addition mechanism and electron transfer-radical coupling sequence in the addition of lithium pinacolone enolate to benzaldehyde. Reprinted with permission from Reference 28. Copyright 1997 American Chemical Society... 

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). 

The mechanism of addition of lithium pinacolone enolate, H2C=C(OLi)Bff, to benzaldehyde has been investigated by the determination of kinetic isotope effects69 (phenyl-t/s 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... 

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),... 

Aldol reactions have continued to attract attention. In order to determine the mechanism of addition of lithium pinacolone enolate [CH2=C(OLi)C(Me)3] to benzaldehyde the carbonyl-carbon KIE 1.019) and the substituent effects... 

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