Carbanions kinetic acidity

It has been found that there is often a correlation between the rate of deprotonation (kinetic acidity) and the thermodynamic stability of the carbanion (thermodynamic acidity). Because of this relationship, kinetic measurements can be used to construct orders of hydrocarbon acidities. These kinetic measurements have the advantage of not requiring the presence of a measurable concentration of the carbanion at any time instead, the relative ease of carbanion formation is judged from the rate at which exchange occurs. This method is therefore applicable to very weak acids, for which no suitable base will generate a measurable carbanion concentration. 

A different approach to the problem of hydrocarbon acidity, and hence carbanion stability, is that of Shatenshtein and Shapiro, who treated hydrocarbons with deuterated potassium amide and measured the rates of hydrogen exchange. The experiments did not measure thermodynamic acidity, since rates were measured, not positions of equilibria. They measured kinetic acidity, that is, which compounds... 

The fundamental aspects of the structure and stability of carbanions were discussed in Chapter 6 of Part A. In the present chapter we relate the properties and reactivity of carbanions stabilized by carbonyl and other EWG substituents to their application as nucleophiles in synthesis. As discussed in Section 6.3 of Part A, there is a fundamental relationship between the stabilizing functional group and the acidity of the C-H groups, as illustrated by the pK data summarized in Table 6.7 in Part A. These pK data provide a basis for assessing the stability and reactivity of carbanions. The acidity of the reactant determines which bases can be used for generation of the anion. Another crucial factor is the distinction between kinetic or thermodynamic control of enolate formation by deprotonation (Part A, Section 6.3), which determines the enolate composition. Fundamental mechanisms of Sw2 alkylation reactions of carbanions are discussed in Section 6.5 of Part A. A review of this material may prove helpful. 

It has been shown, by comparison of AGT j (gas phase) and kinetic acidities measured in MeONa-MeOH, that proton transfer to form a hydrogen-bonded carbanion and the subsequent breaking of that weak bond to form a free carbanion in MeOH may differ greatly even for compounds of comparable acidity, such as 9-phenylfluorene... 

Kinetic Acidities in the Condensed Phase. For very weak acids, it is not always possible to establish proton-transfer equilibria in solution because the carbanions are too basic to be stable in the solvent system or the rate of establishing the equilibrium is too slow. In these cases, workers have turned to kinetic methods that rely on the assumption of a Brpnsted correlation between the rate of proton transfer and the acidity of the hydrocarbon. In other words, log k for isotope exchange is linearly related to the pK of the hydrocarbon (Eq. 13). The a value takes into account the fact that factors that stabilize a carbanion generally are only partially realized at the transition state for proton transfer (there is only partial charge development at that point) so the rate is less sensitive to structural effects than the pAT. As a result, a values are expected to be between zero and one. Once the correlation in Eq. 13 is established for species of known pK, the relationship can be used with kinetic data to extrapolate to values for species of unknown pAT. 

Studies on the influence of halogen on the acidity of hydrogen in 1-chloro-2-fluoroethene showed that the kinetic acidity of the hydrogen a- to chlorine is greater than that for hydrogen a- to fluorine, in accordance with lower repulsions for chlorine a- to the carbanion centre [79]. 

Most of the preceding conclusions are based on kinetic acidity determinations and the assumption that relative rates reflect relative carbanion stabilities. This assumption has been appropriately challenged however, the limited equilibrium acidity data that are available are in complete accord with the above summary (see Table 2). 

Furthermore, it was first shown nearly 20 years ago that a-lithioamines could be produced by the transmetalation of a-aminostaimanes." Thus, the thermodynamic stability of a-amino anions is reasonably good, even if the kinetic acidity of the conjugate acids is low. Although some authors have suggested that a-amino carbanions constitute a reversal of normal reactivity, 4 n we suggest that this notion is inappropriate and should be discontinued. 

The stereochemistry of the reaction products is dependent on the nature of the a-sulfinyl carbanion. Thus (i) its kinetic acidity, controls the stereochemistry of the organometallics initially formed (ii) its thermodynamic acidity defines the stereochemistry or the conformation of the intermediate organometal-lic and (iii) reactivity of the organometallic towards the electrophile controls the stereochemistry of the product. The alkylation reaction has proved to be far more selective than is the metallation. Therefore the contribution of kinetic acidity can be neglected because the carbanion in THF has sufficient time to reorganize into its most stable conformation before it reacts with an electrophile. The a-sulfinyl benzyllithiums produced from S(srd) and S(r -(2) should adopt the more stable conformations shown in... 

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