Stabilized by Functional Groups

SECTION 7.2. CARD ANIONS STABILIZED BY FUNCTIONAL GROUPS 

This property greatly accelerates the rate at which the organometallic compound can cause deprotonation. 

Perhaps the data that provide the best basis for comparison between these groups in terms of internal consistency are those of Bordwell and co-workers/ These workers determined relative equilibrium acidities of the substituted methanes with reference to aromatic hydrocarbon indicators in DMSO. The data are given in Table 7.3. The ordering N02 C=0 S02 CN is established by these data. Both inductive and resonance effects are involved in the ability of these functional groups to stabilize the negative charge. The inductive effect is probably dominant for sulfones  

Carbanions derived from carbonyl compounds are often referred to by the name etiolate. This name is derived from the name for the enol tautomer of carbonyl compounds. The resonance-stabilized enolate anion is the conjugate base of both the keto and the enol forms of carbonyl compounds  

There have been numerous studies of the rates of deprotonation of carbonyl compounds. These data are of interest not only because they define the relationship between thermodynamic and kinetic acidity in these compounds, but also because they are necessary for defining mechanisms of reactions in which enolates are involved as intermediates. Rates of enolate formation can be measured conveniently by following isotopic exchange using either deuterium or tritium  

There have been numerous studies of the rates of deprotonation of carbonyl compounds. These data are of interest not only because they define the relationship 

An older technique is to measure the rate of halogenation of the carbonyl compound. Ketones and aldehydes in their carbonyl forms do not react rapidly with the halogens but the enolate is rapidly attacked. The rate of halogenation is therefore a measure of the rate of deprotonation. 

Yukawa, H. Morishita, H. Ikeda, and Y. Goto, Chem. Pharm. Bull, 39, 2475 (1991). 

The synthetic importance of the EDA and LiHMDS type of deprotonation has led to studies of enolate composition under various conditions. Deprotonation of 2-pentanone was examined with EDA in THE, with and without HMPA. C(l)-deprotonation was favored under both conditions, but the Z E ratio for C(3) deprotonation was sensitive to the presence of HMPA (0.75 M). More Z-enolate is formed when HMPA is present. 

CHAPTER 7 CARBANIONS AND OTHER NUCLEOPHILIC CARBON SPECIES 

Solvation may also play a role. If bulky groups prohibit effective solvation of the developing negative charge, the rate of proton abstraction will be reduced. 

Carbanion-stabilizing effects have been calculated at several levels of theory. Table 7.6 gives some gas-phase data. The AMI and PM3 semiempirical calculations have also been done in water. The order NO2 CH=0 CN Ph CH2=CH is in accord with the experimental trends and reflects charge delocalization. The electronegative substituents F, OH, and NH2 are stabilizing by virtue of polar effects. The small stabilization provided by CH3 is presumabfy a polarization effect. 

Structural effects on the rates of deprotonation of ketones have also been studied using veiy strong bases under conditions where complete conversion to the enolate occurs. In solvents such as THF or DME, bases such as lithium di-/-propylamide (LDA) and potassium hexamethyldisilylamide (KHMDS) give solutions of the enolates in relative proportions that reflect the relative rates of removal of the different protons in the carbonyl compound (kinetic control). The least hindered proton is removed most rapidly under these 

These and many other organolithium structures have been compared in a review of this topic. ° 

Nitroalkanes show a related relationship between kinetic acidity and thermodynamic acidity. Additional alkyl substituents on nitromethane retard the rate of proton removal although the equilibrium is more favorable for the more highly substituted derivatives. The alkyl groups have a strong stabilizing effect on the nitronate ion, but unfavorable steric effects are dominant at the transition state for proton removal. As a result, kinetic and thermodynamic acidity show opposite responses to alkyl substitution. 

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Carbocations stabilized by functional groups can also effect 3-alkylalion of indoles. From a synthetic point of view the most important are jV.jV-dialkyl-methyleneiminium ions which can be generated under Mannich conditions from formaldehyde and secondary amines[13]. The products, 3-(A/,A-dialkyl-aminornethyl)indoles, are useful synthetic intermediates (see Chapter 12). 

Silver reduction from its complex precursors is of interest to produce silver nanoparticles [1,2]. Metal colloids can be stabilized by functional groups in polyelectrolytes and surfactants [1], The stabilization is a useful method for the directional drug delivery and the prolongation effect. 

Reactions via Carbanions Stabilized by Functional Groups Other than Carbonyl... 

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