Solvent effects carbanion nucleophiles

The range of nucleophiles which have been observed to participate in nucleophilic aromatic substitution is similar to that for 8 2 reactions and includes alkoxides, " phenoxides, sulfides,fluoride ion, and amines." Substitutions by carbanions are somewhat less common. This may be because there are frequently complications resulting from electron-transfer processes with nitroaromatics. Solvent effects on nucleophilic aromatic substitutions are similar to those discussed for S 2 reactions. Dipolar... 

Steric effects provide examples of hard cases with respect to predicting reactivities. The same might be said to be true of solvent effects for reactions of n-nucleophiles or carbanions. However, while values of N may vary with solvent the differences can be exploited, for example, in promoting a desired reaction in synthesis. Moreover, in attempting to interpret solvent effects, it is possible that comparing measurements of reaction rates and (preferably)... 

There have been a large number of detailed studies, especially involving kinetic measurements, that have helped to determine the reactivity of various nucleophiles, solvent effects, and the finer details of aromatic nucleophilic substitutions proceeding via the addition-elimination mechanism. We will not attempt to summarize these results here, since reviews are available. Carbanions, alkoxides, and amines are all reactive in nucleophflic aromatic substitution and provide most of the cases in which this reaction has been used preparatively. Some examples are given in Scheme 7.7. 

In general these reactions are base-catalysed in that it is necessary to remove a proton from HCXYZ in order to generate the carbanion, eCXYZ, the effective nucleophile one or more of X, Y and Z are usually electron-withdrawing in order to stabilise it. The initial adduct (84) acquires a proton from the solvent (often H20 or ROH) to yield the simple addition product (85). Whether or not this undergoes subsequent dehydration (86) depends on the availability of an H atom, either on an a-carbon or where X, Y or Z = H, and also on whether the C=C so introduced would, or would not, be conjugated with other C=C or C=0 linkages in the product ... 

Classical C,C-coupling reactions of AN anions (Henry, Michael, and Mannich) involve complex systems of equilibria and, consequently, generally not performed in protic solvents. The introduction of the silyl protecting group allows one to perform these reactions in an aprotic medium to prepare or retain products unstable in the presence of active protons. In addition, the use of nucleophiles which are specifically active toward silicon (e.g., the fluoride anion) enables one to design a process in which the effective concentration of a-nitro carbanions is maintained low. 

As noted in Section 4.2.1, the gas phase has proven to be a useful medium for probing the physical properties of carbanions, specifically, their basicity. In addition, the gas phase allows chemists to study organic reaction mechanisms in the absence of solvation and ion-pairing effects. This environment provides valuable data on the intrinsic, or baseline, reactivity of these systems and gives useful clues as to the roles that solvent and counterions play in the mechanisms. Although a variety of carbanion reactions have been explored in the gas phase, two will be considered here (1) Sn2 substitutions and (2) nucleophilic acyl substitutions. Both of these reactions highlight some of the characteristic features of gas-phase carbanion chemistry. 

The crucial step in this mechanism is the second one in which the a-haloether moiety 115 solvolyzes to give an oxocarbocation. In order to obtain the ionic bicyclobutane this step has to compete effectively with both protonation of the carbanion and the 1,3-elimination reaction. By using oxygen nucleophiles, e.g. MeO", EtO" and CF3CH2O", in pro tic solvents, the rate of these three reactions was found to decrease in the order solvolysis > elimination > protonation. Although an apolar medium is expected to enhance the elimination reaction and to slow down the solvolytic step, it was shown that for MeO" in THF, the ionic bicyclobutane route still prevails. ... 

The stereochemical outcome of the addition of carbanions to ketones yielding tertiary alcohols (or secondary alcohols in the case of aldehydes) is variable and depends on the substrate, the counterion and the solvent. Numerous applications of this strategy to natural product synthesis from carbohydrates can be found in the literature and this approach was fruitful in pioneering syntheses of polyketide-type products. Here again, the template effect of the sugar plays a tremendous role in the stereochemical outcome of the reaction. Chelation controlled nucleophilic addition can also be used to form chiral centers in a highly predictable way. 

The phenoxide anion is formed by the action of the base on phenol. This resultant anion then attacks the cyanoethene to give an adduct, which (after reprotonation from the solvent) yields a product in which a three-carbon unit has in effect been added to the phenol. This three-carbon unit has a terminal functionality that might then be used in further synthetic steps. This reaction is called cyanoethylation and may be performed with many other nucleophiles such as amines and the related anions, alkoxide anions, and even carbon anions. When it is performed with carbon anions it is called the Michael reaction, which in general is the attack by a carbanion on a substituted alkene. This reaction is particularly useful in forming carbon/carbon bonds. If this reaction is viewed from the perspective of the cyanoethene molecule, instead of the other molecule involved, then it becomes apparent that there has been an addition to a conjugated system, namely to the CH2=CH-C=N... 

---