Carbanions proton-transfer reactions

Two types of electrogenerated carbon bases have commonly been used (1) dianions derived from activated alkenes, and (2) carbanions formed by reductive cleavage of halogen compounds or by direct reduction of weak carbon acids. In both cases, the efficiency of the proton transfer reaction relies on a thermodynamically favored proton transfer or a fast follow-up reaction of the deproto-nated substrate. 

There are other factors that contribute to the reduction in the imbalance. This can be seen by comparing intrinsic rate constants of reactions that create the same carbanions as in proton transfer reactions, e.g., comparing reactions 41 and 42. These reactions do involve sp3 > sp2 rehydrization just as in proton transfers and hence, if hydrization were the only important factor,... 

We can consider decarboxylation reactions in terms that are analogous to those in proton transfer reactions the reactivity of the carbanion in carboxylation reactions is analogous to internal return observed in proton transfer reactions from Bronsted acids. Kresge61 estimated that the rate constant for protonation of the acetylide anion, a localized carbanion (P A 21), is the same as the diffusional limit (1010 M s1). However, achieving this rate is highly dependent on the extent of localization of the carbanion. Jordan62 has shown that intermediates in thiazolium derivatives are also likely to be localized carbanions, which implies that protonation of these intermediates could occur at rates approaching those of other localized carbanions. 

The interposed acid-base reactions which are most frequently observed, belong to two categories acid-base reactions following a one-electron transfer, as observed for numerous carbonyl compounds at higher pH values and for some hydrocarbons and proton-transfer reactions involving the product of a two-electron reduction process, usually carbanions. 

Many reactions become possible only in such superbasic solutions, while others can be carried out under much milder conditions. Only some examples of preparative interest (which depend on the ionization of a C—H or N—H bond) will be mentioned here. The subsequent reaction of the resulting carbanion may involve electrophilic substitution, isomerization, elimination, or condensation [321, 322]. Systematic studies of solvent effects on intrinsic rate constants of proton-transfer reactions between carbon acids and carboxylate ions as well as amines as bases in various dimethyl sulfoxide/ water mixtures have been carried out by Bernasconi et al. [769]. 

Similar Bronsted exponents, 0.94 0.02 for phenolate ions and 0.98 0.08 for secondary amines, were observed but the Bronsted plots for these two types of catalyst were separated by about half a unit in log 0 k. The values of the Bronsted exponents are close to the limiting values of unity expected for normal proton transfer. Reaction (78) is thermodynamically favourable in the reverse direction and for fully normal proton transfer the rate coefficients for recombination of the carbanions with phenols and ammonium ions should be around 101 0 1 mole"1 sec"1. Calculations using the approximate pif 21 for this acid measured [69] in dimethyl... 

These mechanistic differences between proton transfer reactions for carbon acids and normal acids can be used to explain qualitatively the results presented in Sect. 4. The idea that the difference in electronic and molecular structure between carbon acids and their carbanions is a major contributing factor in controlling the proton transfer behaviour of a particular carbon acid has frequently been discussed [59, 198]. Large... 

The barrier to thermodynamically unfavorable deprotonation of carbon acids (AGfl, Fig. 1.1) in water is equal to the sum of the thermodynamic barrier to proton transfer (AG°) and the barrier to downhill protonation of the carbanion in the reverse direction (AGr Eq. (1.2)). The observation of significant activation barriers AGr for strongly thermodynamically favorable protonation or resonance stabilized carbanions shows that there is some intrinsic difficulty to proton transfer. The Marcus equation defines this difficulty with greater rigor as the intrinsic barrier A, which is the activation barrier for a related but often hypothetical thermoneutral proton transfer reaction (Fig. 1.2B) [46]. 

In these reactions, the C2-atom of ThDP must be deprotonated to allo v this atom to attack the carbonyl carbon of the different substrates. In all ThDP-dependent enzymes this nucleophilic attack of the deprotonated C2-atom of the coenzyme on the substrates results in the formation of a covalent adduct at the C2-atom of the thiazolium ring of the cofactor (Ila and Ilb in Scheme 16.1). This reaction requires protonation of the carbonyl oxygen of the substrate and sterical orientation of the substituents. In the next step during catalysis either CO2, as in the case of decarboxylating enzymes, or an aldo sugar, as in the case of transketo-lase, is eliminated, accompanied by the formation of an a-carbanion/enamine intermediate (Ilia and Illb in Scheme 16.1). Dependent on the enzyme this intermediate reacts either by elimination of an aldehyde, such as in pyruvate decarboxylase, or with a second substrate, such as in transketolase and acetohydroxyacid synthase. In these reaction steps proton transfer reactions are involved. Furthermore, the a-carbanion/enamine intermediate (Ilia in Scheme 16.1) can be oxidized in enzymes containing a second cofactor, such as in the a-ketoacid dehydrogenases and pyruvate oxidases. In principal, this oxidation reaction corresponds to a hydride transfer reaction. 

In the next section, the mechanism of the C2-H deprotonation of ThDP in enzymes is considered, followed by a discussion of the proton transfer reactions during catalysis. Finally, the oxidation mechanism of the a-carbanion/enamine intermediate in pyruvate oxidase is discussed. 

Besides resonance stabilization of the carbanion, solvation has a major effect on k0 of proton-transfer reactions. In a first approximation, we only consider the solvation of ionic species. For the solvation of the carbanion, equation 5 takes on the form... 

R,2S)-Ephedrine has found most application, e.g., as a catalyst in photochemical proton transfer reactions (Section D.2.1.). and as its lithium salt in enantioselective deprotonations (Section D.2.1.). The amino function readily forms chiral amides with carboxylic acids and enamines with carbonyl compounds these reagents perform stereoselective carbanionic reactions, such as Michael additions (Sections D.1.5.2.1. and D. 1.5.2.4.), and alkylations (Section D.1.1.1.3.1.). They have also been used to obtain chiral alkenes for [1 +2] cycloadditions (Section D. 1.6.1.5.). 

A different type of photoreaction in ILs has been studied by Jones and co-workers the photoreduction of benzophenones by primary amines. Prior work by Cohen demonstrated that photolysis of benzophe-none in benzene in the presence of sec-butylamine afforded benzopinacol (and an imine). This reaction proceeds through a radical pair formed by hydrogen-atom abstraction by the triplet excited state ben-zophenone from the amine. In the much more polar environment of an IL, the radical pair may instead undergo single electron transfer to form an iminium cation and a hydroxyl-substituted carbanion. Proton transfer from the cation to the anion will yield benzhydrol and an imine. 

When drawn in this way, the anion exhibits a negative charge on a carbon atom (called a carbanion), which is a very strong base (because it is the conjugate base of a very, very weak acid). If compound 3 were treated with H2O, we would expect the following proton-transfer reaction ... 

The cyanide ion plays an important role in this reaction, for it has three functions in addition to being a good nucleophile, its electron-withdrawing effect allows for the formation of the carbanion species by proton transfer, and it is a good leaving group. These features make the cyanide ion a specific catalyst for the benzoin condensation. 

When the reaction is carried out in MeOH neither step (2), the formation of the carbanion (127), nor step (3), addition of this carbanion to the carbonyl carbon of the acceptor molecule (128), is completely rate-limiting in itself. These steps are followed by rapid proton transfer, (129)— (130), and, finally, by rapid loss of eCN—a good leaving group—i.e. reversal of cyanohydrin formation (cf. p. 212) on the product... 

For polymerizations of butadiene in toluene at 50°C with the Ba-Li catalyst, we have observed a reduction in molecular weight and the incorporation of benzyl groups in chains of polybutadiene. We conclude from this result that proton abstraction from toluene occurs to give benzyl carbanions which are capable of forming new polymer molecules in a chain transfer reaction. 

Alternatively, some conclusions can be derived from the relative reactivities of car-banions. For example, DePuy and colleagues13 made use of a clever method involving reactions of silanes with hydroxide ion to deduce acidities of such weak acids as alkanes and ethylene. The silane reacts with hydroxide ion to form a pentacoordinate anion that ejects a carbanion held as a complex with the hydroxysilane rapid proton transfer gives the stable silanoxide ion and the carbon acid (equation 5). 

It was recognized in early examples of nucleophilic addition to acceptor-substituted allenes that formation of the non-conjugated product 158 is a kinetically controlled reaction. On the other hand, the conjugated product 159 is the result of a thermodynamically controlled reaction [205, 215]. Apparently, after the attack of the nucleophile on the central carbon atom of the allene 155, the intermediate 156 is formed first. This has to execute a torsion of 90° to merge into the allylic carbanion 157. Whereas 156 can only yield the product 158 by proton transfer, the protonation of 157 leads to both 158 and 159. 

The first chemical transformations carried out with Cjq were reductions. After the pronounced electrophilicity of the fullerenes was recognized, electron transfer reactions with electropositive metals, organometallic compounds, strong organic donor molecules as well as electrochemical and photochemical reductions have been used to prepare fulleride salts respectively fulleride anions. Functionalized fulleride anions and salts have been mostly prepared by reactions with carbanions or by removing the proton from hydrofullerenes. Some of these systems, either functionalized or derived from pristine Cjq, exhibit extraordinary solid-state properties such as superconductivity and molecular ferromagnetism. Fullerides are promising candidates for nonlinear optical materials and may be used for enhanced photoluminescence material. 

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