Proton transfer carbanionic species

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. 

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. 

The interest in proton transfer to and from carbon arises partly because this process occurs as an elementary step in the mechanisms of a number of important reactions. Acid and base catalysed reactions often occur through intermediate carbonium ions or carbanions which are produced by reactions (1) and (2). A knowledge of the acid—base properties of carbonium ions or carbanions may also help in understanding reactions in which these species are present as reactive intermediates, even when they are generated by processes other than proton transfer. Kinetic studies of simple reactions such as proton transfer are also important in the development of theories of kinetics. Since both rates and equilibrium constants can often be measured for (1) and (2) these reactions have been useful in the investigation of correlations between rate coefficients and equilibrium constants (linear free energy relations). 

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... 

Fig. 17. Rates of proton transfers involving cyano-compounds, disulphones, and their anions. (Values from Refs. 18 and 19, statistically corrected.) Reactions involving solvent species or steric hindrance have been omitted. Curve (a), reaction of carbon acids with bases curve (b), reaction of carbanions with acids open circles, cyano-compounds filled circles, (EtS02)2CHMe.

The preceding reactions dealt with the use of chiral auxiliaries linked to the electrophilic arene partner. The entering nucleophile can also serve as a chiral controller in diastereoselective SjjAr reactions. This approach was successfully employed for the arylation of enolates derived from amino acids. To illustrate the potential of the method, two examples have been selected. Arylation of Schollkopf s bislactim ether 75 with aryne 77 as electrophilic arylation reagent was demonstrated by Barrett to provide substitution product 81 with good yield (Scheme 8.18) [62, 63]. Aryne 77 arises from the orf/jo-lithiation of 76 between the methoxy and the chlorine atom followed by elimination of LiCl. Nucleophilic attack of 77 by the lithiated species 78 occurs by the opposite face to that carrying the i-Pr substituent. Inter- or intramolecnlar proton transfer at the a-face of the newly formed carbanion 79 affords the anionic species 80. Subsequent diastereoselective reprotonation with the bulky weak acid 2,6-di-f-butyl-4-methyl-phenol (BHT) at the less hindered face provides the syn product 81. Hydrolysis and N-Boc protection give the unnatural arylated amino acid 82. The proposed mechanism is supported by a deuterium-labeling experiment. Unnatural arylated amino acids have found application as intermediates for the construction of pharmaceutically important products such as peptidomi-metics, enzyme inhibitors, etc. [64, 65]. 

The carbanion of the dimer can abstract a proton from any other species. It is not necessary that the proton transfer in every propagation step is intramolecular. 

The first step is formation of the ketyl of 6. This species can undergo fragmentation to form the C2-C3 enolate and a radical at C4. A second electron transfer gives a carbanion at C4, which deprotonates NH3. Upon workup, CIO is protonated to give 7. 

The reductive cleavage of sulphonium salts in aprotic solvents leads to the generation of radical and then carbanions in a further electron transfer step. Protonation of the carbanion by extraneous water leaves a hydroxide ion. Basic species formed in this way can abstract a proton from sulphonium ion to give the ylid, which is not reducible. A good example is the reduction of 9 in dimethylsulphox-ide, which consumes only one Faraday and follows the course shown [58]. 

Fig. 3. Decarboxylation of malonyl CoA to create the resonance-stabilized carbanion that is the nucleophilic species of the condensation reaction. A hypothetical interaction with a neutral (as shown) or positively charged basic group on the enzyme is indicated [51, 54]. Although the interaction is shown as a hydrogen bond, an equally feasible mechanism involves complete transfer of the proton...

Completion of the reaction by transfer of a proton from the solvent to the carbanion will then give a product (3a -f- 3b) of composition corresponding to thermodynamic equilibrium of the anionic species. That this approximates closely to an equilibrated mixture of the alcohols has been confirmed by subjecting some steroid alcohols to equilibration with alkoxide ions, under conditions sufficiently Mastic to allow thermodynamic equilibrium to be attained through a reversible oxidation/reduction process. Reduction of steroidal 20 ketones is of considerable interest in providing a mixture of epimers, each present in considerable proportion. The reduced mixture contains a modest preponderance of the 20a-epimer [34], although recent experiments [34M] confirm indications from molecular models that the 20/ -alcohol is the more stable. Further work is needed to clarifythis situation (see alsop. 139). 

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