Carbanions formation

Chapter I first describes some common synthons and corresponding reagents. Emphasis is on regioselective carbanion formation. In the second part some typical synthetic procedures in the following order of "arrangements of functionality in the target molecule" are given ... 

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. 

Goering and coworkers201 studied the kinetics of base-promoted dehydrohalogenation of several series of cis- or frans-2-chlorocycloalkyl aryl sulfones. For the trans-2-chlorocyclohexyl series reacting with sodium hydroxide in 80% ethanol at 0 °C the p value was 1.42. The mechanism was considered to involve rate-determining carbanion formation, with the subsequent loss of chloride ion in a fast step. 

It should be mentioned here that if no other leaving group is present, sulfonyl can act as its own leaving group in hydroxide- or alkoxide-catalyzed elimination from sulfones. Carbanion formation is not involved in this but the promotion of the ionization of a C—H bond by the sulfonyl group is seen at the /1-carbon rather than the a-carbon, e.g. equation 21. 

Finally, the most significant mechanistic feature of the Ramberg-Backlund rearrangement is the stereoselective formation of ds-olefin products, as a result of the preferential cis-positioning of the pair of R groups in the episulfone-forming transition state, variously attributed to London forces , to diastereoselectivity in carbanion formation and to steric attraction . However, with the use of stronger bases such as potassium t-butoxide °, the trans-olefin predominates (equation 52), apparently due to prior epimerization of the kinetically favoured cts-episulfone, and subsequent loss of the sulfur dioxide. Similarly, when the episulfone intermediates possess unusually acidic... 

Classically the base catalyst, eOEt, is introduced by adding just over one mole of sodium (as wire, or in other finely divided form) plus just a little EtOH to generate an initial small concentration of Na eOEt. Further EtOH is generated in step (1), which yields further Na eOEt with sodium, and the concentration of eOEt is thereby maintained. A whole mole is required as it is essential for the / -keto ester (114) to be converted (step 3) into its anion (115)—MeCOCH2-COzEt is more acidic than EtOH (cf. p.272)—if the overall succession of equilibria is to be displaced to the right. This is necessary because the carbanion-formation equilibrium—step (1)—lies even further over to the left than that with, for example, CH3CHO this reflects the less effective stabilisation through delocalisation in the ester carbanion (111) than in that from the aldehyde (116) ... 

The reaction was carried out with eOEt in EtOD, and (11) re-isolated after half-conversion to (13) it was found to contain no deuterium, i.e. no (14) nor did the alkene (13) contain any deuterium, as might have been expected by elimination from any (14) formed. This potentially favourable case thus does not proceed by an ElcB pathway of the form described above though we have not ruled out the case where k2 k, i.e. essentially irreversible carbanion formation. 

There are, however, other methods of generating carbanions than by proton removal as we shall see below. Carbanion formation is important—apart from the inherent interest of the species—because of... 

Scheme 11 Carbanion formation from alkyl halides and cobalt (III) species.

EtsN suggest that both reactions proceed via carbanion formation, to give the corresponding aryl vinyl and aryl styryl sulfones, respectively." ... 

The acidifying influence of the sulfonyl group, combined with its ability to transmit electronic effects is apparent from results of Hammett studies of the dehydrochlorination of P-RC6H4SO2CH2CH2CI and RC6H4S02CH2CHClPh, on reaction with EtsN the nearly identical positive p values indicate that for each series reaction proceeds via carbanion formation." ... 

The Ad -E mechanism proposed to account for the kinetics of substitution of 9-(a-bromo-a -arylmethylene)fluorenes by thiolate ions in aqueous acetonitrile also features elimination of the leaving group in a fast step following rate-determining carbanion formation (by nucleophilic addition). ... 

It is important that this process results in the preferential formation of a thermodynamically stable alcohol diastereomer. The anion-radicals contain an almost undoubtedly planar C-0 and give rise to pyramidal hydroxy carboradicals. The hydroxy carboradicals form pyramidal hydroxy carbanions, which cannot exist in the presence of ammonium cation for a long time. Therefore, the equilibrium including pyramidal inversion, probably, takes place at the step of carboradical formation, rather than carbanion formation. Transformation of a carboradical into a carbanion obviously proceeds faster than its dimerization or disproportionation. As a consequence, the reduction of an optically active ketone into an alcohol goes without racemization (Rautenstrauch et al. 1981). 

Ring and substituent carbanions situated not only a-, but also /3- and y-to unsaturated (sp ) heterocyclic nitrogen are discussed. Some of the heterocyclic systems mentioned here have also been individually reviewed elsewhere, and in these cases the present work concentrates on more recent aspects. However, earlier work is still discussed where it is felt appropriate or necessary, in order to provide a unified coverage of the subject. The greatest emphasis is placed on methods for overcoming the reluctance often shown by nitrogen heterocycles toward carbanion formation, and the direction of metalation to specific sites where more than one is available. 

However, dipole stabilization is less significant as an aid to carbanion formation with unsaturated azaheterocycles, since the nitrogen lone-pair electrons are normally incorporated into the 77-electron system of the heterocycle, and are therefore less readily available for donation to the substituent group. In fact, dipole-stabilization can even be a hindrance in some systems where exocyclic ip -carbanion formation is competitive with internal ip -carbanion formation. In these cases it is the heterocycle itself that is responsible for the dipole-stabilization of the external carbanion. 

With heterocycles containing an sp--nitrogen atom, a totally different problem can occur, namely nucleophilic addition of the base to the azo-methine (C=N) bond. The use of very sterically hindered bases such as lithium tetramethylpiperidide (LiTMP) can prevent this type of addition in certain cases, but bases of this sort tend to be expensive and not suitable for general use. However, two different approaches to overcoming the problem of azomethine addition have been developed over the years, both relying on the fact that the addition is temperature dependent, and that by enabling metalation reactions to be performed at low temperatures, the desired carbanion formation can often be achieved. 

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