Stabilization, of carbanions

Inductive and resonance stabilization of carbanions derived by proton abstraction from alkyl substituents a to the ring nitrogen in pyrazines and quinoxalines confers a degree of stability on these species comparable with that observed with enolate anions. The resultant carbanions undergo typical condensation reactions with a variety of electrophilic reagents such as aldehydes, ketones, nitriles, diazonium salts, etc., which makes them of considerable preparative importance. 

A simple experimental test of the potential configurational stability of carbanions was recently published26 48 it is based on double stereodifferentiation3 and can be carried out with the racemates. 

V. STABILIZATION OF CARBANIONIC CENTERS BY SULFINYL AND SULFONYL GROUPS... 

The fundamental aspects of the structure and stability of carbanions were discussed in Chapter 6 of Part A. In the present chapter we relate the properties and reactivity of carbanions stabilized by carbonyl and other EWG substituents to their application as nucleophiles in synthesis. As discussed in Section 6.3 of Part A, there is a fundamental relationship between the stabilizing functional group and the acidity of the C-H groups, as illustrated by the pK data summarized in Table 6.7 in Part A. These pK data provide a basis for assessing the stability and reactivity of carbanions. The acidity of the reactant determines which bases can be used for generation of the anion. Another crucial factor is the distinction between kinetic or thermodynamic control of enolate formation by deprotonation (Part A, Section 6.3), which determines the enolate composition. Fundamental mechanisms of Sw2 alkylation reactions of carbanions are discussed in Section 6.5 of Part A. A review of this material may prove helpful. 

The effect of groups on the stability of carbanions when present in a position is in the order. 

It is commonly supposed that the stabilization of carbanions by +R groups is due to delocalization of negative charge from the carbanionic carbon. In the case of NO2, resonance structures as in 24 are written184 ... 

A recent paper (199 3)195 is devoted largely to the behaviour of cyano carbanions. It is concluded that the stabilization of carbanions by CN does not actually involve considerable transfer of 7r charge from the carbanionic carbon to CN. This does not, however, appear to have any implications for the explanation of stabilization of carbanions by the nitro group in terms of delocalization. 

In organic chemistry this stabilizing effect is well known the stability of carbanions is known to be enhanced by nitro groups. The stability of the cyclopentadienide anion is increased by complexing with a typical Lewis acid so that it becomes less reactive. For example, ferrocene is not ionized in nitromethane solution. Addition of a Lewis acid such as aluminum chloride facilitates the occurrence of intramolecular race-mization (75) a process which is believed to involve ionic intermediates [16). This belief is supported by kinetic evidence and the failure of the reaction to occur in nearly inert solvents like methylene chloride and in those of high donidty. Whereas the former do not support the solvation of the cation formed in the process of ionization, the latter will react preferentially with the Lewis acid, which is then no longer available for the stabilization of the carbanion. 

The effect of the 1,2,5-thiadiazole system on the reactions of carbon-bound substituents can be summarized as follows (i) stabilization of carbanions (ii) destabilization of carbenium ions (iii) enhanced Sn2 reactivity and repressed SnI reactivity <68AHC(9)107>. Aryl substituents are rendered more reactive to nucleophiles <72US(A)25> and deactivated in reactions with electrophiles, which are directed to the orthojpara positions by the thiadiazole ring <72IJS(A)25,78MI409-01>. 

This chapter will begin with a brief overview of the development of carbanion chemistry followed by a section devoted to the structure and stability of carbanions. Methods of measuring carbon acidity and systematic trends in carbanion stability will be key elements in this chapter. Next, processes in which carbanions appear as transient, reactive intermediates will be presented and typical carbanion mechanisms will be outlined. Finally, some new developments in the field will be described. Although the synthetic utility of carbanions will be alluded to many times in this chapter, specific uses of carbanion-like reagents in synthesis will not be explored. This topic is exceptionally broad and well beyond the scope of this chapter. 

Except for the most highly stabilized carbanions, carbanion chemistry in solution is always complicated by the presence of the counterion, usually a metal, which is a Lewis acid and almost invariably is involved in the course of the reaction. Relative stabilities of carbanions in solution are difficult to establish for the same reason. In recent years, much information has been gathered about carbanion stabilities, structures, and reactiv-... 

The ElcB mechanism has the same features as the E2 mechanism except that proton abstraction by the base proceeds essentially to completion prior to departure of the leaving group. A variant of this mechanism may intervene whenever the leaving group is a poor leaving group or an exceptionally stable carbanion may be formed (i.e., due to the presence of Z substituents in addition to the polar a bond and/or a hybridization effect). The factors which lead to stabilization of carbanions have been discussed in Chapter 7. 

Answer. Two factors contribute to the stabilization of carbanions by an adjacent trifluoromethyl group or other perfluorinated groups. Most obviously, the strong inductive effect of the highly electronegative fluorine atoms will tend to increase the... 

The fact that a-silyl substitution leads to a significant stabilization of carbanionic species is well-known and has been exploited in synthetic chemistry. On the other hand, silyl anions themselves are in general much more stable than their carbon analogues. The stabilization of carbanions by silyl substituents in the a position has been measured by Brauman and coworkers37. The anions were generated via nucleophilic displacement reactions (equation 2) of a silyl group with F- (see also Section III.B). 

When an electrophilic substitution at saturated carbon occurs, either a car-banion is liberated as such or, if no carbanion is actually formed, the carbon atom undergoing substitution has a certain amount of carbanion character . Thus a knowledge of the factors governing the formation and the stability of carbanions might be of help in the understanding of the mechanism of electrophilic substitution at saturated carbon. 

The basicity of the anion CH2X , as a function of X, has been found to decrease in groups 16 (from OH to SH), 15 (from NH2 to PH2), and 14 (from CH3 to SiHs), because the a-stabilization of CH2X increases.5 In contrast, the basicity of CH2X along the series X = F, Cl, Br, I does not decrease, as commonly assumed. Fluorine has been found more effective than the heavier halogens for a-stabilization of carbanions. 

The a-deprotonation of conformationally constrained thioethers can proceed with high diastereoselectivity (Scheme 2.16) [54]. That equatorial protons are removed much more rapidly than axial protons suggests that stabilization of carbanions Qt -S-Q by sulfur is mainly a result of hyperconjugation between the carbanion lone pair and the antibonding S-Ca- orbital [55]. 

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