Reactions of Carbanions

Carbanions take part in the usual types of reactions, viz., addition, elimination, displacement, oxidation and rearrangement. 

Carbanions are involved as intermediates in ElcB elimination reactions. 

The alkynyl (or acetylide) carbanions undergo alkylation in a similar manner. 

Under suitable conditions the carbanions can be oxidized. Thus, triphenylmethyl carbanion is oxidized to triphenylmethyl radical slowly by air. The triphenylmethyl radical so obtained can be reduced back to the carbanion by shaking with sodium amalgam. 

This is a useful reaction for the formation of a carbon-carbon bond via dimerization of the radicals formed by the oxidation of carbanions. 

Because of the localization of electron density and negative charge, carbanions are both bases and nucleophiles. As a base, a carbanion can abstract a proton from any substance with a pKa smaller than that of the protonated carbanion, and the use of isotopically labeled proton donors affords a useful synthesis of labeled compounds. For example, abstraction of a proton from the methyl group of exo-3-acetyl-endo-tricyclo[3.2.1.0 ]octane (88) gave an enolate ion that could abstract a deuterium ion from the solvent to produce a monodeuterated compound. Repeated exchange of the methyl protons led to a nearly quantitative yield of trideuterio product 89 (equation 

As a nucleophile, a carbanion can react readily with a carbon atom bearing a good leaving group, which is a useful method for forming new carbon-carbon bonds. The aldol reaction and the Claisen condensation are familiar examples of carbanions (tis enolates) undergoing nucleophilic addition to carbon-oxygen double bonds. Carbanions may also act as nucleophiles in Sn2 reactions. The reaction of phenylacetic acid (90) with sodium in liquid ammonia leads to a carbanion (91) that reacts with benzyl chloride to produce 23-diphenylpropionic acid (92, equation 5.66).  

Carbanions are much less prone to unimolecular rearrangements than are carbocations or radicals, particularly with regard to 1,2-alkyl shifts 

The 5-hexenyl carbanions, where M is sodium, potassium, rubidium, and cesium, undergo rearrangement from a primary carbanion to the isomeric allylic carbanions in THF at —50 C (equation 5.68). However, 5-hexenyl-lithium rearranges to a cyclic structure (equation 5.69).  

Another example is the rearrangement of the carbanion formed by deprotonation of the spirodiene 95 by -BuLi in THF. The product is the 2-phenylethyllithium species 96 (equation 5.70).  

A carbanion may act as base or nucleophile depending on the reaction conditions. Action as a base involves electron pair donation to H, whereas nucleophilic reactions involve electron pair donation to other atoms such as carbon. Can we relate base strength to nucleophilic reactivity Here are some comparisons  

The concepts are linked but are not the same. Nucleophilic reactivity is measured by the rate of reaction, whereas base strength is measured by the equilibrium constant, K. Here, we can use the acidity of the acid HX to get an idea of the ability of X as a leaving group in nucleophilic substitution, since both Eqs. (3.8) and (3.9) have X on the right-hand side  

Carbanions frequently add to the carbonyl double bond. The aldol reaction, Claisen reaction, Dieckmann reaction, Michael reaction, and Knoevenagel condensation are familiar examples of carbanions (as enolates) undergoing nucleophilic addition to carbon-oxygen double bonds. 

Compounds which will form stable or transitory carbanions commonly undergo two different kinds of reactions. They are displacement reac- 

A number of carbanion displacement reactions are discussed in Chapter 

Carbanion additions occur frequently at carbonyl or nitrile groups and occasionally at carbon-carbon double bonds. The Grignard synthesis of alcohols is an example  

Arenes usually undergo electrophilic substitution, and are inert to nucleophilic attack. However, nucleophile attack on arenes occurs by complex formation. Fast nucleophilic substitution with carbanions with pKa values 22 has been extensively studied [44]. The nucleophiles attack the coordinated benzene ring from the exo side, and the intermediate i/2-cvclohexadienyl anion complex 171 is generated. Three further transformations of this intermediate are possible. When Cr(0) is oxidized with iodine, decomplexation of 171 and elimination of hydride occur to give the substituted benzene 172. Protonation with strong acids, such as trifluoroacetic acid, followed by oxidation of Cr(0) gives rise to the substituted 1,3-cyclohexadiene 173. The 5,6-trans-disubstituted 1,3-cyclohexadiene 174 is formed by the reaction of an electrophile. 

The carbon nucleophiles listed in eq. (9.1) are known to react. But no reaction occurs with some nucleophiles such as malonate and Grignard reagents. 

the preparation of the substituted benzene 172 is explained. In the reaction of substituted benzene complex 175 with carbanions, the meta orientation to give 176 is observed even in the presence of ortho- and para-orienting electron-donating groups, such as methoxy and amino groups [45], Using this property, the nucleophilic substitution reaction, complementary to ordinary electrophilic substitution reaction, is 

Cr(CO)3 coordinates to the benzene ring of indole (181) selectively and the reaction occurs mainly at the normally inaccessible C(4) carbon to give 182, and substitution at C(7) to give 183 is a minor reaction [47]. With the uncomplexed indole, substitution at C(2) is common. 

Formation of cyclohexadiene 173 by protonation is a useful reaction. Cyclohex-enone can be prepared from anisole by this reaction. Meta-substitution of the 

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The stereochemistry observed in hydrogen-exchange reactions of carbanions is very dependent on the conditions under which the anion is formed and trapped by proton... 

Carbanions are very useful intermediates in the formation of carbon-carbon bonds. This is true both for unstabilized structures found in organometallic reagents and stabilized structures such as enolates. Carbanions can participate as nucleophiles both in addition and in substitution reactions. At this point, we will discuss aspects of the reactions of carbanions as nucleophiles in reactions that proceed by the 8 2 mechanism. Other synthetic aj lications of carbanions will be discussed more completely in Part B. 

The most common reaction of carbanions is combination with a positive species, usually a proton, or with another species that has an empty orbital in its outer shell (a Lewis acid-base reaction) ... 

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. 

It is important to keep the position of the equilibria in mind as we consider reactions of carbanions. The base and solvent used determine the extent of deprotonation. Another important physical characteristic that has to be kept in mind is the degree of aggregation of the carbanion. Both the solvent and the cation influence the state of aggregation. This topic is discussed further in Section 1.1.3. 

A further interesting, and synthetically useful, reaction of carbanions— and of organometallic compounds acting as sources of negative carbon—is addition to the very weak electrophile C02, to form the corresponding carboxylate anion (36)—carbonation ... 

The nitration of active methylene compounds generally proceeds via the reaction of carbanionic intermediates with an electrophilic nitrating agent such as alkyl nitrate (alkyl nitrate nitration). Details of this process are well documented in the reviews.38 The alkyl nitrate nitration method has been used extensively for the preparation of arylnitromethanes. The toluene derivatives, which have electron-withdrawing groups are nitrated with alkyl nitrates in the presence of KNH2 in liquid ammonia (Eqs. 2.19 and 2.20).39... 

In some reactions of carbanions or organometallic compounds with very weak acids the base has a choice of protons and can give more than one salt. An example is the nuclear metallation of a substituted benzene in which the product may be oriented ortho, meta, or para. The actual results of a few such reactions are shown in Table XII. 

In general, the reaction of carbanions with carbenes takes place smoothly to form primary product carbanions. However, they react further with electrophiles and this secondary reaction is difficult to control.36 To overcome this disadvantage, carbanions bearing an appropriate leaving group were designed and utilized for olefin synthesis (Scheme 23). 

The elimination reactions of carbanions have been put under different classes. These are (a) a eliminations (jb) P eliminations... 

The synthesis of oc/S-unsaturated sulphoxides from the anion (122) has been described.113 The reaction is non-stereospecific, but good yields are obtained from cyclopentanones and acetophenones. Good yields of mono-alkylated products are obtained from the reaction of carbanions of diethyl 2-oxophosphonates (123) and reactive halides 114 alkylation of the compounds (124) has also been achieved.115 The... 

In this chapter, C—N couplings, e.g. substitution reactions of carbanions on nitrogen atom of oximes to yield primary amines, have been reviewed. A list of oximes and 0-sulfonyloximes used for electrophilic amination is given in Table 6. These reagents aminate carbanions to A-organylimines as isolable intermediates which are hydrolyzed to primary amines (Scheme 53, path d Scheme 54). Depending on the organometaUic... 

Scheme 2.4. Addition Reactions of Carbanions Derived from Esters, Carboxylic Acids, Amides, and Nitriles... 

In a novel kinetic approach, Dorfman et al. developed methods for rapidly generating very reactive carbanions such as the benzyl anion in solvent mixtures containing water and alcohols. With pulsed radiolysis techniques, they have been able to study the fast and very exothermic reactions of carbanions with these solvents. The studies have shown that despite the high exothermicity, the protonation is not diffusion controlled and depends on the nature of the carbanion s counterion. 

Thus, the reaction of living anionic polystyrene with AIBN, leading to chain coupling with elimination of CN , seems to be similar to that proposed by YOSHIMURA (15) for the reaction of carbanions with substituted a aminonitriles. 

Coupling Reactions of Carbanionic Polymers by Elemental Compounds Such as Oxygen and Sulfur... 

To account for these results we can propose the following mechanism for the reaction of carbanions onto elemental sulfur ... 

Reactions of carbanions, anions of weak organic acids (e.g., indole or carbazole), and dihalocarbenes may be carried out in liquid-liquid systems, in which concentrated aqueous sodium hydroxide is the aqueous phase. The term phase transfer catalysis is mechanistically incorrect these are often referred to as catalytic two-phase systems. Numerous reactions of carbanions including alkylation, nitroarylation, addition, the Darzens condensation, cyclopropanation, and also a variety of reactions of dihalocarbenes are conveniently carried out in this way. 

Reaction of carbanions with dialkynic ketones, the so-called skipped diynes, can produce pyranones through an initial Michael condensation. It should be noted however that diynones are vulnerable to attack at several sites and that mixed products can be formed. Addition of the anions derived from diethyl malonate and ethyl cyanoacetate to hepta-2,5-diyn-4-one (313 R1 = Me) gives the pyranones (314 R2 = C02Et or CN Scheme 91) (74JOC843). The former carbanion reacts similarly with the diynone (313 R1 = Bun) (68T4285). The second alkyne moiety appears to have little effect on the course of the reaction, which parallels the synthesis of pyranones from monoalkynic ketones. 

A further illustration of the reaction of carbanionic species with o-hydroxybenzaldehydes is provided by the use of phosphorus ylides in coumarin synthesis. Thus, ethoxycarbonyl-methylenetriphenylphosphorane affords simple coumarins via the ester (380 R = H), whilst with o-hydroxyacetophenone a 4-methylcoumarin results (381 R = Me) (77S464), and 4-methylsulfinylmethylcoumarin (381 R = CH2SOMe) is obtained from o-hydroxy-a>-methylsulfinylacetophenone (Scheme 120) (72JHC175). 

Although alkynes are highly reactive toward a wide range of transition metals, few instances of metal-catalyzed reactions of carbanions with alkynes are known. The most extensively developed system involves cationic iron complexes of internal alkynes. These complexes underwent alkylation by a range of carbanions to produce stable [Pg.582]

Photostimulated, S r k 1 reactions of carbanion nucleophiles in DMSO have been used to advantage in C—C bond formation (Scheme 1).25-27 Thus, good yields of substitution products have been obtained from neopentyl iodide on reaction with enolates of acetophenone and anthrone, but not with the conjugate base of acetone or nitromethane (unless used in conjunction, whereby the former acts as an entrainment agent).25 1,3-Diiodoadamantane forms an intermediate 1-iodo mono substitution product on reaction with potassium enolates of acetophenone and pinacolone and with the anion of nitromethane subsequent fragmentation of the intermediate gives derivatives of 7-methylidenebicyclo[3.3.1]nonene. Reactions of 1,3-dibromo- and 1-bromo-3-chloro-adamantane are less effective.26... 

Reviews have featured epoxidation, cyclopropanation, aziridination, olefination, and rearrangement reactions of asymmetric ylides 66 non-phosphorus stabilized carbanions in alkene synthesis 67 phosphorus ylides and related compounds 68 the Wittig reaction 69,70 and [2,3]-Wittig rearrangement of a-phosphonylated sulfonium and ammonium ylides.71 Reactions of carbanions with electrophilic reagents, including alkylation and Wittig-Homer olefination reactions, have been discussed with reference to Hammett per correlations.72... 

Review articles have addressed advances in photochemical generation and reactions of carbanions,165 the [l,2]-WMg rearrangement stereochemistry and synthetic application,167 and the aza-Wittig rearrangement.168... 

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