Carbanion-based nucleophiles

Like amines, carbanions are nucleophilic and basic. A carbanion has a negative charge on its carbon atom, however, making it a more powerful base and a stronger nucleophile than an amine. For example, a carbanion is sufficiently basic to remove a proton from ammonia. 

The literature in this area is often ambiguous because although carbanions are common intermediates in electrosynthesis, especially as the result of cathodic cleavage, their followup reactions include involvement as nucleophiles or as bases. Also, as we shall see, electrogenerated carbanion bases may be used to generate nucleophiles from other acidic components of the reaction mixture. A comprehensive review [53] of this topic covers both types of behavior. Here an attempt is made to concentrate on those reactions where basic behavior of the electrogenerated carbanion is paramount. 

Carbanions, being strong bases and nucleophiles, react readily with acids and undergo the SN2 reactions considered in Chapter 1 and the bimolecular E2 eliminations considered in Chapter 3. Other important reactions of carbanions (and nucleophiles) include addition to unsaturated compounds, especially those containing carbonyl groups, fragmentation (the reverse of addition) and elimination to give carbenes. 

Define the terms base, nucleophile, carbanion and carbene. List the common reactions of carbanions and carbencs. 

Many important organic reactions involve carbanions as nucleophiles. The properties of carbanions were introduced in Section 3.4.2, and their reactivity is discussed in more detail in Chapter 6. Most C—H bonds are very weakly acidic and have no tendency to ionize spontaneously to form carbanions. Reactions that involve carbanion intermediates are therefore usually carried out in the presence of a base that can generate the reactive carbanion intermediate. Base-catalyzed addition reactions of carbonyl compounds provide many examples of this type of reaction. The reaction... 

The reaction of a-halo esters with carbonyl compounds in the presence of sodium ethoxide leads to 2-(ethoxycarbonyl)oxiranes (Darzens 1904). They are known as glycidic esters. In the first step, the a-halo ester is deprotonated by the base to the corresponding carbanion. This nucleophile adds to the carbonyl compound in a rate-determining step. Finally, the halogen atom is intramolecularly substituted, e.g. ... 

Carbon-based nucleophiles are generally regarded as soft bases, and Li is a hard acid. From this perspective alone, it would be difficult to rationalize that this reaction heavily favors the products, since the softness of the bases n-butyl and phenyl carbanions is similar. The significantly higher Br0nsted-Lowry basicity of the n-butyl carbanion (pK of n-butane is 50) relative to the phenyl carbanion (pKa of benzene is 43) plays a vital role in rationalizing the formation of phenyllithium. 

Oxazoles are acidic at C2 with a theoretical pKg value of 21 Metalation is facile at C2 with strong bases. C2-metalated oxazoles are in equilibrium with their ring-opened isonitrile. Due to this equilibrium, C2-metalated oxazoles are nucleophilic at either C2 or C4, and care must be taken when quenching the C2-metalated oxazole to ensure proper chemoselectivity (see Section 6.3.3). Benzoxazoles are acidic at C2 like oxazoles (experimental pKa 24.8), and the metalated benzoxazole is also in equilibrium with its ring opened isonitrile. Isoxazoles, without a C-H group flanked by two heteroatoms, are acidic at the C5 position with a theoretical pKa value of 27 however, in practice, deprotonation with hydroxide occurs at C3 to give a ring-opened P-ketonitrile intermediate. All of these heterocycles can be deprotonated with metal amides or carbanion bases. 

Reaction with butyllithium (a strong base) firstly deprotonates the more acidic alcohol, and only then deprotonates the benzylic methyl group to give a resonance stabilised carbanion this nucleophilic carbanion is quenched with bromoethane (5 2 reaction), but only the most reactive benzylic carbon centre reacts with the... 

The most general methods for the syntheses of 1,2-difunctional molecules are based on the oxidation of carbon-carbon multiple bonds (p. 117) and the opening of oxiranes by hetero atoms (p. 123fl.). There exist, however, also a few useful reactions in which an a - and a d -synthon or two r -synthons are combined. The classical polar reaction is the addition of cyanide anion to carbonyl groups, which leads to a-hydroxynitriles (cyanohydrins). It is used, for example, in Strecker s synthesis of amino acids and in the homologization of monosaccharides. The ff-hydroxy group of a nitrile can be easily substituted by various nucleophiles, the nitrile can be solvolyzed or reduced. Therefore a large variety of terminal difunctional molecules with one additional carbon atom can be made. Equally versatile are a-methylsulfinyl ketones (H.G. Hauthal, 1971 T. Durst, 1979 O. DeLucchi, 1991), which are available from acid chlorides or esters and the dimsyl anion. Carbanions of these compounds can also be used for the synthesis of 1,4-dicarbonyl compounds (p. 65f.). 

Nonanedione, another 1,3-difunctional target molecule, may be obtained from the reaction of hexanoyl chloride with acetonide anion (disconnection 1). The 2,4-dioxo substitution pattern, however, is already present in inexpensive, symmetrical acetylacetone (2,4-pentanedione). Disconnection 2 would therefore offer a tempting alternative. A problem arises because of the acidity of protons at C-3 of acetylacetone. This, however, would probably not be a serious obstacle if one produces the dianion with strong base, since the strongly basic terminal carbanion would be a much more reactive nucleophile than the central one (K.G. Hampton, 1973 see p. 9f.). 

Facile reaction of a carbon nucleophile with an olefinic bond of COD is the first example of carbon-carbon bond formation by means of Pd. COD forms a stable complex with PdCl2. When this complex 192 is treated with malonate or acetoacetate in ether under heterogeneous conditions at room temperature in the presence of Na2C03, a facile carbopalladation takes place to give the new complex 193, formed by the introduction of malonate to COD. The complex has TT-olefin and cr-Pd bonds. By the treatment of the new complex 193 with a base, the malonate carbanion attacks the cr-Pd—C bond, affording the bicy-clo[6.1,0]-nonane 194. The complex also reacts with another molecule of malonate which attacks the rr-olefin bond to give the bicyclo[3.3.0]octane 195 by a transannulation reaction[l2.191]. The formation of 194 involves the novel cyclopropanation reaction of alkenes by nucleophilic attack of two carbanions. 

A synthetically useful reaction known as the Michael reaction, or Michael addition, involves nucleophilic addition of carbanions to a p unsaturated ketones The most common types of carbanions used are enolate 10ns derived from p diketones These enolates are weak bases (Section 18 6) and react with a p unsaturated ketones by conjugate addition... 

The nucleophilic attack of nitrogen bases leads to a variety of products as the result of addition or addition-elimination reactions The regioselectivity resembles that of attack by alcohols and alkoxides an intermediate carbanion is believed to be involved In the absence of protic reagents, the fluorocarbanion generated by the addition of sodium azide to polyfluonnated olefins can be captured by carbon dioxide or esters of fluonnated acids [J 2, 3] (equation I)... 

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