Generation of carbanions

A common procedure for the synthesis of organometallic compoimds is the reduction of a carbon-halogen bond with a metal (M), as illustrated in equation 5.60. (This simple equation ignores the role of solvent molecules and aggregated species.) 

Reagents such as n-butyllithium, methyllithium, and phenyllithium manufactured by this process are commercially available. Carbanions can also be formed by an acid-base reaction involving heterolytic dissociation of a carbon-hydrogen bond by a strong base. An example is the deprotonation of limonene (86) by -butyllithium complexed with tetramethylethylenedia-mine (TMEDA), as shown in equation 5.61. Note that there is more than one kind of allylic proton in 86, but the deprotonation preferentially produces the least-substituted carbanion.  

Carbanion Chemistiy, Springer-Verlag Berlin, 1983 Stowell, J. C. Carbanions in Organic Synthesis John Wiley ns New York, 1979 Ayres, D. C. Carbanions in Synthesis Oldboume Book Co. London, 1966. 

in Buncel, E. Durst, T., Eds. Comprehensive Carbanion Chemistry. Part B. Selectivity in Carbon-Carbon Bond Forming Reaction Elsevier Amsterdam, 1984 pp. 239-291. 

Because carbon-hydrogen bonds exhibit very low acidity (see Chapter 7), very strong bases are required for such reactions. However, C—H bonds adjacent to substituents such as carbonyl or cyano groups are more acidic. Nitrogen bases have been used effectively in these reactions to minimize the nucleophilic addition that can compete with proton removal when an orga-nometallic compoimd such as n-butyllithium is used as the base. For example, methyl ketones react with lithium diisopropylamide (LDA) to form the enolate ion (equation 5.64),  

Following methods are generally used for the generation of carbanions. 

An appropriate organic substrate having a C—H bond on treatment with a suitable base results in the abstraction of hydrogen to generate a carbanion. 

Addition of a nucleophile to carbon-carbon double bond generates a carbanion. 

Reduction of carbon-halogen bond by metal yields carbanion. Reaction of alkyl halide with Mg in the presence of anhydrous ether as solvent generates Grignard reagent. The Grignard reagent behaves like a carbanion. Alkyllithiums are also obtained from alkyl halides and behave as carbanions. 

We know how stabilized carbanions such as enols and enolated enamines are key intermediates in biological isomerization reactions and in carbon-carbon bond-forming and bond-breaking events. In this chapter, we will look at two more important reaction types, called Michael additions and -eliminations, which involve stabilized carbanion species as intermediates. In a Michael addition, a nucleophile and a proton are added to the two carbons of an alkene that is conjugated to a carbonyl group. The reverse of a Michael addition is called a -elimination. 

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Stereochemical constraints in cyclic sulfones and sulfoxides impart increased weight to strain and conformational factors in the generation of carbanions and their stability, causing distinct differences between the behavior of cyclic and open-chain systems233, due primarily to the prevention of extensive rotation about the C —S bond, which is the major way that achiral carbanions racemize. Study of the a-H/D exchange rate fce and the racemization rate ka may provide information concerning the acidity-stereochemical relationships in optically active cyclic sulfone and sulfoxide systems. 

Michael addition has been employed as a key step in the formation of four-membered ring compounds.6 As outlined, indirect generation of carbanions from 3,3-dimethyl-4-tosyloxybut-... 

For the generation of carbanions, carbenes, etc., sodium hydroxide can be used as a base. Thus use of dangerous, expensive, and inconvenient reagents (t-BuOK, NaNH2, or NaH) is eliminated. Thanks to this, the use of large quantities of meticulously dried organic solvents is also avoided. 

The generation of carbanions and their reactions with aromatic aldehydes and ketones... 

The vast utilization of hindered secondary amines like diisopropylamine or dicyclohexylamine in carbanion chemistry is also based on the difference in their behavior toward protons and other electrophiles. Thus quite a number of the methods depend upon the use of the lithium or magnesium salts of these amines for the generation of carbanionic species. These salts are very strong kinetic bases and therefore are able to abstract a proton from a variety of C-H acids. At... 

For practical purposes, it would seem useful to have an overview of methods for the generation of carbanions and guidelines on compatibility with various polymers and linkers. In the following list, we summarize certain commonly used carbanions, linkers, supports, and methods of generation (Table 8). 

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