Generation of Nucleophilic Carbon Reagents

The three major classes of nucleophilic carbon species are organometallic compounds, enolate derivatives and related carbanionic compounds, and neutral enol derivatives  

Organometallic compounds which contain a carbon-metal bond are the most reactive carbon nucleophiles. In most cases they are also powerful bases and must be prepared and used under strictly anhydrous and aprotic conditions. A very common way to produce organometallic compounds is to reduce alkyl halides with active metals. Grignard reagents and organolithium compounds are routinely produced in this manner. The transformation is a two-electron reduction of the alkyl halide to a carbanion equivalent the metal is oxidized. 

A second way to make organometallic compounds for use as carbanion nucleophiles is to use halogen-metal exchange. In this process an alkyl halide 

One requirement is diat the pKa of die new organometallic compound is lower than die pKa of die starting organometallic. This in essence means that the equilibrium is driven to products by die formation of a more stable anion. This metiiod is commonly used to make vinyl lithiums from vinyl halides and alkyl lithiums and aryl lithiums from aryl halides and alkyl litiiiums because the electron pair in an sp2 orbital of a vinyl or aryl litiiium compound is more stable than the electron pah in an sp3 orbital of an alkyl lithium. 

Enolates and related carbanionic nucleophiles are routinely generated by removal of an acidic proton in a molecule with a base. Carbonyl groups acidify their a protons somewhat and make dieir removal by a base a common process. However, structural features other than carbonyl groups can also acidify protons bound to carbon and thus facilitate dieir removal by bases. For example, pK values for structurally acidified C-H protons include the ones given below. 

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