Alkylation
Enolates, negatively charged and therefore with an excess of electrons, are good nucleophiles for nucleophilic substitution reactions on a suitable compound bearing a good leaving group.
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The result of this reaction is the alkylation of the aldehyde or ketone at its α position, which increases the complexity of the original molecule.
The base must be strong enough to convert the aldehyde or ketone quantitatively (100%) into its enolate.
Bases customarily used:
Metal hydrides (NaH) Alkoxides (t-BuOK) Metal amides [NaNH2 or LiN(i-Pr)2]
The solvents must be inert, such as dimethoxyethane (DME), dimethylformamide (DMF), tetrahydrofuran (THF) and hexamethylphosphoric triamide (HMPT).
This reaction has some problems:
Polyalkylation of symmetric ketones is difficult to avoid, even using one equivalent of alkylating agent.
Instead of being alkylated, aldehydes usually react with themselves in a reaction that we will see next: the aldol condensation.
The best way to avoid these problems and achieve regioselective monoalkylations is to use enamines.
We can now look at enamines from a practical point of view: as if they were stable enolates without a formal charge, whose formation does not require a strong base.
Enamines are less reactive than enolate ions and therefore allow regioselective monoalkylations without the problems mentioned above.
Always use enamines when you want to alkylate an aldehyde or ketone!