Alpha Carbon Reactions

Alkylation Reactions

In alkylation reactions, an alkyl group attaches to another molecule, usually in the place of an acidic hydrogen. Alkylation reactions include the acetoacetic ester and malonic ester synthesis, the Stork enamine synthesis, and Michael additions.
Acetoacetic ester synthesis is a method for ketone preparation in which alkylation of the enolate of ethyl acetoacetate is followed by reaction with H3O+ and heat to decarboxylate the acetic ester. Decarboxylation is the removal of a carboxylic acid (as a CO2 group) by the addition of heat. Malonic ester synthesis is the preparation of a carboxylic acid by alkylation of the enolate of diethyl malonate. Acetoacetic ester synthesis and malonic ester synthesis are two methods that generate CC {\rm{C{-}C}} bonds. The first step in both processes is the formation of a resonance-stabilized enolate followed by the alkylation of the enolate. An enolate is the anion formed when the alpha hydrogen is removed as a hydrogen ion. In the next step, the ester is hydrolyzed by an acid, forming a carboxylic acid intermediate. For the malonic ester synthesis, this intermediate has two carboxylic acid groups. Finally, decarboxylation results from heating of the carboxylic acid. The alkylated acetoacetic ester yields a ketone, and the alkylated malonic ester yields a carboxylic acid.

Acetoacetic Ester Synthesis and Malonic Ester Synthesis

Acetoacetic ester synthesis and malonic ester synthesis proceed through the same mechanisms-alkylation, hydrolysis, and decarboxylation-to produce a ketone and a carboxylic acid.
In the Stork enamine reaction, ketones are alkylated or acylated through intermediate enamines. An enamine is an amino group containing the double bond linkage C=CN{\rm{C{=}C{-}N}}. In Stork enamine alkylation, an enamine adds to an alpha,beta-unsaturated carbonyl acceptor. The resulting molecule is hydrolyzed into a 1,5-dicarbonyl compound. The process is named after Gilbert Stork, a Belgian chemist. In many cases, the Stork method is preferred for preparing alkylated or acylated carbonyl compounds because enamines are neutral and use of the enamine prevents any overreaction that is often encountered when using enolates.

Stork Enamine Alkylation

Stork enamine alkylation is a three-step process, which includes formation of an enamine from a ketone, addition of the enamine to an α\alpha,β\beta-unsaturated aldehyde or ketone, and hydrolysis back to the aldehyde or ketone.