15.39 : Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction

The Stork enamine reaction generates α-substituted carbonyls via enamine intermediates.

In enamines, the conjugation between nitrogen's lone pair and the C=C bond leads to its resemblance to enolate ions, with both accommodating a nucleophilic α carbon atom.

Despite this, enamines are neutral and less reactive than enolates that carry a net negative charge.

Enamines, therefore, serve as effective Michael donors and add to Michael acceptors, like α,β-unsaturated carbonyls, via Michael addition.

The reaction generates an enolate-iminium intermediate, which upon treatment with an aqueous acid, gives an α-substituted 1,5-dicarbonyl compound.

The reaction doesn't work with regular enolates as they are not efficient Michael donors, unlike their enamine analogs.

Enamines also endure a substitution reaction pathway with alkyl or acyl halides, producing respective iminium salts. Subsequent hydrolysis gives the corresponding alkylated and acylated carbonyl compounds.

Overall, in the Stork enamine reaction, ketones and secondary amines react to give nucleophilic enamine intermediates that add to suitable electrophiles, followed by hydrolysis to give α-substituted ketones.