15.39: Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction
α-Substituted ketones or aldehydes can be synthesized from enamines by the Stork enamine reaction, named after its pioneer Gilbert Stork. Enamines are useful synthetic intermediates where the lone pair on nitrogen is in conjugation with the C=C bond. They resemble enolate ions, as the resonance forms of both species have a nucleophilic α carbon.
However, enamines are neutral and less reactive than enolates, which bear a net negative charge. Consequently, enamines are effective Michael donors that undergo Micheal addition with acceptors like α,β-unsaturated carbonyl compounds. The reaction yields an enolate-iminium intermediate that reacts with aqueous acid to give an α-substituted 1,5-dicarbonyl compound. Similarly, upon treatment with alkyl or acyl halides, enamines generate respective iminium salts, and subsequent hydrolysis produces respective alkylated and acylated carbonyl compounds.
