Stork enamine reaction

What is Stork enamine reaction?

The Stork enamine reaction is a method for synthesizing α-alkyl or α-acyl carbonyl compounds from enamines and alkyl or acyl halides. The discoverer of this reaction, Gilbert Stork, was the Eugene Higgins Professor of Chemistry Emeritus at Columbia University.

This reaction, also known as the Stork enamine alkylation reaction and Stork enamine acylation reaction, gives moderate yields when using simple alkyl halides. However, when more electrophilic reactants such as allylic, benzylic, or propargylic halides, or α-halo ethers, α-halo esters, or α-halo ketones are used, the yields can be improved for the alkylated product.

Stork enamine alkylation reaction
Stork enamine alkylation reaction
Stork enamine acylation reaction
Stork enamine acylation reaction

Enamines play a crucial role as intermediates in organic synthesis. This is due to the nucleophilic nature of the β-carbon atom, as depicted in the resonance structures shown in the figure. The reactivity of enamines arises from the presence of the negative charge on the β-carbon atom.

enamine resonance structures
Enamine resonance structures

Enamines that correspond to ketones or aldehydes can be obtained by using p-toluenesulfonic acid (TsOH) in combination with secondary amines, as illustrated in the figure. Cyclic secondary amines, such as piperidine, pyrrolidine, and morpholine, are commonly utilized in this process.

formation of enamine from ketone and aldehyde - Stork enamine alkylation and acylation reactions
Formation of enamines from ketones and aldehydes

In order to shift the equilibrium, it is common practice to eliminate the water produced during the enamine formation reaction through azeotropic distillation with either benzene or toluene.