Stork Enamine

Reaction

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Stork Enamine Reaction

It is by the process of converting a starting carbonyl material (aldehyde and ketone) with a
secondary amine to yield enamine, an unsaturated compound that derived from the
condensation of carbonyl material which further undergoes Michael Addition, Acylation, or
Alkylation.

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Synthesis of Enamine

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 Synthesis of Enamine
Key processes:
a. Nucleophilic addition of secondary Amine
b. Proton transfer to form hemiaminal
c. Protonation of the hemiaminal’s hydroxyl
d. Elimination of water
e. Loss of a proton from the alpha carbon
f. Formation of enamine

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 Formation of Enamine

a. Nucleophilic addition of
secondary Amine
b. Proton transfer to form
hemiaminal

..
c. Protonation of the ..

..

..
hemiaminal’s hydroxyl

..
..

..
Hemiaminal

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 Formation of Enamine

c. Elimination of water
d. Loss of a proton from the
alpha carbon
f. Formation of enamine

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Predicting the enamine product of the reaction between
a carbonyl compound and an Amine

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Enamine Reactions
• Michael Addition
..

• Acylation
• Alkylation

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Stork Enamine Reaction:
Michael Addition

Michael reaction is a process that occurs when an α,β-unsaturated carbonyl compound has its β-
carbon attacked by an enolate.

Why is the concept of Michael Addition involved in stork Enamine

Reaction? ..
Enamine can act as a nucleophile in a similar fashion as an

..
enolate since both can have a nucleophilic alpha carbon. For this

..
reason, it can undergo a reaction with an α,β-unsaturated carbonyl
compound in the same process as the Michael Reaction.

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Stork Enamine Reaction:
Michael Addition
The Stork reaction has the net reaction of enamine attacking the α,β-unsaturated
carbonyl compound. By conjugate addition, a 1,5-dicarbonyl compound is being
produced.

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Stork Enamine Reaction:
Michael Addition

Key processes:
a. Formation of enamine
b. Nucleophilic attack of enamine
c. Protonation
d. Tautomerization
e. Formation of iminium ion
f. Hydrolysis
i. Addition of water to the iminium ion
ii. Deprotonation of oxygen
iii. Protonation of nitrogen
iv. Elimination of amine moiety
v. Deprotonation to reform the carbonyl

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Stork Enamine Reaction:
Michael Addition

a. Formation of enamine

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Stork Enamine Reaction:
Michael Addition
b. Nucleophilic attack to the beta carbon
c. Protonation of the alkoxide
d. Tautomerization of enol
e. Formation of iminium ion

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Stork Enamine Reaction:
Michael Addition
f. Hydrolysis
i. Addition of water to the iminium ion
ii. Deprotonation of oxygen
iii. Protonation of nitrogen
iv. Elimination of amine moiety
v. Deprotonation to reform the carbonyl

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Predicting the product using
Stork Enamine Reaction(Michael Addition)

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Alkylation and Acylation

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Mechanism of Enamine
Alkylation

Alkylation of enamine is a somewhat straightforward process and can be achieved by treating the enamine with an
alkyl halide.
Key processes:
• Formation of enamine
• Nucleophilic attack
(SN2 reaction)
• Formation of iminium ion
• Hydrolysis

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Predicting the product for alkylating a carbonyl
compound

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Mechanism for Enamine
Acylation

Acylation of enamine can be achieved by reacting the enamine with acid halides to form β-dicarbonyls.

Key processes:
• Nucleophilic attack forming
A tetrahedral alkoxide
• Leaving group removal
• Formation of iminium ion
• Hydrolysis

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Predicting the product for acylating a carbonyl
compound

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Answers:

Pp. 15 Pp. 18
Pp. 7

Pp. 20

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• Stork enamine reactions are utilized for the alkylation and acylation of carbonyl
compounds.
• Enamine results from the reaction with a starting carbonyl material and a
secondary amine (commonly used is the pyrrolidine).
• Stork enamine reaction via Michael-like reaction occurred when enamine is treated
with an α,β-unsaturated carbonyl compound.
• Alkylation of enamine can be achieved by treating an enamine with an alkyl halide.
• Acylation of enamine can be achieved by treating an enamine with an acyl halide.

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References

McMurry, J. (2015). Organic Chemistry (Ninth Edition). Cengage Learning.

Anonymous. (2022, February 28). Carbonyl Condensation with Enamines-The Stork Reaction. ChemistryLibreText.
https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Organic_Chemistry_(McMurry)/23%3A_Carbonyl_Condensatio
n_Reactions/23.11%3A_Carbonyl_Condensations_with_Enamines_-_The_Stork_Reaction

Ashenhurst, J. (2022, March 28). All about Enamines. Master Organic Chemistry. Retrieved from:
https://www.masterorganicchemistry.com/2010/05/24/imines-and-enamines/

Anonymous. (2020, September 13). Enamine Reaction ChemistryLibreText.

https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Supplemental_Modules_(Organic_Chemistry)/Reactions/Reacti
vity_of_Alpha_Hydrogens/Enamine_Reactions

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