Skip to main content
Chemistry LibreTexts

23.11 Carbonyl Condensations with Enamines - The Stork Reaction

[ "article:topic", "showtoc:no" ]
  • Page ID
    91024
  • Objectives

    After completing this section, you should be able to

    1. write an equation to illustrate the three‑step Stork enamine reaction.
    2. write a detailed mechanism for each of the three steps of the Stork enamine reaction.
    3. identify the product formed, and the various intermediates (i.e., the enamine, the Michael‑type adduct), in a given Stork enamine reaction.
    4. identify the reagents needed to synthesize a given compound by a Stork enamine reaction.

    Key Terms

    • Stork enamine reaction

    Study Notes

    If we try to use a monoketone as a donor molecule in a Michael reaction, we will obtain a poor yield. An alternative route to the product that would be expected from such a synthesis is via the Stork enamine reaction. You may wish to review the formation of enamines (from ketones and secondary amines) before you proceed with this section; if so, review Section 19.8.

    Overview

    As previously seen, aldehydes and ketones react with 2o amines to reversibly form enamines.

    Example

    1.jpg

    Reversible

    2.jpg

    Enamines act as nucleophiles in a fashion similar to enolates.  Because of this enamines can be used as synthetic equivalents as enolates in many reactions.  This process requires a three steps: 1) Formation of the enamine, 2) Reaction with an eletrophile to form an iminium salt, 3) Hydrolysis of the iminium salt to reform the aldehyde or ketone.  Some of the advantages of using an enamine over and enolate are enamines are neutral, easier to prepare, and usually prevent the overreaction problems plagued by enolates.  These reactions are generally known as the Stork enamine reaction after Gilbert Stork of Columbia University who originated the work.

    3.jpg

    Typically we use the following 2o amines for enamine reactions

    4.jpg

    Alkylation of an Enamine

    Enamined undergo an SN2 reaction with reactive alkyl halides to give the iminium salt.  The iminium salt can be hydrolyzed back into the carbonyl. 

    Individual steps

    1) Formation of an enamine

    5.jpg

    2)  SN2 Alkylation

    6.jpg

    3)  Reform the carbonyl by hydrolysis

    7.jpg

    All three steps together:

    8.jpg

    Acylation of Enamines

    Enamine can react with acid halides to form β-dicarbonyls

    1) Formation of the enamine

    9.jpg

    2) Nucleophilic attack

    10.jpg

    3) Leaving group removal

    11.jpg

    4)  Reform the carbonyl by hydrolysis

    12.jpg

    All three steps together:

    13.jpg

    Michael Addition using Enamines

    Enamines, like other weak bases, add 1,4 to enones.  The end product is a 1,5 dicarbonyl compound.

    14.jpg

    Exercises

    Questions

    Q23.11.1

    Draw the product of the reaction with the enamine prepared from cyclopentanone and pyrrolidine, and the following molecules.

    (a)

    (b)

    (c)
     

    Q23.11.2

    Propose a synthesis for the following compounds via an enamine.

    (a)

    (b)

    Solutions

    S23.11.1

    (a)

    (b)

    (c)

     

    S23.11.2

    (a) cyclopentanone enamine + 2-cyanopropene

    (b) cyclohexanone enamine + ethyl acrylate

    Contributors