The Stork enamine alkylation involves the addition of an enamine to a Michael acceptor (e.g., an
The Stork enamine synthesis:
- formation of an enamine from a ketone
- addition of the enamine to an alpha, beta-unsaturated aldehyde or ketone
- hydrolysis of the enamine back to a ketone
![The Stork enamine reaction](https://upload.wikimedia.org/wikipedia/commons/thumb/a/ac/Stork_enamine_reaction.png/400px-Stork_enamine_reaction.png)
The reaction also applies to acyl halides as electrophiles, which results in the formation of 1,3-diketones (Stork acylation).[2]
It is also effective for activated sp3 alkyl electrophiles, including benzylic, allylic/propargylic,
The reaction is named after its inventor, Gilbert Stork (Columbia University).
Variations
editBy using an anionic version of an enamine, known as an azaenolate or metalloenamine, it is also possible to alkylate ketones or aldehydes with alkyl halides as less reactive electrophiles:[4]
In this method a carbonyl compound is condensed to a Schiff base. The imine then reacts with a Grignard reagent to the corresponding Hauser base. This species' negative charge enables displacing a less reactive alkyl halide, including methyl, ethyl, and other nonactivated halides. Hydrolysis then yields the alkylated ketone.
In the Corey-Enders reaction, a hydrazone replaces the amine for enantioselection.
References
edit- ^ McMurry, John (21 March 2003). Organic Chemistry (Hardcover) (6th ed.). Belmont, CA: Thomson-Brooks/Cole. ISBN 0-534-38999-6.
- ^ March, Jerry (1985), Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 3rd edition, New York: Wiley, ISBN 9780471854722, OCLC 642506595
- ^ Stork, Gilbert.; Brizzolara, A.; Landesman, H.; Szmuszkovicz, J.; Terrell, R. (January 1963). "The Enamine Alkylation and Acylation of Carbonyl Compounds". Journal of the American Chemical Society. 85 (2): 207–222. doi:10.1021/ja00885a021. ISSN 0002-7863.
- ^ A New Method for the Alkylation of Ketones and Aldehydes: the C-Alkylation of the Magnesium Salts of N-Substituted Imines Gilbert Stork and Susan R. Dowd J. Am. Chem. Soc.; 1963; 85(14) pp 2178–80; doi:10.1021/ja00897a040