Stork enamine alkylation
The Stork enamine alkylation involves the addition of an
α,β -unsaturated carbonyl compound) or another electrophilic alkylation reagent to give an alkylated iminium product, which is hydrolyzed by dilute aqueous acid to give the alkylated ketone or aldehyde.[1]
Since enamines are generally produced from ketones or aldehydes, this overall process (known as the Stork enamine synthesis) constitutes a selective monoalkylation of a ketone or aldehyde, a process that may be difficult to achieve directly.
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 reaction also applies to
It is also effective for activated sp3 alkyl electrophiles, including benzylic, allylic/propargylic, α-carbonyl (e.g.,
methoxymethyl chloride) alkyl halides. However, nonactivated alkyl halides, including methyl and other primary alkyl halides, generally only give low to moderate yields of the desired alkylation product (see below).[3]
The reaction is named after its inventor, Gilbert Stork (Columbia University).
Variations
By using an anionic version of an enamine, known as an azaenolate or metalloenamine, it is also possible to alkylate
alkyl halides as less reactive electrophiles:[4]
In this method a carbonyl compound is
displacing a less reactive alkyl halide, including methyl, ethyl, and other nonactivated halides. Hydrolysis
then yields the alkylated ketone.
In the
enantioselection
.
References
- ISBN 0-534-38999-6.
- OCLC 642506595
- ISSN 0002-7863.