The Stork enamine alkylation involves the addition of an

enamine An enamine is an unsaturated compound derived by the condensation of an aldehyde or ketone with a secondary amine. Enamines are versatile intermediates. : The word "enamine" is derived from the affix ''en''-, used as the suffix of alkene, and t ...

to a

Michael acceptor In organic chemistry, the Michael reaction or Michael addition is a reaction between a Michael donor (an enolate or other nucleophile) and a Michael acceptor (usually an α,β-unsaturated carbonyl) to produce a Michael adduct by creating a carbo ...

(e.g, an α,β -unsaturated carbonyl compound) or another electrophilic alkylation reagent to give an alkylated

iminium In organic chemistry, an iminium cation is a polyatomic ion with the general structure . They are common in synthetic chemistry and biology. Structure Iminium cations adopt alkene-like geometries. The central C=N unit is nearly coplanar with al ...

product, which is hydrolyzed by dilute aqueous acid to give the alkylated ketone or aldehyde. 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 In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...

or ketone # hydrolysis of the enamine back to a ketone The reaction also applies to acyl halides as electrophiles, which results in the formation of 1,3-

diketones In organic chemistry, a dicarbonyl is a molecule containing two carbonyl () groups. Although this term could refer to any organic compound containing two carbonyl groups, it is used more specifically to describe molecules in which both carbonyls ...

(Stork

acylation In chemistry, acylation (or alkanoylation) is the chemical reaction in which an acyl group () is added to a compound. The compound providing the acyl group is called the acylating agent. Because they form a strong electrophile when treated with ...

). It is also effective for activated sp³ alkyl electrophiles, including benzylic, allylic/propargylic, α-carbonyl (e.g.,

bromoacetone Bromoacetone is an organic compound with the formula . It is a colorless liquid although impure samples appear yellow or even brown. It is a lachrymatory agent and a precursor to other organic compounds. Occurrence in nature Bromoacetone is pr ...

), and α-alkoxy (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''). The reaction is named after its inventor,

Gilbert Stork Gilbert Stork (December 31, 1921 – October 21, 2017) was an organic chemist. For a quarter of a century he was the Eugene Higgins Professor of Chemistry Emeritus at Columbia University. He is known for making significant contributions to the t ...

(Columbia University).

Variations

By using an anionic version of an enamine, known as an azaenolate or metalloenamine, it is also possible to alkylate ketones or

s with

alkyl halide The haloalkanes (also known as halogenoalkanes or alkyl halides) are alkanes containing one or more halogen substituents. They are a subset of the general class of halocarbons, although the distinction is not often made. Haloalkanes are widely us ...

s as less reactive

electrophile In chemistry, an electrophile is a chemical species that forms bonds with nucleophiles by accepting an electron pair. Because electrophiles accept electrons, they are Lewis acids. Most electrophiles are positively charged, have an atom that carrie ...

s:''A New Method for the Alkylation of Ketones and Aldehydes: the C-Alkylation of the Magnesium Salts of N-Substituted Imines''

and Susan R. Dowd

J. Am. Chem. Soc. The ''Journal of the American Chemical Society'' is a weekly peer-reviewed scientific journal that was established in 1879 by the American Chemical Society. The journal has absorbed two other publications in its history, the ''Journal of Analytic ...

; 1963; 85(14) pp 2178–80; In this method a carbonyl compound is converted to an

imine In organic chemistry, an imine ( or ) is a functional group or organic compound containing a carbon–nitrogen double bond (). The nitrogen atom can be attached to a hydrogen or an organic group (R). The carbon atom has two additional single bon ...

alkylimino-de-oxo-bisubstitution In organic chemistry, alkylimino-de-oxo-bisubstitution is the organic reaction of carbonyl compounds with amines to imines. The reaction name is based on the IUPAC Nomenclature for Transformations. The reaction is acid catalyzed and the reaction ...

with a primary

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen Hydrogen is the chemical element wi ...

. The imine is then reacted with a Grignard reagent to the corresponding magnesium azaenolate. By virtue of the negative charge of this species, it is capable of displacing a halide from less reactive alkyl halides, including methyl, ethyl, and other nonactivated halides.

Hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolys ...

once again yields the alkylated ketone.

References

{{reflist Carbon-carbon bond forming reactions Name reactions Enamines