Stork enamine alkylation

Stork enamine alkylation, also known as the Stork-Enamine reaction, involves the addition of an enamine to an alpha,beta-unsaturated carbonyl acceptor in a process similar to the Michael reaction [cite book | last =McMurry | first =John | authorlink = John E. McMurry | title =Organic Chemistry | format =Hardcover | edition =6th edition | date =2003-03-21 | publisher =Thomson-Brooks/Cole | location =Belmont, CA | id =ISBN 0-534-38999-6 ] . The product is then hydrolyzed by an aqueous acid to produce a 1,5-dicarbonyl compound.

The process:

# formation of an enamine from a ketone
# addition of the enamine to and alpha, beta-unsaturated aldehyde or ketone
# hydrolysis of the enamine back to a ketone

When the electrophile is an acyl halide, a 1,2-diketone is formed (Stork acylation) [JerryMarch] . The reaction is named after its inventor: Gilbert Stork.

Variations

In a special case of this reaction type it is also possible to alkylate ketones or aldehydes with alkyl halides as less reactive electrophiles ["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 - 2180; DOI|10.1021/ja00897a040] :

In this method a carbonyl compound is converted to an imine by alkylimino-de-oxo-bisubstitution with a primary amine. The imine is then reacted with an Grignard reagent to the corresponding magnesium salt to an intermediate capable of displacing a halide. Hydrolysis once again yields the alkylated ketone.

References