Stork Enamine Synthesis
The Stork enamine synthesis involves the alkylation or acylation of an enamine with the corresponding reagent.
General features:
1. The preparation of the enamines takes place with one equivalent of a secondary amine. 2. Unsymmetrical ketones deliver enamine regioisomers, being the less substituted favored. Thus, the alkylation takes place on the less substituted side of the ketone. 3. Tertiary alkyl halides undergo elimination rather than alkylation. 4. The best electrophiles are activated alkyl and acyl halides; however, Michael acceptors and epoxides can be used. 5. The alkylation of the enamine takes place under neutral conditions. Besides, polyalkylated products are seldom observed.
Stork Enamine Synthesis
Reaction Mechanism
1. Formation of the enamine. 2. Alkylation of the enamine. 3. Hydrolysis with dilute acid.
Example
Experimental Procedure
To a solution of isobutyraldehyde (0.273 mmol, 1.0 equiv) in THF (4.10 mL) was added Bu2BOTF (273 µL of a 1.0 M solution in DCM) at ambient temperature. To a reaction mixture was immediately added a solution of the enamine (1.0 equiv) in THF (1.36 mL) via cannula. After being stirred for 3 h, the reaction mixture was quenched with water and extracted with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel to afford the corresponding aldehyde (77% yield, E : Z = 7 : 1).
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