TheDakin–West reaction is achemical reaction that transforms anamino-acid into aketo-amide using anacid anhydride and a base, typicallypyridine.[1][2][3][4][5] It is named forHenry Drysdale Dakin and Randolph West. In 2016 Schreiner and coworkers reported the first asymmetric variant of this reaction employing short oligopeptides as catalysts.[6]
With pyridine as a base andsolvent, refluxing conditions are required.[7] However, with the addition of4-dimethylaminopyridine (DMAP) as a catalyst, the reaction can take place at room temperature.[8]
With some acids, this reaction can take place even in the absence of an α-amino group.
This reaction should not be confused with theDakin reaction.
The reaction mechanism involves the acylation and activation of the acid1 to the mixed anhydride3. The amide will serve as a nucleophile for the cyclization forming theazlactone4. Deprotonation and acylation of the azlactone forms the keycarbon-carbon bond. Subsequent ring-opening of6 anddecarboxylation give the final keto-amide product.[9][10]
Modern variations on the Dakin–West reaction permit many enolizable carboxylic acids – not merely amino acids – to be converted to their corresponding methyl ketones. For example, β-aryl carboxylic acids can be efficiently converted to β-aryl ketones by treatment of anacetic anhydride solution of the acid with catalyticN-methylimidazole. This reactivity is attributed in part to generation of acetylimidazolium, a powerful cationic acetylating agent,in situ.[11]
