Dakin–West reaction

Not to be confused with Dakin reaction.

The Dakin–West reaction is a chemical reaction that transforms an amino-acid into a keto-amide using an acid anhydride and a base, typically pyridine.^{[1][2][3][4][5]} It is named for Henry Drysdale Dakin and Randolph West. In 2016 Schreiner and coworkers reported the first asymmetric variant of this reaction employing short oligopeptides as catalysts.^[6]

The Dakin–West reaction

With pyridine as a base and solvent, refluxing conditions are required.^[7] However, with the addition of 4-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 the Dakin reaction.

Reaction mechanism

The reaction mechanism involves the acylation and activation of the acid 1 to the mixed anhydride 3. The amide will serve as a nucleophile for the cyclization forming the azlactone 4. Deprotonation and acylation of the azlactone forms the key carbon-carbon bond. Subsequent ring-opening of 6 and decarboxylation give the final keto-amide product.^[9][10]

The mechanism of the Dakin-West reaction

General ketone synthesis

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 an acetic anhydride solution of the acid with catalytic N-methylimidazole. This reactivity is attributed in part to generation of acetylimidazolium, a powerful cationic acetylating agent, in situ.^[11]

Modified Dakin-West reaction

See also

• Robinson–Gabriel synthesis - A process for converting the keto-amide products of this reaction into oxazoles