Dakin–West reaction
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Reaction that converts amino acids into a keto-amides
Not to be confused with
Dakin reaction
.The Dakin–West reaction is a
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 (1880–1952) and Randolph West (1890–1949). In 2016 Schreiner and coworkers reported the first asymmetric variant of this reaction employing short oligopeptides as catalysts.[6]
With pyridine as a base and
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]
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
N-methylimidazole. This reactivity is attributed in part to generation of acetylimidazolium, a powerful cationic acetylating agent, in situ.[11]
See also
- Robinson–Gabriel synthesis - A process for converting the keto-amide products of this reaction into oxazoles