Dakin-West reaction

The Dakin-West reaction is a chemical reaction that transforms an amino-acid into an amino-ketone using a acid anhydride and a base, typically pyridine.Ref|Dakin1928Ref|Wiley1947Ref|Buchanan1988 It is named for Henry Drysdale Dakin (1880–1952) and Randolph West (1890–1949). Of special note, the amino-ketone product is always racemic.

With pyridine as a base and solvent, refluxing conditions are required.Ref|Wiley1953 However, with the addition of 4-dimethylaminopyridine (DMAP) as a catalyst, the reaction can take place at room temperature.Ref|DMAP

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 amino-ketone product.Ref|Knorr1970Ref|Allinger1974

References

# (a) Dakin, H. D.; West, R. "J. Biol. Chem." 1928, "78", 91. (b) Dakin, H. D.; West, R. "J. Biol. Chem." 1928, "78", 745. (c) Dakin, H. D.; West, R. "J. Biol. Chem." 1928, "78", 757.
# Wiley, R. H. "J. Org. Chem." 1947, "12", 43-46. (DOI|10.1021/jo01165a006)
# Buchanan, G. L. "Chem. Soc. Rev." 1988, "17", 91-109. (Review)
# Wiley, R. H.; Borum, O. H. "Organic Syntheses", Coll. Vol. 4, p.5 (1963); Vol. 33, p.1 (1953). ( [http://www.orgsyn.org/orgsyn/prep.asp?prep=cv4p0005 Article] )
# Hoefle, G.; Steglich, W.; Vorbrueggen, H. "Angew. Chem. Int. Ed. Engl." 1978, "17", 569.
# Knorr, R.; Huisgen, R. "Ber." 1970, "103", 2598.
# Allinger, N. "et al." "J. Org. Chem." 1974, "39", 1730. (DOI|10.1021/jo00925a029)