179

DakinWest reaction

The direct conversion of an D-amino acid into the corresponding D-acetylamino-alkyl methyl ketone, via oxazoline (azalactone) intermediates. The reaction pro-ceeds in the presence of acetic anhydride and a base such as pyridine with the evo-lution of CO2.

R CO2H

NH2

Ac2O R

NHAc

O

CO2n

R CO2H

NH2

O

OO

R

HN

O

OH

O

OO

AcO

R

NH

OOH

OH+

:

H

NO

R OHO

H

NO

RO OH

O

NO

RO

H

O

OH

AcO H

H

oxazolone (azalactone) intermediate

HN O

RO

O

O

H N OH

ROH

R

NHAc

OCO2 tautomerization

Example 112

Me CO2H

NH2Me

NHAcMe

OAc2O, AcOH, Et3N

DMAP, 50 oC, 14 h, > 90%

180

Example 214

NH

OBn

O OOHO Ac2O, pyr.

90 oC, 2 h, 58%NH

OBn

O OOMe

References:

1. Dakin, H. D.; West, R. J. Biol. Chem. 1928, 78, 91, 745, and 757. In 1928, Henry Da-kin and Rudolf West, a clinician, reported on the reaction of D-amino acids with acetic anhydride to give D-acetamido ketones via azalactone intermediates. Interestingly, one year before this paper by Dakin and West, Levene and Steiger had observed both tyrosine and D-phenylananine gave abnormal products when acetylated under these conditions.2,3 Unfortunately, they were slow to identify the products and lost an op-portunity to be immortalized by a name reaction.

2. Levene, P. A.; Steiger, R. E. J. Biol. Chem. 1927, 74, 689. 3. Levene, P. A.; Steiger, R. E. J. Biol. Chem. 1928, 79, 95. 4. Cornforth, J. W.; Elliott, D. F. Science 1950, 112, 534. 5. Allinger, N. L.; Wang, G. L.; Dewhurst, B. B. J. Org. Chem. 1974, 39, 1730. 6. Buchanan, G. L. Chem. Soc. Rev. 1988, 17, 91. (Review). 7. Jung, M. E.; Lazarova, T. I. J. Org. Chem. 1997, 62, 1553. 8. Kawase, M.; Hirabayashi, M.; Koiwai, H.; Yamamoto, K.; Miyamae, H. Chem. Com-

mun. 1998, 641. 9. Kawase, M.; Okada, Y.; Miyamae, H. Heterocycles 1998, 48, 285. 10. Kawase, M.; Hirabayashi, M.; Kumakura, H.; Saito, S.; Yamamoto, K. Chem. Pharm.

Bull. 2000, 48, 114. 11. Kawase, M.; Hirabayashi, M.; Saito, S. Recent Res. Dev. Org. Chem. 2001, 4,. (Review).

12. Fischer, R. W.; Misun, M. Org. Proc. Res. Dev. 2001, 5, 581. 13. Orain, D.; Canova, R.; Dattilo, M.; Klppner, E.; Denay, R.; Koch, G.; Giger, R.

Synlett 2002, 1443. 14. Godfrey, A. G.; Brooks, D. A.; Hay, L. A.; Peters, M.; McCarthy, J. R.; Mitchell, D. J.

Org. Chem. 2003, 68, 2623. 15. Khodaei, M. M.; Khosropour, A. R.; Fattahpour, P. Tetrahedron Lett. 2005, 46, 2105.