ORGANIC
LETTERS
2008
Vol. 10, No. 22
5199-5202
An Ireland-Claisen Approach to
ꢀ-Alkoxy r-Amino Acids
James P. Tellam, Gabriele Kociok-Ko¨hn, and David R. Carbery*
Department of Chemistry, UniVersity of Bath, Bath, BA2 7AY, U.K.
Received September 17, 2008
ABSTRACT
A diastereoselective Ireland-Claisen approach to ꢀ-alkoxy r-amino acid esters is reported. Amino acid esters of enol ethereal allylic alcohols
undergo facile syn-selective [3,3]-sigmatropic rearrangement via silyl ketene acetals. Substrate synthesis, rearrangement development,
stereoselectivity, and product elaboration are discussed.
ꢀ-Hydroxy-R-amino acids are biologically important mol-
ecules with two key examples, serine and threonine, taken
together representing 10% of nature’s proteinogenic amino
acids. The ꢀ-hydroxy R-amino acid unit is featured promi-
nently in a number of important natural products.1 For
example, kaitocephalin,2 sphingofungins E + F,3 altemici-
din,4 and the acyl derivatives, lactacystin,5 salinosporamide
A,6 oxazolomycin,7 and neooxazolomycin8 have represented
significant synthetic challenges in recent years. The impor-
tance of these molecules is reflected in the large number of
reported synthetic routes to ꢀ-hydroxy-R-amino acids. Strate-
gies include aldol reactions,9 enzymatic aldol reactions,10
(6) For selected recent synthetic approaches, see: (a) Caubert, V.; Masse,
J.; Retailleau, P.; Langlois, N. Tetrahedron Lett. 2007, 48, 381. (b) Endo,
A.; Danishefsky, S. J. J. Am. Chem. Soc. 2005, 127, 8298. (c) Ling, T. T.;
Macherla, V. R.; Manam, R. R.; McArthur, K. A.; Potts, B. C. M. Org.
Lett. 2007, 9, 2289. (d) Ma, G.; Nguyen, H.; Romo, D. Org. Lett. 2007, 9,
2143. (e) Margalef, I. V.; Rupnicki, L.; Lam, H. W. Tetrahedron 2008, 64,
7896. (f) Reddy, L. R.; Saravanan, P.; Corey, E. J. J. Am. Chem. Soc. 2004,
126, 6230. (g) Takahashi, K.; Midori, M.; Kawano, K.; Ishihara, J.;
Hatakeyama, S. Angew. Chem., Int. Ed. 2008, 47, 6244.
(1) (a) Kang, S. H.; Kang, S. Y.; Lee, H. S.; Buglass, A. J. Chem. ReV.
2005, 105, 4537. (b) Ohfune, Y.; Shinada, T. Eur. J. Org. Chem. 2005,
5127.
(2) For recent synthetic work, see: (a) Kawasaki, M.; Shinada, T.;
Hamada, M.; Ohfune, Y. Org. Lett. 2005, 7, 4165. (b) Takahashi, K.;
Haraguchi, N.; Ishihara, J.; Hatakeyama, S. Synlett 2008, 671. (c) Vaswani,
R. G.; Chamberlin, A. R. J. Org. Chem. 2008, 73, 1661.
(7) For recent work, see: (a) Bulger, P. G.; Moloney, M. G.; Trippier,
P. C. Org. Biomol. Chem. 2003, 1, 3726. (b) Mohapatra, D. K.; Mondal,
D.; Gonnade, R. G.; Chorghade, M. S.; Gurjar, M. K. Tetrahedron Lett.
2006, 47, 6031. (c) Papillon, J. P. B.; Taylor, R. J. K. Org. Lett. 2000, 2,
1987. (d) Wang, Z. Y.; Moloney, M. G. Tetrahedron Lett. 2002, 43, 9629.
(8) (a) Bennett, N. J.; Prodger, J. C.; Pattenden, G. Tetrahedron 2007,
63, 6216. (b) Kende, A. S.; Kawamura, K.; Devita, R. J. J. Am. Chem. Soc.
1990, 112, 4070. (c) Onyango, E. O.; Tsurumoto, J.; Imai, N.; Takahashi,
K.; Ishihara, J.; Hatakeyama, S. Angew. Chem., Int. Ed. 2007, 46, 6703.
(9) For recent aldol approaches to ꢀ-hydroxy R-amino acids, see: (a)
Ma, B.; Parkinson, J. L.; Castle, S. L. Tetrahedron Lett. 2007, 48, 2083.
(b) Willis, M. C.; Cutting, G A.; Piccio, V. J.-D.; Durbin, M. J.; John,
M. P. Angew. Chem., Int. Ed. 2005, 44, 1543. (c) Thayumanavan, R.;
Tanaka, F.; Barbas, C. F. Org. Lett. 2004, 6, 3541. (d) Kobayashi, J.;
Nakamura, M.; Mori, Y.; Yamashita, Y.; Kobayashi, S. J. Am. Chem. Soc.
2004, 126, 9192. (e) MacMillan, J. B.; Molinski, T. F. Org. Lett. 2002, 4,
1883.
(3) For recent synthetic work, see: (a) Horn, W. S.; Smith, J. L.; Bills,
G. F.; Raghoobar, S. L.; Helms, G. L.; Kurtz, M. B.; Marrinan, J. A.;
Frommer, B. R.; Thornton, R. A.; Mandala, S. M. J. Antibiot. 1992, 45,
1692. (b) Kobayashi, S.; Furuta, T.; Hayashi, T.; Nishijima, M.; Hanada,
K. J. Am. Chem. Soc. 1998, 120, 908. (c) Kobayashi, S.; Matsumura, M.;
Furuta, T.; Hayashi, T.; Iwamoto, S. Synlett 1997, 301. (d) Lee, K. Y.; Oh,
C. Y.; Ham, W. H. Org. Lett. 2002, 4, 4403. (e) Li, M.; Wu, A. M. Synlett
2006, 2985. (f) Liu, D. G.; Wang, B.; Lin, G. Q. J. Org. Chem. 2000, 65,
9114. (g) Trost, B. M.; Lee, C. B. J. Am. Chem. Soc. 1998, 120, 6818.
(4) (a) Kan, T.; Kawarnoto, Y.; Asakawa, T.; Furuta, T.; Fukuyama, T.
Org. Lett. 2008, 10, 169. (b) Kende, A. S.; Liu, K.; Brands, K. M. J. J. Am.
Chem. Soc. 1995, 117, 10597.
(5) For selected recent synthetic approaches, see: (a) Balskus, E. P.;
Jacobsen, E. N. J. Am. Chem. Soc. 2006, 128, 6810. (b) Brennan, C. J.;
Pattenden, G.; Rescourio, G. Tetrahedron Lett. 2003, 44, 8757. (c) Donohoe,
T. J.; Sintim, H.; Sisangia, L.; Harling, J. D. Angew. Chem., Int. Ed. 2004,
43, 2293. (d) Fukuda, N.; Sasaki, K.; Sastry, T.; Kanai, M.; Shibasaki, M.
J. Org. Chem. 2006, 71, 1220. (e) Page, P. C. B.; Hamzah, A. S.; Leach,
D. C.; Allin, S. M.; Andrews, D. M.; Rassias, G. A. Org. Lett. 2003, 5,
353. (f) Panek, J. S.; Masse, C. E. Angew. Chem., Int. Ed. 1999, 38, 1093.
(g) Wardrop, D. J.; Bowen, E. G. Chem. Commun. 2005, 5106.
(10) (a) Sagui, F.; Conti, P.; Roda, G.; Contestabile, R.; Riva, S.
Tetrahedron 2008, 64, 5079. (b) Steinreiber, J.; Fesko, K.; Mayer, C.;
Reisinger, C.; Schu¨rmann, M.; Griengl, H. Tetrahedron 2007, 63, 8088.
(c) Steinreiber, J.; Fesko, K.; Reisinger, C.; Schu¨rmann, M.; van Assema,
F.; Wolberg, M.; Mink, D.; Griengl, H. Tetrahedron 2007, 63, 918.
10.1021/ol802169j CCC: $40.75
Published on Web 10/18/2008
2008 American Chemical Society