ORGANIC
LETTERS
2
000
Vol. 2, No. 10
461-1463
An Enantioconvergent Route to
−)-Shikimic Acid via a
1
(
Palladium-Mediated Elimination Reaction
Naoyuki Yoshida and Kunio Ogasawara*
Pharmaceutical Institute, Tohoku UniVersity, Aobayama, Sendai 980-8578, Japan
Received March 14, 2000
ABSTRACT
(−)-Shikimic acid, the key intermediate in the shikimate pathway in plants and microorganisms, has been synthesized in an enantioconvergent
manner from both enantiomeric starting materials by employing a palladium-mediated elimination reaction as the key step.
1
We found a novel palladium-mediated reaction to convert
the cis-1,4-enediol monoacetate (+)-1 into the R,â-unsatur-
ated ketone (-)-2 by elimination of acetic acid involving a
suprafacial 1,4-hydrogen shift, without losing its original
chiral integrity (Scheme 1).
enantiomeric purity (Scheme 2). In this paper we report a
diastereoselective synthesis of (-)-shikimic acid 5, starting
4
from either of the resolved products, (+)-3 and (+)-4 and
by employing the palladium-mediated reaction above as the
key step. (-)-Shikimic acid is the pivotal biogenetic precur-
sor in the biosynthesis of a variety of aromatic natural
products in the biogenetic pathway in plants and microorgan-
5
isms known as the shikimate pathway.
Scheme 1
To acetylate the more hindered hydroxy functionality, the
diol (+)-3 (>97% ee) was first silylated at the less hindered
2
9
site and then acetylated to give (+)-6, [R]
D
+35.5 (c 0.97,
CHCl ), which was further desilylated to give the desired
3
(
2) Yoshida, N.; Konno, H.; Kamikubo, T.; Takahashi, M.; Ogasawara,
K. Tetrahedron: Asymmetry 1999, 10, 3849.
3) White, J. D.; Shin, H.; Kim, T.-S.; Cutshall, N. S. J. Am. Chem. Soc.
997, 119, 2404.
4) For pertinent reviews on the synthesis of shikimic acid, see:
(
1
(
Campbell, M. M.; Sainsbury, M.; Searle, P. A. Synthesis 1993, 179. Jiang,
S.; Singh, G. Tetrahedron 1998, 54, 4697. For more recent syntheses, see:
(a) Adrio, J.; Carretero, J. C.; Ruano, J. L. G.; Cabrejas, L. M. M.
Tetrahedron: Asymmetry 1997, 8, 1623. (b) Fernandez, S.; Diaz, M.;
Ferrero, M.; Gotor, V. Tetrahedron Lett. 1997, 38, 5225. (c) Mehta, G.;
Mohal, N. Tetrahedron Lett. 1998, 39, 3285. (d) Shinada, T.; Yoshida, Y.;
Ohfune, Y. Tetrahedron Lett. 1998, 39, 6027. (e) Refence 4b. (f) Alves,
C.; Barros, M. T.; Maycock, C. D.; Ventura, M. R. Tetrahedron 1999, 55,
2
Quite recently, we also found that the tricyclic diol (()-
3
3
, readily prepared from methyl 2,5-dihydroxybenzoate, is
resolved under lipase-mediated transesterification conditions
to give the acetate (+)-4 and the alcohol (+)-3 in high
8
443. For alternative enantiocontrolled syntheses developed by the present
(
1) (a) Takano, S.; Higashi, Y.; Moriya, M.; Ogasawara, K. J. Chem.
group, see: (g) Kamikubo, T.; Ogasawara, K. Chem. Lett. 1996, 987. (h)
Hiroya, K.; Ogasawara, K. Chem. Commun. 1998, 2033.
(5) Haslam, E. Progress in the Chemistry of Organic Natural Products;
Herz, W., Kirby, G. W., Moore, R. E., Steglich, W., Tamm, C., Eds.;
Springer-Verlag: New York, 1996; Vol. 69, p 158. Dewick, P. M. Nat.
Prod. Rep. 1998, 15, 17 and references therein.
Soc., Chem. Commun. 1993, 788. (b) Takano, S.; Higashi, Y.; Kamikubo,
T.; Moriya, M.; Ogasawara, K. Synthesis 1993, 948. (c) Takano, S.; Moriya,
M.; Kamikubo, T.; Hiroya, K.; Ogasawara, K. Tetrahedron Lett. 1993, 34,
485. (d) Kamikubo, T.; Shimizu, M.; Ogasawara, K. Enantiomer 1997, 2,
97.
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2
1
0.1021/ol005805q CCC: $19.00 © 2000 American Chemical Society
Published on Web 04/26/2000