ORGANIC
LETTERS
2006
Vol. 8, No. 10
2019-2021
Regiospecific Hydration of
-Hydroxy- -acetylenic Esters: A
γ
r,â
Novel Asymmetric Synthesis of Tetronic
Acids
Amaresh R. Rajaram and Lin Pu*
Department of Chemistry, UniVersity of Virginia, CharlottesVille, Virginia 22904-4319
lp6n@Virginia.edu
Received February 13, 2006
ABSTRACT
The optically active
γ-hydroxy-r,â-acetylenic esters are obtained from the enantioselective reaction of methyl propiolate with both aliphatic
and aromatic aldehydes. These compounds can undergo regiospecific hydration in the presence of Zeise’s dimer, [PtCl2(C2H4)]2, to generate
the optically active tetronic acids.
Optically active γ-hydroxy-R,â-acetylenic esters are a class
of highly functional compounds with versatile synthetic ap-
plications.1,2 These compounds are generally prepared by
Scheme 1. Synthesis of Optically Active
γ-Hydroxy-R,â-acetylenic Esters by Asymmetric Reduction
oxidation of the racemic γ-hydroxy-R,â-acetylenic esters to
the corresponding γ-oxo-R,â-acetylenic esters followed by
asymmetric reduction (Scheme 1).2 The racemic γ-hydroxy-
R,â-acetylenic esters are normally prepared from the treat-
ment of a propynoate, e.g., methyl propiolate, with nBuLi at
very low temperature, often e -78 °C, followed by addition
to an aldehyde.1a Although it would be much more efficient
to synthesize the optically active γ-hydroxy-R,â-acetylenic
esters by the asymmetric addition of methyl propiolate to
aldehydes, no such process was developed until recently.3,4
We discovered that 1,1′-bi-2-naphthol (BINOL) in combina-
(1) (a) Midland, M. M.; Tramontano, A.; Cable, J. R. J. Org. Chem.
tion with Et2Zn, Ti(OiPr)4, and HMPA can catalyze the
1980, 45, 28-29. (b) Molander, G. A.; St. Jean, D. J., Jr. J. Org. Chem.
2002, 67, 3861-3865. (c) Trost, B. M.; Ball, Z. T. J. Am. Chem. Soc. 2004,
highly enantioselective reaction of methyl propiolate with
aromatic aldehydes at room temperature (Scheme 2).3 In this
paper, we describe a further expansion of the scope of the
substrates for this reaction to include various types of ali-
126, 13942-13944. (e) Tejedor, D.; Garcia-Tellado, F.; Marrero-Tellado,
J. J.; de Armas, P. Chem. Eur. J. 2003, 9, 3122-3131. (f) Meta, C. T.;
Koide, K. Org. Lett. 2004, 6, 1785-1787.
(2) (a) Midland, M. M.; McDowell, D. C.; Hatch, R. L.; Tramontano,
A. J. Am. Chem. Soc. 1980, 102, 867-869. (b) Noyori, R.; Yamada, T.
M.; Nishizawa, M. J. Am. Chem. Soc. 1984, 106, 6717-6725. (c) Duvold,
T.; Rohmer, M. Tetrahedron Lett. 2000, 41, 3875-3878. (d) Mulzer, J.;
Csybowski, M.; Bats, J.-W. Tetrahedron Lett. 2001, 42, 2961-2964. (e)
Johansson, M.; B. Ko¨pcke, B.; Anke, H.; Sterner, O. Tetrahedron 2002,
58, 2523-2528.
(3) Gao, G.; Wang, Q.; Yu, X.-Q.; Xie, R.-G.; Pu, L. Angew. Chem.,
Int. Ed. 2005, 45, 122-125.
(4) Trost, B. M.; Weiss, A. H.; von Wangelin, A. J. J. Am. Chem. Soc.
2006, 128, 8-9.
10.1021/ol060377v CCC: $33.50
© 2006 American Chemical Society
Published on Web 04/15/2006