ORGANIC
LETTERS
2008
Vol. 10, No. 4
565-567
Highly Stereoselective Oxy-Michael
Additions to -Unsaturated -Keto
Esters: Rapid Enantioselective
â
,
γ
r
Synthesis of 3-Hydroxybutenolides
Xin Xiong, Caroline Ovens, Adam W. Pilling, John W. Ward, and Darren J. Dixon*
School of Chemistry, The UniVersity of Manchester, Oxford Road,
Manchester M13 9PL, U.K.
Received November 6, 2007
ABSTRACT
The highly diastereoselective oxy-Michael addition of the “naked” anion of (6S)-methyl
δ
-lactol to
γ-substituted â,γ-unsaturated r-keto esters
leading to the direct formation of THP*-protected
affords the 3-hydroxybutenolides in high yields.
γ-hydroxy r-keto ester derivatives is described. Subsequent acid-mediated deprotection
The stereoselective addition of oxygen-centered nucleophiles
is an emerging area in the Michael addition field.1 Our group2
and others3 have been involved with the development of
chiral water equivalents for the addition to reactive nitro
olefin-4 and malonate-derived acceptors.5 Although useful
for the asymmetric synthesis of 1,2-amino alcohols and
protected â-hydroxy esters, we believed an extension of this
chemistry to incorporate other types of Michael acceptors,
while maintaining reaction efficiency and diastereoselectivity,
would expand significantly the utility and scope of the
reaction.
(1) For reviews, see: (a) Misra, M.; Luthra, R.; Singh, K. L.; Sushil, K.
ComprehensiVe Natural Products Chemistry; Barton, D. H. R., Nakunisha,
K., Meth-Chon, O., Eds.; Pergamon Press: Oxford, UK, 1999; Vol. 4, p
25. (b) Berkessel, A. In Houben-Weyl Methods of Organic Synthesis, Vol.
E21e; Helmchen, G., Hoffman, R. W., Mulzer, J., Schaumann, E., Eds.;
Thieme: Stuttgart, 1996; pp 4818-4856. For recent catalytic asymmetric
examples, see: (c) Dine´r, P.; Nielsen, M.; Bertelsen, S.; Niess, B.; Jørgensen
K. A. Chem. Commun. 2007, 3646-3648. (d) Kano, T.; Tanaka, Y.;
Maruola, K. Tetrahedron 2007, 63, 8658-8664. (e) Li, H.; Wang, J.;
E-Nunu, T.; Zu, L.; Jiang, W.; Wei, S.; Wang, W. Chem. Commun. 2007,
507-509. (f) Sunde´n, H.; Ibrahem, I.; Zhao, G.-L.; Eriksson, L.; Co´rdova,
A. Chem. Eur. J. 2007, 13, 574-581. (g) Vanderwal, C. D.; Jacobsen, E.
N. J. Am. Chem. Soc. 2004, 126, 14724-14725. (h) Govender, T.; Hojabri,
L.; Moghaddam, F. M.; Arvidsson, P. I. Tetrahedron: Asymmetry 2006,
17, 1763-1767. For a phosphine-catalyzed example, see: (i) Stewart, I.
C.; Bergman, R. G.; Toste, F. D. J. Am. Chem. Soc. 2003, 125, 8696-
8697.
(2) (a) Adderley, N. J.; Buchanan, D. J.; Dixon, D. J.; Laine´, D. I. Angew.
Chem., Int. Ed. 2003, 35, 4241-4244. (b) Buchanan, D. J.; Dixon, D. J.;
Scott, M. S.; Laine´, D. I. Tetrahedron: Asymmetry 2004, 15, 195-197.
(c) Buchanan, D. J.; Dixon, D. J.; Hernandez-Juan, F. Org. Lett. 2004, 6,
1357-1360. (d) Buchanan, D. J.; Dixon, D. J.; Hernandez-Juan, F. Org.
Biomol. Chem. 2004, 2, 2932-2934. (e) Buchanan, D. J.; Dixon, D. J.;
Looker, B. E. Synlett 2005, 1948-1950. (f) Hernandez-Juan, F. A.; Xiong,
X.; Brewer, S. E.; Buchanan, D. J.; Dixon, D. J. Synthesis 2005, 3283-
3286. (g) Hernandez-Juan, F. A.; Richardson, R. D.; Dixon, D. J. Synlett
2006, 2673-2675.
(3) (a) Enders, D.; Haertwig, A.; Raabe, G.; Runsink, J. Angew. Chem.,
Int. Ed. 1996, 35, 2388-2390. (b) Enders, D.; Haertwig, A.; Raabe, G.;
Runsink, J. Eur. J. Org. Chem. 1998, 1771-1792. (c) Enders, D.; Haertwig,
A.; Runsink, J. Eur. J. Org. Chem. 1998, 1793-1801.
(4) For diastereoselective/non-enantioselective additions to nitro olefin
acceptors, see: (a) Dumez, E.; Faure, R.; Dulce`re, J.-P. Eur. J. Org. Chem.
2001, 2577-2588. (b) Yakura, T.; Tsuda, T.; Matsumura, Y.; Yamada, S.;
Ikeda, M. Synlett 1996, 985-986.
(5) For non-enantioselective additions of oxygen-centred nucleophiles
to benzylidene-(or alkylidene-)malonates and related Michael acceptors
see: (a) Cavicchioli, M.; Marat, X.; Monteiro, N.; Hartmann, B.; Balme,
G. Tetrahedron Lett. 2002, 43, 2609-2611. (b) Marat, X.; Monteiro, N.;
Balme, G. Synlett 1997, 845-847. (c) Monteiro, N.; Balme, G. J. Org.
Chem. 2000, 65, 3223-3226. For an asymmetric diastereoselective substrate
controlled addition of achiral oxygen-centred nucleophiles, see, for ex-
ample: (d) Paquette, L. A.; Tae, J.; Arrington, M. P.; Sadoun, A. H. J. Am.
Chem. Soc. 2000, 122, 2742-2748. For an interesting (non-enantioselective)
synthesis of tetrahydrofurans using an oxy-Michael/Michael cyclization
strategy, see: (e) Greatrex, B. W.; Kimber, M. C.; Taylor, D. K.; Tiekink,
R. T. J. Org. Chem. 2003, 68, 4239-4246.
10.1021/ol702693m CCC: $40.75
© 2008 American Chemical Society
Published on Web 01/23/2008