Communications
[10] A proline-catalyzed trimerization of propionaldehyde to form
nearly racemic tetrahydropyrans in good diastereoselectivities
with low yields has been reported: N. S. Chowdari, D. B.
Ramachary, A. Cordova, C. F. Barbas III, Tetrahedron Lett.
2002, 43, 9591.
[11] For examples of metal-mediated direct aldol reactions see:
a) Y. M. A. Yamada, N. Yoshikawa, H. Sasai, M. Shibasaki,
Angew. Chem. 1997, 109, 1290; Angew. Chem. Int. Ed. Engl.
1997, 36, 1871;b) N. Yoshikawa, N. Kumagai, S. Matsunaga, G.
Moll, T. Oshima, T. Suzuki, M. Shibasaki, J. Am. Chem. Soc.
2001, 123, 2466;c) N. Kumagai, S. Matsunaga, N. Yoshikawa, T.
Oshima, M. Shibasaki, Org. Lett. 2001, 3, 1539;d) B. M. Trost, H.
Ito, J. Am. Chem. Soc. 2000, 122, 12003;e) B. M. Trost, E. R.
Silcoff, H. Ito, Org. Lett. 2001, 3, 2497;f) D. A. Evans, J. S.
Tedrow, J. T. Shaw, C. W. Downey, J. Am. Chem. Soc. 2002, 124,
392;g) G. Lalic, A. Aloise, M. Shair, J. Am. Chem. Soc. 2003,
125, 2852.
readily participate in enamine formation (entries 5 and 6,
ꢀ 33% yield ꢀ 7:1 anti:syn, 96–99% ee). It should be noted,
however, that significant quantities of the homodimers 2 f and
2b were generated in these respective cases.
These organocatalytic results stand in marked contrast to
metal-mediated direct aldol technologies[11] where the
increased acidity and nucleophilicity afforded by a-oxygen-
ated aldol donors greatly enhances their effectiveness relative
to their all-alkyl counterparts. We are currently investigating
the mechanistic origins of such divergent reactivity between
metal and organic catalysts in aldol reactions with a-oxy-
genated substrates.
In summary, we have documented the first direct enan-
tioselective catalytic aldol reaction using a-oxygenated alde-
hydes as both the aldol donor and the aldol acceptor.
Significantly, this method allows direct and enantioselective
access to differentially protected polyols and monoprotected
anti-1,2 diols. A full account of these studies will be presented
in due course.
Received: January 9, 2004 [Z53716]
Published Online: March 22, 2004
Keywords: aldehydes · aldol reaction · carbohydrates ·
.
enantioselectivity · homogeneous catalysis
[1] a) Glycoscience: Chemistry and Chemical Biology I-III (Eds.: B.
Fraser-Reid, K. Tatsuta, J. Thiem), Springer, 2001;b) Glyco-
chemistry: Principles, Synthesis, and Applications (Eds.: P. Wang,
C. Bertozzi), Marcel Dekker, 2001.
[2] While the term carbohydrate can be applied to many hydrated
forms of carbon structure, we employ this terminology in the
more commonly used and specific sense to describe hexose
architecture.
[3] a) K. M. Koeller, C.-H. Wong, Chem. Rev. 2000, 100, 4465;
b) K. C. Nicolaou, H. J. Mitchel, Angew. Chem. 2001, 113, 1624;
Angew. Chem. Int. Ed. 2001, 40, 1576.
[4] For some reviews of the aldol reaction, see: a) B. Alcaide, P.
Almendros, Eur. J. Org. Chem. 2002, 10, 1595;b) T. D. Macha-
jewski, C.-H. Wong, Angew. Chem. 2000, 112, 1406; Angew.
Chem. Int. Ed. 2000, 39, 1352;c) R. Mahrwald, Chem. Rev. 1999,
99, 1095;d) D. A. Evans, J. V. Nelson, T. Taber in Topics in
Stereochemistry, Vol. 13, Wiley, 1982, p. 1.
[5] For recent examples of aldol reactions in the syntheses of
carbohydrates, see: a) D. A. Evans, E. Hu, J. S. Tedrow, Org.
Lett. 2001, 3, 3133;b) S. G. Davies, R. L. Nicholson, A. D. Smith,
Synlett 2002, 10, 1637;c) M. P. Sibi, J. Lu, J. Edwards, J. Org.
Chem. 1997, 62, 5864;d) for a review of aldolase enzymes in
carbohydrate synthesis, see: S. Takayama, G. J. McGarvey, C.-H.
Wong, Chem. Soc. Rev. 1997, 26, 407.
[6] A two-step carbohydrate synthesis has recently been accom-
plished in our laboratories. Details of this work will be published
at a later date.
[7] For examples of enamine-catalyzed aldol reactions between a-
oxyketones and -aldehydes, see: a) W. Noltz, B. List, J. Am.
Chem. Soc. 2000, 122, 7386;b) K. Sakthivel, W. Notz, T. Bui,
C. F. Barbas III, J. Am. Chem. Soc. 2001, 123, 5260.
[8] A. B. Northrup, D. W. C. MacMillan, J. Am. Chem. Soc. 2002,
124, 6798.
[9] For uses of erythrose in synthesis, see: a) W. H. Pearson, E. J.
Hembre, J. Org. Chem. 1996, 61, 7217;b) M. Ruiz, V. Ojea, J. M.
Quintela, Synlett 1999, 2, 204;c) J. G. Buchanan, A. R. Edgar,
B. D. Hewitt, J. Chem. Soc. Perkin Trans. 1 1987, 2371.
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ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2004, 43, 2152 –2154