ORGANIC
LETTERS
2002
Vol. 4, No. 7
1221-1223
Catalytic, Asymmetric trans-Selective
Hetero Diels−Alder Reactions Using a
Chiral Zirconium Complex
Yasuhiro Yamashita, Susumu Saito, Haruro Ishitani, and Shu¯ Kobayashi*
Graduate School of Pharmaceutical Sciences, The UniVersity of Tokyo, CREST,
Japan Science and Technology Corporation (JST), Hongo, Bunkyo-ku,
Tokyo 113-0033, Japan
Received February 19, 2002
ABSTRACT
The first catalytic, asymmetric 2,3-trans-selective hetero Diels−Alder reaction has been developed. The reactions of aldehydes with Danishefsky’s
dienes proceeded smoothly to afford the pyranone derivatives in high yields with high trans-selectivities and enantioselectivities in the presence
of a chiral zirconium complex, which was prepared from zirconium tert-butoxide and (R)-3,3′-diiodobinaphthol or its derivatives, primary
alcohol, and a small amount of water. This reaction was applied to the concise synthesis of (+)-prelactone C.
Hetero Diels-Alder (HDA) reactions of aldehydes with
1-alkoxy-3-trialkylsilyloxy-1,3-butadiene (Danishefsky’s di-
ene) mediated by a chiral Lewis acid provide one of the most
powerful synthetic tools to construct chiral 2,3-dihydro-4H-
pyranone derivatives.1 Recently, some effective chiral cata-
lysts for HDA reactions have been developed and applied
to the total synthesis of natural products.2 However, the main
products of the HDA reactions are 3-unsubstituted or 2,3-
cis-disubstituted pyranone derivatives in most cases, and no
catalyst system to afford trans-2,3-disubstituted products has
been reported.3 In this Letter, we report the first catalytic,
asymmetric trans-selective HDA reactions of aldehydes using
a chiral zirconium catalyst.
We have recently shown that several chiral zirconium
complexes having 1,1′-bi-2-naphthol (BINOL) moieties are
effective catalysts for asymmetric carbon-carbon bond-
forming reactions such as Mannich reactions,4 aza Diels-
Alder reactions,5 Strecker reactions,6 allylation reactions,7
(1) Reviews: (a) Danishefsky, S. J. Chemtracts: Org. Chem. 1989, 273.
(b) Danishefsky, S. J. Aldrichimica Acta 1986, 19, 59. (c) Boger, D. L. In
ComprehensiVe Organic Synthesis; Trost B. M., Ed.; Pergamon Press:
Oxford, 1991; Vol. 5, p 451. (d) Waldmann H. Synthesis 1994, 535. (e)
Jørgensen, K. A. Angew. Chem., Int. Ed. 2000, 39, 3558.
(2) For catalytic asymmetric HDA reactions of aldehydes involving
Danishefsky’s diene and its analogues, see: (a) Bednarski, M.; Danishefsky,
S. J. J. Am. Chem. Soc. 1983, 105, 3716. (b) Bednarski, M.; Danishefsky,
S. J. J. Am. Chem. Soc. 1986, 108, 7060. (c) Maruoka, K.; Itoh, T.;
Shirasaka, T.; Yamamoto, H. J. Am. Chem. Soc. 1988, 110, 310. (d) Togni,
A. Organometallics 1990, 9, 3106. (e) Corey, E. J.; Cywin, C. L.; Roper,
T. D. Tetrahedron Lett. 1992, 33, 6907. (f) Gao, Q.; Ishihara, K.; Maruyama,
T.; Mouri, M.; Yamamoto, H. Tetrahedron. 1994, 50, 979. (g) Keck, G.
E.; Li, X.-Y.; Krishnamurthy, D. J. Org. Chem. 1995, 60, 5998. (h)
Matsukawa, S.; Mikami, K. Tetrahedron: Asymmetry. 1997, 8, 815. (i)
Hanamoto, T.; Furuno, H.; Sugimoto, Y.; Inanaga, J. Synlett 1997, 79. (j)
Schaus, S. E.; Brånalt, J.; Jacobsen, E. N. J. Org. Chem. 1998, 63, 403. (k)
Dossetter, A. G.; Jamison, T. F.; Jacobsen, E. N. Angew. Chem., Int. Ed.
1999, 38, 2398. (l) Simonsen, K. B.; Svenstrup, N.; Roberson, M.; Jørgensen,
K. A. Chem. Eur. J. 2000, 6, 123. (m) Aikawa, K.; Irie, R.; Katsuki, T.
Tetrahedron 2001, 57, 845. (n) Kezuka, S.; Mita, T.; Ohtsuki, N.; Ikeno,
T.; Yamada, T. Bull. Chem. Soc. Jpn. 2001, 74, 1333.
(3) trans-Selective HDA reactions of aldehydes mediated by achiral
Lewis acids have been reported. (a) Danishefsky, S. J.; Larson, E.; Askin,
D.; Kato, N. J. Am. Chem. Soc. 1985, 107, 1246. (b) Mujica, M. T.; Afonso,
M. M.; Galindo, A.; Palenzuela, J. A. Tetrahedron 1996, 52, 2167. trans-
Selective catalytic asymmetric aza Diels-Alder reactions have been
reported. (c) Yao, S.; Johannsen, M.; Hazell, R. G.; Jørgensen, K. A. Angew.
Chem., Int. Ed. 1998, 37, 3121.
10.1021/ol025745j CCC: $22.00 © 2002 American Chemical Society
Published on Web 03/15/2002