ORGANIC
LETTERS
2
001
Vol. 3, No. 10
559-1562
Catalytic Enantioselective Diels−Alder
Reactions of 1,4-Quinone Monoketals
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Matthias Breuning and E. J. Corey*
Department of Chemistry and Chemical Biology, HarVard UniVersity,
12 Oxford Street, Cambridge, Massachusetts 02138
Received March 15, 2001
ABSTRACT
Achiral 1,4-quinone monoketals function well as dienophiles in enantioselective Diels−Alder reactions catalyzed by a chiral Ti(IV) Lewis acid.
For more than six decades the Diels-Alder reaction subtype
In each of these cases the initial Diels-Alder reaction
generated a racemic adduct from which the synthesis of the
chiral natural product was possible only with an intervening
resolution step and the usual loss of material (>50%). At
present, methodology is not available for conducting the key
quinone Diels-Alder reactions for these syntheses under
circumstances that would lead enantioselectively to chiral
adducts. This gap in methodology has persisted despite the
great progress that has been made in recent years in the
development of enantioselective versions of other Diels-
involving quinones as dienophiles has provided a powerful
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construction for functionalized cis-fused decalin systems.
Many syntheses of complex natural products have been
recorded in which the quinone Diels-Alder reaction has been
used to set in place an initial arrangement of rings and
stereocenters, paving the way for elaboration of the final
target structure by a subsequent series of selective reactions.
Examples include some of the most notable achievements
2
in complicated synthetic chemistry, for instance: steroids,
3
4
5
6
10
reserpine, ibogamine, dendrobine, gibberellic acid, tri-
Alder subtypes involving chiral Lewis acid catalysts. It
7
8,9
chodermol, and euonyminol.
seems likely that most of the chiral catalysts developed thus
far for Diels-Alder reactions are ineffective for controlling
enantioselection with quinones as dienophiles. In fact, only
a few examples of such enantioselective reactions have
(
1) Alder, K. The Diene Synthesis. In Newer Methods of PreparatiVe
Organic Chemistry; Interscience Publishers: New York, 1948; p 381.
2) Woodward, R. B.; Sondheimer, F.; Taub, D. J. Am. Chem. Soc. 1952,
4, 4223.
3) Woodward, R. B.; Bader, R. E.; Bickel, H.; Frey, A. J.; Kierstead,
R. W. Tetrahedron 1958, 2, 1.
(
7
appeared in the literature to our knowledge (see, e.g., Scheme
(
11,12
1
).
The catalyst used was that derived from the reaction
Ti(Oi-Pr) in the presence of 4 Å
of (R)-BINOL with Cl
2
2
(4) Salley, S. I. J. Am. Chem. Soc. 1967, 89, 6762.
(
5) Kende, A. S.; Bently, T. J.; Mader, R. A.; Ridge, D. J. Am. Chem.
Soc. 1978, 100, 3599.
6) Corey, E. J.; Danheiser, R. L.; Chandrasekaran, S.; Siret, P.; Keck,
G. E.; Gras, J.-L. J. Am. Chem. Soc. 1978, 100, 8031.
(10) (a) Carmona, D.; Pilar Lamata, M.; Oro, L. A. Coord. Chem. ReV.
2000, 717. (b) Corey, E. J.; Guzman-Perez, A. Angew. Chem., Int. Ed. 1998,
37, 388. (c) Kagan, H. B.; Riant, O. Chem. ReV. 1992, 92, 1007. (d) Pindur,
U.; Lutz, G.; Otto, C. Chem. ReV. 1993, 93, 741. (e) Deloux, L.; Srebnik,
M. Chem. ReV. 1993, 93, 763. (f) Narasaka, K. Synthesis 1991, 1.
(11) (a) Mikami, K.; Terada, M.; Motoyama, Y.; Nakai, T. Tetrahe-
dron: Asymmetry 1991, 2, 643. (b) Mikami, K.; Motoyama, Y.; Terada,
M. J. Am. Chem. Soc. 1994, 116, 2812. (c) White, J. D.; Choi, Y. Org.
Lett. 2000, 2, 2373.
(
(
(
7) Still, W. C.; Tsai, M. Y. J. Am. Chem. Soc. 1980, 102, 3654.
8) White, J. D.; Cutshall, N. S.; Kim, T. S.; Shin, H. J. Am. Chem. Soc.
1
995, 117, 9780.
(
9) For further examples of 1,4-quinone Diels-Alder reactions in natural
product synthesis, see: (a) Bird, C. W.; Brown, A. L.; Chan, C. C.; Lewis,
A. Tetrahedron Lett. 1989, 30, 6223. (b) Roush, W. R. J. Am. Chem. Soc.
1
978, 100, 3599. (c) Oda, K.; Ichihara, A.; Sakamura, S. Tetrahedron Lett.
975, 16, 3187. (d) Ichihara, A.; Oda, K.; Kobayashi, M.; Sakamura, S.
(12) (a) Engler, T. A.; Letavic, M. A.; Lynch, K. O. Jr.; Takusagawa, F.
J. Org. Chem. 1994, 59, 1179. (b) Engler, T. A.; Letavic, M. A.;
Takusagawa, F. Tetrahedron Lett. 1992, 33, 6731.
1
Tetrahedron Lett. 1974, 15, 4235.
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0.1021/ol015852y CCC: $20.00 © 2001 American Chemical Society
Published on Web 04/04/2001