variety of natural products.7 The selective formation of the
exo-isomer has long proven to be difficult.8 For instance,
the Diels-Alder reactions of cyclopentadiene with acrolein,
methyl acrylate, and methyl vinyl ketone all afford predomi-
nantly the endo-isomer. This endo-selectivity is enhanced
by Lewis acid.9 Even in the recently developed Diels-Alder
reaction catalyzed by organocatalyst,10 selective formation
of the exo-isomer can be a challenging problem; MacMillan
reported the first asymmetric Diels-Alder reaction catalyzed
by organocatalyst of cyclopentadiene and R,â-unsaturated
aldehydes which proceeded with excellent enantioselectivity
in spite of low diastereoselectivity.10a On the other hand,
Maruoka and co-workers reported an elegant exo- and
enantioselective Diels-Alder reaction catalyzed by binaph-
thyl-based diamine salts.10h While excellent exo- and enan-
tioselectivities were achieved, the scope was limited to
cyclopentadiene and three R,â-unsaturated aldehydes. De-
velopment of an exo-selective and enantioselective Diels-
Alder reaction of wider generality is desirable. In this paper,
we will disclose such a reaction using the catalyst diaryl-
prolinol silyl ether.
Figure 1. The diphenylprolinol-organocatalysts examined in this
study.
our5 groups. We have found that they promote the enanti-
oselective Michael reaction of nitroalkene and aldehyde to
afford the adduct with excellent diastereo- and enantio-
selectivities.5aEnders and co-workers elegantly applied this
reaction to a triple-cascade organocatalytic reaction for the
synthesis of chiral cyclohexanecarbaldehydes.6i Recently we
reported that diphenylprolinol silyl ether catalyzes the
enantioselective ene reaction of an R,â-unsaturated aldehyde
with cyclopentadiene to afford substituted cyclopentadienes
with excellent enantioselectivity (Scheme 1).5b In the course
As a model we studied the reaction of cinnamaldehyde
and cyclopentadiene in the presence of several diarylprolinol
silyl ethers (results summarized in Table 1). As we have
reported, in the presence of p-nitrophenol the tert-butyldim-
ethylsilyl ether of diphenylprolinol (1) is an effective catalyst
of an enantioselective ene reaction, affording the cyclopen-
tadiene derivative 4 with excellent enantioselectivity (Scheme
1).5b
Scheme 1. Asymmetric Ene Reaction
However when the reaction was performed under acidic
conditions, its course changed dramatically. When cinna-
maldehyde and cyclopentadiene were treated with catalyst
1 in the presence of CF3CO2H in toluene, the cyclopentadiene
derivative 4 was not formed but rather Diels-Alder adduct
of developing this reaction further, we happened to find that
an exo- and enantioselective Diels-Alder reaction proceeds
on changing the reaction conditions. That is, in the presence
of an acid catalyst, the Diels-Alder reaction becomes the
principle pathway, affording the exo-isomer with high
diastereo- and excellent enantioselectivities.
The Diels-Alder reaction is a synthetically powerful
method for the construction of regio and stereochemically
defined cyclohexane frameworks, key components of a wide
(7) For recent reviews of enantioselective Diels-Alder reactions: (a)
Evans, D. A.; Johnson, J. S. In ComprehensiVe Asymmetric Catalysis;
Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: New York,
1999; Vol. 3, p 1177. (b) Oppolzer, W. In ComprehensiVe Organic Synthesis;
Trost, B. M., Ed.; Pergamon Press: New York, 1991; Vol. 5. (c) Kagan,
H. B.; Riant, O. Chem. ReV. 1992, 92, 1007. (d) Diaz, L. C.; Braz. J. Chem.
Soc. 1997, 8, 289. (e) Corey, E. J. Angew. Chem., Int. Ed. 2002, 41, 1650.
(f) Nicolaou, K. C.; Snyder, S. A.; Montagnon, T.; Vassilikogiannakis, G.
Angew. Chem., Int. Ed. 2002, 41, 1668. (g) Hayashi, Y. Catalytic
Asymmetric Diels-Alder Reactions. In Cycloaddition Reaction in Organic
Synthesis; Kobayashi, S., Jørgensen, K.A., Eds.; Wiley-VCH: Weinheim,
Germany, 2002; pp 5-55.
(8) (a) Gouverneur, V. E.; Houk, K. N.; de Pascual-Teresa, B.; Beno,
B.; Janda, K. D.; Lerner, R. A. Science 1993, 262, 204. (b) Powers, T. S.;
Jiang, W.; Su, J.; Wulff, W. D.; Waltermire, B. E.; Rheingold, A. L. J.
Am. Chem. Soc. 1997, 119, 6438. (c) Maruoka, K.; Imoto, H.; Yamamoto,
H. J. Am. Chem. Soc. 1994, 116, 12115. (d) Kundig, E. P.; Saudan, C. M.;
Alezra, V.; Viton, F.; Bernardinelli, G. Angew. Chem., Int. Ed. 2001, 40,
4481. (e) Cavill, J. L.; Peters, J.-U.; Tomkinson, N. C. O. Chem. Commun.
2003, 728.
(9) Smith, M. B.; March, J. March’s AdVanced Organic Chemistry, 5th
ed.; John Wiley & Sons, Inc.: New York, 2001; pp 1062-1075.
(10) (a) Ahrendt, K. A.; Borths, C. J.; MacMillan, D. W. C. J. Am. Chem.
Soc. 2000, 122, 4243. (b) Northup, A. B.; MacMillan, D. W. C. J. Am.
Chem. Soc. 2002, 124, 2458. (c) Ishihara, K.; Nakano, K. J. Am. Chem.
Soc. 2005, 127, 10504. (d) Wilson, R. M.; Jen, W. S.; MacMillan, D. W.
C. J. Am. Chem. Soc. 2005, 127, 11616. (e) Kim, K. H.; Lee, S.; Lee, D.-
W.; Ko, D.-H.; Ha, D.-C. Tetrahedron Lett. 2005, 46, 5991. (f) Lemay,
M.; Ogilvie, W. W. Org. Lett. 2005, 7, 4141. (g) Sakakura, A.; Suzuki, K.;
Nakano, K.; Ishihara, K. Org. Lett. 2006, 8, 2229. (h) Kano, T.; Tanaka,
Y.; Maruoka, K. Org. Lett. 2006, 8, 2687. (i) Sakakura, A.; Suzuki, K.;
Ishihara, K. AdV. Synth. Catal. 2006, 348, 2457.
(6) Other group’s application of diarylprolinol ether, see; (a) Chi, Y.;
Gellman, S. H. Org. Lett. 2005, 7, 4253. (b) Sunden, H.; Ibrahem, I.;
Cordova, A. Tetrahedron Lett. 2006, 47, 99. (c) Ibrahem, I.; Cordova, A.
Chem. Commun. 2006, 1760. (d) Govender, T.; Hojabri, L.; Moghaddam,
F. M.; Arvidsson, P. I. Tetrahedron: Asymmetry 2006, 17, 1763. (e) Chi,
Y.; Gellman, S. H. J. Am. Chem. Soc. 2006, 128, 6804. (f) Zu, L.; Li, H.;
Wang, J.; Yu, X.; Wang, W. Tetrahedron Lett. 2006, 47, 5131. (g) Wang,
W.; Li, H.; Wang, J.; Zu, L. J. Am. Chem. Soc. 2006, 128, 10354. (h) Zhao,
G.-L.; Corvoda, A. Tetrahedron Lett. 2006, 47, 7417. (h) Rios, R.; Sunden,
H.; Ibrahem, I.; Zhao, G.-L.; Eriksson, L.; Cordova, A. Tetrahedron Lett.
2006, 47, 8547. (i) Enders, D.; Huttl, M. R. M.; Grondal, C.; Raabe, G.
Nature 2006, 441, 861. (j) Enders, D.; Huttl, M. R. M.; Runsink, J.; Raabe,
G.; Wendt, B. Angew. Chem., Int. Ed. 2007, 46, 467. (k) Vesely, J.; Ibrahem,
I.; Zhao, G.-L.; Rios, R.; Cordova, A. Angew. Chem., Int. Ed. 2007, 46,
778. (l) Zhao, G.-L.; Xu, Y.; Sunden, H.; Eriksson, L.; Sayah, M.; Cordova,
A. Chem. Commun. 2007, 734. (m) Ibrahem, I.; Rios, R.; Vesely, J.; Zhao,
G.-L.; Cordova, A. Chem. Commun. 2007, 849. (n) Li, H.; Wang, J.;
E-Nunu, T.; Zu, L.; Jiang, W.; Wei, S.; Wang, W. Chem. Commun. 2007,
507. (o) Li, H.; Wang, J.; Xie, H.; Zu, L.; Jiang, W.; Duesler, E. N.; Wang,
W. Org. Lett. 2007, 9, 965. (p) Li, H.; Zu. L.; Xie, H.; Wang, J.; Jiang, W.;
Wang, W. Org. Lett. 2007, 9, 1833. (q) For a review, see: Palomo, C.;
Mielgo, A. Angew. Chem., Int. Ed. 2006, 45, 7876.
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