3908
S. Muramulla, C.-G. Zhao / Tetrahedron Letters 52 (2011) 3905–3908
Supplementary data
CF3
S
Supplementary data (HPLC chromatograms for compounds
H
N
18a–n) associated with this article can be found, in the online ver-
F3C
N
H
Ar
NH
H2N
NC
O
NH
O2C
N
H
References and notes
CN
NC
H2N
O
1. For reviews, see: (a) Berkessel, A.; Groeger, H. Asymmetric Organocatalysis;
Wiley-VCH: Weinheim, 2005; (b) Pellissier, H. Tetrahedron 2007, 63, 9267–9331.
2. Mandal, T.; Zhao, C.-G. Angew. Chem., Int. Ed. 2008, 47, 7714–7717.
3. For examples, see: (a) Clarke, M. L.; Fuentes, J. A. Angew. Chem. 2007, 119, 948–
951. Angew. Chem., Int. Ed. 2007, 46, 930–933; (b) Xu, D.-Q.; Yue, H.-D.; Luo, S.-
P.; Xia, A.-B.; Zhang, S.; Xu, Z.-Y. Org. Biomol. Chem. 2008, 6, 2054–2057; (c) Bella,
M.; Schietroma, D. M. S.; Cusella, P. P.; Gasperi, T.; Visca, V. Chem. Commun.
2009, 597–599; (d) El-Hamdouni, N.; Companyo, X. R. R.; Moyano, A. Chem. Eur.
J. 2010, 16, 1142–1148; (e) Demir, A. S.; Eymur, S. Tetrahedron: Asymmetry 2010,
21, 112–115; (f) Oh, K.; Li, J.-Y.; Ryu, J. Org. Biomol. Chem. 2010, 8, 3015–3024;
(g) Reis, Ö.; Eymur, S.; Reis, B.; Demir, A. S. Chem. Commun. 2009, 9, 1088–1090;
(h) Uraguchi, D.; Ueki, Y.; Ooi, T. Science 2009, 326, 120–123; For a review, see:
Meeuwissen, J.; Reek, J. N. H. Nat. Chem. 2010, 2, 615–621.
4. (a) Wang, J. L.; Liu, D.; Zhang, Z. J.; Shan, S.; Han, X.; Srinivasula, S. M.; Croce, C.
M.; Alnemri, E. S.; Huang, Z. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 7124–7129; (b)
El-Tamany, E. S.; El-Shahed, F. A.; Mohamed, B. H. J. Serb. Chem. Soc. 1999, 64, 9–
18; (c) Zaki, M. E. A.; Soliman, H. A.; Hiekal, O. A.; Rashad, A. E. Z. Naturforsch., C
2006, 61, 1–5; (d) Ismail, Z. H.; Aly, G. M.; El-Degwi, M. S.; Heiba, H. I.; Ghorab,
M. M. Egypt. J. Biotechnol. 2003, 13, 73–82; (e) Abdelrazek, F. M.; Metz, P.;
Metwally, N. H.; El-Mahrouky, S. F. Arch. Pharm. 2006, 339, 456–460; (f)
Abdelrazek, F. M.; Metz, P.; Kataeva, O.; Jaeger, A.; El-Mahrouky, S. F. Arch.
Pharm. 2007, 340, 543–548; (g) Foloppe, N.; Fisher, L. M.; Howes, R.; Potter, A.;
Robertson, G. S.; Surgenor, A. E. Bioorg. Med. Chem. 2006, 14, 4792–4802.
5. (a) Otto, H. H. Arch. Pharm. 1974, 307, 444–447; (b) Otto, H. H.; Schmelz, H. Arch.
Pharm. 1979, 312, 478–486; (c) Sharanin, Y. A.; Sharanina, L. G.; Puzanova, V. V.
Zh. Org. Khim. 1983, 19, 2609–2615; (d) Shestopalov, A. M.; Yakubov, A. P.;
Tsyganov, D. V.; Emelyanova, Y. M.; Nesterov, V. N. Chem. Heterocycl. Compd.
2002, 38, 1180–1189; (e) Vasuki, G.; Kumaravel, K. Tetrahedron Lett. 2008, 49,
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367. and references cited therein.
NH
N
Figure 2. Proposed transition state for the MDO-catalyzed reaction (Ar = 6-meth-
oxyquinolin-4-yl).
bonding if the deprotonation is not complete). The other substrate
benzylidenemalononitrile (17a), interacts with the thiourea moi-
ety of the MDO through hydrogen bonds. The attack of the enol
of 16 onto the Re face of the 17a leads to an intermediate, which
after cyclization and rearrangement gives the observed R-enantio-
mer as the major product.
In summary, during the study of the MDO-catalyzed tandem
Michael addition–cyclization reaction between 3-methyl-2-pyraz-
olin-5-one and benzylidenemalononitriles, we have demonstrated
unequivocally a new catalytic mode of the MDOs, in which the
MDO is used as a Lewis base catalyst. Although the enantioselectiv-
ity obtained in this reaction is highly substrate dependent due to
the nature of this reaction, we are very optimistic that these results
will lead to more applications of the MDOs in organic synthesis
since there are more reactions catalyzed by Lewis base than
through the enamine mechanism. Study along this line is currently
under way in our lab.
6. Gogoi, S.; Zhao, C.-G. Tetrahedron Lett. 2009, 50, 2252–2255.
7. General procedure: In a vial equipped with a magnetic stirring bar were added
quinidine thiourea (11, 5.0 mol %),
L-proline (1, 5.0 mol %), 3-methyl-2-
pyrazolon-5-one (16, 0.10 mmol) and finally benzylidenemalononitrile (17a,
0.10 mmol) in dichloromethane (2.0 mL) with stirring. The mixture was further
stirred at room temperature until the completion of the reaction (monitored by
TLC). The reaction mixture was directly transferred to a silica gel column and
was purified by column chromatography (with EtOAc as the eluent) to furnish
the desired product.
Acknowledgments
The generous financial support of this project from the NSF
(Grant No. CHE-0909954) and the Welch Foundation (Grant No.
AX-1593) is gratefully acknowledged.