ChemComm
Communication
Chem., 2004, 8, 1547; (d) T. Mendgen, C. Steuer and C. D. Klein,
J. Med. Chem., 2012, 55, 743–753.
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2 For a review, see: T. Tomasic and L. P. Masic, Curr. Org. Chem., 2009,
16, 1596.
3 A. A. Lugovskoy, A. I. Degterev, A. F. Fahmy, P. Zhou, J. D.
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Scheme 1 Elaboration of the Diels–Alder cycloaddition product.
4 M. Soltero-Higgin, E. E. Carlson, J. H. Phillips and L. L. Kiessling,
J. Am. Chem. Soc., 2004, 126, 10532.
5 E. E. Carlson, J. F. May and L. L. Kiessling, Chem. Biol., 2006, 13,
825
substituent on the aromatic rings had very limited influence on
the reaction in terms of stereoselectivities, while the electron-
donating substituent afforded relatively low yield (6e, 64% yield).
Interestingly, rhodanine derivatives with R3 substituent of the
p-F-C6H4 group afforded the desired products with slightly
decreased dr values (6b, 6k, 10 : 1 dr). The substituents on the
nitrogen atom of 5 barely affected the asymmetric process.
We then paid our attention to the substrate scope of the
2,4-dienals. Gratifyingly, when 4-ethyl-2,4-dienal was employed,
products 6o to 6r were obtained with much higher yields and
enantioselectivities compared to that of 4a. It was noteworthy
that structurally more complicated 4-phenyl-2,6-dienal gave the
desired products 6s–6v with almost perfect stereoselectivities.
Products 6k–6n that bore four consecutive chiral centers could
also be easily prepared using 4,6-disubstitued-2,4-hexadienal as
diene, with up to 98% yield and excellent diastereo- and
enantioselectivities. It should be noted that the established
method was also applicable to the reaction with the N-aryl-
thiohydantoin derivative. As shown in Table 2, products (6w, 6x)
could be easily prepared in good yields with excellent enantio-
(>90% ee) and slightly decreased diastereoselectivities (10 : 1 dr).
The relative and absolute configurations of the sequential
6 (a) W. J. Brouillette, V. P. Jestkov, M. L. Brown, M. S. Akhtar,
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7 (a) C. J. Mappes, E. H. Pommer, C. Rentzea and B. Zeeh, U.S. Pat.,
1980, 4, 198; (b) C. Cseke, B. C. Gerwick, G. D. Crouse,
M. G. Murdoch, S. B. Green and D. R. Heim, Pestic. Biochem. Physiol.,
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8 (a) F. Nique, S. Hebbe, C. Peixoto, D. Annoot, J.-M. Lefrancois,
E. Duval, L. Michoux, N. Triballeau, J.-M. Lamoullec, P. Mollat,
´
´
M. Thauvin, T. Prange, D. Minet, P. Clement-Lacroix, C. Robin-
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Jagerschmidt, D. Fleury, D. Guedin and P. Deprez, J. Med. Chem.,
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J.-M. Lefrancois, H. Jary, L. Alvey, M. Manioc, C. Housseman,
´
H. Klaassen, K. V. Beeck, D. Guedin, F. Namour, D. Minet,
´
E. V. der. Aar, J. Feyan, S. Fletcher, R. Blanque, C. Robin-Jagersch-
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9 For recent example see: W. Wu, H. Huang, X. Yuan, K. Zhu and J. Ye,
Chem. Commun., 2012, 48, 9180.
reaction products were assigned on the basis of X-ray crystal 10 For reviews, see: (a) K. C. Nicolaou, S. A. Snyder, T. Montagnon and
G. Vassilikogiannakis, Angew. Chem., Int. Ed., 2002, 41, 1668;
(b) E. M. Stocking and R. M. Williams, Angew. Chem., Int. Ed.,
structural analysis of the product 6j (see the ESI†).
As an effort to transform the N-aryl-thiohydantoin motif into
2003, 42, 3078.
the corresponding N-aryl-hydantoin motif, the Diels–Alder cyclo- 11 (a) H. B. Kagan and O. Riant, Chem. Rev., 1992, 92, 1007; (b) E. J.
Corey, Angew. Chem., Int. Ed., 2002, 41, 1650; (c) S. Reymond and
addition product 6w was then converted into the corresponding
J. Cossy, Chem. Rev., 2008, 108, 5359; (d) K. A. Ahrendt, C. J. Borths
a,b-unsaturated ester, followed by treatment with H2O2 to afford
and D. W. C. MacMillan, J. Am. Chem. Soc., 2000, 122, 4243;
the desired structure that incorporated the hydantoin motif.
The product 7a could be obtained in high yield with simple
manipulation (Scheme 1).
(e) Y. Huang, A. K. Unni, A. N. Thadani and V. H. Rawal, Nature,
2003, 424, 146.
12 For a review, see: J.-L. Li, T.-Y. Liu and Y.-C. Chen, Acc. Chem. Res.,
2012, 45, 1491.
To conclude, the asymmetric Diels–Alder cycloaddition of 13 Z.-J. Jia, H. Jiang, J.-L. Li, B. Gschwend, Q.-Z. Li, X. Yin, J. Grouleff,
Y.-C. Chen and K. A. Jøgensen, J. Am. Chem. Soc., 2011, 133,
5053.
14 (a) H. Jiang, B. Gschwend, L. Albrecht, S. G. Hansen and
2,4-dienals 4 and rhodanine derivatives has been established
with high yield and excellent diastereo- and enantioselectivities.
The optimized reaction condition was also applicable to the
reaction of 2,4-dienals and thiohydantoin derivatives, the
adducts of which may serve as valuable scaffolds in new drug
discovery and natural product synthesis. Exploration of the
application of the Diels–Alder cycloaddition product in medicinal
chemistry is currently under way in our laboratories.
We thank the National Natural Science Foundation of China
(20902018, 21272068), Shanghai Municipal Education Commis-
sion (11ZZ56), the Fundamental Research Funds for the Central
Universities, and 111 project (B07023) for financial support.
K. A. Jørgensen, Chem.–Eur. J., 2011, 17, 9032; (b) Z.-J. Jia,
Q. Zhou, Q.-Q. Zhou, P.-Q. Chen and Y.-C. Chen, Angew. Chem.,
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T.-Y. Liu and Y.-C. Chen, Angew. Chem., Int. Ed., 2012, 51, 4401;
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Soc., 2011, 133, 15212; (e) Y. Liu, M. Nappi, E. C. Escudero-Adan and
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15 For
a highlight on trienamine catalysis, see: E. Arceo and
P. Melchiorre, Angew. Chem., Int. Ed., 2012, 51, 5290.
16 For reviews of diaryl prolinol ethers catalysis, see: (a) A. Mielgo and
C. Palomo, Chem.–Asian J., 2008, 3, 922; (b) K. L. Jensen,
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Notes and references
1 For selected reviews, see: (a) F. C. Brown, Chem. Rev., 1961, 61, 463;
(b) S. P. Singh, S. S. Parmar, K. Raman and V. I. Stenberg, Chem. Rev., 17 CDCl3 was used for the convenience of 1H NMR analysis. CHCl3 gave
1981, 81, 175; (c) R. B. Lesyk and B. S. Zimenkovsky, Curr. Org.
the same result.
c
This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 2157--2159 2159