pubs.acs.org/joc
the reported water-containing organocatalytic systems,2
Water-Compatible Iminium Activation: Highly
Enantioselective Organocatalytic Michael Addition
of Malonates to r,β-Unsaturated Enones
nitroalkenes and enals are the most frequently used sub-
strates in the Michael reactions,3 but to the best of our
knowledge, research aimed at using enones as Michael
acceptors in an aqueous system remains a more significant
challenge.4 Recently, primary amine salts have successfully been
applied in the iminium catalysis of enones;5 however, no success
has been met in aqueous system.
Zhifeng Mao,† Yaomei Jia,† Wenyi Li,† and Rui Wang*,†,‡
†Key Laboratory of Preclinical Study for New Drugs of Gansu
Province, State Key Laboratory of Applied Organic
Chemistry and Institute of Biochemistry and Molecular
Biology, Lanzhou University, Lanzhou, 730000 China, and
‡Department of Applied Biology and Chemical Technology,
The Hong Kong Polytechnic University, Kowloon, Hong Kong
Many kinds of catalysts such as proline salts,6 chiral metal
compounds,7 chiral ionic liquids,8 phase-transfer catalysts,9
and other organocatalysts10 have been developed for the
Michael reaction of malonates with enones. Although great
success has been achieved over the past few years in these
important reactions, all of them were performed in organic
media or in neat condition. Thus, the development of organo-
catalytic version of this Michael reaction in water is a highly
desirable topic in organic synthesis. Moreover, chalcones are
Received July 13, 2010
(3) (a) Perlmutter, P. Conjugate Addition Reactions in Organic Synthesis;
Pergamon Press: Oxford, 1992. (b) Tomioka, K.; Nagaoka, Y. In Compre-
hensive Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H.,
Eds.; Springer: Berlin, 1999; Vol. 3, Chapter 31.1. (c) Sibi, M. P.; Manyem, S.
Tetrahedron 2000, 56, 8033. (d) Kanai, M.; Shibasaki, M. In Catalytic
Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley: New York, 2000;
€
p 569. (e) Krause, N.; Hoffman-Roder, A. Synthesis 2001, 171. (f) Hayashi,
T.; Yamasaki, K. Chem. Rev. 2003, 103, 2829. (g) Tsogoeva, S. B. Eur. J. Org.
Chem. 2007, 1701. (h) Vicario, J. L.; Badıa, D.; Carrillo, L. Synthesis 2007,
ꢁ
2065. (i) Almas-i, D.; Alonso, D. A.; Najera, C. Tetrahedron: Asymmetry
2007, 18, 299.
(4) Northrup, A. B.; D. MacMillan, W. C. J. Am. Chem. Soc. 2002, 124,
2458.
The highly enantioselective Michael addition of malonates to
R,β-unsaturated ketones in water was reported to be catalyzed
by a primary-secondary diamine catalyst containing a long
alkyl chain. This asymmetric Michael addition process was
found to be effective for a variety of R,β-unsaturated ketones.
(5) For selected examples, see: (a) Reisinger, C. M.; Wang, X.; List, B.
Angew. Chem., Int. Ed. 2008, 47, 8112. (b) Xie, J.-W.; Yue, L.; Chen, W.; Du,
W.; Zhu, J.; Deng, J.-G.; Chen, Y.-C. Org. Lett. 2007, 9, 413. (c) Liu, T.-Y.;
Cui, H.-L.; Zhang, Y.; Jiang, K.; Du, W.; He, Z.- Q.; Chen, Y.-C. Org. Lett.
2007, 9, 3671. (d) Chen, W.; Du, W.; Duan, Y.-Z.; Wu, Y.; Yang, S.-Y.;
Chen, Y.-C. Angew. Chem., Int. Ed. 2007, 46, 7667. (e) Wang, X.; Reisinger,
C. M.; List, B. J. Am. Chem. Soc. 2008, 130, 6070. (f) Singh, R. P.; Bartelson,
K.; Wang, Y.; Su, H.; Lu, X.; Deng, L. J. Am. Chem. Soc. 2008, 130, 2422. (g)
Xie, J.-W.; Chen, W.; Li, R.; Zeng, M.; Du, W.; Yue, L.; Chen, Y.-C.; Wu,
Y.; Zhu, J.; Deng, J.-G. Angew. Chem., Int. Ed. 2007, 46, 389. (h) Lu, X.; Liu,
Y.; Sun, B.; Cindric, B.; Deng, L. J. Am. Chem. Soc. 2008, 130, 8134. For
some leading reviews, see: (i) Xu, L.-W.; Lu, Y.-X. Org. Biomol. Chem. 2008,
6, 2047. (j) Chen, Y.-C. Synlett 2008, 1919. (k) Bartoli, G.; Melchiorre, P.
Synlett 2008, 1759.
Over the past few decades, reactions in which water is used
as the solvent have received a great deal of attention.1 In all
(1) (a) Grieco, P. A., Ed. Organic Synthesis in Water; Blackie: London,
1998. (b) Lindstrom, U. M. Chem. Rev. 2002, 102, 2751. (c) Kobayashi, S.;
Manabe, K. Acc. Chem. Res. 2002, 35, 209. (d) Li, C.-J. Chem. Rev. 2005, 105,
3095. (e) Pirrung, M. C. Chem.;Eur. J. 2006, 12, 1312. (f) Mase, N.; Barbas,
C. F., III. Org. Biomol. Chem. 2010, 8, 4043.
(2) For some selected examples of aldol reactions in aqueous media: (a)
Dickerson, T. J.; Janda, K. D. J. Am. Chem. Soc. 2002, 124, 3220. (b) Torii, H.;
Nakadai, M.; Ishihara, K.; Saito, S.; Yamamoto, H. Angew. Chem., Int. Ed. 2004,
43, 1983. (c) Hayashi, Y.; Aratake, S.; Okano, T.; Takahashi, J.; Sumiya, T.; Shoji,
(6) (a) Yamaguchi, M.; Shiraishi, T.; Hirama, M. J. Org. Chem. 1996, 61,
3520. (b) Yamaguchi, M.; Shiraishi, T.; Hirama, M. Angew. Chem., Int. Ed.
1993, 32, 1176.
(7) For recent examples: (a) Park, S.-Y.; Morimoto, H.; Matsunaga, S.;
Shibasaki, M. Tetrahedron Lett. 2007, 48, 2815. (b) Chen, C.; Zhu, S.-F.; Wu,
X.-Y.; Zhou, Q.-L. Tetrahedron: Asymmetry 2006, 17, 2761. (c) Kumaras-
wamy, G.; Jena, N.; Sastry, M. N. V.; Rao, G. V.; Ankamma, K. J. Mol.
Catal. A 2005, 230, 59. (d) Agostinho, M.; Kobayashi, S. J. Am. Chem. Soc.
2008, 130, 2430. (e) Naka, H.; Kanase, N.; Ueno, M.; Kondo, Y. Chem.;
Eur. J. 2008, 14, 5267. (f) Chen, D.; Chen, Z.; Xiao, X.; Yang, Z.; Lin, L.; Liu,
X.; Feng, X. Chem.;Eur. J. 2009, 15, 6807.
(8) Wang, Z.; Wang, Q.; Zhang, Y.; Bao, W. Tetrahedron Lett. 2005, 46,
4657.
(9) (a) Ooi, T.; Ohara, D.; Fukumoto, K.; Maruoka, K. Org. Lett. 2005, 7,
3195. (b) Dere, R. T.; Pal, R. R.; Patil, P. S.; Salunkhe, M. M. Tetrahedron
Lett. 2003, 44, 5351. (c) Kim, D. Y.; Huh, S. C.; Kim, S. M. Tetrahedron Lett.
2001, 42, 6299.
(10) (a) Halland, N.; Aburel, P. S.; Jørgensen, K. A. Angew. Chem., Int.
Ed. 2003, 42, 661. (b) Halland, N.; Aburel, P. S.; Jørgensen, K. A. Angew.
Chem., Int. Ed. 2004, 43, 1272. (c) Wang, J.; Li, H.; Zu, L.; Jiang, W.; Xie, H.;
Duan, W.; Wang, W. J. Am. Chem. Soc. 2006, 128, 12652. (d) Knudsen,
K. R.; Mitchell, C. E. T.; Ley, S. V. Chem. Commun. 2006, 66. (e)
Wascholowski, V.; Knudsen, K. R.; Mitchell, C. E. T.; Ley, S. V. Chem.;
Eur. J. 2008, 14, 6155. (f) Jiang, Z.; Ye, W.; Yang, Y.; Tan, C.-H. Adv. Synth.
Catal. 2008, 350, 2345. (g) Yang, Y.-Q.; Zhao, G. Chem.;Eur. J. 2008, 14,
10888. (h) Li, P.; Wen, S.; Yu, F.; Liu, Q.; Li, W.; Wang, Y.; Liang, X.; Ye, J.
Org. Lett. 2009, 11, 753.
ꢀ
M. Angew. Chem., Int. Ed. 2006, 45, 5527. (d) Font, D.; Jimeno, C.; Pericas, M. A.
Org. Lett. 2006, 8, 4653. (e) Wu, Y.; Zhang, Y.; Yu, M.; Zhao, G.; Wang, S. Org.
Lett. 2006, 8, 4417. (f) Mase, N.; Nakai, Y.; Ohara, N.; Yoda, H.; Takabe, K.;
Tanaka, F.; Barbas, C. F., III. J. Am. Chem. Soc. 2006, 128, 734. Mannich
reaction: (g) Cheng, L.; Wu, X.; Lu, Y. Org. Biomol. Chem. 2007, 5, 1018. (h)
Hayashi, Y.; Urushima, T.; Aratake, S.; Okano, T.; Obi, K. Org. Lett. 2008, 10,
21. (i) Amedjkouh, M.; Brandberg, M. Chem. Commun. 2008, 3043. For some
selected examples of Michael reactions: (j) Mase, N.; Watanabe, K.; Yoda, H.;
Takabe, K.; Tanaka, F.; Barbas, C. F., III. J. Am. Chem. Soc. 2006, 128, 4966. (k)
Zu, L.; Wang, J.; Li, H.; Wang, W. Org. Lett. 2006, 8, 3077. (l) Luo, S.; Mi, X.;
Liu, S.; Xu, H.; Cheng, J.-P. Chem. Commun. 2006, 3687. (m) Carlone, A.;
Marigo, M.; North, C.; Landa, A.; Jørgensen, K. A. Chem. Commun. 2006, 4928.
(n) Singh, V.; Singh, V. K. Org. Lett. 2007, 9, 1117. (o) Zhu, S. L.; Yu, S. Y.; Ma,
D. W. Angew. Chem., Int. Ed. 2008, 47, 545. (p) Palomo, C.; Landa, A.; Mielgo,
ꢁ
A.; Oiarbide, M.; Puente, A.; Vera, S. Angew. Chem., Int. Ed. 2007, 46, 8431. (q)
Belot, S.; Massaro, A.; Tenti, A.; Mordini, A.; Alexakis, A. Org. Lett. 2008, 10,
4557. (r) Wang, J.; Yu, F.; Zhang, X.; Ma, D. Org. Lett. 2008, 10, 2561. (s) Zheng,
Z.; Perkins, B. L.; Ni, B. J. Am. Chem. Soc. 2010, 132, 50for a recent review:. (t)
Raj, M.; Singh, V. K. Chem. Commun. 2009, 6687.
7428 J. Org. Chem. 2010, 75, 7428–7430
Published on Web 10/11/2010
DOI: 10.1021/jo101188m
r
2010 American Chemical Society