A Bifunctional Cinchona Alkaloid-Squaramide Catalyst
Stereochem. 1986, 16, 87; c) P. McDaid, Y. G. Chen, L.
Deng, Angew. Chem. 2002, 114, 348; Angew. Chem. Int.
Ed. 2002, 41, 338; d) T. C. Wabnitz, J. B. Spencer, Org.
Lett. 2003, 5, 2141; e) B.-J. Li, L. jiang, M. Liu, Y.-C.
Chen, L.-S. Ding, Y. Wu, Synlett 2005, 603; f) H. Li, J.
Wang, L.-S. Zu, W. Wang, Tetrahedron Lett. 2006, 47,
2585; g) Y. Liu, B.-F. Sun, B.-M. Wang, M. Wakem, L.
Deng, J. Am. Chem. Soc. 2009, 131, 418; h) K. Kimmel,
M. T. Robak, J. A. Ellman, J. Am. Chem. Soc. 2009,
131, 8754; i) N. K. Rana, S. Selvakumar, V. K. Singh, J.
Org. Chem. 2010, 75, 2089; j) D. Enders, K. Hoffman,
Eur. J. Org. Chem. 2009, 1665; k) J. Sun, G. C. Fu, J.
Am. Chem. Soc. 2010, 132, 4568.
bearing hydrogen bond accepting substituents, such as
carbonyl or ether groups (entries 16–18).
In conclusion, we have prepared a variety of bifunc-
tional squaramide organocatalysts and identified 4e as
a most efficient and enantioselective catalyst for the
conjugate addition of various thiols to trans-chalcones.
This process is characterized by mild conditions, high
stereocontrol and excellent yields. An inverstigation
on the full scope of this new catalyst in asymmetric
transformations is ongoing in our laboratory.
[6] For examples of organocatalytic tandem reactions of
thiols, see: a) M. Marigo, T. Schulte, J. FranzØn, K. A.
Jørgensen, J. Am. Chem. Soc. 2005, 127, 15710; b) S.
Brandau, E. Maerten, K. A. Jørgensen, J. Am. Chem.
Soc. 2006, 128, 14986; c) W. Wang, H. Li, J. Wang, L.-S.
Zu, J. Am. Chem. Soc. 2006, 128, 10354; d) L.-S. Zu, J.
Wang, H. Li, H.-X. Xie, W. Jiang, W. Wang, J. Am.
Chem. Soc. 2007, 129, 1036; e) L.-S. Zu, H.-X. Xie, H.
Li, J. Wang, W. Jiang, W. Wang, Adv. Synth. Catal.
2007, 349, 1882; f) G.-L. Zhao, J. Vesely, R. Rios, I.
Ibrahem, H. SundØn, A. Córdova, Adv. Synth. Catal.
2008, 350, 237; g) R. Dodda, J. J. Goldman, T. Mandal,
C.-G. Zhao, G. A. Broker, E. R. T. Tiekink, Adv. Synth.
Catal. 2008, 350, 537.
Experimental Section
Typical Procedure for the Organocatalytic Sulfa-
Michael Addition to trans-Chalcone
To a solution of trans-chalcone 5a (0.25 mmol) in toluene
(1 mL) was added squaramide catalyst 4e (1.5 mg,
0.0025 mmol) and benzyl thiol 6a (1.5 equiv.). After stirring
at room temperature for 3 h, the solvent was evaporated
under reduced pressure. The residue was purified by column
chromatography to give 7a as a white solid.
References
[7] a) P. Ricci, A. Carlone, G. Bartoli, M. Bosco, L.
Sambri, P. Melchiorre, Adv. Synth. Catal. 2008, 350, 49;
[1] a) T. Kondo, T.-A. Mitsudo, Chem. Rev. 2000, 100,
3205; b) M. Sibi, S. Manyem, Tetrahedron 2000, 56,
8033.
´
b) J. Skarz˙ewski, M. Zielinska-Błajet, I. Turowska-Tyrk,
Tetrahedron: Asymmetry 2001, 12, 1923; c) P. Suresh,
K. Pitchumani, Tetrahedron: Asymmetry 2008, 19, 2037;
d) H. Li, L. Zu, J. Wang, W. Wang, Tetrahedron Lett.
2006, 47, 3145.
[2] a) J. J. R. Frafflsto da Silva, Robert J. P. Williams, The
Biological Chemistry of the Elements, 2nd edn., Oxford
University Press, New York, 2001; b) P. Metzner, A.
Thuillier, Sulfur Reagents in Organic Synthesis, Aca-
demic Press, New York, 1994; c) A. Nudelman, The
Chemistry of Optically Active Sulfur Compounds,
Gordon and Breach, New York, 1984; d) C. Chatgilia-
loglu, K.-D. Asmus, in: Sulfur-Centered Reactive Inter-
mediates in Chemistry and Biology, Springer, New
York, 1991.
[8] For reviews of H-bonding organocatalysis, see: a) M. S.
Taylor, E. N. Jacobsen, Angew. Chem. 2006, 118, 1550;
Angew. Chem. Int. Ed. 2006, 45, 1520; b) Y. Takemoto,
Org. Biomol. Chem. 2005, 3, 4299; c) X. Yu, W. Wang,
Chem. Asian J. 2008, 3, 516.
[9] For selected examples of the bifunctional Cinchona al-
kaloid derivatives, see: a) B. Vakulya, S. Varga, A.
Csµmpai, T. Soós, Org. Lett. 2005, 7, 1967; b) A. Pe-
schiulli, Y. Gun’ko, S. J. Connon, J. Org. Chem. 2008,
73, 2454; c) S. H. McCooey, S. J. Connon, Angew.
Chem. 2005, 117, 6525; Angew. Chem. Int. Ed. 2005, 44,
6367; d) P. DinØr, M. Nielsen, S. Bertelsen, B. Niess,
K. A. Jørgensen, Chem. Commun. 2007, 3646; e) S. H.
McCooey, T. McCabe, S. J. Connon, J. Org. Chem.
2006, 71, 7494; f) S. H. Oh, H. S. Rho, J. W. Lee, J. E.
Lee, S. H. Youk, J. Chin, C. E. Song, Angew. Chem.
2008, 120, 1; Angew. Chem. Int. Ed. 2008, 47, 1.
[10] a) J. P. Malerich, K Hagihara, V. H. Rawal, J. Am.
Chem. Soc. 2008, 130, 14416; b) Y. Zhu, J. P. Malerich,
V. H. Rawal, Angew. Chem. Int. Ed. 2010, 49, 153; c) Y.
Qian, G.-Y. Ma, A.-F. Lv, H.-L. Zhu, J. Zhao, V. H.
Rawal, Chem. Commun. 2010, 46, 3004; d) H. Konishi,
T. Y. Lam, J. P. Malerich, V. H. Rawal, Org. Lett. 2010,
12, 2028.
[3] D. Enders, K. Lüttgen, A. A. Narine, Synthesis 2007,
959.
[4] For examples of organometallic-catalyzed Michael ad-
dition of thiols, see: a) K. Nishimura, M. Ono, Y. Na-
gaoka, K. Tomioka, J. Am. Chem. Soc. 1997, 119,
12974; b) E. Emori, T. Arai, H. Sasai, M. Shibasaki, J.
Am. Chem. Soc. 1998, 120, 4043; c) S. Kanemasa, Y.
Oderaotoshi, E. Wada, J. Am. Chem. Soc. 1999, 121,
8675; d) E. Emori, T. Iida, M. Shibasaki, J. Org. Chem.
1999, 64, 5318; e) S. Kobayashi, C. Ogawa, M. Kawa-
mura, M. Sugiura, Synlett 2001, 983; f) K. Matsumoto,
A. Watanabe, T. Uchida, K. Ogi, T. Katsuki, Tetrahe-
dron Lett. 2004, 45, 2385; g) A. M. M. Abe, S. J. K. Sau-
erland, A. M. P. Koskinen, J. Org. Chem. 2007, 72,
5411; h) M. Kawatsura, Y. Komatsu, M. Yamamoto, S.
Hayase, T. Itoh, Tetrahedron 2008, 64, 3488; i) A.
˘
Badoiu, G. Bernardinelli, C. Besnard, E. P. Kündig,
[11] a) J. W. Lee, T. H. Ryu, J. S. Oh, H. Y. Bae, H. B. Jang,
C. E. Song, Chem. Commun. 2009, 7224; b) D.-Q. Xu,
Y.-F. Wang, W. Zhang, S.-P. Luo, A.-G. Zhong, A.-B.
Xia, Z.-Y. Xu, Chem. Eur. J. 2010, 16, 4177.
Org. Biomol. Chem. 2010, 8, 193.
[5] For examples of organocatalyzed asymmetric sulfa-Mi-
chael addition, see: a) H. Hiemstra, H. Wynberg, J.
Am. Chem. Soc. 1981, 103, 417; b) H. Wynberg, Top.
Adv. Synth. Catal. 2010, 352, 2137 – 2141
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