C O M M U N I C A T I O N S
Table 2. Variation of Electrophile in Reaction with 6a
addition reactions of 1,3-dicarbonyl compounds to nitroolefins, cinchona
derivative 5 was a remarkably active catalyst, affording the conjugate
addition products in high yields and enantioselectivities. The modular
nature of the synthesis means that a wide range of squaramide catalysts,
tuned with regard to the pKa of the hydrogens as well as the chiral
environment, should be readily accessible. Further investigation of these
catalysts, as well as structures in which the distance between the donor
hydrogens is increased even further, can be expected to open new
opportunities for H-bond mediated asymmetric catalysis.
Acknowledgment. Financial support from the NIH is gratefully
acknowledged. We thank Kyowa-Hakko Kogyo Co., Japan, for a
sabbatical fellowship for K.H. and Dr. Ian Steele (U. Chicago, Dept. of
Geophysical Sciences) for obtaining the crystal structure of 5.
Supporting Information Available: Procedure for catalyst preparation,
characterization data, NMR spectra for new compounds, and HPLC data for
conjugate addition products. This information is available free of charge via
References
(1) (a) Doyle, A. G.; Jacobsen, E. N. Chem. ReV. 2007, 107, 5713. (b) McGilvra,
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(3) Examples of reactions catalyzed by chiral thioureas include the Strecker
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Friedel-Crafts reaction: Wang, Y. Q.; Song, J.; Hong, R.; Li, H. M.; Deng,
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Miyabe, H.; Takemoto, Y. J. Am. Chem. Soc 2007, 129, 6686. Pictet-
Spengler cyclization : (f) Raheem, I. T.; Thiara, P. S.; Peterson, E. A.;
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L. J. Am. Chem. Soc. 2008, 130, 2422.
a Reactions were carried out on 0.500 mmol of 9 with 2.0 equiv of 6 and
0.5 mol % 5 in 1.5 mL of CH2Cl2.
Table 3. Variation of Nucleophile in Reaction with 7
(4) Other chiral H-bond donor scaffolds include, inter alia, cinchona alkaloid
derivatives: (a) Hiemstra, H.; Wynberg, H. J. Am. Chem. Soc. 1981, 103,
417. Dipeptides: (b) Oku, J. I.; Inoue, S. J. Chem. Soc., Chem Commun.
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V. H. Nature 2003, 424, 146. (e) Thadani, A. N.; Stankovic, A. R.; Rawal,
V. H. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5846. Phosphoric acids : (f)
Akiyama, T.; Itoh, J.; Yokota, K.; Fuchibe, K. Angew. Chem., Int. Ed. 2004,
43, 1566. (g) Uraguchi, D.; Terada, M. J. Am. Chem. Soc. 2004, 126, 5356.
Amidinium ions: (h) Nugent, B. M.; Yoder, R. A.; Johnston, J. N. J. Am.
Chem. Soc. 2004, 126, 3418.
(5) Structures were optimized with Hartree-Fock calculations using the 6-31G*
basis set (Spartan ’04 for Macintosh, Wavefunction, Inc.). The calculated
H-H distance in the thiourea approximates that found in the crystal structure
of Takemoto’s thiourea catalyst: Okino, T.; Hoashi, Y.; Furukawa, T.; Xu,
X. N.; Takemoto, Y. J. Am. Chem. Soc. 2005, 127, 119.
(6) Squaramides have been used in molecular recognition studies: (a) Tomas,
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A. J. Org. Chem. 1996, 61, 9394. (b) Ramalingam, V.; Domaradzki, M. E.;
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therein.
(7) Squaramides have been recognized as bioisosteres of ureas: Merritt, J. R.;
Rokosz, L. L.; Kingsley, H. N.; Kaiser, B.; Wang, W.; Stauffer, T. M.;
Ozgur, L. E.; Schilling, A.; Li, G.; Baldwin, J. J.; Taveras, A. G.; Dwyer,
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Please see Supporting Information for more details.
(9) Previous reports of organocatalytic conjugate additions of 1,3-dicarbonyl
compounds to nitroolefins include: (a) Li, H. M.; Wang, Y.; Tang, L.; Deng,
L. J. Am. Chem. Soc. 2004, 126, 9906. (b) Kotrusz, P.; Toma, S.; Schmalz,
H. G.; Adler, A. Eur. J. Org. Chem. 2004, 1577. (c) Li, H. M.; Wang, Y.;
Tang, L.; Wu, F. H.; Liu, X. F.; Guo, C. Y.; Foxman, B. M.; Deng, L.
Angew. Chem., Int. Ed. 2005, 44, 105. (d) McCooey, S. H.; Connon, S. J.
Angew. Chem., Int. Ed. 2005, 44, 6367. (e) Wang, J.; Li, H.; Duan, W. H.;
Zu, L. S.; Wang, W. Org. Lett. 2005, 7, 4713. (f) Terada, M.; Ube, H.;
Yaguchi, Y. J. Am. Chem. Soc. 2006, 128, 1454. (g) McCooey, S. H.;
McCabe, T.; Connon, S. J. J. Org. Chem. 2006, 71, 7494. (h) Comer, E.;
Rohan, E.; Deng, L.; Porco, J. A. Org. Lett. 2007, 9, 2123. (i) Lubkoll, J.;
Wennemers, H. Angew. Chem., Int. Ed. 2007, 46, 6841. (j) Andres, J. M.;
Manzano, R.; Pedrosa, R. Chem.sEur. J. 2008, 14, 5116. (k) Peng, F. Z.;
Shao, Z. H.; Fan, B. M.; Song, H.; Li, G. P.; Zhang, H. B. J. Org. Chem.
2008, 73, 5202.
a Values are listed for major and minor diastereomers respectively.
b Reaction was carried out with 0.500 mmol of 7, 2.0 equiv of 11,
and 0.5 mol % 5 in 1.5 mL of CH2Cl2. c Reaction was carried out
with 0.200 mmol of 7, 2.0 equiv of 11, and 2.0 mol % 5 in 0.6 mL
of CH2Cl2.
(10) The absolute stereochemistry of 8 was assigned by comparison of the optical
rotation with the value determined in ref 9e.
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