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Q. Xu, Z. Li / Tetrahedron Letters 50 (2009) 6838–6840
4. Lee, Y.-J.; Lee, J.; Kim, M.-J.; Jeong, B.-S.; Lee, J.-H.; Kim, T.-S.; Lee, J.; Ku, J.-M.;
Jew, S.-S.; Park, H.-G. Org. Lett. 2005, 7, 3207.
N-(2-hydroxyethyl)trans-cinnamamide also resulted in a high yield
of the oxazoline (entry 6). The reaction of bis-N,N-(2-hydroxy-
ethyl)amide with PPh3–DDQ also occurred, even though it pro-
ceeded slowly, requiring 24 h for a complete conversion (entry
7), whereupon a bisoxazoline was obtained.
5. (a) Caplan, N. A.; Hancock, F. E.; Page, P. C. B.; Hutchings, G. J. Angew. Chem., Int.
Ed. 2004, 43, 1685; (b) Moyano, A.; Rosol, M.; Moreno, R. M.; López, C.; Maestro,
M. A. Angew. Chem., Int. Ed. 2005, 44, 1865; (c) Evans, D. A.; Wu, J. J. Am. Chem.
Soc. 2005, 127, 8006; (d) Evans, D. A.; Fandrick, K. R.; Song, H.-J. J. Am. Chem. Soc.
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Amides derived from chiral amino alcohols may form enantio-
pure oxazolines if no racemization occurs in the conversion. Thus,
(S)-N-(2-hydroxy-1-phenyl-ethyl)-benzamide and (S)-N-(1-ben-
zyl-2-hydroxyethyl)benzamide of >98% ee were used as the start-
ing materials. Under the same reaction conditions, enantiopure
oxazolines of >98% ee were obtained25 (entries 8 and 9). The use
6. Bandgar, B. P.; Pandit, S. S. Tetrahedron Lett. 2003, 44, 2331.
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7019.
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1998, 9, 2865.
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Asymmetry 2002, 13, 1551.
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Kurosu, M.; Porter, J. R.; Foley, M. A. Tetrahedron Lett. 2004, 45, 145; (c) Davies,
I. W.; Gerena, L.; Lu, N.; Larsen, R. D.; Reider, P. J. J. Org. Chem. 1996, 61, 9629;
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Shirai, N.; Ikeda, S.; Odashima, K. Chem. Eur. J. 2006, 12, 7733.
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19. Ishihara, M.; Togo, H. Tetrahedron 2007, 63, 1474. 19.
of substrate 1j, which bears an
a-chiral center, also yielded opti-
cally active product in high yield in a short time. However, the
reaction was slow when the substrate was a secondary alcohol.
For example, the amide derived from (1S,2R)-2-amino-1,2-diphen-
ylethanol did not react completely even after 24 h at room
temperature.
According to the literature, 2-alkyloxazolines are more difficult
to synthesize than their aryl analogues.26 Therefore, the cycliza-
tions of N-(2-hydroxyethyl)alkylamides were also explored. In
these cases, longer reaction times of about 24 h are necessary to
produce the oxazolines in high yields (entries 11 and 12). The pres-
ence of a cyclopropyl ring is tolerated in the process (entries 13–
15). When trans-, cis-cyclopropyl carboxylic amides were used,
the expected corresponding products were obtained. The stereo-
chemistry of the cyclopropyl ring was largely unchanged in the
cyclization of the trans isomer (entry 15), while a slight isomeriza-
tion of the cis amide to the trans oxazoline was observed (entry 14).
In summary, the cyclization of N-2-hydroxylamides with PPh3–
DDQ is an efficient method to synthesize 2-oxazolines. It is appli-
cable to aliphatic and aromatic carboxylic acid derivatives, and
the synthesis procedure is simple and high yielding.
20. Iranpoor, N.; Firouzabadi, N. H.; Nowrouzi, N. Tetrahedron Lett. 2006, 47, 8247.
21. Iranpoor, N.; Firouzabadi, H.; Akhlaghinia, B.; Nowrouzi, N. J. Org. Chem. 2004,
69, 2562.
22. Firouzabadi, H.; Iranpoor, N.; Sobhani, S. Tetrahedron 2004, 60, 203.
23. Li, Z.; Crosignani, S.; Linclau, B. Tetrahedron Lett. 2003, 44, 8143–8147.
24. Typical procedure for the conversion of N-2-hydroxyethylamide into 2-oxazoline:
PPh3 (0.393 g, 1.5 mmol), DDQ (0.341 g, 1.5 mmol), and 5 mL of DCM were
added to a dried Schlenk tube under an argon atmosphere, and the mixture
was stirred at room temperature for 3 min. N-(2-Hydroxyethyl)benzamide (1a,
0.165 g, 1 mmol) was then added. The color of the mixture changed to yellow
and a precipitate was formed. After 20 min, TLC showed the absence of the
substrate, and the presence of a spot corresponding to a new compound. The
mixture was then washed with aqueous NaOH solution (5%, 40 mL), and the
separated water layer was back-extracted with DCM (15 mL ꢀ 4). The
combined organic layers were washed with brine, and dried with anhydrous
Na2SO4. Filtration and evaporation of the solvent followed by column
chromatographic separation (silica gel) using petroleum ether/ethyl acetate
(4:1, v/v) gave the corresponding 2-phenyloxazoline (1a, 0.156 g, 96%). oil, 1H
NMR (400 MHz, CDCl3, 25 °C): d 7.95 (d, J = 7.2 Hz, 2H), 7.48–7.40 (m, 3H), 4.44
(t, J = 9.6 Hz, 2H), 4.07 (t, J = 9.6 Hz, 2H); 13C NMR (100 MHz, CDCl3, 25 °C) d
164.5, 131.2, 128.2, 128.0, 127.6, 67.5, 54.8 ppm. MS: m/z = 147. 148 (7)
[M+1]+, 147 (67) [M]+, 117 (100). IR (Nujol): 2931, 1651, 1529, 1493, 1456,
Acknowledgments
We are grateful to the NSFC for financial support (Grant No.
20672016). Ms. Huiying Chen is thanked for recording the NMR
spectra.
Supplementary data
Supplementary data associated with this article can be found, in
References and notes
1346, 1269, 1201, 1038, 967, 899, 712, 607 cmꢁ1
.
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