S. H. Hwang, M. J. Kurth / Tetrahedron Letters 43 (2002) 53–56
55
1.0 mmol) and ethyl isocyanoacetate (0.13 mL, 1.2
mmol) in THF (6 mL) was added dropwise a solution
of 60% sodium hydride (0.054 g, 1.35 mmol) and
1,1,1,3,3,3-hexamethyldisilazane in THF (4 mL) at 0°C.
DMSO (0.59 mL) was added to this reaction mixture,
which was stirred overnight (0°Croom temperature).
The reaction mixture was quenched with saturated
aqueous NH4Cl (10 mL) and extracted with EtOAc
(3×30 mL). The combined extracts were washed with
water and brine, dried (MgSO4), and evaporated in
vacuo. Column chromatography of the residue over
silica gel eluting with n-hexane/EtOAc (4:1) gave 10a
(0.22 g, 78%). Other products (10b–d) were also pre-
pared in 66, 75, and 74% yields, respectively, under
similar reaction conditions.
11. (a) 5-((E)-2-Benzenesulfonylvinyl)-3-phenyl-4,5-dihydrois-
oxazole (5a): White solid (CH2Cl2/Et2O); mp 180°C; IR
(neat) 1303.0, 1142.8 cm−1 1H NMR l 7.90–7.87 (m,
;
2H), 7.64–7.61 (m, 3H), 7.57–7.52 (m, 2H), 7.44–7.40 (m,
3H), 6.98 (dd, J=15.0 and 4.7 Hz, 1H), 6.72 (dd, J=15.0
and 1.4 Hz, 1H), 5.40–5.32 (m, 1H), 3.65 (dd, J=16.6
and 11.3 Hz, 1H), 3.23 (dd, J=16.6 and 7.1 Hz, 1H); 13C
NMR l 156.03, 142.04, 139.67, 133.78, 132.10, 130.68,
129.46, 128.90, 128.59, 127.89, 126.86, 78.01, 40.73. Anal.
calcd for C17H15NO3S: C, 65.16; H, 4.82; N, 4.47; S,
10.23. Found: C, 65.05; H, 4.87; N, 4.47; S, 10.43;
(b) 2-[5-((E)-2-Benzenesulfonylvinyl)-4,5-dihydroisoxazol-
3-yl]pyridine (5b): Separated and purified by recrystalliza-
tion using CH2Cl2/Et2O. White solid; mp 194.5°C; IR
1
(neat) 1302, 1280, 1144 cm−1; H NMR l 8.61–8.59 (m,
1H), 7.98 (dt, J=8 and 1 Hz, 1H), 7.91–7.87 (m, 2H),
7.73 (dt, J=8 and 1.8 Hz, 1H), 7.67–7.61 (m, 1H),
7.60–7.52 (m, 2H), 7.32 (ddd, J=7.5, 4.9 and 1.2 Hz,
1H), 6.99 (dd, J=15 and 4.5 Hz, 1H), 6.71 (dd, J=15
and 1.6 Hz, 1H), 5.44–5.35 (m, 1H), 3.75 (dd, J=17.6
and 11.5 Hz, 1H), 3.41 (dd, J=17.6 and 7.2 Hz, 1H); 13C
NMR l 158.00, 149.43, 148.43, 142.10, 139.67, 136.54,
133.75, 131.90, 129.44, 127.90, 124.74, 121.92, 78.63,
40.41. Anal. calcd for C16H14N2O3S: C, 61.13; H, 4.49; N,
8.91; S, 10.20. Found: C, 60.90; H, 4.56; N, 8.71; S,
Acknowledgements
We thank the National Science Foundation and Cystic
Fibrosis Foundation for financial support of this
research. The 300 and 400 MHz NMR spectrometers
used in this study were funded in part by a grant from
the NSF (CHE-9808183).
10.08;
(c)
5-((E)-2-Benzenesulfonylvinyl)-5-methyl-3-
References
phenyl-4,5-dihydroisoxazole (5c): Separated and purified
by recrystallization using CH2Cl2/Et2O. White solid; mp
1. Grundmann, C.; Grunanger, G. The Nitrile Oxides;
Springer: New York, 1971.
158°C; IR (neat) 1314, 1306, 1143 cm−1 1H NMR l
;
7.89–7.86 (m, 2H), 7.63–7.51 (m, 5H), 7.42–7.37 (m, 3H),
7.03 (d, J=14.8 Hz, 1H), 6.70 (d, J=14.8 Hz, 1H), 6.64
(dd, J=25.0 and 16.8 Hz, 2H), 1.62 (s, 3H); 13C NMR l
156.03, 145.86, 139.76, 133.70, 130.50, 130.21, 129.42,
128.98, 128.83, 127.79, 126.64, 85.00, 46.47, 25.42. Anal.
calcd for C18H17NO3S: C, 66.03; H, 5.23; N, 4.28; S, 9.79.
Found: C, 65.97; H, 5.30; N, 4.16; S, 9.69; (d) 2-[5-((E)-2-
Benzenesulfonylvinyl)-5-methyl-4,5-dihydroisoxazol-3-yl]-
pyridine (5d): Separated and purified by recrystallization
using CH2Cl2/Et2O. White solid; mp 149.2°C; IR (neat)
2. (a) Lathbury, D. C.; Parsons, P. J. J. Chem. Soc., Chem.
Commun. 1982, 291–292; (b) Quilico, A.; Grunanger, P.;
Mazzini, R. Gazz. Chim. Ital. 1952, 82, 349–361.
3. (a) Vita-Finzi, P. The Chemistry of Heterocyclic Com-
pounds; John Wiley & Sons: New York, 1991; Vol. 4,
Part 1, p. 417; (b) Jones, R. A. The Chemistry of
Pyrroles; Academic Press: New York, 1977; p. 1.
4. Arai, M. A.; Arai, T.; Sasai, H. Org. Lett. 1999, 1,
1795–1797.
5. (a) Magnus, P.; Or, Y.-S. J. Chem. Soc., Chem. Commun.
1983, 26–27; (b) Halazy, S.; Magnus, P. Tetrahedron Lett.
1984, 1421–1424; (c) Carter, P.; Fitzjohn, S.; Halazy, S.;
Magnus, P. J. Am. Chem. Soc. 1987, 109, 2711–2717.
6. (a) Scho¨llkopf, U.; Hoppe, D.; Jentsch, R. Chem. Ber.
1975, 108, 1580–1592; (b) Scho¨llkopf, U.; Hantke, K.
Liebigs Ann. Chem. 1973, 1571–1582.
1304, 1146 cm−1 1H NMR l 8.59–8.56 (m, 1H), 7.97–
;
7.94 (m, 1H), 7.89–7.86 (m, 2H), 7.72 (dt, J=8 and 1.8
Hz, 1H), 7.65–7.60 (m, 1H), 7.56–7.51 (m, 2H), 7.32–7.25
(m, 1H), 7.04 (d, J=14.9 Hz, 1H), 6.67 (d, J=14.9 Hz,
1H), 3.47 (dd, J=28.5 and 17.6 Hz, 2H), 1.63 (s, 3H); 13
C
NMR l 157.98, 149.37, 148.80, 145.92, 139.84, 136.48,
133.67, 130.11, 129.41, 127.83, 124.59, 121.66, 85.78,
46.15, 25.47. Anal. calcd for C17H16N2O3S: C, 62.18; H,
4.91; N, 8.53; S, 9.76. Found: C, 61.87; H, 5.00; N, 8.40;
S, 10.01.
7. Ba¨ckvall, J.-E.; Chinchilla, R.; Na´jera, C.; Yus, M.
Chem. Rev. 1998, 98, 2291–2312.
8. (a) Tanaskov, M. M.; Stadnichuk, M. D.; Kekisheva, L.
V. Zh. Obshch. Khim. 1980, 50, 1738–1744; (b) Guittet,
E.; Julia, S. Synth. Commun. 1981, 11, 709–722.
9. Oxley, P.; Partridge, M. W.; Robson, T. D.; Short, W. F.
J. Chem. Soc. 1946, 763–771.
12. Lee, G. A. Synthesis 1982, 508–509.
13. Barton, D. H. R.; Zard, S. Z. J. Chem. Soc., Chem.
Commun. 1985, 1098–1100.
14. Uno, H.; Tanaka, M.; Inoue, T.; Ono, N. Synthesis 1999,
471–474.
10. (a) Wada, E.; Pei, W.; Yasuoka, H.; Chin, U.; Kanemasa,
S. Tetrahedron 1996, 52, 1205–1220; (b) Compound 3b:
White solid (CH2Cl2/n-hexane); mp 77°C; IR (neat) 3450,
15. Compound 8: white solid; mp 111.5°C; IR 1308, 1135
1
cm−1; H NMR l 7.96–7.93 (m, 2H), 7.74–7.56 (m, 5H),
1283, 1134 cm−1 1H NMR l 7.98–7.94 (m, 2H), 7.72–
;
7.46–7.42 (m, 3H), 6.33 (s, 1H), 3.55–3.50 (m, 2H),
3.30–3.25 (m, 2H); 13C NMR l 168.58, 162.53, 138.36,
134.18, 130.13, 129.54, 128.94, 128.68, 128.13, 126.74,
100.44, 53.59, 20.99. Anal. calcd for C17H15NO3S: C,
65.16; H, 4.82; N, 4.47; S, 10.23. Found: C, 65.36; H,
4.83; N, 4.44; S, 10.13.
7.57 (m, 3H), 5.04 (d, J=0.9 Hz, 1H), 4.90 (m, 1H), 4.60
(d, J=9 Hz, 1H), 3.32 (dd, J=14 and 9 Hz, 1H), 3.27 (br
s, 1H), 3.24 (dd, J=14 and 2.5 Hz, 1H), 1.68 (s, 3H); 13C
NMR l 143.61, 139.22, 134.14, 129.49, 128.06, 113.11,
69.80, 61.30, 18.09. Anal. calcd for C11H14O3S: C, 58.38;
H, 6.24; S, 14.17. Found: C, 58.49; H, 6.26; S, 13.96.