H.-W. Shih, W.-C. Cheng / Tetrahedron Letters 49 (2008) 1008–1011
1011
11. (a) Groselj, U.; Drobnic, A.; Recnil, S.; Svete, J.; Stanovnik, B.;
Golobic, A.; Lah, N.; Leban, I.; Meden, A.; Golic-Grdadolinik, S.
Helv. Chim. Acta 2001, 84, 4303; (b) Foti, F.; Grassi, G.; Risitano, F.;
Rotondo, E.; Zona, D. Synlett 2004, 1577.
chemistry is applied in the generation of an 18-member
library with high yield, high purity, and excellent
regioselectivity.
12. Carlstrom, A.-S.; Frejd, T. Synthesis 1989, 414.
Acknowledgments
13. (a) Huisgen, R. Angew. Chem., Int. Ed. Engl. 1963, 2, 565; (b) Cheng,
W.-C.; Wong, M.; Olmstead, M. M.; Kurth, M. J. Org. Lett. 2002, 4,
741.
14. Manis, P. A.; Rathke, M. W. J. Org. Chem. 1980, 4952.
15. Cheng, W.-C.; Liu, Y.; Wong, M.; Olmstead, M. M.; Lam, K. S.;
Kurth, M. J. J. Org. Chem. 2002, 67, 5673; and its references.
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Kamimura, A.; Hori, K. Tetrahedron 1994, 50, 7969.
This work is supported by National Science Council and
Academia Sinica.
Supplementary data
17. Hwu, J. R.; Jain, M. L.; Tsay, S.-C.; Hakimelahi, G. H. Tetrahedron
Lett. 1996, 37, 2035.
18. (a) Ravindranathan, T.; Hiremath, S. V.; Gosavi, K.; Rajagopal, R.
D. Synthesis 1989, 38; (b) Pham, T. Q.; Pyne, S. G.; Skelton, B. W.;
White, A. H. Tetrahedron Lett. 2002, 43, 5953.
Supplementary data associated with this article can be
References and notes
19. Zhong, J.; Gan, X.; Alliston, K. R.; Lai, Z.; Yu, H.; Groutas, C. S.;
Wong, T.; Groutas, W. C. J. Comb. Chem. 2004, 6, 556.
20. Typical procedure for the transformation (9?13): To a solution of 9
(0.26 g, 0.94 mmol) in CH2Cl2 (5 mL) under a nitrogen atmosphere at
0 °C was added phenyl isocyanate (0.33 g, 2.81 mmol, 3 equiv) and
triethylamine (0.47 g, 4.68 mmol). The mixture was stirred for 30 min
at room temperature, then warmed to 50 °C and stirred overnight.
The product was diluted with CH2Cl2 and washed with water several
times. The organic layer was dried over anhydrous MgSO4 and
concentrated in vacuo. The crude product was washed with CH2Cl2
by normal phase (silica gel) solid-phase extraction to give 13 (0.24 g,
0.86 mmol, 92%) as an oil. 1H NMR (400 MHz, CDCl3, ambient
temperature) d 4.79 (d, 1H, J = 2.4 Hz), 4.86 (s, 2H), 5.46 (d, 1H,
J = 2.4 Hz), 7.24–7.52 (m, 10H); 13C NMR (150 MHz, CDCl3) d
169.75, 155.36, 136.06, 131.81, 128.56, 128.40, 128.13, 128.07, 127.79,
126.63, 105.08, 47.01; HRMS calcd for C17H14N2O2 [M+H]+
279.1134, found 279.1144.
21. Typical procedure for the transformation (13?14a): 13 (0.24 g,
0.86 mmol) and 2,6-dichlorobenzaldehyde oxime (0.16 g, 0.86 mmol,
1 equiv) were dissolved in CH2Cl2 (4 mL) and the solution was
cooled to 0 °C. Aqueous NaOCl (5%, 2 equiv, 2.5 g, 1.72 mmol) was
added dropwise over 30 min, and the reaction mixture was stirred
vigorously for 8 h (0 °C?room temperature). The layers were
separated, and the aqueous layer was extracted with CH2Cl2. The
combined organic layers were dried with MgSO4 and concentrated
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to give 14a (0.36 g, 0.76 mmol, 89%) as
characterized without further purification. 14a: 1H NMR
(600 MHz, CDCl3, ambient temperature) 3.30 (d, 1H,
a white solid and
d
J = 18 Hz), 3.77 (d, 1H, J = 18 Hz), 4.67 (d, 1H, J = 18 Hz), 4.87
(d, 1H, J = 18 Hz), 7.15–7.45 (m, 13H); 13C NMR (150 MHz,
CDCl3) d 29.83, 31.04, 41.34, 43.87, 95.38, 125.83, 126.83, 127.60,
127.81, 127.95, 128.08, 128.23, 128.48, 128.54, 128.79, 128,96,
129.25, 131.24, 131.94, 135.24, 136.36, 153.95, 154.63, 168.23;
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HRMS calcd for
466.0757.
C24H17Cl2N3O3[M +
H]+ 466.0725, found
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22. Two alkyl halides (benzyl bromide and 4-bromobenzyl bromide),
three isocyanates (phenyl isocyanate, propanyl isocyanate, and
cyclohexanyl isocycanate), and three oximes (2,6-dichlorobenzalde-
hyde oxime, 4-bromobenzaldehyde oxime, and 2,5-dimethoxybenzal-
dehyde oxime) were utilized for diversification of R1, R2 and R3,
respectively.