H. Brunner et al. / Tetrahedron: Asymmetry 14 (2003) 2177–2187
2187
the reaction mixture was cooled to rt and chro-
Acknowledgements
matographed with CH2Cl2 on a short silica gel
column to remove the catalyst and decomposition
products. After removal of the solvent, further purifi-
cation was made possible by recrystallisation from
hexane. 1H NMR (300 MHz, CDCl3): l=1.50–2.06
(m, <8H, CH2, 7a/7b), 2.09 (s, <3H, NCH3, 7b), 2.29
(sb, <1H, NH, 7b), 2.39–2.55 (m, <2H, CH2, 7b),
2.70–2.84 (m, 1H, CH2, 7b), 3.00 (s, <3H, NCH3, 7a),
H.B. and H.B.K. thank the Alexander von Humboldt
Foundation for a cooperation on the basis of a Max-
Planck Award for International Cooperation. We
thank the Deutsche Forschungsgemeinschaft and the
CNRS for a transnational German-French CERC3
project.
5.50 (s, <1H, OH, 7a), 7.02–7.10 (m, <1H, CHarom
,
References
7a), 7.19–7.38 (m, <3H, CHarom, 7a/7b), 7.40–7.48 (m,
<1H, CHarom, 7a), 7.54 (dd, J=7.8 Hz, J=1.8 Hz,
<1H, CHarom, 7b). 1H NMR of 7b (250 MHz, 1
equiv. (R)-(−)-mandelic acid, CDCl3, NCH3 signal
splits enabling enantiomeric analysis): l=1.37–2.10
(m, 5H, CH2), 2.23/2.25 (2s, 2×1.5H, NCH3), 2.42–
2.66 (m, 2H, CH2), 2.86–3.06 (m, 1H, CH2), 5.00 (s,
1H, CHOH), 6.10 (sb, 3H, NH/OH/COOH), 7.20–
7.51 (m, 9H, CHarom).
1. Brunner, H.; Sto¨hr, F. Eur. J. Org. Chem. 2000, 2777
related literature cited therein.
2. Brunner, H.; Kagan, H. B.; Kreutzer, G. Tetrahedron:
Asymmetry 2001, 12, 497.
3. Kreutzer, G. Ph.D. Thesis, Universita¨t Regensburg, 2003.
4. Honzl, J.; Lo¨vy, J. Tetrahedron 1984, 40, 1885.
5. Nishiyama, H.; Kondo, M.; Nakamura, T.; Itoh, K.
Organometallics 1991, 10, 500.
6. Collin, J.; Namy, J.-L.; Dallemer, F.; Kagan, H. B. J.
3.9. Synthesis of new ligands used in catalysis
Org. Chem. 1991, 56, 3118.
7. Organikum, 20. Auflage, Wiley-VCH: Weinheim, 1999,
286.
8. Dwyer, F. P.; Garvan, F. L.; Shulman, A. J. Am. Chem.
3.9.1.
(S)-(+)-N,N,N%,N%-Tetramethyl-1,2-diamino-3-
(S)-(+)-1,2-Diamino-3-methylbutane
methylbutane.
(1.13 g, 11.1 mmol) was methylated by Eschweiler–
Clarke methylation according to literature.9 Colour-
less liquid; 0.28 g, 15% yield; bp 120°C/5 mm Hg;
[h]D=178 (c=2.61, CHCl3); IR (film): 2980 (s, wCH),
Soc. 1959, 81, 290.
9. Clarke, H. T.; Gillespie, H. B.; Weisshaus, Z. J. Am.
Chem. Soc. 1933, 55, 4571.
10. Kurganov, A. A.; Davankov, V. A.; Ya. Zhuchkova, L.;
Ponomaryova, T. M. Inorg. Chim. Acta 1980, 39, 237.
11. Brunner, H.; Schmidt, M.; Unger, G. Eur. J. Med.
Chem.—Chim. Ther. 1985, 20, 509.
12. Howarth, J.; Gillespie, K. Molecules 2000, 5, 993.
13. Nishiyama, H.; Tomonori, T.; Takayama, M.; Itoh, K.
Tetrahedron: Asymmetry 1993, 4, 1461.
1
2840 (s, wCH), 2800 cm−1 (s, wNCH3); H NMR (300
MHz, CDCl3): l=0.87 (d, J=6.4 Hz, 3H, CH3), 0.91
(d, J=6.4 Hz, 3H, CH3), 1.73–1.85 (m, 1H,
CH(CH3)), 2.02 (dd, J=12.8 Hz, J=4.2 Hz, 1H,
CH2), 2.14–2.22 (m, 1H, CH), 2.17 (s, 6H, NCH3),
2.23 (s, 6H, NCH3), 2.39 (dd, J=12.8 Hz, J=7.2 Hz,
1H, CH2); 13C NMR (75.48 MHz, CDCl3): l=19.32
(1C, CH3), 21.43 (1C, CH3), 28.53 (1C, CH), 41.69
(2C, NCH3), 45.94 (2C, NCH3), 58.00 (1C, CH2),
66.46 (1C, CH); MS (CIMS, NH3): m/z (%) 159.1
(100.0) [MH].
14. Brunner, H.; Obermann, U.; Wimmer, P. J. Organomet.
Chem. 1986, 316, C1.
15. Brunner, H.; Obermann, U. Chem. Ber. 1989, 122, 499.
16. Brunner, H.; Nishiyama, H.; Itoh, K. In Catalytic Asym-
metric Synthesis; Ojima, I., Ed. Asymmetric Hydrosilyla-
tion; VCH: New York, 1993; p. 303.
17. Chelucci, G.; Medici, S.; Saba, A. Tetrahedron: Asymme-
try 1999, 10, 543.
18. Cheng, J.; Deming, T. J. Macromolecules 1999, 32, 4745.
19. Benson, S. C.; Cai, P.; Haiza, M. A.; Tokles, M.; Snyder,
J. K. J. Org. Chem. 1988, 53, 5335.
3.9.2. 2-[4-(S)-Isopropyloxazolin-2-yl]-3-methylpyridine.
Synthesis starting from 2-cyano-3-methylpyridine
according to the literature procedure17 with the amino
alcohol (S)-(+)-2-amino-3-methyl-1-butanol obtained
from (S)-(+)-valine.31 Colourless crystals; 1.07 g, 52%
yield; mp 58°C; [h]D=−82 (c=0.93, CHCl3); IR
(KBr): 3040 (w, wCHarom), 2960 (s, wCH), 1640 cm−1
20. Brunner, H.; Henning, F.; Weber, M. Tetrahedron:
Asymmetry 2002, 13, 37.
1
21. Brunner, H.; Zettler, C. Chem. Monthly, in press.
22. Bolm, C.; Bienewald, F.; Seger, A. Angew. Chem. 1996,
108, 1767; Angew. Chem., Int. Ed. Engl. 1996, 35, 1657.
23. Preiss, D. Patent DE 44 09 671 C1, 1995.
24. Menhart, V.; Mitinko, V. Patent CS 277268, 1992.
25. Klose, R.; Hoppe, U. (S)-Ketamin; Springer Verlag:
Berlin, Heidelberg, New York, 2002.
(s, wCꢀN); H NMR (300 MHz, CDCl3): l=0.94 (d,
J=6.8 Hz, 3H, CH3), 1.03 (d, J=6.8 Hz, 3H, CH3),
1.76–1.90 (m, 1H, CH(CH3)2), 2.59 (s, 3H, CH3),
4.08–4.21 (m, 2H, CHCH2), 4.35–4.49 (m, 1H,
CHCH2), 7.22 (dd, J=7.8 Hz, J=4.7 Hz, 1H,
CHarom), 7.53–7.57 (m, 1H, CHarom), 8.47–8.51 (m,
1H, CHarom); 13C NMR (75.48 MHz, CDCl3): l=
18.42 (1C, CH(CH3)2), 18.95 (1C, CH(CH3)2), 20.52
(1C, CH3), 32.92 (1C, CH(CH3)2), 69.75 (1C, CH2),
73.54 (1C, CH), 124.64 (1C, CHarom), 134.93 (1C,
Carom), 139.18 (1C, CHarom), 145.82 (1C, Carom),
146.78 (1C, CHarom), 162.20 (1C, CꢀN); MS (EIMS):
m/z (%) 204.1 (51.4) [M]; HRMS: found 204.1268;
C12H16N2O (204.1): calcd C, 70.56; H, 7.90; N, 13.71;
found C, 70.49; H, 8.79; N, 13.76.
8
26. Heinz, T. W. Deutsches Arzteblatt 1999, 96, 2724.
27. Steiner, K. Patent WO 97/43244, 1997.
28. Russo, T.; Freire, V. Patent WO 01/98265 A2, 2001.
29. Menzer, M.; Kazmirowski, H.-G. Mo¨ller, G.; Laban, G.
Patent DD 217 511 A1, 1985.
30. Creary, X.; Inocencio, P. A.; Underiner, T. L.; Kostro-
min, R. J. Org. Chem. 1985, 50, 1932.
31. Vogl, O.; Po¨hm, M. Monatsh. Chem. 1952, 83, 541.