278
E. Cesarotti et al. / Tetrahedron: Asymmetry 19 (2008) 273–278
4.2. General procedure for asymmetric hydrogenation
Acknowledgments
`
In a Schlenk tube under argon, a suspension of substrate
and the proper amount of HBF4 in ether is stirred for
30 min at room temperature. The resulting solution is
transferred with a cannula to a Schlenk tube containing
the proper amount of Rh(I) catalyst and then into a glass
autoclave connected to a gas burette filled with H2 or D2.
This work has been funded by the FIRST, Universita degli
Studi di Milano and by Flamma s.p.a. Via Bedeschi, 22-
24040 Chignolo D’Isola-BG-Italy. We also wish to thank
Johnson Matthey Plc; indeed this work has been realized
by using their generous loan of RhCl3ꢁ3H2O.
4.3. Preparation of racemic and (S)-(ꢀ)-methyl 2-benz-
amido-3-(4,5-dihydro-1H-imidazol-5-yl)propanoate as
HPLC standards
References
1. Asymmetric Catalysis on Industrial Scale; Blaser, H. U.,
Schmidt, E., Eds.; Wiley-VCH, 2003.
2. Vineyard, B. D.; Knowles, W. S.; Sabaky, M. J.; Bachman,
G. L.; Weinkauff, D. J. J. J. Am. Chem. Soc. 1977, 99, 5946.
3. Knowles, W. S. Acc. Chem. Res. 1983, 16, 106.
4. Kagan, H. B.; Dang, T. P. J. Chem. Soc., Chem. Commun.
1971, 481.
5. The Handbook of Homogeneous Hydrogenation; de Vries, J.
G., Elsevier, C. J., Eds.; Willey-VCH: Weinheim, 2007; Vol.
1–3.
6. Comprehensive Asymmetric Catalysis; Jacobsen, E. N., Pfaltz,
A., Yamamoto, H., Eds.; Springer: Berlin, 1999.
7. Fenselau, C. J. Chromatogr. B: Anal. Technol. Biomed. Life
Sci. 2007, 855, 14–20.
8. Aldini, G.; Facino, R. M.; Beretta, G.; Carini, M. Biofactors
2005, 24, 77–87.
9. Aldini, G.; Dalle Donne, I.; Colombo, R.; Maffei Facino, R.;
Milzani, A.; Carini, M. Chem. Med. Chem. 2006, 1, 1045–
1058.
10. Redox Proteomics: From Protein Modifications to Cellular
Dysfunction and Diseases; Carini, M., Aldini, G., Maffei
Facino, R., Dalle-Donne, I., Scaloni, A., Butterfield, D. A.,
Eds.; Wiley, 2006.
Thionyl chloride (1.05 mL, PM = 118.97, d = 1.63, 14.38
mmol) is added dropwise to the suspension of commer-
cially available (S)-(+)-histidine monohydrochloride
(2.2967 g, PM = 193, 11.9 mmol) in 50 mL of methanol
and the solution is refluxed for 12 h then reduced under
vacuum to give racemic or (S)-(+)-histidine methyl ester
dihydrochloride as a white solid. Elemental Anal. Calcd
for C7H13N3O2Cl2: C, 34.73; H, 5.41; N, 17.36. Found:
1
C, 34.66; H, 5.52; N, 17.52. H NMR: ppm 2.25 (m, 2H),
3.73 (s, 3H), 7.52 (s, 1H), 9.07 (s, 1H), 14.63 (s, 2H).
2.7799 g, yield 96.6%.
Under an inert atmosphere, a solution of benzoyl chloride
(2.1 mL, PM = 140, d = 1.212, 18.5 mmol) and TEA
(5.12 mL, PM = 101, d = 0.726, 36.8 mmol) is added drop-
wise to the suspension of racemic or (S)-(+)-histidine
methyl ester dihydrochloride (2.2118 g, 9.2 mmol) in
30 mL of dry chloroform. The suspension is stirred at room
temperature for 2 days, then 30 mL of water is added and
the solution is extracted with 2 ꢂ 20 mL of chloroform.
11. Vistoli, G.; Pedretti, A.; Cattaneo, M.; Aldini, G.; Testa, B. J.
Med. Chem. 2006, 49, 3269–3277.
12. Erlenmeyer, E.; Halsey, J. T. Justus Liebig’s Ann. Chem. 1899,
307, 138.
13. Masquelin, T.; Broger, E.; Muller, K.; Schmid, R.; Obrecht,
¨
D. Helv. Chim. Acta 1994, 77, 1395.
14. Schmidt, U.; Langer, B.; Kirschbaum, B.; Braun, C. Synthesis
1994, 1138.
15. Cesarotti, E.; Chiesa, A. Tetrahedron Lett. 1982, 43, 275.
16. Cativela, C.; Mayoral, J.; Melendes, E.; Oro, L.; Pinillos, M.;
Uson, R. J. Org. Chem. 1984, 49, 2502.
17. Do¨bler, C.; Kreuzfeld, H. J.; Michalik, M.; Krause, H. W.
Tetrahedron: Asymmetry 1996, 7, 117.
18. Bozell, J. J.; Voght, C. E.; Gozum, J. J. J. Org. Chem. 1991,
56, 2584.
19. Halpern, J.. In Asymmetric Synthesis; Morrison, J. D., Ed.;
Academic: Orlando, FL, 1985; Vol. 5, and references cited
therein.
20. Feldgus, S.; Landis, C. R. J. Am. Chem. Soc. 2000, 122,
12714.
The combined organic layers are dried and evaporated in
vacuum to give yellow oil. The crude oil residue is dissolved
in 50 mL of MeOH saturated with NaHCO3; after 15 min
of vigorous stirring at room temperature the excess of
NaHCO3 is neutralized with glacial acetic acid. The solvent
is removed in vacuum and the oily residue is dissolved in
25 mL of water and extracted with 4 ꢂ 20 mL of chloro-
form. The combined organic layers are dried and evapo-
rated to leave yellow oil. The oil is triturated with 30 mL
of hexane to give (S)-(ꢀ)-methyl 2-benzamido-3-(4,5-
dihydro-1H-imidazol-5-yl)propanoate as a white solid
(PM = 273, 1.9 mmol, yield 21%).
Elemental Anal. Calcd for C14H15N3O3: C, 61.53; H, 5.53;
1
N, 15.38. Found: C, 61.30; H, 5.51; N, 15.64. H NMR:
ppm 3.2 (d, 2H), 3.65 (s, 3H), 4.8 (q, 1H), 6.8 (s, 1H), 7.5
(m, 4H), 7.8 (d, 2H), 8.8 (d, 1H). For (S)-(ꢀ)-methyl
21. Genet, J. P. Acc. Chem. Res. 2003, 36, 908–918.
22. Erlenmeyer, E.; Halsey, J. T. Justus Liebig’s Ann. Chem. 1899,
307, 138.
2-benzamido-3-(4,5-dihydro-1H-imidazol-5-yl)propanoate
25
½aꢃD ¼ ꢀ70:7 (c 0.5 in HBF4 1.6 M in CH3OH).