2740
D. Heller et al. / Tetrahedron: Asymmetry 13 (2002) 2735–2741
4. Experimental
MHz, CDCl3) l 1.45 (9H, s, CH3), 2.29 (3H, s, CH3),
3.66 (3H, s, OCH3), 4.82 (1H, s, ꢀCH), 10.38 (1H, s(br),
NH); 13C NMR (100 MHz, CDCl3) l 21.2 (CH3), 28.1
(C(CH3)3), 50.8 (OCH3), 81.0 (O-C), 94.0 (ꢀCH), 151.8,
155.5 (ꢀC-, N-CꢀO), 169.5 (CꢀO). Calcd for C10H17O4N
(215.25) C, 55.80; H, 7.96; N 6.51; found: C, 56.06; H,
7.92; N, 6.53.
4.1. General
Solvents were dried and freshly distilled under argon
before use. The syntheses of b-acylamido acrylates 2a–c
used as substrates were carried out following known
protocols.3b Flash chromatography was carried out
with silica gel 60 (particle size 0.040–0.063 mm, Merck).
NMR spectra were recorded at the following frequen-
cies: 400.13 MHz (1H) and 100.63 MHz (13C). Chemical
Acknowledgements
shifts of H and 13C NMR spectra are reported in ppm
1
The authors are grateful for the financial support pro-
vided by the Bmbf (03C0304A), Degussa AG (Du¨ssel-
dorf) and the Fonds der Chemischen Industrie. We
thank Dr. C. Fischer for the analysis of the hydrogena-
tion products by HPLC. It is a pleasure for us to
acknowledge skilled technical assistance by Mrs. C.
Pribbenow and Mrs. G. Wenzel. We thank Dr. I.
Grayson for critical reading of the manuscript.
downfield from TMS as internal standard. Signals are
quoted as s (singlet), br (broad) and m (multiplet).
Hydrogenation experiments have been carried out
under normal pressure and isobaric conditions with an
automatically registering gas measuring device (1.0 atm
overall pressure over the solution). The experiments
were performed with 0.01 mmol precatalyst, 1.0 mmol
of prochiral olefin in 15.0 mL MeOH at 25.0°C. The
conversion of the prochiral dehydroamino acids and
the %ee were determined by GC or HPLC: methyl
3-acetamido butenoate (2a): 50 m Chiraldex b-PH,
130°C; methyl 3-acetamido-2-pentenoate (2b): 25 m
Lipodex E, 130°C; methyl 4-methyl-3-acetamido-2-pen-
tenoate (2c): 25 m Lipodex E, 130°C; methyl 3-benzoyl-
oxycarbonylamido butenoate (2d): Chiralpak OD, n-
hexane: EtOH=97:3; methyl 3-t-butyloxycarbonyl-
amido butenoate (2e): Chiralpak OD, n-hexane:
EtOH=95:5.
References
1. (a) Sewald, N. In Bioorganic Chemistry, Highlights and
New Aspects; Diederichsen, U.; Lindhorst, T. K.; Wester-
mann, B.; Wessjohann, L. A.; Eds.; Wiley-VCH, 1999;
Chapter 4.2, p. 193; (b) Seebach, D.; Matthews, J. L.
Chem. Commun. 1997, 2015.
2. (a) Cole, D. C. Tetrahedron 1994, 50, 9517; (b) Juaristi,
E. Enantioselective Synthesis of i-Amino Acids; Wiley-
VCH: New York, 1997; (c) Liu, M.; Sibi, P. Tetrahedron
2002, 58, 7991.
3. (a) Achiwa, K.; Soga, T. Tetrahedron Lett. 1978, 1119;
(b) Zhu, G.; Chen, Z.; Zhang, X. J. Org. Chem. 1999, 64,
6907; (c) Yasutake, M.; Gridnev, I. D.; Higashi, N.;
Imamoto, T. Org. Lett. 2001, 3, 1701; (d) Heller, D.;
Holz, J.; Drexler, H.-J.; Lang, J.; Krimmer, H.-P.; Drauz,
K.; Bo¨rner, A. J. Org. Chem. 2001, 66, 6816; (e) Lee,
S.-g.; Zhang, Y. J. Org. Lett. 2002, 4, 2429; (f) Heller, D.;
Drexler, H.-J.; Spannenberg, A.; Heller, B.; You, J.;
Baumann, W. Angew. Chem., Int. Ed. 2002, 41, 777; (g)
Holz, J.; Monsees, A.; Jiao, H.; You, J.; Komarov, I. V.;
Fischer, C.; Drauz, K.; Bo¨rner, A. J. Org. Chem. 2002, in
press.
4.2. General procedure for the preparation of Boc- and
Cbz-protected enamides 2d,e
To ethyl acetoacetate (20 mM, 2.32 g) t-butyl carba-
mate (40 mM, 4.68 g) and benzyl carbamate (40 mM,
6.04 g), respectively, dissolved in toluene (100 mL),
p-toluene sulfonic acid (2 mM, 360 mg) was added. The
mixture was heated under reflux for 24 h. After cooling
to rt the solution was washed with aq. NaHCO3 solu-
tion (1N, 100 mL) and water (100 mL). After drying
(Na2SO4) and filtration the solvent was evaporated. The
products were purified by flash chromatography (n-hex-
ane: AcOEt=9:1).
4. Heller, D.; Drexler, H.-J.; You, J.; Baumann, W.; Drauz,
K.; Krimmer, H.-P.; Bo¨rner, A. Chem. Eur. J. 2002,
5196.
4.2.1. Z-Methyl 3-benzyloxycarbonylamido-2-butenoate
(Z-2d). The raw product was first purified by bulb-to-
bulb distillation. Under these conditions the corre-
sponding benzoate was also formed as a side product.
5. Zhou, Y.-G.; Tang, W.; Wang, W.-B.; Li, W.; Zhang, X.
J. Am. Chem. Soc. 2002, 124, 4952.
6. (a) Lubell, W. D.; Kitamura, M.; Noyori, R. Tetra-
hedron: Asymmetry 1991, 2, 543; (b) Komarov, I. V.;
Monsees, A.; Kadyrov, R.; Fischer, C.; Schmidt, U.;
Bo¨rner, A. Tetrahedron: Asymmetry 2002, 13, 1615.
7. (a) Burk, M. J. J. Am. Chem. Soc. 1991, 113, 8518; (b)
Burk, M. J.; Feaster, J. E.; Nugent, W. A.; Harlowe, R.
L. J. Am. Chem. Soc. 1993, 115, 10125.
8. Kagan, H. B.; Dang, T. P. J. Am. Chem. Soc. 1972, 94,
6429.
9. (a) Bo¨rner, A.; Holz, J.; Kless, A.; Heller, D.; Berens, U.
Tetrahedron Lett. 1994, 35, 6071; (b) Holz, J.; Bo¨rner, A.;
Kless, A.; Borns, S.; Trinkhaus, S.; Selke, R.; Heller, D.
Tetrahedron: Asymmetry 1995, 6, 1973.
1
Colorless syrup, 2.20 g (44%), bp0,2=150°C; H NMR
(400 MHz, CDCl3) l 2.33 (3H, s, CH3), 3.66 (3H, s,
OCH3), 4.90 (1H, s, ꢀCH), 5.13 (2H, s, CH2Ph), 7.33–
7.39 (5H, m, arom. H), 10.69 (1H, s(br), NH); 13C
NMR (100 MHz, CDCl3) l 21.1 (CH3), 50.9 (OCH3),
67.0 (CH2Ph), 95.0 (=CH), 128.1, 128.3, 128.5, 135.6
(arom. C), 152.6, 154.7 (-Cꢀ, N-CꢀO), 169.3 (CꢀO).
Calcd for C13H15O4N (249.27): C, 62.64; H, 6.07; N,
5.62; found: C, 63.04; H, 6.22; N, 5.45.
4.2.2. Z-Methyl 3-t-butyloxycarbonylamido-2-butenoate
1
(Z-2e). Colorless syrup, 2.40 g (56%); H NMR (400