T. Ikenaga et al. / Tetrahedron 61 (2005) 2105–2109
2109
Previously, Nishimura and co-workers reported13 that the
hydrogenation of III over Pd metal catalyst overwhelmingly
gave the b-alcohol isomer. This result has been explained on
the basis of an attractive interaction of the steroid a-face
with the Pd catalyst. In the reductive amination, the
structure of the steroid imine intermediate may be similar
to that of III. Therefore it is presumed that the addition of
hydrogen to the a-side of the steroid imine intermediate may
occur predominantly, as in the hydrogenation of III.
temperature was raised to 260 8C at 5 8C/min after holding
60 8C for 20 min for the reaction mixture of I. For the
reaction mixture of II, it was raised to 200 8C at 5 8C/min
after holding at 70 8C for 10 minutes. The temperature was
maintained constant at 280 8C for the reaction mixture of
III. The structure of bornylamine (the endo isomer),
isobornylamine (the exo isomer), and a- and b-5a-
cholestan-3-amines produced from II and III were con-
firmed by GC-MS (JMS-Automass 150, JEOL Ltd, Tokyo)
and 1H NMR (Fourier Transform NMR Spectrometer
Model R-90H, Hitachi, Ltd, Tokyo). The structure of
N-ethylbornylamine and N-ethylisobornylamine were con-
The reductive amination of III over Ru and 5% Ru–C also
gave the b-amino isomer in greater amounts than the
a-amino isomer and the selectivity to the b-amino isomer
further increased in the presence of ammonium chloride. It
is probable that the stereochemistry is controlled more to
give the b-amino isomer by the hydrogenation step of the
steroid imine which would be produced more rapidly in the
presence of ammonium chloride.
1
firmed by measurements with GC-MS and H NMR, and a
related study14 for their analysis. The surface area of Pd
metal blacks was measured by SHIMADZU FLOW SORB
II 2300, Shimadzu Co., Ltd Tokyo.
Acknowledgements
3. Experimental
We are grateful to Professor emeritus Shigeo Nishimura of
Tokyo Univ. of Agriculture and Technology for his helpful
comments.
Catalyst. The Pd or Ru metal catalysts were prepared by
reducing the corresponding metal hydroxides (1.0 g) in
distilled water (20 cm3) for 30 min at room temperature and
under 0.2–0.3 MPa of hydrogen pressure in a Parr
hydrogenation apparatus. The metal black thus produced
was washed with distilled water until the washing was
neutral, and then dried in a desiccator under vacuum at room
temperature.
References and notes
1. (a) Emerson, W. S. Org. React. 1948, 4, 174. (b) Rylander,
P. N. Catalytic Hydrogenation over Platinum Metals;
Academic: New York, 1967; pp 291–303. (c) Freifelder, M.
Practical Catalytic Hydrogenation; Wiley-Interscience: New
York, 1971; pp 333–345. (d) Nishimura, S. Handbook of
Heterogeneous Catalytic Hydrogenation for Organic
Synthesis; Wiley: New York, 2001; p 226.
Commercial 5% Pd or Ru on carbon catalysts were
purchased from N.E.Chemcat Co., Ltd.
2. Yada, S.; Yazawa, N.; Yamada, Y.; Sukegawa, S.; Takagi, Y.
Nippon Kagaku Kaishi 1989, 641.
Material. Compound I (a purity of over 98%), compound II
(a purity of over 98%) and compound III (a purity of over
97%) were purchased from Wako Pure Chemical Ind., Ltd,
Tokyo, Tokyo Kasei Kogyo Co., Ltd Tokyo, and Aldrich
Chemical Co., USA, respectively. These compounds in a
purity of over 97–98% as judged by gas chromatography
were used without further purification.
3. Yada, S.; Takagi, Y. Nippon Kagaku Kaishi 1991, 20.
4. Yada, S.; Takagi, Y.; Hiyamizu, M. Nippon Kagaku Kaishi
1995, 107.
5. Yada, S.; Hiyamizu, M.; Takagi, Y. Nippon Kagaku Kaishi
1998, 525.
6. Layer, R. W. Chem. Rev. 1963, 63, 489.
7. Alexander, E. R.; Misegades, L. A. J. Am. Chem. Soc. 1948,
70, 1315.
Reductive amination and analysis of reaction mixtures: A
30 cm3 autoclave (for reaction of I) and a 100 cm3 autoclave
(for reaction of II and III) of an electromagnetically stirring
type were charged with the catalyst (0.01 g of Pd or Ru
metal, or 0.2 g of 5% Pd or Ru metal on carbon catalyst), the
carbonyl compound [I (0.30 g, 2.5!10K3 mol), II (0.77 g,
5.0!10K3 mol), and III (0.077 g, 2.0!10K4 mol)], and
10–20 cm3 of the solvent EtOH at an initial hydrogen
pressure of 6-8 MPa. The temperature was maintained
constant at 50 8C for I, at 200 8C for II and at 50 8C for III,
during the reductive amination. Ammonia gas was led into
chilled ethanol solvent (10–20 cm3) through a soda-lime
tube from the ammonia bomb and then the amount of
ammonia dissolved [about 1.0 g (6.0!10K2 mol)] was
determined by balance. Ammonium chloride [0.2 g (3.73!
10K3 mol)] was added to the solvent. After the completion
of the reaction, all products were analyzed by gas
chromatography (SHIMADZU GC-14A) using a capillary
column (25 m for reaction mixture of I and II and 50 m for
reaction mixture of III) containing CBP1 and also identified
by direct comparison with authentic samples. The
8. Kindler, K.; Helling, H. G.; Sussner, E. Justus Liebigs Ann.
Chem. 1957, 605, 200.
9. Robinson, J. C., Jr.; Snyder, H. R. Org. Synth., Coll. Vol. 3
1955, 717.
10. Nishimura, S. Handbook of Heterogeneous Catalytic Hydro-
genation for Organic Synthesis; Wiley: New York, 2001; p
231.
11. Frank, J. P.; Martine, G. P. In Deactivation and Poisoning of
Catalysts; Ouder, J., Wise, H., Eds.; Marcel Dekker: New
York, 1985; p 241.
12. (a) Feghouli, G.; Vanderesse, Y.; Fort, Y.; Caubere, P.
Tetrahedron Lett. 1988, 29, 1383. (b) Wilcox, C. F.; Sexton,
M.; Wilcox, M. F. J. Org. Chem. 1961, 26, 3504. (c) For
example, borneol (the endo isomer) is the more stable of the
borneol/isoborneol (the exo isomer) mixture and constitutes
74G3% at an equilibrium. Similarly, bornylamine (the endo
isomer) is considered to be more stable than isobornylamine
(the exo isomer).
13. Nishimura, S.; Ishige, M.; Shiota, M. Chem. Lett. 1977, 535.
14. Kiyooka, S.; Suzuki, K. Bull. Chem. Soc. Jpn. 1974, 47, 2081.