PAPER
Catalytic Hydrogen Transfer Reductions Using Ammonium Formate/Pd-C
2025
a,b-unsaturated steroid ketones, which otherwise require silica gel (Merck, 70–230 mesh) column and/or crystallized from
2
3
the appropriate solvent (see Figure 1 for products).
more vigorous conditions and/or platinum catalyst.
1
Thus, the unhindered D -double bond in 5a-cholest-1-en-
-one (30) was easily reduced to ketone 31, while the
highly hindered 8,9-double bond in 3b-acetoxy-5a-
lanost-8-en-7-one was unchanged after prolonged reac-
tion.
4
0
3
Acknowledgment
Financial support of the work by the State Committee for Scientific
Research (Project No. 7 T09A 110 21) is gratefully acknowledged.
Interestingly, cholest-4-en-3-one (32) was stereoselec-
4
1
References
tively reduced to 5b-cholestan-3-one (33). This stereo-
chemical outcome of the reaction is important since
(1) Brieger, G.; Nestrick, T. J. Chem. Rev. 1974, 74, 567.
(2) Johnstone, R. A. W.; Wilby, A. H.; Entwistle, J. D. Chem.
Rev. 1985, 85, 129; and references cited therein.
4
catalytic reduction of steroid D -3-ketones usually affords
a mixture of 5a- and 5b-3-ketones, while reduction with
metals in liquid ammonia results in formation of 5a-ste-
(3) Anderson, J. R. Structure of Metallic Catalysts; Academic
Press: New York, 1975.
2
3
5
roids. The D -double in 3b-acetoxycholest-5-en-7-one
(
(
4) Ram, S.; Ehrenkaufer, R. E. Synthesis 1988, 91.
5) Gartiser, T.; Selve, C.; Delpuech, J. J. Tetrahedron Lett.
4
2
43
(
34) was stereoselectively reduced to 7-ketone 35 hav-
ing the 5a configuration. The efficient and fast reduction
1983, 24, 1609.
1
6
of D -double bond was found in the reaction of 3b-ace-
toxypregna-5,16-dien-20-one (24). The product 25 was
(6) Entwistle, I. D.; Jackson, A. E.; Johnstone, R. A. W.;
Telford, R. P. J. Chem. Soc., Perkin Trans.1 1977, 443.
(7) (a) Ram, S.; Ehrenkaufer, R. E. Tetrahedron Lett. 1984, 25,
1
slightly contaminated with the 17b-H isomer ( H NMR).
3415. (b) Ram, S.; Ehrenkaufer, R. E. Synthesis 1986, 133.
Other examples of effective hydrogenation include reduc-
tion of ethyl cinnamate to 2-phenylpropionic acid ethyl
ester (96%, 1.5 h) and maleic anhydride, which gave suc-
cinic anhydride and succinic acid in the ratio 2:3 (0.6 h).
(
8) Kabalka, G. W.; Pace, R. D.; Wadgaonkar, P. P. Synth.
Commun. 1990, 20, 2453.
(9) Brown, G. R.; Foubister, A. J. Synthesis 1982, 1036.
10) Ram S., Spicer L. D.; Tetrahedron Lett. 1988, 29: 3741.
11) Anwer, M. K.; Spatola, A. F. Tetrahedron Lett. 1985, 26,
(
(
In summary, these results demonstrate that the reducing
system Pd/C-HCO NH /MeOH is simple, effective, and
1381.
2
4
(12) Berdini, V.; Cesta, M. C.; Curti, R.; D’Anniballe, G.; Di
Bello, N.; Nano, G.; Nicolini, L.; Topai, A.; Allegretti, M.
Tetrahedron 2002, 58, 5669.
13) (a) Anwer, M. K.; Spatola, A. F. Synthesis 1980, 929.
b) Anwer, M. K.; Spatola, A. F. J. Org. Chem. 1983, 48,
503.
applicable for reduction of a variety of carbon–carbon
double bonds under mild conditions. The reduction may
be chemoselective if the double bonds under consider-
ation differ markedly in steric hindrance.
(
(
3
An important benefit is an easy isolation of the products
from the reaction mixture. It requires only filtration of the
catalyst followed by removal of the solvent. In some cases
filtration of the crude product through a short column of
silica gel, followed by crystallization is preferable. This
hydrogenation procedure offers an attractive alternative to
other methods available for reduction of carbon–carbon
double bonds.
(14) ElAmin, B.; Anantharamaiah, G. M.; Royer, G. P.; Means,
G. E. J. Org. Chem. 1979, 44, 3442.
(15) Bieg, T.; Szeja, W. Synthesis 1985, 76.
(16) Zacharie, B.; Moreau, N.; Dockendorff, C. J. Org. Chem.
2
001, 66, 5264.
17) Lee, S. H.; Park, Y. J.; Yoon, C. h. M. Tetrahedron Lett.
000, 41, 887.
(
2
(18) Tabaczka, B.; Paryzek, Z. Org. Prep. Proced. Int. 2001, 33,
400.
(
(
(
19) Hannon, S. J.; Kundu, N. G.; Hertzberg, R. P.; Shatt, R. S.;
Heidelberger, C. Tetrahedron Lett. 1980, 21, 1105.
20) Nowak, P.; Błaszczyk, K.; Paryzek, Z. Org. Prep. Proced.
Int. 1994, 26, 374.
1H NMR spectra were recorded with a Varian Gemini 300 VT spec-
trometer at 300 MHz in CDCl using TMS as an internal standard.
3
Electron-impact mass spectra were recorded with an AMD 402
spectrometer using ionization energy of 70 eV. The substrates were
either commercial products and were used as purchased or were
prepared according to literature procedures. The progress of the re-
action was followed by TLC on silica gel (Merck 60 F254) plates im-
21) Aranda, G.; Lallemand, J.-Y.; Azerad, R. Synth. Commun.
1994, 24, 2525.
(
(
22) Hammert, F. Bull. Soc. Chim. Fr. 1966, 976.
23) Loewenthal, H. J. E. Tetrahedron 1959, 269.
(24) Pines, M. Steroids 1966, 31, 877.
1
pregnated with silver nitrite and/or H NMR analysis. The reduction
(
(
25) Emmons, G. T.; Willson, W. K.; Schroepfer, G. J. Magn.
Res. Chem. 1989, 27, 1012.
26) (a) Bentley, H. R.; Henry, J. A.; Irvine, D. S.; Spring, F. S.
J. Chem. Soc. 1953, 3673. (b) Nagai, M.; Ando, T.; Tanaka,
N.; Tanaka, O.; Shibata, S. Chem. Pharm. Bull. 1972, 20,
1
products were identified by comparison of their H NMR and mass
spectra with those of authentic samples.
Catalytic Transfer Hydrogenation of Unsaturated Compounds;
General Procedure
1
212. (c) Mills, J. S. J. Chem. Soc. 1956, 2196. (d) Marker,
R. E.; Wittle, E. L.; Mixon, L. W. J. Am. Chem. Soc. 1937,
9, 1368.
27) Drefahl, G.; Ponsold, K.; Schick, H. Chem. Ber. 1965, 98,
04.
28) Dang, H. S.; Roberts, B. P. J. Chem. Soc., Perkin Trans. 1
002, 1161.
(29) Gschwendtner, W.; Schneider, H.-J. J. Org. Chem. 1980, 45,
507.
To a solution of an olefin or enone (see Figure 1) (1 mmol) in
MeOH (5 mL), the catalyst 10% Pd/C (Fluka) (10% of olefin by
weight) and ammonium formate (630 mg, 10 mmol) was added.
The mixture was refluxed until reduction was complete (TLC mon-
itoring, time given in Table 1). After cooling, the mixture was fil-
tered and the solvent evaporated under reduced pressure. To the
5
(
(
6
2
residue, CHCl (few mL) was added to precipitate the excess of am-
3
monium formate. After filtration, the solvent was evaporated to give
crude product of sufficient purity. This was filtered through a short
3
Synthesis 2003, No. 13, 2023–2026 © Thieme Stuttgart · New York