Chemoselective reduction of aldehydes in the presence of ketones utilizing Raney nickel

Article abstract of DOI:10.1055/s-2000-6498

Raney nickel is an effective reagent to achieve the chemoselective reduction of aldehydes in the presence of ketones, which takes place in high yield. Only highly hindered aldehydes do not undergo reduction.

Full text of DOI:10.1055/s-2000-6498

LETTER
197
Chemoselective Reduction of Aldehydes in the Presence of Ketones Utilizing
Raney Nickel
Alejandro F. Barrero,* E. J. Alvarez-Manzaneda, Rachid Chahboun, R. Meneses
Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Granada, 18071 Granada, Spain
Fax +34 58 24 33 18; E-mail: afbarre@goliat.ugr.es
Received 26 October 1999
have been reported: acetone, benzophenone and acetophe-
Abstract: Raney nickel is an effective reagent to achieve the
none were transformed into the corresponding secondary
chemoselective reduction of aldehydes in the presence of ketones,
alcohols after hydrogenation at 1-3 atm.
which takes place in high yield. Only highly hindered aldehydes do
not undergo reduction.
During our research into the use of Raney nickel as
Key words: chemoselectivity, reduction, aldehydes, ketones
chemoselective reductor we have found that the low reac-
tivity of this agent makes possible to achieve the selective
reduction of the aldehyde group in the presence of the ke-
tone function under mild conditions. Some representative
examples are summarized in the Table. The treatment of a
solution of an equimolecular mixture of acetophenone
(1a) and benzaldehyde (2a) in tetrahydrofuran with Raney
nickel at room temperature for 10 min afforded benzyl al-
cohol in a quantitative yield, with acetophenone being re-
covered unaltered. The behaviour of ketoaldehydes 3a-
13a, having different structural features, against Raney
nickel is shown in the Table. In most cases the corre-
sponding primary ketoalcohol was obtained in a high
yield. Aldehydes bearing formyl group on a quaternary
carbon were also reduced. Only the very highly hindered
aldehydes were unreactive; for example, compounds 10a
and 13a, in which the aldehyde group has a 1,3-diaxial in-
teraction with the angular methyl, remained unaltered af-
ter prolongued exposure to the reducing agent.
In a previous paper1 the effectiveness of Raney nickel to
accomplish the chemoselective reduction of conjugated
olefins in a,b-unsaturated carbonyl compounds, that also
contain isolated carbon-carbon double bond, was report-
ed. Our recent research has revealed that this reagent may
also be very effective for carrying out the selective reduc-
tion of aldehydes in the presence of ketones.
The selective reduction of aldehydes in the presence of
ketones constitutes an important challenge in organic syn-
thesis, due to the similar reactivity of these functions; in
most cases it is necessary to use expensive reagents and/
or work at low temperatures. This can be accomplished by
using aminoborane or tert-butylaminoborane.2 High se-
lectivity is also achieved with tributylstannane,3 especial-
ly in the presence of low-valency titanium.4 The use of
bulky hydrides has also demonstrated to be effective.
Thus, tetrabutylammonium triacetoxyborohydride affords
high yields of primary alcohols.5 Potassium triphenyl-
borohydride is effective when used at -78 °C.6 Lithium tri-
alkoxyaluminium hydrides also convert ketoaldehydes
into the corresponding ketoalcohols at a low temperature:7
for example, lithium tris(triethylmethoxy)aluminium hy-
dride shows high selectivity against the system hexanal-
cyclohexanone at temperatures below 0 °C.
In summary, Raney nickel is an effective reagent for
achieving the chemoselective reduction of aldehydes in
the presence of ketones. Only highly hindered aldehydes
do not undergo reduction.
Acknowledgement
We should like to thank the CICYT (Project PB-95 1192) for finan-
cial support. One of us (R. Meneses) thanks to the Instituto de Co-
operación Iberoamericana (ICI) (Agencia Española de Cooperación
Internacional, AECI) for tha award of a scholarship.
Although heterogeneous catalytic hydrogenation is a clas-
sical method of hydrogenation in preparative organic
chemistry, it has not been very widely used for reducing
carbonyl groups; however some studies into the catalytic
hydrogenation of aldehydes and ketones have been report-
ed. The use of Raney nickel and other modified nickel cat-
alysts for this purpose has been described.8-10 Saturated
aliphatic aldehydes are converted to the corresponding
alcohols quantitatively using Raney nickel. Unsaturated
aliphatic aldehydes undergo complete reduction, includ-
ing both the aldehyde and carbon-carbon double bond;
thus, cinnamaldehyde was converted into hydrocinnamyl
alcohol by treating with Raney nickel.8 This reagent also
allows the hydrogenation of benzaldehyde into benzyl
alcohol practically without any hydrogenolysis.8 Some
examples of the reduction of ketones with Raney nickel
References and Notes
(1) Barrero, A.F.; Manzaneda, E.A.; Chahboun, R.; Meneses, R.
Synlett 1999 1663.
(2) Andrews, G.C. Tetrahedron Letters 1980, 21, 697.
(3) Fung, N.Y.M.; de Mayo, P.; Schauble, J.H.; Weedom, A.C.
J. Org. Chem. 1978, 43, 3977.
(4) Adams, C.M.; Schemenaur, J.E. Synth. Commun. 1990, 20,
2359.
(5) Nutaitis, C.F.; Gribble, G.W. Tetrahedron Letters 1983, 24
4287.
(6) Yoon, N.M.; Kim, K.E.; Kang, J. J. Org. Chem. 1986, 51, 226.
(7) Krishnamurthy, S. J. Org. Chem. 1981, 46, 4628.
(8) Adkins, H.; Billica, H.R. J. Am. Chem. Soc. 1948, 70, 695.
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A. F. Barrero et al.
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Table Chemoselective Reduction of Aldehydes in the Presence of Ketones with Raney Nickel
Synlett 2000, No. 2, 197–200 ISSN 0936-5214 © Thieme Stuttgart · New York

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Chemoselective Reduction of Aldehydes in the Presence of Ketones Utilizing Raney Nickel
Table (continued)
199
(9) Brunet, J.J.; Gallois, P.; Caubère, P. J. Org. Chem. 1980, 45,
1937.
(10) Brunet, J.J.; Gallois, P.; Caubère, P. J. Org. Chem. 1980, 45,
1946.
(11) Barrero, A.F.; Sánchez, J.F.; Altarejos, J. Tetrahedron Lett.
1989, 30, 5515.
(12) Barrero, A.F.; Manzaneda, E.A.; Chahboun, R.; Páiz, M.C.
Tetrahedron Lett. 1998, 39, 9543.
(13) Barrero, A.F.; Manzaneda, E.A.; Manzaneda, R.A.;
Chahboun, R.; Meneses, R.; Aparicio, M. Synlett 1999, 713.
(14) All new compounds were fully characterized spectroscop-
ically and had satisfactory high resolution mass spectroscopy
data. For preparation of compounds 8a, 9a and 12a see
references 12, 11 and 13, respectively. Compounds 10a and
11a are intermediates of our synthetic research and are a part
of unpublished results. Compounds 5a and 7a were prepared
by ozonolysis of caryophyllene and of the O-silylderivative of
drimenol, respectively. 13a was obtained by ozonolysis of
ent-kaur-16-en-18-ol and further oxidation with PCC.
Selected data:
7b 1H NMR (300 MHz, CDCl3) d: -0.06 (s, 3H), -0.04 (s, 3H),
0.73 (s, 3H), 0.78 (s, 9H), 0.85 (s, 6H), 1.40 (m, 3H), 1.71 (dq,
J = 13.2 and 2.8 Hz, 1H), 1.96 (t, J = 4.7 Hz, 1H), 2.11 (s, 3H),
2.44 (d, J = 4.2 Hz, 1H), 2.61 (dd, J = 10.3 and 4.1 Hz, 1H),
3.75 (dd, J = 9.2 and 4.1 Hz, 1H), 3.85 (dd, J = 10.3 and 9.2
Hz, 1 H), 9.77 (t, J = 1.3 Hz, 1H).
8a 1H NMR (400 MHz, CDCl3) d:0.91 (s, 3H), 0.95 (s, 3H),
1.18 (s, 3H), 1.20-1.78 (m, 9H), 2.09 (s, 3H), 2.29 (ddd,
J = 17.1, 10.6 and 5.5 Hz, 1H), 2.39 (ddd, J = 17.1, 10.8 and
5.6 Hz, 1H), 9.28 (s, 1H).
8b 1H NMR (300 MHz, CDCl3) d:0.71 (s, 3H), 0.82 (s, 3H),
0.84 (s, 3H), 2.08 (s, 3H), 2.46 (ddd, J = 16.5, 9.7 and 6.9 Hz,
1H), 2.60 (ddd, J = 16.5, 9.7 and 6.9 Hz, 1H), 2.96 (d, J = 11.1
Hz, 1H), 3.36 (d, J = 11.1 Hz, 1H).
9a 1H NMR (300 MHz, CDCl3) d: 0.56 (s, 3H), 1.28 (s, 3H),
2.05-2.50 (m, 2H), 2.25 (dd, J = 17.2 and 2.6 Hz, 1H), 2.90
(m, 2H), 3.62 (s, 3H), 9.79 (s, 1H). 13C NMR (75 MHz,
CDCl3) d: 13.5 (C-20), 19.5 (C-2), 24.9 (C-6), 28.6 (C-18),
37.1 (C-11), 37.8 (C-3), 39.5 (C-1), 41.8 (C-7), 41.9 (C-10),
44.2 (C-4), 51.3 (MeO), 54.4 (C-5), 56.9 (C-9), 176.9 (C-19),
201.0 (C-12), 209.7 (C-8).
5a 1H NMR (400 MHz, CDCl3) d: 1.03 (s, 3H), 1.05 (s, 3H),
1.61 (m, 2H), 1.73 (t, J = 10.3 Hz, 2H), 1.87 (t, J = 9.2 Hz,
2H), 2.10 (s, 3H), 2.34 (dd, J = 6.7 and 2.8 Hz, 1H), 2.36 (dd,
J = 7.5 and 2.8 Hz), 1H), 2.65 (m, 2H), 2.73 (m, 2H), 2.79 (d,
J = 9.4 Hz, 1H), 2.84 (d, J = 9.4 Hz, 1H), 9.79 (s, 1H).
5b 1H NMR (300 MHz, CDCl3) d: 1.04 (s, 3H, 1.06 (s, 3H),
1.63 (m, 2H), 1.84 (m, 4H), 2.10 (s, 3H), 2.39 (m, 4H), 2.50
(dt, J = 6.7 and 1.6 Hz, 2H), 2.78 (d, J = 9.5 Hz, 1H), 2.85 (d,
J = 9.5 Hz, 1H), 3.63 (t, J = 6.1 Hz, 2H).
9b 1H NMR (300 MHz, CD3COCD3) d: 0.50 (s, 3H), 1.25 (s,
3H, 2.1-2.4 (m, 3H), 3.60 (m, 2H), 3.61 (s, 3H). 13C NMR (75
MHz, CD3COCD3) d:13.5 (C-20), 20.5 (C-2), 26.1 (C-6), 26.2
(C-11), 28.9 (C-18), 38.6 (C-3), 39.9 (C-1), 43.3 (C-7), 43.5
(C-10), 44.9 (C-4), 51.5 (MeO), 55.2 (C-5), 59.4 (C-9), 61.7
(C-12), 177.4 (C-19), 211.9 (C-8).
11a 1H NMR (300 MHz, CDCl3) d: 0.88 (s, 3H), 0.90 (s, 3H),
0.97 (d, J = 6.5 Hz, 3H), 1.24 (s, 3H), 1.39 (dd, J = 13.7 and
3.6 Hz, 1H), 1.64 (dt, J = 13.4 and 3.4 Hz, 1H), 1.75 (br d,
J = 12.5 Hz), 2.12 (dd, J = 12.1 and 3.5 HZ, 1H), 2.36 (t,
J = 14.6 Hz, 1H), 2.48 (dd, J = 14.6 and 3.6 Hz), 1H), 2.87
(dq, J = 12.2 and 6.4 Hz, 1H), 9.78 (d, J = 3.5 Hz, 1H).
7a 1H NMR (300 MHz, CDCl3) d: -0.05 (s, 3H), -0.02 (s, 3H),
0.80 (s, 9H), 0.84 (s, 3H), 0.85 (s, 3H), 0.87 (s, 3H), 1.60 (m,
2H), 1.72 (dq, J = 13.4 and 2.8 Hz, 1H), 2.15 (s, 3H), 2.96 (dd,
J = 9.8 and 3.5 Hz, 1H), 3.95 (m, 2H), 3.64 (dd, J = 9.4 and
3.5 Hz, 1H), 3.87 (t, J = 9.4 Hz, 1H).
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A. F. Barrero et al.
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11b 1H NMR (300 MHz, CDCl3) d: 0.82 (s, 3H), 0.87 (s, 3H),
1.11 (d, J = 6.7 Hz, 3H), 1.15 (s, 3H), 1.23 (dd, J = 13.7 and
3.7 Hz), 1.65 (dt, J = 13.5 and 3.5 Hz), 1.95 (bd, J = 12.5 Hz,
1H), 2.32 (t, 14.5 Hz, 1H), 2.43 (dd, J = 14.5 and 3.5 Hz, 1H),
2.56 (dq, J = 12.2 and 6.5 Hz, 1H), 3.78 (dd, J = 11.1 and 3.9
Hz, 1H), 3.84 (dd, J = 11.1 and 2.5 Hz, 1H).
13a 1H NMR (300 MHz, CDCl3) d: 0.88 (s, 3H), 0.96 (s, 3H),
2.10 (br d, J = 13.4 Hz, 1H), 2.22 (dd, J = 11.9 and 2.5 Hz,
1H), 2.34 (br s, 1H), 9.70 (d, J = 1.2 Hz, 1H).
(15) Typical experimental procedure:
0.8 g of an aqueous suspension of Raney nickel (Fluka, cat.
no. 83440) was added to a stirred solution of compound (1.0
mmol) in tetrahydrofuran (10 ml) and the mixture was further
stirred at room temperature for the specified time (Table). The
mixture was diluted with ether and filtered through celite, and
the solvent was evaporated to yield the reduced compound.
12b 1H NMR (400 MHz, CDCl3) d: 0.92 (s, 3H), 1.23 (d,
J = 6.9 Hz, 3H), 1.25 (s, 3H), 2.24 (dd, J = 11.1 and 6.6 Hz,
1H), 2.31 (br d, J = 12.9 Hz, 1H), 2.63 (dd, J = 17.8 and 6.6
Hz, 1H), 2.64 (dd, J = 17.8 and 11.1 Hz, 1H), 2.89 (h, J = 6.9
Hz, 1H), 3.14 (d, J = 10.9 Hz, 1H), 3.43 (d, J = 10.9 Hz, 1H),
7.28 (d, J = 8.1 Hz, 1H), 7.37 (dd, J = 8.1 and 1.5 Hz, 1H),
7.82 (d, J = 1.5 Hz, 1H).
Article Identifier:
1437-2096,E;2000,0,02,0197,0200,ftx,en;L19999ST.pdf
Synlett 2000, No. 2, 197–200 ISSN 0936-5214 © Thieme Stuttgart · New York