Reduction of ketones to alcohols using a decaborane/pyrrolidine/cerium(III) chloride system in methanol

Article abstract of DOI:10.1016/S0040-4039(01)00005-3

Decaborane was found to be an effective agent for the chemoselective reduction of ketones to alcohols in the presence of pyrrolidine and cerium(III) chloride heptahydrate in methanol.

Full text of DOI:10.1016/S0040-4039(01)00005-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 2137–2139
Reduction of ketones to alcohols using a
decaborane/pyrrolidine/cerium(III) chloride system in methanol
Jong Woo Bae, Seung Hwan Lee, Yeon Joo Jung, Choon-Ock Maing Yoon and Cheol Min Yoon*
Department of Life Science & Biotechnology, Graduate School of Biotechnology, Korea University, Seoul, South Korea
Received 9 November 2000; revised 20 December 2000; accepted 22 December 2000
Abstract—Decaborane was found to be an effective agent for the chemoselective reduction of ketones to alcohols in the presence
of pyrrolidine and cerium(III) chloride heptahydrate in methanol. © 2001 Elsevier Science Ltd. All rights reserved.
Reduction of ketones is a general synthetic method for
the preparation of secondary alcohol in organic synthe-
sis. Even if a wide variety of reagents are available for
the reduction of ketone,1 the development of mild
methods without affecting other functional groups has
been of interest in organic chemistry.2
the reduction of ketone proceeded in the presence of
cerium chloride heptahydrate with 30 mol% of decabo-
rane, it was slow and the yield of 2a was low due to the
formation of the reductive etherification side product
3a and the incomplete reaction (Scheme 2).4 When
pyrrolidine as a base was added to the reaction, the
yield of 2a was found to be improved. The optimum
amount of pyrrolidine needed in the reaction was stud-
ied and results are shown in Table 1. When 10 mol% of
pyrrolidine was used in the reaction (entry 2), the
formation of side product was reduced and the yield of
2a was increased. The side product and starting ketone
were not detected in TLC at all when 3:1 mole ratio of
pyrrolidine and cerium chloride heptahydrate was used
(entry 4).
Decaborane is quite a stable white boron cluster and is
therefore easy to handle. During the continuous study
on the reductive amination using decaborane as a mild
reducing agent,3 we found that ketones with a variety
of other functional groups were reduced to the corre-
sponding secondary alcohols with decaborane in meth-
anol at ca. 50°C in the presence of pyrrolidine and cerium-
(III) chloride heptahydrate (Scheme 1). The optimum
amounts of reagents were 30 mol% of decaborane, 30
mol% of pyrrolidine and 10 mol% of cerium(III)
chloride heptahydrate (with respect to ketones).
The effects of the reaction temperature and additives
were studied in detail. Without cerium chloride hep-
tahydrate, the reaction did not proceed at all. Although
Scheme 1.
Scheme 2.
Keywords: reduction; ketone; decaborane; pyrrolidine; cerium chloride heptahydrate; alcohol.
* Corresponding author. Tel.: +82-2-3290-3433; fax: +82-2-3290-3433; e-mail: cmyoon@tiger.korea.ac.kr
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00005-3

2138
J. W. Bae et al. / Tetrahedron Letters 42 (2001) 2137–2139
Table 1. Results depending on the ratio of base and cerium chloride heptahydrate
Entry
Ketone
Pyrrolidine (equiv.)
CeCl3·7H2O (equiv.)
Yield (%)a
1
2
3
4
5
6
None
0.1
0.2
0.3
0.1
0.1
0.1
0.1
0.1
0.2
0.3
30
81
84
95
83
81
0.1
a Isolated yields.
Table 2. Results depending on the amines useda
Entry
Ketone
Amine (equiv.)
CeCl3·7H2O (equiv.)
Time (h)
Yield (%)b
1
2
3
4
Piperidine (0.3)
Pyrrolidine (0.3)
Triethylamine (0.3)
Pyridine (0.3)
0.1
0.1
0.1
0.1
4
4
4
4
97
95
85
84
a To a solution of 5-bromo-2-hydroxy acetophenone (100 mg, 0.465 mmol) in methanol (5 ml) was added amine (30 mol%), cerium(III) chloride
heptahydrate (10 mol%) and decaborane (30 mol%). The resulting solution was stirred at ca. 50°C under nitrogen for 4 h.
b Isolated yield of 2a.
Table 3. Reduction of ketones5

J. W. Bae et al. / Tetrahedron Letters 42 (2001) 2137–2139
2139
Among amines examined, the secondary amines (pyrro-
References
lidine and piperidine) were more efficient than triethyl-
amine and pyridine (Table 2). The roles of the amine in
the present reduction are not clear5 and are under
investigation.
1. (a) Iwasaki, F.; Onomura, O.; Mishima, K.; Maki, T.;
Matsumura, Y. Tetrahedron Lett. 1999, 40, 7507; (b) Fleet,
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Kad, G. L.; Sharma, M.; Dhillon, R. S. Synth. Commun.
1998, 28, 2253.
3. (a) Bae, J. W.; Lee, S. H.; Cho, Y. J.; Yoon, C. M. J.
Chem. Soc., Perkin Trans. 1 2000, 2, 145; (b) Bae, J. W.;
Cho, Y. J.; Lee, S. H.; Maing Yoon, C.-O.; Yoon, C. M.
J. Chem. Soc., Chem. Commun. 2000, 1857; (c) Lee, S. H.;
Park, Y. J.; Yoon, C. M. Tetrahedron Lett. 1999, 40, 6049.
4. When excess amounts of cerium chloride (20, 50 and 100
mol%) were used, similar results (low yield) were obtained
due to the same reason.
5. Representative experimental procedure: To a solution of
benzophenone (100 mg, 0.548 mmol) in methanol (5 ml)
was added pyrrolidine (14 mg, 0.164 mmol), cerium(III)
chloride heptahydrate (20.4 mg, 0.0548 mmol) and deca-
borane (20.1 mg, 0.164 mmol). The resulting solution was
stirred at ca. 50°C under nitrogen for 8 h. The reaction
was followed by TLC using a solution of ethyl acetate and
hexane (1:10). The reaction was concentrated under
reduced pressure and chromatographed on a short pad of
silica gel using a solution of ethyl acetate and n-hexane
(1:15) to give the product alcohol as a white solid.
The reaction proceeded at room temperature but
slowly. The reaction rate was increased when the reac-
tion temperature was increased. The reaction was fast
enough at ca. 50°C using the aforementioned optimum
amount of additives (pyrrolidine, cerium chloride hep-
tahydrate and decaborane). Under our reaction condi-
tions, the reduction of ketones was completed within 8
h to give the corresponding alcohols in high yields. This
system is also effective for the reduction of the rela-
tively less reactive benzophenone (entry 10, Table 3).
Other functional groups such as nitro (entry 7), ester
(entry 5) and bromide (entries 1, 6, 7, and 8) remained
unaffected under the reaction conditions. The reduction
of the double bond in conjugated ketones (entries 3 and
4) was not observed at all. Pyrrolidene rather than
piperidine was chosen in the reaction because it is
cheaper than piperidine.
In conclusion, ketones were reduced to the correspond-
ing alcohols using decaborane in the presence of pyrro-
lidine and cerium(III) chloride heptahydrate in
methanol. The reaction is efficient and compatible with
other functional groups such as nitro, ester, bromide
and the double bond of conjugated ketone.
Acknowledgements
The authors wish to acknowledge the financial support
of the Korea Science and Engineering Foundation,
1999.
.