A novel reduction of polycarboxylic acids into their corresponding alkanes using n-butylsilane or diethylsilane as the reducing agent

Article abstract of DOI:10.1016/j.tetlet.2006.03.111

A convenient one-pot reaction has been developed for the reduction of polycarboxylic acids on aliphatic and aromatic systems to their corresponding alkanes. The reduction utilises either diethylsilane or n-butylsilane as the reducing agent in the presence of the Lewis acid catalyst tris(pentafluorophenyl)borane.

Full text of DOI:10.1016/j.tetlet.2006.03.111

Tetrahedron Letters 47 (2006) 3505–3508
A novel reduction of polycarboxylic acids into their corresponding
alkanes using n-butylsilane or diethylsilane as the reducing agent
Rama D. Nimmagadda and Christopher McRae*
Department of Chemistry and Biomolecular Sciences, Division of Environmental and Life Sciences, Macquarie University,
Sydney, NSW 2109, Australia
Received 7 February 2006; revised 15 March 2006; accepted 17 March 2006
Available online 5 April 2006
Abstract—A convenient one-pot reaction has been developed for the reduction of polycarboxylic acids on aliphatic and aromatic
systems to their corresponding alkanes. The reduction utilises either diethylsilane or n-butylsilane as the reducing agent in the pres-
ence of the Lewis acid catalyst tris(pentafluorophenyl)borane.
ꢀ
2006 Elsevier Ltd. All rights reserved.
1. Introduction
order to become a hydride source. Tris(pentafluoro-
1
4
phenyl)borane [B(C F ) ] is a convenient Lewis acid
6
5 3
In synthetic chemistry, the reduction of a carboxylic acid
carbon to a methyl group is an important conversion.
Carbonyl functions can be readily converted to a meth-
ylene group in a single-step by a variety of methods.
However, the conversion of carboxylic acids into methyl
groups usually requires a multi-step process. Typically,
carboxylic acids are first converted to either aldehydes
or alcohols, which are then subsequently reduced to a
methyl group. Multi-step procedures for the reduction
of aromatic carboxylic acid groups to methyl groups,
without purification of the intermediates have been pre-
that has previously been used in conjunction with trieth-
ylsilane for the selective reduction of carbonyl and
carboxylic functions to methylene/methyl groups.
2
However, this method was limited to aliphatic monocar-
boxylic acids and required the use of ammonium fluo-
ride to cleave the silyl ethers formed with the aromatic
carboxylic acids. When this method was applied to a
di-carboxylic acid, the major product was a silyl ether
rather than the corresponding alkane. In this work, we
present a method for the successful reduction of both
aliphatic and aromatic polycarboxylic acid functions
to methyl groups using n-butylsilane or diethylsilane
and tris(pentafluorophenyl)borane.
1
viously reported. Recently, procedures for the reduc-
tion of aliphatic monocarboxylic acids to methyl
groups in a one-pot reaction have also been reported.2
To date, however, there is no established method for
the conversion of di- and polycarboxylic acids into their
corresponding alkanes via one-pot reduction. The meth-
od described here reduces di-carboxylic and polycarb-
oxylic acids on both aliphatic and aromatic systems.
Several alkyl silanes, including triethylsilane (TES),
dimethylethylsilane (DMES), diethylsilane (DES) and
n-butylsilane (n-BS) in the presence of tris(pentafluor-
phenyl)borane (B(C F ) ), were investigated in this
6
5 3
study for the purpose of carboxylic acid reduction.
3
4,5
Silanes are mild reducing agents that have been com-
TES and DES were found to reduce straight chain di-
carboxylic acids readily into their corresponding alk-
anes, however; alicyclic and aryl dicarboxylic acids were
converted into their corresponding silyl ethers requiring
2
,6–13
monly used in selective reductions.
require either strong acid or Lewis acid catalysts in
Silane reagents
6
equiv of TES for each carboxylic acid group. HF or
2
NH F can cleave these silyl ethers as already reported.
4
Keywords: Reduction; Polycarboxylic acids; TES: triethylsilane;
DES: diethylsilane; DMES: dimethylethylsilane; n-BS: n-butylsilane;
B(C F ) : tris(pentafluorophenyl)borane.
6 5 3
The ability of various silanes to reduce carboxylic acids
was found to be dependent upon steric hindrance, thus
the less sterically hindered silanes proved to be more effi-
cient. TES and DMES were able to reduce straight chain
*
Corresponding author. Tel.: +61 2 98508288; fax: +61 2 98508313;
e-mail: christopher.mcrae@mq.edu.au
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.03.111

3506
R. D. Nimmagadda, C. McRae / Tetrahedron Letters 47 (2006) 3505–3508
di-carboxylic acids. The length of reaction with DMES
was less than that for TES reduction. This is because
of the less bulky substituents on DMES. These studies
encouraged the use of DES, with only two alkyl substit-
uents on the silane, as a reducing agent. DES was suc-
cessful in the reduction of di-carboxylic acids and
polycarboxylic acids (Table 1) for which DMES was
not. Although DES was able to reduce polycarboxylic
acids, the yields were low and compounds, such as
Table 1. Reduction of polycarboxylic acids on aliphatic and aromatic
systems with n-butylsilane (n-BS) or diethylsilane (DES)
Substrate
Product
GC yield
(%)
n-BS DES
1
2
COOH
COOH
COOH
73
78
87
64
1
,2,3,4,5,6-hexacarboxylic acid cyclohexane 10 and
,2,3,4,5,6-hexacarboxylic acid benzene 20, did not yield
1
any of the desired alkane products. Thus, the less steri-
cally hindered n-BS was chosen as the reducing agent.
n-BS was found to reduce di- and polycarboxylic acids
to their corresponding methyl groups in high yields com-
pared to diethylsilane (Table 1). The condition of the
catalyst and the silane were found to be crucial to the
reaction. If freshly prepared catalyst and silane were
not used, considerably lower yields were observed.
HOOC
3
4
87
63
79
46
COOH
COOH
HOOC
HOOC
COOH
COOH
The proposed reaction mechanism is described in Figure
5
6
87
83
82
71
1
and is based on the intermediate products observed
during the reaction. Silanes are typically only considered
to be hydride sources when substituted with bulky alkyl
substituents; however, the silylation products formed
indicate that silanes with less bulky substituents can also
act as hydride sources I. The ability of n-BS to serve as a
hydride source was tested with various other catalysts,
such as palladium, platinum oxide, AlCl , BF ÆEt O,
COOH
HOOC
COOH
COOH
7
52
34
3
3
2
COOH
BBr , BCl and rhodium. However, no conversion of
3
3
polycarboxylic acids to the methyl groups was observed.
n-BS and DES are effective reducing agents only in the
presence of tris(pentafluorophenyl)borane, which is able
to abstract the hydrogen even on n-BS. The siloxane
formed is further condensed to form cyclotrisiloxanes
and higher polymers in the presence of the polycarboxy-
lic acids.
HOOC
COOH
8
9
64
57
61
37
COOH
COOH
HOOC
COOH
COOH
We have developed a simple, one-pot and direct reduc-
tion of aliphatic and aromatic mono-, di- and polycarb-
oxylic acid moieties into the corresponding methyl
group. This work also describes the application of the
two reducing agents, n-BS and DES, in the field of syn-
thetic chemistry.
COOH
COOH
HOOC
HOOC
10
32
—
COOH
COOH
1
1
1
2
HOOC–(CH
HOOC–(CH
2
)
)
8
–COOH
16–COOH
H
H
3
C–(CH
C–(CH
2
)
)
8
–CH
16–CH
3
94
87
91
81
2
3
2
3
2. Experimental
COOH
A Shimadzu Gas Chromatograph 17A coupled with a
QP5000 mass spectrometer was used for qualitative
analysis. A Shimadzu Gas Chromatograph 17A with
flame ionisation detector was used for quantitative anal-
ysis. In both cases the gas chromatograph was fitted
with an SGE BPX-5 column (30 m · 0.25 mm i.d.,
13
74
59
1
1
4
5
89
89
91
69
COOH
0
.5 lm film thickness). An oven dried 25 mL round bot-
tom flask was purged with nitrogen. Carboxylic acid
1 mmol) was weighed into the flask which was then
COOH
(
closed with a septum and purged with argon. The cata-
lyst (B(C F ) , 5–10 mol %) was introduced via syringe
6
5 3
as a freshly prepared solution in 5 mL of anhydrous
dichloromethane. Stirring was continued for 10 min
and then 2 equiv of n-BS (99% pure) or DES (99% pure)
was added per carbonyl group (4 equiv for each carbox-
COOH
COOH
1
6
69
53

R. D. Nimmagadda, C. McRae / Tetrahedron Letters 47 (2006) 3505–3508
3507
Table 1 (continued)
was excluded for the duration of the reaction to prevent
photolytic HCl production from the degradation of
dichloromethane, which was found to hamper the reac-
tion. The reaction progress was monitored by GC–MS.
After complete conversion of the starting material, the
reaction mixture was quenched with 0.1 mL of triethyl-
amine. The crude mixture was purified over silica gel
with hexane as eluent or hexane/ethyl acetate (50:1).
Substrate
Product
GC yield
%)
(
n-BS DES
COOH
17
18
19
83
71
65
71
34
41
COOH
COOH
References and notes
COOH
1
2
. Benkeser, R. A.; Foley, K. M.; Gaul, J. M.; Li, G. S. H.
J. Am. Chem. Soc. 1970, 92, 3232–3233.
. Bajracharya, G. B.; Nogami, T.; Jin, T.; Matsuda, K.;
Gevorgyan, V.; Yamamoto, Y. Synthesis 2004, 2, 308–
COOH
COOH
3
11.
. Jenkins, J. W.; Post, H. W. J. Org. Chem. 1950, 15, 556–
59.
COOH
3
5
COOH
4. Nagai, Y. Org. Prep. Proced. Int. 1980, 12, 13–48.
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W. P., Jr.; Silverman, S. B. J. Org. Chem. 1978, 43, 374–
COOH
COOH
COOH
HOOC
3
75.
20
19
—
7
. Yamamoto, Y.; Gevorgyan, V.; Liu, J. X. Book of
Abstracts, 218th ACS National Meeting, New Orleans,
August 22–26, 1999; ORGN-435.
HOOC
COOH
COOH
8
. Chandrasekhar, S.; Reddy, C. R.; Babu, B. N. J. Org.
Chem. 2002, 67, 9080–9082.
ylic acid) present in the substrate. A static atmosphere of
argon was established using an argon balloon. The reac-
tion mixture was stirred for about 6–20 h depending
upon the number of carboxylic acids present. Light
9
. Parks, D. J.; Piers, W. E. J. Am. Chem. Soc. 1996, 118,
9
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O
H
Si
B(C F )
H
H
H
6
5
3
R
+
R
H
OH
CH
2
Cl
2
H
O
SiH2
R
C
OH
O
H
H
I
Si
H
B(C F )
5 3
6
R
OH
H
B(C F )
6
5
3
H2
H2
Si
SiH2
SiH2
O
SiH
2
Si
O
O
R
R
H OH
H
H
OH
H
Si
H
B(C
6
F
5
)
3
II
H
R
OH
H
B(C F )
6 5 3
H
H
H
H
HO
R
Si
H2
H
R
HO
Si
H
OH
H
H
H
H
III
H
Si
B(C
6
F
5
)
3
R
H
B(C F )
6 5 3
H
H
R
H
Figure 1. Proposed reduction mechanism.

3508
R. D. Nimmagadda, C. McRae / Tetrahedron Letters 47 (2006) 3505–3508
1
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