Selective reduction of carboxylic acids to aldehydes by a ruthenium-catalyzed reaction with 1,2-bis(dimethylsilyl)benzene

Article abstract of DOI:10.1246/cl.2012.229

Novel transformation of carboxylic acids to aldehydes is achieved by a one-pot procedure consisting of a rutheniumcatalyzed hydrosilane reduction with 1,2-bis(dimethylsilyl)benzene (2) followed by hydrolysis of the resulting cyclic disilylacetals 4.

Full text of DOI:10.1246/cl.2012.229

doi:10.1246/cl.2012.229
Published on the web February 18, 2012
229
Selective Reduction of Carboxylic Acids to Aldehydes by a Ruthenium-catalyzed Reaction
with 1,2-Bis(dimethylsilyl)benzene
Konoka Miyamoto,1 Yukihiro Motoyama,1,2 and Hideo Nagashima*1,2
1Department of Molecular and Materials Science, Graduate School of Engineering Sciences,
Kyushu University, 6-1 Kasuga-koen, Kasuga, Fukuoka 816-8580
2Institute for Materials Chemistry and Engineering, Kyushu University,
6-1 Kasuga-koen, Kasuga, Fukuoka 816-8580
(Received November 25, 2011; CL-111135; E-mail: nagasima@cm.kyushu-u.ac.jp)
Novel transformation of carboxylic acids to aldehydes is
achieved by a one-pot procedure consisting of a ruthenium-
catalyzed hydrosilane reduction with 1,2-bis(dimethylsilyl)ben-
zene (2) followed by hydrolysis of the resulting cyclic
disilylacetals 4.
Although reduction of carboxylic acids to aldehydes is a
synthetic protocol frequently required in organic synthesis,
selective and direct transformation by alumino- or borohydride
reduction is difficult due to higher reactivity of aldehydes than
carboxylic acids leading to facile formation of alcohols.1 Thus,
the transformation is usually performed by a two-step procedure.
One of the general procedures is hydride reduction of carboxylic
acid to alcohols, and subsequent oxidation of the resulting
alcohols gives aldehydes.2 Another well-established procedure
is conversion of carboxylic acids to more reactive acyl
Scheme 1.
chlorides,1a,3a acid anhydrides,3b and activated esters,1a,3c which
is followed by catalytic hydrogenation or hydride reduction to
aldehydes. Development of direct methods to achieve conversion
of carboxylic acids to aldehydes or their equivalents has attracted
attention of organic chemists; several successful examples were
achieved by discovery of novel reducing reagents. Reduction of
carboxylic acids with thexylborane gives the corresponding
boryl esters in the first step. Further reaction of thexylborane
provides diborylacetals, which hardly undergo further reduction
to the corresponding alkoxy borane. Aqueous work-up of the
diborylacetal gives the aldehyde.4 The reduction with alane
derivatives5 and in situ prepared magnesium hydrides by
titanocene-catalyzed reaction with i-BuMgBr6 proceed in similar
fashion to achieve selective transformation of carboxylic acids to
aldehydes. A unique reduction of carboxylic acids was reported
by Corriu and co-workers who prepared certain pentacoordinated
silyl carboxylates, from which intramolecular hydride migration
afforded aldehydes.7 Although these direct methods are attractive
for preparation of aldehydes from carboxylic acids, handling of
the reducing reagent is not easy in the reactions with boranes,
alanes, and in situ formed magnesium hydrides,4-6 whereas harsh
conditions (100-180 °C) are required for the Corriu’s reaction.7
In this context, it is desirable to develop a new method for the
preparation of aldehydes from carboxylic acids using a reducing
reagent, which can be handled with ease and proceeding under
mild conditions. Hydrosilanes, especially tertiary silanes, are
attractive from this viewpoint, however, they are essentially
stable, and new catalysts which enable the reduction of
carboxylic acids to aldehydes are required.8
sis,8,9 we have reported that hydrosilane reduction of carboxylic
acids is facilely achieved by catalysis of (®3, ©2, ©3, ©5-
acenaphthylene)Ru3(CO)7 (1); the reduction of carboxylic acids
to silyl ethers is achieved with monofunctional tertiary silanes
such as PhMe2SiH and EtMe2SiH under mild conditions.9b As
shown in Scheme 1, the reduction of carboxylic acids consists of
three steps, dehydrogenative silylation leading to formation of
silyl esters (step 1), Si-H addition of C=O bond of the silyl
esters to disilylacetals (step 2), and reductive cleavage of a C-O
bond in the disilylacetals to give silyl ethers (step 3). Hydrolysis
of the resulting silyl ethers gave alcohols in good yields. Of
interest is a possibility of selective formation of the disilylace-
tals, which can be achieved by making the reaction rate of step 3
slow enough to produce the disilylacetals without contamination
of the silyl ethers. Acceleration of step 2 would help the
selective formation of the disilylacetals. In this paper, we wish to
report that a bifunctional organosilane, 1,2-bis(dimethylsilyl)-
benzene (2) is a suitable reducing reagent for this purpose,
providing a new synthetic protocol for aldehydes from carbox-
ylic acids.
In a typical example, the reaction of 4-methoxybenzoic acid
(3a) was carried out as follows: the catalyst 1 (1 mol % to the
carboxylic acid 3a) is dissolved in minimum amounts of
tetrahydropyran (THP) and treated with 2 (1.2-2.0 equiv to 3a)
at room temperature for 30 min. Then, 3a and THP (2 mL) are
added, and the mixture is kept at 25 or 40 °C. Hexamethylben-
zene is added as an internal standard to determine conversion of
1
In our continuous efforts to develop transition-metal-
catalyzed reactions of hydrosilanes useful in organic synthe-
3a and yield of the products by H NMR. After removal of the
volatiles, NMR spectra of the mixture show a singlet appearing
Chem. Lett. 2012, 41, 229-231
© 2012 The Chemical Society of Japan www.csj.jp/journals/chem-lett/

230
Table 1. Optimization of the reaction conditions10
Table 2. Reduction of various carboxylic acids
Isolated
yield/%
Hydro-
lysisb
Product
5
Temp Time
/°C
Entry
Carboxylic acid 3
/h
Yield of
4a + 5a
/%
40
5
1
90
A
A
5a
5b
2
Temp Solvent for Solvent for Additive Time
1
2
MeO
CO2H
90c
Entry
25
/equiv /°C activation reaction
/equiv
/h
3a
40
24
A
90
THP
(0.2 mL)
THP
THP
(2 mL)
THP
(2 mL)
THP
(2.2 mL)
THP
(2.2 mL)
THP
(2 mL)
THP
(2 mL)
THP
(2 mL)
CO2H
1
2
3
4
5
6
7
1
2
2
2
1
1
1
25
25
none
none
none
none
24
24
24
5
52
64
69
90
90
64
5
3b
3
4
Cl
CO2H
50
50
24
24
A
A
5c
5d
69
90
(0.2 mL)
3c
25 none
40 none
25 none
25 none
25 none
Ph
CO2H
3d
CO2H
40
40
18
18
90
20c
B
B
Et3N
(0.2)
Et3N
(1)
pyridine
(0.2)
5
5e
5f
1
3e
3
40
40
18
18
59
C
C
CO2H
90c
6
7
3f
1
aAll reactions were carried out with 3a (1 mmol) and 1
(1 mol %).
50
70
18
18
C
C
5g
5h
58
71
CO2H
3g
CO2H
8
at ¤ 6.3 which indicates formation of a disilylacetal 4a. 1H NMR
peaks due to 4-methoxybenzaldehyde (5a) are also observed.
Formation of the disilylacetal is supported by experiments of
acid-promoted hydrolysis of the mixture of 4a and 5a, which
result in quantitative conversion of 4a to 5a. Optimized reaction
conditions are shown in Table 1. As shown in Entry 1,
disilylacetal 4a was obtained in 52% when the reaction was
performed with 1 equiv of 2 at room temperature for 24 h. In
increasing the amount of 2 to 2.0 equiv, the yield of 4a was
increased to 64% (Entry 2). The reaction with no solvent gave
4a in 69%. A better yield (90%) was obtained when the reaction
was carried out at 40 °C for 5 h. As reported earlier, addition of
amine causes functional group selective poisoning of the catalyst
1.9d Addition of Et3N accelerated the reaction (Entries 5 and 6),
while presence of pyridine inhibited the catalysis of 1
(Entry 7).11 In the presence of Et3N (0.2 equiv to 3a), the yield
of the products exceeded 90% even at room temperature within
1 h.
Reduction of carboxylic acids followed by hydrolysis of the
resulting disilylacetals can be done by one-pot process. In
Table 2 are shown several examples of reduction of carboxylic
acids to aldehydes under the conditions shown in Entry 4,
Table 1. Three procedures were used for the hydrolysis step,
treatment of the intermediary disilylacetals with CF3CO2H(aq)
(Entries 1-4), HCl(aq) (Entry 5), or TBAF(aq) (Entries 6-8).
Reactions of substituted benzoic acids are listed in Entries 1-4.
Anisaldehyde, benzaldehyde, and p-phenylbenzaldehyde
were obtained in over 90% isolated yields. Electron-donating
substituents tend to increase the reaction rate. Benzoic acid
having electron-withdrawing Cl group was slow, giving the
corresponding aldehyde in lower yield. Aliphatic carboxylic
3h
aAll reactions were carried out in a similar manner as that
descried in Entry 4, Table 1. Hydrolysis is by A: CF3CO2H/
H2O, B: HCl/H2O, C: TBAF/H2O. Details are described in
the Supporting Information.16 cAddition of Et3N (0.2 equiv to
the carboxylic acid).
b
acids also underwent the selective reduction to give the
corresponding aldehydes. The reaction rate and the yield of
the product were dependent on steric circumstances around the
carbonyl group of the carboxylic acid. For example, 3-phenyl-
propanal (5e) was obtained from 3-phenylpropanoic acid (3e) in
90% (Entry 5), whereas slower reaction of 2-phenyl analogue 3f
gave the aldehyde 5f in 59% isolated yield (Entry 6).12 Two
aldehydes, 1-adamantanecarbaldehyde (5g) and 2-phenyliso-
butylaldehyde (5h) were obtained in 58% and 71% respectively
from the corresponding carboxylic acids as shown in Entries 7
and 8. As described above, addition of a small amount of Et3N
contributed to increase the yield of a mixture of the silylacetal 4a
and the aldehyde 5a in the reduction of 3a with 2 under milder
conditions. Addition of Et3N is also effective in the one-pot
conversion of 3a to 5a. We expected similar additive effects in
the reduction of other carboxylic acids, too; however, the results
were dependent on the structure of the carboxylic acid. For
example, addition of Et3N improved the isolated yield of 2-
phenylpropanal (5f) from 2-phenylpropanoic acid (3f), whereas
the reduction of 3-phenylpropanoic acid (3e) in the presence of
Et3N made the reaction slower to result in decrease of the yield
of 5e.
Chem. Lett. 2012, 41, 229-231
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

231
References and Notes
1
a) M. B. Smith, J. March, March’s Advanced Organic Chemitry: Reactions,
Mechanisms, and Structure, 6th ed., Wiley-Interscience, New York, 2007.
b) J. Seyden-Penne, Reductions by the Alumino- and Borohydrides in
Organic Synthesis, 2nd ed., Wiley, New York, 1997. c) H. C. Brown, S.
Krishnamurthy, Tetrahedron 1979, 35, 567. d) E. R. Burkhardt, K. Matos,
Chem. Rev. 2006, 106, 2617.
2
3
A recent typical example: S. Hanessian, S. Guesné, E. Chénard, Org. Lett.
2010, 12, 1816.
See, these representative papers and references cited therein: a) P. Four, F.
Guibe, J. Org. Chem. 1981, 46, 4439. b) K. Nagayama, I. Shimizu, A.
Yamamoto, Bull. Chem. Soc. Jpn. 2001, 74, 1803. c) C. O. Kangani, D. E.
Kelley, B. W. Day, Tetrahedron Lett. 2006, 47, 6289.
4
5
H. C. Brown, J. S. Cha, B. Nazer, N. M. Yoon, J. Am. Chem. Soc. 1984,
106, 8001.
J. S. Cha, S. H. Jang, J. H. Park, S. K. Lee, C.-S. Lee, Y. R. Lee, Bull.
Korean Chem. Soc. 2003, 24, 9.
Figure 1. The ORTEP drawing of 4g. The crystallographic
data are listed in the Supporting Information.16
6
7
8
F. Sato, T. Jinbo, M. Sato, Synthesis 1981, 871.
R. J. P. Corriu, G. F. Lanneau, M. Perrot, Tetrahedron Lett. 1987, 28, 3941.
For general reviews on the catalytic hydrosilylation: a) I. Ojima, in The
Chemistry of Organic Silicon Compounds, ed. by S. Patai, Z. Z. Rappoport,
John Wiley & Sons, New York, 1989. b) Comprehensive Handbook
on Hydrosilylation, ed. by B. Marciniec, Pergamon, Oxford, 1992. c)
In all cases listed in Table 2, intermediary disilylacetals
were unstable toward moisture leading to facile hydrolysis to
aldehydes; however, careful manipulations made the isolation of
the disilylacetal possible in several cases.10 For example, the
reaction of 3a under the conditions described in Table 1, Entry 3
gave a mixture of 4a and unreacted 2. Purification by
chromatography with florisil, followed by removal of the silicon
by-products in vacuum, afforded 4a containing a small amount
of a cyclic siloxane 6, which was produced by hydrolysis of 2
and 4a. The data of 1H, 13C, and mass spectrometry are in accord
with the structure of 4a (see, the Supporting Information16).
Similarly, a disilylacetal 4g prepared from 1-adamantanoic acid
(3g) was isolated, and identified by spectroscopy.13 Although
many of the silylacetals are liquid, 4g gave a single crystal of
which X-ray structure determination provided unequivocal
evidence for the formation of disilylacetals. The ORTEP
drawing of 4g is depicted in Figure 1.
In summary, the present ruthenium-catalyzed reduction of
carboxylic acids with bifunctional hydrosilane 2 followed by
hydrolysis of the resulting disilylacetals is demonstrated to be a
new method to synthesize aldehydes from carboxylic acids
under mild conditions. Both the catalyst 1 and reducing reagent
2 are stable toward air and moisture, and manipulations are
very easy. Suppression of step 3 in Scheme 1 is a key to
achieve this new transformation, which is due to the fact that
the seven-membered ring of the intermediary disilylacetal is
rigid, and four methyl groups on the silicon atoms effectively
protect the acetal function from further attack of Si-H in step 3.
It is also worthwhile to point out that earlier studies showed
proximate effect of two SiH groups accelerates the hydro-
silylation,14 which is likely to take part in accelerating the
step 2 in the present reduction. These results add a new aspect
in recent progress of transition-metal-catalyzed hydrosilane
reductions in the point that use of the bifunctional hydrosilanes
2 plays an essential role in accelerating the reaction and in
raising the selectivity of aldehydes in the reduction of
carboxylic acids.15
Hydrosilylation:
A Comprehensive Review on Recent Advances in
Advances in Silicon Science, ed. by B. Marciniec, Springer-Verlag, Oxford,
2009, Vol. 1. doi:10.1007/978-1-4020-8172-9. d) D. Addis, S. Das, K.
Junge, M. Beller, Angew. Chem., Int. Ed. 2011, 50, 6004.
a) H. Nagashima, A. Suzuki, T. Iura, K. Ryu, K. Matsubara, Organo-
metallics 2000, 19, 3579. b) K. Matsubara, T. Iura, T. Maki, H. Nagashima,
J. Org. Chem. 2002, 67, 4985. c) Y. Motoyama, K. Mitsui, T. Ishida, H.
Nagashima, J. Am. Chem. Soc. 2005, 127, 13150. d) H. Sasakuma, Y.
Motoyama, H. Nagashima, Chem. Commun. 2007, 4916.
9
10 The catalyst 1 (6.7 mg, 0.01 mmol) was pretreated with hydrosilane 2
(0.44 mL, 2 mmol) at room temperature for 30 min. Then, p-methoxyben-
zoic acid (3a) (152 mg, 1 mmol) suspended in THP (2.2 mL) was added,
and the mixture was heated at 40 °C for 5 h. Unreacted 2 was quenched by
adding diethyl ether saturated by water, and the mixture was concentrated
in vacuo. The crude mixture consisiting of a mixture of 4a and 5a was
dissolved in ether (5 mL) and treated with CH3CO2H and water at room
temperature for 3 h. From the organic phase, 5a was obtained, of which
purification by silica gel column gave 5a in pure form in 90% yield.
11 In the ruthenium-catalyzed hydrosilane reduction of carbonyl compounds,
addition of pyridine generally inhibits the reaction presumably due to
deactivation of the catalyst. In contrast, inhibition by Et3N is also observed
for the reduction of ketones and esters, but not for that of amides.9d Since
acceleration of the disilylacetal formation by Et3N presented in this paper is
observed only for a limited number of the carboxylic acids, it is difficult to
explain the mechanism at present.
12 Careful manipulation is necessary for reduction of optically active
carboxylic acids. Treatment of (R)-2-phenylpropanoic acid, (R)-3f (>99%
ee), with 2 gave the corresponding disilylacetal 4f. For checking the
possible racemization during the reduction, the reaction mixture was treated
with DIBAL to afford (R)-2-phenylpropanol (7f) in 75% yield. Chiral GC
analysis of the resulting 7f showed its optical purity to be 97% ee. As noted
earlier, disilylacetals is often unstable to moisture to give aldehydes as a
by-product. At present, we consider that the loss of optical purity should be
ascribed to the formation of a small amount of aldehyde at the work-up
process of the reduction of (R)-3f with 2. Contamination of the racemized
aldehyde in the DIBAL reduction caused the loss of optical purity.
13 The compound 4g: colorless crystals (Mp 102-107 °C), 1H NMR (270.1
MHz, C6D6): ¤ 7.4 (dd, J = 5.3, 3.3 Hz, 2H), 7.2 (dd, J = 5.3, 3.3 Hz, 2H),
4.7 (s, 1H), 2.0 (m, 3H), 1.7 (m, 6H), 1.7 (m, 6H), 0.4 (s, 6H), 0.4 (s, 6H).
13C NMR (67.8 MHz, C6D6): ¤ 142.6, 131.2, 126.5, 97.0, 36.1, 35.2, 34.5,
26.2, 0.0, ¹3.5. 29Si NMR (119.2 MHz, C6D6): ¤ 9.1. MS (m/z): M+ 372,
373, 374. HRMS (m/z): M+ calcd for C21H32O2Si2, 372.1941; found,
372.1937.
14 Rate acceleration by proximate Si-H groups: a) Rh: H. Nagashima, K.
Tatebe, T. Ishibashi, A. Nakaoka, J. Sakakibara, K. Itoh, Organometallics
1995, 14, 2868. b) Ru: ref. 9a. c) Pt: S. Hanada, E. Tsutsumi, Y. Motoyama,
H. Nagashima, J. Am. Chem. Soc. 2009, 131, 15032. d) Ir: Y. Motoyama, M.
Aoki, N. Takaoka, R. Aoto, H. Nagashima, Chem. Commun. 2009, 1574.
15 Reduction of ketones or nitriles by the bifunctional hydrosilane 2: a) H.
Nagashima, K. Tatebe, K. Itoh, J. Chem. Soc., Perkin Trans. 1 1989, 1707.
b) Y. Sunada, Y. Fujimura, H. Nagashima, Organometallics 2008, 27, 3502.
c) R. J. P. Corriu, J. J. E. Moreau, M. Pataud-Sat, J. Organomet. Chem.
1982, 228, 301.
This study was partially supported by the Global COE
program, “New Carbon Resource Sciences” and Grants-in-Aid
for Scientific Research from the Ministry of Education, Culture,
Sports, Science and Technology. Experimental assistance by
Dr. Hironori Tsutsumi and Mr. Taisuke Matsumoto is acknowl-
edged. The author (H.N.) is thankful for a JST-CREST program
(Creation of Innovative Functions of Intelligent Materials on the
Basis of the Element Strategy) to complete this work.
16 Supporting Information is available electronically on the CSJ-Journal Web
site, http://www.csj.jp/journals/chem-lett/index.html.
Chem. Lett. 2012, 41, 229-231
© 2012 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/