New method for synthesis of aldehydes from esters by sodium diisobutyl-t-butoxyaluminum hydride

Article abstract of DOI:10.1246/cl.2007.886

A new reducing agent, sodium diisobutyl-t-butoxyaluminum hydride (SDBBA), easily prepared by addition of sodium t-butoxide to DIBALH in THF at 0°C or room temperature, readily reacts with representative esters to give the corresponding aldehydes in very good yields under mild conditions (0°C). Copyright

Full text of DOI:10.1246/cl.2007.886

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86
Chemistry Letters Vol.36, No.7 (2007)
New Method for Synthesis of Aldehydes from Esters
by Sodium Diisobutyl-t-butoxyaluminum Hydride
Ã
Jung In Song and Duk Keun An
Department of Chemistry, Kangwon National University, Chunchon 200-701, Korea
(Received April 25, 2007; CL-070451; E-mail: dkan@kangwon.ac.kr)
A new reducing agent, sodium diisobutyl-t-butoxyalumi-
num hydride (SDBBA), easily prepared by addition of sodium
tion of lithium piperilide with DIBALH and exhibits excellent
b
5
reducing ability of various aromatic nitriles and tertiary ami-
5c
ꢀ
t-butoxide to DIBALH in THF at 0 C or room temperature,
readily reacts with representative esters to give the correspond-
des to the corresponding aldehydes in almost quantitative
yield. However, the LDBPA was less effective for the partial
ꢀ
5a
ing aldehydes in very good yields under mild conditions (0 C).
reduction of esters (47–83%) than other carboxylic acid
derivatives such as nitriles and tertiary amides. In the course
of our program for developing a new and better selectivity for
the partial reduction of esters to aldehydes than LDBPA,
we found that sodium diisobutyl-t-butoxyaluminum hydride
Partial reduction of ester to aldehyde is one of the most
important and highly desirable methods in organic synthesis,
and a large number of reducing agents for this purpose have
6
(SDBBA) easily prepared from commercially available
DIBALH smoothly reduced esters to aldehydes in very good
been reported. Among them, diisobutylaluminum hydride
1
ꢀ
(
DIBALH), which is commercially available, is used as one
yields at 0 C. Herein, we wish to report a new alternative and
of the most popular reducing agents. However, the yields of
aromatic aldehydes (48–70%) are considerably lower than those
of aliphatic aldehydes (80–88%) and this reagent requires a very
efficient method for partial reduction of esters to aldehydes by
SDBBA under mild conditions.
SDBBA was easily prepared by reacting an equimolar
ꢀ
ꢀ
low temperature (À78 C). It has also been reported that several
amount of sodium t-butoxide with DIBALH in THF at 0 C
substituted metal hydrides for partial reduction of esters, such as
2
or room temperature (Scheme 1). Next, we examined partial
reduction of representative aromatic and aliphatic esters, such
as ethyl benzoate (Entry 1 in Table 1) and ethyl hexanoate
lithium tri-t-butoxyaluminum hydride (LTBA), bis(4-methyl-1-
3
piperazinyl)aluminum hydride, and sodium diethylpiperidino-
4
ꢀ
hydroaluminate (SDP A), can be used. Of these reagent, LTBA
can be applied only for phenyl esters and bis(4-methyl-1-piper-
azinyl)aluminum hydride required elevated reaction temperature
(Entry 13 in Table 1), with SDBBA in THF at 0 C. The
reduction of these esters provides corresponding aldehydes
in very good yields in 6–12 h. Thus, we applied SDBBA for
the synthesis of aldehydes from various esters. The results for
representative esters are summarized in Table 1.
As shown in Table 1, ethyl benzoate was smoothly reduced
to produce benzaldehyde in 84% yield (Entry 1 of Table 1).8
Under identical conditions, reduction with DIBALH itself
provided only benzyl alcohol (Entry 2 of Table 1). The case of
ꢀ
(
65 C). Additionally sodium diethyldihydroaluminate (SDDA),
which is the precursor for synthesis of SDPA, is not commercial-
ly available. And, also these reagents cannot achieve very gener-
al reduction of both aliphatic and aromatic esters.
Recently, we have reported that lithium diisobutylpiperidi-
nohydroaluminate (LDBPA) was readily prepared by the reac-
Table 1. Yields of aldehydes in the reduction of representative esters with SDBBA at 0 C7
ꢀ
Reaction condition
Entry
Ester
Ethyl benzoate
Product
Benzaldehyde
Yield/%a
34
À
H /Ester
Time/h
1
2
3
4
5
6
7
8
9
1.2
(1.2)
1.5
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.5
1.2
1.2
6
(6)
24
6
6
6
6
6
6
24
1
b
(0)
85
91
91 (79)c
91
92
90 (77)c
83
73
89
83
91
94
93
81
Isopropyl benzoate
Ethyl 4-fluorobenzoate
Methyl 3-chlorobenzoate
Ethyl 2-bromobenzoate
Ethyl 4-bromobenzoate
Ethyl 4-nitrobenzoate
Ethyl 2-toluate
Ethyl 4-methoxybenzoate
Ethyl 2-naphthalate
Ethyl 2-furoate
Benzaldehyde
4-Fluorobenzaldehyde
3-Chlorobenzaldehyde
2-Bromobenzaldehyde
4-Bromobenzaldehyde
4-Nitrobenzaldehyde
2-Methylbenzaldehyde
4-Methoxybenzaldehyde
2-Naphthylaldehyde
2-Furoylaldehyde
hexanal
1
1
1
1
1
1
1
0
1
2
3
4
5
6
1
Ethyl hexanoate
12
12
12
12
Isopropyl hexanoate
Ethyl undecanoate
Ethyl cyclohexanecarboxylate
b
hexanal
Undecanal
Cyclohexanecarboxaldehyde
a
c
Yields were determined by GC. Yields obtained with DIBALH alone are shown in parentheses. Isolated yields.
Copyright Ó 2007 The Chemical Society of Japan

Chemistry Letters Vol.36, No.7 (2007)
887
O
References and Notes
1
i-Bu
i-Bu
NaO-t-Bu
i-Bu
R
OR'
0 °C
O
L. I. Zakharkin, I. M. Khorlina, Tetrahedron Lett. 1962, 3,
19.
Al
H
O
Al i-Bu Na
6
R
H
H
2
3
4
P. M. Weissman, H. C. Brown, J. Org. Chem. 1966, 31, 283.
M. Muraki, T. Mukaiyama, Chem. Lett. 1975, 215.
a) N. M. Yoon, J. H. Ahn, D. K. An, Y. S. Shon, J. Org. Chem.
DIBALH
SDBBA
73–93%
Scheme 1.
1993, 58, 1941. b) N. M. Yoon, Y. S. Shon, J. H. Ahn, J. W.
An, Bull. Korean Chem. Soc. 1993, 14, 522.
isopropyl benzoate needed a larger amount of hydride (1.5
equiv.) and a longer reaction time (24 h) than unhindered esters
such as ethyl benzoate, presumably due to the bulky isopropyl
group (Entry 3 in Table 1). Also, esters of electron-withdrawing
substituents such as ethyl 4-fluorobenzoate, methyl 3-chloroben-
zoate, ethyl 2-bromobenzoate, ethyl 4-bromobenzoate, and ethyl
5
6
a) J. H. Ahn, J. I. Song, J. E. Ahn, D. K. An, Bull. Korean
Chem. Soc. 2005, 26, 377. b) J. H. Ha, J. H. Ahn, D. K. An,
Bull. Korean Chem. Soc. 2006, 27, 121. c) S. M. Woo,
M. E. Kim, D. K. An, Bull. Korean Chem. Soc. 2006, 27,
1913.
4
2
-nitrobenzoate, and electron-donating substituents such as ethyl
-toluate and ethyl 4-methoxybenzoate were readily reduced to
To a solution of sodium t-butoxide (5.05 g, 52.5 mmol) in
THF (25 mL) was added dropwise DIBALH (50 mL, 1.0 M
ꢀ
the corresponding aldehydes in 73–92% yields (Entries 4–10
of Table 1). Among them, the reduction of ethyl 4-methoxyben-
zoate required a longer reaction time (24 h) than that of common
esters. This may be attributed to the strong electron-donating
effect of the methoxy group. Reduction of other aromatic esters
such as ethyl 2-naphthalate, a poly-aromatic ester and ethyl 2-
furoate, a heterocyclic ester gave the corresponding aldehydes
in 89% and 83% yield, respectively (Entries 11 and 12 in
Table 1). Furthermore, aliphatic esters such as ethyl hexanoate,
isopropyl hexanoate, ethyl undecanoate and ethyl cyclohexane-
carboxylate were smoothly reduced to the corresponding alde-
hydes under the same reaction conditions in 81–94% yields
in hexane, 50 mmol) at 0 C and the mixture was stirred
for 2 h at room temperature to give a colorless homogeneous
solution. The concentration of SDBBA solution in THF–
hexane was measured gasometrically by hydrolysis of an
aliquot of the solution with a hydrolyzing mixture of t-butyl
ꢀ
alcohol–THF (1:1) at 0 C.
7
All glassware used was dried thoroughly in an oven, assem-
bled hot, and cooled under a stream of dry nitrogen prior to
use. All reactions and manipulation of air- and moisture-
sensitive materials were carried out by standard techniques
for handling air-sensitive materials. All chemicals were
commercial products of the highest pure which were purified
further by standard methods before use. THF was dried over
sodium–benzophenone and distilled. Diisobutylaluminum
hydride (DIBALH) and sodium t-butoxide were purchased
from Aldrich Chemical Company. GC analyses were per-
formed on a Doman DS 6200 FID chromatograph using a
HP-1 (crosslinked methyl siloxane) capillary column (30 m).
All GC yields were determined with the use of a suitable
internal standard and authentic mixture.
(
Entries 13–16 in Table 1).
In summary, we easily prepared SDBBA by reacting com-
mercially available DIBALH with sodium t-butoxide. Further-
more, we have established a convenient method for the conver-
sion of esters to corresponding aldehydes in very good yields by
the new reducing agent (SDBBA). Especially, this reagent has
the great advantage that this aldehyde synthesis can be carried
ꢀ
ꢀ
out at 0 C instead of a very low temperature (À78 C) or a
very high temperature (reflux) and it can achieve very general
reduction of both aliphatic and aromatic esters in very good
yields. Therefore, SDBBA is believed to be a reagent of choice
for the synthesis of aldehydes from esters, instead of DIBALH,
LDBPA, and other reducing agents.
8
The following procedure for the reduction of ethyl benzoate
with SDBBA is representative. To a solution of ethyl benzoate
(
an internal standard was added LDBPA (1.2 mL, 0.5 M in
0.07 mL, 0.5 mmol) in THF (5 mL) containing naphthalene as
ꢀ
THF–hexane) at 0 C. After 6 h, the reaction mixture was
hydrolyzed with 5 mL of 1 M HCl (aq) and the product was
extracted with 10 mL of diethyl ether. The ether layer was
dried over anhydrous magnesium sulfate. GC analysis showed
an 84% yield of benzaldehyde.
This work was supported by the Research Institute for Basic
Science, Kangwon National University, Korea.
Published on the web (Advance View) June 9, 2007; doi:10.1246/cl.2007.886