Tishchenko reactions and Oppenauer oxidation reactions of aldehydes promoted by diisobutylaluminum hydride

Article abstract of DOI:10.1016/j.tetlet.2004.02.145

The aliphatic aldehydes react with catalytic amount of Dibal-H in n-pentane to give the corresponding Tishchenko products in good to excellent yields. Contrary, α-silyloxyaldehydes give α-silyloxyketones via Oppenauer oxidation under similar condition.

Full text of DOI:10.1016/j.tetlet.2004.02.145

Tetrahedron
Letters
Tetrahedron Letters45 (2004) 3313–3315
Tishchenko reactions and Oppenauer oxidation reactions
of aldehydes promoted by diisobutylaluminum hydride
a
a
Yung-Son Hon,a,b, Chun-Ping Chang and Ying-Chieh Wong
*
aDepartment of Chemistry and Biochemistry, National Chung Cheng University, Chia-Yi 621, Taiwan, ROC
bInstitute of Chemistry, Academia Sinica, Nankang, Taipei 115, Taiwan, ROC
Received 14 October 2003; revised 9 February 2004; accepted 12 February 2004
Abstract—The aliphatic aldehydesreact with catalytic amount of Dibal-H in n-pentane to give the corresponding Tishchenko
productsin good to excellent yields. Contrary, a-silyloxyaldehydes give a-silyloxyketones via Oppenauer oxidation under similar
condition.
Ó 2004 Elsevier Ltd. All rights reserved.
The Tishchenko reaction involves the aldehydes dimer-
ization giving the corresponding esters under the influ-
ence of aluminum alkoxides.1 The reaction hasbeen
carried out with a number of other catalysts2 such as
alkali metal,3 alkali earth metal oxide,4 boric acid,5
alumina supported KF,6 Cp2MH2 (M¼Zr, Hf),7 EtLnI
(Ln¼Pr, Nd, Sm),8 SmI2,9 LiWO2,10 Fe(CO)4,11
RuH2(PPh3)4,12 RhH(CO)(PPh3)3,13 trans-ROIr(CO)-
(PPh3)2,14 nickel complex,15 and Cu(I).16 Diisobutylalu-
minum hydride (Dibal-H) isa useful reducing agent to
reduce an aldehyde to the corresponding alcohol. To the
best of our knowledge, there is no report on using Dibal-
H as catalyst to promote the Tishchenko or Oppenauer
reaction of aldehydes. In this report, we will describe our
results on such transformations.
the reaction of the Grignard reagent with the ester 3,
which isgenerated from the Tishchenko reaction via an
intermediate A. Intrigued by this hypothesis, we were
curiousto know whether the aluminum analogue B is
applicable to ester formation.
R
R
H
O
R
Metal
X
O
H
O
O
R
O
R=Cyclohexyl 3
R
X= Allyl, Metal = MgCl A
X= H, Metal = Al(i-Bu)2
B
In order to avoid the solvation effect of the etheric sol-
vent with the aluminum reagent, slow addition of Dibal-
H to a solution of aldehyde 6a in anhydrous n-pentane
was first tried. The typical procedure is described as
follows. To a solution of aldehyde 6a (4.92 mmol) in
n-pentane (8 mL), a solution of Dibal-H (0.49 mL, 1.0 M
solution in hexane) in 1 mL of n-pentane wasadded
dropwise by a syringe pump over a period of 1 h at 0 °C.
After stirring at ambient temperature for 5 h, ester 7a
wasioslated in 77% yield (Table 1, entry 1). The pro-
posed mechanism of this reaction is shown in Figure 1.
The reaction of Dibal-H with aldehyde 6a givesalumi-
num alkoxide i, which undergo nucleophilic addition to
aldehyde 6a to give the corresponding aluminum alk-
oxide ii. The six-membered ring transition state B0,
which isformed from the reaction of intermediate ii with
aldehyde 6a, undergoesTishchenko reaction to give not
only the corresponding ester, but also aluminum
OH
HO
1.2 equiv.
HO
CH2=CHCH2MgCl
+
+
RCHO
ð1Þ
Slow addition, 0 oC,
THF
R
R
R
27%
5
4
2
1
28%
R=Cyclohexyl
40%
When aldehyde 1 wastreated with allylmagneiusm
chloride in THF by a syringe pump over a period of 1 h
at 0 °C, we isolated not only the desired product 2 (40%),
but also primary alcohol 4 (28%) and tertiary alcohol 5
(27%) (Eq. 1). Presumably, the alcohol 5 isformed from
Keywords: Tishchenko reaction; Oppenauer oxidation; a-silyloxyalde-
hyde; a-silyloxyketone.
* Corresponding author. Tel.: +886-5-2720411x6262; fax: +886-5-27-
21040; e-mail: cheysh@ccu.edu.tw
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.02.145

3314
Y.-S. Hon et al. / Tetrahedron Letters 45 (2004) 3313–3315
Table 1. Tishchenko reaction and Oppenauer oxidation of aldehydes
promoted by Dibal-H
OTBS
(Bui)2Al
TBSO
Dibal-H
O
H
O
O
Entry Aldehyde
Time
(h)
Product Yield
(%)
TBSO
H
R
6k
iii
R
8k
R
1
2
3
4
5
6
7
8
PhCH2CH2CHO (6a)
Cyclohexyl-CHO (1)
tert-Butyl-CHO (6c)
5
5
7a
7b
7c
7d
7e
7f
77
93
95
77
97
61
50
60
1,4-silyl
Oppenauer
oxidation
migration
5
(Buii)2Al
OTBS
(Bui)2Al
OTBS
(R)-(þ)-Citronellal (6d)
H2C@CH(CH2)8CHO (6e)
MeO2C(CH2)6CHO (6f)
5
O
H
H
5
12
TBS O
O
O
H
iv
R
R
(MeO)2CH(CH2)6CHO (6g) 12
10
7g
7h
6k
(R)-(ꢀ)-Glyceraldehyde
acetonide (6h)
R
B"
9
BnOCH2CHO (6i)
TrOCH2CHO (6j)
Ph(CH2)3CH(OTBS)-CHO
(6k)
8
6
7i
52
83
78
Figure 2. The possible reaction mechanism of a-silyloxyaldehydes with
Dibal-H via Oppenauer oxidation (R¼PhCH2)3–).
10
11
7j
8k
12
12
13
14
C6H9CH(OTBS)CHO (6l)
t-BuCH(OTBS)CHO (6m)
Ph(CH2)2CH(OTBS)-
CH2CHO (6n)
7
12
12
8l
45
0
8m
7n
retard the reaction at all (entries9 and 10). Interestingly,
a-silyloxyaldehyde 6k reacted with Dibal-H afforded
a-silyloxyketone 8k instead of the corresponding Tish-
chenko product (Eq. 3, entry 11). The proposed mech-
anism of this reaction is shown in Figure 2. The reaction
of Dibal-H with aldehyde 6k givesthe aluminum alk-
oxide iii, which undergoes1,4-islyl group migration to
give the corresponding aluminum alkoxide iv. The six-
membered ring transition state B00, which isformed from
52
8n
29
O
(Bui)2Al
Dibal-H
RCHO
O
R
O
the reaction of intermediate iv with aldehyde 6k,
18
1 or 6
7
i
undergoesOppenauer oxidation
to give not only the
R
R
corresponding a-silyloxyketone 8k, but also aluminum
alkoxide iii, which can undergo the second cycle of the
reaction. The failure of secondary aluminum alkoxide iv
to proceed the Tishchenko pathway may be due to the
steric reason. a-Silyloxyaldehydes 6l also gave the
Oppenauer oxidation product 8l in good yields(entry
12). These results indicate that the migration of the silyl
group from secondary alkoxysilyl ether iii to the pri-
mary alkoxysilyl ether iv is a favorable process. How-
ever, there isno reaction for a-silyloxyaldehyde 6m
probably due to the steric effect (entry 13). Interestingly,
Dibal-H reactswith b-silyloxyaldehyde 6n to give both
Tishchenko product 7n (52%) and Oppenauer oxidation
product 8n (29%) (entry 14). The formation of product
8n results from the 1,5-silyl group migration, which is
not a facile process, and hence the Tishchenko pathway
becomesa predominant one.
RCHO
Tishchenko
reaction
Al(iBu)2
Al(iBu)2
O
O
O
O
H
O
H
R
R
R
H
ii
R
R
RCHO
B'
Figure 1. The possible reaction mechanism of aldehydes with Dibal-H
via Tishchenko reaction.
alkoxide i, which can undergo the second cycle of the
Tishchenko reaction. It is worthy to mention that the
alkoxy group of intermediate i isthe only tranfserable
group in the reaction. Therefore, the present reaction
mechanism is different from the Tishchenko reaction
catalyzed by aluminum trialkoxides.1
Cat. Dibal-H
RCO2CH2R
RCHO
6
Pentane, 0 oC
ð2Þ
ð3Þ
Thisreaction conditionshave been applied to aldehydes
with secondary, tertiary, or quarternary a-carbon in
excellent yields(Eq. 2, Table 1, entries1–3). The alde-
hydeswith isolated alkene moieties 6d and 6e gave the
corresponding esters in excellent yields (entries 4 and 5).
Unfortunately, the a,b-unsaturated aldehydes and aryl
aldehydesdid not give the deisred productsand we
recovered most of the starting materials. The aldehydes
tethered with either methoxycarbonyl 6f, dimethyl acetal
6g and acetonide 6h also underwent Tishchenko reac-
7
O
OTBS
Cat. Dibal-H
OTBS
8k-8l
H
R
Pentane, 0 oC
R
6k-6l
O
In conclusion, the slow addition of the catalytic amount
of Dibal-H to the aldehydesin n-pentane givesthe
corresponding Tishchenko products in good yields. The
reactionswork quite well for aldehydesbearing 2 °-, 3°-,
and 4°-a-carbon. However, a-silyloxyaldehyde affords
the Oppenauer oxidation product in good yield under
similar condition.
tionsin good yields(entries6–8). The Thischenko
17
product 7h isoptically pure,
indicating that no
epimerization occursduring the reaction. Furthermore,
a-alkoxyaldehydes 6i and 6j underwent Tishchenko
reaction in good yields. The bulky trityl group does not

Y.-S. Hon et al. / Tetrahedron Letters 45 (2004) 3313–3315
3315
Nishiyama, Y.; Ishii, Y. J. Org. Chem. 1997, 62, 3409–
3412.
Acknowledgements
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We are grateful to the National Science Council,
National Chung Cheng University and Academia Sinica
for the financial support.
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