Tishchenko reaction using an iridium-ligand bifunctional catalyst

Article abstract of DOI:10.1055/s-2005-868493

Tishchenko reaction of aldehydes in the presence of an amino alcohol-based Ir bifunctional catalyst was developed. The reaction proceeds with 1 mol% of the catalyst and 20-30 mol% of K₂CO₃ in acetonitrile at room temperature to give the corresponding dimeric esters in good yield. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-868493

1450
LETTER
Tishchenko Reaction Using an Iridium-Ligand Bifunctional Catalyst
Tishchenko
R
ea
a
ction
U
sin
k
gan Iridium-
e
LigandBif
y
unctional
C
a
u
talyst ki Suzuki,* Taichiro Yamada, Tomohito Matsuo, Kazuhiro Watanabe, Tadashi Katoh*
Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-Ku, Sendai, Miyagi 981-8558, Japan
Fax +81(22)2752013; E-mail: suzuki-t@tohoku-pharm.ac.jp; E-mail: katoh@tohoku-pharm.ac.jp
Received 8 March 2005
When a MeCN suspension of 3-phenylpropanal (1,
Scheme 1), K2CO3, and an Ir catalyst prepared from 311a
and 2-propanol (1:K2CO3:Ir = 100:30:1 mol ratio) was
allowed to stand at room temperature for 13 hours, 3-phe-
nylpropyl 3-phenylpropanoate (2a) was obtained in 91%
yield. The reaction in CH2Cl2 gave a higher yield of 95%.
Other solvents such as hexane, toluene, THF, EtOAc, ac-
etone, and butanone are usable, and the reactions in these
solvents proceeded in 79–87% yield. However, the reac-
tion in t-BuOH gave 2a in only 40% yield, accompanied
with formation of aldol-related products. To obtain the
dimeric ester in high yield, the use of K2CO3 is crucial.
Without the base, the reaction proceeded in only 6% yield
after 10 hours. However, the yield increased to 85% in the
presence of just 10 mol% of K2CO3.13
Abstract: Tishchenko reaction of aldehydes in the presence of an
amino alcohol-based Ir bifunctional catalyst was developed. The re-
action proceeds with 1 mol% of the catalyst and 20–30 mol% of
K2CO3 in acetonitrile at room temperature to give the corresponding
dimeric esters in good yield.
Key words: aldehydes, esters, hydrogen transfer, iridium catalyst,
Tishchenko reaction
In 1906, Tischtschenko reported the conversion of alde-
hydes to dimeric esters in the presence of Al alkoxide and
Mg alkoxide catalysts.1,2 Since then, the Tishchenko reac-
tion has been used as an efficient method for the prepara-
tion of dimeric esters in industry. Other catalyst systems
have also been developed, including boric acid3 and tran-
sition metal catalysts such as Fe,4 Ru,5 Zr,6 lanthanide,7
Ir(I),8 and Os,9 and more recently, sophisticated Al alkox-
ide catalysts.10 Although the catalyst system developed by
Shvo has excellent activity,5b heating is required. Some
catalyst systems can be used at room temperature, but the
reaction of simple aliphatic aldehydes is suffered from the
formation of aldol-related products,7 and the reactions of
aromatic aldehydes proceed in only modest yields.10
Thus, there is still great room for improvement of the
synthetic efficiency. Herein, we wish to report a mild
Tishchenko reaction with broad generality using an
iridium complex developed by our group.11,12
Having succeeded in optimizing the reaction conditions,
we next investigated Tishchenko reaction of other sub-
strates. As shown in Table 1, both aliphatic and aromatic
aldehydes could be converted to the corresponding dimer-
ic esters in high yields.14 Thus, the reaction of the unsat-
urated aldehyde 1b gave 2b in 90% yield, albeit with a
longer reaction time (entry 2). The product 2b is a precur-
sor of epoxy resin. Various aromatic aldehydes were con-
verted to the corresponding dimeric esters in good yields
(entries 3–8). Thus, the reaction of aromatic aldehydes
with a substituent such as alkyl, sulfide, halogen, or nitro
proceeded without any difficulties. As anticipated from
the literature,10b however, a,b-unsaturated aldehyde such
as cinnamaldehyde is a difficult substrate and the reaction
of 1i gave 2i in only 34% yield, along with a mixture of
partially or fully saturated esters in 19% yield (entry 9).
Ir
HN
O
3
A probable mechanism for the Ir-catalyzed Tishchenko
reaction is shown in Scheme 2.15 We believe that treat-
ment of the Ir complex 3 with 2-propanol gives the hy-
dride species 4,16 which reduces the aldehyde 1 to give the
corresponding alcohol 5 and the Ir complex 3.17 Then, the
aldehyde-hemiacetal equilibrium generates the hemiace-
tal 6. The Ir complex 3 oxidizes the hemiacetal 6, giving
the dimeric ester 2 and Ir hydride 4.
Ph Ph
i-PrOH
O
O
Ir cat. (1 mol%)
R
H
R
O
R
K2CO3 (20–30 mol%)
MeCN, r.t.
1
2
Scheme 1
In summary, we have developed a mild Tishchenko
dimerization using an Ir-ligand bifunctional catalyst. The
reaction proceeds at room temperature and is effective
with a wide range of aldehydes. This simple and econom-
ical process should be useful in contemporary organic
synthesis. Further studies, including structural elucidation
of the active species, are under way.
SYNLETT 2005, No. 9, pp 1450–1452
0
1.
0
6.
2
0
0
5
Advanced online publication: 25.04.2005
DOI: 10.1055/s-2005-868493; Art ID: U06605ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Tishchenko Reaction Using an Iridium-Ligand Bifunctional Catalyst
1451
General Procedure for the Tishchenko Reaction
Table 1 Tishchenko Reaction of Aldehydes Catalyzed by an Ir
Catalysta
2-PrOH (0.15 mL, 2.0 mmol) was added to a 10 mL test tube
charged with 5.4 mg (0.01 mmol) of Ir complex 3 (red purple) under
Ar. Immediately, a yellow solution was obtained with stirring at r.t.
After 10 min, the volatile material was removed under vacuum. The
residue was dissolved in MeCN (0.2 mL) under Ar and stirred with
aldehyde (1.0 mmol) in the presence of K2CO3 (0.2 mmol) at r.t.
The mixture was passed through a short silica gel column (12 g,
Et2O) to remove the catalyst and inorganic base. The products of 2
were purified by silica gel column chromatography (hexane–
EtOAc).
Entry
1
Aliphatic Aromatic aldehyde
aldehyde
Time (h) Yield (%)b
CHO
1a
1b
1c
13
39
22
91
90
97
2
3
CHO
CHO
CHO
Acknowledgment
Me
This work was financially supported by a Grant-in-Aid for
Encouragement of Young Scientists (B) from JSPS.
4
1d
18
89
MeS
5
1e
1f
12
13
86
93
CHO
References
(1) (a) Tischtschenko, W. Chem. Zentralbl. 1906, 77, 1309.
(b) Larock, R. C. Comprehensive Organic Transformations;
VCH Publishers, Inc.: New York, 1989, 840. (c) For a
recent review: Törmäkangas, O. P.; Koskinen, A. M. P.
Recent Res. Dev. Org. Chem. 2001, 5, 225.
(2) For recent examples of Tishchenko-related reactions, see:
Gnanadesikan, V.; Horiuchi, Y.; Ohshima, T.; Shibasaki, M.
J. Am. Chem. Soc. 2004, 126, 7782; and references cited
therein.
6c
CHO
CHO
Cl
7
8
1g
1h
18
18
89
88
Br
CHO
(3) Stapp, P. R. J. Org. Chem. 1973, 38, 1433.
(4) Yamashita, M.; Watanabe, Y.; Mitsudo, T.-a.; Takegami, Y.
Bull. Chem. Soc. Jpn. 1976, 49, 3597.
O2N
9
1i
18
34
CHO
(5) (a) Ito, T.; Horino, H.; Koshiro, Y.; Yamamoto, A. Bull.
Chem. Soc. Jpn. 1982, 55, 504. (b) Menashe, N.; Shvo, Y.
Organometallics 1991, 10, 3885.
(6) Morita, K.; Nishiyama, Y.; Ishii, Y. Organometallics 1993,
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(7) (a) Onozawa, S.-y.; Sakakura, T.; Tanaka, M.; Shiro, M.
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3078.
a Unless otherwise stated, the reaction was carried out using 1 (1.0
mmol), Ir catalyst (0.01 mmol, 1 mol%), and K2CO3 (0.2 mmol) in
MeCN at r.t.
b Isolated yield.
c The amount of 0.3 mmol of K2CO3 was used.
O
R
H
R
OH
1
5
O
OH
O
R
H
1
Ir
Ir
Ir
H
H
N
O
O
N
O
H
H
N
Ph
Ph
Ph
Ph
Ph
H
4
Ph
3
3
O
OH
R
O
R
R
O
R
6
2
Scheme 2 Proposed mechanism for the Ir-catalyzed Tishchenko reaction
Synlett 2005, No. 9, 1450–1452 © Thieme Stuttgart · New York

1452
T. Suzuki et al.
LETTER
(8) (a) Bernard, K. A.; Atwood, J. D. Organometallics 1988, 7,
235. (b) Bernard, K. A.; Atwood, J. D. Organometallics
1989, 8, 795.
(9) Barrio, P.; Esteruelas, M. A.; Oñate, E. Organometallics
2004, 23, 1340.
(13) Although Cs2CO3 also showed similar reactivity (ca. 90%),
the use of other bases, such as Na2CO3, KHCO3, KOAc, and
Et3N resulted in lower reactivity (<10% yield). t-BuOK
afforded the aldol condensation product without forming the
dimeric ester.
(10) (a) Ooi, T.; Miura, T.; Takaya, K.; Maruoka, K. Tetrahedron
Lett. 1999, 40, 7695. (b) Simpura, I.; Nevalainen, V.
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were roughly calculated to be in range between 43 and 49 for
most substrates.
(15) Although the role of the K2CO3 is not clear at present, it
might increase the nucleophilicity of the reduced alcohol 5
to the corresponding aldehyde for the formation of the
hemiacetal 6. For the mechanistic study of acid- and base-
catalyzed formation of the hemiacetal, see: Sorensen, P. E.;
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(16) In a control experiment, no reaction took place without Ir
complex (in the presence of K2CO3).
(11) (a) Suzuki, T.; Morita, K.; Tsuchida, M.; Hiroi, K. Org. Lett.
2002, 4, 2361. (b) Suzuki, T.; Morita, K.; Matsuo, Y.; Hiroi,
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K.; Tsuchida, M.; Hiroi, K. J. Org. Chem. 2003, 68, 1601.
For a related synthesis of dimeric esters using oxidative
dimerization of primary alcohol, see: (d) Suzuki, T.;
Matsuo, T.; Watanabe, K.; Katoh, T. Synlett 2005, in press.
(12) Recent examples of hydrogen transfer reaction using Cp*Ir
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Lett. 1998, 1199. (b) Murata, K.; Ikariya, T.; Noyori, R. J.
Org. Chem. 1999, 64, 2186. (c) Ogo, S.; Makihara, N.;
Watanabe, Y. Organometallics 1999, 18, 5470. (d) Ogo, S.;
Makihara, N.; Kaneko, Y.; Watanabe, Y. Organometallics
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Tetrahedron Lett. 2004, 45, 3215. (j) Fujita, K.; Fujii, T.;
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the aldehyde was completely consumed.
Synlett 2005, No. 9, 1450–1452 © Thieme Stuttgart · New York