Ruthenium-catalyzed, one-pot alcohol oxidation-wittig reaction producing αβ unsaturated esters

Article abstract of DOI:10.1002/ejoc.200900274

By a one-pot process, αβ-unsaturated esters were synthesized in high yield through the Ru-catalyzed oxidation of primary alcohols and the coupling of the resulting aldehydes and stabilized Wittig reagents. The ruthenium catalyst is composed of ruthenium nanoparticles embedded in aluminum oxyhydroxide and can be recovered simply by filtration or decantation. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009.

Full text of DOI:10.1002/ejoc.200900274

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200900274
Ruthenium-Catalyzed, One-Pot Alcohol Oxidation–Wittig Reaction Producing
α,β-Unsaturated Esters
Eun Young Lee,[a] Youngkwon Kim,[b] Jae Sung Lee,[b] and Jaiwook Park*[a]
Keywords: Heterogeneous catalysis / Wittig reactions / Ruthenium / Oxidation
By a one-pot process, α,β-unsaturated esters were synthe-
sized in high yield through the Ru-catalyzed oxidation of pri-
mary alcohols and the coupling of the resulting aldehydes
and stabilized Wittig reagents. The ruthenium catalyst is
composed of ruthenium nanoparticles embedded in alumi-
num oxyhydroxide and can be recovered simply by filtration
or decantation.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
the presence of base at 150 °C for 72 h.[8] However, the alk-
enylation products could be isolated and dihydrocinnamate
derivatives were obtained as the major products in moder-
ate yields as a result of hydrogenation by iridium hydride
intermediates. They have improved the coupling reaction by
using a ruthenium N-heterocyclic carbene complex in the
presence of vinyltrimethylsilane at 80 °C.[9] However, the
major products are still dihydrocinnamate derivatives.
Recently, we developed a method for heterogeneous
metal catalysts, which are composed of metal nanoparticles
entrapped in highly porous aluminum oxyhydroxide.[10]
Among the catalysts, ruthenium catalyst 1 [Ru/AlO(OH)]
shows high activity for the dehydrogenation of various
alcohols.[10d] Herein, we describe the application of 1 for a
one-pot oxidation–Wittig reaction. α,β-Unsaturated esters
were obtained in high yield from primary alcohols and sta-
bilized Wittig reagents by using 1 (1 mol-% of Ru) and an
oxygen balloon (Scheme 1).
Introduction
The Wittig reaction is an important reaction to provide
α,β-unsaturated esters, which are essential intermediates in
natural product synthesis.[1] Although the Wittig reaction
using aldehydes and phosphorus ylides has a long history,[2]
the reaction is limited frequently by the oxidation, decom-
position, or polymerization of the aldehydes employed.
Since the discovery of the one-pot Swern oxidation–
Wittig reaction reported by Ireland and Norbeck,[3] several
methods for the one-pot oxidation–Wittig reaction have
been devised.[4–6] However, most of them suffer from the
use of hazardous oxidants and/or the requirement of an
activation process. For example, Barrett and co-workers
used Dess–Martin periodinane, which is not only hazard-
ous but also difficult to handle.[5] Oxidation using manga-
nese dioxide was reported by Taylor and co-workers, which
requires preactivation of manganese dioxide.[6] Recently,
aerobic oxidation was attempted by Kim and co-workers by
using a ruthenium catalyst for the one-pot oxidation–Wittig
reaction.[7] However, this system requires stoichiometric
Cs2CO3 and provides alkenyl esters generally in low yields.
Meanwhile, Williams and co-workers reported the synthesis
of dihydrocinnamate derivatives by a one-pot process,
wherein coupling of the resulting aldehydes obtained from
dehydrogenation of primary benzylic alcohols with β-car-
bonyl phosphonates were achieved by using [IrCl(cod)]2 in
Scheme 1. One-pot oxidation–Wittig reaction.
Results and Discussion
Catalyst 1 was prepared from ruthenium(III) chloride hy-
[a] Department of Chemistry, Pohang University of Science and drate, ethanol, and Al(sec-OBu)3 according to the pro-
cedure described previously.[10d] The reaction of benzyl
Technology (POSTECH),
San 31 Hyojadong, Pohang, Kyeongbuk 790-784, Republic of
alcohol with methyl (triphenylphosphoranylidene)acetate
was carried out under various conditions to find optimum
conditions (Table 1). When the reaction was performed by
using 1 (1 mol-% of Ru) under an atmosphere of argon,
methyl cinnamate and benzyl cinnamate were formed in 59
and 8% yield, respectively, by heating at 110 °C for 30 h
(Table 1, Entry 1). However, methyl dihydrocinnamate was
Korea
Fax: +82-54-279-3399
E-mail: pjw@postech.ac.kr
[b] Department of Chemical Engineering, Pohang University of
Science and Technology (POSTECH),
San 31 Hyojadong, Pohang, Kyeongbuk 790-784, Republic of
Korea
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200900274.
Eur. J. Org. Chem. 2009, 2943–2946
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2943

E. Y. Lee, Y. Kim, J. S. Lee, J. Park
SHORT COMMUNICATION
not detected. Notably, changing the reaction atmosphere benzylic alcohols as well as aliphatic alcohols, whereas the
from argon to oxygen greatly enhanced the reaction effi- yields were somewhat low in the reactions of aliphatic
ciency; methyl cinnamate was formed in 91% and the for- alcohols (Table 2, Entries 1 and 2). A substituent effect was
mation of benzyl cinnamate decreased to less than 2% at not significant in the reactions of benzylic alcohols (Table 2,
80 °C for 20 h (Table 1, Entry 2). The reaction was complete Entries 3–8). The reaction of 1,4-phenylenedimethanol gave
within 12 h at 110 °C with an increased yield of methyl cin- the corresponding diester in 82% yield (Table 2, Entry 7).[11]
namate (Table 1, Entry 3). The reaction in the air was a The vinyl group, which has a capacity to be applied in poly-
little slower than that under an atmosphere of oxygen mer synthesis, survived during the coupling reaction
(Table 1, Entry 4). It is clear that 1 is an excellent catalyst (Table 2, Entry 8).[12] The carbon–carbon double bond in
for the one-pot reaction in comparison with commercially an allyl alcohol and the triple bond in a propargyl alcohol
available catalysts and those reported for related reactions were also compatible with the reaction conditions (Table 2,
(Table 1, Entries 5–8); the reaction with the use of 1 is much Entries 9 and 10). It is notable that the reaction of the pro-
more selective and faster for the formation of methyl cinna- pargyl alcohol is much more efficient than that using [(η6-
mate than those using other catalysts. In addition, in our p-cymene)RuCl2]2 as a homogeneous catalyst, which gave
reaction system, molecular oxygen was the terminal oxidant the corresponding α,β-unsaturated ester only in 28%
and does not require any additives such as base or ligand.
yield.[7] Our catalyst system was also applicable for the reac-
tions of alcohols containing heteroaromatic rings (Table 2,
Entries 11 and 12). The reaction of thiophen-2-ylmethanol
was as efficient as those of benzyl alcohols, but that of pyr-
idin-3-ylmethanol was hard to improve.
Table 1. Catalytic activity comparison.[a]
Entry Catalyst
T
t
Yield [%][b]
[°C]
[h]
2
3
4
Scheme 2. Ru-catalyzed, one-pot oxidation–Wittig reaction with
benzyl alcohol and stabilized Wittig reagents.
1[c]
2
1
110
80
30
20
12
12
12
14
72
24
59
91 Ͻ2
94 Ͻ2
77
48
77
21
8
0
0
0
0
0
0.6
68
78[h]
1
3
1
1
110
110
110
110
150
80
4[d]
5
1
2
8
3
[e]
0.5% Ru/Al2O3
6
7
8
5% Ru/C[e]
Conclusions
[f]
[IrCl(cod)]2
Ru(IMes)(PPh3)(CO)H2
[g]
In summary, we have developed a simple and efficient
method to prepare α,β-unsaturated esters from primary
alcohols and stabilized Wittig reagents through a one-pot
process. The method is applicable to aliphatic alcohols as
well as benzylic ones and does not require any additives
except oxygen, which helps the catalytic dehydrogenation of
alcohols.
[a] A mixture of benzyl alcohol (1.0 mmol), Ph3P=CHCO2Me
(1.1 mmol), and a catalyst (1 mol-% of Ru) in toluene (2.0 mL) was
heated under an oxygen atmosphere (balloon). [b] Determined by
1H NMR spectroscopy. [c] Under an argon atmosphere. [d] In the
air. [e] Commercial Ru catalysts. [f] See ref.[8] [g] See ref.[9] [h] Isola-
tion yield.
The recyclability of 1 was tested in the reaction of benzyl
alcohol with ethyl (triphenylphosphoranylidene)acetate un-
der the conditions outlined in Entry 3 of Table 1. The cata-
lyst could be recovered simply by decantation, but a de-
crease in activity was observed with reuse: first use, 93%;
second use, 85%; third use, 77%; fourth use, 60%.
Experimental Section
Synthesis of Ru/AlO(OH) (1): A mixture of RuCl3·3H2O (Ru con-
tent: 41.25%; 130 mg, 0.53 mmol of Ru) and Al(sec-OBu)3 (9.4 g,
38 mmol) in ethanol (4.6 mL) was heated at 100 °C for 1 h to give
a black suspension. Distilled water (9.0 mL) was added into the
suspension to give a black gel. The gel was filtered at room tem-
perature, washed with acetone, and dried under an argon atmo-
sphere to give 1 as a gray powder (3.2 g, 1.7 wt.-% of Ru).
We tested three more Wittig reagents for the coupling
reaction with benzyl alcohol (Scheme 2). Under the condi-
tions of the Entry 3 of Table 1, ethyl cinnamate and benzyl
cinnamate were obtained in 96 (E/Z = 15:1) and 94% (E/Z
= 14:1) yield, respectively. In the case of the Wittig reagent
containing one additional methyl group at the α carbon
atom, the reaction was relatively slow and required more
catalyst (2.0 mol-% Ru) to give (E)-ethyl 2-methyl-3-phenyl-
acrylate in 81% yield. Then, various primary alcohols were
employed in the coupling reactions with ethyl (triphenyl-
phosphoranylidene)acetate (Table 2). The expected α,β-un-
One-Pot Oxidation–Wittig Reaction: A mixture of benzyl alcohol
(100 µL, 1.0 mmol), methyl (triphenylphosphoranylidene)acetate
(380 mg, 1.1 mmol), and Ru/AlO(OH) (1; 59 mg, 1.0 mol-% of Ru)
in toluene (2.0 mL) was stirred for 12 h at 110 °C under an oxygen
atmosphere (balloon). The reaction mixture was filtered through a
glass filter, and the filtrate was concentrated under reduced pres-
sure. The crude product was purified by column chromatography
saturated esters were formed selectively in the reactions of to give methyl cinnamate (153 mg, 94%).[13]
2944 Eur. J. Org. Chem. 2009, 2943–2946
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Ru-Catalyzed One-Pot Alcohol Oxidation–Wittig Reaction
Table 2. Reactions of ethyl (triphenylphosphoranylidene)acetate and primary alcohols.[a]
[a] A mixture of an alcohol (1.0 mmol), ethyl (triphenylphosphoranylidene)acetate (1.1–2.2 mmol), and 1 in toluene was heated to reflux
under an oxygen atmosphere (balloon). [b] The products were isolated by column chromatography. [c] The E/Z ratio was determined by
GC. [d] The reaction mixture was heated at 80 °C. [e] A 87:13 mixture of (E,E)-diene and (E,Z)-diene was obtained.
5694–5707; b) C. Thirsk, A. Whiting, J. Chem. Soc. Perkin
Trans. 1 2002, 8, 999–1023.
Supporting Information (see footnote on the first page of this arti-
cle): Syntheses of 4-vinylbenzyl alcohol and ethyl 3-(4-vinylphenyl)-
acrylate; recycling test for 1; characterization data for the α,β-un-
saturated esters.
[2]
a) B. E. Maryanoff, A. B. Reitz, Chem. Rev. 1989, 89, 863–927;
b) Y. Shen, Acc. Chem. Res. 1998, 31, 584–592; c) A. El-Batta,
C. Jiang, W. Zhao, R. Anness, A. L. Cooksy, M. Bergdahl, J.
Org. Chem. 2007, 72, 5244–5259; d) V. K. Aggarwal, J. R. Ful-
ton, C. G. Sheldon, J. de Vicente, J. Am. Chem. Soc. 2003, 125,
6034–6035; e) S. Frattini, M. Quai, E. Cereda, Tetrahedron
Lett. 2001, 42, 6827–6829; f) R. Robiette, J. Richardson, V. K.
Aggarwal, J. N. Harvey, J. Am. Chem. Soc. 2006, 128, 2394–
2409.
R. E. Ireland, D. W. Norbeck, J. Org. Chem. 1985, 50, 2198–
2200.
a) F. R. P. Crisóstomo, R. Carrillo, T. Martín, F. García-Tel-
lado, V. S. Martín, J. Org. Chem. 2005, 70, 10099–10101; b) J.-
M. Vatèle, Tetrahedron Lett. 2006, 47, 715–718; c) R. N. Mac-
Acknowledgments
We are grateful for financial support from the Korea Research
Foundation (KRF-2008-314-C00203) and the Korean Ministry of
Education through the BK21 project for our graduate program.
[3]
[4]
[1] a) A. S. Kireev, O. N. Nadein, V. J. Agustin, N. E. Bush, A.
Evidente, M. Manpadi, M. A. Ogasawara, S. K. Rastogi, S.
Rogelj, S. T. Shors, A. Kornienko, J. Org. Chem. 2006, 71,
Eur. J. Org. Chem. 2009, 2943–2946
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2945

E. Y. Lee, Y. Kim, J. S. Lee, J. Park
SHORT COMMUNICATION
Coss, E. P. Balskus, S. V. Ley, Tetrahedron Lett. 2003, 44, 7779–
7781; d) S. Shuto, S. Niizuma, A. Matsuda, J. Org. Chem. 1998,
63, 4489–4493; e) A. R. Bressette, L. C. Glover IV, Synlett
2004, 738–740.
S. H. Seo, I. S. Park, R. K. Cheedrala, J. Park, Angew. Chem.
Int. Ed. 2005, 44, 6913–6915; c) I. S. Park, M. S. Kwon, N.
Kim, J. S. Lee, K. Y. Kang, J. Park, Chem. Commun. 2005,
5667–5669; d) W.-H. Kim, I. S. Park, J. Park, Org. Lett. 2006,
8, 2543–2545; e) I. S. Park, M. S. Kwon, K. Y. Kang, J. S. Lee,
J. Park, Adv. Synth. Catal. 2007, 349, 2039–2047; f) I. S. Park,
M. S. Kwon, Y. Kim, J. S. Lee, J. Park, Org. Lett. 2008, 10,
497–500; g) S. Kim, S. W. Bae, J. S. Lee, J. Park, Tetrahedron
2009, 65,1461–1466.
[5] A. G. M. Barrett, D. Hamprecht, M. Ohkubo, J. Org. Chem.
1997, 62, 9376–9378.
[6] a) L. Blackburn, X. Wei, R. J. K. Taylor, Chem. Commun. 1999,
1337–1338; b) R. J. K. Taylor, M. Reid, J. Foot, S. A. Raw, Acc.
Chem. Res. 2005, 38, 851–869.
[7] G. Kim, D. G. Lee, S. Chang, Bull. Korean Chem. Soc. 2001,
22, 943–944.
[8] a) M. G. Edwards, J. M. J. Williams, Angew. Chem. Int. Ed.
2002, 41, 4740–4743; b) P. J. Black, M. G. Edwards, J. M. J.
Williams, Eur. J. Org. Chem. 2006, 4367–4378.
[9] M. G. Edwards, R. F. R. Jazzar, B. M. Paine, D. J. Shermer,
M. K. Whittlesey, J. M. J Williams, D. D. Edney, Chem. Com-
mun. 2004, 90–91.
[10] a) M. S. Kwon, N. Kim, C. M. Park, J. S. Lee, K. Y. Kang, J.
Park, Org. Lett. 2005, 7, 1077–1079; b) M. S. Kwon, N. Kim,
[11]
[12]
a) O. Guney-Altay, D. Pestov, G. Tepper, J. Am. Chem. Soc.
2007, 129, 13957–13962; b) T. Koizumi, K. Tsutsui, K. Tanaka,
Eur. J. Org. Chem. 2003, 4528–4532.
M. J. Farrall, Polym. Bull. 1984, 11, 191–194.
[13] a) Z. Zhang, Z. Wang, J. Org. Chem. 2006, 71, 7485–7487; b)
M. I. Hall, S. J. Pridmore, J. M. J. Williams, Adv. Synth. Catal.
2008, 350, 1975–1978.
Received: March 13, 2009
Published Online: May 11, 2009
2946
www.eurjoc.org
© 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2009, 2943–2946