Aerobic oxidative transformation of primary azides to nitriles by ruthenium hydroxide catalyst

Article abstract of DOI:10.1021/jo2004956

In the presence of an easily prepared supported ruthenium hydroxide catalyst, Ru(OH)_x/Al₂O₃, various kinds of structurally diverse primary azides including benzylic, allylic, and aliphatic ones could be converted into the corresponding nitriles in moderate to high yields (13 examples, 65-94% yields). The gram-scale (1 g) transformation of benzyl azide efficiently proceeded to give benzonitrile (0.7 g, 90% yield) without any decrease in the performance in comparison with the small-scale (0.5 mmol) transformation. The catalysis was truly heterogeneous, and the retrieved catalyst could be reused for the transformation of benzyl azide without an appreciable loss of its high performance. The present transformation of primary azides to nitriles likely proceeds via sequential reactions of imide formation, followed by dehydrogenation (β-elimination) to produce the corresponding nitriles. The Ru(OH)_x/Al₂O₃ catalyst could be further employed for synthesis of amides in water through the transformation of primary azides (benzylic and aliphatic ones) to nitriles, followed by sequent hydration of the nitriles formed. Additionally, direct one-pot synthesis from alkyl halides and TBAN₃ (TBA = tetra-n-butylammonium) could be realized with Ru(OH)_x/Al₂O₃, giving the corresponding nitriles in moderate to high yields (10 examples, 64-84% yields).

Full text of DOI:10.1021/jo2004956

ARTICLE
pubs.acs.org/joc
Aerobic Oxidative Transformation of Primary Azides to Nitriles by
Ruthenium Hydroxide Catalyst
Jinling He, Kazuya Yamaguchi, and Noritaka Mizuno*
Department of Applied Chemistry, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
S Supporting Information
b
ABSTRACT: In the presence of an easily prepared supported ruthenium hydroxide
catalyst, Ru(OH)x/Al2O3, various kinds of structurally diverse primary azides including
benzylic, allylic, and aliphatic ones could be converted into the corresponding nitriles
in moderate to high yields (13 examples, 65ꢀ94% yields). The gram-scale (1 g)
transformation of benzyl azide efficiently proceeded to give benzonitrile (0.7 g, 90%
yield) without any decrease in the performance in comparison with the small-scale (0.5 mmol) transformation. The catalysis was
truly heterogeneous, and the retrieved catalyst could be reused for the transformation of benzyl azide without an appreciable loss of
its high performance. The present transformation of primary azides to nitriles likely proceeds via sequential reactions of imide
formation, followed by dehydrogenation (β-elimination) to produce the corresponding nitriles. The Ru(OH)x/Al2O3 catalyst could
be further employed for synthesis of amides in water through the transformation of primary azides (benzylic and aliphatic ones) to
nitriles, followed by sequent hydration of the nitriles formed. Additionally, direct one-pot synthesis from alkyl halides and TBAN3
(TBA = tetra-n-butylammonium) could be realized with Ru(OH)x/Al2O3, giving the corresponding nitriles in moderate to high
yields (10 examples, 64ꢀ84% yields).
’ INTRODUCTION
acceptors or strong oxidants, e.g., bromine trifluoride (BrF3),6a
phenyliodonium diacetate,6b 2,3-dichloro-5,6-dicyanobenzoqui-
none,6c,d Pd metal/alkynes,6e and CuI/tert-butyl hydroperoxide.6f
As far as we know, catalytic oxidative transformation of primary
azides to nitriles with O2 (or air) as a sole oxidant has never been
reported so far. If heterogeneously catalyzed transformation with O2
(or air) could be realized, it would become one of the greenest pro-
cedures because (i) only N2 and H2O are formed as byproducts
[eq 1], (ii) use of toxic metal cyanide reagents can be avoided, and
(iii) catalyst/product(s) separation and reuse of catalyst are very easy.
Nitriles have been recognized as very efficient and useful
synthons for preparation of amines, amides, carbonyl compounds,
and heterocycles.1 Classically, nitriles have been synthesized by
SN2 displacementofalkyl halideswith inorganic cyanides(for alkyl
nitriles), Sandmeyer reaction (for benzonitrile derivatives), Wittig
reaction (for unsaturated nitriles), and gas-phase ammoxidation
(for industrial production of acrylonitrile and benzonitrile).
Although these procedures are very useful, developments of novel
environmentally friendly procedures for synthesis of nitriles are
highly desirable. Recently, several efficient catalytic procedures,
e.g., dehydration of aldoximes or amides2 and oxidative transfor-
mation of alcohols or aldehydes (or halides) with NH3 (or its
surrogates such as urea and ammonium salts),3 have been reported.
Azides are one of the most attractive functional groups in
organic synthesis because of the dipolar character (reactivity)
and can easily be introduced into organic substances by many
convenient methods, e.g., SN2 displacement of alkyl halides with
NaN3, even in the presence of the other functional groups.4 In
addition, azides are stable toward moisture and air. Although
azides have been recognized as efficient and useful synthons for
organic synthesis, surprisingly little is known of their authorized
application as synthons at present except for Staudinger reduc-
tion, Schmidt reaction, Curtius rearrangement, decomposition to
carbonyl compounds, and click reaction to triazoles.1e,4b,5
Oxidative transformation of primary azides to nitriles is an
alternative attractive approach to synthesis of nitriles without
elongation of the skeletal carbon chains. With regard to the
transformation, several examples have been reported to date (see
Table S1 in the Supporting Information).6 Reported procedures
requirereactive stoichiometric oxidants, or catalysts withhydrogen
Recently, we have developed efficient heterogeneous catalysts
for functional group transformations including oxidative dehy-
drogenation, oxygenation, hydrogen transfer reactions, and
hydration.7 Our strategy to design efficient heterogeneous
catalysts is creation of highly (monomerically) dispersed metal
hydroxide species on appropriate supports (especially ruthenium
hydroxide species).7 Herein, we report that novel transformation
of aerobic oxidative synthesis of nitriles from primary azides (or
alkyl halides and TBAN3 (TBA = tetra-n-butylammonium))
could be realized with an easily prepared supported ruthenium
hydroxide catalyst, Ru(OH)x/Al2O3.
’ RESULTS AND DISCUSSION
Initially, transformations of benzyl azide (1a) to benzonitrile
(2a) were carried out with various catalysts under different
conditions (Scheme 1 and Table S2). When the transformation
Received: March 10, 2011
Published: April 20, 2011
r
2011 American Chemical Society
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Scheme 1. Ru(OH)x/Al2O3-Catalyzed Transformation of 1a
to 2aa
a Reaction conditions: 1a (0.5 mmol), catalyst (metal, 4 mol %), solvent
(2 mL), 80°C, 5 h. Yields are based on 1a and were determined by GC.
Scheme 2. Possible Reaction Mechanism for the Ru(OH)x/
Al2O3-Catalyzed Transformation of Primary Azides to
Nitriles
Figure 1. Verification of heterogeneous catalysis for transformation of
1a to 2a. The reaction was carried out under the conditions described in
Scheme 1. The arrow indicates the removal of Ru(OH)x/Al2O3 by hot
filtration.
(3a, 50%) was formed as a byproduct. Under Ar atmosphere,
there are several paths for the regeneration of the Ru-OH species:
(i) hydrolytic decomposition of the imide intermediate, (ii)
hydrogenation of an imine, and (iii) hydrogenation of a nitrile
(Scheme S1). Therefore, the amount of a nitrile can exceed that
of the ruthenium catalyst used. However, under Ar atmosphere,
the selectivity to the desired nitrile was low because of side
reactions (ii) and (iii). In contrast, under aerobic conditions, the
reaction of the Ru-H species with O2 easily takes place.9 Thus,
the corresponding alkylimines were hardly detected and the
selectivity to the desired nitrile was high under aerobic conditions
(Scheme 1).
Various kinds of supported metal hydroxide catalysts and
ruthenium-based catalysts were applied to the transformation of
1a to 2a (Table S2). Under the present conditions, no reaction
proceeded in the absence of the catalyst or in the presence of just
of 1a was carried out with Ru(OH)x/Al2O3 (4 mol % with respect
to 1a) in toluene at 80 °C under an air atmosphere, 85% yield of 2a
was obtained for 5 h.8 In this case, a small amount of benzaldehyde
(4a) was formed as a byproduct (3%). It was confirmed by mass
analysis of the gas phase that H2 gas was not formed and N2 gas
was formed during transformation of 1a to 2a. Reaction rates were
almost independent of partial pressures of O2 (0.2ꢀ1 atm).
The ruthenium hydroxide (Ru-OH) species possess both
Lewis acid and Brønsted base sites on the same metal sites.7
Therefore, the Ru(OH)x/Al2O3-catalyzed transformation of
primary azides to nitriles possibly proceeds via the concerted
activation of primary azides by the Lewis acid and Brønsted base
sites to form imide intermediates. Then, β-elimination takes
place to produce the corresponding nitriles with formation of the
hydride (Ru-H) species.7b The Ru-OH species is easily regener-
ated by reaction of the Ru-H species with O2 (even air),9 and the
catalytic cycle would be completed (Scheme 2).
Al2O3 or the catalyst precursor RuCl3 nH2O. Among various
3
supported metal hydroxide catalysts examined (for example, Ru,
Au, Ag, Cu, Pd, Rh, and Ir), only Ru(OH)x/Al2O3 showed the
high catalytic performance. Commonly utilized ruthenium com-
plexes such as Ru(acac)3 (acac = acetylacetonato), RuCl2-
(PPh3)3, Ru3(CO)12, and RuCl2(bpy)3 6H2O (bpy =2,20-
3
bipyridyl) were not effective. Other ruthenium-based heteroge-
neous catalysts such as Ru/C (Ru metal supported on activated
carbon), Ru-hydroxyapatite (Ru3þ-exchanged hydroxyapatite),10
and RuO2 anhydrous (bulk oxide) did not show high catalytic
performance. The catalytic activity of Ru(OH)x/Al2O3 was much
higher than those of Ru(OH)x (unsupported bulk hydroxide) and
a simple physical mixture of Ru(OH)x and Al2O3. Therefore, the
highly dispersed ruthenium hydroxide species would play an
important role for the present transformation.
In order to show practical usefulness of the present procedure
in organic synthesis, the gram-scale transformation of 1a (1 g, 15-
fold scale-up) was carried out. The transformation efficiently
proceeded to give 0.70 g of 2a (90% yield) without any decrease
in the performance in comparison with the small-scale transfor-
mation in Scheme 1 [eq 2].
To verify whether the observed catalysis is derived from solid
Ru(OH)x/Al2O3 or leached ruthenium species, the transforma-
tion of 1a to 2a was carried out under the conditions described in
Scheme 1, and Ru(OH)x/Al2O3 was removed from the reaction
mixture by hot filtration at ca. 50% conversion of 1a. Then, the
reaction was again carried out with the filtrate under the same
conditions. In this case, no further production of 2a was observed
(Figure 1). In addition, it was confirmed by inductively coupled
plasma atomic emission spectroscopy analysis that no ruthenium
was detected in the filtrate (below 0.03%). All of these experimental
When the transformation of 1a was carried out under Ar
atmosphere, a significant amount of N-benzylidenebenzylamine
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Scheme 3. Scope of the Ru(OH)x/Al2O3-Catalyzed Trans-
formation of Primary Azides to Nitrilesb
Scheme 5. Scope of the Ru(OH)x/Al2O3-Catalyzed One-Pot
Synthesis of Nitrilesb
a Ru(OH)x/Al2O3 (8 mol %). b Reaction conditions: substrate (0.5
mmol), TBAN3 (0.55 mmol), Ru(OH)x/Al2O3 (6 mol %), acetonitrile
(2 mL), air (1 atm), 80°C. Yields are based on alkyl halides and were
determined by GC.
a Ru(OH)x/Al2O3 (8 mol %). b Reaction conditions: substrate (0.5
mmol), Ru(OH)x/Al2O3 (4 mol %), toluene (2 mL), air (1 atm), 80°C.
Yields are based on azides and were determined by GC.
(5l) in 87% and 63% yields, respectively (with the formation of
aldehydes as main byproducts (∼10%)) (Scheme 4).12 The
reaction profiles for the transformation of 1a in water showed
that 2a was initially formed, followed by the formation of 5a. In
addition, it was confirmed in a separate experiment that the
hydration of 2a to 5a efficiently proceeded in the presence of
Ru(OH)x/Al2O3 under the similar conditions.7d,13 Therefore,
the transformation of primary azides to primary amides in water
proceeds by sequential reactions, namely, the oxidative transfor-
mation of primary azides to nitriles, followed by the hydration to
afford the corresponding primary amides.
Scheme 4. Scope of the Ru(OH)x/Al2O3-Catalyzed Trans-
formation of Primary Azides to Amidesa
Additionally, direct one-pot synthesis of nitriles from alkyl
halides and TBAN3 could be realized with Ru(OH)x/Al2O3
(Scheme 5). The present one-pot procedure can completely
avoid isolation of primary azides (explosive in some cases), which
is very important advantage in comparison with the step-by-step
synthesis.
a Reaction conditions: substrate (0.5 mmol), Ru(OH)x/Al2O3 (5 mol
%), water (3 mL), air (3 atm), 130°C, 24 h. Yields are based on azides
and were determined by GC.
results can rule out any contribution to the observed catalysis from
ruthenium species that leached into the reaction solution, and the
observed catalysis is intrinsically heterogeneous.11
’ CONCLUSION
Next, scope of the present Ru(OH)x/Al2O3-catalyzed system
with regard to various kinds of structurally diverse primary azides
was examined (Scheme 3). Transformations of benzylic azides
1aꢀ1i, which contain electron-donating as well as electron-
withdrawing substituents, efficiently proceeded to afford the
corresponding aromatic nitriles in moderate to high yields. Reac-
tion rates for benzylic azides with electron-donating substituents
were larger than those with electron-withdrawing ones, suggesting
the electrophilic nature of the present Ru(OH)x/Al2O3-catalyzed
transformation. Reactive functional groups such as chloro and
nitro groups intrinsically remained intact; no dechlorination and
reduction of the nitro group proceeded. Also, 3-(azidemethyl)-
pyridine 1j was converted into the corresponding nitrile. In the
transformation of an allylic azide 1k, the corresponding unsatu-
rated nitrile could be obtained without isomerization, hydrogena-
tion, and hydration of the double bond. Aliphatic nitriles could
efficiently synthesized in the present system using azides as
substrates. After the reaction was completed, Ru(OH)x/Al2O3
could easily be retrieved from the reaction mixture by simple
filtration. The retrieved catalyst could be reused for the trans-
formation of 1a to 2a without an appreciable loss of the catalytic
performance; 2a was obtained in 80% and 81% yields for the
first and the second reuse experiments, respectively, under the
conditions described in Scheme 3.
In summary, novel transformation of aerobic oxidative synth-
esis of nitriles from primary azides (or alkyl halides and TBAN3)
could be realized for the first time with Ru(OH)x/Al2O3. The
catalysis was truly heterogeneous, and the retrieved catalyst could
be reused. The results demonstrated herein will become a good
candidate for green nitrile synthesis, which can completely avoid
use of harsh reaction conditions and conventional hazardous
stoichiometric reagents such as inorganic cyanides.
’ EXPERIMENTAL SECTION
General. GC analyses were performed with a FID detector equipped
with a capillary column. Mass spectra were recorded at an ionization
voltage of 70 eV. 1H and 13C NMR spectra were measured at 270 and
67.8 MHz, respectively, with TMS as an internal standard. Alkyl halides,
benzyl azide (1a), nitriles, amides, and solvents were commercially
available and purified prior to the use.14 Ru hydroxyapatite (Ru 9.1 wt %)
and Ru/C (5.0 wt %) were also commercially available. Organic azides
(1b,15a 1c,15b 1d,15c,d 1e,15e 1f,15f 1g,15g 1h,15e 1i,15f 1j,15h 1k,15i 1l,15c,d
and 1m15i) were prepared by the nucleophilic substitution of the
corresponding alkyl halides with NaN3.
Preparation of Catalysts. Supported ruthenium hydroxide cata-
lyst, Ru(OH)x/Al2O3, was prepared as follows.7 Al2O3 powder (2.0 g)
pretreated at 550 °C for 3 h was vigorously stirred with 60 mL of an
aqueous solution of RuCl3 (8.3 mM) at room temperature (ca. 20 °C).
After 15 min, the pH of the solution was adjusted to 13.2 by addition of
aqueous solution of NaOH (1 M), and the resulting slurry was stirred for
24 h. The solid was then filtered off, washed with a large amount of
When the transformation of primary azides was carried out in
water, the corresponding primary amides were obtained as major
products. For example, transformations of 1a (benzylic azide)
and 1l (aliphatic azide) gave benzamide (5a) and n-octanamide
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ARTICLE
deionized H2O, and dried in vacuo to afford Ru(OH)x/Al2O3. The
contents of ruthenium were 2.1ꢀ2.2 wt %. Other metal hydroxide
catalysts were prepared in the similar way.7
Grants-in-Aid for Scientific Researches from Ministry of Educa-
tion, Culture, Sports, Science and Technology.
Transformation of 1a to 2a. Into a Pyrex-glass screw cap vial
were successively placed Ru(OH)x/Al2O3 (96 mg, Ru 4 mol %), 1a
(66.6 mg, 0.5 mmol), and toluene (2 mL) (Figure S1). A Teflon-coated
magnetic stir bar was added, and the reaction mixture was vigorously
stirred (800 rpm) at 80 °C for 5 h in 1 atm of air. After the reaction was
completed, the Ru(OH)x/Al2O3 catalyst was removed by filtration.
Then, the filtrate was analyzed by GC and GCꢀMS (conversion of 1a,
99%; yield of 2a, 85%; yield of 4a, 3%). The product (2a) was isolated by
silica gel column chromatography (initial, n-hexane; after toluene was
eluted, ethyl acetate) (42.8 mg, 83% isolated yield).
Gram-Scale Transformation of 1a to 2a. Into a Pyrex-glass
screw cap vial were successively placed Ru(OH)x/Al2O3 (1.4 g, Ru 4
mol %), 1a (1.0 g, 7.5 mmol), and toluene (30 mL). A Teflon-coated
magnetic stir bar was added, and the reaction mixture was vigorously
stirred (800 rpm) at 80 °C for 5 h in 1 atm of air. After the reaction was
completed, the Ru(OH)x/Al2O3 catalyst was removed by filtration.
Then, the filtrate was analyzed by GC and GCꢀMS (conversion of 1a,
>99%; yield of 2a, 92%; yield of 4a, 2%). The product (2a) was isolated
by silica gel column chromatography (initial, n-hexane; after toluene was
eluted, ethyl acetate) (0.70 g, 90% isolated yield).
Transformation of 1a to 5a. 1a (66.6 mg, 0.5 mmol), Ru(OH)x/
Al2O3 (120 mg, Ru 5 mol %), and water (3 mL) were placed in a Teflon
vessel with a magnetic stir bar. The Teflon vessel was attached inside an
autoclave, and the reaction mixture was vigorously stirred (800 rpm) at
130 °C (bath temperature) for 24 h in 3 atm of air. After the reaction was
completed, the Ru(OH)x/Al2O3 catalyst was removed by filtration. The
filtrate was diluted with ethanol (10 mL) and then analyzed by GC and
GCꢀMS (conversion of 1a, >99%; yield of 5a, 87%; yield of 2a, 1%;
yield of 4a, 9%).
Transformation of 6a to 2a. Into a Pyrex-glass screw cap vial
were successively placed Ru(OH)x/Al2O3 (144 mg, Ru 6 mol %), 6a
(63.0 mg, 0.5 mmol), TBAN3 (156 mg, 0.55 mmol), and toluene
(2 mL). A Teflon-coated magnetic stir bar was added, and the reaction
mixture was vigorously stirred (800 rpm) at 80 °C for 10 h in 1 atm of air.
After the reaction was completed, the Ru(OH)x/Al2O3 catalyst and the
TBA halide formed were removed by filtration. Then, the filtrate was
analyzed by GC and GCꢀMS (conversion of 6a, >99%; yield of 2a, 83%;
yield of 1a, 8%; yield of 4a, 4%).
’ REFERENCES
(1) (a) Fatiadi, A. J. In Preparation and Synthetic Applications of
Cyano Compounds; Patai, S., Rappaport, S. Z., Eds.; Wiley: New York,
1983. (b) Larock, R. C. Comprehensive Organic Transformations; VCH:
New York, 1989. (c) Miller, J. S.; Manson, J. L. Acc. Chem. Res. 2001,
34, 563–570. (d) Magnus, P.; Scott, D. A.; Fielding, M. R. Tetrahedron
Lett. 2001, 42, 4127–4129.(e) Smith, M. B.; March, J. March’s Advanced
Organic Chemistry: Reactions, Mechanisms, and Structure, 6th ed.; John
Wiley & Sons: Hoboken, 2007.
(2) (a) Ishihara, K.; Furuya, Y.; Yamamoto, H. Angew. Chem., Int. Ed.
2002, 41, 2983–2986. (b) Yan, P.; Batamack, P.; Prakash, G. K. S.; Olah,
G. A. Catal. Lett. 2005, 101, 141–143. (c) Yang, S. H.; Chang, S. Org.
Lett. 2001, 3, 4209–4211. (d) Choi, E.; Lee, C.; Na, Y.; Chang, S. Org.
Lett. 2002, 4, 2369–2371. (e) Yamaguchi, K.; Fujiwara, H.; Ogasawara,
Y.; Kotani, M.; Mizuno, N. Angew. Chem., Int. Ed. 2007, 46, 3922–3925.
(3) (a) Oishi, T.; Yamaguchi, K.; Mizuno, N. Angew. Chem., Int. Ed.
2009, 48, 6286–6288. (b) Yamaguchi, K.; He, J. L.; Oishi, T.; Mizuno, N.
Chem.—Eur. J. 2010, 16, 7199–7207. (c) Iida, S.; Ohmura, R.; Togo, H.
Tetrahedron 2009, 65, 6257–6262. (d) Iida, S.; Togo, H. Synlett 2008,
11, 1639–1642.
(4) (a) Biffin, M. E. C.; Miller, J.; Paul, D. B. In The Chemistry of the
Azide Group; Patai, S., Ed.; Interscience: New York, 1971; pp 57ꢀ190.
(b) Organic Azides: Syntheses and Applications; Br€ase, S., Banert, K., Eds.;
John Wiley & Sons: Chichester, 2009.
(5) (a) Sheradsky, T. In The Chemistry of the Azide Group; Patai, S.,
Ed.; Interscience: New York, 1971; pp 331ꢀ395. (b) Rostovtsev, V. V.;
Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem., Int. Ed. 2002,
41, 2596–2599. (c) Tornøe, C. W.; Christensen, C.; Meldal, M. J. Org.
Chem. 2002, 67, 3057–3064. (d) Maddani, M.; Prabhu, K. R. Tetra-
hedron Lett. 2008, 49, 4526–4530. (e) Bartoli, G.; Antonio, G. D.;
Giovannini, R.; Giuli, S.; Lanari, S.; Paoletti, M.; Marcantoni, E. J. Org.
Chem. 2008, 73, 1919–1924. (f) Becer, C. R.; Hoogenboom, R.;
Schubert, U. S. Angew. Chem., Int. Ed. 2009, 48, 4900–4908. (g) Jung,
Y. J.; Chang, Y. M.; Lee, J. H.; Yoon, C. M. Tetrahedron Lett. 2002,
43, 8735–8739. (h) Koutsuki, H.; Ohishi, T.; Araki, T. Tetrahedron Lett.
1997, 38, 2129–2132 and references therein.
(6) (a) Sasson, R.; Rozen, S. Org. Lett. 2005, 7, 2177–2179. (b) Zhou,
W.; Zhang, L.; Jiao, N. Angew. Chem., Int. Ed. 2009, 48, 7094–7097. (c)
Qin, C.; Jiao, N. J. Am. Chem. Soc. 2010, 132, 15893–15895. (d) Zhou, W.;
Xu, J.; Zhang, L.; Jiao, N. Org. Lett. 2010, 12, 2888–2891. (e) Hayashi, H.;
Ohno, A.; Oka, S. Bull. Chem. Soc. Jpn. 1976, 49, 506–509. (f) Lamani, M.;
Prabhu, K. R. Angew. Chem., Int. Ed. 2010, 49, 6622–6625.
(7) (a) Yamaguchi, K.; Mizuno, N. Angew. Chem., Int. Ed. 2002,
41, 4538–4542. (b) Yamaguchi, K.; Mizuno, N. Angew. Chem., Int. Ed.
2003, 42, 1480–1483. (c) Yamaguchi, K.; Mizuno, N. Chem.—Eur. J.
2003, 9, 4353–4361. (d) Yamaguchi, K.; Matsushita, M.; Mizuno, N.
Angew. Chem., Int. Ed. 2004, 43, 1576–1580. (e) Kim, J. W.; Yamaguchi,
K.; Mizuno, N. Angew. Chem., Int. Ed. 2008, 47, 9249–9251. (f)
Yamaguchi, K.; Koike, T.; Kim, J. W.; Ogasawara, Y.; Mizuno, N.
Chem.—Eur. J. 2008, 14, 11480–11487.
(8) Transformations of 1a in non- and low-polar solvents such as
toluene, acetonitrile, and 1,4-dioxane efficiently proceeded to give 2a in
high yields. On the other hand, transformations in highly polar solvents
such as dimethyl sulfoxide and N,N-dimethylformamide gave moderate
yields of 2a (Table S2).
Catalyst Reuse. After the reaction was completed, the spent
Ru(OH)x/Al2O3 catalyst was retrieved by filtration, washed with
acetone, aqueous solution of NaOH (0.01 M), and deionized H2O,
and then dried in vacuo prior to being recycled.
’ ASSOCIATED CONTENT
S
Supporting Information. Full experimental details, Tables
b
S1 and S2, Figure S1, and Scheme S1. This material is available free
of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
*Phone: þ81-3-5841-7272. Fax: þ81-3-5841-7220. E-mail:
(9) Nikaidou, F.; Ushiyama, H.; Yamaguchi, K.; Yamashita, K.;
Mizuno, N. J. Phys. Chem. C 2010, 114, 10873–10880.
tmizuno@mail.ecc.u-tokyo.ac.jp.
(10) Yamaguchi, K.; Mori, K.; Mizugaki, T.; Ebitani, K.; Kaneda, K.
J. Am. Chem. Soc. 2000, 122, 7144–7145.
(11) Sheldon, R. A.; Wallau, M.; Arends, I. W. C. E.; Schuchardt, U.
Acc. Chem. Res. 1998, 31, 485–493.
(12) When the transformation of 1a in water was carried out in 1 atm
of air, 5a was obtained in 65% yield with the formation of a large amount
of 4a (30%) likely due to hydrolytic decomposition of the imide
’ ACKNOWLEDGMENT
This work was supported in part by the Global COE Program
(Chemistry Innovation through Cooperation of Science and
Engineering), Japan Chemical Innovation Institute (JCII), and
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intermediate (Scheme S1). The formation of 4a could be suppressed by
increasing the pressure of air. For example, 5a was obtained in 87% yield
with the formation of 4a (9%) in 3 atm of air (Scheme 4).
(13) In the presence of Ru(OH)x/Al2O3 (4 mol%), the hydration of
2a (1 mmol) in water (3 mL) at 140 °C (bath temperature) efficiently
proceeded to afford 5a in 99% yield for 6 h.
(14) Purification of Laboratory Chemicals, 3rd ed.; Perrin, D. D.;,
Armarego, W. L. F., Eds.; Pergamon Press: Oxford, U.K., 1988.
(15) (a) Sirion, U.; Kim, H. J.; Lee, J. H.; Seo, J. W.; Lee, B. S.; Lee,
S. J.; Oh, S. J.; Chi, D. Y. Tetrahedron Lett. 2007, 48, 3953–3957. (b)
Mayer, T.; Maier, M. E. Eur. J. Org. Chem. 2007, 4711–4720. (c) Kamata,
K.; Nakagawa, Y.; Yamaguchi, K.; Mizuno, N. J. Am. Chem. Soc. 2008,
130, 15304–15310. (d) Yamaguchi, K.; Oishi, T.; Katayama, T.; Mizuno,
N. Chem.—Eur. J. 2009, 15, 10464–10472. (e) Wang, X.-L.; Wan, K.;
Zhou, C.-H. Eur. J. Med. Chem. 2010, 45, 4631–4639. (f) Lee, L. V.;
Mitchell, M. L.; Huang, S.-J.; Fokin, V. V.; Sharpless, K. B.; Wong, C.-H.
J. Am. Chem. Soc. 2003, 125, 9588–9589. (g) Asano, K.; Matsubara, S.
Org. Lett. 2010, 12, 4988–4991. (h) Dou, D.; He, G.; Li, Y.; Lai, Z.; Wei,
L.; Alliston, K. R.; Lushington, G. H.; Eichhorn, D. M.; Groutas, W. C.
Bioorg. Med. Chem. 2010, 18, 1093–1102. (i) Campbell-Verduyn, L. S.;
Mirfeizi, L.; Dierckx, R. A.; Elsinga, P. H.; Feringa, B. L. Chem. Commun.
2009, 2139–2141. (j) Pardin, C.; Roy, I.; Lubell, W. D.; Killor, J. W.
Chem. Biol. Drug Des. 2008, 72, 189–196.
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