Dehydrogenative oxidation of alcohols in aqueous media using water-soluble and reusable Cp*Ir catalysts bearing a functional bipyridine ligand

Article abstract of DOI:10.1021/ja210857z

A new catalytic system for the dehydrogenative oxidation of alcohols using a water-soluble Cp*Ir complex bearing a bipyridine-based functional ligand as catalyst has been developed. With this catalytic system, a variety of primary and secondary alcohols have been efficiently converted to aldehydes and ketones, respectively, in aqueous media without using any oxidant. Reuse of the catalyst by a very simple procedure has been also accomplished.

Full text of DOI:10.1021/ja210857z

Communication
pubs.acs.org/JACS
Dehydrogenative Oxidation of Alcohols in Aqueous Media Using
Water-Soluble and Reusable Cp*Ir Catalysts Bearing a Functional
Bipyridine Ligand
Ryoko Kawahara,† Ken-ichi Fujita,*,†,‡ and Ryohei Yamaguchi*,†
‡
†Graduate School of Human and Environmental Studies, Graduate School of Global Environmental Studies, Kyoto University,
Sakyo-ku Kyoto 606-8501, Japan
S
* Supporting Information
First, we planned to synthesize a new catalyst suitable for the
ABSTRACT: A new catalytic system for the dehydrogen-
ative oxidation of alcohols using a water-soluble Cp*Ir
complex bearing a bipyridine-based functional ligand as
catalyst has been developed. With this catalytic system, a
variety of primary and secondary alcohols have been
efficiently converted to aldehydes and ketones, respec-
tively, in aqueous media without using any oxidant. Reuse
of the catalyst by a very simple procedure has been also
accomplished.
dehydrogenative oxidation of alcohols in aqueous media with
respect to stability, solubility in water, and catalytic efficiency.
We have previously reported the dehydrogenative oxidation of
alcohols under reflux in toluene catalyzed by a Cp*Ir complex
bearing 2-hydroxypyridine as a functional ligand, in which
″ligand-promoted dehydrogenation″ were the most crucial step in
the reaction pathway.6b On the basis of this concept, we designed
a bipyridine-based functional ligand, such as 6-hydroxy-2,2′-
bipyridine (1a) or 6,6′-dihydroxy-2,2′-bipyridine (1b) that should
lead to stable catalysts ligated by N,N-chelation. As a Cp*Ir
precursor, water-soluble aqua complex, [Cp*Ir(H2O)3](OTf)2,
was employed. Thus, treatment of [Cp*Ir(H2O)3](OTf)2 with 1a
and 1b in water at room temperature gave new dicationic Cp*Ir
complexes 2a and 2b in 98 and 93% yields, respectively (eq 1).
he increasing environmental concerns have led chemists to
T
develop cleaner and greener reactions for chemical trans-
formations. It is one of the central subjects in synthetic organic
chemistry to develop efficient, selective, and atom-economical
reactions which can be performed under safe and mild conditions
with the aid of transition metal catalysts.
The oxidation of alcohols to aldehydes and ketones is
fundamental transformation in organic chemistry and has
profound importance in laboratory and industrial chemistry.
Various transition metal catalyzed systems for the oxidation of
alcohols have been developed using environmentally acceptable
oxidants such as molecular oxygen,1 hydrogen peroxide,2 or
acetone.3 Dehydrogenative oxidation accompanied by the release
of hydrogen gas without using any oxidant must be superior from
the viewpoint of atom economy.4 To date, several homogeneous
catalytic systems for the dehydrogenative oxidation of alcohols
using ruthenium,5 iridium,6,7 and other transition metal catalysts5f
have been reported.8,9 However, all of these catalytic reactions
have to be carried out under reflux in organic solvent such as
toluene. From the standpoint of green chemistry, it must be very
important to develop a new catalytic system which can be
performed in a greener solvent such as water.10
Recently, we have reported the synthesis of a water-soluble
Cp*Ir−ammine complex, [Cp*Ir(NH3)3]2+, and its high catalytic
activity for the N-alkylation of ammonia and organic amines in
aqueous media.11 On the basis of this discovery, we became
interested in the design of new water-soluble catalysts and their
application to efficient, and atom-economical reactions under
environmentally benign conditions. Herein, we report the
synthesis of new water-soluble Cp*Ir complexes bearing a
bipyridine-based functional ligand and their high catalytic
performance for the dehydrogenative oxidation of primary and
secondary alcohols in aqueous media. In addition, reuse of the
catalyst by a very simple procedure is also demonstrated.
The structures of 2a and 2b were elucidated by their
spectroscopic data and single-crystal X-ray analysis (see the
Supporting Information). The complexes 2a and 2b were
highly soluble in water and stable in air for months. Analogous
complexes 3 and 4 having PF6 and BF4 as counteranions
were prepared by the reaction of 1b with [Cp*Ir(H2O)3](PF6)2
and [Cp*Ir(H2O)3](BF4)2, respectively (eq 1). In order to
evaluate the catalytic activities of the complexes 2-4, the
complexes 5 and 6 having 2,2′-bipyridine and 4,4′-dihydroxy-
2,2′-bipyridine as a ligand were prepared, respectively,
according to the literature methods.12
−
−
Received: November 18, 2011
Published: February 16, 2012
© 2012 American Chemical Society
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With these water-soluble Cp*Ir complexes in hand, we next
examined the dehydrogenative oxidation of benzyl alcohol (7a)
to benzaldehyde (8a) in the presence of a catalytic amount
(0.5−1.5 mol % Ir) of the Cp*Ir complexes in water under
reflux. The results are summarized in Table 1. The oxidation of
To explore the scope of the present catalytic system, reactions
of various alcohols were conducted under the optimized condi-
tions. Results of the dehydrogenative oxidation of primary alcohols
to the corresponding aldehydes in water are shown in Table 2.14
The reactions of benzylic alcohols (7a−i) bearing electron-donating
Table 1. Dehydrogenative Oxidation of Benzyl Alcohol (7a)
Table 2. Dehydrogenative Oxidation of Primary Alcohols to
Aldehydes in Water
a
to Benzaldehyde (8a) Catalyzed by Cp*Ir Complexes under
a
Various Conditions
a
Reaction was carried out with a primary alcohol (0.25 mmol) and 2b
b
(1.5−3.0 mol %) in water (5 mL) under reflux for 20 h. Determined
by GC.
a
and -withdrawing substituents at the aromatic ring proceeded
smoothly to give the corresponding aldehydes in good to high
yields (entries 1−9). Methoxy-, chloro-, bromo-, trifluoromethyl-,
and methoxycarbonyl-substituents were tolerant (entries 2 and
6−9). The reaction of sterically demanding 2-methylbenzyl alcohol
also proceeded to give the corresponding aldehyde in high yield
(entry 3).15
Reaction was carried out with 7a (0.25 mmol) and Cp*Ir catalyst (0.5−
b
1.5 mol % Ir) in water (5 mL) under reflux for 20 h. Conversion of 7a
determined by GC. Yield of 8a determined by GC. Reaction was
carried out with 7a (0.50 mmol) in water (10 mL). Yield of the
evolved hydrogen gas was 89%. Reaction was carried out under air.
c
d
e
f
7a never occurred in the absence of catalyst (entry 1). Water-
insoluble [Cp*IrCl2]2 (0.5 mol % Ir) showed almost no
catalytic activity (entry 2). While the water-soluble aqua
complex [Cp*Ir(H2O)3](OTf)2 showed low catalytic activity to
give benzaldehyde (8a) in 12% yield (entry 3), employment of
the complex 2a bearing the α-monohydroxyl ligand 1a as a
catalyst improved the yield up to 50% (entry 4). The dicationic
complex 2b with the α,α′-dihydroxyl ligand 1b showed higher
activity than 2a (entry 5, 62% yield). Analogous complexes 3
and 4 having PF6 and BF4 as counteranions showed lower
catalytic activity than 2b (entries 6 and 7). Other Cp*Ir
complexes 5 and 6 were apparently inferior as the catalyst
(entries 8 and 9, 25% and 22% yields, respectively), indicating
the α-hydroxyl substituent in the ligand was indispensable for
high catalytic performance.
We next investigated the dehydrogenative oxidation of
secondary alcohols to ketones in water. As shown in Table 3,14
Table 3. Dehydrogenative Oxidation of Secondary Alcohols
a
to Ketones in Water
−
−
The excellent yield was achieved with a slightly larger
amount of 2b (1.5 mol % Ir): 8a was obtained in 92% yield
with complete selectivity (entry 10). Evolution of the hydrogen
gas was confirmed by the analysis of the gas phase using a
hydrogen sensor. Additionally, quantitative analysis was also
carried out: the volume of the evolved hydrogen gas was
measured using a gas buret, showing the yield of hydrogen was
89% (entry 11).13 When the reaction time was reduced to 6 h,
the yield of 8a was moderate (entry 12). It should be noted that
the reaction under air gave a similar result to that of the
reaction under an argon atmosphere (entry 13), showing the
operational advantage of this system because the reaction can
be performed under air. Thus, the present catalytic system
produces the aldehyde 8a in high yield with almost complete
selectivity using harmless water as a solvent without the
formation of any harmful byproducts.
a
Reaction was carried out with a secondary alcohol (0.25 mmol) and
2b (0.02−3.0 mol %) in water (5 mL) under reflux for 20 h.
b
Determined by GC (entries 1, 8−11) or 1H NMR (entries 2−7).
c
Reaction was carried out with 9b (2.5 mmol) and 2b (0.02 mol %) in
d
e
water (50 mL) under reflux for 100 h. Turnover number. Water
(4.5 mL) and tert-butyl alcohol (0.5 mL) were used as a cosolvent.
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the reactions of 1-arylethanols (9a−f) bearing electron-donating
and -withdrawing substituents at the aromatic ring proceeded
smoothly to give the corresponding acetophenone derivatives in
good to excellent yields (entries 1−7). The highest turnover
number (2550) was accomplished when the reaction of 9b was
carried out under reflux in water for 100 h with a very small
catalyst loading (0.02 mol %) (entry 3). Reactions of both
sterically hindered and unhindered substrates proceeded well
(entries 2 and 4). Aliphatic secondary alcohols were also oxidized
successfully, although an addition of a small amount of tert-butyl
alcohol (0.5 mL) was required because of the low solubility of
these substrates in water (entries 8−11).
Scheme 1. Reuse of the Catalyst 2b in the Dehydrogenative
Oxidation of Primary and Secondary Alcohols in Aqueous
Media
To demonstrate the additional advantage of the present
dehydrogenative oxidation system in aqueous media, we turned
our attention to reuse of the catalyst. In fact, the use of a
water-soluble catalyst 2b made it easy to separate the organic
product from the catalyst by a simple phase separation: after the
oxidation of an alcohol catalyzed by 2b was conducted in water
[Figure 1a], hexane was added to the system, and the organic and
Scheme 2. A Possible Mechanism for the Dehydrogenative
Oxidation of Alcohols Catalyzed by 2b
Figure 1. (a) Reaction mixture including the water-soluble catalyst 2b.
(b) Organic phase including the product and the aqueous phase
including the catalyst 2b after phase separation using hexane.
aqueous phases were separated [Figure 1b]. By this simple
procedure, isolation of the carbonyl product in the organic phase
and recovery of the 2b in the aqueous phase were achieved.16
The aqueous phase including the recovered catalyst 2b
could be subjected to the next run, showing that high catalytic
activity was still maintained. When the dehydrogenative oxidation
of secondary alcohol 9b was repeated eight times, the recovered
catalyst did not lose its high activity until the eighth run (eq 2).17
unsaturated species A having a 2-pyridonate-based ligand.18 Then,
the activation of an alcohol would occur to afford an alkoxo
iridium species B. β-Hydrogen elimination of the alkoxo moiety in
B would occur to give a carbonyl product and a hydrido iridium
species C. Finally, reaction of the hydride on iridium with the
hydroxyl proton on the functional ligand would occur to release
dihydrogen (ligand-promoted dehydrogenation) accompanied by
the regeneration of A.
In summary, we have synthesized a new water-soluble Cp*Ir
catalyst 2b bearing a bipyridine-based functional ligand and
developed a new catalytic system for the dehydrogenative
oxidation of alcohols which can be performed in water under
mild conditions with high turnover numbers. To the best of our
knowledge, the present catalytic system is the first example of
the dehydrogenative oxidation of alcohols in aqueous media.
Furthermore, reuse of the catalyst for the dehydrogenative
oxidation of different alcohols was accomplished (Scheme 1). In
the first run, the oxidation of 9d was conducted by 2b (1.0 mol %)
to give 10d in 92%. After the recovery of the catalyst, the second
run using 7e gave 8e in 90% yield. Finally, the third run using 9b
gave 10b in 95% yield. Thus it should be very interesting that an
efficient reusable catalytic system can be realized not only for
oxidation of the same substrate but also for oxidation of different
substrates.
ASSOCIATED CONTENT
■
S
* Supporting Information
Experimental procedures and X-ray crystallographic data for 2b
(CIF). This material is available free of charge via the Internet
at http://pubs.acs.org.
A possible mechanism for the present dehydrogenative
oxidation of alcohols catalyzed by 2b is shown in Scheme 2.
The mechanism is closely related to the one we have previously
proposed for the dehydrogenative oxidation catalyzed by the
Cp*Ir complex bearing 2-hydroxypyridine as a functional ligand.6b
The initial step of the reaction would involve elimination of
HOTf from the dicationic catalyst 2b to afford a monocationic
AUTHOR INFORMATION
■
Corresponding Author
fujitak@kagaku.mbox.media.kyoto-u.ac.jp; yamaguchi.ryohei.8c@
kyoto-u.ac.jp
Notes
The authors declare no competing financial interest.
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Chem. 1992, 429, 269. (d) Zhang, J.; Leitus, G.; Ben-David, Y.;
Milstein, D. J. Am. Chem. Soc. 2005, 127, 10840. (e) Zhao, J.; Hartwig,
J. F. Organometallics 2005, 24, 2441.
ACKNOWLEDGMENTS
■
This work was supported by KAKENHI (No. 23550121).
(10) For recent reviews on organic reactions in aqueous media, see:
(a) Lindstrom, U. M. Chem. Rev. 2002, 102, 2751. (b) Kobayashi, S.;
̈
REFERENCES
■
Manabe, K. Acc. Chem. Res. 2002, 35, 209. (c) Manabe, K.; Kobayashi,
S. Chem.Eur. J. 2002, 8, 4094. (d) Li, C.-J. Chem. Rev. 2005, 105,
3095. (e) Chanda, A.; Fokin, V. V. Chem. Rev. 2009, 109, 725.
(11) (a) Kawahara, R.; Fujita, K.; Yamaguchi, R. J. Am. Chem. Soc.
2010, 132, 15108. (b) Kawahara, R.; Fujita, K.; Yamaguchi, R. Adv.
Synth. Catal. 2011, 353, 1161.
(12) (a) Ogo, S.; Makihara, N.; Kaneko, Y.; Watanabe, Y.
Organometallics 2001, 20, 4903. (b) Himeda, Y.; Onozawa-
Komatsuzaki, N.; Miyazawa, S.; Sugihara, H.; Hirose, T.; Kasuga, K.
Chem.Eur. J. 2008, 14, 11076. (c) Himeda, Y. Green Chem. 2009, 11,
2018.
(1) (a) Marko,
́
I. E.; Giles, P. R.; Tsukazaki, M.; Brown, S. M.; Urch,
C. J. Science 1996, 274, 2044. (b) Nishimura, T.; Onoue, T.; Ohe, K.;
Uemura, S. J. Org. Chem. 1999, 64, 6750. (c) Sheldon, R. A.; Arends,
I. W. C. E.; Ten Brink, G.-J.; Dijksman, A. Acc. Chem. Res. 2002, 35,
́
774. (d) Csjernyik, G.; Ell, A. H.; Fadini, L.; Pugin, B.; Backvall, J.-E. J.
Org. Chem. 2002, 67, 1657. (e) Sigman, M. S.; Jensen, D. R. Acc. Chem.
Res. 2006, 39, 221.
(2) (a) Barak, G.; Dakka, J.; Sasson, Y. J. Org. Chem. 1988, 53, 3553.
(b) Sato, K.; Aoki, M.; Takagi, J.; Noyori, R. J. Am. Chem. Soc. 1997,
119, 12386. (c) Noyori, R.; Aoki, M.; Sato, K. Chem. Commun. 2003,
1977.
̈
(13) Generated hydrogen gas could be used for the hydrogena-
tion of an alkene (1-decene). Details are shown in Scheme S1 in the
Supporting Information.
(3) (a) Almeida, M. L. S.; Beller, M.; Wang, G.-Z.; Backvall, J.-E.
̈
Chem.Eur. J. 1996, 2, 1533. (b) Backvall, J.-E. J. Organomet. Chem.
̈
2002, 652, 105. (c) Fujita, K.; Furukawa, S.; Yamaguchi, R.
J. Organomet. Chem. 2002, 649, 289. (d) Gauthier, S.; Scopelliti, R.;
Severin, K. Organometallics 2004, 23, 3769. (e) Hanasaka, F.; Fujita,
K.; Yamaguchi, R. Organometallics 2005, 24, 3422. (f) Levy, R.;
Azerraf, C.; Gelman, D.; Rueck-Braun, K.; Kapoor, P. N. Catal.
Commun. 2009, 11, 298. (g) Coleman, M. G.; Brown, A. N.; Bolton,
B. A.; Guan, H. Adv. Synth. Catal. 2010, 352, 967. (h) Moyer, S. A.;
Funk, T. W. Tetrahedron Lett. 2010, 51, 5430.
(14) We have also carried out the dehydrogenative oxidation
reactions in 0.5 mmol scale with the isolation of the carbonyl products.
Results are shown in Table S1 in the Supporting Information.
(15) At present, aliphatic primary alcohols were not efficiently
oxidized by the present system: the reaction of 1-octanol in the
presence of catalyst 2b (3.0 mol %) in water under reflux for 20 h gave
octanal in 16% yield (conversion of 1-octanol was 17%).
1
(16) H NMR analysis of the aqueous phase revealed that 2b was
(4) (a) Friedrich, A.; Schneider, S. ChemCatChem 2009, 1, 72.
(b) Johnson, T. C.; Morris, D. J.; Wills, M. Chem. Soc. Rev. 2010, 39,
81. (c) Dobereiner, G. E.; Crabtree, R. H. Chem. Rev. 2010, 110, 681.
(5) (a) Dobson, A.; Robinson, S. D. J. Organomet. Chem. 1975, 87,
C52. (b) Ligthart, G. B. W. L.; Meijer, R. H.; Donners, M. P. J;
Meuldijk, J.; Vekemans, J. A. J. M.; Hulshof, L. A. Tetrahedron Lett.
2003, 44, 1507. (c) Zhang, J.; Gandelman, M.; Shimon, L. J. W.;
Rozenberg, H.; Milstein, D. Organometallics 2004, 23, 4026. (d) Adair,
G. R. A.; Williams, J. M. J. Tetrahedron Lett. 2005, 46, 8233. (e) Van
Buijtenen, J.; Meuldijk, J.; Vekemans, J. A. J. M.; Hulshof, L. A.;
Kooijman, H.; Spek, A. L. Organometallics 2006, 25, 873. (f) Baratta,
W.; Bossi, G.; Putignano, E.; Rigo, P. Chem.Eur. J. 2011, 17, 3474.
(g) Prades, A.; Peris, E.; Albrecht, M. Organometallics 2011, 30, 1162.
(h) Zhang, J.; Balaraman, E.; Leitus, G.; Milstein, D. Organometallics
2011, 30, 5716.
quantitatively recovered without decomposition.
(17) We have also carried out the reuse of 2b in the reactions of a
variety of substrates. Results are shown in eq. S1 and Table S2 in the
Supporting Information.
(18) In order to support the mechanism proposed, preparation of a
monocationic Cp*Ir complex related to A was accomplished.
Treatment of 2b with NaOtBu (1.0 equiv.) in water gave a
monocationic complex 11 in 82% yield. Compositional formula of
11 was determined to be C21H24O6F3N2SIr by element analysis, which
is consistent with the structure illustrated below. The complex 11
exhibited a high catalytic activity: When the reaction of 7a was carried
out in the presence of 11 (1.5 mol %) in water under reflux for 20 h,
8a was obtained in 93% yield.
(6) (a) Lin, Y.; Ma, D.; Lu, X. Tetrahedron Lett. 1987, 28, 3115.
(b) Fujita, K.; Tanino, N.; Yamaguchi, R. Org. Lett. 2007, 9, 109.
(c) Royer, A. M.; Rauchfuss, T. B.; Wilson, S. R. Inorg. Chem. 2008, 47,
395. (d) Royer, A. M.; Rauchfuss, T. B.; Gray, D. L. Organometallics
2010, 29, 6763. (e) Musa, S.; Shaposhnikov, I.; Cohen, S.; Gelman, D.
Angew. Chem., Int. Ed. 2011, 50, 3533. (f) Fujita, K.; Yoshida, T.;
Imori, Y.; Yamaguchi, R. Org. Lett. 2011, 13, 2278.
(7) For recent reviews on the catalytic chemistry of iridium in
oxidative transformation of organic substrates. (a) Fujita, K.;
Yamaguchi, R. Synlett 2005, 560. (b) Fujita, K.; Yamaguchi, R. In
Iridium Complexes in Organic Synthesis; Oro, L. A., Claver, C., Eds.;
Wiley-VCH Verlag GmbH & Co. KgaA: Weinheim, Germany, 2009;
Chapter 5, pp 107−143. (c) Suzuki, T. Chem. Rev. 2011, 111, 1825.
(8) Transition metal catalyzed hydrogen production from alcohols
has been also reported. (a) Dobson, A.; Robinson, S. D. Inorg. Chem.
1977, 16, 137. (b) Jung, C. W.; Garrou, P. E. Organometallics 1982, 1,
658. (c) Morton, D.; Cole-Hamilton, D. J. J. Chem. Soc., Chem.
Commun. 1987, 248. (d) Morton, D.; Cole-Hamilton, D. J. J. Chem.
Soc., Chem. Commun. 1988, 1154. (e) Morton, D.; Cole-Hamilton,
D. J.; Utuk, I. D.; Paneque-Sosa, M.; Lopez-Poveda, M. J. Chem. Soc.,
Dalton Trans. 1989, 489. (f) Junge, H.; Beller, M. Tetrahedron Lett.
2005, 46, 1031. (g) Junge, H.; Loges, B.; Beller, M. Chem. Commun.
2007, 522. (h) Nielsen, M.; Kammer, A.; Cozzula, D.; Junge, H.;
Gladiali, S.; Beller, M. Angew. Chem., Int. Ed. 2011, 50, 9593.
(9) Closely related dehydrogenation of alcohols leading to esters has
been reported. (a) Blum, Y.; Shvo, Y. J. Organomet. Chem. 1985, 282,
C7. (b) Murahashi, S.-I.; Naota, T.; Ito, K.; Maeda, Y.; Taki, H. J. Org.
Chem. 1987, 52, 4319. (c) Lin, Y.; Zhu, X.; Zhou, Y. J. Organomet.
3646
dx.doi.org/10.1021/ja210857z | J. Am. Chem. Soc. 2012, 134, 3643−3646