Ligand-promoted dehydrogenation of alcohols catalyzed by Cp*Ir complexes. A new catalytic system for oxidant-free oxidation of alcohols

Article abstract of DOI:10.1021/ol062806v

An efficient catalytic system for oxidant-free oxidation of alcohols has been developed. A new Cp*Ir catalyst bearing a 2-hydroxypyridine ligand has been designed on the concept of "ligand-promoted dehydrogenation". Various secondary alcohols can be dehydrogenatively oxidized to ketones under neutral conditions with high turnover numbers by using the new Cp*Ir catalyst. (Chemical Equation Presented)

Full text of DOI:10.1021/ol062806v

ORGANIC
LETTERS
2007
Vol. 9, No. 1
109-111
Ligand-Promoted Dehydrogenation of
Alcohols Catalyzed by Cp*Ir Complexes.
A New Catalytic System for
Oxidant-Free Oxidation of Alcohols
Ken-ichi Fujita,*,†,‡ Nobuhide Tanino,† and Ryohei Yamaguchi*,†
Graduate School of Human and EnVironmental Studies, and Graduate School of
Global EnVironmental Studies, Kyoto UniVersity, Sakyo-ku, Kyoto 606-8501, Japan
fujitak@kagaku.mbox.media.kyoto-u.ac.jp; yama@kagaku.mbox.media.kyoto-u.ac.jp
Received November 18, 2006
ABSTRACT
An efficient catalytic system for oxidant-free oxidation of alcohols has been developed. A new Cp*Ir catalyst bearing a 2-hydroxypyridine
ligand has been designed on the concept of “ligand-promoted dehydrogenation”. Various secondary alcohols can be dehydrogenatively oxidized
to ketones under neutral conditions with high turnover numbers by using the new Cp*Ir catalyst.
The oxidation of alcohols to carbonyl compounds is one of
the most fundamental and important reactions in synthetic
organic chemistry, and it is quite important to develop a mild
and less toxic oxidation system. Recently, much effort have
been devoted to the transition-metal-catalyzed oxidation of
alcohols using environmentally friendly oxidants such as
oxygen,1 hydrogen peroxide,2 or acetone.3 However, from
the viewpoint of atom efficiency and safety of the reaction,
an oxidant-free reaction to give carbonyl products should
be ideal.
catalyst have been reported,4-6 most of them require acidic
or basic reaction conditions and turnover numbers of the
catalyst are not so high. It has been generally recognized
that the most critical step in the catalytic dehydrogenative
oxidation of alcohols would be the release of dihydrogen
(4) (a) Dobson, A.; Robinson, S. D. J. Organomet. Chem. 1975, 87, C52.
(b) Dobson, A.; Robinson, S. D. Inorg. Chem. 1977, 16, 137. (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) 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. (g) Zhang, J.;
Gandelman, M.; Shimon, L. J. W.; Rozenberg, H.; Milstein, D. Organo-
metallics 2004, 23, 4026. (h) Junge, H.; Beller, M. Tetrahedron Lett. 2005,
46, 1031. (i) Adair, G. R. A.; Williams, J. M. J. Tetrahedron Lett. 2005,
46, 8233. (j) van Buijtenen, J.; Meuldijk, J.; Vekemans, J. A. J. M.; Hulshof,
L. A.; Kooijman, H.; Spek, A. L. Organometallics 2006, 25, 873.
(5) Heterogeneous catalytic systems for the oxidant-free oxidation of
alcohols have been also reported. (a) Choi, J. H.; Kim, N.; Shin, Y. J.;
Park, J. Tetrahedron Lett. 2004, 45, 4607. (b) Kim, W.-H.; Park, I. S.; Park,
J. Org. Lett. 2006, 8, 2543.
Although several oxidant-free (dehydrogenative) systems
for the oxidation of alcohols using ruthenium and rhodium
† Graduate School of Human and Environmental Studies.
‡ Graduate School of Global Environmental Studies.
(1) (a) Marko´, I. E.; Giles, P. R.; Tsukazaki, M.; Brown, S. M.; Urch,
C. J. Science 1996, 274, 2044. (b) Sheldon, R. A.; Arends, I. W. C. E.; ten
Brink, G.-J.; Dijksman, A. Acc. Chem. Res. 2002, 35, 774. (c) Csjernyik,
G.; EÄ ll, A. H.; Fadini, L.; Pugin, B.; Ba¨ckvall, J.-E. J. Org. Chem. 2002,
67, 1657. (d) Sigman, M. S.; Jensen, D. R. Acc. Chem. Res. 2006, 39, 221.
(2) Noyori, R.; Aoki, M.; Sato, K. Chem. Commun. 2003, 1977.
(3) (a) Almeida, M. L. S.; Beller, M.; Wang, G.-Z.; Ba¨ckvall, J.-E. Chem.
Eur. J. 1996, 2, 1533. (b) Hanasaka, F.; Fujita, K.; Yamaguchi, R.
Organometallics 2005, 24, 3422.
(6) Closely related dehydrogenative esterification of alcohols has been
recently reported: (a) Zhao, J.; Hartwig, J. F. Organometallics 2005, 24,
2441. (b) Zhang, J.; Leitus, G.; Ben-David, Y.; Milstein, D. J. Am. Chem.
Soc. 2005, 127, 10840.
10.1021/ol062806v CCC: $37.00
© 2007 American Chemical Society
Published on Web 12/06/2006

from metal hydride intermediate generated by â-elimination
of an metal alkoxide to regenerate a catalytically active
species. When a metal complex A ligated with a ligand
bearing a protic functional group could be employed, a metal
hydride C should be formed via metal alkoxide B (eq 1).
Then, an intramolecular reaction of the hydride on the metal
with the protic hydrogen on the ligand could readily take
place to facilitate the release of dihydrogen. The resulting
hydride-free metallacycle D would react with an alcohol to
reproduce B.
Table 1. Oxidant-Free Oxidation of 1-Phenylethanol Catalyzed
by Cp*Ir Complexes under Various Conditionsa
entry
catalyst
additive convnb (%) yieldb (%) TON
1
2
3
4
5
6
7
1a
1b
1c
none
none
none
70
10
13
10
20
22
14
54
70
10
13
9
17
22
13
53
700
100
130
90
170
220
130
2120
Cp*Ir(pyridine)Cl2 none
[Cp*IrCl2]2
[Cp*IrCl2]2
[Cp*IrCl2]2
none
K2CO3
phenol
none
8c 1a
a The reaction was carried out with 1-phenylethanol (20 mmol), catalyst
(0.10 mol % of Ir), and additive (0.10 mol %) in toluene (6 mL) under
reflux for 20 h. b Determined by GC. c The reaction was carried out with
1-phenylethanol (40 mmol) and 1a (0.025 mol % of Ir) in xylene (6 mL)
under reflux for 100 h.
Considering the above working hypothesis, we have started
to design the metal catalyst suitable for dehydrogenative
oxidant-free oxidation of alcohols. In this paper, we wish to
report a new and efficient system for the oxidant-free
oxidation of secondary alcohols to give ketones catalyzed
by a Cp* (pentamethylcyclopentadienyl)iridium complex
having 2-hydroxypyridine ligand. With this catalytic system,
the reaction can be conducted under neutral conditions, and
high turnover numbers up to 2000 have been achieved.
Cp*Ir catalysts used in this study were prepared as
illustrated in eq 2. Treatment of [Cp*IrCl2]2 with hydroxy-
pyridine derivatives in dichloromethane at room temperature
gave complexes 1a-c. Single-crystal X-ray analyses of 1a-c
demonstrate that hydroxypyridine ligands are coordinated to
the iridium center in monodentate κN fashion (Figure 1
Figures S1 and S2, Supporting Information).
also examined, but the yields of acetophenone were low
(entries 5-7). The highest turnover number (2120) was
accomplished when the reaction was carried out under reflux
in xylene for 100 h with catalyst 1a (0.025 mol % of Ir)
(entry 8).
To evaluate the scope of this system, the oxidation
reactions of various secondary alcohols were undertaken
(Table 2). The reactions of 1-arylethanols with electron-
Table 2. Oxidant-Free Oxidation of Various Secondary
Alcohols Catalyzed by 1aa
With these new Cp*Ir hydroxypyridine complexes in hand,
we next examined their catalytic activity for the oxidant-
free oxidation of alcohols. At first, the reactions of 1-phen-
ylethanol to give acetophenone under various conditions were
investigated (Table 1). When the reaction was carried out in
the presence of 1a (0.10 mol % of Ir) under reflux in toluene
for 20 h, acetophenone was formed in 70% yield selectively
(conversion of 1-phenylethanol was 70%) (entry 1).7 Other
Cp*Ir catalysts having a 3- or 4-hydroxypyridine ligand (1b
and 1c) or Cp*Ir(pyridine)Cl2 showed lower catalytic activity
than 1a, indicating the hydroxyl substituent at the 2-position
was indispensable for high catalytic performance (entries
2-4). The reaction using [Cp*IrCl2]2 as a catalyst under
neutral, basic (K2CO3), or acidic (phenol) conditions were
a The reaction was carried out with alcohol (1.0-5.0 mmol) and catalyst
1a (0.20-1.0 mol % of Ir) in toluene (2-6 mL) under reflux. b Isolated
yield. c The reaction was carried out in the presence of K2CO3 (1.0 mol
%). d Determined by GC.
(7) Evolution of dihydrogen was confirmed by the analysis of gas phase
using a hydrogen sensor, although quantitative analysis was not carried out.
110
Org. Lett., Vol. 9, No. 1, 2007

donating and withdrawing substituents at the aromatic ring
proceeded to give corresponding ketones in good to excellent
yields with high turnover numbers (entries 1-8). The
oxidation of acid-sensitive 1-(2-furyl)ethanol was possible
to give 2-acetylfuran in good yield by the reaction in the
presence of a catalytic amount of K2CO3 (entry 9). Other
aromatic, aliphatic, and cyclic secondary alcohols were also
applicable to this system (entries 10-15). Unfortunately,
primary alcohols were not efficiently oxidized by this system;
the reaction of benzyl alcohol catalyzed by 1a (1.0 mol %)
for 20 h gave benzaldehyde in 24% yield.
Figure 1. ORTEP drawings of 1a (left) and 2 (right) with 50%
thermal probability ellipsoids. Hydrogen atoms are omitted for
clarity.
A possible mechanism for the present reaction is shown
in Scheme 1. The first step of the reaction would involve
activity comparable to 1a in the oxidation of 1-phenylethanol
(eq 4), indicating its importance as a catalytic active species.
Additionally, when the oxidation of 1-phenylethanol was
carried out using 1a as a catalyst (2.0 mol % of Ir) in a sealed
NMR tube, the formation of dihydrogen besides acetophe-
Scheme 1. Possible Mechanism for the Oxidant-Free
Oxidation of Alcohols Catalyzed by 1a
1
none was confirmed by H NMR analysis (δ 4.46).9
In summary, we have accomplished the design and the
synthesis of new Cp*Ir complexes bearing hydroxypyridine
ligands and developed a new efficient catalytic system for
oxidant-free oxidation of alcohols, which can be conducted
under neutral conditions with high turnover numbers. We
have also disclosed that the protic functional group on the
ligand promotes the release of dihydrogen from the metal
hydride intermediate and that 2-hydroxypyridine chelated
Cp*Ir complex acts as a highly active catalyst, supporting
the proposed catalytic cycle.
the formation of an alkoxo iridium intermediate E by the
reaction of 1a with alcohol. â-Hydrogen elimination of E
would occur to give the ketone product and an iridium
hydride species F. Then, the reaction of the hydride on
iridium with the hydroxyl proton on the ligand would occur
to release dihydrogen accompanied by the formation of
2-hydroxypyridinate chelated intermediate G, which would
be subjected to the addition of alcohol to regenerate E. The
much lower catalytic activities of the complexes 1b and 1c
could be in accordance with the supposed mechanism.
To verify this mechanism, 2-hydroxypyridinate-chelated
iridium complex corresponding to G was prepared, and its
catalytic activity was examined. The treatment of [Cp*IrCl2]2
with sodium 2-hydroxypyridinate in benzene gave 2 (eq 3).
Supporting Information Available: General experi-
mental procedure, characterization data of the catalysts
and products, and X-ray crystallographic data. This ma-
terial is available free of charge via the Internet at
http://pubs.acs.org.
OL062806V
(8) X-ray study indicated a contribution of another resonance form of
pyridonate 2′, which is also supported by the result of 13C{1H} NMR
analysis.
(9) The reaction was carried out using 1-phenylethanol (0.75 mmol) and
1a (2.0 mol % of Ir) in benzene-d6 at 130 °C for 3 h in a sealed NMR tube.
In the 1H NMR analysis, a signal of H2 was observed at δ 4.46 besides the
signals of acetophenone (7%) and 1-phenylethanol (93%).
The structure of 2 was confirmed by X-ray diffraction
study (Figure 1).8 The complex 2 exhibited a high catalytic
Org. Lett., Vol. 9, No. 1, 2007
111