Dehydrogenative oxidation of primary and secondary alcohols catalyzed by a Cp*Ir complex having a functional C,N-chelate ligand

Article abstract of DOI:10.1021/ol2005424

Chemical equations presented. A new catalytic system for the dehydrogenative oxidation of alcohols using a Cp*Ir complex having a functional C,N-chelate ligand has been developed. With this catalytic system, both primary and secondary alcohols were efficiently converted to aldehydes and ketones, respectively. Mechanistic investigations of this catalytic system have revealed that the catalytically active species is a hydrido iridium complex with a functional C,N-chelate ligand.

Full text of DOI:10.1021/ol2005424

ORGANIC
LETTERS
2011
Vol. 13, No. 9
2278–2281
Dehydrogenative Oxidation of Primary
and Secondary Alcohols Catalyzed
by a Cp*Ir Complex Having a Functional
C,N-Chelate Ligand
Ken-ichi Fujita,*,†,‡ Tetsuya Yoshida,† Yoichiro Imori,† 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 February 28, 2011
ABSTRACT
A new catalytic system for the dehydrogenative oxidation of alcohols using a Cp*Ir complex having a functional C,N-chelate ligand has been
developed. With this catalytic system, both primary and secondary alcohols were efficiently converted to aldehydes and ketones, respectively.
Mechanistic investigations of this catalytic system have revealed that the catalytically active species is a hydrido iridium complex with a functional
C,N-chelate ligand.
The oxidation of alcohols to carbonyl compounds is one
ofthemostfundamental and important transformationsin
synthetic organic chemistry. To develop an environmen-
tally benign system, much effort has been devoted to the
studies on the transition-metal-catalyzed oxidation of
alcohols using less-toxic oxidants such as oxygen,1 hydro-
gen peroxide,2 or acetone.3 However, an oxidant-free
reaction to give carbonyl products via dehydrogenative
oxidation accompanied by the release of hydrogen gas
must be superior from the viewpoint of atom economy.4
Several systems for the dehydrogenative oxidation of
secondary alcohols to ketones using ruthenium5 and
iridium6 catalysts have been developed.7 In contrast, there
(4) (a) Johnson, T. C.; Morris, D. J.; Wills, M. Chem. Soc. Rev. 2010,
39, 81. (b) Friedrich, A.; Schneider, S. ChemCatChem 2009, 1, 72.
(5) (a) Dobson, A.; Robinson, S. D. J. Organomet. Chem. 1975, 87,
C52. (b) Dobson, A.; Robinson, S. D. Inorg. Chem. 1977, 16, 137. (c)
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.
(d) Zhang, J.; Gandelman, M.; Shimon, L. J. W.; Rozenberg, H.;
Milstein, D. Organometallics 2004, 23, 4026. (e) Adair, G. R. A.;
Williams, J. M. J. Tetrahedron Lett. 2005, 46, 8233. (f) van Buijtenen,
J.; Meuldijk, J.; Vekemans, J. A. J. M.; Hulshof, L. A.; Kooijman, H.;
Spek, A. L. Organometallics 2006, 25, 873.
(6) (a) Fujita, K.; Tanino, N.; Yamaguchi, R. Org. Lett. 2007, 9, 109.
(b) Royer, A. M.; Rauchfuss, T. B.; Wilson, S. R. Inorg. Chem. 2008, 47,
395. (c) Royer, A. M.; Rauchfuss, T. B.; Gray, D. L. Organometallics
2010, 29, 6763.
(7) Transition-metal-catalyzed hydrogen production from alcohols
has been also reported. (a) Morton, D.; Cole-Hamilton, D. J. J. Chem.
Soc., Chem. Commun. 1987, 248. (b) Morton, D.; Cole-Hamilton, D. J.
J. Chem. Soc., Chem. Commun. 1988, 1154. (c) Morton, D.; Cole-
Hamilton, D. J.; Utuk, I. D.; Paneque-Sosa, M.; Lopez-Poveda, M.
J. Chem. Soc., Dalton Trans. 1989, 489. (d) Junge, H.; Beller, M.
Tetrahedron Lett. 2005, 46, 1031. (e) Junge, H.; Loges, B.; Beller, M.
Chem. Commun. 2007, 522.
† 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.; Ell, A. H.; Fadini, L.; Pugin, B.; Backvall, J.-E. J. Org. Chem. 2002,
67, 1657. (d) Sigman, M. S.; Jensen, D. R. Acc. Chem. Res. 2006, 39, 221.
(e) Schultz, M. J.; Sigman, M. S. Tetrahedron 2006, 62, 8227. (f) Jiang, B.;
Feng, Y.; Ison, E. A. J. Am. Chem. Soc. 2008, 130, 14462.
(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.
€
(3) (a) Almeida, M. L. S.; Beller, M.; Wang, G.-Z.; Backvall, J.-E.
Chem.;Eur. J. 1996, 2, 1533. (b) Fujita, K.; Furukawa, S.; Yamaguchi,
R. J. Organomet. Chem. 2002, 649, 289. (c) Hanasaka, F.; Fujita, K.;
Yamaguchi, R. Organometallics 2005, 24, 3422. (d) Coleman, M. G.;
Brown, A. N.; Bolton, B. A.; Guan, H. Adv. Synth. Catal. 2010, 352, 967.
(e) Moyer, S. A.; Funk, T. W. Tetrahedron Lett. 2010, 51, 5430.
r
10.1021/ol2005424
Published on Web 04/07/2011
2011 American Chemical Society

have been no homogeneous systems which efficiently
catalyze the dehydrogenation of primary alcohols to
aldehydes.8,9
Table 1. Dehydrogenative Oxidation of Benzyl Alcohol (4)
under Various Conditionsa
We have recently reported the dehydrogenative oxida-
tion of alcohols catalyzed by Cp*Ir complexes 1 having
2-hydroxypyridine as a functional ligand, in which N,
O-chelated complex 2 could act as a catalytically active
species.6a Use of the catalyst achieved extremely high
turnover numbers up to 2000 in the oxidation of secondary
alcohols. However, such catalysts did not exhibit a high
activity for the reaction of primary alcohols (vide infra).
entry catalyst
base
none
solvent
convb(%) yieldb (%)
1
3
3
3
3
3
3
3
6
1
1
2
2
toluene
toluene
toluene
59
66
77
86
91
81
91
8
59
62
75
84
90
66
88
8
2
Na2CO3
K2CO3
3
4
NaHCO3 toluene
5
NaOMe
toluene
toluene
6
NaOtBu
7
NaHCO3 p-xylene
8
NaOMe
none
toluene
toluene
toluene
toluene
toluene
Here, we report a new catalytic system for the dehydro-
genative oxidation of alcohols using a Cp*Ir complex
having a functional C,N-chelate ligand. Both primary
and secondary alcohols were efficiently converted to alde-
hydes and ketones, respectively. Mechanistic studies of this
catalytic system are also demonstrated.
The Cp*Ir catalyst used in this study was prepared as
illustrated in eq 1. The reaction of [Cp*IrCl2]2 with 6-phenyl-
2-pyridone in the presence of NaOAc (1.3 equiv) in dichlor-
omethane at room temperature gave a C,N-chelated complex
3 in 62% yield via coordination of the nitrogen atom in the
pyridine ring followed by orthometalation at the phenyl
group.10 The complex 3 was obtained as a stable yellow
powder, and its structure was elucidated by spectroscopic
data and single-crystal X-ray analysis (see the Supporting
Information).
9
63
31
52
17
63
30
50
17
10
11
12
NaOMe
none
NaOMe
a The reaction was carried out with 4 (1.0 mmol), catalyst (2.0 mol %),
and base (5.0 mol %) in toluene (18 mL) under reflux for 20 h.
b Detemined by GC.
First, reactions of benzyl alcohol (4) under various
conditions were conducted in order to find optimum
conditions (Table 1). When the solution of 4 in toluene
was refluxed for 20 h in the presence of 3 (2.0 mol %),
benzaldehyde (5) was selectively formed in 59% yield
(entry 1).11 The yield of 5 was improved by the addi-
tion of a base. When the reactions were carried out in
the presence of Na2CO3, K2CO3, NaHCO3, and
NaOMe, the yields of 5 were improved up to 62%,
75%, 84%, and 90%, respectively (entries 2À5).12 The
best result was obtained by using NaOMe (entry 5),
while the reaction using NaOtBu resulted in a lower
selectivity for 5 (entry 6). A high yield of 5 (88%) was
also achieved by the reaction using NaHCO3 as a base
under reflux in p-xylene (entry 7).13 The hydroxy
group in the C,N-chelate ligand was indispensable to
attain high catalytic activity: when the reaction was
carried out using Cp*IrCl[2-(2-pyridyl)phenyl]Cl
(6)10,14 as the catalyst, 5 was formed in only 8% yield
(entry 8). Other Cp*Ir catalysts 1 and 2, those exhib-
ited high activity for the dehydrogenative oxidation of
The catalytic performance of 3 for the dehydrogena-
tive oxidation of primary alcohols was investigated.
(8) Robinson has reported the dehydrogenation of primary alcohols
catalyzed by Ru(OCOCF3)(CO)(PPh3)2 in refs 5a and 5b. However,
quantitative study with respect to the fate of the alcohols was not
demonstrated. Additionally, Hulshof noted in ref 5c that dehydrogena-
tive oxidation of primary alcohols catalyzed by the same ruthenium
complex resulted in low conversions and selectivities.
(9) Heterogeneously catalyzed systems for the dehydrogenative oxi-
dation 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. (c) Mitsudome, T.; Mikami,
Y.; Funai, H.; Mizugaki, T.; Jitsukawa, K.; Kaneda, K. Angew. Chem.,
Int. Ed. 2008, 47, 138. (d) Mitsudome, T.; Mikami, Y.; Ebata, K.;
Mizugaki, T.; Jitsukawa, K.; Kaneda, K. Chem. Commun. 2008, 4804.
(e) Shimizu, K.; Sugino, K.; Sawabe, K.; Satsuma, A. Chem.;Eur. J.
2009, 15, 2341.
(11) Evolution of the hydrogen gas was confirmed by an analysis of
the gas phase using a hydrogen sensor.
(12) We have also carried out the reaction of 4 by using equimolar
amounts of 3 (2.0 mol %) and NaOMe (2.0 mol %) under reflux in
toluene for 20 h, resulting in a lower yield (70%) of 5.
(13) The addition of NaHCO3 as a base gave the best result for the
reaction under p-xylene reflux. The addition of NaOMe lowered the
yield of 5 to 58%.
(14) The catalytic activity of complex 6 has been recently reported. (a)
Hull, J. F.; Balcells, D.; Blakemore, J. D.; Incarvito, C. D.; Eisenstein,
O.; Brudvig, G. W.; Crabtree, R. H. J. Am. Chem. Soc. 2009, 131, 8730.
(b) Blakemore, J. D.; Schley, N. D.; Balcells, D.; Hull, J. F.; Olack,
G. W.; Incarvito, C. D.; Eisenstein, O.; Brudvig, G. W.; Crabtree, R. H.
J. Am. Chem. Soc. 2010, 132, 16017.
(10) Synthesis of a C,N-chelated complex by the reaction of
[Cp*IrCl2]2 with 2-phenylpyridine in the presence of NaOAc has been
reported. (a) Scheeren, C.; Maasarani, F.; Hijazi, A.; Djukic, J.-P.;
ꢀ
Pfeffer, M.; Zaric, S. D.; Le Goff, X.-F.; Ricard, L. Organometallics
2007, 26, 3336. (b) Li, L.; Brennessel, W. W.; Jones, W. D. J. Am. Chem.
Soc. 2008, 130, 12414. (c) Boutadla, Y.; Al-Duaji, O.; Davies, D. L.;
Griffith, G. A.; Singh, K. Organometallics 2009, 28, 433.
Org. Lett., Vol. 13, No. 9, 2011
2279

secondary alcohols,6a showed lower activity than 3 in
the reaction of 4 (entries 9À12)
benzylic alcohols could be converted to aldehydes in high
yields by the reactions under condition A. When the yield
of the aldehyde under condition A was unsatisfactory, the
reaction under condition B was conducted to improve the
yield of aldehyde (entries 3 and 9). Reactions of electron-
poor benzylic alcohols were relatively slow: thus, condition
B was applied to obtain better results (entries 11À18). The
present catalytic system was also applicable to aliphatic
primary alcohols, although the yields of corresponding
aldehydes were moderate (entries 20À23). When the reac-
tions of cyclohexanemethanol and 1-octanol were carried
out under condition B using 5.0 mol % of 3, cyclohexane-
carbaldehyde and octanal were formed in 62% and 46%
yield, respectively (entries 21 and 23).
Table 2. Dehydrogenative Oxidation of Various Primary Alco-
hols Catalyzed by 3a
Table 3. Dehydrogenative Oxidation of Various Secondary
Alcohols Catalyzed by 3a
a The reaction was carried out with secondary alcohol (1.5À15
mmol) and catalyst 3 (0.10À0.50 mol %) in toluene or p-xylene
(0.50À5.0 M solution) under reflux for 20 h. b Determined by GC.
Reactions of secondary alcohols proceeded to give ketones
with much lower catalyst loadings (0.10À0.50 mol %) with-
out the addition of base (Table 3).11,15 1-Arylethanols with
electron-donating and -withdrawing substituents proceeded
to give corresponding ketones in excellent yields with com-
plete selectivity (entries 1À5). Aliphatic secondary alcohols
including cyclic alcohols were also converted to ketones in
excellent yields (entries 6À9).
a Condition A: The reaction was carried out with primary alcohol
(1.0 mmol), catalyst 3 (2.0 mol %), and NaOMe (5.0 mol %) in toluene
(18 mL) under reflux for 20 h. Condition B: The reaction was carried out
with primary alcohol (1.0 mmol), catalyst 3 (2.0 mol %), and NaHCO3
(5.0 mol %) in p-xylene (18 mL) under reflux for 20 h. b Determined by GC.
The value in parentheses is isolated yield. c 5.0 mol % of catalyst 3 was used.
Having the optimum conditions A and B (A: reflux in
toluene with NaOMe, B: reflux in p-xylene with NaHCO3)
in hand, we next investigated the dehydrogenative oxida-
tion of various primary alcohols catalyzed by 3 (Table 2).
The reactions of benzylic alcohols with electron-donating
and -withdrawing substituents at the aromatic ring pro-
ceeded to give corresponding aldehydes in moderate to
excellent yields (entries 1À18). Most of the electron-rich
A possible mechanism for the present dehydrogena-
tive oxidation is shown in Scheme 1. The first step of the
reaction would involve the formation of an alkoxo
iridium species 7 by the reaction of 3 with an alcohol
(15) Generated hydrogen gas could be used for the hydrogenation of
an alkene (1-decene). Details are shown in the Supporting Information.
2280
Org. Lett., Vol. 13, No. 9, 2011

with liberation of hydrogen chloride, which would
be accelerated by the addition of a base. β-Hydrogen
elimination of 7 would occur to give the dehydrogenated
product and a hydrido iridium complex 8. Then, pro-
tonolysis of the iridium hydride with the hydroxy
proton in the C,N-chelate ligand would occur to release
hydrogen gas accompanied by the formation of an
unsaturated pyridonate complex 9. Addition of the
alcohol to 9 would regenerate species 7.
was carried out in toluene under reflux for 20 h in the
presence of 8 (2.0 mol %) without a base, 5 was formed
in 78% yield (eq 3),16 indicating its importance as a
catalytically active species.
Furthermore, the formation of the hydrido complex 8 in
the early stage of the dehydrogenative reaction was confirmed
by NMR study. 1H NMR analysis of the substoichiometric
reaction of 3 with 4 (4 equiv) and NaOMe (2.4 equiv) in
toluene-d8 at 50 °C for 10 min revealed the formation of 8
(eq4),17 strongly supporting the proposed mechanism (see the
Supporting Information).
Scheme 1. A Possible Mechanism for the Dehydrogenative
Oxidation of Alcohols Catalyzed by 3
In summary, we have developed a new Cp*Ir catalyst
having a functional C,N-chelate ligand, which exhibited a
high activity for the dehydrogenative oxidation of both
primary and secondary alcohols. A variety of primary and
secondary alcohols were converted to aldehydes and ke-
tones accompanied by the release of hydrogen gas. The
mechanistic investigations have revealed that the catalyti-
cally active species is a hydrido iridium complex with a
functional C,N-chelate ligand.
The hydrido complex 8 mentioned above was actu-
ally prepared by the reaction of 3 with NaBH4 in THF
at 0 °C for 1 h in 84% yield (eq 2). Complex 8 was
obtained as a relatively unstable pale-yellow powder.
The structure of 8 was determined by spectroscopic
data (see the Supporting Information).
Acknowledgment. This work was supported by
KAKENHI (No. 19750075). We also thank Johnson
Matthey, Inc. for a generous loan of iridium trichloride.
Note Added in Proof. Very recently, dehydrogenative
oxidation of primary and secondary benzylic alcohols
catalyzed by homogeneous triazolylidene ruthenium
complexes was reported. Prades, A.; Peris, E.; Albrecht,
M. Organometallics 2011, 30, 1162.
Supporting Information Available. General experimen-
tal procedure, characterization data of the catalysts and
products, and X-ray crystallographic data for 3. This
material is available free of charge via the Internet at
http://pubs.acs.org.
To verify the proposed mechanism, the catalytic
activity of 8 was examined. When the reaction of 4
(16) The yield of 5 in the reaction of 4 catalyzed by 8 (78%) was higher
than that catalyzed by 3 without a base (59%), but lower than that
catalyzed by 3 with NaOMe (90%). Instability of the hydrido complex 8
would cause the lower yield of 5 compared to the reaction catalyzed by
stable complex 3 with NaOMe.
(17) In addition to the hydrido complex 8, the formation of 5 was
confirmed by 1H NMR analysis.
Org. Lett., Vol. 13, No. 9, 2011
2281