Application and mechanistic studies of a water-oxidation catalyst in alcohol oxidation by employing oxygen-transfer reagents

Article abstract of DOI:10.1002/chem.201202266

By using a dimeric ruthenium complex in combination with tert-butyl hydrogen peroxide (TBHP) as stoichiometric oxidant, a mild and efficient protocol for the oxidation of secondary benzylic alcohols was obtained, thereby giving the corresponding ketones in high yields within 4 h. However, in the oxidation of aliphatic alcohols, the TBHP protocol suffered from low conversions owing to a competing Ru-catalyzed disproportionation of the oxidant. Gratifyingly, by switching to Oxone (2 KHSO₅×KHSO ₄×K₂SO₄ triple salt) as stoichiometric oxidant, a more efficient and robust system was obtained that allowed for the oxidation of a wide range of aliphatic and benzylic secondary alcohols, giving the corresponding ketones in excellent yields. The mechanism for these reactions is believed to involve a high-valent Ru^V-oxo species. We provide support for such an intermediate by means of mechanistic studies. Biphasinating: The use of a dimeric ruthenium complex in the oxidation of alcohols to their corresponding carbonyl compounds in high yields with various oxygen-transfer reagents is reported. This provides support for a mechanism that involves a high-valent Ru^V-oxo species (see scheme). Copyright

Full text of DOI:10.1002/chem.201202266

FULL PAPER
DOI: 10.1002/chem.201202266
Application and Mechanistic Studies of a Water-Oxidation Catalyst in
Alcohol Oxidation by Employing Oxygen-Transfer Reagents
[
a]
[a]
[a]
[a]
Oscar Verho, Marlꢀne D. V. Dilenstam, Markus D. Kꢁrkꢁs, Eric V. Johnston,
[
b]
[a]
[a]
Torbjçrn ꢂkermark, Jan-E. Bꢁckvall, and Bjçrn ꢂkermark*
Abstract: By using a dimeric rutheni-
um complex in combination with tert-
butyl hydrogen peroxide (TBHP) as
stoichiometric oxidant, a mild and effi-
cient protocol for the oxidation of sec-
ondary benzylic alcohols was obtained,
thereby giving the corresponding ke-
tones in high yields within 4 h. Howev-
er, in the oxidation of aliphatic alco-
hols, the TBHP protocol suffered from
low conversions owing to a competing
Ru-catalyzed disproportionation of the
oxidant. Gratifyingly, by switching to
Oxone (2KHSO ·KHSO ·K SO triple
salt) as stoichiometric oxidant, a more
efficient and robust system was ob-
tained that allowed for the oxidation of
a wide range of aliphatic and benzylic
secondary alcohols, giving the corre-
sponding ketones in excellent yields.
The mechanism for these reactions is
5
4
2
4
V
believed to involve a high-valent Ru –
oxo species. We provide support for
such an intermediate by means of
mechanistic studies.
Keywords: alcohols · biphasic catal-
ysis · oxidation · Oxone · ruthenium
Introduction
Selective oxidation of alcohols into their corresponding al-
dehydes and ketones is a fundamental transformation in or-
ganic synthesis and is of major importance in both laborato-
[1]
ry and industrial synthetic chemistry. The transformations
are still widely carried out with stoichiometric amounts of
VI
VII [2]
high-valent metal reagents such as Cr and Mn
.
These
protocols suffer from high costs, poor atom utilization, and
production of stoichiometric amounts of toxic metal waste,
thus making them unattractive from both an economical
and environmental perspective. However, in recent decades,
major efforts have been dedicated to developing new effi-
cient catalytic oxidation protocols based on transition
water oxidation. The use of WOCs for the oxidation of or-
ganic substrates has lately attracted considerable interest,
[8]
and this has inspired us to investigate the potential applica-
tions of 1 for similar transformations. Herein, we report on
the use of 1 in the oxidation of alcohols to their correspond-
ing carbonyl compounds with various two-electron oxidants
and provide support for a mechanism involving a high-
[3]
[4]
[5]
[6]
metals (e.g., Pd, Ru, Cu, and Au ) that employ envi-
ronmentally benign oxidants.
Recently, our group has developed and synthesized the di-
meric ruthenium complex 1, which displayed excellent activ-
ity as a water-oxidation catalyst (WOC) in chemical- and
V
valent Ru –oxo species.
[7]
light-driven water oxidation. The introduction of negative-
ly charged ligands into WOCs lowers the redox potentials
and allows for the formation of high-valent metal–oxo com-
plexes. Furthermore, the bioinspired ligand was designed to
withstand the highly oxidative conditions associated with
Results and Discussion
Initial screenings: A screening of suitable oxidants for Ru
complex 1 was performed and the results are summarized in
Table 1. Unfortunately, complex 1 exhibited poor solubility
in most organic solvents, and among all the tested solvents
only dichloromethane (CH Cl ) was found to provide suffi-
[
a] O. Verho, M. D. V. Dilenstam, M. D. Kꢀrkꢀs, Dr. E. V. Johnston,
Prof. J.-E. Bꢀckvall, Prof. B. ꢁkermark
Department of Organic Chemistry
2
2
Arrhenius Laboratory, Stockholm University
cient solubility. Some of the tested oxidants were slightly
soluble in CH Cl , but this problem could be circumvented
1
06 91 Stockholm (Sweden)
2
2
E-mail: bjorn.akermark@organ.su.se
by employing a two-phase system consisting of CH Cl and
2
2
[
b] Dr. T. ꢁkermark
H O. Because of the oxidative stability of complex 1, the re-
2
Department of Materials and Environmental Chemistry
Arrhenius Laboratory, Stockholm University
actions could be carried out under normal conditions with-
out the use of an inert atmosphere.
1
06 91 Stockholm (Sweden)
Chem. Eur. J. 2012, 18, 16947 – 16954
ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
16947

Table 1. Oxidation of 1-phenylethanol (2a) with ruthenium complex 1 by
using different oxidants.
tested with simpler ruthenium precursors, and the results
are summarized in Table 2. The simpler ruthenium com-
plexes displayed lower activity per molar equivalent of
ruthenium than that of 1 when using either TBHP or Oxone
[
a]
[
b]
Entry
Oxidant
Conv. [%]
1
2
3
4
5
H
NaOCl
TBHP
2
O
2
8
32
55
>99
>99
Table 2. Oxidation of 1-phenylethanol (2a) with various ruthenium pre-
iodosobenzene
Oxone
[
a]
[
c]
cursors.
[
b]
[b]
Entry
Catalyst
Conv. TBHP [%]
Conv. Oxone [%]
[
a] Conditions: 2a (0.26 mmol), 1 (0.75 mol%), oxidant (1.04 mmol),
CH Cl (2.0 mL), H O (2 mL, pH 6), 408C, 4 h. [b] Determined by GC
analysis. [c] After 2 h.
[
c]
[d]
2
2
2
1
2
3
1
55
40
4
99 (48)
[
d]
RuCl
RuO
3
66 (7)
10
2
[
a] Conditions (TBHP): 2a (0.26 mmol), Ru (1.5 mol%), TBHP
1.04 mmol), CH Cl (2.0 mL), H O (2.0 mL, pH 6), 408C, 4 h. Conditions
Oxone): 2a (0.26 mmol), Ru (1.5 mol%), Oxone (0.78 mmol), CH Cl
2.0 mL), H O (2.0 mL, pH 6), 408C, 4 h. [b] Determined by GC analysis.
c] After 2 h. [d] After 1 h at room temperature, under otherwise un-
(
(
(
2
2
2
Oxidants such as hydrogen peroxide (H O ; Table 1,
2
2
2
2
entry 1), sodium hypochlorite (NaOCl; Table 1, entry 2),
and tert-butyl hydrogen peroxide (TBHP; Table 1, entry 3)
all resulted in low to moderate conversion in the oxidation
of 1-phenylethanol (2a) at 408C. Furthermore, significant
gas evolution could be observed from the reaction mixture
when using these oxidants. The most probable reason
seemed to be a disproportionation reaction of the oxidants,
which led to the evolution of molecular oxygen. A sub-
stantial decrease in pH (from pH 6 to 1) could also be ob-
served during these reactions. This suggests that water oxi-
dation could be a competing reaction, since it would involve
2
[
changed conditions as in [a].
as oxidant. However, when TBHP was used, the difference
between complex 1 and RuCl in the oxidation of 1-phenyle-
thanol (2a) was found to be small. This can be explained by
complex 1 being more efficient in catalyzing the dispropor-
tionation of TBHP than RuCl , which negatively affects its
efficiency towards alcohol oxidation. However, when the ox-
idant is changed to the more stable Oxone that is less prone
to undergo disproportionation, a significant difference in ef-
3
[9]
3
an attack by H O on an intermediate metal–oxo species, ul-
2
timately generating molecular oxygen and protons. Howev-
er, in the case of TBHP, the disproportionation reaction
turned out to be slower. It was therefore possible to obtain
higher conversions by adding the TBHP over one hour and
slightly modifying the catalyst/oxidant loadings (see below).
TBHP is inexpensive, has high oxygen availability, and the
byproduct tert-butanol formed from the reaction can be
easily separated from the product by evaporation. These ad-
vantages have led to the development of a wide variety of
catalytic systems for the oxidation of alcohols that employ
ficiency between 1 and RuCl can be observed. To further
3
prove this difference in efficiency, the reaction was also per-
formed at room temperature. This resulted in a conversion
of 48% after 1 h when using 1, compared with 7% conver-
sion when using RuCl . This difference in efficiency also
holds true when comparing complex 1 and RuCl in the re-
action of the slower-reacting aliphatic alcohol, 2-octanol
(not shown in Table 2). Performing the reaction under
standard conditions at room temperature with 1 gave a con-
version of 47% after 2 h, compared with 6% with RuCl3.
For further studies of the substrate scope, we decided to
investigate both TBHP and Oxone as terminal oxidants.
3
3
[10]
TBHP as stoichiometric oxidant.
Employing iodosobenzene resulted in quantitative conver-
sion after 4 h (Table 1, entry 4). However, from an economic
and environmental point of view, the use of iodosobenzene
is undesirable. Interestingly, the best result was obtained
with Oxone (2 KHSO ·KHSO ·K SO triple salt), which re-
Oxidation using TBHP as stoichiometric oxidant: After fur-
ther optimizations of the reaction conditions with TBHP as
oxidant, we found the optimal amount of this oxidant to be
6 equivalents. The scope of the reaction was investigated,
and the results are summarized in Table 3. Aryl methyl alco-
hols 2a–8a (Table 3, entries 1–7) with varying electronic
properties proved to be readily oxidized to their correspond-
ing ketones by using this system. The bulkier cyclohexyl
phenyl carbinol (9a; Table 3, entry 8) was also tolerated by
this system, but the reaction was found to be slow, thereby
resulting in a lower yield. The a-hydroxycarbonyl compound
10a (Table 3, entry 9) and the naphthyl compound 11a
(Table 3, entry 10) were also oxidized in good to high yields.
We were also interested in investigating whether the pro-
tocol allowed for the oxidation of primary alcohols (Table 3,
entry 11) and whether it was possible to obtain selectivity
towards either the aldehyde or the carboxylic acid. Unfortu-
nately, the reaction displayed poor selectivity when using
5
4
2
4
sulted in quantitative conversion after only 2 h (Table 1,
entry 5). Furthermore, in the reactions in which Oxone was
employed, gas evolution was less pronounced than with
other oxidants (see below).
Oxone is an attractive oxidant owing to its high stability,
simple handling, and low cost. It has been well studied in
the literature as an oxidant for the Shi epoxidation reac-
[
11]
[12]
[13]
tions; cleavage of alkenes and alkynes to ketones and
[14]
carboxylic acids; a-hydroxylation of aryl alkyl ketones;
and in the oxidation of tertiary amines to the corresponding
nitrones. However, the examples of Oxone-based proto-
cols for the oxidation of alcohols are scarce.
[15]
To prove that Ru complex 1 is responsible for the catalyt-
ic activity, control experiments with various oxidants were
carried out in its absence. All control experiments exhibited
no or minor conversions (<10%). The reaction was also
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Studies of a Water-Oxidation Catalyst
FULL PAPER
Table 3. Ruthenium-catalyzed oxidation of alcohols into carbonyl com-
pounds by using TBHP as the oxidant.
Oxidation using Oxone as stoichiometric oxidant: Since the
disproportionation reaction appeared to be significantly
slower for Oxone, it was possible to use fewer equivalents of
oxidant than in the TBHP protocol. After optimization of
the reaction conditions, it was found that 3 equivalents of
Oxone and 0.75 mol% of complex 1 was enough for an effi-
cient oxidation in short reaction times. As shown in Table 4,
aryl methyl alcohols, both electron rich and electron poor,
were efficiently oxidized to their corresponding ketones in
[
a]
[
b]
Entry
Substrate
Product
t [h] Yield [%]
[
c]
1
4
4
3
4
4
4
4
4
4
3
82 (76)
90
2
3
4
5
6
7
8
9
Table 4. Ruthenium-catalyzed oxidation of alcohols into carbonyl com-
pounds by using Oxone as the oxidant.[
a]
[c]
97 (90)
89
[
b]
Entry
1
Substrate
Product
t [h] Yield [%]
2
2
>99
>99
95
84
2
3
4
5
6
[c]
93 (89)
88
5
4
>99
82
69
10
5
5
43/38
22/78
[
d]
78
7
8
4
4
>99
1
0
88
99
4
4
28/59
9/80
[
d]
1
1
2
9
3
4
93
96
1
5
38
[
c]
[
a] Conditions: alcohol (0.26 mmol), 1 (0.75 mol%), TBHP (6 equiv),
10
CH Cl (2.0 mL), H O (2.0 mL, pH 6), 408C. [b] Determined by GC,
2
2
2
using dodecane as internal standard. [c] Isolated yield by column chroma-
tography. [d] TBHP (9 equiv) was used.
1
1
3
4
89
the standard conditions with 6 equivalents of TBHP. A
better selectivity was obtained by increasing the loading of
TBHP to 9 equivalents, which resulted in 80% conversion
to benzoic acid (12c). A drawback of this protocol is that it
does not work well with aliphatic alcohols. Hence alcohol
[
c]
12
>99
[
a] Conditions: Alcohol (0.26 mmol), 1 (0.75 mol%), Oxone (3 equiv),
CH Cl (2.0 mL), H O (2.0 mL, pH 6), 408C. [b] Determined by GC,
using dodecane as internal standard. [c] Decane as internal standard.
[d] 6 equivalents Oxone.
2
2
2
13a was not accepted by this system and the reaction stop-
ped at low conversation (Table 3, entry 12).
Chem. Eur. J. 2012, 18, 16947 – 16954
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16949

B. ꢁkermark et al.
excellent yields (Table 4, entries 1–3). However, in the case
of alcohol 11a (Table 4, entry 5), extended reaction times
were required to obtain acceptable yields of 2-acetonap-
thone (11b). The stability of Oxone also allowed for the ex-
tension of the protocol, towards aliphatic alcohols, which
were not readily accepted by the TBHP protocol. The linear
aliphatic alcohols 2-octanol (13a; Table 4, entry 7) and
TBHP. By contrast, only a minor evolution of oxygen could
be observed when using Oxone, thus suggesting that almost
no disproportionation reaction occurs in parallel with the al-
cohol oxidation. Measurements of the pH of the aqueous
layer revealed that the pH changed from 6 to 1 upon addi-
tion of Oxone to the reaction. The explanation of the high
stability of Oxone can probably be ascribed to its acidic
nature. It is well known that the oxidation potential for
water oxidation follows the Nernst equation, thus the oxida-
2-decanol (14a; Table 4, entry 8) were oxidized to the corre-
sponding ketones within 4 h. More sterically hindered aro-
matic (Table 4, entry 4) and aliphatic alcohols (Table 4, en-
tries 9–12) were also well tolerated by this protocol and the
corresponding ketones were obtained in high to excellent
yields. In the case of 17a, the formation of the Baeyer–
Villiger byproduct was observed, which led to a slight de-
crease in the yield of this reaction. The oxidation of primary
alcohols still proved to be difficult in terms of selectivity,
and resulted in mixtures of the aldehyde and carboxylic acid
tion potential of H O becomes significantly higher at lower
2
pH values, and it is believed that it can therefore not com-
pete with alcohol oxidation under highly acidic conditions.
Mechanistic studies: We believe that the catalytic cycle with
Ru complex 1 and peroxides involves the generation of Ru–
oxo intermediates through two-electron oxidation by
oxygen-atom transfer. Ru–oxo intermediates are well known
in the literature and are believed to be involved in several
(
Table 4, entry 6).
[16]
reactions, such as CÀH bond activation, epoxidation of al-
[17]
[8b,c,18]
[19]
Gas-evolution studies: To explain the difference in efficiency
between the different oxidants, a gas-evolution study was
performed by using mass spectrometry (Figure 1). H O ,
kenes, alcohol oxidations,
and water oxidation.
To gain insight into the mechanism of the oxidation, a ki-
netic study was performed to investigate how the initial rate
of the oxidation of 1-phenylethanol (2a) varied with varying
concentrations of 1. This was done by first mixing 2a
(0.26 mmol) with 0.25, 0.50, and 0.75 mol% of Ru complex
2
2
TBHP, and Oxone were chosen as oxidants for this study
since they displayed different efficiencies in the catalytic al-
cohol oxidation.
1
in CH Cl (2 mL) and then adding Oxone (3 equiv) dis-
2 2
solved in water (2 mL) at room temperature. From the plots
of initial rates versus catalyst concentration, it can be seen
that the reaction displays a first-order dependence on the
concentration of dimeric complex 1 (Figure 2). This would
suggest that the reaction proceeds by means of mono-oxy-
genation of the complex, which is subsequently cycled in the
reaction. Mono-oxygenation of catalyst 1 should produce a
III,V
IV,IV
Ru
complex that rapidly disproportionates to a Ru
complex, which consequently should be the active catalyst.
The kinetics of the dependence of the substrate were also
studied (Figure 3). By varying the concentration of the sub-
strate and plotting the initial rates versus the concentration
of the substrate, it was evident that the reaction also exhibit-
ed a first-order dependence on the substrate concentration.
This implies that the substrate is involved in the rate-deter-
mining step(s).
Figure 1. O
or Oxone as oxidants. Conditions: A deoxygenated solution of complex 1
1.0 mm) and 1-phenylethanol (0.13m) in CH Cl (0.50 mL) was added to
an aqueous solution of the oxidant (0.50 mL, 0.52m): *) no oxidant,
D) Oxone, !) H , and &) TBHP as oxidant.
2 2 2
evolution during alcohol oxidation when using H O , TBHP,
The electrochemistry of complex 1 was further studied by
cyclic voltammetry (CV). It was found that the oxidation of
(
2
2
III
IV
2
O
2
Ru to Ru occurs at approximately 0.9 V versus the
normal hydrogen electrode (NHE; Figure 4), whereas the
V
further oxidation to Ru that corresponds to the oxo
[7]
As expected, by means of mass spectrometry the gas
could be identified as oxygen. Both H O and TBHP, which
complex requires approximately 1.5 V. However, when
3
+
[Ru ACHTUNGTERNN(UNG bpy) ] (bpy=2,2’-bipyridyl) with an oxidation poten-
3
2
2
were less efficient than Oxone, gave rise to significantly
more oxygen evolution. However, the kinetics for the
oxygen evolution were different for the two oxidants. In the
case of THBP, a rapid generation of oxygen was observed,
which approached 20 mmol after just 10 min. With H O , on
the other hand, the evolution of oxygen was much slower,
but the release remained constant for a longer time (3–4 h)
and in the end approached the same amount as produced by
tial of approximately 1.2 V versus NHE was used as oxidant,
no alcohol oxidation could be observed. Since the potential
of [Ru ACHTUNGTRENN(UNG bpy) ] is only sufficient to convert 1 to the Ru
3
state, a mechanism that involves such species can therefore
be ruled out. In contrast, we favor a reaction path by which
complex 1 undergoes rapid and reversible dissociation into
two mononuclear species to form the iodide complex 1a and
the aqua complex 1b prior to the mono-oxygenation event.
3
+
IV,IV
2
2
16950
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Studies of a Water-Oxidation Catalyst
FULL PAPER
Figure 4. Cyclic voltammogram of complex 1 (0.1 mm) in CH
2
Cl
2
record-
À1
ed at a scan rate of 0.1 Vs with Bu
4
NPF
6
(0.1m) as supporting electro-
lyte, using a glassy carbon disk (diameter 3 mm) as the working elec-
trode, a platinum wire as counter-electrode, and Ag/AgNO
ence electrode.
3
as the refer-
This is supported by an earlier study performed on com-
plex 1 by MS that showed two major peaks of essentially
equal intensity, which corresponded to complexes 1a and
Figure 2. a) Kinetic plots for the oxidation of 1-phenylethanol (2a) into
acetophenone (2b) by complex 1 versus time. Conditions: An aqueous
solution of Oxone (0.39m, 2.0 mL) was added to a solution of 1 (0.33,
[7]
1b. It is then proposed that complex 1b is the mononu-
clear species that undergoes the subsequent mono-oxygena-
tion by the two-electron oxidant, since the aqua ligand is ex-
pected to be more rapidly displaced by the oxo group than
the iodide of complex 1a. Strong support for this mechanism
is derived from the fact that the formation of the relatively
0
.67 or 1.0 mm), 2a (130 mm), and dodecane (130 mm) in CH
2 2
Cl
(
2.0 mL). b) Initial rates for the formation of 2b plotted against concen-
tration of complex 1; ^) 0.17, &) 0.33, and ~) 0.50 mm.
V
labile Ru –oxo species 1c took place when treating a solu-
tion of Ru complex 1 in CH Cl with 5 equivalents of aque-
2
2
ous Oxone or TBHP (see the Experimental Section for fur-
ther details). The formation of complex 1c was established
by high-resolution mass spectrometry (HRMS), whereby a
major peak was detected at m/z 526.0211, which could be as-
V
signed to the mononuclear Ru –oxo complex 1c (Figure 5).
IV
It is noteworthy that no evidence for a corresponding Ru
species could be obtained by HRMS. To further support the
V
possibility of a mononuclear Ru –oxo species being the
active catalyst in the alcohol oxidation, we employed a mon-
onuclear ruthenium catalyst that bears a great resemblance
[20]
to 1b. To our delight, it was established that this mononu-
clear catalyst gave comparable results to that of dinuclear
complex 1 in the oxidation of 1-phenylethanol (2a) when
using Oxone as oxidant.
During the last few years, extensive studies of ruthenium-
catalyzed oxidation processes largely based on UV/Vis spec-
[8b,c,21]
troscopy have been conducted.
Therefore, the oxida-
tion of complex 1 was also spectrophotometrically moni-
tored by UV/Vis spectroscopy by subjecting it to 10, 20, and
3
0 equivalents of Oxone (Figure 6). The UV/Vis spectral ti-
tration of complex 1 upon oxidation of Oxone in an aqueous
medium resulted in a bleaching of the broad absorption in
the visible region. In these titrations, isosbestic points were
observed at 205 and 216 nm. However, the UV/Vis experi-
ment did not provide any unambiguous support for either
Figure 3. a) Kinetic plots for the oxidation of 1-phenylethanol (2a) into
acetophenone (2b) by complex 1 versus time. Conditions: An aqueous
solution of Oxone (0.39m, 2.0 mL) was added to a solution of 1 (1.0 mm),
2
2 2
a (65, 130, or 195 mm), and dodecane (130 mm) in CH Cl (2.0 mL).
IV
V
the generation of a Ru or a Ru species, since these spe-
b) Initial rates for the formation of 2b plotted against concentration of
substrate 2a; ^) 33, &) 65, and ~) 98 mm.
[21]
cies have similar absorption spectra.
Chem. Eur. J. 2012, 18, 16947 – 16954
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16951

B. ꢁkermark et al.
Figure 5. High-resolution mass spectra of the plausible active catalytic in-
V
termediate, Ru =O, obtained upon mixing catalyst
5 equiv; top) and calculated spectra (bottom).
1 with Oxone
(
It is also interesting to compare our results to those of
Meyer and co-workers, who recently studied the oxidation
II
of benzyl alcohol to benzaldehyde by using an Ru complex
Figure 6. UV/Vis spectral changes of ruthenium complex 1 as a function
of the addition of Oxone in H O. Conditions: Oxone (10, 20, 30 equiv)
2
was added to an aqueous solution of complex 1 (6.6 mm, 3.0 mL).
d) Complex 1 without any added oxidant, a) 10 equivalents Oxone
added, c) 20 equivalents Oxone added, b) 30 equivalents Oxone
added.
attached to a TiO electrode. They found that the stepwise
2
IV
two-electron oxidation yields a Ru –oxo complex, which is
the active catalyst for the reaction. At low pH, the poten-
tial for oxidation of Ru to Ru is approximately 1.2 V
versus NHE for Meyerꢃs complex. The further oxidation to
Ru of approximately 1.5 V versus NHE is fairly similar to
[8c]
II
III
IV
III
V
our potentials for the oxidation of Ru to Ru , which we
can only reach by two-electron oxidation with Oxone. A dif-
ference between our results is that Meyerꢃs complex selec-
tively oxidizes benzyl alcohol to benzaldehyde, whereas our
ruthenium complex 1 tends to give further oxidation to the
carboxylic acid. It is not clear if these results demonstrate
the occurrence of different mechanisms due to different spin
Conclusion
The water-oxidizing ruthenium complex 1 was successfully
employed in the oxidation of secondary alcohols by using a
variety of oxygen-transfer reagents. Of these, TBHP and
Oxone showed the most promising results and two different
oxidation protocols that involved 1 were developed. In the
case of TBHP, a competing disproportionation reaction was
observed, but this problem could be overcome by slow addi-
tion of the oxidant. The protocol was applied in the oxida-
tion of benzylic secondary alcohols to give the correspond-
ing ketones in good to high yields. When changing the oxi-
dant from THBP to Oxone, a more efficient protocol was
obtained, and the more stable oxidant Oxone allowed for an
extension of the scope towards aliphatic as well as sterically
hindered secondary alcohols. To explain the difference in re-
activity for the different oxidants, gas-evolution measure-
ments by mass spectrometry were conducted. Molecular
oxygen could be detected when H O and TBHP were used
V
states, or if our Ru –oxo species is a stronger oxidant than
IV
the corresponding Ru species.
Based on our result, we suggest a mechanism according to
Scheme 1, in which the dimeric Ru complex 1 reversibly dis-
sociates into the two mononuclear complexes 1a and 1b. It
is then assumed that, because of the coordinated iodide in
complex 1a, reaction with Oxone is much faster for complex
V
1
b, which gives the reactive Ru –oxo complex 1c. This is
then suggested to react with the alcohol substrate to give an
alkoxy complex 1d. After b-hydride elimination, the ketone
III
is formed together with a Ru –hydroxy complex 1e, which
regenerates complex 1b on protonation.
2
2
16952
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Chem. Eur. J. 2012, 18, 16947 – 16954

Studies of a Water-Oxidation Catalyst
FULL PAPER
silica-gel-coated plates with indicator (Merck, silica gel 60). Column
chromatography was performed on silica gel (Grace Division, Davsil,
0
.035–0.070 mm) if not mentioned otherwise. After chromatography the
1
fraction was pooled, evaporated to dryness, and dried under vacuum. H
and C NMR spectroscopy were recorded using a Bruker Avance spec-
trometer at 400 and 100 MHz, respectively. Chemical shifts are reported
1
3
in ppm relative to the residual solvent peak (CDCl
3 H
; d =7.26 ppm and
d
C
=77.0 ppm). GC analysis was performed using a Varian 3800 gas chro-
matograph with CP-Chirasil-Dex CB (25 mꢄ0.32 mmꢄ0.25 mm) column.
Identification of products by NMR spectroscopy and GC was done by
comparison to references of authentic samples obtained from commercial
suppliers. The UV/Vis absorption spectra were measured using a CARY
3
00 Bio UV/Vis spectrophotometer.
Electrochemistry: Cyclic voltammetry (CV) was measured using an Au-
tolab potentiostat with a GPES electrochemical interface (Eco Chemie)
with a glassy carbon disk (diameter 3 mm) as the working electrode, a
platinum wire as counter electrode, and Ag/AgNO
trode. The electrolyte used was 0.1m Bu NPF in CH
are versus NHE by using the Fc /Fc couple (0.630 V) as stand-
3
as the reference elec-
4
+
6
2
Cl . Potentials in
2
CH
2 2
Cl
ard.
General procedure for oxidation of alcohols using TBHP as oxidant:
Complex 1 (3.0 mg, 2.0 mmol), dodecane (44.3 mg, 0.26 mmol), and sub-
strate alcohol (0.26 mmol) were dissolved in a 1:1 mixture of CH
O (4 mL, pH 6). The reaction was heated to 408C and aqueous TBHP
70 wt%, 1.56 mmol) was added slowly over 1 h, after which the reaction
2 2
Cl /
H
2
(
was allowed to stir for the appropriate time. The reaction was followed
by removal of periodical aliquots for GC analysis, and the yield of the re-
action was determined against an internal standard (dodecane).
General procedure for oxidation of alcohols using Oxone as oxidant:
Complex 1 (3.0 mg, 2.0 mmol), dodecane (44.3 mg, 0.26 mmol), and sub-
Scheme 1. Proposed catalytic cycle for the oxidation of alcohols with
complex 1a and two-electron oxidants (L=4-picoline or tridentate
ligand).
strate alcohol (0.26 mmol) were dissolved in a 1:1 mixture of CH
(4 mL, pH 1). The reaction was heated to 408C and Oxone
0.78 mmol) was added, after which the reaction was allowed to stir for
2 2
Cl /
2
H O
(
an appropriate time. The reaction was followed by removal of periodical
aliquots for GC analysis and the yield of the reaction was determined
against an internal standard (dodecane).
as oxidants. With Oxone, on the other hand, only a minor
amount of oxygen was evolved. These results clearly demon-
strate the difference in the kinetics between the dispropor-
tionation of the oxidant and in the catalysis of alcohol oxi-
dation for the different oxidants. Furthermore, mechanistic
studies were carried out to gain insight into the mechanism
and to establish the identity of the catalytically active spe-
cies. These studies favored a path that proceeds by means of
a reversible dissociation of 1 into the iodo complex 1a and
the aqua complex 1b. Subsequent mono-oxygenation of spe-
Oxygen-evolution measurements: The mass spectrometer consisted of
three separate parts connected by gas valves: a reaction chamber, a gas
handling system (GHS), and a mass spectrometer (MKS Spectra Prod-
ucts, Microvision Plus, 0–100 mass units) in ultra high vacuum (base pres-
À10
sure 2ꢄ10 mbar). A rough pump was used to evacuate the GHS, so
the pressure can be regulated within 0.1–1000 mbar. By using this setup,
the enclosed volume in the reaction chamber was continuously probed by
the mass spectrometer by means of an inlet through the leak valve. The
change over time of the measured pressure of masses 0–100 in the mass
spectrometer was then converted to the amount in the enclosed volume
by calibrating the system. Any leakage of air could be continuously
V
cies 1b resulted in the formation of the Ru –oxo species 1c,
measured by mass spectrometry (by observing an increase in both O
).
A solution that consisted of complex 1 (1 mm) and 1-phenylethanol
0.13m) was prepared in CH Cl . This solution was then deoxygenated by
2
and
which could be detected by high-resolution mass spectrome-
try. It is proposed that this species plays a key role in the
catalytic mechanism of alcohol oxidation, and future work
will be dedicated to studying the mechanism in greater
detail with this catalyst and structurally similar ones (like
those in Ref. [20]). We believe that these results will be of
great value for the development and mechanistic under-
standing of future Ru catalysts in water oxidation as well as
in organic transformations.
N
2
(
2
2
bubbling with N2 for at least 15 min before being used in the experi-
ments. In a typical run, an aqueous solution of the oxidant (0.5 mL,
0
.52m) was placed in the reaction chamber and the reaction chamber was
evacuated with a rough pump. He (42 mbar) was then introduced into
the system. After a couple of minutes, the deoxygenated catalyst solution
(
0.50 mL) was injected into the reaction chamber. The generated oxygen
gas was then measured and recorded versus time by mass spectrometry.
Kinetic studies of catalytic alcohol oxidation:
Catalyst dependence: An aqueous solution of Oxone (0.39m, 2 mL) was
added to a CH Cl solution (2 mL) that contained complex 1 (0.33, 0.67,
2 2
Experimental Section
or 1.0 mm), alcohol 2a (130 mm), and dodecane (130 mm). The reactions
were performed at room temperature and were followed by removal of
periodical aliquots for GC analysis after 1–2 min by using dodecane as in-
ternal standard.
Materials and methods: All reagents were obtained from commercial
suppliers. They were of analytical grade or higher and were used without
further purification. Complex 1 was prepared as previously described.
The reactions were monitored by thin layer chromatography (TLC) using
[
7]
Substrate dependence: An aqueous solution of Oxone (0.39m, 2 mL) was
added to a solution of complex 1 (1.0 mm), alcohol 2a (65, 130 or
Chem. Eur. J. 2012, 18, 16947 – 16954
ꢂ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
16953

B. ꢁkermark et al.
1
95 mm), and dodecane (130 mm) in CH
2
Cl
2
(2 mL). The reactions were
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Published online: November 13, 2012
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