Efficient room-temperature oxidation of hydrocarbons mediated by tricopper cluster complexes with different ligands

Article abstract of DOI:10.1002/adsc.201200474

Six tricopper cluster complexes of the type [Cu^ICu ^ICu^I(L)]¹⁺ supported by a series of multidentate ligands (L) have been developed as oxidation catalysts. These complexes are capable of mediating the facile oxygen-atom transfer to hydrocarbon substrates like cyclohexane, benzene, and styrene (C ₆H₁₂, C₆H₆ and C₈H ₈) upon activation by hydrogen peroxide at room temperature. The processes are catalytic with high turnover frequencies (TOF), efficiently oxidizing the substrates to their corresponding alcohols, aldehydes, and ketones in moderate to high yields. The catalysts are robust with turnover numbers (TON) limited only by the availability of hydrogen peroxide used to drive the catalytic turnover. The TON is independent of the substrate concentration and the TOF depends linearly on the hydrogen peroxide concentration when the oxidation of the substrate mediated by the activated tricopper complex is rapid. At low substrate concentrations, the catalytic system exhibits abortive cycling resulting from competing reduction of the activated catalyst by hydrogen peroxide. This behaviour of the system is consistent with activation of the tricopper complex by hydrogen peroxide to generate a strong oxidizing intermediate capable of a facile direct "oxygen-atom" transfer to the substrate upon formation of a transient complex between the activated catalyst and the substrate. Some substrate specificity has also been noted by varying the ligand design. These properties of the tricopper catalyst are characteristic of many enzyme systems, such as cytochrome P450, which participate in biological oxidations. Copyright

Full text of DOI:10.1002/adsc.201200474

FULL PAPERS
DOI: 10.1002/adsc.201200474
Efficient Room-Temperature Oxidation of Hydrocarbons
Mediated by Tricopper Cluster Complexes with Different Ligands
Penumaka Nagababu,a Suman Maji,a Manyam Praveen Kumar,a Peter P.-Y. Chen,b
Steve S.-F. Yu,a,* and Sunney I. Chana,*
a
Institute of Chemistry, Academia Sinica, No. 128, Sec. 2, Academia Road, Nankang, Taipei 11529, Taiwan
Fax : (+886)-2-2783-1237; phone: (+886)-2-2789-8654; e-mail: sfyu@gate.sinica.edu.tw or sunneychan@yahoo.com
Department of Chemistry, National Chung Hsing University, 250 Kuo Kuang Road, Taichung 402, Taiwan
b
Received: May 30, 2012; Revised: August 15, 2012; Published online: November 13, 2012
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200474.
Abstract: Six tricopper cluster complexes of the type complex is rapid. At low substrate concentrations,
[CuICuICuI(L)]1+ supported by a series of multiden- the catalytic system exhibits abortive cycling result-
tate ligands (L) have been developed as oxidation ing from competing reduction of the activated cata-
catalysts. These complexes are capable of mediating lyst by hydrogen peroxide. This behaviour of the
the facile oxygen-atom transfer to hydrocarbon sub- system is consistent with activation of the tricopper
strates like cyclohexane, benzene, and styrene complex by hydrogen peroxide to generate a strong
(C6H12, C6H6 and C8H8) upon activation by hydrogen oxidizing intermediate capable of a facile direct
peroxide at room temperature. The processes are “oxygen-atom” transfer to the substrate upon forma-
catalytic with high turnover frequencies (TOF), effi- tion of a transient complex between the activated
ciently oxidizing the substrates to their correspond- catalyst and the substrate. Some substrate specificity
ing alcohols, aldehydes, and ketones in moderate to has also been noted by varying the ligand design.
high yields. The catalysts are robust with turnover These properties of the tricopper catalyst are charac-
numbers (TON) limited only by the availability of teristic of many enzyme systems, such as cytochrome
hydrogen peroxide used to drive the catalytic turn- P450, which participate in biological oxidations.
over. The TON is independent of the substrate con-
centration and the TOF depends linearly on the hy-
drogen peroxide concentration when the oxidation Keywords: C H activation; copper; epoxidation; ho-
of the substrate mediated by the activated tricopper mogeneous catalysis; hydroxylation
À
Introduction
Nature has optimized this process with time
through evolution to develop enzymes, which do the
À
À
Oxidation of unactivated C H, C C and C=C bonds job efficiently at ambient temperatures and pressures
in hydrocarbons is an important process in many ap- with high turnover frequency (TOF) and without or
plications, starting from the synthesis of fine chemi- minimal generation of undesirable by-products. Infor-
cals in synthetic organic chemistry to the industrial mation on the active site structure and function of en-
conversion of basic building block materials. The vast zymes, especially metalloenzymes, can help in the de-
reserve of naturally occurring hydrocarbons and basic velopment of efficient “bioinspired” catalysts with
synthetic hydrocarbons can be transformed to useful high TOF even at ambient conditions and with
oxygenated derivatives and feedstocks through hy- chemo- or regiospecificity and stereoselectivity.[15]
droxylation, epoxidation, or degradation of intermedi- These designed catalysts could be tuned to the need
ates.[1–4] Catalytic processes[5] can offer a quick, eco- of a specific substrate or scale of production, and will
nomical, and environmentally friendly way over the find applications in the development of environmen-
conventional methods[6] that use high valent metal tally friendly catalytic processes, where there is the
ions like permanganate or dichromate to accomplish specific need to avoid undesirable by-products, use of
the oxidation.[7–9] Towards this end, a number of effi- expensive and potentially toxic metal reagents, oxi-
cient copper-based oxidation catalysts has been re- dants, and solvents, and the reduction of high-energy-
ported in recent years.[10–14]
consuming multiple steps.[16]
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Particulate methane monooxygenase (pMMO) is to the formation of the dead-end product [CuIICuII
ACHTUNGTRENNUNG(m-
a membrane-bound enzyme that oxidizes methane to O)CuII(L)]2+,[21] multi-turnovers are possible when
methanol in methanotrophic bacteria with ease even H2O2 is employed as the oxidant. H2O2 is also a reduc-
under ambient conditions. We have proposed, based tant and we have demonstrated that the “spent” tri-
on evidence derived from biochemical/biophysical copper catalyst is efficiently re-reduced by H2O2 to re-
data,[17–19] that the enzyme contains a CuICuICuI clus- generate the [CuICuICuI(L)]1+ catalyst for successive
ter and dioxygen activation of this tricopper cluster cycles until the H2O2 in the solution is exhausted.[22]
ACTHNUTRGNEUNG
produces a mixed-valence [CuIICuII(m-O)2CuIII(L)]1+ Hydrogen peroxide is the most useful oxygen source
intermediate, which harnesses a highly reactive “sin- for homogeneous catalysis.[23] It can oxidize organic
À
glet oxene” for facile concerted insertion into C H compounds with an atom efficiency of 47% generat-
and C=C bonds during the hydroxylation of simple al- ing water as the only co-product and is relatively
kanes and epoxidation of small alkenes, respectively.
cheap. Thus, our tricopper complexes offer an oppor-
Inspired by this suggestion, two [CuICuICuI(L)]1+ tunity to evaluate their potential as oxidation catalysts
tricopper complexes based on the multidentate li- for hydrocarbons under economically viable and envi-
gands
(dimethylamino)ethyl]
Me) and 3,3’-(1,4-diazepane-1,4-diyl)bis(1-{[2- six additional tricopper clusters that are capable of
(diethylamino)ethyl](ethyl)amino}propan-2-ol) (7-Et) mediating facile conversion of organic substrates like
have been developed and demonstrated to facilitate cyclohexane (C6H12), benzene (C6H6), and styrene
(L)
3,3’-(1,4-diazepane-1,4-diyl)bis(1-{[2- ronmentally friendly conditions.
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
À
À
facile O-atom insertion into C H and C C bonds of (C8H8) to their corresponding alcohols, ketones, alde-
small organic substrates such as benzil, 2,3-butane- hydes and epoxides at room temperature with high
dione and CH3CN under mild conditions.[20] On the turnover frequencies.
basis of experiments using isotopically labeled oxygen
(18O2) together with the examination of ESI-MS data
on product distributions, it has been confirmed that Results and Discussion
the reaction proceeds according to a mechanism that
involves concerted insertion of the harnessed “singlet Ligand Design
oxene”.
1
Oxene in its D singlet state is a powerful oxidizing The ligand environment of the tricopper complex af-
agent, but it is not the isolated naked “oxene” that is fects the formation or stability of the activated tricop-
À
À
inserted into C H and C C bonds here. Rather the per complex as well as the approach of the substrate
“singlet oxene” is “harnessed” by the activated tricop- towards the active site of the catalyst. For productive
per complex and it is transferred in the transition oxo transfer, the substrate must form at least a weak
state during the reaction between the activated transient complex with the catalyst to reach the ap-
ACHTUNGTRENNUNG
[CuIICuII(m-O)2CuIII(L)]1+ intermediate and the sub- propriate transition state. For this reason, the tricop-
strate molecule. By design, the mixed-valence activat- per complexes assembled by 7-Me and 7-Et are de-
ed tricopper complex is created in an overall “singlet” signed to allow the b-dicarbonyls of benzil or 2,3-but-
state and the chemistry that ensues with the substrate
ACHTUNGTRENaNUNG nedione to interact with the two copper ions at the
proceeds over a “singlet” potential surface. This con- base of the triad to facilitate “O-atom” insertion
À
servation of the overall spin-state of the system across the central C C bond in these b-diketones.
during the reaction pathway is important as it facili- Similarly, the CH3CN coordinates weakly to these
tates the concerted insertion of the oxene (Scheme 1). copper ions, which allows the methyl group to ap-
Although only a single turnover is usually observed proach the “harnessed” oxene provided that there is
with these complexes in the presence of oxygen due no steric hindrance from the alkyl substituents at-
tached to the base of the tricopper complex.[20]
In this study, new ligands have been synthesized
with different donor atoms (N, O, and S) and steric
environments around the active site of the tricopper
complexes for oxidation of hydrocarbons (Figure 1).
The apical copper in the tricopper complexes with the
new ligands 7-Dipy, 7-Ethppz, 7-Mehppz, 7-Bn, 7-
Thio and 7-Morph shares the same environment as 7-
Me and 7-Et, with two neutral amines and two hy-
droxy groups. However, the steric environment and
Scheme 1. Facile “singlet oxene” transfer to methane from
molecular surface surrounding the two basal coppers
are designed to suppress the coordination of CH3CN
(solvent) and to promote van der Waals interactions
a dioxygen-activated tricopper cluster in the singlet state to
form the transition state complex. › and fl denote “up” and
“down” directions of the electron spins.
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Efficient Room-Temperature Oxidation of Hydrocarbons Mediated by Tricopper Cluster Complexes
Figure 1. Ligands.
with hydrocarbon substrates. The ligands 7-Dipy, 7- Catalytic Oxidation of Substrates. Product
Ethppz, 7-Mehppz and 7-Bn provide amine nitrogens Distributions
along with the bridging hydroxy oxygens for coordina-
tion of the basal copper ions. In the case of 7-Thio To assess the efficacy and chemo- and/or regioselec-
and 7-Morph, there are coordinating sulfur or oxygen tivity of the various [CuICuICuI(L)]1+ complexes as
atoms from thioethers or ethers, in addition to the catalysts for hydrocarbon oxidation by H2O2, we have
amine nitrogens and bridging hydroxy oxygens. In any chosen three representative substrates C6H12, C6H6
case, all these various ligand scaffolds can trap three and C8H8. The thiomorpholine, morpholine, picolyl-
CuI ions to form an isosceles triad without the metal
ACHTUNGTRENaNGNU mine, ethylhomopiperazine, methylhomopiperazine,
sites becoming coordinately saturated except for sol- and benzyldimethylethylenediamine groups of 7-Thio,
vent molecules that might be readily displaced during 7-Morph, 7-Dipy, 7-Ethppz, 7-Mehppz, and 7-Bn, re-
activation of the complex by dioxygen.
spectively, are designed to provide a molecular sur-
face to facilitate the binding of different substrates
near the base of the triad of copper ions. Since the
substrate oxidation occurs via an inner-sphere mecha-
nism involving formation of a transient complex be-
tween the substrate and the activated tricopper com-
Reaction of the Tricopper Complexes with Dioxygen
and H2O2
As in our earlier work[20] with [CuICuICuI
and [CuICuICuI
tions of [CuICuICuI(L)]
7-Dip, 7-Ethppz, 7-Mehppz, and 7-Bn) in CH3CN at
(7-Me)]1+ plex, even the formation of a relatively weak complex
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
room temperature causes an instantaneous color and C8H8 by the tricopper complexes constructed
change from pale yellow to deep green in each case. with the new ligands are summarized in Figure 2. The
The spectroscopic features of the oxygen adducts are oxidation of these hydrocarbon substrates mediated
similar for all the [CuICuICuI(L)]1+ complexes (see by four of the tricopper complexes, [CuICuICuI(L)]1+
the Supporting Information). Typically, in the absence (L=7-Thio, 7- Morph, 7-Dipy, and 7-Ethppz), in the
ACTHNUTRGNEUNG
of substrate, only the [CuIICuII(m-O)CuII(L)]2+ oxygen presence of H2O2 as the O-atom source, has turned
adduct is formed.[21] The same results were obtained out to be extremely efficient (Scheme 2). To study the
with H2O2 as the oxidant. This outcome indicates that catalytic reaction, 200 equiv. of H2O2 from 35% aque-
H2O2 can also activate the [CuICuICuI(L)]1+ com- ous solution, 500 equiv. of substrate, and one equiv. of
ACTHNUTRGNEUNG
plexes to produce the [CuIICuII(m-O)2CuIII(L)]1+ inter- [CuICuICuI(L)]1+ were mixed together in CH3CN with
mediate. The two scenarios of activating the tricopper a total volume of 3 mL at room temperature and ex-
complexes, by dioxygen or H2O2, can be depicted by amined for 1 h. According to GC- MS analysis, the
the following chemical equations:
products consist of a mixture of cyclohexanol and cy-
clohexanone in roughly equal amounts in the case of
C6H12. With C6H6 as substrate, the products are
phenol and hydroquinone with the latter as the major
product. In the case of C8H8, the major product is
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benzaldehyde, with acetophenone and styrene oxide
(small or trace amounts, if any) as minor products
(Table 1). For all three substrates, the extent of prod-
uct formation varies with the starting level of H2O2
with the overall turnover numbers limited by the
H2O2 available. The distribution of products for each
of the three substrates is summarized in Table S1,
Table S2 and Table S3 in the Supporting Information.
Pathways of the Catalytic Oxidations
We have studied the time course of formation of the
products for each tricopper complex. The results for
ACTHNUTRGNEUNG
C6H6 catalyzed by [CuICuICuI(7-Thio)]1+ are summar-
ized in Figure 3. Based on these data, it is evident
that the reaction is completed within 30–45 min when
Figure 2. Product analysis after a 1 hr catalytic oxidation of
C6H6, C8H8 and C6H12 by H2O2 in CH3CN mediated by vari-
ous tricopper complexes at room temperature. The products
are given in equivalents produced. Reaction mixture:
500 equiv. of substrate, 200 equiv. of H2O2 and one equiv.
(24 mmol) of [CuICuICuI(L)]1+. As a control, with the com-
plex [CuACHTUNGTRENNUNG(CH3CN)4]ClO4 as the catalyst, only very low levels
of substrate oxidation are obtained, if any.
Scheme 2. The catalytic mechanism proposed for the activa-
tion of [CuICuICuI(L)]1+ by H2O2 to generate the [CuIICuII-
A
Figure 3. Time course of product formation in the catalytic
(m-O)2CuIII(L)]1+ for the oxidation of substrate A to the
ACTHNGUTERNNUG
turnover of the [CuICuICuI(7-Thio)]1+ complex during the
oxo-substrate B, followed by rearrangement to give product
C or further direct oxidation by H2O2 to produce D.
oxidation of C6H6 and C6D6 to the corresponding phenol
and hydroquinone by 200 equiv. of H2O2 at the start.
Table 1. Product formation (in equivalents) during catalytic oxidation of different substrates (500 equiv.) by tricopper com-
plexes (1 equiv.) in the presence of H2O2 (200 equiv.).
Ligands supporting tricopper complex
Products
Benzene oxidation
Styrene oxidation
Cyclohexane oxidation
7-Thio
7-Morph
7-Dipy
7-Ethppz
7-Mehppz
7-Bn
14
7.8
8
14.3
0.1
1.5
36
38.5
31
23
6
6.6
2.5
1.7
3
0.2
0.32
50
8.8
2
1.3
1.2
1.5
0.1
28
15
32.5
41.8
49.5
11.4
4.5
31.5
30.9
30
10
3.6
14.4
25.3
16.2
7.5
2.3
1.6
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Efficient Room-Temperature Oxidation of Hydrocarbons Mediated by Tricopper Cluster Complexes
mise that benzaldehyde results from the nucleophilic
attack of the epoxide by a molecule of H2O2. A
simple rearrangement of the epoxide would give ace-
tophenone, the other minor product. This scenario
predicts an H2O2 consumption of [4ꢁbenzaldehyde+
3ꢁ(styrene oxide+acetophenone)], in good agree-
ment with experiment.
The oxidation of C6H12 is straightforward, with cy-
clohexanol and cyclohexanone as the products. Based
on the consumption of H2O2, both steps of the oxida-
À
tion require insertion of an O-atom into the two C H
bonds, with the formation of cyclohexanone coupled
to the loss of an H2O molecule (Scheme 3). This sce-
nario predicts an H2O2 consumption of [3ꢁcyclohexa-
nol+6ꢁcyclohexanone)], in excellent accord with ex-
periment. It is interesting that the different tricopper
catalysts yield somewhat different distributions of cy-
clohexanol and cyclohexanone. Presumably the ob-
served product distributions reflect the different affin-
ity of the various tricopper catalysts for the two sub-
strates cyclohexane and cyclohexanol.
Scheme 3. Oxidation schemes for the various substrates.
the H2O2 is exhausted. The products formed in this
reaction are phenol and hydroquinone. The product
distribution is consistent with initial activation of the Catalytic Mechanism
p-system by cis-addition of an O-atom across one of
the C=C bonds followed by rapid 1,2 hydride shift re- From our earlier studies on the reactivity of the tri-
arrangement to form phenol (Scheme 3). We surmise copper complexes [CuICuICuI(L)]1+, L=7-Me and 7-
that this initial activation step involves O-atom trans- Et, as well as a recent in-depth study on the dioxygen
ACTHNUTRGNEUNG
fer from the mixed-valence [CuIICuII(m-O)2CuIII(L)]1+ chemistry of these complexes,[20,21] we have concluded
species, the intermediate that harnesses the highly re- that the catalytic reaction proceeds by way of a puta-
active “singlet oxene”. In the absence of the tricopper tive [CuIICuII(m-O)2CuIII(L)]1+ believed to be the
AHCTUNGTRENNUNG
complex, no phenol is detected under otherwise iden- active oxidizing species. This transient species trans-
tical conditions. Although resonance stabilization of fers the “singlet oxene” to the substrate in the transi-
the aromatic nucleus renders the benzene ring resist- tion state when it forms a bimolecular complex with
ant to oxidation, p-electron activation is more favora- the substrate. However, because of the high redox po-
ble than direct s-activation of one of the C H bonds. tential of the [CuIICuII
(m-O)2CuIII(L)]1+, it can also be
À
Evidently, hydroquinone is also derived from the p- readily deactivated by reduction with a molecule of
activated intermediate (Scheme 3), as phenol is not H2O2 present in the reaction mixture. This is an abor-
converted directly to hydroquinone by H2O2 over a 2- tive process that competes with productive transfer of
h period at room temperature without the tricopper the harnessed “singlet oxene” to a substrate molecule
catalyst. Finally, since activation of the [CuICuICuI
ACTHNUTRGNE(NUG 7- to form product. These competing processes can be
Thio)]1+ consumes three molecules of H2O2 per turn- described by the following two chemical equations:
over of the catalyst whereas the formation of the hy-
droquinone requires an additional H2O2, the total
amount of H2O2 consumed at any given time should
be given by [3ꢁphenol+4ꢁhydroquinone], in agree-
ment with experiment.
The oxidation of C8H8 mediated by the
[CuICuICuI(L)]1+ catalysts in the presence of H2O2 at
room temperature begins with epoxidation of the
C=C bond. The main product, however, is benzalde-
hyde, accounting for 75% of the H2O2 consumed over
the 45 min reaction (see Figure S8 in the Supporting
Information). A reaction scenario that is consistent
with the products and product distribution is given in
Scheme 3. First, styrene oxide is produced by epoxi-
Thus, unless k2 [substrate]=kOT [substrate]@kabortive
dation of styrene by the activated catalyst. We sur- [H2O2], abortive cycling will compete effectively with
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productive cycling. These two parallel reaction path-
ways consume H2O2 differently. In the oxidation of
cyclohexane, 3 equivalents of H2O2 will be consumed
during a productive cycle, two molecules of H2O2 to
activate the tricopper complex and another H2O2 mol-
ecule to regenerate the “spent” catalyst:
As expected, the regeneration of the “spent” cata-
lyst is the rate-limiting step, and the turnover frequen-
cies of the catalysts are found to depend linearly on
Figure 4. Total product formation (equiv.) as a function of
the starting substrate concentration determined after one
the H2O2 concentration with a second-order rate con- hour of incubation of the three substrates, C6H6, C6H12, and
C8H8, in the presence of l equiv. of the [CuICuICuI
ACHTUNGTRENNUNG(7-
stant of ca. 2ꢁ10À1 MÀ1 sÀ1 regardless of the catalyst or
the substrate. An abortive cycle will consume an addi-
tional H2O2 molecule. In effect the tricopper complex
is acting merely as a catalyst to disproportionate the
four molecules of H2O2 to produce two O2 and four
H2O. In practice, the two pathways are tightly linked,
Thio)]1+ complex and 200 equiv. of H2O2 at room tempera-
ture. The turnovers are H2O2-limited in these experiments,
except possibly at the lowest substrate concentrations
(below 50 equiv.).
with substrate oxidation predominating at very high the oxidation of C6H6 and C6D6 to their correspond-
substrate concentrations relative to the H2O2 concen- ing phenol and hydroquinone by 200 equiv. of H2O2
tration present in the reaction mixture, but abortive at the start are shown in Figure 3. Only a small H/D
cycling prevailing at high H2O2 and low substrate con- kinetic isotope effect (KIE) (kH/kD of ~1.5) is ob-
centrations.
served for the formation of the two products. At the
To test these ideas, we have studied the TON as concentration of C6H6 and C6D6 (500 equiv.) em-
a function of substrate concentration in the oxidation ployed in these experiments, it is evident that the
of C6H12, C6H6, as well as C8H8 by the [CuICuICuI
ACTHNUTRGNEUNG(7- overall process is rate-limited by regeneration of the
Thio)]1+ complex. The results obtained are shown in catalyst by H2O2 rather than by the kinetic steps lead-
Figure 4. In these experiments, the substrate concen- ing to the formation of the observed productÀs. Thus,
À
C
C D
tration has been varied from 20 equiv. to 500 equiv. the observed KIE must arise from kOT H/kOT
upon
À
with the turnover driven by an initial H2O2 concentra- deuterium substitution of the C H bond. An isotope
À
C
D
tion of 200 equiv. It is evident that the TON is essen- effect on TON is expected if kOT
[C6D6]0 becomes
tially independent of the substrate concentration comparable to kabortive [H2O2]0 under the conditions of
when the starting substrate concentration is greater our experiment, namely, [C6D6]0 =500 equiv. and
than 200 equiv. Presumably there is no abortive cy- [H2O2]0 =200 equiv. In case of C6H6, the onset of
cling of the catalyst at these substrate concentrations. abortive cycling does not become apparent until
However, the TON begins to fall off at lower sub- [C6H6]0 ꢀ100 equiv. Thus, theÀ KIE on the substrate
À
C
C
strate concentrations, and at [substrate]0 ꢀ100 equiv. oxidation, namely kOT H/kOT D, is not large, no more
the TON becomes ca. 50% of the maximum TON ob- than 5, which would rule out any mechanism involv-
served. A precipitous drop-off in the TON will be ing hydrogen abstraction from the hydrocarbon. This
manifested when kOT [substrate]ꢀkabortive [H2O2].
conclusion holds for cyclohexane as well as benzene.
The behavior of the catalytic system to varying
Another scenario where abortive cycling might
become evident is when the rate constant of “O- levels of H2O2 and C6H6, and to C6D6 is consistent
atom” transfer, namely, kOT, is reduced by isotope with a process in which the tricopper complex is acti-
À
substitution, as when the C H bond is replaced by vated by H2O2 to generate a transient intermediate
C D in the oxidation of cyclohexane or benzene. We capable of facile “O-atom” transfer to substrate
À
have examined the impact of the H/D isotope effect rather than a mechanism involving the participation
on the TON for both of these substrates when they of freely diffusing radical species produced by the re-
ACTHNUTRGNEUNG
are oxidized by the [CuICuICuI(7-Thio)]1+ complex. action between the tricopper complex and H2O2. In
The time courses of product formation in the catalytic support of this conclusion, no characteristic EPR sig-
turnover of the [CuICuICuI(7-Thio)]1+ complex during nals are detected in the presence of 5,5-dimethylpyr-
AHCTUNGTRENNUNG
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Efficient Room-Temperature Oxidation of Hydrocarbons Mediated by Tricopper Cluster Complexes
temperature was maintained at 1208C for the 10 min dura-
roline N-oxide (DMPO), a nitrone spin trap that be-
comes converted to the persistent nitroxide radical
with its distinctive EPR signal at room temperature in
the presence of COH or COOH.[24] If COOH radicals are
involved, the primary product would be cyclohexyl
hydroperoxide if the substrate is cyclohexane,[25] but
no evidence was found for any involvement of this hy-
droperoxide during the catalytic cycle of any of our
tricopper complexes.
tion of the analysis. The flow rate used was 1.9 mLminÀ1.
GC-MS analysis were carried out on an HP 6890 Plus (GC)
with HP 5973 (MS) analyzer equipped with a DB-1MS
column (60 mꢁ0.25 mmꢁ0.25 micron). Split injection was
conducted with split ratio of 35:1 and split flow 28 mLminÀ1
at an injector temperature of 3008C. The column tempera-
ture was maintained at 1208C for the 15 min duration of the
analysis. The flow rate used was 1.4 mLminÀ1.
Ligand Synthesis
The ligands (L) 3,3’-[1,4-diazepane-1,4-diyl]bis(1-thiomor-
pholinopropan-2-ol) (7-Thio), 3,3’-[1,4-diazepane-1,4-diyl]-
bis(1-morpholinopropan-2-ol) (7-Morph), 3,3’-(1,4-diaze-
Conclusions
In summary, we have demonstrated here that the tri-
copper cluster system is an active and robust oxida-
tion catalyst capable of mediating the efficient oxida-
tion of both aliphatics and aromatics at room temper-
ature. Our CuICuICuI complexes are the first catalysts
that can be activated by H2O2 to harness a “singlet
oxene” for direct transfer to a hydrocarbon substrate
upon complex formation.
pane-1,4-diyl)bis{1-ACTHNUTRGNEUG[N bis(pyridin-2-yl)methyl]amino}propan-2-
ol) (7-Dipy), 3,3’-(1,4-diazepane-1,4-diyl)bis[1-(4-ethyl-1,4-
diazepan-1,4-diyl)propan-2-ol] (7-Ethppz), 3,3’-(1,4-diaze-
pane-1,4-diyl)bis[1-(4-methyl-1,4-diazepan-1-yl)propan-2-ol]
(7-Mehppz), and 3,3’-(1,4-diazepane-1,4-diyl)bis{1-[2-benzyl-
(2-dimethylethylene)amino]propan-2-ol} (7-Bn) were syn-
thesized according to established procedures. Details on the
synthesis and characterization of the ligands are given in the
Supporting Information (Figure S1, Figure S2, and Fig-
ure S3).
Experimental Section
Formation of the Tricopper Cluster
The ligands (L) form [CuICuICuI(L)]1+ complexes in
General Remarks
CH3CN, as previously described for 7-Et and 7-Me.[20,21] The
All chemicals were purchased from commercial sources as
reagent grade quality and used as received unless stated oth-
erwise. Acetonitrile (CH3CN) was distilled under nitrogen
from CaH2 or P2O5; and stored in dried, N2-filled flasks over
4 ꢂ molecular sieves. Nitrogen was purged through these
solvents before use. Oxygen gas (99.8%, Fong Ming), used
for oxygenation, was dried by passing it through two short
columns in succession of P2O5 and Drierite. Manipulations,
reactions, and transfers were conducted under nitrogen ac-
cording to Schlenk techniques or in a glove box (nitrogen
gas).
ACTHNUTRGNEUNG
nuclearity of the [CuICuICuI(7-Dipy)]1+ complex was estab-
lished by electrospray ionization (ESI) mass analysis of the
[CuICuICuI
(7-Dipy)(CO)2A(CH3CN)2](X) complex formed by
purging CO into a solution of the [CuICuICuI
(7-Dipy)](X),
A
CHTUNGTRENNUNG
AHCTUNGTRENNUNG
X=BF4 or ClO4 in CH3CN (Supporting Information, Figure
1
S4A and B) and by H NMR.
Catalytic Oxidation of Substrates
We have carried out the catalytic oxidation of the substrates
benzene, styrene and cyclohexane with 50, 100, and
200 equiv. of H2O2 as 35% aqueous solution, 500 equiv. of
substrate, and one equiv of [CuICuICuI(L)]1+ (L=7-Thio, 7-
Morph, 7-Dipy, 7-Ethppz, 7-Mehppz and 7-Bn) in CH3CN
(total volume 3 mL) at room temperature for 1 h. According
to GC-MS analysis, the products consisted of a mixture of
cyclohexanol and cyclohexanone when cyclohexane was
used as the substrate. For benzene as substrate, we obtained
phenol and hydroquinone as products. For styrene, the
major product was benzaldehyde, with acetophenone and
styrene oxide as minor products. GC chromatograms are
shown for three starting H2O2 concentrations in the Sup-
porting Information (Figure S5A, B, and C). With benzene
as the substrate, peaks were observed at retention time (tR)
3.23 for the substrate (benzene), tR 4.76 min for phenol, and
tR 4.4 min for hydroquinone. For cyclohexane, GC peaks
were observed at tR 3.4, 4.1, and 4.2 min for cyclohexane, cy-
clohexanol, and cyclohexanone, respectively. In the case of
styrene, the GC peaks were at tR 4.2 min for the styrene sub-
strate, tR 4.9 min for benzaldehyde, tR 6.0 min for styrene
oxide, and tR 6.39 min for acetophenone. Nitrobenzene (tR
6.8 min) was used as an internal standard in all the GC ex-
periments. The extents of product formation with different
Physical Measurements
NMR spectra were recorded on a Bruker 400 spectrometer.
Chemical shifts (in ppm) were referenced either to an inter-
nal standard of Me4Si, or to the residual solvent peak. UV-
visible spectra were recorded on an HP 8453 diode array
spectrometer. Electrospray ionization (ESI) mass spectra
were collected on a Finnigan LCQ mass spectrometer
(Thermo Finnigan, San Jose, CA, USA). FAB mass spectra
were collected on a JMS 700 double focusing mass spec-
trometer (JEOL, Tokyo, Japan) with a resolution of 8000
(3000) (5% valley definition). For FAB mass spectra, the
source accelerating voltage was operated at 10 kV with a Xe
gun, using 3-nitrobenzyl alcohol (NBA) as the matrix. EPR
spectra were recorded on a Bruker E-500 spectrometer
equipped with a Bruker TE102 cavity. In the EPR experi-
ments, the sample temperature was maintained at 77 K by
using a liquid nitrogen finger Dewar. GC analyses were car-
ried out on an HP 6890 plus analyzer equipped with an HP5
column (60 mꢁ0.25 mmꢁ0.25 micron). Splitless injection at
an injector temperature of 2808C was used. The column
Adv. Synth. Catal. 2012, 354, 3275 – 3282
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3281

Penumaka Nagababu et al.
FULL PAPERS
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Table S2 and Table S3 (Supporting Information) for the
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