Aliphatic C-H bond activation initiated by a (μ-η2: η2-peroxo)dicopper(II) complex in comparison with cumylperoxyl radical

Article abstract of DOI:10.1021/ja809822c

A (μ-η²:η²-peroxo)dicopper(II) complex, [Cu₂(H-L)(O₂)]²⁺ (1-O₂), supported by the dinucleating ligand 1,3-bis[bis(6-methyl-2-pyridylmethyl)aminomethyl] benzene (H-L) is capable of initiating C-H bond activation of a variety of external aliphatic substrates (SH_n): 10-methyl-9,10-dihydroacridine (AcrH₂), 1,4-cyclohexadiene (1,4-CHD), 9,10-dihydroanthracene (9,10-DHA), fluorene, tetralin, toluene, and tetrahydrofuran (THF), which have C-H bond dissociation energies (BDEs) ranging from ～75 kcal mol^-1 for 1,4-CHD to ～92 kcal mol^-1 for THF. Oxidation of SH _n afforded a variety of oxidation products, such as dehydrogenation products (SH_(n-2)), hydroxylated and further-oxidized products (SH_(n-1)OH and SH_(n-2)=O), dimers formed by coupling between substrates (H_(n-1)S-SH_(n-1)) and between substrate and H-L (H-L-SH_(n-1)). Kinetic studies of the oxidation of the substrates initiated by 1-O₂ in acetone at -70°C revealed that there is a linear correlation between the logarithms of the rate constants for oxidation of the C-H bonds of the substrates and their BDEs, except for THF. The combination of this correlation and the relatively large deuterium kinetic isotope effects (KIEs), k₂^H/k₂^D (13 for 9,10-DHA, ?29 for toluene, and ～34 for THF at -70°C and ～9 for AcrH₂ at -94°C) indicates that H-atom transfer (HAT) from SH_n (SD_n) is the rate-determining step. Kinetic studies of the oxidation of SH_n by cumylperoxyl radical showed a correlation similar to that observed for 1-O₂, indicating that the reactivity of 1-O₂ is similar to that of cumylperoxyl radical. Thus, 1-O ₂ is capable of initiating a wide range of oxidation reactions, including oxidation of aliphatic C-H bonds having BDEs from ～75 to ～92 kcal mol^-1, hydroxylation of the m-xylyl linker of H-L, and epoxidation of styrene (Matsumoto, T.; et al. J. Am. Chem. Soc. 2006, 128, 3874).

Full text of DOI:10.1021/ja809822c

Published on Web 06/16/2009
Aliphatic C-H Bond Activation Initiated by a
(µ-η2:η2-Peroxo)dicopper(II) Complex in Comparison with
Cumylperoxyl Radical
Takahiro Matsumoto,† Kei Ohkubo,‡ Kaoru Honda,† Akiko Yazawa,†
Hideki Furutachi,† Shuhei Fujinami,† Shunichi Fukuzumi,*,‡ and Masatatsu Suzuki*,†
Department of Chemistry, DiVision of Material Sciences, Graduate School of Natural Science
and Technology, Kanazawa UniVersity, Kakuma-machi, Kanazawa 920-1192, Japan, and
Department of Material and Life Science, Graduate School of Engineering, Osaka UniVersity,
and SORST, Japan Science and Technology Agency (JST), Suita, Osaka 565-0871, Japan
Received December 17, 2008; E-mail: fukuzumi@chem.eng.osaka-u.ac.jp;
suzuki@cacheibm.s.kanazawa-u.ac.jp
Abstract: A (µ-η2:η2-peroxo)dicopper(II) complex, [Cu2(H-L)(O2)]2+ (1-O2), supported by the dinucleating
ligand 1,3-bis[bis(6-methyl-2-pyridylmethyl)aminomethyl]benzene (H-L) is capable of initiating C-H bond
activation of a variety of external aliphatic substrates (SHn): 10-methyl-9,10-dihydroacridine (AcrH2), 1,4-
cyclohexadiene (1,4-CHD), 9,10-dihydroanthracene (9,10-DHA), fluorene, tetralin, toluene, and tetrahy-
drofuran (THF), which have C-H bond dissociation energies (BDEs) ranging from ∼75 kcal mol-1 for 1,4-
CHD to ∼92 kcal mol-1 for THF. Oxidation of SHn afforded a variety of oxidation products, such as
dehydrogenation products (SH(n-2)), hydroxylated and further-oxidized products (SH(n-1)OH and SH(n-2)dO),
dimers formed by coupling between substrates (H(n-1)S-SH(n-1)) and between substrate and H-L
(H-L-SH(n-1)). Kinetic studies of the oxidation of the substrates initiated by 1-O2 in acetone at -70 °C
revealed that there is a linear correlation between the logarithms of the rate constants for oxidation of the
C-H bonds of the substrates and their BDEs, except for THF. The combination of this correlation and the
D
relatively large deuterium kinetic isotope effects (KIEs), k2H/k2 (13 for 9,10-DHA, J29 for toluene, and
∼34 for THF at -70 °C and ∼9 for AcrH2 at -94 °C) indicates that H-atom transfer (HAT) from SHn (SDn)
is the rate-determining step. Kinetic studies of the oxidation of SHn by cumylperoxyl radical showed a
correlation similar to that observed for 1-O2, indicating that the reactivity of 1-O2 is similar to that of
cumylperoxyl radical. Thus, 1-O2 is capable of initiating a wide range of oxidation reactions, including
oxidation of aliphatic C-H bonds having BDEs from ∼75 to ∼92 kcal mol-1, hydroxylation of the m-xylyl
linker of H-L, and epoxidation of styrene (Matsumoto, T.; et al. J. Am. Chem. Soc. 2006, 128, 3874).
Introduction
lecular oxidation reactions of the supporting ligands have
provided a fundamental chemical basis for the reactivity of the
Oxidation of organic substances by Cu2/O2 complexes such
as (µ-η2:η2-peroxo)dicopper(II) and bis(µ-oxo)dicopper(III) spe-
cies has attracted particular interest in biological systems and
industrial processes. Many well-defined Cu2/O2 complexes have
been developed using a variety of supporting ligands, and their
oxidation reactions, such as intramolecular aromatic and ali-
phatic ligand hydroxylation as well as intermolecular arene
hydroxylation, H-atom transfer (HAT), and oxo-transfer reac-
tions have been explored extensively (Scheme 1).1-7 Intramo-
Cu2/O2 complexes and their reaction mechanism. It has been
shown that some (µ-η2:η2-peroxo)dicopper(II) complexes have
an electrophilic nature capable of hydroxylating the arene groups
of the supporting ligands via an electrophilic aromatic substitu-
tion mechanism8-13 that is similar to that performed by
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† Kanazawa University.
(9) Pidcock, E.; Obias, H. V.; Zhang, C. X.; Karlin, K. D.; Solomon,
E. I. J. Am. Chem. Soc. 1998, 120, 7841–7847.
‡ Osaka University and SORST.
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9258 J. AM. CHEM. SOC. 2009, 131, 9258–9267
10.1021/ja809822c CCC: $40.75  2009 American Chemical Society

(µ-η2:η2-Peroxo)dicopper(II) Complex
A R T I C L E S
Scheme 1. Representative Oxidation Reactions Initiated by Cu2/O2 Complexes
Chart 1
tyrosinase.14 A similar arene hydroxylation reaction of a
supporting ligand was also reported for a bis(µ-oxo)dicopper(III)
complex.15 Extensive studies of the ligand oxidation reactions
by bis(µ-oxo)dicopper(III) complexes have also revealed that
they tend to activate aliphatic C-H bonds of the supporting
ligands.16-21
It has also been demonstrated that some distinct Cu2/O2
complexes can oxidize a variety of external substrates. Both
(µ-η2:η2-peroxo)dicopper(II) and bis(µ-oxo)dicopper(III) com-
plexes have been shown to oxidize external phenolates to the
corresponding catechols and/or quinones.22-26 Some kinetic
studies have shown that substrate binding to the copper center
is important, as observed for intramolecular hydroxylation
(proximity effect), and that the reactions also proceed via an
electrophilic aromatic substitution pathway. Cu2/O2 complexes
can also oxidize phenols to produce C-C coupling dimers.27-29
Detailed kinetic studies of the oxidation of a series of phenols
having various redox potentials by (µ-η2:η2-peroxo)dicopper(II)
and bis(µ-oxo)dicopper(III) complexes supported by the triden-
tate ligand LPy2-d2 and the bidentate ligand LPy1-d2 (Chart 1),
respectively, have revealed that the reactions proceed via proton-
coupled electron transfer (PCET, also known as CPET),30 in
contrast to those performed by cumylperoxyl radical (C), which
reacts via HAT.29
In contrast to such oxidation of phenols, intermolecular
oxidation reactions of aliphatic C-H bonds have been less well
demonstrated.31-37 It has been shown that a bis(µ-oxo)dicop-
per(III) complex with LPy1-d2 is capable of oxidizing 10-methyl-
9,10-dihydroacridine (AcrH2) and 1,4-cyclohexadiene (1,4-
(14) Yamazaki, S.; Itoh, S. J. Am. Chem. Soc. 2003, 125, 13034–13035.
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9
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A R T I C L E S
Matsumoto et al.
Chart 2
CHD) to 10-methylacridinium ion (AcrH+) and benzene,
respectively.31 In this case, however, a kinetic study suggested
that the reactive species was not a bis(µ-oxo)dicopper(III)
species but a (µ-oxo)(µ-oxyl radical)dicopper(III) complex
derived from a disproportionation reaction of two molecules of
the bis(µ-oxo)dicopper(III) complex or a tetranuclear copper-oxo
species.
Recently, hydroxylation of tetrahydrofuran (THF) to 2-hy-
droxytetrahydrofuran (2-OH-THF) by a series of (µ-η2:η2-
peroxo)dicopper(II) complexes having tridentate ligands R-Me-
PY2 (Chart 1) has been found,32,33b although they contain bis(µ-
oxo)dicopper(III) species to some extent.38 In these reactions,
THF binding to the copper center is also important. Unlike THF,
9,10-dihydroanthracene (9,10-DHA), which has a much lower
C-H bond dissociation energy (BDE ≈ 78 kcal mol-1)39,40 than
THF (BDE ≈ 92 kcal mol-1),41,42 is not oxidized by the
R-MePY2 complexes. This indicates that binding of the substrate
to the copper center is essential for C-H bond activation.
Detailed mechanistic studies, including mechanistic probe
experiments using N-cyclopropyl-N-methylaniline (CMA) and
(p-methoxyphenyl)-2,2-dimethylpropanol (MDP), have revealed
that there is a mechanistic change from PCET to HAT depending
upon the redox potential (E1/2) for a series of R-MePY2 Cu2/O2
complexes. Decreasing the thermodynamic driving force (i.e.,
E1/2) for substrate oxidation tends to facilitate the PCET process,
but a highly unfavorable ET process leads to the HAT
process.33b Unlike the R-MePY2 complexes, a series of the
closely related (µ-η2:η2-peroxo)dicopper(II) complexes having
similar tridentate ligands R-PYAN (Chart 1), which also contain
some amounts of bis(µ-oxo)dicopper(III) species, have been
shown to oxidize 9,10-DHA to anthracene.34
Very recently, oxidation of toluene (BDE ≈ 88 kcal mol-1)43
to benzaldehyde by a bis(µ-oxo)dicopper(III) complex bearing
the tetradentate tripodal ligand 6tBP (Chart 2) has been
reported.35,36 Similar oxidations of toluene initiated by a (µ-
1,2-peroxo)dicopper(II) complex with the anisole-containing
tetradentate tripodal ligand OL and a bis(µ-oxo)dicopper(III)
complex having the tridentate ligand BzL (Chart 2) have also
been reported.37 In the case of the (µ-1,2-peroxo)dicopper(II)
complex, some other unobservable Cu2/O2 species, such as a
bis(µ-oxo)dicopper(III) species, have also been proposed as
reactive intermediate(s). In addition to these oxidation reactions,
catalytic hydroxylation of cyclohexane, which has a high C-H
BDE (∼98 kcal mol-1) has also been reported in the reaction
of copper(II) complexes supported by the ꢀ-diketiminate ligands
R1,R2L [R1 ) CN, NO2; R2 ) H (Chart 2)] with H2O2 at room
temperature, where a bis(µ-oxo)dicopper(III) species was pro-
posed as an active species.44 Thus, it is of particular interest to
synthesize Cu2/O2 complexes that are reactive toward various
external organic substrates that have various BDEs and cannot
coordinate to the metal center.
We have previously reported that the (µ-η2:η2-peroxo)dicop-
per(II) complex [Cu2(H-L)(O2)]2+ (1-O2), supported by the
dinucleating ligand 1,3-bis[bis(6-methyl-2-pyridylmethyl)ami-
nomethyl]benzene (H-L), can hydroxylate the m-xylyl linker
of H-L via an electrophilic aromatic substitution mechanism,
as shown in Scheme 2.11,12 1-O2 can also epoxidize styrene via
electrophilic addition to the CdC bond and hydroxylate THF
by HAT.11 Although the structure of 1-O2 is not exactly known,
the structure of a closely related bis(µ-hydroxo)dicopper(II)
complex of H-L, ([Cu2(H-L)(OH)2]2+ (1-OH), suggests the
presence of a reaction cavity around the Cu2/O2 core that is
accessible to substrates (Scheme 3). Despite extensive studies
of the reactivity of (µ-η2:η2-peroxo)dicopper(II) complexes, there
has to date been no report on a (µ-η2:η2-peroxo)dicopper(II)
complex that can initiate the oxidation of the aliphatic C-H
bonds of external substrates having relatively large BDEs, such
as toluene.
(30) Although the terminology of PCET, CPET, and HAT is a matter of
discussion, in this work PCET (also referred to as CPET) and HAT
are used as proposed in the following papers: (a) Mayer, J. M. Annu.
ReV. Phys. Chem. 2004, 55, 363–390. (b) Mayer, J. M.; Rhile, I. J.;
Larsen, F. B.; Mader, E. A.; Markle, T. F.; DiPasquale, A. G.
Photosynth. Res. 2006, 87, 3–20. (c) Costentin, C.; Evans, D. H.;
Robert, M.; Save´ant, J.-M.; Singh, P. S. J. Am. Chem. Soc. 2005, 127,
12490–12491. (d) SI in: Manner, V. W.; DiPasquale, A. G.; Mayer,
J. M. J. Am. Chem. Soc. 2008, 130, 7210–7211. (e) Huynh, M. H. V.;
Meyer, T. J. Chem. ReV. 2007, 107, 5004–5064.
(31) Taki, M.; Itoh, S.; Fukuzumi, S. J. Am. Chem. Soc. 2001, 123, 6203–
6204.
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Kim, E.; Kaderli, S.; Incarvito, C. D.; Zuberbu¨hler, A. D.; Rheingold,
A. L.; Karlin, K. D. J. Am. Chem. Soc. 2003, 125, 634–635.
(33) (a) Shearer, J.; Zhang, C. X.; Hatcher, L. Q.; Karlin, K. D. J. Am.
Chem. Soc. 2003, 125, 12670–12671. (b) Shearer, J.; Zhang, C. X.;
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Karlin, K. D. Inorg. Chem. 2006, 45, 3004–3013.
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(36) Maiti, D.; Woertink, J. S.; Sarjeant, A. A. N.; Solomon, E. I.; Karlin,
K. D. Inorg. Chem. 2008, 47, 3787–3800.
We report herein the first extensive study of 1-O2-initiated
oxidation reactions of aliphatic C-H bonds of the external
substrates AcrH2, 1,4-CHD, 9,10-DHA, fluorene, tetralin,
toluene, and THF, which have C-H BDEs ranging from ∼75
(37) Lucas, H. R.; Li, L.; Sarjeant, A. A. N.; Vance, M. A.; Solomon,
E. I.; Karlin, K. D. J. Am. Chem. Soc. 2009, 131, 3230–3245.
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Karlin, K. D.; Solomon, E. I. J. Am. Chem. Soc. 1999, 121, 1870–
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9
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(µ-η2:η2-Peroxo)dicopper(II) Complex
A R T I C L E S
Scheme 2. Reactivity of [Cu2(H-L)(O2)]2+ (1-O2)
methods. All other reagents and solvents were commercially
available and used without further purification.
Physical Measurements. Electronic spectra were measured with
a Shimadzu Multispec-1500 photodiode array spectrometer with a
Unisoku thermostatted cell holder designed for low-temperature
experiments or an Otsuka Electronics MCPD-2000 photodiode array
spectrometer with an Otsuka Electronics optical-fiber attachment.
The temperature was controlled with the Unisoku thermostatted
cell holder for the former instrument and with an EYELA PSL-
1800 low-temperature pair stirrer for the latter one. 1H NMR spectra
were measured with a JEOL JNM-LM300 or JNM-LM400 instru-
ment using tetramethylsilane as an internal standard. GC-MS
analysis was performed on a Shimadzu GCMS-QP5050A GC-MS
instrument equipped with a fused silica capillary column (100%
dimethylpolysiloxane, 0.32 mm diameter × 25 m, QUADREX
Corp.). ESI-TOF/MS spectra were measured using a Micromass
LCT spectrometer.
Kinetics Measurements on 1-O2. The rates of 1-O2 decomposi-
tion in the presence of various concentrations of the external
substrates 1,4-CHD, 9,10-DHA, 9,10-DHA-d4, fluorene, tetralin,
toluene, toluene-d8, THF, and THF-d8 in acetone at -70 °C were
measured by monitoring the electronic spectral change at 351 nm
using the Otsuka Electronics MCPD-2000 photodiode array spec-
trometer with an Otsuka Electronics optical-fiber attachment (light
path length ) 1 cm). Complex 1 in acetone (0.026 mM, 19.75 mL)
in a three-neck flask (25 mL) at -70 °C was oxygenated by
bubbling of O2 for a few minutes to give dark-green 1-O2, after
which O2 was removed by gentle bubbling of N2 for ∼20 min.
Next, to the resulting solution was added a cold acetone solution
(100 mM, 0.25 mL) containing 9,10-DHA at -70 °C. In the case
of tetralin, toluene, and toluene-d8, the substrate was directly added
to an acetone solution of 1-O2; cold toluene and toluene-d8 were
quickly added by a cannulation method. The final concentrations
of 1-O2 and substrate are given in Table S1 in the Supporting
Information (SI). Pseudo-first-order rate constants kobs were deter-
mined by least-squares curve fitting using a microcomputer (Figures
S1 and S2 and Table S1 in the SI). Plots of kobs versus substrate
concentration were linear (Figure S3 in the SI), yielding the rate
equation V ) kobs[1-O2], in which kobs ) k1 + k2[substrate], where
k1 and k2 are the rate constants for self-decomposition (ligand
hydroxylation) of 1-O2 and substrate oxidation, respectively. The
self-decomposition rate constant of 1-O2 under the above conditions
was k1 ) (5.3 ( 0.1) × 10-5 s-1, which is in reasonable agreement
with the value 6.9 × 10-5 s-1 estimated from an extrapolation using
the activation parameters (∆Hq and ∆Sq).11 The reaction with
toluene-d8 in a 4.7 M toluene-d8/acetone solution yielded a very
small kobs value of 2.2 × 10-5 s-1, which is ∼2.5 times smaller
than the self-decomposition rate constant (k1) in acetone at -70
°C. This seems to be attributable to changes in the solvent properties
in going from acetone to the ∼1:1 toluene/acetone mixture.
Decomposition rates of 1-O2 in the presence of AcrH2 and AcrD2
in acetone at -94 °C were measured by monitoring the electronic
spectra at 351 nm using the Shimadzu photodiode array Multispec-
1500 spectrometer with 1 cm cell. Typically, 1 in acetone (0.050
mM, 3 mL) at -94 °C was oxygenated by bubbling of O2 into an
acetone solution of 1 for a few minutes, after which O2 was removed
by gentle bubbling of N2 into the solution for ∼20 min. To the
resulting solution was then added an acetone solution (63 mM, 0.050
mL) containing AcrH2 or AcrD2 (Figures S2 and S3 and Table S1
in the SI).
Scheme 3. Structure of [Cu2(H-L)(OH)2]2+ (1-OH)a
a Hydrogen atoms were placed at calculated positions (C-H ) 1.10 Å).
Color code: green, copper; red, oxygen; dark-blue, nitrogen; gray, carbon;
light-blue, hydrogen.
kcal mol-1 for 1,4-CHD41,45 to ∼92 kcal mol-1 for THF.41,42
We also studied the reactivity of cumylperoxyl radical (C)
toward this same series of substrates and found a striking
similarity between the reactivities of 1-O2 and C toward aliphatic
C-H bond activation of the external substrates. The present
study provides valuable mechanistic insights into C-H bond
activation initiated by “Cu2O2” species.
Experimental Section
Materials. Acetone used in the kinetics measurements was dried
over 4 Å molecular sieves and distilled under N2 before use. For
electrospray ionization-time of flight mass spectrometry (ESI-TOF/
MS) measurements, spectrophotometric-grade acetone (Sigma-
Aldrich) was used without further purification. 1,4-CHD was dried
over CaH2 and distilled under vacuum. 9,10-DHA, 9,10-DHA-d4,
and fluorene were recrystallized three times from EtOH under N2.
Tetralin was purified by washing with concentrated H2SO4 (20
times), water (three times), 10% NaHCO3 (three times), and water
again (three times) and then dried over Na2SO4 and 4 Å molecular
sieves under N2. Toluene and toluene-d8 were washed with cold
concentrated H2SO4 (once), water (three times), 10% NaHCO3
(three times), and water again (three times), after which they were
dried over MgSO4 and then distilled under N2 in the presence of
Na. AcrH2,46 [9,9′-2H2]-AcrH2 (AcrD2),47 9,10-DHA-d4,48 H-L, and
[Cu2(H-L)](PF6)2 (1)11 were synthesized according to literature
Kinetics Measurements on Cumylperoxyl Radical. Photoir-
radiation of an oxygen-saturated acetone solution containing di-
tert-butyl peroxide (1.0 M) and cumene (1.0 M) with a 1000 W
(46) Fukuzumi, S.; Ohkubo, K.; Tokuda, Y.; Suenobu, T. J. Am. Chem.
Soc. 2000, 122, 4286–4294.
(47) Fukuzumi, T.; Tokuda, Y.; Kitano, T.; Okamoto, T.; Otera, J. J. Am.
Chem. Soc. 1993, 115, 8960–8968.
(45) Burkey, T. J.; Majewski, M.; Griller, D. J. Am. Chem. Soc. 1986,
108, 2218–2221.
(48) Goldsmith, R. C.; Jonas, R. T.; Stack, T. D. P. J. Am. Chem. Soc.
2002, 124, 83–96.
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A R T I C L E S
Matsumoto et al.
Hg lamp resulted in the formation of C (g ) 2.0156), which was
detected at -70 °C using electron spin resonance (ESR) spectros-
copy. The g value was calibrated using an Mn2+ marker. When
the light was cut off, the decay of the ESR intensity was recorded
with time. The decay rate was accelerated by the presence of AcrH2,
AcrD2, 1,4-CHD, 9,10-DHA, 9,10-DHA-d4, fluorene, tetralin,
toluene, toluene-d8, THF, or THF-d8. The rate of HAT from the
external substrate (SHn) to C in each case was measured by
monitoring the decay of the ESR signal intensity in the presence
of various concentrations of SHn in acetone at -70 °C (-94 °C
for AcrH2 and AcrD2) (Figures S4 and S5 in the SI). Pseudo-first-
order rate constants were determined by least-squares curve fitting
using a microcomputer. The first-order rate law plots [ln(I - I∞)
versus t, where I and I∞ are the ESR intensity at time t and the
final intensity, respectively] were linear for three or more half-
lives, with correlation coefficients r > 0.99. Plots of the pseudo-
first-order rate constants against the substrate concentrations were
linear (Figure S6 and Table S2 in the SI).
benzaldehyde from benzyl alcohol was ∼90% (93 and 88%).
Oxidation of fluorene gave no fluoren-9-ol or fluoren-9-one, but
some amount of a coupling dimer was detected and tentatively
assigned on the basis of the GC-MS library and mechanistic
considerations. The amount was not determined because of the lack
of an authentic sample.
2. 18O2 Labeling Experiment for Toluene Oxidation. The
procedure was the same as that for the 16O2 experiment except for
the use of 18O2 (95%). The content of 18O in benzyl alcohol was
∼95% [18O-benzyl alcohol m/z (relative intensity): 110 (63, M+),
79 (100), 51 (34)]. The content of 18O in benzaldehyde was ∼40%
[18O-benzaldehyde m/z (relative intensity): 108 (34, M+(18O)), 106
(55, M+(16O)), 77 (100), 51 (64)]. The oxygen of 18O-benzaldehyde
was easily exchanged by adventitious H216O, which was confirmed
by the reaction of 16O-benzaldehyde with H218O.
3. Analysis of the Green Powders (Cu-P-SHn). The green
powders obtained in the above oxidation reactions of SHn (Cu-P-
CHD, Cu-P-DHA, Cu-P-Fluorene, Cu-P-Tetralin, and Cu-P-
Toluene) were subjected to ESI-TOF/MS measurements. All of
the ESI-TOF/MS spectra of acetone solutions of the green powders
suggested the presence of [Cu2(H-L)(OH)2]2+, [Cu2(H-L)(O-
H)(OCH3)]2+, and complexes involving coupling dimers of H-L
and SHn-1 (H-L-SH(n-1), designated as H-L-CHD, H-L-DHA, H-L-
Fluorene, H-L-Tetralin, and H-L-Toluene, respectively), together
with [Cu2(H-L-O)(OH)]2+ (where H-L-O is hydroxylated ligand
H-L) and some unidentified species in some cases (see below). The
presence of [Cu2(H-L)(OH)(OCH3)]2+ was due to methanol present
as an impurity in the spectrophotometric-grade acetone used.
4. Ligand-Recovery Experiments and Identification of H-L-
SH(n-1). We also tried ligand-recovery experiments for the oxidations
of 9,10-DHA and toluene. A green powder (Cu-P-Toluene) was
dissolved in CH3CN, and the solution was evaporated under a
reduced pressure to afford a green oily product, to which CHCl3
(20 mL) and concentrated aqueous ammonia (20 mL) were added
with stirring. Organic compounds were extracted with CHCl3 (3 ×
20 mL). The combined extracts were dried over Na2SO4, and CHCl3
was removed by evaporation under reduced pressure to give a
yellow oil. ESI-TOF/MS of an acetone solution of the oil revealed
the presence of a coupling dimer of H-L and SHn (H-L-SH(n-1)).
ESI-TOF/MS (acetone solution containing a small amount of
formic acid) m/z (relative intensity): H-L-Toluene: 324.2 (56) [M
+ 2H]2+, 647.3 (7) [M + H]+. H-L: 279.2 (100) [M + 2H]2+, 557.3
(24) [M + H]+. Hydroxylated ligand (H-L-OH): 287.2 (19) [M +
2H]2+, 573.3 (13) [M + H]+, and some unidentified signals as
shown in Figure S7 in the SI. In the case of DHA oxidation, both
H-L-DHA and its oxidized species were observed, the latter of
which seemed to be generated by the oxidation of H-L-DHA during
the workup procedure.
Oxidation of 1,4-CHD, 9,10-DHA, Fluorene, Tetralin, Toluene,
and Benzyl Alcohol by 1-O2. 1. Analysis of the SHn Oxidation
Products. Complex 1 (5 mM, 3.0 mL) in acetone at ca. -80 °C
was oxygenated by bubbling of O2 for a few minutes to give a
dark-green solution of 1-O2, after which O2 was removed by
bubbling of N2 for ∼20 min. To the resulting solution was added
an acetone solution of SHn [2 mL of 15 mM 1,4-CHD (2 equiv),
2 mL of 150 mM 9,10-DHA (20 equiv), 2 mL of 75 mM fluorene
(10 equiv), 2 mL of 750 mM tetralin (100 equiv), 3 mL of 9.4 M
toluene (∼1900 equiv), or 2 mL of 121 mM benzyl alcohol (∼15
equiv)]. After decomposition of 1-O2 at ca. -70 °C overnight, each
resulting solution was warmed to room temperature, and 10 mL of
hexane was added to precipitate a green powder (designated as Cu-
P-CHD for 1,4-CHD, Cu-P-DHA for 9,10-DHA, Cu-P-Fluorene
for fluorene, Cu-P-Tetralin for tetralin, or Cu-P-Toluene for
toluene). After the precipitate was removed by filtration and washed
[using 3:10 (v/v) acetone/hexane mixture for toluene or benzyl
alcohol or a 1:4 (v/v) acetone/hexane mixture for 9,10-DHA,
fluorene, or tetralin], a 3:10 (v/v) acetone/hexane solution of
2-bromo-m-xylene (15 mM, 500 µL) was added to the combined
filtrate and washings as an internal standard for GC-MS measure-
ments (except in the case of fluorene). The volume of the solution
was then adjusted to 25 mL by addition of 3:10 (v/v) acetone/
hexane and subjected to GC-MS analysis.
The GC-MS conditions [starting temperature (holding time),
heating rate (final temperature, holding time), He flow rate] and
results [retention time (m/z, ion)] were as follows: Benzene: 50 °C
(1 min), 30 °C/min, 77.6 mL s-1; 0.63 min (78, M+). Anthracene:
100 °C, 30 °C/min (220 °C), 84.8 mL s-1; 3.32 min (178, M+).
Fluoren-9-ol, fluoren-9-one, and 9H,9′H-[9,9′]bifluorenyl: 80 °C
(2.5 min), 5.0 °C/min (160 °C, 1 min) then 40 °C/min (300 °C, 5
min), 55.2 mL s-1; 16.62 min (180, M+) for fluoren-9-one, 16.80
min (182, M+) for fluoren-9-ol, and 24.39 min (330, M+) for
9H,9′H-[9,9′]bifluorenyl. 1,2,3,4-Tetrahydronaphthalen-1-ol and
1,2,3,4-tetrahydronaphthalen-1-one: 100 °C (2 min), 10 °C/min (130
°C, 1 min) then 40 °C/min (300 °C, 5 min), 55.3 mL s-1; 4.33 min
(148, M+) for 1,2,3,4-tetrahydronaphthalen-1-ol and 4.60 min (146,
M+) for 1,2,3,4-tetrahydronaphthalen-1-one. Benzaldehyde, benzyl
alcohol, and 1,2-diphenylethane: 40 °C (1 min), 5 °C/min (80 °C)
then 40 °C/min (220 °C), 50.0 mL s-1; 4.30 min (106, M+) for
benzaldehyde, 6.05 min (108, M+) for benzyl alcohol, and 11.80
min (182, M+) for 1,2-diphenylethane. Quantitative analyses of the
oxidation products were carried out by comparison with calibration
curves for authentic samples.
H-L-Toluene was isolated by silica gel column chromatography
(95:5 MeOH/CHCl3). 1H NMR (CDCl3, 400 MHz, ppm): 7.52-6.89
(21H, m, xyl-H, py-H, Tol-H), 3.79-3.77 (8H, m, NCH2py),
3.67-3.66 (4H, m, NCH2xyl), 3.10-3.00 (4H, m, pyCH2CH2Tol),
2.51-2.50 (9H, m, pyCH3) (see Figure S8a in the SI).
5. Quantitative Analysis of H-L-Toluene. The oil obtained by
the above ligand-recovery experiment was dissolved in a CDCl3
solution containing 2,6-dimethyl-1,4-benzoquinone (8.4 mM, 1 mL),
which was added as an internal standard. The amount of H-L-
Toluene was determined using 1H NMR by comparing the integra-
tion of the ethylene group of H-L-Toluene (3.0-3.1 ppm multiplet
signal) with that of 2,6-dimethyl-1,4-benzoquinone (6.5 ppm signal).
Yields of H-L-Toluene were ∼19 and ∼25% for two experiments.
1
On the basis of the H NMR data, H-L-OH was hardly formed
(see Figure S8b in the SI).
The yields (all based on 1-O2, two experiments in each case) of
benzene from 1,4-CHD and anthracene from 9,10-DHA were ∼40%
(41 and 39%) and ∼20% (22 and 19%), respectively. The yields
of benzyl alcohol, benzaldehyde, and 1,2-diphenylethane from
toluene were ∼17% (18 and 16%), ∼2% (2 and 2%), and ∼6% (7
and 6%), respectively. The yield of 1,2,3,4-tetrahydronaphthalen-
1-ol from tetralin was ∼19% (19 and 20%). The yield of
Results and Discussion
Oxidation of the External Substrates Initiated by 1-O2. Self-
decomposition of 1-O2 in acetone at -70 °C in the absence of
SHn followed first-order kinetics, resulting in almost quantitative
hydroxylation of the xylyl linker of H-L (Scheme 2). In the
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9262 J. AM. CHEM. SOC. VOL. 131, NO. 26, 2009

(µ-η2:η2-Peroxo)dicopper(II) Complex
A R T I C L E S
Scheme 4
[Cu2(H-L)(OH)(OCH3)]2+ (m/z 365.1), and [Cu2(H-L-O)(OH)]2+
(m/z 357.1), as shown in Figure 1a-c and Figure S9 in the SI.
A ligand-recovery experiment revealed that the yield of the
coupling dimer of the supporting ligand (H-L-Toluene) was
∼19-25% and that of the hydroxylated ligand (H-L-OH) was
negligible, as determined by 1H NMR (Figure S8a,b in the SI).
The total oxidation yield identified in this study was ∼50%,
and half of the oxidation equivalent could not be identified for
the oxidation of toluene.
Table 1. Products of SHn Oxidation Initiated by 1-O2
substrate
identified oxidation products (yield)a
1,4-CHD
benzene (∼40%), H-L-CHD
9,10-DHA
fluorene
tetralin
anthracene (∼20%), H-L-DHA
9H,9′H-[9,9′]bifluorenyl, H-L-Fluorene
1,2,3,4-tetrahydronaphthalen-1-ol (∼19%),
H-L-Tetralin
toluene
benzyl alcohol (∼17%), benzaldehyde (∼2%),
1,2-diphenylethane (∼6%), H-L-Toluene (∼22%)
2-OH-THF (62%)
THF
The oxidation of THF gave 2-OH-THF (∼62%),11 and no
measurable H-L-THF was detected. The oxidations of 1,4-CHD
and 9,10-DHA afforded benzene and anthracene in yields of
∼40 and ∼20%, respectively. ESI-TOF/MS of the correspond-
ing powders Cu-P-CHD and Cu-P-DHA revealed the formation
of coupling dimers of the methyl radical of H-L and the substrate
benzyl alcohol
benzaldehyde (∼90%)
a Yields are based on 1-O2. Reaction conditions are given in the
Experimental Section.
presence of SHn (AcrH2, 1,4-CHD, 9,10-DHA, fluorene, tetralin,
toluene, THF, and benzyl alcohol), decomposition of 1-O2 was
accelerated significantly. We investigated the oxidation products
of SHn in acetone at -70 °C (with [Cu2] ≈ 5 mM and 2 equiv
of 1,4-CHD, 20 equiv of 9,10-DHA, 10 equiv of fluorene, 100
equiv of tetralin, 100 equiv of THF, or ∼1900 equiv of toluene).
The oxidation products of SHn identified in this study are shown
in Scheme 4 and Table 1. Although the oxidation products have
yet to be fully identified, the combined results of the analysis
of the major oxidation products and the kinetic measurements
(see below) provide valuable insight into the reactivity of 1-O2.
Oxidation of toluene gave benzyl alcohol (∼17%), benzal-
dehyde (∼2%), and 1,2-diphenylethane (∼6%), which were
determined by GC-MS measurement. The oxygens of benzyl
alcohol and benzaldehyde came from dioxygen, which was
confirmed by the 18O2 labeling experiment. A separate experi-
ment involving the oxidation of benzyl alcohol ([Cu2] ≈ 5 mM,
15 equiv of benzyl alcohol) revealed that benzyl alcohol can
be oxidized to benzaldehyde in ∼90% yield. The ESI-TOF/
MS measurement of an acetone solution of the green powder
of Cu-P-Toluene (see the Experimental Section) isolated after
the oxidation reaction indicated the formation of a complex
involving the coupling dimer of the 6-methyl radical of H-L
and the methyl radical of toluene ([Cu2(H-L-Toluene)(OH)2]2+
(m/z 403.1) together with [Cu2(H-L)(OH)2]2+ (m/z 358.1),
Figure 1. ESI-TOF/MS spectra of an acetone solution of a solid sample
(Cu-P-Toluene) obtained after oxidation of toluene by 1-O2 at -70 °C: (a)
[Cu2(H-L)(OH)2]2+ (m/z 358.1); (a′) [Cu2(H-L)(OH)(OCH3)]2+ (m/z 365.1);
(b) [Cu2(H-L-Toluene)(OH)2]2+ (m/z 403.1); (b′) [Cu2(H-L-Toluene)-
(OH)(OCH3)]2+ (m/z 410.1); (c) [Cu2(H-L-O)(OH)]2+ (m/z 357.1). The
presence of OH and OCH3 was confirmed via replacement by OD and
OCD3, respectively, and the presence of the methoxo species was due to a
methanol impurity present in the spectrophotometric-grade acetone used.
IS denotes the internal standard [{CH3(CH2)3}4N+] (m/z 242.2848).
9
J. AM. CHEM. SOC. VOL. 131, NO. 26, 2009 9263

A R T I C L E S
Matsumoto et al.
Figure 3. Electronic spectral change for the reaction of 1-O2 (0.026 mM)
with 9,10-DHA (1.25 mM) in acetone at -70 °C under N2 (time interval
360 s). Inset: Decay time profile of the absorbance at 351 nm (curve) and
the pseudo-first-order plot (linear plot).
Figure 2. ESI-TOF/MS spectra of acetone solutions of the solid samples
(A) Cu-P-DHA and (B) Cu-P-Fluorene obtained after oxidation of 9,10-
DHA and fluorene, respectively, by 1-O2 at -70 °C: (a) [Cu2(H-L)(OH)2]2+
(m/z 358.1); (a′) [Cu2(H-L)(OH)(OCH3)]2+ (m/z 365.1); (b) [Cu2(H-L-
DHA)(OH)2]2+ (m/z 447.1); (b′) [Cu2(H-L-DHA)(OH)(OCH3)]2+ (m/z
454.1); (c) [Cu2(H-L-O)(OH)]2+ (m/z 357.1); (d) [Cu2(H-L-Fluorene)-
(OH)2]2+ (m/z 440.1); (d′) [Cu2(H-L-Fluorene)(OH)(OCH3)]2+ (m/z 447.1).
IS denotes the internal standard [{CH3(CH2)3}4N+] (m/z 242.2848).
radicals (H-L-CHD and H-L-DHA) more or less together with
H-L and H-L-OH, as shown in Figure 2A (also see Figures
S10A and S11A in the SI for Cu-P-CHD and Cu-P-DHA,
respectively). We tried to isolate H-L-DHA by silica gel column
chromatography. However, during the workup procedure, some
amount of H-L-DHA was oxidized to give an oxidized H-L-
DHA, as confirmed by ESI-TOF/MS measurements. Efforts
to reliably estimate their amounts by NMR measurement have
been in vain to date because of the coexistence of some
unidentified signals. The oxidation of fluorene gave no fluorene-
9-ol, judging from the GC-MS analysis, but a coupling dimer
of fluorene radicals (9H,9′H-[9,9′]bifluorenyl), which was
tentatively assigned on the basis of GC-MS analysis using the
GC-MS library, was found. Also, ESI-TOF/MS of Cu-P-
Fluorene revealed the formation of a coupling dimer of H-L
radical and fluorene radical (H-L-Fluorene) together with H-L
and a small amount of H-L-OH (Figure 2B). The oxidation of
tetralin afforded 1,2,3,4-tetrahydronaphthalen-1-ol (∼19%) and
a coupling dimer of H-L radical and tetralin radical (H-L-
Tetralin) (Figure S10B in the SI). Although the products have
yet to be fully characterized, all of the identified products suggest
the formation of C-H-bond-cleaved radicals, as indicated in
Scheme 4 and Table 1.
Kinetics of the Oxidation of the C-H Bond of External
Substrates Initiated by 1-O2. The oxidation reactions of the
external aliphatic substrates having various C-H BDEs by 1-O2
were also followed by the decomposition of 1-O2 monitored
via the electronic spectral change at 351 nm in acetone at -70
or -94 °C. The reactions obeyed first-order kinetics under the
conditions of a large excess of the substrates, and the pseudo-
first-order rate constants were proportional to the concentrations
of substrates (Figures 3 and 4 and Figures S1 and S2 in the
SI), yielding the rate law given in eq 1:
Figure 4. Plots of kobs vs the concentrations of 9,10-DHA and 9,10-DHA-
d4 for the reactions with 1-O2 in acetone at -70 °C.
with
kobs ) k1 + k2[substrate]
where kobs is the pseudo-first-order rate constant and k1 and k2
are the rate constants for self-decomposition of 1-O2 (hydroxy-
lation of the xylyl linker of H-L) and oxidation of the external
substrate, respectively. The self-decomposition rate constant for
1-O2 (k1) in acetone at -70 °C was determined as (5.3 ( 0.1)
× 10-5 s-1 in the absence of the substrate; this is in reasonable
agreement with the value of 6.9 × 10-5 s-1 estimated from an
extrapolation using previously reported kinetic activation pa-
rameters (∆Hq and ∆Sq).11 The second-order rate constants (k2)
for the oxidation of SHn were determined from the slopes of
plots of kobs versus SHn concentration (Figure 4, Table 2, and
Figure S3 and Table S1 in the SI). Thus, the oxidation reactions
proceed through a bimolecular process.
Notably, there is a correlation between the second-order rate
constants (k2) and the BDEs of SHn (see below). We also
H
D
measured the deuterium kinetic isotope effects (KIEs), k2 /k2 ,
and obtained values of 13 for 9,10-DHA/9,10-DHA-d4, >29 for
toluene/toluene-d8, and ∼34 for THF/THF-d8 at -70 °C and
∼9 for AcrH2/AcrD2 at -94 °C. Such large KIE values indicate
that the oxidation reactions proceed through the HAT process.
Kinetics of the Oxidation of the C-H Bonds of SHn by
Cumylperoxyl Radical (C). Cumylperoxyl radical is known to
be able to abstract a hydrogen atom from organic substrates
V ) kobs[1-O2]
(1)
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(µ-η2:η2-Peroxo)dicopper(II) Complex
A R T I C L E S
Table 2. Second-Order Rate Constants and Kinetic Isotope Effects (KIEs) for the Oxidations of SHn by the (µ-η2:η2-Peroxo)dicopper(II)
Complex (1-O2) and PhC(CH3)2OO· (C) Along with Bond Dissociation Energies (BDEs) of SHn
1-O2
C
SHn
k2 (M-1 s-1
)
KIE
k2C (M-1 s-1
)
KIE
BDE (kcal mol-1
)
refs for BDE
T (°C)
1,4-CHD
9,10-DHA
9,10-DHA-d4
fluorene
tetralin
toluene
toluene-d8
THF
THF-d8
AcrH2
AcrD2
AcrH2
AcrD2
9.0 ( 0.4
3.7
75 ( 2
78 ( 2
-
80 ( 2
85 ( 2
88 ( 2
-
92 ( 2
-
73.7 ( 1
-
41, 45
39, 40
-70
-70
-70
-70
-70
-70
-70
-70
-70
-94
-94
-70
-70
(2.19 ( 0.05) × 10-1
(1.7 ( 0.1) × 10-2
(2.85 ( 0.03) × 10-2
(2.2 ( 0.2) × 10-3
(9.9 ( 1.1) × 10-5
kobs ≈ 2.2 × 10-5 s-1
(1.2 ( 0.1) × 10-2
(3.5 ( 0.6) × 10-4
57 ( 6
13
9.6 × 10-1
1.2 × 10-1
1.3 × 10-1
2.0 × 10-2
3.2 × 10-4
∼8
39, 40
40-42
43
>29b
∼34
∼9
>4
a
c
<1 × 10-4
1.9 × 10-3
2.3 × 10-4
2.7
∼8.3
∼9
41, 42
49
6.6 ( 0.9
3.0 × 10-1
7.5 × 10
2.9 × 10
2.6
73.7 ( 1
-
a The value listed is kobs measured under the conditions [toluene-d8] ) 4.7 M and [1-O2] ) 2.6 × 10-5 M. b This KIE value was estimated by
comparing the kobs values of toluene (6.5 × 10-4 s-1) and toluene-d8 (2.2 × 10-5 s-1) measured under identical conditions ([toluene] or [toluene-d8] )
4.7 M and [1-O2] ) 2.6 × 10-5 M). The kobs of toluene-d8 was ∼2.5 times smaller than that of the self-decomposition of 1-O2 [k1 ) (5.3 ( 0.1) × 10-5
s-1] in acetone. This seemed to be attributable to changes in the solvent properties in going from acetone to the ∼1:1 acetone/toluene mixture. c The
value was too small to be determined accurately.
Figure 6. Plots of kCobs vs the concentrations of 9,10-DHA and 9,10-DHA-
Figure 5. Decay time course of the ESR intensity due to cumylperoxyl
d4 in the reactions with C in acetone at -70 °C.
radical in the reaction of C with 9,10-DHA (50 mM) in acetone at -70 °C
(curve) and the pseudo-first-order plot (linear plot).
such as phenols and N,N-dimethylanilines.29,50 In order to
the BDEs for SHn was observed (see below). The deuterium
KIEs were ∼8 for 9,10-DHA/9,10-DHA-d4, >4 for toluene/
compare the reactivity of 1-O2 with that of C, kinetics studies
toluene-d8, and 8.3 for THF/THF-d8 at -70 °C and ∼9 for
of the oxidation reactions of SHn by C were also performed
AcrH2/AcrD2 at -94 °C.
using the same series of SHn as employed for 1-O2. C was
generated by photoirradiation of an oxygen-saturated acetone
solution containing di-tert-butylperoxide and cumene with a
1000 W Hg lamp via a radical chain process, and C was readily
detected by ESR spectroscopy at low temperature.29,50 After
the light was cut off, the decay rates of C in the reactions with
SHn were monitored by the change in the ESR intensity of C,
as shown in Figure 5 and Figures S4 and S5 in the SI. In all
cases, the decay rates were much higher than those in the
absence of the substrates. The rates obeyed first-order kinetics
under the conditions of a large excess of SHn, and the pseudo-
first-order rate constants (kCobs) were linearly dependent on the
concentrations of SHn, as shown in Figure 6 and Figure S6 in
the SI. The second-order rate constants (kC2 ) for HAT from SHn
were determined from the slopes of the linear plots (Table 2
and Table S2 in the SI).
Comparison of the Reactivities of 1-O2 and C. As mentioned
already, both sets of second-order rate constants, k2 and kC2 ,
correlate well with the BDEs of the C-H bonds of the
substrates. For comparison of the observed second-order rate
constants with the BDEs of the SHn C-H bonds, the k2 and k2C
values were corrected to give k2c and kC2c by dividing k2 and kC2
by the number of hydrogen atoms of SHn that can be oxidized.
In each case, a good linear correlation between log k2c or log
kC2c and the BDEs of SHn except for THF (see below) was
observed, as shown in Figure 7. Such linear correlations have
been well-established for HAT reactions performed by not only
organic radicals but also metal complexes,30a,51 such as [MnVII
-
53
54
O4]-,52 [RuIV(O)(bpy)2(py)]2+
,
[FeIV(O)(N4Py)]2+
,
and
[FeIII(PY5)(OMe)]2+.48 The linear correlation observed for 1-O2
(51) Mayer, J. M. Acc. Chem. Res. 1998, 31, 441–450.
(52) Gardner, K. A.; Kuehnert, L. L.; Mayer, J. M. Inorg. Chem. 1997,
36, 2069–2078.
As in the case of the oxidation reactions initiated by 1-O2, a
good correlation between the second-order rate constants kC2 and
(53) Bryant, J. R.; Mayer, J. M. J. Am. Chem. Soc. 2003, 125, 10351–
10361.
(49) Zhu, X.-Q.; Li, H.-R.; Li, Q.; Lu, J.-Y.; Yang, Y.; Cheng, J.-P.
Chem.sEur. J. 2003, 9, 871–880.
(54) Kaizer, J.; Klinker, E. J.; Oh, N. Y.; Rohde, J.-U.; Song, W. J.; Stubna,
A.; Kim, J.; Mu¨nck, E.; Nam, W.; Que, L., Jr. J. Am. Chem. Soc.
2004, 126, 472–473.
(50) Fukuzumi, S.; Shimoosako, K.; Suenobu, T.; Watanabe, Y. J. Am.
Chem. Soc. 2003, 125, 9074–9082.
9
J. AM. CHEM. SOC. VOL. 131, NO. 26, 2009 9265

A R T I C L E S
Matsumoto et al.
Scheme 5
reported for the aromatic hydroxylation reactions mediated by
tyrosinase (-2.4 at 25 °C)14 and some synthetic peroxo and bis(µ-
oxo)dicopper(III) complexes (F ) -1.8 to -2.2).8b,22b,25 In
addition, 1-O2 is also capable of oxidizing p-R-styrenes to the
corresponding styrene oxides, where the Hammett F value at -60
°C was -1.9, which is the same as that for the above aromatic
ligand hydroxylation. Thus, 1-O2 can initiate a wide range of
oxidation reactions.
Figure 7. Plots of log k2c and log kC2c vs SHn BDE for the C-H bond
activation of SHn initiated by 1-O2 (red O) and C (black 0) in acetone at
-70 °C.
Possible Reaction Mechanism. It has been shown that some
bis(µ-oxo)dicopper(III) complexes are capable of oxidizing aliphatic
C-H bonds via HAT. Although no bis(µ-oxo)dicopper(III) species
was detected in the present reaction system by resonance Raman
spectroscopy,11 a small amount of bis(µ-oxo)dicopper(III) species
present in a pre-equilibrium (Scheme 5) may not be excluded as a
reactive species.
suggests that 1-O2 has enough space around the Cu2O2 moiety
to allow access of the external substrates irrespective of their
spatial demands.
It has been shown that the rate constants for HAT reactions
by a series of oxidants, including oxygen radicals (RO · ) such
as tert-butoxyl radical and sec-butylperoxyl radical30a,51 and
high-valent metal-oxo species such as [MnVIIO4]-,52
If this pre-equilibrium exists, two rate-determining steps are
possible. In the case of a slower equilibrium between (µ-η2:η2-
peroxo)dicopper(II) and bis(µ-oxo)dicopper(III) species and a large
k2′, the rate-determining step becomes the formation of bis(µ-
oxo)dicopper(III) species by O-O bond cleavage, and the observed
rate constant becomes kf. In this extreme case, the oxidation rate
is not dependent upon the concentration of the substrate and a large
KIE may not be observed. Itoh and co-workers have suggested
that such O-O bond cleavage of the (µ-η2:η2-peroxo)dicopper(II)
complex is involved as a rate-determining step for hydroxylation
of the aliphatic C-H bond of the supporting ligand.18 We tried to
study this possibility using 10-methyl-9,10-dihydroacridine (AcrH2)
as an oxidation substrate, since AcrH2 is much more readily
oxidized than the above substrates. The kinetic study at -94 °C
showed that the reaction rate was significantly accelerated (k2 ≈
5.7 × 10 M-1 s-1) and that kobs remained proportional to the
concentration of AcrH2. In addition, a relatively large KIE (∼9)
was observed. Thus, there is no indication of a slow equilibrium
between (µ-η2:η2-peroxo)dicopper(II) and bis(µ-oxo)dicopper(III)
species in the present system. However, definitive proof of the
nonexistence of a fast equilibrium between (µ-η2:η2-peroxo)dicop-
per(II) and bis(µ-oxo)dicopper(III) species has yet to be obtained.
In contrast to the copper complex, we very recently found that a
bis(µ-oxo)dinickel(III) complex supported by H-L can be generated
in the reaction of a bis(µ-hydroxo)dinickel(II) complex with H2O2
and can also hydroxylate the xylyl linker of H-L.58 Easy access to
the bis(µ-oxo)dinickel(III) species by O-O bond cleavage is due
to a higher d-orbital energy of the nickel complexes compared with
the corresponding copper complexes.59 It has also been found that
the bis(µ-oxo)dinickel(III) complex has no reactivity toward
styrene.
53
55
[RuIV(O)(bpy)2(py)]2+
,
and [MnIII,VI2(O)2(phen)4]3+
,
also
correlate with the BDEs of the O-H bonds formed by those
oxidants. A remarkable similarity between the linear cor-
relations observed in the oxidation reactions initiated by 1-O2
and C suggests that they have a similar reactivity and that
the BDEs of the O-H bonds formed by the oxidants [i.e.,
the BDEs of the O-H bonds of a putative CuII(µ-OH)(µ-
O)CuIII species (see below) and cumene hydroperoxide] are
comparable.
As mentioned already, the oxidation reactivity of THF with both
1-O2 and C is significantly higher than that of toluene. Such higher
reactivity of THF, despite the larger BDE of THF (∼92 kcal mol-1)
than of toluene (∼88 kcal mol-1), has also been reported for HAT
by tert-butoxyl radical, with a larger rate constant for THF (7.4 ×
106 M-1 s-1) than for toluene (1.9 × 105 M-1 s-1) at 298 K.56 It
has been suggested that there is a pronounced stereoelectronic effect
resulting in higher reactivity toward abstraction from those C-H
bonds adjacent to oxygen that have a relatively small dihedral angle
(∼30°) with respect to the p-type orbital on the oxygen, such as in
THF.57
As mentioned earlier, 1-O2 is also capable of hydroxylating the
m-xylyl linker of H-L. The kinetic study of the hydroxylation of a
series of the para-substituted m-xylyl linkers of [Cu2(R-L)(O2)]2+
(R ) MeO, t-Bu, H, and NO2) showed a Hammett F value of -1.9
at -50 °C, indicating that the reactions proceed via an electrophilic
aromatic substitution mechanism, which is consistent with the lack
of a KIE by deuterium substitution at the hydroxylated position
and 1,2-methyl migration upon the self-hydroxylation of the (µ-
η2:η2-peroxo)dicopper(II) complex [Cu2(Me2-L-Me)(O2)]2+ (Me2-
L-Me
) 1,3-bis[bis(6-methyl-2-pyridylmethyl)aminomethyl]-
2,4,6-trimethylbenzene).11,12 Similar F values have also been
The oxidation of the external substrates afforded not only
oxidized substrates (SH(n-1)OH, SH(n-2)dO, SH(n-2), and/or
H(n-1)S-SH(n-1)) but also the coupling dimers of H-L and SHn
(55) Larsen, A. S.; Wang, K.; Lockwood, M. A.; Rice, G. L.; Won, T.-J.;
Lovell, S.; Sad´ılek, M.; Turecˇek, F.; Mayer, J. M. J. Am. Chem. Soc.
2002, 124, 10112–10123.
(56) Finn, M.; Friedline, R.; Suleman, N. K.; Wohl, C. J.; Tanko, J. M.
J. Am. Chem. Soc. 2004, 126, 7578–7584.
(58) Honda, K.; Cho, J.; Matsumoto, T.; Roh, J.; Furutachi, H.; Tosha, T.;
Kubo, M.; Fujinami, S.; Ogura, T.; Kitagawa, T.; Suzuki, M. Angew.
Chem., Int. Ed. 2009, 48, 3304–3307.
(57) (a) Malatesta, V.; Ingold, K. U. J. Am. Chem. Soc. 1981, 103, 609–
614. (b) Malatesta, V.; Scaiano, J. C. J. Org. Chem. 1982, 47, 1455–
1459.
(59) Schenker, R.; Mandimutsira, B. S.; Riordan, C. G.; Brunold, T. C.
J. Am. Chem. Soc. 2002, 124, 13842–13855.
9
9266 J. AM. CHEM. SOC. VOL. 131, NO. 26, 2009

(µ-η2:η2-Peroxo)dicopper(II) Complex
A R T I C L E S
Scheme 6
(H-L-SH(n-1)), as shown in Scheme 6. The observed linear
correlations of log k2c and log kC2c with BDE in Figure 7 and the
relatively large KIEs for the k2 values clearly indicate that the rate-
determining step is HAT from SHn to generate ·SH(n-1) radical
and a putative CuII(µ-OH)(µ-O)CuIII. Rebound of OH from CuII(µ-
OH)(µ-O)CuIII then produces SH(n-1)OH, as shown in path (1) in
Scheme 6. The formation of the coupling dimers (H(n-1)S-SH(n-1)
and H-L-SH(n-1)) indicates that rebound of OH is not fast enough
oxidation reactions initiated by Cu2/O2 species have been demon-
strated for the first time in this study. Similar diverse oxidation
reactions have also been demonstrated by iron(IV)-oxo porphyrin
π-cation radicals and non-heme iron(IV)-oxo complexes.62 Oxida-
tion of the C-H bonds of the aliphatic substrates proceeds via a
H-atom transfer process, which is evident by the linear correlation
between log k2c and substrate BDE and the relatively large kinetic
isotope effects of k2. Comparison of the linear correlations of log
k2c and log k2Cc with the BDEs of the same series of substrates
suggests that the BDE of the O-H bond of a putative CuII(µ-
OH)(µ-O)CuIII species formed after HAT from the substrates is
comparable to that of cumene hydroperoxide. Although the
oxidation products of the external substrates in this study have yet
to be fully identified, formation of the coupling dimers of the
substrate radicals (e.g., 1,2-diphenylethane), and those of the
6-methylpyridyl radical of H-L with substrate radicals (H-
L-SH(n-1)) indicate that the rebound of OH from CuII(µ-OH)(µ-
O)CuIII to the substrate radical is rather slow and that CuII(µ-OH)(µ-
O)CuIII is also capable of oxidizing the C-H bond of additional
substrate and/or the 6-methylpyridyl group of H-L ligand. This
reactivity of CuII(µ-OH)(µ-O)CuIII is in marked contrast to the
selective hydroxylation of the m-xylyl linker of H-L. Thus, 1-O2
has a high potential for the oxidation of a variety of substrates.
to preclude the coupling of ·SH(n-1) radicals, which affords H(n-1)
-
S-SH(n-1). In the case of the formation of H-L-SH(n-1), the radical
of the 6-methylpyridyl group of H-L may also be generated via
HAT by ·SH(n-1) and/or CuII(µ-OH)(µ-O)CuIII. Formation of H-L-
CHD and H-L-DHA may exclude the H-atom abstraction by the
radicals of 1,4-CHD and 9,10-DHA, since their BDEs (∼75 to
∼78 kcal mol-1) are significantly lower than that of the C-H bond
of the 6-methylpyridyl group of H-L (the BDE of the C-H bond
of 2-methylpyridine has been estimated to be ∼93 kcal mol-1).60
Thus, CuII(µ-OH)(µ-O)CuIII seems to abstract the H atom of the
6-methylpyridyl group of H-L. The formation of such mixed-
valence MII(µ-OH)(µ-O)MIII species (M ) Cu, Ni) in the oxidation
reactions of (µ-η2:η2-peroxo)dicopper(II) complexes,33b bis(µ-
oxo)dicopper(III) complex,36 and bis(µ-oxo)dinickel(III) complex61
has also been proposed. Such stepwise reactivity is in marked
contrast to the reaction of 1-O2 with H-L, in which the xylyl linker
is selectively hydroxylated. In addition, oxidation of benzyl alcohol
by 1-O2 occurred smoothly with an oxidation yield of ∼90%, and
no coupling dimer of H-L was detected.
Acknowledgment. This work was partly supported by Grants-
in-Aid for Scientific Research, a Grant-in-Aid, and the Global COE
Program “The Global Education and Research Center for Bio-
Environmental Chemistry” from the Ministry of Education, Culture,
Sports, Science and Technology, Japan, and by KOSEF/MEST through
WCU Project (R31-2008-000-10010-0).
Summary and Conclusions
The (µ-η2:η2-peroxo)dicopper(II) complex 1-O2 [and/or Cu2/O2
species such as the bis(µ-oxo)dicopper(III) complex derived from
1-O2] has diverse oxidation reactivity that is capable of not only
hydroxylating the xylyl linker of the supporting ligand and
epoxidizing styrene but also activating the aliphatic C-H bond of
external substrates having BDEs of 75-92 kcal mol-1. Such diverse
Supporting Information Available: Tables S1 and S2 and
Figures S1-S11. This material is available free of charge via
the Internet at http://pubs.acs.org.
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