Fine-tuning of copper(I)-dioxygen reactivity by 2-(2-pyridyl)ethylamine bidentate ligands

Article abstract of DOI:10.1021/ja026047x

Copper(I)-dioxygen reactivity has been examined using a series of 2-(2-pyridyl)ethylamine bidentate ligands ^R1Py1^R2,R3. The bidentate ligand with the methyl substituent on the pyridine nucleus ^MePy1^Et,Bz (N-benzyl-N-ethyl-2-(6-methylpyridin-2-yl)ethylamine) predominantly provided a (μ-η²:η²-peroxo)dicopper(II) complex, while the bidentate ligand without the 6-methyl group ^HPy1^Et,Bz (N-benzyl-N-ethyl-2-(2-pyridyl)ethylamine) afforded a bis(μ-oxo)dicopper(III) complex under the same experimental conditions. Both Cu₂O₂ complexes gradually decompose, leading to oxidative N-dealkylation reaction of the benzyl group. Detailed kinetic analysis has revealed that the bis (μ-oxo)dicopper(III) complex is the common reactive intermediate in both cases and that O-O bond homolysis of the peroxo complex is the rate-determining step in the former case with ^MePy1^Et,Bz. On the other hand, the copper(I) complex supported by the bidentate ligand with the smallest N-alkyl group (^HPy1^Me,Me, N,N-dimethyl-2-(2-pyridyl)ethylamine) reacts with molecular oxygen in a 3:1 ratio in acetone at a low temperature to give a mixed-valence trinuclear copper(II, II, III) complex with two μ₃-oxo bridges, the UV-vis spectrum of which is very close to that of an active oxygen intermediate of lacase. Detailed spectroscopic analysis on the oxygenation reaction at different concentrations has indicated that a bis(μ-oxo)dicopper(III) complex is the precursor for the formation of trinuclear copper complex. In the reaction with 2,4-di-tert-butylphenol (DBP), the trinuclear copper(II, II, III) complex acts as a two-electron oxidant to produce an equimolar amount of the C-C coupling dimer of DBP (3,5,3′,5′tetra-tert-butyl-biphenyl-2,2′-diol) and a bis(μ-hydroxo)dicopper(II) complex. Kinetic analysis has shown that the reaction consists of two distinct steps, where the first step involves a binding of DBP to the trinuclear complex to give a certain intermediate that further reacts with the second molecule of DBP to give another intermediate, from which the final products are released. Steric and/or electronic effects of the 6-methyl group and the N-alkyl substituents of the bidentate ligands on the copper(I)-dioxygen reactivity have been discussed.

Full text of DOI:10.1021/ja026047x

Published on Web 05/09/2002
Fine-Tuning of Copper(I)-Dioxygen Reactivity by
2-(2-Pyridyl)ethylamine Bidentate Ligands
Masayasu Taki,‡ Shinichi Teramae,‡ Shigenori Nagatomo,§ Yoshimitsu Tachi,†
Teizo Kitagawa,§ Shinobu Itoh,*,† and Shunichi Fukuzumi*,‡
Contribution from the Department of Chemistry, Graduate School of Science,
Osaka City UniVersity, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan, Department of
Material and Life Science, Graduate School of Engineering, Osaka UniVersity, CREST, Japan
Science and Technology Corporation, 2-1 Yamada-oka, Suita, Osaka 565-0871, Japan, and
Institute for Molecular Science, Myodaiji, Okazaki 444-8585, Japan
Received January 27, 2002
Abstract: Copper(I)-dioxygen reactivity has been examined using a series of 2-(2-pyridyl)ethylamine
bidentate ligands R1Py1R2,R3. The bidentate ligand with the methyl substituent on the pyridine nucleus
MePy1Et,Bz (N-benzyl-N-ethyl-2-(6-methylpyridin-2-yl)ethylamine) predominantly provided a (µ-η2:η2-peroxo)-
dicopper(II) complex, while the bidentate ligand without the 6-methyl group HPy1Et,Bz (N-benzyl-N-ethyl-2-
(2-pyridyl)ethylamine) afforded a bis(µ-oxo)dicopper(III) complex under the same experimental conditions.
Both Cu2O2 complexes gradually decompose, leading to oxidative N-dealkylation reaction of the benzyl
group. Detailed kinetic analysis has revealed that the bis(µ-oxo)dicopper(III) complex is the common reactive
intermediate in both cases and that O-O bond homolysis of the peroxo complex is the rate-determining
step in the former case with MePy1Et,Bz. On the other hand, the copper(I) complex supported by the bidentate
ligand with the smallest N-alkyl group (HPy1Me,Me, N,N-dimethyl-2-(2-pyridyl)ethylamine) reacts with molecular
oxygen in a 3:1 ratio in acetone at a low temperature to give a mixed-valence trinuclear copper(II, II, III)
complex with two µ3-oxo bridges, the UV-vis spectrum of which is very close to that of an active oxygen
intermediate of lacase. Detailed spectroscopic analysis on the oxygenation reaction at different concentra-
tions has indicated that a bis(µ-oxo)dicopper(III) complex is the precursor for the formation of trinuclear
copper complex. In the reaction with 2,4-di-tert-butylphenol (DBP), the trinuclear copper(II, II, III) complex
acts as a two-electron oxidant to produce an equimolar amount of the C-C coupling dimer of DBP (3,5,3′,5′-
tetra-tert-butyl-biphenyl-2,2′-diol) and a bis(µ-hydroxo)dicopper(II) complex. Kinetic analysis has shown that
the reaction consists of two distinct steps, where the first step involves a binding of DBP to the trinuclear
complex to give a certain intermediate that further reacts with the second molecule of DBP to give another
intermediate, from which the final products are released. Steric and/or electronic effects of the 6-methyl
group and the N-alkyl substituents of the bidentate ligands on the copper(I)-dioxygen reactivity have been
discussed.
Introduction
thoroughly investigated is the dinuclear copper-dioxygen species
Cu2O2, where 2-(2-pyridyl)ethylamine derivatives have played
A growing amount of information about copper(I)-dioxygen
reactivity has recently been accumulated, providing profound
insight into the mechanism of O2-binding and activation at
copper reaction sites involved in many biological systems as
well as in a variety of catalytic oxidation processes.1-7 The most
important roles as the supporting ligands. The dinucleating
ligand (XYL) containing two bis[2-(2-pyridyl)ethyl]amine tri-
dentate metal binding units connected by m-xylyl group (Chart
1) was first reported by Karlin and co-workers to develop a
functional model of tyrosinase, in which aromatic moiety of
the m-xylyl group was quantitatively hydroxylated in the
reaction of its dinuclear copper(I) complex and dioxygen.8
Reversible dioxygen binding (functional model of hemocyanin)
was also accomplished by the same research group using a series
of dinucleating ligands which consist of the same tridentate
* To whom correspondence should be addressed. E-mail: shinobu@
sci.osaka-cu.ac.jp, fukuzumi@chem.eng.osaka-u.ac.jp.
† Osaka City University.
‡ Osaka University.
§ Institute for Molecular Science.
(1) Karlin, K. D., Tyekla´r, Z., Eds. Bioinorganic Chemistry of Copper;
Chapman & Hall: New York, 1993.
(2) Fox, S.; Karlin, K. D. In ActiVe Oxygen in Biochemistry; Valentine, J. S.,
Foote, C. S., Greenberg, A., Liebman, J. F., Eds.; Chapman and Hall:
London, 1995; pp 188-231.
(5) Kopf, M.-A.; Karlin, K. D. In Biomimetic Oxidations Catalyzed by
Transition Metal Complexes; Meunier, B., Ed.; Imperial College Press:
London, 1999; pp 309-362.
(3) Ito, M.; Fujisawa, K.; Kitajima, N.; Moro-oka, Y. In Oxygenases and Model
Systems; Funabiki, T., Ed.; Kluwer Academic Publishers: Dordrecht, 1997;
pp 345-376.
(6) Solomon, E. I.; Sundaram, U. M.; Machonkin, T. E. Chem. ReV. 1996, 96,
2563-2605.
(4) Blackman, A. G.; Tolman, W. B. In Metal-Oxo and Metal-Peroxo Species
in Catalytic Oxidations; Meunier, B., Ed.; Springer: Berlin, 2000; pp 179-
211.
(7) Klinman, J. P. Chem. ReV. 1996, 96, 2541-2561.
(8) Karlin, K. D.; Gultneh, Y.; Hutchinson, J. P.; Zubieta, J. J. Am. Chem.
Soc. 1982, 104, 5240-5242.
9
10.1021/ja026047x CCC: $22.00 © 2002 American Chemical Society
J. AM. CHEM. SOC. 2002, 124, 6367-6377
6367

A R T I C L E S
Taki et al.
Chart 1
Scheme 2
Chart 2
Scheme 1
metal binding units connected by C3-C5 alkyl linker chains
(Chart 1, Nn; n ) 3-5).9 In these reactions, (µ-η2:η2-peroxo)-
dicopper(II) species have been identified as the Cu2O2 inter-
mediate, for which they assigned a bent structure (butterfly
shape) due to the structural restriction induced by the alkyl linker
groups.10,11 The side-on peroxo dicopper(II) complexes having
a flat structure can also be assessed by the oxygenation reaction
of mononuclear copper(I) complexes supported by a series of
N-alkyl-bis[2-(2-pyridyl)ethyl]amine tridentate ligands (Py2R in
Chart 1).12-15 The (µ-η2:η2-peroxo)dicopper(II) complex (A)
thus formed has recently been demonstrated to have an ability
to hydroxylate phenolates to the corresponding catechols via
an electrophilic aromatic substitution mechanism, providing
important mechanistic insight into the phenolase activity of
tyrosinase (Scheme 1).15
Another important finding of this series is the aliphatic ligand
hydroxylation in the reaction of copper(I) complex of Py2Phe
[R ) -CH2CH2Ph (Phe) in Chart 1] and O2.16,17 In this case as
well, a (µ-η2:η2-peroxo)dicopper(II) complex (A) has been
identified as an initially formed intermediate.13 However,
detailed kinetic analysis on this reaction has suggested that the
(µ-η2:η2-peroxo)dicopper(II) complex (A) is not the real active
species, but, instead, another type of Cu2O2-intermediate derived
from the peroxo complex (A) is involved as the real active
Scheme 3
intermediate (Scheme 2).13 Ligand modification from the
tridentate (Py2Phe) to bidentate (HPy1Et,Phe, Chart 2) resulted in
formation of a bis(µ-oxo)dicopper(III) intermediate (B), from
which the same type of aliphatic ligand hydroxylation occurred
at its benzylic position of the phenethyl sidearm (Scheme 3).18
Thus, we concluded that the bis(µ-oxo)dicopper(III) complex
(B) was the real active oxygen intermediate both in the Py2Phe
and in the HPy1Et,Phe ligand systems and that the bidentate ligand
enhanced the O-O bond homolysis of the (µ-η2:η2-peroxo)-
dicopper(II) (A) to give the bis(µ-oxo)dicopper(III) complex (B)
predominantly.18 Detailed kinetic studies have also indicated
that the aliphatic ligand hydroxylation proceeds via hydrogen
atom abstraction by the high valent copper-oxo speceis in B
and subsequent oxygen rebound mechanism or its concerted
varient.18 The bis(µ-oxo)dicopper(III) complex supported by the
bidentate ligand HPy1Et,Bz-d2 (Chart 2) has recently been shown
to have an ability to oxo-transfer reaction toward sulfides.19
Furthermore, it has been demonstrated that a disproportionation
reaction of B could occur to afford a more reactive intermediate
such as a (µ-oxo)(µ-oxyl radical)dicopper(III) species (C)
(Scheme 4). Such an oxyl radical dicopper(III) species can
(9) Karlin, K. D.; Haka, M. S.; Cruse, R. W.; Gultneh, Y. J. Am. Chem. Soc.
1985, 107, 5828-5829.
(10) Pidcock, E.; Obias, H. V.; Zhang, C. X.; Karlin, K. D.; Solomon, E. I. J.
Am. Chem. Soc. 1998, 120, 7841-7847.
(11) Pidcock, E.; Obias, H. V.; Abe, M.; Liang, H.-C.; Karlin, K. D.; Solomon,
E. I. J. Am. Chem. Soc. 1999, 121, 1299-1308.
(12) Sanyal, I.; Mahroof-Tahir, M.; Nasir, M. S.; Ghosh, P.; Cohen, B. I.;
Gultneh, Y.; Cruse, R. W.; Farooq, A.; Karlin, K. D.; Liu, S.; Zubieta, J.
Inorg. Chem. 1992, 31, 4322-4332.
(13) Itoh, S.; Nakao, H.; Berreau, L. M.; Kondo, T.; Komatsu, M.; Fukuzumi,
S. J. Am. Chem. Soc. 1998, 120, 2890-2899.
(14) Pidcock, E.; DeBeer, S.; Obias, H. V.; Hedman, B.; Hodgson, K. O.; Karlin,
K. D.; Solomon, E. I. J. Am. Chem. Soc. 1999, 121, 1870-1878.
(15) Itoh, S.; Kumei, H.; Taki, M.; Nagatomo, S.; Kitagawa, T.; Fukuzumi, S.
J. Am. Chem. Soc. 2001, 123, 6708-6709.
(16) Itoh, S.; Kondo, T.; Komatsu, M.; Ohshiro, Y.; Li, C.; Kanehisa, N.; Kai,
Y.; Fukuzumi, S. J. Am. Chem. Soc. 1995, 117, 4714-4715.
(17) Re´glier et al. reported closely related systems: (a) Blain, I.; Bruno, P.;
Giorgi, M.; Lojou, E.; Lexa, D.; Re´glier, M. Eur. J. Inorg. Chem. 1998,
1297-1304. (b) Blain, I.; Giorgi, M.; De Riggi, I.; Re´glier, M. Eur. J.
Inorg. Chem. 2000, 393-398. (c) Blain, I.; Giorgi, M.; De Riggi, I.; Re´glier,
M. Eur. J. Inorg. Chem. 2001, 205-211.
(18) Itoh, S.; Taki, M.; Nakao, H.; Holland, P. L.; Tolman, W. B.; Que, L., Jr.;
Fukuzumi, S. Angew. Chem. 2000, 112, 409-411; Angew. Chem., Int. Ed.
2000, 39, 398-400.
(19) Taki, M.; Itoh, S.; Fukuzumi, S. J. Am. Chem. Soc. 2002, 124, 998-1002.
9
6368 J. AM. CHEM. SOC. VOL. 124, NO. 22, 2002

Fine-Tuning of Copper(I)-Dioxygen Reactivity
A R T I C L E S
Scheme 4
Scheme 5
participate in the C-H bond activation of external substrates
such as 1,4-cyclohexadiene and related substrates.20 Thus, the
reactivity studies of the Cu2O2 complexes using the tridentated
and bidentate ligands have provided significantly important
information about the dioxygen activation mechanism at the
dinuclear copper reaction centers. However, fine-tuning of
copper(I)-dioxygen reactivity by the subtle ligand modification
of bidentate or tridentate ligands has yet to be achieved.
We report herein that a small perturbation of the ligand
structure of the bidentate ligands (Chart 2) leads to drastic
changes in the structure and reactivity of the reactive Cu2O2
intermediates. The side-on peroxo dicopper(II) complex (A) and
the bis(µ-oxo)dicopper(III) complex (B) as well as a mixed-
valence trinuclear copper(II, II, III) complex with two µ3-oxo
bridges exhibiting a similar absorption spectrum of an active
oxygen intermediate of lacase (E, see Scheme 6)21 have been
Figure 1. ORTEP drawings of the cationic parts of [Cu(HPy1Et,Bz-d2)(PPh3)]-
PF6 (A) and [Cu(HPy1Me,Me)(PPh3)]PF6 (B) showing 50% probability
thermal-ellipsoid. Hydrogen atoms and counteranions are omitted for clarity.
in THF under anaerobic conditions (in a glovebox) gave the
corresponding copper(I) complexes, in which one CH3CN
molecule is involved as an external ligand to complete a three-
coordinate trigonal planar structure (see Experimental Section).
Reaction of HPy1Me,Me with an equimolar amount of [CuI-
(CH3CN)4]CF3SO3 in acetone also gave the corresponding
copper(I) complex under anaerobic conditions. In this case,
CF3SO3- binds to the metal center, but no acetonitrile molecule
is involved. Such a three-coordinate copper(I) complex with a
trigonal planar structure has been structurally characterized
by using air-stable phosphine complexes. Thus, the treatment
of the copper(I) complexes with PPh3 gave the copper(I)-
phosphine complexes, [CuI(HPy1Et,Bz-d2)(PPh3)]PF6 and
[CuI(HPy1Me,Me)(PPh3)]PF6, for which X-ray crystallographic
analyses have been performed as shown in Figure 1. The
crystallographic data and selected bond lengths and angles of
them are summarized in Tables 1 and 2, respectively.
The copper(I)-phosphine complex [CuI(HPy1Et,Bz-d2)(PPh3)]PF6
exhibits a trigonal planar structure in which the copper ion exists
just on the N(1)-N(2)-P(1) plane (Figure 1A). [CuI(HPy1Me,Me)-
(PPh3)]PF6 (Figure 1B) also exhibits a trigonal planar structure
with little deviation (0.14 Å) of the copper ion from the N(1)-
N(2)-P(1) plane. In the case of [CuI(HPy1Et,Bz-d2)(PPh3)]PF6,
the Cu(1)-N(1) and Cu(1)-N(2) bonds are slightly elongated
as compared to those values of [CuI(HPy1Me,Me)(PPh3)]PF6
(∆dCu(1)-N(1) ) 0.07 Å, ∆dCu(1)-N(2) ) 0.032 Å), and the
angle of N(1)-Cu(1)-N(2) becomes smaller (93.9° for
[CuI(HPy1Et,Bz-d2)(PPh3)]PF6 and 102.2° for [CuI(HPy1Me,Me)-
(PPh3)]PF6, see Table 2). These structural differences between
the two copper(I) complexes could be attributed to a steric
repulsion between the bulkier N-alkyl groups and the copper(I)
ion in the HPy1Et,Bz-d2 system. Such steric effects of the N-alkyl
assessed by using the simple bidentate ligands MePy1Et,Bz
,
HPy1Et,Bz, and HPy1Me,Me, respectively (Chart 2). The reactivity
of such dinuclear and trinuclear copper-dioxygen complexes and
the formation mechanism have been investigated in detail to
provide profound insight into the mechanism of dioxygen
activation and multielectron reduction of dioxygen to water at
dinuclear and trinuclear copper reaction centers in biological
systems.
Results and Discussion
Synthesis and Characterization of Ligands and Copper(I)
Complexes. The bidentate ligands HPy1Et,Bz and MePy1Et,Bz
(Chart 2) were prepared by Michael addition of benzylamine
to 2-vinylpyridine or 6-methyl-2-vinylpyridine in refluxing
methanol in the presence of an equimolar amount of acetic acid.
The resulting monoalkylated 2-(2-pyridyl)ethylamine derivatives
were then treated with ethyl bromide in refluxing methanol to
give HPy1Et,Bz and MePy1Et,Bz, respectively. The dideuterated
ligands at their benzylic position, HPy1Et,Bz-d2 and MePy1Et,Bz-d2
,
were prepared in the same way using PhCD2NH2 instead of
PhCH2NH2. Ligand HPy1Me,Me was prepared by reductive
alkylation of 2-(2-pyridyl)ethylamine using paraformaldehyde
and NaBH3CN in MeOH-water (9:1) containing acetic acid at
room temperature.
Treatment of the bidentate ligands HPy1Et,Bz(-d2) and
MePy1Et,Bz(-d2) with an equimolar amount of [CuI(CH3CN)4]PF6
(20) Taki, M.; Itoh, S.; Fukuzumi, S. J. Am. Chem. Soc. 2001, 123, 6203-
6204.
(21) Cole, A. P.; Root, D. E.; Mukherjee, P.; Solomon, E. I.; Stack, T. D. P.
Science 1996, 273, 1848-1850.
9
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A R T I C L E S
Taki et al.
Table 1. Summary of X-ray Crystallographic Data
I H
I H
II
[Cu( Py1Et,Bz-d2)(PPh3)]PF •H O
[Cu( Py1Me,Me)(PPh3)]PF
[Cu 2(HPy1Me,Me)2(µ-OH)2](CF SO )
6
2
6
3 3 2
empirical formula
formula weight
crystal system
space group
a, Å
C34H35D2N2OP2F6Cu
731.15
C27H29N2P2F6Cu
621.02
orthorhombic
Pna21 (No. 33)
22.512(2)
C20H30N4O8S2F6Cu2
759.68
monoclinic
P21/n (No. 14)
14.3075(3)
14.7516(4)
16.6486(4)
103.4220(7)
3417.9(1)
4
monoclinic
P21/c (No. 14)
10.515(1)
12.2207(8)
12.041(1)
106.414(3)
1484.2(2)
2
b, Å
c, Å
8.2258(7)
14.925(1)
â, deg
V, Å3
2763.7(4)
4
1.492
Z
D
calc, g/cm3
1.466
1.700
T, °C
-115
-50
23
crystal size, mm
µ (Mo KR), cm-1
no. of reflns measd
no. of reflns obsd
no. of variables
Ra
0.20 × 0.20 × 0.10
0.20 × 0.20 × 0.10
0.40 × 0.40 × 0.50
7.98
31 595
5056 [I > 1.0σ(I)]
441
0.057
0.087
9.66
22 498
3053 [I > 0.8σ(I)]
344
0.043
0.034
16.60
3546
2442 [I > 0.8σ(I)]
206
0.045
0.079
b
Rw
2
a R ) ∑||Fo| - |Fc||/∑|Fo|. b Rw ) {∑w(|Fo| - |Fc|)2/∑wFo }1/2
.
Table 2. Selected Bond Lengths (Å) and Angles (deg)
[CuI(HPy1Et,Bz-d2)(PPh3)]PF6
Cu(1)-N(1)
Cu(1)-N(2)
Cu(1)-P(1)
2.108(4)
2.020(5)
2.1821(14)
N(1)-Cu(1)-N(2)
N(1)-Cu(1)-P(1)
N(2)-Cu(1)-P(1)
93.80(18)
137.99(13)
128.03(14)
[CuI(HPy1Me,Me)(PPh3)]PF6
Cu(1)-N(1)
Cu(1)-N(2)
Cu(1)-P(1)
2.082(7)
1.989(6)
2.176(2)
N(1)-Cu(1)-N(2)
N(1)-Cu(1)-P(1)
N(2)-Cu(1)-P(1)
102.5(3)
133.2(2)
122.7(2)
[CuII2(HPy1Me,Me)2(µ-OH)2](CF3SO3)2
Cu(1)-N(1)
Cu(1)-N(2)
Cu(1)-O(1)
Cu(1)-O(1*)
Cu(1)‚‚‚Cu(1*)
O(1)‚‚‚O(1*)
2.066(3)
2.001(3)
1.918(3)
1.945(2)
2.949(1)
2.494(5)
N(1)-Cu(1)-N(2)
N(1)-Cu(1)-O(1)
N(2)-Cu(1)-O(1*)
O(1)-Cu(1)-O(1*)
Cu(1)-O(1)-Cu(1*)
95.07(11)
94.0(1)
90.98(9)
80.50(9)
99.63(9)
Figure 2. UV-vis spectra of the (µ-η2:η2-peroxo)dicopper(II) complex
[{(MePy1Et,Bz-d2)(CuII)}2(µ-O2)]2+ (A) and the bis(µ-oxo)dicopper(III) com-
plex [{(HPy1Et,Bz-d2)(CuIII)}2(µ-O)2]2+ (B) in acetone at -94 °C.
groups may become larger in the reaction with O2 as discussed
below. Despite our great efforts, single crystals of the copper(I)
complex of MePy1Et,Bz-d2 suitable for X-ray analysis could not
be obtained so far.
[spectrum (A) in Figure 2]. Such an absorption spectrum of the
oxygenated product is reminiscent of formation of a side-on
peroxo dicopper(II) complex. The resonance Raman spectrum
of the oxygenated compound excited at 364.8 nm gave
resonance enhanced peaks at 737 and 284 cm-1 (with 16O2),
the former of which shifted to 696 cm-1 upon 18O2-substitution
as demonstrated by the 16O-18O difference spectrum (Figure
3, lower) and was assigned to the O-O streching mode of the
side-on peroxo ligand.4,5,13-15 The Raman band around 280-
290 cm-1 has recently been assigned to an Ag “breathing” mode
of the Cu2O2 peroxo core involving predominantly Cu-Cu
streching motion.22 The stoichiometry of the reaction was
determined as Cu:O2 ) 2:1 ((0.05), and the resulting solution
was also ESR silent. These results unambiguously confirmed
that the Cu2O2 intermediate had a µ-η2:η2-peroxo bridge as
illustrated in Scheme 5. Thus, introduction of just a methyl group
into the 6-position of the pyridine nucleus of the bidentate ligand
drastically alters the reactiVity of the copper(I) complex toward
O2, and this is the first example of quantitatiVe formation of
the (µ-η2:η2-peroxo)dicopper(II) complex (A) using a bidentate
ligand.23
Dioxygen Reactivity of Copper(I) Complexes with HPy1Et,Bz
and MePy1Et,Bz. As stated above, we have already demonstrated
that oxygenation of the copper(I) complexes supported by
bidentate ligands HPy1Et,R3 (R3 ) Bz or Phe) affords the bis-
(µ-oxo)dicopper(III) complexes at a low temperature (Scheme
3).18-20 For example, [CuI(HPy1Et,Bz-d2)(CH3CN)]PF6 readily
reacted with O2 in a 2:1 ratio at -94 °C in acetone to give an
ESR-silent bis(µ-oxo)dicopper(III) complex exhibiting a char-
acteristic absorption band at 400 nm [ꢀ ) 17 400 M-1 cm-1
,
spectrum (B) in Figure 2] together with a resonance Raman
band at 606 cm-1 (with 16O2) that shifted to 577 cm-1 upon
18O2 substitution (B in Scheme 5).19,20
When the bidentate ligand HPy1Et,Bz-d2 was replaced by
MePy1Et,Bz-d2, which has the 6-methyl group on the pyridine
nucleus, the oxygenated product of [CuI(MePy1Et,Bz-d2)(CH3CN)]-
PF6 was found to be totally different from that derived from
[CuI(HPy1Et,Bz-d2)(CH3CN)]PF6 under the same experimental
conditions. The copper(I) complex of MePy1Et,Bz-d2 reacts with
dioxygen at -94 °C in acetone to afford the product which
exhibits an absorption band at 365 nm (ꢀ ) 17 900 M-1 cm-1
)
(22) Henson, M. J.; Mahadevan, V.; Stack, T. D. P.; Solomon, E. I. Inorg. Chem.
2001, 40, 5068-5069.
together with a weak band at 518 nm (860 M-1 cm-1
)
9
6370 J. AM. CHEM. SOC. VOL. 124, NO. 22, 2002

Fine-Tuning of Copper(I)-Dioxygen Reactivity
A R T I C L E S
Figure 4. Eyring plots for the decomposition process of (A) [{(MePy1Et,Bz)-
(CuII)}2(µ-O2)]2+ (b) and [{(MePy1Et,Bz-d2)(CuII)}2(µ-O2)]2+ (9) and (B)
[{(HPy1Et,Bz)(CuIII)}2(µ-O)2]2+ (O) and [{(HPy1Et,Bz-d2)(CuIII)}2(µ-O)2]2+ (0).
η2:η2-peroxo)dicopper(II) complex supported by Py2Phe(-d4)
(Scheme 2).13 Thus, the (µ-η2:η2-peroxo)dicopper(II) species
(A) is not the actual active oxygen intermediate for the benzylic
C-H bond activation (the initial step of the oxidative N-
dealkylation), but O-O bond homolysis of the peroxo inter-
mediate would occur prior to the following C-H bond activation
process. If the O-O bond homolysis is solely the rate-
determining step, the KIE value would be 1.0. The observed
small KIE values suggest that the O-O bond homolysis (kh) is
much slower than the back reaction (k-h) which competes with
the facile C-H bond activation (kCH). In such a case, the
Figure 3. Resonance Raman spectra of [{(MePy1Et,Bz-d2)(CuII)}2(µ-16O2)]2+
(solid line) and [{(MePy1Et,Bz-d2)(CuII)}2(µ-18O2)]2+ (dashed line) in acetone
at -100 °C excited at 363.8 nm; “s” denotes a solvent band (upper) and a
difference spectrum between the 16O and the 18O derivatives in the O-O
stretching region (lower).
observed rate constant k is given by equation k ) khkCH/(k-h
+
k
CH). The O-O bond homolysis may be largely the rate-
determining step, that is, kCH . k-h, but the ligand deuteration
may result in a significant decrease in the rate of the C-D
cleavage (kCD), which becomes partially rate-determining.
Decomposition of the bis(µ-oxo)dicopper(III) complex de-
rived from HPy1Et,Bz or HPy1Et,Bz-d2 which has no 6-methyl
group on the pyridine nucleus also led to oxidative N-
dealkylation reaction of the benzyl group. In this case, however,
a very large kinetic deuterium isotope effect (KIE) of 32.9 (at
-55 °C) was obtained. Such a large KIE value and the activation
The (µ-η2:η2-peroxo)dicopper(II) complexes generated by
using MePy1Et,Bz and MePy1Et,Bz-d2 decomposed gradually to
afford the oxidative N-dealkylation products, benzaldehyde and
N-ethyl-2-(6-methylpyridin-2-yl)-ethylamine (see Experimental
Section). The decomposition rates were determined from the
decay of the absorption band at 365 nm due to the peroxo
complex at various temperatures. The rates obeyed first-order
kinetics, and the logarithm of the first-order rate constants (log
k
obs) is plotted against 1/T to give the Eyring plots as shown in
parameters (∆HH ) 13.1 ( 0.2 kcal mol-1, ∆SH ) -7.3 (
q
q
Figure 4A. The kinetic isotope effect (KIE) is relatively small
as 3.5 at -80 °C that can be extrapolated to 1 at -16 °C as
shown in Figure 4A (the cross point of the two lines).
Furthermore, the activation parameters determined from the
q
q
1.1 cal K-1 mol-1, ∆HD ) 15.9 ( 0.6 kcal mol-1, ∆SD
)
-1.3 ( 2.7 cal K-1 mol-1) determined from the Eyring plots
shown in Figure 4B are similar to those reported for the aliphatic
ligand hydroxylation in the bis(µ-oxo)dicopper(III) core sup-
Eyring plots in Figure 4A (∆HHq ) 7.5 ( 0.1 kcal mol-1, ∆SH
q
ported by Py1Et,Phe(-d4) (∆HH ) 9.3 ( 0.1 kcal mol-1, ∆SH
H
q
q
q
) -28.9 ( 0.5 cal K-1 mol-1, ∆HD ) 9.8 ( 0.6 kcal
) -17.4 ( 0.5 cal K-1 mol-1, ∆HDq ) 12.6 ( 0.1 kcal mol-1
,
mol-1, ∆SDq ) -20.1 ( 3.4 cal K-1 mol-1) are fairly close to
those reported for the aliphatic ligand hydroxylation in the
(µ-η2:η2-peroxo)dicopper(II) complex supported by the tridentate
∆SDq ) -7.4 ( 0.5 cal K-1 mol-1) (Scheme 3).18 This indicates
that the oxidative N-dealkylation reaction proceeds via a similar
mechanism: rate-determining hydrogen atom abstraction and
oxygen rebound or its concerted variant as stated above.
The (µ-η2:η2-peroxo)dicopper(II) and bis(µ-oxo)dicopper(III)
complexes are known to have similar thermodynamic stability
such that changes in ligand substituents as well as solvent and/
or counteranion are sufficient to result in formation of one or
the other form.23-27 Steric repulsion between the bulky substit-
ligand Py2Phe(-d4) (KIE ) 1.8 at -40 °C, 5.9 at -80 °C, ∆HH
q
q
) 6.7 ( 0.2 kcal mol-1, ∆SH ) -37.0 ( 0.7 cal K-1 mol-1
,
∆HD ) 9.6 ( 0.2 kcal mol-1, ∆SD ) -25.6 ( 0.7 cal K-1
mol-1) (Scheme 2).13 Such a small KIE (3.5 at -80 °C) and
the disappearance of KIE ()1) at the higher temperature (-16
°C) could be interpreted by the mechanism that is similar to
that proposed for the aliphatic ligand hydroxylation in the (µ-
q
q
(24) Tolman, W. B. Acc. Chem. Res. 1997, 30, 227-237.
(25) Mahapatra, S.; Halfen, J. A.; Wilkinson, E. C.; Pan, G.; Cramer, C. J.;
Que, L., Jr.; Tolman, W. B. J. Am. Chem. Soc. 1995, 117, 8865-8866.
(26) Halfen, J. A.; Mahapatra, S.; Wilkinson, E. C.; Kaderli, S.; Young, V. G.,
Jr.; Que, L., Jr.; Zuberbu¨hler, A. D.; Tolman, W. B. Science 1996, 271,
1397-1400.
(23) A mixture of the (µ-η2:η2-peroxo)dicopper(II) and bis(µ-oxo)dicopper(III)
complexes has been obtained in the reaction of copper(I) complex of N,N′-
dimethyl-N,N′-di-tert-butylethylenediamine bidentate ligand with O2.
Mahadevan, V.; Henson, M. J.; Solomon, E. I.; Stack, T. D. P. J. Am.
Chem. Soc. 2000, 122, 10249-10250.
9
J. AM. CHEM. SOC. VOL. 124, NO. 22, 2002 6371

A R T I C L E S
Taki et al.
Chart 3
uents of the capping ligands as well as the interaction between
the Cu2O2 core and solvent and/or counteranion have been
invoked as the major factors that control the equilibrium position
between the two species, although the mechanistic details of
their functions have yet to be clearly understood.
Figure 5. Spectral change observed upon introduction of O2 gas into an
acetone solution of [CuI(HPy1Me,Me)(CF3SO3)] (5.0 × 10-3 M) at -94 °C.
Inset: First-order plot based on the absorbance change at 515 nm.
The selective formation of the (µ-η2:η2-peroxo)dicopper(II)
complex (A) using the bidentate ligand (MePy1Et,Bz) can be
explained by the steric effect of the 6-methyl group of the
pyridine nucleus. The bis(µ-oxo)dicopper(III) complex (B)
requires a shorter Cu-Npy distance (∼1.9 Å) than the (µ-η2:
η2-peroxo)dicopper(II) complex (A) (∼2.0 Å).28,29 The steric
repulsion between the 6-methyl group and the metal center may
inhibit the Cu2O2 complex of MePy1Et,Bz to adapt to such a
shorter Cu-Npy distance, enforcing the equilibrium strongly
toward the peroxo species.30 The donor ability of the pyridine
nitrogen is also reduced by the steric effect of the 6-methyl
group,31 destabilizing the higher oxidation state of the metal
centers in the bis(µ-oxo) species. Such steric and/or electronic
effects of the 6-methyl group have recently been reported in
the tridentate ligand system.32 Introduction of just a methyl
group into the 6-position of the pyridine nuclei to give MePy2Phe
(Chart 3) induces strong binding of MeCN to copper(I) in the
cuprous complex, resulting in loss of its reactivity toward
dioxygen.32 The 6-methyl group may prevent the cuprous
complex to adopt three-coordinate geometry with a shorter Cu-
Npy distance that is required for the ligand exchange between
MeCN and O2.
important roles of the trinuclear copper active sites in biological
dioxygen processing, there has been a limited number of model
compounds of trinuclear copper/dioxygen complexes reported
so far.21,34 Stack and co-workers have demonstrated that the
copper(I) complex of a bidentate ligand, N,N,N′,N′-tetramethyl-
trans-cyclohexanediamine, reacts with molecular oxygen in a
3:1 ratio at a relatively high concentration (>10 mM) of the
copper(I) complex to give a mixed-valence trinuclear copper(II,
II, III) complex with two µ3-oxo bridges.21 This reaction models
the four-electron reduction of dioxygen at the trinuclear copper
active site in the enzymes and provides another possible reaction
pattern in copper(I)-dioxygen chemistry in model systems.
However, the formation mechanism and reactivity of the
trinuclear copper complex have yet to be elucidated. In this
study, the bidentate ligand with the smallest N-alkyl substituents,
HPy1Me,Me, has been adopted to clarify the formation mechanism
and reactivity of the mixed-valence trinuclear copper(II, II, III)
complex.
Treatment of a 5.0 mM acetone solution of [CuI(HPy1Me,Me)-
(CF3SO3)] with dioxygen at -94 °C resulted in color change
of the solution from pale yellow to dark brown. A typical
example of the spectral change for the oxygenation reaction of
[CuI(HPy1Me,Me)(CF3SO3)] is shown in Figure 5 (measured by
using a 1 mm path length UV cell), where a strong absorption
band at 342 nm (ꢀ ) 12 000 M-1 cm-1) together with two small
bands at 515 (1000) and 685 nm (800 M-1 cm-1) rapidly
developed. The final spectrum of the reaction is significantly
different from that of the bis(µ-oxo)dicopper(III) complex (λmax
) 400 nm, ꢀ ) 17 400 M-1 cm-1) generated in the reaction of
copper(I) complex with bulkier bidentate ligand such as
[CuI(HPy1Et,Bz-d2)(CH3CN)]PF6 with O2 in acetone [spectrum
(B) in Figure 2], but is fairly close to that of the bis(µ3-oxo)-
Dioxygen Reactivity of Copper(I) Complex with HPy1Me,Me
.
Four-electron reduction of dioxygen to water is accomplished
at a trinuclear copper active center in multi-copper enzymes
such as ascorbate oxidase, laccase, and ceruloplasmin.6
A
trinuclear copper site has also been invoked as the reaction
center of particulate methane monooxygenase (pMMO), which
catalyzes hydroxylation of methane to methanol.33 Despite such
(27) Cahoy, J.; Holland, P. L.; Tolman, W. B. Inorg. Chem. 1999, 38, 2161-
2168.
(28) Mahapatra, S.; Halfen, J. A.; Wilkinson, E. C.; Pan, G.; Wang, X.; Young,
V. G., Jr.; Cramer, C. J.; Que, L., Jr.; Tolman, W. B. J. Am. Chem. Soc.
1996, 118, 11555-11574.
(29) Kitajima, N.; Fujisawa, K.; Fujimoto, C.; Moro-oka, Y.; Hashimoto, S.;
Kitafawa, T.; Toriumi, K.; Tatsumi, K.; Nakamura, A. J. Am. Chem. Soc.
1992, 114, 1277-1291.
tricopper(II, II, III) complex reported by Stack et al. [λmax
)
355 (15 000), 480 (1400), and 620 nm (800 M-1 cm-1)].21
Stoichiometry of Cu:O2 of the reaction has been determined by
manometry as 3:1 ((0.05). Furthermore, the acetone solution
of the oxygenated intermediate was ESR silent. These features
of the oxygenated intermediate, being quite similar to those of
the reported trinuclear mixed valence copper(II, II, III) bis(µ3-
oxo) complex, strongly indicate formation of the same type of
(30) Interaction between two 6-methylpyridines and the copper(III) ion in the
Suzuki’s bis(µ-oxo)dicopper(III) complex supported by bis[(6-methyl-
pyridin-2-yl)methyl](2-pyridinylmethyl)amine (Me2TPA) is known to be
very weak (Cu-NMePy: 2.48, 2.55 Å), while the remaining pyridine
without the substituent strongly bound to the metal center (Cu-NPy: 1.91
Å) to stabilize the copper(III) state. See: Hayashi, H.; Fujinami, S.;
Nagatomo, S.; Ogo, S.; Suzuki, M.; Uehara, A.; Watanabe, Y.; Kitagawa,
T. J. Am. Chem. Soc. 2000, 122, 2124-2125.
(31) Nagao, H.; Komeda, N.; Mukaida, M.; Suzuki, M.; Tanaka, K. Inorg. Chem.
1996, 35, 6809-6815.
(32) Osako, T.; Tachi, Y.; Taki, M.; Fukuzumi, S.; Itoh, S. Inorg. Chem. 2001,
40, 6604-6609.
H
intermediate in the present Py1Me,Me system (Scheme 6).
(33) Chan, S. I.; Nguyen, H. T.; Shiemke, A. K.; Lidstrom, M. E. In Bioinorganic
Chemistry of Copper; Karlin, K. D., Tyekla´r, Z., Eds.; Chapman & Hall:
New York, 1993; pp 184-195.
(34) Karlin, K. D.; Gan, Q.-F.; Farooq, A.; Liu, S.; Zubieta, J. Inorg. Chem.
1990, 29, 2549-2551.
9
6372 J. AM. CHEM. SOC. VOL. 124, NO. 22, 2002

Fine-Tuning of Copper(I)-Dioxygen Reactivity
A R T I C L E S
sensitive Raman bands around 600 cm-1 in copper/dioxygen
chemistry are now well recognized as diagnostic for formation
of the bis(µ-oxo)dicopper(III) complex.35,36 Interestingly enough,
addition of another 0.1 mM acetone solution of [CuI(HPy1Me,Me)-
(SO3CF3)] into the mixture under anaerobic conditions (Ar gas
was bubbled for 15 min before the additional addition of
copper(I) complex) resulted in a decrease of the absorption band
at 386 nm due to the bis(µ-oxo)dicopper(III) complex together
with an increase of the bands at 342, 515, and 685 nm due to
the trinuclear copper(II, II, III) complex as depicted in Figure
6 [spectrum (b)]. Thus, the bis(µ-oxo)dicopper(III) complex in
the mixture is converted into the bis(µ3-oxo) trinuclear copper(II,
II, III) species by the reaction with the copper(I) starting
material. This indicates that the former is the precursor of
formation of the later as indicated in Scheme 6. At higher
concentration of the copper(I) starting material (mM order), the
reaction between the bis(µ-oxo)dicopper(III) intermediate (B)
and another molecule of copper(I) may be fast enough to gen-
erate the trinuclear complex predominantly. On the other hand,
at the lower copper(I) concentration, there is not enough
copper(I) complex remaining in the solution for the complete
conversion of B to E. Thus, the reaction at the lower concentra-
tion gave a mixture of the two species (B and E). Further addi-
tion of the copper(I) complex to the mixture under Ar resulted
in conversion of the coexisting bis(µ-oxo)dicopper(III) complex
(B) to the trinuclear complex (E) as depicted in Figure 6. From
the spectral change shown in Figure 6 was determined the
second-order rate constant kf(2) for the reaction between B and
the copper(I) complex as 3.4 ((0.2) × 102 M-1 s-1 at -94 °C.
As suggested by the crystal structures of the copper(I)-
phosphine complexes (Figure 1), steric bulkiness of the N-alkyl
substituents in HPy1R2,R3 is the major factor that controls the
reactivity of the copper complexes. In fact, ligand HPy1Et,Bz-d2
afforded predominantly the bis(µ-oxo)dicopper(III) complex
even at the higher concentration (3.0 mM) of the starting
copper(I) complex under otherwise the same reaction conditions
(Figure S2). Thus, the N-substituents of the bidentate ligand
significantly alter the copper(I)-dioxygen reactivity.
Figure 6. UV-vis spectrum obtained upon addition of O2 gas into an
acetone solution of [CuI(HPy1Me,Me)(CF3SO3)] (0.2 × 10-3 M) at -94 °C
(A, dashed line) and that obtained after another addition of [CuI(HPy1Me,Me)-
(CF3SO3)] (0.1 × 10-3 M) under anaerobic conditions (before the addition
of the copper(I) complex Ar gas was bubbled for 15 min) (B, solid line).
Scheme 6
The formation rate of the bis(µ3-oxo) trinuclear copper
complex (E) obeys first-order kinetics as shown in the inset of
Figure 5. The first-order dependence of the formation process
has also been confirmed by the fact the pseudo-first-order-rate
constants (kfobs; the suffix “f” denotes “formation process”) are
nearly the same within an experimental error when the
concentration of the starting copper(I) complex is changed from
3.0 to 8.0 mM (kfobs ) 5.9 ((0.2) × 10-2 s-1). The first-order
kinetics have clearly indicated that the primary reaction between
the copper(I) complex (starting material) and dioxygen to form
a mononuclear copper(II)-superoxo intermediate (D in Scheme
6) is the rate-determining step (kfobs ) kf(1)), and the subsequent
steps, D to B through A and B to E, are much faster. In contrast,
Reactivity of the Bis(µ3-oxo) Trinuclear Copper(II, II, III)
Complex. The bis(µ3-oxo) trinuclear copper(II, II, III) complex
E (1.7 mM) reacted with 2,4-di-tert-butylphenol (DBP, 10 mM)
in acetone at -80 °C to give 3,5,3′,5′-tetra-tert-butyl-biphenyl-
1
2,2′-diol (C-C coupling dimer) as the oxidation product. H
NMR spectrum of the organic product mixture obtained by
extraction of the final reaction mixture with ether has indicated
that the yield of the C-C coupling dimer is 97% based on the
trinuclear complex used. This unambiguously indicates that the
copper(II, II, III) complex E acts formally as a two-electron
oxidant. When the final reaction mixture was allowed to stand
for several hours, single crystals of a product derived from the
copper complex were obtained, for which X-ray crystallographic
analysis has also been carried out. The crystal structure of the
product is shown in Figure 7 together with the crystallographic
data and the selected bond lengths and angles in Tables 1 and
2, respectively. It is a bis(µ-hydroxo)dicopper(II) complex,
the oxygenation reaction of the copper(I) complex of HPy1Et,Bz-d2
,
that is, the formation of the bis(µ-oxo)dicopper(III) (B), followed
the second-order rate law.18 This indicates that the reaction of
superoxo-copper(II) intermediate D and the copper(I) complex
is rate-limiting in the HPy1Et,Bz-d2 system. The bulkier N-
substituents in HPy1Et,Bz-d2 may retard the self-assembling
dimerization reaction (D to A), whereas the small methyl group
H
in Py1Me,Me may not.
When the reaction was carried out at a lower concentration
of the copper(I) complex such as 0.2 mM, a different spectrum
was obtained as shown in Figure 6 [spectrum (a)], where co-
existence of a bis(µ-oxo)dicopper(III) complex with the tri-
nuclear copper complex was implicated by the appearance of a
characteristic absorption band at 386 nm together with the bands
due to the trinuclear copper complex. In fact, the solution gave
a resonance Raman band at 628 cm-1 with 16O2 that shifted to
594 cm-1 upon 18O2 substitution (Figure S1). The isotope
[CuII (HPy1Me,Me)2(µ-OH)2](CF3SO3)2 (F), having an imposed
2
(35) Holland, P. L.; Cramer, C. J.; Wilkinson, E. C.; Mahapatra, S.; Rodgers,
K. R.; Itoh, S.; Taki, M.; Fukuzumi, S.; Que, L., Jr.; Tolman, W. B. J. Am.
Chem. Soc. 2000, 122, 792-802.
(36) Henson, M. J.; Mukherjee, P.; Root, D. E.; Stack, T. D. P.; Solomon, E. I.
J. Am. Chem. Soc. 1999, 121, 10332-10345.
9
J. AM. CHEM. SOC. VOL. 124, NO. 22, 2002 6373

A R T I C L E S
Taki et al.
Figure 7. ORTEP drawing of the cationic parts of [CuII2(HPy1Me,Me)2(µ-
OH)2](CF3SO3)2 showing 50% probability thermal-ellipsoid. Hydrogen
atoms except the hydroxyl H and counteranions are omitted for clarity.
center of symmetry in the Cu2O2 core. Each copper ion exhibits
a square planar geometry which consists of a N2O2 donor set
provided from the bidentate ligands and the bridging OH groups.
The complex F was ESR silent due to strong magnetic
interaction between the two cupric ions through the m-hydroxo
bridges. Because the Cu-O-Cu angle in F is 99.63(9)° (see
Table 2), the magnetic interaction is antiferromagnetic. Crawford
et al. have established the linear correlation between the Cu-
O-Cu angle (θ) of a series of bis(µ-hydroxo)dicopper(II)
complexes and their singlet-triplet exchange parameter as J )
-74.53θ + 7270 cm-1 37
From this correlation, it can be
.
concluded that when θ is larger than 97.55°, the overall magnetic
behavior is antiferromagnetic. Complex F exhibits absorption
bands at 355 nm (ꢀ ) 1400 M-1 cm-1) and 595 nm (ꢀ ) 180
M-1 cm-1), the latter of which is used to estimate the yield of
the dicopper(II) complex in a UV-vis scale reaction (vide infra).
In Figure 8A is shown the spectral change observed upon
addition of DBP (1.0 × 10-2 M) to an acetone solution of
complex E (1.0 × 10-3 M) at -90 °C, where the characteristic
absorption bands at 515 and 685 nm due to E decrease to attain
spectrum (a) exhibiting a λmax at 570 nm.38 The time course of
the absorption change obeys first-order kinetics, and the pseudo-
first-order rate constant (krobs(1); the suffix “r” denotes “reaction”)
increases linearly with increasing substrate concentration as
shown in the inset of Figure 8A. From the slope of the linear
line was determined the second-order rate constant kr(1) as
0.46 ( 0.02 M-1 s-1 at -90 °C.
When the same reaction was carried out at -70 °C [Figure
8B], the absorption bands due to E (515 and 685 nm) rapidly
changed to the spectrum (a), which further changed slowly to
the spectrum (b) that is exactly the same as the spectrum of
bis(µ-hydroxo)dicopper(II) complex E (λmax ) 595 nm). Judging
from the absorption intensity at 595 nm of the final spectrum
(b), the amount of F formed in this reaction is nearly equal to
that of the starting material E. In other words, one molecule of
the bis(µ-hydroxo)dicopper(II) complex (F) is produced from
one molecule of the trinuclear copper(II, II, III) complex (E).
Thus, it is apparent that the reaction between E and DBP to
give F and the C-C coupling dimer proceeds stepwise through
an intermediate X exhibiting the spectrum (a).
Figure 8. Spectral changes for (A) the first process of the reaction between
complex E (1.0 × 10-3 M) and DBP (1.0 × 10-2 M) in acetone at -90 °C
(Inset: Plot of krobs(1) vs [DBP]) and for (B) the reaction of E (1.0 × 10-3
M) and DBP (7.0 × 10-2 M) in acetone at -70 °C (Inset: Time course of
the absorbance change at 515 nm); (a) the spectrum of intermediate X
indicated in Scheme 7; (b) the final spectrum of the reaction that is exactly
the same as that of the bis(µ-hydroxo)dicopper(II) complex (F).
The second slow process also obeys pseudo-first-order
kinetics, but a plot of the pseudo-first-order rate constant krobs(2)
against the DBP concentration gave a Michaelis-Menten type
saturation curve as shown in Figure S3. This implicates that
the second slow process involves a complex formation between
intermediate X and DBP to give another intermediate Y. From
the double reciprocal plot shown in the inset of Figure S3 were
determined the equilibrium constant K and the rate constant
kr(2) as 44.6 ( 2.2 M-1 and 9.5 ((0.5) × 10-3 s-1 at -70 °C,
respectively.
A possible mechanism for the reaction between E and DBP
is illustrated in Scheme 7. In the first process, trinuclear
copper(II, II, III) complex E reacts with DBP to give an
intermediate X. The intermediate X exhibits an absorption band
at 570 nm (spectrum (a) in Figure 8) which could be assigned
to the d-d transitions of the copper(II) ions of the intermediate.
Because no reaction took place when the sterically bulkiest
phenol, 2,4,6-tri-tert-butylphenl (TBP), was used as the substrate
instead of DBP, the first process with DBP may involve
coordination of the phenol to one of the copper ion (probably
copper(III) site) in the trinuclear copper(II, II, III) complex E.
Although structural details about intermediate X have yet to be
clarified, we presume that the three copper ions are still
associated in the intermediate X, since no ESR active species
is detected during the course of the reaction. The intermediate
X then further reacts with another molecule of DBP to give an
(37) Drawford, V. H.; Richardson, H. W.; Wasson, J. R.; Hodgson, D. J.;
Hatfield, W. E. Inorg. Chem. 1976, 15, 2107-2110.
(38) The trinuclear copper(II, II, III) complex (E) is fairly stable at the low
temperature, so that self-decomposition of the complex is negligible below
-70 °C.
9
6374 J. AM. CHEM. SOC. VOL. 124, NO. 22, 2002

Fine-Tuning of Copper(I)-Dioxygen Reactivity
A R T I C L E S
complexes of MePy1Et,Bz(-d2) and HPy1Et,Bz(-d2) with O2, the KIE
and the activation parameters have indicated that the bis(µ-oxo)-
dicopper(III) complex is a common intermediate for the intra-
molecular C-H bond activation of the ligand sidearm.
Scheme 7
Adoption of the small N-alkyl substituents of the bidentate
ligand and higher concentration of the starting material allows
us to attain the trinuclear copper complex E via the reaction
involving the copper(II)-superoxo and bis(µ-oxo)dicopper(III)
intermediates (D and B) as shown in Scheme 6. The trinuclear
H
copper(II, II, III) complex E supported by Py1Me,Me has been
demonstrated to act as a two-electron oxidant in the reaction
with the phenol substrate (Scheme 7). The two-oxidation ability
of E has also been demonstrated in the reaction with AcrH2.39
Recently, Solomon et al. and Sakurai et al. independently
reported formation of a similar type of active oxygen intermedi-
ate in the oxygenation reaction of modified multi-copper oxidase
(lacase) carrying three cuprous ions in the enzyme active
site.40-42 Although they proposed that the active oxygen
intermediate involved a hydroperoxo or a peroxo structure, it
is interesting to note that the UV-vis spectra of their active
oxygen intermediates (Solomon’s intermediate, 340, 470, and
680 nm; Sakurai’s intermediate, 340, 475, and 680 nm) are very
close in shape and peak positions to those of the trinuclear
copper(II, II, III) complex reported here. Further model studies
will be merited to provide structural information about the active
oxygen intermediates of the multi-copper enzymes.
intermediate Y, from which one molecule of bis(µ-hydroxo)-
dicopper(II) complex F and the dimer product are released to
complete the reaction (Scheme 7). Because the trinuclear
copper(II, II, III) complex acts formally as a two-electron
oxidant to give an equimolar amount of the dicopper(II) complex
and the dimer product of DBP, 1 equiv of copper(I) complex
should be released as indicated in Scheme 7. Although we could
not estimate the yield of such colorless copper(I) complex by
UV-vis, ESI-MS measurement did confirm the existence of
copper(I) complex [CuI(HPy1Me,Me)]+ in the final reaction
mixture. Importance of the coordinative interaction between the
phenol substrate and the copper sites of intermediates is also
implicated by the fact that 1,4-cyclohexadiene (CHD) having a
similar weak C-H bond did not react with E under the same
experimental conditions.39
Experimental Section
General. All chemicals used in this study except the ligands and
the complexes were commercial products of the highest available purity
and were further purified by the standard methods, if necessary.43
6-Methyl-2-vinylpyridine was kindly supplied by Koei Chemical Co.
Ltd. and was purified by fractional distillation. FT-IR spectra were
recorded with a Shimadzu FTIR-8200PC. UV-vis spectra were
measured using a Hewlett-Packard HP8453 diode array spectropho-
tometer with a Unisoku thermostated cell holder designed for low-
temperature measurements. Mass spectra were recorded with a JEOL
JMS-700T Tandem MS station. ESI-MS (electrospray ionization mass
spectra) measurements were performed on a PE SCIEX API 150EX.
1H NMR spectra were recorded on a JEOL FT-NMR Lambda 300WB.
ESR measurements were performed on a JEOL JES-ME-2X spectrom-
eter at -196 °C (liquid N2 temperature).
Synthesis. HPy1Et,Bz (N-Benzyl-N-ethyl-2-(2-pyridyl)ethylamine).
A mixture of benzylamine (2.14 g, 20 mmol), 2-vinylpyridine (2.10 g,
20 mmol), and acetic acid (1.20 g, 20 mmol) in methanol (70 mL) was
refluxed for 40 h. After removal of the solvent by evaporation, the
resulting residue was dissolved in CH2Cl2 (100 mL), and the CH2Cl2
solution was washed with 10% aqueous NaOH three times and dried
over anhydrous K2CO3. After removal of K2CO3 by filtration, evapora-
tion of the organic solvent gave brown oily material, from which
N-benzyl-2-(2-pyridyl)ethylamine was isolated by SiO2 column chro-
matography (CHCl3-AcOEt) in 72% yield. 1H NMR (270 MHz,
CDCl3): δ 3.00-3.07 (m, 4H, -CH2-CH2-Py), 3.83 (s, 2H, -CH2-
Ph), 7.12 (1H, d, J ) 5.4 Hz, Hpy-3), 7.13 (1H, dd, J ) 3.5, 5.4 Hz,
Conclusion
A series of simple bidentate ligands, R1Py1R2,R3, allowed us
to assess three totally different copper-active oxygen complexes,
(µ-η2:η2-peroxo)dicopper(II) complex (A), bis(µ-oxo)dicop-
per(III) complex (B), and mixed-valence bis(µ3-oxo) trinuclear
copper(II, II, III) complex (E). The bidentate ligand with the
6-methyl substituent on the pyridine nucleus MePy1Et,Bz pre-
dominantly provided the (µ-η2:η2-peroxo)dicopper(II) complex
(A), while the bidentate ligand without the 6-methyl group
HPy1Et,Bz afforded the bis(µ-oxo)dicopper(III) complex (B) under
the same experimental conditions (Scheme 5). Such a drastic
effect of the 6-methyl group on the Cu2O2 intermediates has
been interpreted by steric repulsion between the 6-methyl group
and the metal center, which inhibits close approach of Cu to
the nitrogen atom of the pyridine nucleus. Such a short distance
of Cu-N is required for the formation of the high valent copper-
oxo complex (B).28 The donor ability of the nitrogen is also
reduced by the steric effect of the 6-methyl group, destabilizing
the bis(µ-oxo)dicopper(III) complex (B) in the MePy1Et,Bz case.
In the oxidative N-dealkylation reactions with the copper(I)
H
H
py-5), 7.22-7.37 (5H, m, -C6H5), 7.60 (1H, dt, J ) 1.4, 5.4 Hz,
py-4), 8.50 (1H, d, J ) 3.5 Hz, Hpy-6). MS (EI+) m/z 212 (M+).
(40) Shin, W.; Sundaram, U. M.; Cole, J. L.; Zhang, H. H.; Hedman, B.;
Hodgson, K. O.; Solomon, E. I. J. Am. Chem. Soc. 1996, 118, 3202-
3215.
(41) Zoppellaro, G.; Sakurai, T.; Huang, H. J. Biochem. 2001, 129, 949-953.
(42) Solomon, E. I.; Chen, P.; Metz, M.; Lee, S.-K.; Palmer, A. E. Angew. Chem.,
Int. Ed. 2001, 40, 4570-4590.
(43) Perrin, D. D.; Armarego, W. L. F.; Perrin, D. R. Purification of Laboratory
Chemicals, 4th ed.; Pergamon Press: Elmsford, NY, 1996.
(39) The trinuclear copper(II, II, III) complex (E) also reacts with 10-methyl-
9,10-dihydroacridine (AcrH2) slowly to give 10-methylacridinium ion
(AcrH+) and the bis(m-hydroxo)dicopper(II) complex (F) at the low
temperature. A very small kinetic deuterium isotope effect (KIE ) 1.3)
obtained using 9,9-dideuterated derivative (AcrD2) instead of AcrH2 has
suggested that oxidation of AcrH2 by complex E involves an electron-
transfer process as the rate-determining step.
9
J. AM. CHEM. SOC. VOL. 124, NO. 22, 2002 6375

A R T I C L E S
Taki et al.
N-Benzyl-2-(2-pyridyl)ethylamine (4.24 g, 20 mmol) was treated
with ethyl bromide (2.18 g, 20 mmol) and triethylamine (2.02 g, 20
mmol) in refluxing methanol for 2 days. After removal of the solvent
by evaporation, the resulting residue was dissolved in CH2Cl2, and the
solution was washed with 10% aqueous NaOH three times and dried
over anhydrous K2CO3. After removal of K2CO3 by filtration, evapora-
tion of the organic solvent gave brown oily material, from which
HPy1Et,Bz was isolated by SiO2 column chromatographic treatment
C18H23N3Cu1P1F6: C, 44.13; H, 4.73; N, 8.58. Found: C, 44.42;
H, 4.57; N, 8.64. Anal. Calcd for [CuI(HPy1Et,Bz-d2)(CH3CN)]PF6,
C18H21D2N3Cu1P1F6: C, 43.95; H, 5.12; N, 8.54. Found: C, 43.81; H,
4.51; N, 8.35.
[CuI(MePy1Et,Bz)(CH3CN)]PF6. This compound was prepared in a
similar manner for the synthesis of [CuI(HPy1Et,Bz)(CH3CN)]PF6 by using
MePy1Et,Bz instead of HPy1Et,Bz in 87% yield. 1H NMR (300 MHz,
acetone-d6): δ 1.40 (3H, t, -CH2-CH3), 2.39 (3H, s, coord. CH3CN),
2.47 (3H, s, -CH3), 2.95-3.11 (10H, m, -CH2-CH3, -CH2-CH2-
Py, and -CH2-CH2-Ph), 7.23 (1H, d, J ) 5.7 Hz, Hpy-5), 7.30 (1H,
d, J ) 5.7 Hz, Hpy-3), 7.33-7.42 (3H, m, -C6H5), 7.55-7.60 (2H, m,
-C6H5), 7.78 (1H, t, J ) 5.7 Hz, Hpy-4). FTIR (KBr): 842 cm-1 (PF6-).
ESI-MS for [CuI(MePy1Et,Bz-d2)(CH3CN)]PF6 (pos.), m/z 319.2 (M+).
Anal. Calcd for [CuI(MePy1Et,Bz)(CH3CN)]PF6‚H2O, C19H27N3O1Cu1P1F6:
C, 43.72; H, 5.21; N, 8.05. Found: C, 44.21; H, 4.85; N, 7.85.
[CuI(HPy1Me,Me)(CF3SO3)]. To a dry acetone solution (5 mL) of
HPy1Me,Me (150 mg, 1 mmol) was added [CuI(CH3CN)4]CF3SO3 (377
mg, 1 mmol) under anaerobic conditions (Ar). After stirring for 1 h,
insoluble material was filtered off. The yellow filtrate was then added
dropwise into deaerated ether (200 mL) to give pale yellow powder,
which was isolated by decantation and washed with ether three times
(67% isolated yield). 1H NMR (400 MHz, acetone-d6): δ 2.98 (6H, s,
-CH3), 3.39-3.58 (4H, m, -CH2-CH2-Py), 7.46 (1H, ddd, J ) 0.8,
4.8, and 7.6 Hz, Hpy-5), 7.59 (1H, d, J ) 7.6 Hz, Hpy-3), 7.97 (1H, dt,
J ) 1.8, 7.6 Hz, Hpy-4), 8.65 (1H, brs, Hpy-6). FTIR (KBr): 638, 1128,
1160, and 1225 cm-1 (CF3SO3-). ESI-MS (pos.), m/z 213.1 (M+).
Anal. Calcd for [CuI(HPy1Me,Me)(CF3SO3)‚0.5H2O, C10H15N2O3.5S1F3Cu1:
C, 32.3; H, 4.07; N, 7.53. Found: C, 32.6; H, 3.86; N, 7.63.
[CuI(HPy1Et,Bz-d2)(PPh3)]PF6. To a suspension of [CuI(HPy1Et,Bz-d2)-
(CH3CN)]PF66 (49.1 mg, 0.1 mmol) in THF (2 mL) was added a THF
(3 mL) solution of triphenylphosphine (52.5 mg, 0.2 mmol) in a
glovebox ([O2] < 0.1 ppm). After stirring the mixture for 5 min at
room temperature, an insoluble material was filtered off. The colorless
filtrate was then added dropwise into ether (70 mL) to give white
powder, which was isolated by decantation and washed with ether
three times (83% isolated yield). Single crystals (colorless prism) for
X-ray structure determination were obtained by recrystallization from
methanol/ether. 1H NMR (400 MHz, acetone-d6): δ 2.59 (6H, s, -CH3),
2.89-2.96 (2H, m, -CH2-CH2-Py), 3.22-3.29 (2H, m, -CH2-
CH2-Py), 7.41 (1H, ddd, J ) 0.8, 5.2, and 7.6 Hz, Hpy-5), 7.50-7.62
(16H, m, Hpy-3 and aromatic), 8.00 (1H, dt, J ) 1.6, 7.6 Hz, Hpy-4),
8.42 (1H, ddd, J ) 0.8, 1.6, and 5.2 Hz, Hpy-6). FTIR (KBr): 840
cm-1 (PF6-). ESI-MS (pos.), m/z 566.9 (M+). Anal. Calcd for
[CuI(HPy1Et,Bz-d2)(PPh3)]PF6, C34H33D2N2P2F6Cu: C, 57.26; H, 5.23;
N, 3.93. Found: C, 57.52; H, 5.24; N, 3.72.
[CuI(HPy1Me,Me)(PPh3)]PF6. To a suspension of [CuI(CH3CN)4]PF6
(186 mg, 0.5 mmol) in CH2Cl2 (2 mL) was added a CH2Cl2 (3 mL)
solution of HPy1Me,Me (75.0 mg, 0.5 mmol) under anaerobic conditions
(Ar in a glovebox). After stirring the mixture for 30 min, triphenylphos-
phine (131 mg, 0.5 mmol) was added into the resulting solution. After
additional stirring for 30 min, an insoluble material was filtered off.
The colorless filtrate was then added dropwise into deaerated ether (100
mL) to give white powder, which was isolated by decantation and
washed with ether three times (64% isolated yield). Single crystals
(colorless prism) for X-ray structure determination were obtained by
recrystallization from CH2Cl2/ether. 1H NMR (400 MHz, acetone-d6):
δ 2.59 (6H, s, -CH3), 2.89-2.96 (2H, m, -CH2-CH2-Py), 3.22-
3.29 (2H, m, -CH2-CH2-Py), 7.41 (1H, ddd, J ) 0.8, 5.2, and
7.6 Hz, Hpy-5), 7.50-7.62 (16H, m, Hpy-3 and aromatic), 8.00 (1H, dt,
J ) 1.6, 7.6 Hz, Hpy-4), 8.42 (1H, ddd, J ) 0.8, 1.6, and 5.2 Hz, Hpy-6).
FTIR (KBr): 839 cm-1 (PF6-). ESI-MS (pos.), m/z 474.9 (M+).
Anal. Calcd for [CuI(HPy1Me,Me)(PPh3)]PF6, C27H29N2P2F6Cu1: C, 52.2;
H, 4.71; N, 4.51. Found: C, 52.3; H, 4.69; N, 4.51.
1
(CHCl3-AcOEt) in 68% yield. H NMR (300 MHz, CDCl3): δ 1.03
(t, 3H, J ) 7.2 Hz, -CH2-CH3), 2.58 (q, 2H, J ) 7.2 Hz, -CH2-
CH3), 2.84-2.99 (m, 4H, -CH2-CH2-Py), 3.64 (s, 2H, -CH2-Ph),
7.08 (1H, dd, J ) 5.1, 7.2 Hz, Hpy-5), 7.12 (1H, d, J ) 7.2 Hz, Hpy-3),
7.18-7.29 (5H, m, -C6H5), 7.56 (1H, dt, J ) 1.8, 7.2 Hz, Hpy-4),
8.50 (1H, dd, J ) 1.8, 5.1 Hz, Hpy-6). HRMS (EI+) m/z 240.1625
(M+) calcd for C16H20N2 240.1626. The R,R-dideuterated derivative
(HPy1Et,Bz-d2) was prepared in the same way by using PhCD2NH2 instead
1
of PhCH2NH2, and its purity (>99%) was confirmed by H NMR.
MePy1Et,Bz (N-Benzyl-N-ethyl-2-(6-methylpyridin-2-yl)ethylamine).
This compound was prepared starting from 6-methyl-2-vinylpyridine
and benzylamine through N-benzyl-2-(6-methylpyridin-2-yl)ethylamine
in a similar manner for the preparation of HPy1Et,Bz in 44% (total yield).
Analytical data for N-benzyl-2-(6-methyl-2-pyridyl)ethylamine, 1H
NMR (300 MHz, CDCl3): δ 2.52 (3H, s, -CH3), 2.95-3.05 (m, 4H,
-CH2-CH2-Py), 3.82 (s, 2H, -CH2-Ph), 6.97 (2H, d, J ) 7.2 Hz,
H
H
py-3 and Hpy-5), 7.19-7.35 (5H, m, -C6H5), 7.47 (1H, t, J ) 7.2 Hz,
py-4). MS (EI+) m/z 226 (M+). Analytical data for MePy1Et,Bz, 1H NMR
(300 MHz, CDCl3): δ 1.02 (3H, t, J ) 7.2 Hz, -CH2-CH3), 2.50
(3H, s, -CH3), 2.57 (2H, q, J ) 7.2 Hz, -CH2-CH3), 2.82-2.96 (4H,
m, -CH2-CH2-Py), 3.63 (2H, s, -CH2-Ph), 6.92 (1H, d, J ) 7.5
Hz, Hpy-5), 6.94 (1H, δ J ) 7.5 Hz, Hpy-3), 7.20-7.28 (5H, m, -C6H5),
7.45 (1H, t, J ) 7.5 Hz, Hpy-4). HRMS (EI+) m/z 254.1786 (M+) calcd
for C17H22N2: 254.1783. The R,R-dideuterated derivative (MePy1Et,Bz-d2
)
was prepared by using PhCD2NH2 instead of PhCH2NH2, and its purity
1
(>99%) was confirmed by H NMR.
HPy1Me,Me (N,N-Dimethyl-2-(2pyridyl)ethylamine). To a solution
of 2-(2-aminoethyl)pyridine (3.67 g, 30 mmol), paraformaldehyde (1.81
g, 60 mmol), and acetic acid (3.60 g, 60 mmol) in methanol/water (90/
10 mL) was added NaBH3CN (3.77 g, 60 mmol) slowly, and the
resulting mixture was stirred for 5 days. The reaction was then quenched
by adding concentrated HCl slowly until the pH of the solution became
unity. After removal of the solvent by evaporation, the resulting oily
material was dissolved into 1 N aqueous NaOH (100 mL) and was
extracted with CHCl3 (100 mL x 3). After drying over anhydrous
K2CO3, evaporation of the organic layer gave brown oily material, from
which HPy1Me,Me was isolated by SiO2 column chromatography
1
(CHCl3-MeOH) in 80% yield. H NMR (300 MHz, CDCl3): δ 2.31
(6H, s, -CH3), 2.68-2.74 (2H, m, -CH2-CH2-Py), 2.94-3.00 (2H,
m, -CH2-CH2-Py), 7.11 (1H, ddd, J ) 0.8, 4.8, and 7.7 Hz, Hpy-5),
7.19 (1H, d, J ) 7.7 Hz, Hpy-3), 7.59 (1H, dt, J ) 1.8, 7.7 Hz, Hpy-4),
8.53 (1H, ddd, J ) 0.8, 1.8, and 4.8 Hz, Hpy-6). HR-MS (EI, pos.)
150.1152 (M+), calcd for C9H14N2: 150.1157.
[CuI(HPy1Et,Bz)(CH3CN)]PF6. Ligand HPy1Et,Bz (240.4 mg, 1 mmol)
was treated with [CuI(CH3CN)4]PF6 (372.7 mg, 1 mmol) in THF (7
mL) in a glovebox ([O2] < 0.1 ppm, [H2O] < 1 ppm). After stirring
the solution for 15 min at room temperature, insoluble material was
removed by filtration. Addition of ether (100 mL) to the filtrate
gradually gave a pale yellow powder that was precipitated by standing
the mixture for several minutes. The supernatant was then removed by
decantation, and the remaining pale yellow solid was washed with ether
1
three times and dried to give the copper(I) complex in 87% yield. H
NMR (300 MHz, acetone-d6): δ 1.39 (3H, t, J ) 7.2 Hz, -CH2-
CH3), 2.36 (s, 3H, coord. CH3CN), 2.93-3.26 (6H, m, -CH2-CH3
and -CH2-CH2-Py), 7.33-7.48 (5H, m, Hpy-3, Hpy-5, and -C6H5),
7.56-7.63 (2H, m, -C6H5), 7.93 (1H, dt, J ) 1.8, 7.2 Hz), 8.32
(1H, br s, Hpy-6). ESI-MS m/z 305.3 ([CuI(HPy1Et,Bz)]+). FTIR (KBr):
840 cm-1 (PF6-). Anal. Calcd for [CuI(HPy1Et,Bz)(CH3CN)]PF6,
[CuII(HPy1Me,Me)(µ-OH)2](CF3SO3)2. The reaction of [CuII2CuIII-
(HPy1Me,Me)3(µ3-O)2](CF3SO3)3 (1.7 mM) and DBP (10 mM) was carried
out in acetone at -80 °C for 24 h. Evaporation of the solvent gave a
9
6376 J. AM. CHEM. SOC. VOL. 124, NO. 22, 2002

Fine-Tuning of Copper(I)-Dioxygen Reactivity
A R T I C L E S
blue color residue, which was washed with ether (30 mL × 2), collected
by filtration, and dried under vacuo. Single crystals (blue prism) for
X-ray structure determination were obtained by recrystallization from
acetone/ether. FTIR (KBr): 3570 cm-1 (µ-OH), 636, 1028, 1159, and
1225 cm-1 (CF3SO3-). ESI-MS (pos.), m/z 608.8 (M+). Anal. Calcd
Oxidation of 2,4-di-tert-butylphenol (DBP) by the bis(µ3-oxo)
trinuclear copper(II, II, III) complex was started by adding the substrate
with use of a microsyringe into the solution at -90 °C (first process)
and -70 °C (second process), after excess O2 was removed by bubbling
Ar gas into the solution of the bis(µ3-oxo) trinuclear copper complex
for 5 min. The reaction was followed by monitoring a decrease in
absorbance at 515 nm due to the bis(µ3-oxo) trinuclear copper(II, II,
III) complex.
for [CuII (HPy1Me,Me)2(µ-OH)2](CF3SO3)2, C20H30N4O8S2F6Cu1: C, 31.78;
2
H, 3.98; N, 7.38. Found: C, 31.78; H, 3.97; N, 7.40.
Product Analysis. Oxidative N-Dealkylation Reaction. The cop-
per(I) complex (0.15 mmol) was dissolved into deaerated acetone (10
mL), and the solution was cooled to -78 °C using an acetone/dry ice
bath, and then dry O2 gas was introduced into the solution at this
temperature. The resulting solution was stirred for several hours at -78
°C. After evaporation of the solvent, the oxidized product was dissolved
into 2.8 M aqueous NH3 (25 mL), extracted with CH2Cl2 (25 mL ×
3), and dried over K2CO3. Identification and quantification of the
oxidized products were carried out by 1H NMR and mass spectroscopy.
Yields of the oxidation products, benzaldehyde and N-ethyl-2-(2-
pyridyl)-ethylamine, were 25-35% based on the Cu2O2 complex
(theoretical maximum is 50%). The lower yields of the oxidation
products are due to difficulty in recovering the small amounts of volatile
benzaldehyde and the amine product which is highly soluble in water.
Oxygenation of 2,4-Di-tert-butylphenol (DBP). The bis(µ3-oxo)
trinuclear copper(II, II, III) complex was generated by the reaction of
[CuI(HPy1Me,Me)(CF3SO3)] (0.10 mmol) and O2 gas at -80 °C in
anhydrous acetone (20 mL) for 10 min. After removal of excess O2 by
bubbling Ar gas into the solution for 10 min, a solution of DBP (0.2
mmol) in 0.5 mL of anhydrous acetone was added into the solution,
and the mixture was stirred for 24 h at this temperature. After
evaporation of the solvent, 50 mL of ether was added to the remaining
residue, and the insoluble material was removed by filtration. The
separated solid was further washed with additional ether (30 mL × 3),
and the combined ether solution was concentrated to give an organic
material, from which 3,5,3′,5′-tetra-tert-butyl-biphenyl-2,2′-diol was
obtained in 97% yield.
Resonance Raman Measurements. The 363.8 nm line of an Ar+
ion laser (model 2080 Spectra Physics) was used as the exciting source
of the Raman scattering. Resonance Raman spectra were detected with
a liquid nitrogen cooled CCD detector (Model LN/CCD-1100 × 330PB,
Princeton Instruments) attached to a 1 m single polychlomator (Model
MC-100DG, Ritsu Oyo Kogaku). The mechanical slit width and slit
height of the polychlomator were set to 200 and 20 mm, respectively.
The corresponding spectral slit width was 11.8 cm-1, and a wavenumber
width per one channel of the array detection was 1.1 cm-1. The laser
power used was 2.5 mW at the sample point. All measurements were
carried out at -100 ((2) °C with a spinning cell (1000 rpm). Raman
shifts were calibrated with indene, and accuracy of the peak positions
of the Raman bands was (1 cm-1
.
X-ray Structure Determination. The single crystals were mounted
on a glass capillary or a CryoLoop (Hampton Research Co. Ltd.). Data
of X-ray diffraction were collected by a Rigaku RAXIS-RAPID imaging
plate two-dimensional area detector using graphite-monochromated Mo
KR radiation (λ ) 0.71070 Å) to 2θ max of 55°. All of the
crystallographic calculations were performed using Crystal Structure
software package of the Molecular Structure Corp. [Crystal Structure:
Crystal Structure Analysis Package version 2.0, Molecular Structure
Corp. and Rigaku Corp. (2001)]. The crystal structure was solved by
the direct methods and refined by the full-matrix least squares using
SIR-92. All non-hydrogen atoms and hydrogen atoms were refined
anisotropically and isotropically, respectively. Atomic coordinates,
thermal parameters, and intramolecular bond distances and angles are
deposited in the Supporting Information (CIF file format).
Manometry. Typically, the O2-uptake measurement was carried
out on the reaction of [CuI(MePy1Et,Bz-d2)(CH3CN)]PF6 (158.5 mg,
0.304 mmol) in deaerated acetone (3 mL) at -80 °C. The volume
of O2 consumed during the oxygenation reaction of the copper(I)
complex was determined to be 3.90 mL as a difference of the O2
consumption between Cu/O2 intermediate formation and the blank
solution without the reactants under exactly the same conditions using
a manometer designed for the small-scale reaction. Thus, the stoi-
chiometry of Cu:O2 was calculated to be 2:1 ((0.05) for the forma-
tion of [{CuII(MePy1Et,Bz-d2)}2(µ-O2)](PF6)2. The stoichiometry of
Cu:O2 for the formation of [{CuIII(HPy1Et,Bz-d2)}2(µ-O)2](PF6)2 and
[{CuIICuIICuIII(HPy1Me,Me)3}(µ3-O)2](CF3SO3)3 was determined as 2:1
((0.05) and 3:1 ((0.05), respectively, by the same procedure.
Kinetics. The copper-dioxygen complexes were generated in situ
by the reaction of Cu(I) complex and dry O2 gas (introduced by gentle
bubbling for a few minutes) in a UV-vis cell (1 cm or 1 mm path
length) which was held in a Unisoku thermostated cell holder designed
for the low-temperature experiments (fixed within (0.5 °C). Rate
constants for the formation and decay of the copper-dioxygen complexes
were determined by monitoring an increase and decrease in the
absorption bands due to the intermediate complexes.
Acknowledgment. This work was financially supported in
part by Grants-in-Aid for Scientific Research on Priority Area
(No. 11228206) and Grants-in-Aid for Scientific Research (No.
13480189) from the Ministry of Education, Culture, Sports,
Science, and Technology, Japan.
Supporting Information Available: The resonance Raman
spectra of the oxygenated intermediate derived from [CuI-
(HPy1Me,Me)(CF3SO3)] at the lower concentration (0.2 mM)
in acetone (Figure S1), the UV-vis spectral change for
the oxygenation reaction of [CuI(HPy1Et,Bz-d2)(CH3CN)]PF6
(3.0 × 10-3 M) at -94 °C in acetone (Figure S2), and the kinetic
data for the reaction between E and DBP in acetone at -70 °C
(Figure S3) (PDF). X-ray structural determination and details
of the crystallographic data are supplied as a CIF file. This
material is available free of charge via the Internet at
http://pubs.acs.org.
JA026047X
9
J. AM. CHEM. SOC. VOL. 124, NO. 22, 2002 6377