On the Metal Cooperativity in a Dinuclear Copper–Guanidine Complex for Aliphatic C?H Bond Cleavage by Dioxygen

Article abstract of DOI:10.1002/chem.201901906

Selective oxidation reactions of organic compounds with dioxygen using molecular copper complexes are of relevance to synthetic chemistry as well as enzymatic reactivity. In the enzyme peptidylglycine α-hydroxylating monooxygenase (PHM), the hydroxylating activity towards aliphatic substrates arises from the cooperative effect between two copper atoms, but the detailed mechanism has yet to be fully clarified. Herein, we report on a model complex showing hydroxylation of an aliphatic ligand initiated by dioxygen. According to DFT calculations, the proton-coupled electron-transfer (PCET) process leading to ligand hydroxylation in this complex benefits from cooperative effects between the two copper atoms. While one copper atom is responsible for dioxygen binding and activation, the other stabilizes the product of intramolecular PCET by copper–ligand charge transfer. The results of this work might pave the way for the directed utilization of cooperative effects in oxidation reactions.

Full text of DOI:10.1002/chem.201901906

A Journal of
Accepted Article
Title: On the Metal Cooperativity in a Dinuclear Copper-Guanidine
Complex for aliphatic C−H Bond Cleavage by Dioxygen
Authors: Florian Schön, Florian Biebl, Lutz Greb, Simone Leingang,
Benjamin Grimm-Lebsanft, Melissa Teubner, Soeren
Buchenau, Elisabeth Kaifer, Michael Alexander Rübhausen,
and Hans-Jörg Himmel
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To be cited as: Chem. Eur. J. 10.1002/chem.201901906
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On the Metal Cooperativity in a Dinuclear Copper-Guanidine Complex for
aliphatic C−H Bond Cleavage by Dioxygen
F. Schön,[a] F. Biebl,[b] L. Greb,[a] S. Leingang,[a] B. Grimm-Lebsanft,[b] M. Teubner,[b] Sören Buchenau,[b]
E. Kaifer,[a] M. A Rübhausen,[b] H.-J. Himmel*[a]
atoms (denoted as CuA and CuB), separated by ~11 Å.[ 31 ]
Abstract: Selective oxidation reactions of organic compounds with
dioxygen using molecular copper complexes are of relevance for
synthetic chemistry as well as enzymatic reactivity. In the enzyme
peptidylglycine α-hydroxylating monooxygenase (PHM), the aliphatic
substrate hydroxylating activity arises from the cooperative effect
between two copper atoms, but the detailed mechanism is still not
completely clarified. Herein we report on a model complex, for which
an aliphatic ligand hydroxylation initiated by dioxygen is observed.
According to DFT calculations, the proton-coupled electron transfer
(PCET) process leading to ligand hydroxylation benefits from
cooperative effects between the two copper atoms in this complex.
While one copper atom is responsible for dioxygen binding and
activation, the other stabilizes the product of intramolecular PCET by
copper-ligand charge-transfer. The results of this work might pave
the way for the directed utilization of cooperative effects in oxidation
reactions.
Crystallographic characterization of the oxidized form of PHM
revealed a mildly activated O2 unit in an end-on superoxo
complex with an O-O bond distance of 1.23 Å.[32] The dioxygen
exclusively binds to the CuB atom. The role of the CuA atom is to
provide electron density to the CuB site for the subsequent
hydroxylation pathway. Scheme 1b sketches one possible
reaction pathway for the hydroxylating mechanism in PHM, as
suggested by Amzel et al.,[30] but other pathways were proposed,
involving e.g. the oxyl radical Cu1O formed from Cu1SE
species.[11,33,34] The mechanism of the electron-transfer pathway
is not completely clear, since the synthesis of model Cu1SE
complexes is generally hampered by their high reactivity. In
some cases, the products of proton-coupled electron transfer
(PCET) reactions, e.g. with TEMPOH (Scheme 1a and b,
TEMPO = 2,2,6,6-tetramethylpiperidinyloxyl), were isolated.[35]
Introduction
The distinguished ability of copper complexes to activate
dioxygen has long been recognized.[1−8] Nature has developed a
number of copper-containing oxidase enzymes with hugely
varying binding modes of dioxygen to the copper in their active
centers,[9−17] the most common ones being sketched in Scheme
1a. There are examples of well characterized, mononuclear
copper(II) end-on superoxo[ 18 − 23 ] (Cu1SE) or side-on (µ2)
superoxo[24−27] (Cu1SS) complexes, and also copper(III) side-on
(µ2) peroxo[ 28 ] (Cu1PS) complexes. However, in the literature
there is still a lack of copper complexes that mimic the structure
or the reactivity of enzymes such as tyramine ß-monooxygenase
(TßM), dopamine ß-monooxygenase (DßM) or peptidylglycine α-
hydroxylating monooxygenase (PHM). Several studies[ 29 , 30 ]
suggested a Cu1SE species as the key reactive intermediate in
aliphatic substrate hydroxylating activity of these enzymes, in
which the active sites consist of two differently bound copper
Scheme 1. a) Overview of some copper-dioxygen complexes and reaction
products. b) Proposed mechanism for dioxygen activation with the enzyme
PHM (adapted from Amzel et al. 1999, see ref. 30).
[a]
[b]
F. Schön, Dr. L. Greb, S. Leingang, Dr. E. Kaifer, Prof. H.-J. Himmel
Anorganisch-Chemisches Institut
Ruprecht-Karls-Universität Heidelberg
Im Neuenheimer Feld 270, 69120 Heidelberg, Germany
E-Mail: hans-jorg.himmel@aci.uni-heidelberg.de
http://www.uni-heidelberg.de/fakultaeten/chemgeo/aci/himmel/
F. Biebl, Dr. B. Grimm-Lebsanft, M. Teubner, Prof. M. A Rübhausen
Institut für Nanostruktur- und Festkörperphysik
There are two types of hydroxylation, initiated by copper-
dioxygen complexes: 1) Aromatic hydroxylation[36] and aliphatic
hydroxylation[ 37 ] due to dinuclear oxo species which are not
relevant for the above-mentioned enzymes, and 2) aliphatic
hydroxylation attributable to mononuclear dioxygen complexes
(Scheme 1a) as described in the following. In 2009, Itoh et al.
reported unique examples for direct aliphatic C−H bond
cleavage reactions, leading to ligand hydroxylation, as
suggested for the above-mentioned enzymes, starting with
Universität Hamburg and Center for Free Electron Laser Science
Luruper Chaussee 149, 22761 Hamburg, Germany
Supporting information for this article is given via a link at the end of
the document.
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Cu1SE complexes exhibiting an N-[2-(2-pyridyl)ethyl]-1,5- Results and Discussion
diazacyclooctane tridentate ligand (1X, Scheme 2).[38,39] Aliphatic
ligand hydroxylation is also known for a Cu1SE complex bearing
Synthesis of the copper(I) complexes
[
52 ]
the
tris[2-(N-tetramethylguanidyl)-ethyl]-amine
ligand
(2,
Reaction between L1
and tetrakis(acetonitrile)copper(I)-
Scheme 2),[38,39] but only after the reaction with an hydrogen-
atom donor (TEMPOH, phenols), or the reaction of the CuI
complex with PhIO. These findings were explained by the
formation of another species, a Cu1PH or Cu1O complex, which
is responsible for the hydroxylating activity.[35] There are a few
more examples for CuI complexes exhibiting aliphatic ligand
oxidation when exposed to dioxygen, but in all these cases a
Cu1SE complex could not be spectroscopically detected.[40−43]
Moreover, a special ligand design with sterically demanding
groups is required to prohibit formation of higher nuclear
complexes, either as peroxo-complexes Cu2PE or Cu2PS [44,45] or
as dioxo-complex Cu2O2 (bis(µ-oxo)-dicopper(III)).[ 46 ] Several
tetrafluoroborate, [Cu(CH3CN)4]BF4, led to the orange dinuclear
complex [(L1Cu)2](BF4)2 in a high yield of 92% (Scheme 3). The
1H NMR spectrum displayed a doublet and a triplet signal from
the pyridine ring, a singlet signal for the methylene bridge and
two singlet signals for the guanidino groups. This finding can be
explained by molecular dynamics, averaging the pyridine NMR
signals by fast migration of the pyridine ligands from one copper
atoms to the other. All signals were low-field shifted with respect
to the free ligand. The UV/Vis spectrum showed a strong
absorption at 210 nm (= 27200 M−1cm−1) together with a
shoulder at 272 nm ( = 8640 M−1 cm−1) and a weak absorption
at 357 nm ( = 883 M−1cm−1). Figure 1a visualizes the structure
groups studied dioxygen binding of guanidine-copper complexes. of the [(L1Cu)2]2+ complex, as derived from X-ray diffraction on
Hence dinuclear oxo- (Cu2O2) and peroxo- (Cu2PS) complexes
of bisguanidine ligands were reported.[46,47] Especially interesting
is the ability of trisguanidine-copper complexes (ligand 2,
Scheme 2) to form remarkably stable copper-superoxo
complexes of typ Cu1SE,[18,21] that allowed the first structural
characterization of a Cu1SE complex and a detailed evaluation of
its reactivity.[19,48]
crystals grown from a CH3CN/Et2O solution (see SI for the
similar structure of crystals grown from an acetone/Et2O
solution). Interestingly, the two CuI atoms in this complex,
separated by 2.871(1) Å, are very differently coordinated. One
copper atom is bound to two guanidino nitrogen atoms and in
addition to the nitrogen atoms of the pyridine rings, leading to a
relatively high coordination number of four. The space-filling
model highlights the buried position of this copper atom in the
core of the complex, leaving virtually no free space for dioxygen
attack.
Scheme 3. Reaction leading to the dinuclear CuI complex [(L1Cu)2](BF4)2.
Scheme 2. Lewis structures of two previously used ligands 1X (X = OMe, Me,
[49]
H, Cl, NO2)[38,39] and 2
in aliphatic ligand hydroxylation reactions via Cu1SE
complexes and the two bisguanidine ligands 2,6-bis(tetramethylguandino-
methyl)-pyridine (L1) and 2,6-bis(1-tetramethyl-guandino-1-methyl-ethyl)-
pyridine (L2) used in this work.
In the last years, our group intensively explored the chemistry of
copper complexes exhibiting guanidino-substituted aromatics as
ligands.[ 50 ] We also demonstrated their use as catalysts for
oxidation reactions with dioxygen.[51] Herein we report two new
copper complexes with the bisguanidine ligands L1 and L2
(Scheme 2). They form mononuclear copper-dioxygen species
that might be interesting in the context of enzymatic aliphatic
C−H bond activation. Due to the ligand design, with three N-
donor atoms for strong coordination and steric shielding of the
coordinated metal center in the binding pocket, the formation of
dinuclear, oxo-bridged complexes is prohibited.
Figure 1. Structure of the complex [(L1Cu)2]2+ in crystals of [(L1Cu)2](BF4)2
grown from CH3CN/Et2O solution (Cu atoms in orange, N atoms in blue and C
atoms in grey). Hydrogen atoms and counterions are omitted for clarity. The
two copper atoms are separated by 2.871(1) Å (see SI for structural details).
a) Structure with thermal ellipsoids (drawn at the 50% probability level).
b) Space-filling model.
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The second CuI atom exhibits a lower coordination number of
two, as it is only bound to two guanidino nitrogen atoms.
Consequently, this copper atom is prone for dioxygen attack
(see the space-filling model in Figure 1b).
additional signal splitting (in difference to [(L1Cu)2](BF4)2), arising
from the formation of diastereomeric centers due to the four
additional methyl groups in L2. Furthermore, nuclear overhauser
enhancement spectroscopy (NOESY) supported these findings
by means of an exchange of signals from the guanidino groups
as well as the aromatics in the major and minor product (see SI).
Finally, we calculated [L2Cu]+ and its dimer, [(L2Cu)2]2+, in
analogy to the complexes with ligand L1, and compared their
energies. Surprisingly, the calculated global energy-minimum
structure of [(L2Cu)2]2+ differed markedly from that of [(L1Cu)2]2+.
Hence one CuI atom in [(L2Cu)2]2+ exhibits a coordination
number of three, being coordinated to two guanidino nitrogen
atoms and one pyridine nitrogen atom. The second CuI atom is
coordinated to two guanidino nitrogen atoms, as in [(L1Cu)2]2+.
Furthermore, the Cu-Cu distance (3.699 Å) is very large (for a
more detailed comparison, see SI). Dimerization of [L2Cu]+ was
calculated to be mildly exothermic (ΔH = −42 kJ mol1) but
endergonic (ΔG = +44 kJ mol1) at room temperature and 1 atm,
in line with the experimental results. The different structures of
the two complexes also led to a different chemical reactivity.
Hence [L2Cu]+ turned out to be much more sensitive to air
contact than [(L1Cu)2]2+.
Similar IR spectra were recorded for the complex in a KBr disk
and dissolved in CH3CN, indicating that the dimeric structure is
preserved in solution (see SI). 1H DOSY NMR spectra were
recorded for further assessment (see SI for details). From these
experiments, the diffusion constant of the free ligand L1 was
estimated to 1.40·10−9 m2 s−1 in CD3CN solution. With 1.01·10−9
m2 s−1, the diffusion constant of the copper complex obtained
upon dissolving [(L1Cu)2](BF4)2 in CD3CN is significantly lower, in
line with the presence of a dimeric complex unit in solution.
Variable-temperature 1H NMR spectroscopy was performed to
study the effect of temperature variations on the dimerization
process. Although the complex revealed dynamic processes
(rotation and inversion of the guanidino groups,[53] see SI), a
monomer-dimer equilibrium can be excluded. To support the
experimental results, DFT calculations (TPSSh+D3/def2-TZVP)
were carried out for the monomer [L1Cu]+ and its dimer
[(L1Cu)2]2+. The solvent effect was estimated with the conductor-
like screening model (COSMO, see SI for details). The
calculated structure of [(L1Cu)2]2+ is in very good agreement with
the experimental structure. The root mean square deviation
(RMSD) for the bond distances, as determined with the program
aRMSD,[54] is only 0.35 Å (see SI for details). According to these
calculations, dimerization of [L1Cu]+ is both exothermic and
exergonic (H = −182 kJ mol1 and G = −107 kJ mol1 at 298 K,
1 bar), in full agreement with the experimental results. Hence all
results confirm that the [(L1Cu)2]2+ units found in the solid state
are preserved in solution.
Next, we synthesized the new ligand L2 (see Lewis structure in
Scheme 2 and experimentally derived solid-state structure in the
SI) bearing methyl groups at the benzylic positions. By reaction
with [Cu(CH3CN)4]BF4, the complex [L2Cu]BF4 was obtained in
88% isolated yield. Its structural characterization in the solid
state was not possible, but all experimental results point to an
equilibrium between a monomeric complex [L2Cu]+ and its dimer
[(L2Cu)2]2+ in acetonitrile solution (Scheme 4), this time with
strong preference for the monomeric complex at room
Scheme 4. Equilibrium between monomer and dimer for the complex
[(L2Cu)]BF4 in acetonitrile solution, favouring the monomer at room
temperature.
Reactivity of the copper(I) complex solutions toward
dioxygen
Next, the reactivity of the two complexes toward dioxygen was
studied. In first experiments, propionitrile solutions of [L2Cu]BF4
and [(L1Cu)2](BF4)2 were cooled to −80 °C and 40 °C,
respectively, and the changes in the UV/Vis spectra upon
addition of a pre-cooled solution of propionitrile, saturated with
dioxygen, were monitored. Figure 2 visualizes the changes in
the UV/Vis spectra upon dioxygen addition.
1
temperature. From H DOSY NMR spectra, a diffusion constant
of 1.45·10−9 m2 s−1 was estimated for the free ligand L2. For the
copper complex, two species with significantly different diffusion
constants were found. The dominating species exhibited a
diffusion constant of 1.16·10−9 m2 s−1, and the second species a
smaller one of 1.04·10−9 m2 s−1, being close to that of
[(L1Cu)2](BF4)2. The obvious inference is that in CD3CN solution
a monomeric complex [L2Cu]+ formed, together with a small
amount of dimeric complex [(L2Cu)2]2+. This conclusion is further
1
supported by variable-temperature H NMR measurements (see
SI). At high temperature (70 °C), only one species, [L2Cu]+, was
present. A weak additional set of signals appeared at room
temperature, indicating the presence of small amounts of the
dimer. A monomer:dimer ratio of 82:18 was estimated by signal
integration. For both species, similar dynamic processes as for
the [(L1Cu)2](BF4)2 complex were detected. At −40 °C the NMR
spectra for the dimeric species [(L2Cu)2](BF4)2 showed an
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vibration, supporting the formulation of an Cu1SE complex. Due
to the monomer-dimer equilibrium, some of the dimeric complex
[(L2Cu)2](BF4)2 should be present at the low temperature used in
the experiment. However, due to a significantly higher reactivity
of the monomeric complex towards dioxygen, it can be assumed
that predominantly monomeric [L2Cu]BF4 reacts with dioxygen in
a steady state manner, even at low temperature.
a)
1.0
359
0.8
0.6
0
5
10
15
t / s
20
25
30
595
1071
1136
0.4
0.2
0.0
16O2
18O2
16O2
-
18O2
[L2Cu]BF4
[L2Cu]BF4+ O2
400
600
l/ nm
800
1000
65 cm-1
b)
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
0,09
0,06
0,03
0,00
341
1000
1050
1100
1150
0
500
1000 1500 2000
t / s
Raman shift / cm-1
Figure 3. Resonance Raman spectra after the oxygenation of [L2Cu]BF4 with
16O2 or 18O2 at 93 °C and difference spectrum (16O–18O), lex = 329 nm also
showing the individual Lorentzians used for fitting the data.
[(L1Cu)2](BF4)2
[(L1Cu)2](BF4)2+ O2
574
In the case of the dimeric complex [(L1Cu)2](BF4)2, a much
slower (> 1500 s) evolution of two new bands (one at 341 nm
(= 4900 L mol1 cm1) and another extremely broad one at
574 nm (= 345 L mol1 cm1)) is observed in the UV/Vis spectra
upon dioxygen addition at a temperature of 40 °C. No further
changes were observed with time, indicating that the
corresponding species is stable at 40 °C. Clearly, the band at
574 nm cannot be attributed to a charge-transfer transition due
to its low extinction coefficient, but rather belongs to a CuII d-d
transition. UV/Vis spectra were also recorded for dioxygen
addition at lower temperatures (80 °C) but gave essentially the
same results. Low-temperature Raman measurements of an
oxygenated solution of [L1Cu]2(BF4)2 at 40 °C (lex = 283 nm)
showed no O-isotope sensitive bands between 500 and
2000 cm1. On these grounds, the bands almost certainly do not
belong to the initial copper-dioxygen complex, but to a rapidly
formed decomposition product. The high positive charge and the
steric hindrance are factors that might be relevant for the
differences in the reactivity toward dioxygen between the dimeric
complex [(L1Cu)2]2+ and the monomeric complex [L2Cu]+.
400
600
800
l / nm
4
1
Figure 2. Spectral changes for the reaction of a) [L2Cu]BF4 (4.34·10 mol L
)
for the first 30 s at 80 °C) (Inset: First-order plot (ln(A A) vs. time) based on
∞
4
1
the absorbance change at 595 nm) and b) [(L1Cu)2](BF4)2 (2.49·10 mol L
)
for the first 2500 s at 40 °C (Inset: Absorbance change at 574 nm) in
propionitrile with dioxygen.
For the monomeric copper complex [L2Cu]BF4, a fast evolution
(10 s) of intense bands at 359 nm (= 1800 L mol1 cm1) and
595 nm (= 970 L mol1 cm1) was observed which follows a first
order kinetics for the reaction with dioxygen at 80 °C. The
wavelengths of the absorption maxima and their extinction
coefficient are close to those reported previously in the literature
for an end-on superoxo complex, Cu1SE.[2,23,35] Due to its high
intensity, the absorption at 595 nm clearly qualifies for a
characteristic copper-dioxygen charge-transfer transition. The
formation of a side-on superoxo complex Cu1SS [2,25] or other
dioxygen species, that typically display only weak d-d transitions
in the region around 600 nm, can be excluded. The bands
assigned to the Cu1SE complex decreased again with time (t1/2 ≈
5 min), indicating that the complex is unstable even at low
temperature. Addition of TEMPOH produced the fast decline of
the bands at 595 and 359 nm (see SI), as typical for end-on
superoxo complexes.[2,23,35] The Resonance Raman (rR)
spectrum (excited with 329 nm light) of an oxygenated solution
of [L2Cu]BF4 at 93 °C included an O-isotope sensitive signal at
1136 cm1 (18O2 = 65 cm1; Figure 3). The peak position and
associated isotope shift is similar to those reported for Cu1SE
complexes [18,21,23, 55 ] and is assigned to the OO stretching
Having studied the reactivity toward dioxygen at low-
temperature with UV/Vis spectroscopy, we repeated the reaction
for [(L1Cu)2]2+ on a larger scale with varying solvents and
temperatures (Scheme 5). In experiments, in which the complex
[(L1Cu)2](PF6)2 was reacted with dioxygen in acetonitrile at room
temperature and the reaction mixture subsequently quenched
with water, complex [3] (Scheme
5 and Figure 4) was
crystallized, after extraction with dichloromethane, from
a
saturated acetonitrile solution. Ligand L1 was not only
hydroxylated, but further oxidized to a diketone. In addition, a
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chloride ion, abstracted from
a
dichloromethane solvent
Scheme 5). This finding led us to the conclusion that the
oxidation to the ketone occurs in a secondary reaction after
ligand hydroxylation. Now, we studied the reaction at low
temperature, using acetone instead of acetonitrile as solvent. In
this experiment, we injected dioxygen for ca. 5 min into a
solution of the complex [(L1Cu)2](PF6)2 in acetone at −78 °C,
resulting in a green-bluish mixture that was stored in the freezer
(−80 °C, 7 d). After purging the solution with argon (~ 5 min),
warming to room temperature and overlaying with Et2O, blue
crystals of the trinuclear copper complex [5] were obtained in
33% isolated yield (Scheme 5 and Figure 4). The three copper
atoms are coordinated by three monoanionic new ligands that
result from oxidative removal of one guanidino group and further
reaction with an acetone solvent molecule. A central six-
membered ring of alternating copper and oxygen atoms is
formed, and coordination of the guanidino group and the
pyridine nitrogen atoms complete the coordination number four
of each copper atom. In all three cases, an aliphatic ligand
hydroxylation occurred in the first place.
molecule, coordinated to the CuII atom. We repeated the
reaction (Scheme 5) at −78 °C and passed Ar through the
reaction mixture (~ 5 min) at this low temperature to remove free
(un-coordinated) dioxygen. After warming to room temperature
and solvent removal in vacuo, dichloromethane was added.
Based on the accumulated experimental results it is assumed
that a labil Cu1SE complex is initially formed, leading to
intramolecular ligand hydroxylation. The formation of higher
nuclear complexes, i. e. Cu2O2 complexes (Scheme 1a), which
are also known for hydroxylating activity, can be excluded due to
the steric hindrance of [(L1Cu)2]2+ (with a stable dimeric structure
in MeCN solutions), as illustrated in the space filling model
(Figure 1), and from the results obtained with the complex
[L2Cu](BF4). Furthermore, we tested the hydroxylating activity of
[(L2Cu)O2]BF4
by
addition
of
10
eq.
of
N2-
benzyltetramethylguanidine (6) to the previously generated
Cu1SE complex at low temperatures in the UV/Vis. Even after
warming to room temperature, no hydroxylation products of 6
were found (GC-MS). Since methylation of the ligand is not
expected to have a great impact on the reactivity at the copper
atom, we exclude monomeric [(L1Cu)O2]BF4 to be responsible
for the hydroxylation reaction in the complexes [3], [4] and [5]
(Scheme 5).
Scheme 5. Formation of the mononuclear CuII complexes [3]PF6 and [4]PF6,
and the trinuclear CuII complex [5](PF6)3 from reaction between [(L1Cu)2](PF6)2
and dioxygen at different conditions (temperature, solvent).
Solid-state reaction of [(L1Cu)2](BF4)2 with dioxygen
Treatment of crushed crystals of [(L1Cu)2](BF4)2 with a mixture of
16O2 and 18O2 resulted in a color change from orange to green.
After removal of the dioxygen with Ar, the reaction product was
dissolved in dichloromethane. The HR ESI-MS analysis (Figure
5a) found peaks at m/z 441.1911 for [L1+Cu+C16O2H]+ and at
m/z 443.1956 and 445.1993, due to [L1+Cu+C16O18OH]+ and
[L1+Cu+C18O2H]+. CID experiments of the isolated ions (MS-MS)
indicated the dissociation of C16O2, C16O18O and C18O2,
respectively, from these species, arguing for the coordination of
formiate to the copper complex. Control experiments without the
addition of dioxygen, as well as the incorporation of the 18O2 into
the carbon dioxide, argue against the presence of impurities in
the copper complex or the ESI-MS spectrometer as sources for
the observed mass signals. Therefore, it is assumed that one of
the tetramethylguanidino groups is hydroxylated and further
oxidized to formiate by the copper complex. IR spectra, recorded
for KBr disks of solid [(L1Cu)2](BF4)2 after the reaction with 16O2
Figure 4. Structures of [3]PF6 and [5](PF6)3 (Cu atoms in orange, N atoms in
blue, Cl atoms in green, O atoms in red and C atoms in grey). Hydrogen
atoms, co-crystallized solvent molecules and counter-ions are omitted for
clarity. Thermal ellipsoids are drawn at the 50% probability level (see SI for
details).
The HR ESI-MS spectra of the reaction mixture displayed a
peak at the mass of the doubly-hydroxylated complex [4] (see
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or 18O2 displayed some differences in the region around 1600
cm1 typically for (C=O) vibrations, indicating that hydroxylation
took place in the solid state. Unfortunately, the presence of
strong (C=N) vibrations of the remaining guanidino groups
hampered an unambiguous assignment of the IR absorption
maxima in this region (see SI).
The triplet state is computed in both cases to be lower in energy
(by 8.8 kJ mol1 for [L2CuO2]+ and by 22.2 kJ mol1 for
[(L1Cu)2O2]2+) than the broken-symmetry state. Figure 6
illustrates the optimized structures for the triplet ground states of
the dinuclear [(L1Cu)2O2]2+ and the mononuclear [L2CuO2]+
Cu1SE complexes. The structural parameters for [L2CuO2]+ are
1.936 and 2.734 Å for the Cu−O distances, and 113.8° for the
Cu−O−O angle. The O−O bond length of 1.300 Å, compares
with a bond length of 1.21 Å in free dioxygen,[56] supporting the
formulation as a strongly activated superoxide. An example for a
Cu1SE complex with a weak degree of charge-transfer is the
enzyme PHM (O−O bond length of 1.23 Å)[32]; whereas a strong
degree of charge-transfer in Cu1SE complexes results in O-O
distances of ca. 1.29 Å.[23,57,58]
a)
[L1+Cu+C16O2H]+
441.1911
[L1+Cu+C18O2H]+
The structural parameters calculated for the dinuclear complex
[(L1Cu)2O2]2+ (2.254 and 3.050 Å for the Cu−O distances, 118.2°
for the Cu−O−O angle and 1.235 Å for the O−O bond length)
indicate much weaker degree of charge-transfer in the copper-
dioxygen complex, nearly identical to that reported for PHM.[32]
In line with the space-filling model (Figure 1b) only one copper
atom is accessible for O2 coordination, the twofold-coordinated
copper atom. The reduced ability of the copper atom in
[(L1Cu)2O2]2+ to donate electron density to the dioxygen unit
might result from its low coordination number. A subsequent
reaction to give higher nuclear complexes (see Scheme 1a) is
prohibited by the steric demand of the ligand. The calculations
found no other energy minima for isomeric copper-dioxygen
complexes. For example, starting with a structure with a side-on
(Cu1SS) bound dioxygen unit, the calculation converged to the
structure of the end-on superoxo (Cu1SE) complex.
445.1993
[L1+Cu+C16O18OH]+
443.1956
436
438
440
442
444
446
448
450
452
454
m / z
b)
[L
1
[L
1
[L
1
+Cu+C16O2H]+
+Cu+C16O18OH]+
+Cu+C18O2H]+
436
438
440
442
444
446
448
450
452
454
m / z
Figure 5. a) ESI-MS spectra recorded in DCM for [(L1Cu)2](BF4)2 after solid-
state reaction with a mixture of 18O2 and 16O2. The Lewis structure of the
suggested fragment is shown in the upper right corner. b) Simulation of the
fragments [L1+Cu+C16O2H]+, [L1+Cu+C16O18OH]+ and [L1+Cu+C18O2H]+.
Figure 6. DFT optimized structures of end-on triplet CuII superoxo complexes
(Cu atoms in orange, O atoms in red, N atoms in blue, C atoms in grey and H
atoms from the methylene bridge (H(CH2) in green). Hydrogen atoms are
omitted for clarity. The shortest Cu-O-O···H(CH2) distance is 3.188 Å.
DFT calculations
The structures of the two Cu1SE complexes were calculated to
obtain more detailed information, considering both triplet and
broken-symmetry states using the TPSSh+D3 functional and the
TZVP basis set. To evaluate the accuracy of our computations,
we first carried out calculations for the unique example of a
structurally characterized Cu1SE complex (for more details, see
SI), featuring the tris[2-(N-tetramethylguanidyl)-ethyl]amine
ligand (2, Scheme 2).[21] The calculated O-O bond length is
1.282 Å, in pleasing agreement with the experimentally
determined bond length of 1.280(3) Å.[21,48]
Subsequently, the low-energy electronic excitations for
[L2CuO2]+ were calculated with TD-DFT and compared with the
excitations observed in the UV/Vis spectra (Figure 7a). For the
monomeric complex [L2CuO2]+, the calculations predict a single
strong electronic transition in the visible region at 596 nm,
involving predominantly orbitals at the CuII atom and the
superoxide unit. Hence the calculations are in excellent
agreement with the experimental spectrum, showing a strong
band at 596 nm. To understand the hydroxylating reactivity of
[(L1Cu)2]2+, we first examined the electronic structure of the
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initially formed Cu1SE complex based on DFT calculations. The
spin density determined by a natural population analysis [ 59 ]
mainly resides on the two oxygen atoms (0.87 and 0.85 e Å−3,
respectively) due to weak charge-transfer in the copper-
could further react to a Cu1O species) by proton transfer from a
solvent molecule to the O2 unit of the Cu1SE complex, as
assumed from DFT calculations in the literature, could be
excluded.[33] The high pKa value of acetonitrile argues against
dioxygen complex, as indicated by the short O-O bond (1.235 Å). this mechanism. In all three cases ([3]PF6, [4]PF6 and [5](PF6)3),
As already mentioned, the low coordination number of two for
the CuB atom (Scheme 6), and the high total charge of 2+ of the
complex could be responsible for this weak charge-transfer in
the copper-dioxygen complex. The spin density at the CuB atom
is 0.20 e Å−3. Interestingly, a small but significant spin density of
0.023 e Å−3 was found at the buried CuA atom. The existence of
spin density at the fourfold coordinated CuA atom indicates its
ability to transfer electron-density to CuB (see below). With
0.0076 e Å−3, the total spin density at the pyridine ring is very
small.
intramolecular proton-coupled electron transfer (PCET, Scheme
6a) to the dioxygen unit attached to CuB is assumed to be the
first step of the reaction sequence, in analogy to the mechanism
reported by Itoh et al.[39]. One could identify two possible
reaction sites for hydrogen atom abstraction at the methylene
bridge, denoted L and R in Scheme 6a.
Hydrogen atom abstraction at the L reaction site can occur after
rotation around the Cu-O bond, reducing the distance between
the outer oxygen atom and the hydrogen atom to ~3.6 Å. A
cooperative effect of the CuA center leads to a stabilization of the
PCET product through delocalization of the spin density to CuA,
as expressed by the two mesomeric structures LI and LII
(Scheme 6a), and the guanidino groups. A natural population
analysis indeed found spin density (Scheme 6b) not only at the
activated methylene bridge (0.52 e Å−3), but also at the pyridine
ring as well as at the guanidino group. In addition, the spin
density at the CuA atom increased from 0.023 e Å−3
([(L1Cu)2(O2)]2+) to 0.084 e Å−3, in line with a partial oxidation of
CuA as expressed by the Lewis structure LII. The relevance of
structure LII is further demonstrated by a significant shortening of
the bonds highlighted in orange (see Scheme 6a, for detailed
comparison see SI). The calculated Gibbs free energy change
(at 298.15 K, 1 atm) for the intramolecular PCET process for
[(L1Cu)2(O2)]2+ of 46 kJ mol1 is lower than that reported by
Itoh et. al.[39] for the analogue process in mononuclear copper
complexes of ligand 1X (69 kJ mol1 for X = H). This result
demonstrates the importance of the cooperative effect of the CuA
atom, that stabilizes the PCET product with respect to the
[(L1Cu)2(O2)]2+ starting complex though the resulting mesomeric
stabilization of LI and LII (Scheme 6a). A transition state TS1
was localized (see SI). The relative free activation energy of
122 kJ mol1 was estimated with a single-point calculation using
COSMO (r = 37.50). The hydrogen atom at reaction site R is
closest to the superoxide oxygen with 3.188 Å, without the need
of a further rotation. In addition, the calculated free energy
change (298.15 K, 1 atm) for the intramolecular PCET process
is only 34 kJ mol1, being by 12 kJ mol1 lower than that
calculated for reaction site L. This can be explained by a better
mesomeric stabilisation of the PCET product in RI and RII,
leading to a high spin density at CuA of 0.13 e Å−3. The spin
density at CuB is 0.45 e Å−3. Unfortunately, we were not able to
find a transition state for this PCET process so that it is not clear
if reaction occurs both at R and L or preferentially at one of
these sites. The relatively high activation energy of 122 kJ mol1
is close to that estimated for the C-H bond cleavage in the
enzyme PHM.[60] As emphasized previously, the environment
plays an important role in calculating the activation barrier in this
process where the experimental value should be significantly
lower. Therefore, we suggest an overestimation of the activation
energy especially due to the inaccuracy in calculating the
solvent effect with COSMO.
Figure 7. a) Comparison between the TD-DFT (TPSSh+D3/def2-TZVP)
results for the 50 lowest-energy electronic excitations and the UV/Vis
spectrum for [L2CuO2]+. b) Isodensity plots for the orbitals involved in the low-
energy (charge-transfer) transition at 596 nm.
Having studied the electronic structure of the initially formed
Cu1SE complex, quantum-chemical calculations for the first
steps in the hydroxylating mechanism were performed.
According to the literature, basically three intermediates (Cu1SE,
Cu1PH, Cu1O) are considered for the hydroxylating activity of the
enzyme PHM.[11,33,34] The formation of a Cu1PH complex (which
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Substrate oxidation experiments
To further illuminate the role of metal cooperativity in ligand
hydroxylation, we tested the hydroxylation of the external
guanidine 6 with complex [(L1Cu)2](PF6)2 and dioxygen (Scheme
7). No reaction was observed, although the reaction was carried
out in neat 6, in accordance with the importance of metal
cooperativity through the mesomeric stabilisation of I and II
(Scheme 6a).
Scheme 7. Attempted hydroxylation of the external substrate
[(L1Cu)2](PF6)2. No reaction occurred, in line with the importance of metal
cooperativity for the hydroxylation of L1 in the [(L1Cu)2]2+ complex.
6 with
Recently, the first example of a nucleophilic copper superoxide
was reported that induces a catalytic aldol reaction, i.e. with
a)
(122)
(45.6)
(34.0)
(0.00)
b)
c)
Scheme 6. a) Energy profile (in kJ mol1) of the proposed hydroxylating pathway (two possible reaction sites L and R). Bonds of LII and RII highlighted in
orange are shortened in comparison with [L1Cu)2(O2)]2+. b) and c) Calculated spin density for [(L1Cu)2(HO2)]2+ (green circles, TPSSh+D3/def2-TZVP),
hydrogen atoms (except OH) omitted for clarity (Cu atoms in orange, N atoms in blue, O atoms in red and C atoms in grey).
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acetone, forming 4-hydroxy-4-methyl-2-pentanone at room
temperature.[61] In this respect, the isolation of diacetone alcohol
(4-hydroxy-4-methyl-2-pentanone, Scheme 8) as a side product
in the course of the formation of [5] motivated us to test the two
complexes [(L1Cu)2](PF6)2 and [L2CuO2]PF6 in the dioxygen
activation in terms of a catalytic conversion of acetone.
Both complexes were applied in catalytic amounts (1.5 mol%)
and clearly showed a catalytic conversion of acetone with a turn-
over number (TON) of 6.50 for [(L1Cu)2](PF6)2 and 2.25 for the
monomeric complex [L2Cu]PF6 .
Experimental Section
The copper complexes were stored under an inert argon
atmosphere in glovebox (MBraun Labmaster dp). All
a
chemicals were purchased from Aldrich and used without further
purification unless stated otherwise below. Solvents were dried
with an MBraun Solvent Purification System, degassed by three
freeze-pump-thaw cycles and stored over molecular sieves prior
to their use. Propionitrile was purified and dried according to a
literature procedure.[62] Dioxygen (Air Liquide, AlphagazTM, purity
≥ 99.998%) was dried by passing through a short column of
supported P4O10. The synthesis of L1 and 2,6-bis(-
aminoisopropyl)pyridine followed literature procedures.[52,
63
]
Elemental analyses were carried out at the Microanalytical
Laboratory of the University of Heidelberg. NMR spectra were
recorded on a Bruker Avance II 400 system (BBFO probe) or
Bruker Avance III 600 spectrometer (QNP Cryoprobe, inner coil
tuned to 13C, cold preamplifier). Prior to variable temperature
measurements, the temperature was calibrated by the method of
Berger et al.[64] Solvent resonances were taken as references for
all 1H NMR or 13C NMR spectra.[ 65 ] UV/Vis spectra were
recorded with a Varian Cary 5000 spectrophotometer. For IR
spectroscopy, KBr disks of the compound were measured with
an FTIR spectrometer (Biorad, Model Merlin Excalibur FT 3000).
ESI-MS and CID experiments of isolated ions (MS-MS) relied on
a Bruker ApexQe hybrid 9.4 T FT-ICR mass spectrometer.
Raman measurements were performed with a UT-3 Raman
spectrometer [66], using a frequency doubled/tripled Ti:sapphire
laser (Tsunami model 3960C-15HP, Spectra Physics Lasers
Inc.) with a pulsewidth of 1.6-2.5 ps. The cryostat was a slightly
modified version of a setup described earlier [67] with a 1.4 ml
screw cap Suprasil cuvette with septum (Hellma Analytics,
Müllheim) for oxygenation, equipped with a Peltier element
(QuickCool QC-127-1.4-6.0MS) and a cooling copper block
which encloses three sides of the cuvette.
Scheme 8. Formation of 4-hydroxy-4-methyl-2-pentanone from acetone
(cat. = [(L1Cu)2](PF6)2 or [L2CuO2]PF6).
Conclusions
Herein we report on the reactions of two new copper(I)
complexes, bearing bisguanidine ligands, with dioxygen. With
2+
ligand L1, a dinuclear complex [(L1)Cu]2 with two significantly
different CuI atoms is formed, both in the solid-state and in
solution. Only one of the copper atoms is able to bind dioxygen,
since the other copper atom is buried inside the ligand shell. By
contrast, the slightly modified ligand L2 prefers formation of a
mononuclear CuI complex [(L2)Cu]+. Both complexes are
suggested to react with dioxygen to thermally labile end-on
superoxo complexes (Cu1SE), that differ in the degree of charge-
transfer. The dimeric complex [(L1Cu)2(O2)]2+ exhibits a weak
degree of charge-transfer, whereas for [(L2)Cu(O2)]+ a strong
degree of charge-transfer is found.
Intramolecular hydrogen atom abstraction from the methylene
bridge of L1 by the O2 unit leads to ligand hydroxylation, initiating
a reaction sequence that leads (depending on the reaction
conditions) either to mononuclear or trinuclear copper
complexes with oxidized ligand units. With respect to the degree
of charge-transfer of the copper-dioxygen complexes and the
2,6-bis(1-tetramethylguandino-1-methyl-ethyl)pyridine (L2).
Tetramethylurea (0.9 mL, 7.4 mmol) is dissolved in chloroform
(6 mL). Oxalyl chloride (3.2 mL, 37 mmol) is added dropwise,
and the solution is heated to reflux (80 °C) for 18 h. Then the
reaction mixture is allowed to cool back to room temperature,
the solvent removed in vacuo, and the pale-yellow precipitate
washed three times with portions of diethyl ether (10 mL). The
colorless guanidinium chloride is dried under vacuum. 2,6-
Bis(-aminoisopropyl)pyridine (840 mg, 2.80 mmol) is dissolved
in dichloromethane (20 mL), and dry triethylamine (1.7 mL,
12 mmol) is added. The chloroformamidinium chloride is
dissolved again in dichloromethane (15 mL) and is subsequently
added slowly to the diamine at –10 °C. The reaction mixture is
stirred at –10 °C for 1 h, 10% HCl (10 mL) is added, the phases
are separated, and the organic layer is washed with 10% HCl
(2 x 10 mL). The combined aqueous layers are washed with
dichloromethane (10 mL), and 50% KOH (20 mL) is added.
Then the aqueous layer is extracted with toluene (3 x 20 mL).
The combined toluene phases are dried with K2CO3, and the
solvent is removed in vacuo to obtain a brown-coloured oil.
Further purification is achieved by crystallization from an
2+
resulting C-H activation, the complex [(L1)Cu]2 might be a
model for the enzyme peptidylglycine α-hydroxylating
monooxygenase (PHM). Further analysis showed that the two
copper atoms in [(L1Cu)2(O2)]2+ communicate via charge-transfer
(like for PHM and cofactor). This cooperative effect on the
hydroxylating reaction between both copper atoms was further
studied by DFT computations and suggested to be the key
driving force for the proton-coupled electron transfer in the C-H
activation process.
Furthermore, both complexes mediate acetone dimerization to
4-hydroxy-4-methyl-2-pentanone, similar to a recently reported
nucleophilic Cu1SE complex.[61,61] Studies on the reactivity of the
complex [(L2)Cu(O2)]+, which is stable for minutes at low
temperatures, as a potential nucleophile are currently on the
way in our laboratories.
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acetonitrile solution of the oil in the freezer (–18 °C) over several
2.72 (s, 12 H), 2.40 (s, 12 H), 1.61 (s, 12 H) ppm; 13C NMR (150
MHz, CD3CN): 167.27, 160.75, 138.37, 117.19, 62.21, 40.32,
39.45, 29.67 ppm. Elemental analysis (%) for C21H39N7BCuF4
(539.94: calcd. C 46.71, H 7.28, N 18.16; found C 46.73, H 7.31,
days. The colorless crystals are dried in vacuo to afford a
1
colorless powder (468 mg, 120 µmol, 43%). H NMR (400 MHz,
CD3CN):  = 7.47 (m, 1 H), 7.19 (d, J = 7.8 Hz, 2 H), 2.63 (br. s,
12 H), 2.26 (br. s, 12 H), 1.50 (s, 12 H) ppm. 13C NMR (100 MHz, N 19.09. UV/Vis (CH3CN, c = 6.00·10−5): lmax ( in L mol−1 cm−1)
CD3CN): = 168.38, 157.41, 135.81, 60.94, 32.14 ppm.
Elemental analysis (%) for C21H39N7 (389.59): calcd. C 64.74, H
10.09, N 25.17; found C 64.38, H 9.90, N 25.25. Crystal data for
L2: C21H39N7, Mr = 389.59 g mol−1, 0.60 mm ✕ 0.40 mm ✕ 0.30
mm, monoclinic, space group C2/c, lattice constants a =
= 212 (3.76·104), 263 (1.44·104), 414 (686) nm.
[3]PF6.
A solution of tetrakis(acetonitrile)copper(I) hexafluorophosphate
(112 mg, 299 µmol) and L1 (100 mg, 299 µmol) in acetonitrile
24.238(5) Å, b = 7.4070(15) Å, c = 13.794(3) Å, V = 2272.1(9) Å3, (1.5 mL) is stirred for a period of 1 h at room temperature.
Z = 4, dcalc = 1.139 g cm−3, Mo Kα radiation (graphite-
monochromated, λ = 0.71073 Å), T = 120 K, θmax = 30.127°,
number of reflections measured: 3326, number of independent
reflections: 2224, final R indices [I > 2(I)]: R1 = 0.0481, wR2 =
0.1319.
Dioxygen is introduced via a syringe (1 bar overpressure) and
the mixture is stirred for 16 h. Then water (10 mL) is added and
the mixture is extracted with dichloromethane (4 x 7 mL). The
combined organic layers are dried over magnesium sulfate and
the solvent is removed in vacuo. Green crystals of [3]PF6 are
grown from slowly evaporating a saturated acetonitrile solution.
Crystal data for [3]PF6: C17H27N7CuO2ClF6P, Mr = 605.41 g mol−1,
0.50 mm ✕ 0.50 mm ✕ 0.3 mm, orthorhombic, space group
Pnma, lattice constants a =11.674(2) Å, b = 14.092(2) Å, c =
15.341(3) Å, V = 2523.7(9) Å3, Z = 4, dcalc = 1.593 g cm−3, Mo Kα
radiation (graphite-monochromated, λ = 0.71073 Å), T = 120 K,
θmax = 30.078°, number of reflections measured: 3836, number
of independent reflections: 2754, final R indices [I > 2(I)]: R1 =
[(L1Cu)2](BF4)2.
A
solution of tetrakis(acetonitrile)copper(I) tetrafluoroborate
(94.0 mg, 299 µmol) and L1 (100 mg, 299 µmol) in acetone
(1 mL) or acetonitrile (1 mL) is stirred for 1 h at room
temperature. Then the solution is overlayered with Et2O (10 mL)
to grow orange crystals overnight. The crystals are dried in
vacuo to afford the product as an orange powder (110 mg, 138
µmol, 92%). 1H NMR (600 MHz, CD3CN): 7.81 (t, J = 7.7 Hz,
1 H), 7.28 (d, J = 7.7 Hz, 2 H), 4.50 (s, 4 H), 2.79 (s, 12 H), 2.52
(s, 12 H) ppm. 13C NMR (150 MHz, CD3CN): 165.85, 160.56,
139.42, 122.89, 57.83, 30.44, 39.37 ppm. Elemental analysis
(%) for C34H62N14B2Cu2F8 (967.68): calcd. C 42.20, H 6.46, N
20.26; found C 41.82, H 6.36, N 21.02 UV/Vis (CH3CN, c =
7.47·10−5): lmax ( in L mol−1 cm−1) = 210 (2.72·104), 272
(8.64·103), 357 (883) nm. Crystal data for [(L1Cu)2(BF4)2]:
C34H62N14B2Cu2F8 from acetonitrile solution, Mr = 967.68 g mol−1,
0.0547, wR2
=
0.1595. HRMS (ESI+): m/z calcd for
C17H27N7O2CuCl [M+] 459.1211, found 459.1213.
[4]PF6.
A solution of tetrakis(acetonitrile)copper(I) hexafluorophosphate
(56.0 mg, 150 µmol) and L1 (50.0 mg, 150 µmol) in propionitrile
(2 mL) is stirred for a period of 1 h at room temperature. The
reaction mixture is cooled to −78 °C, dioxygen is introduced via
a syringe (0.2 bar overpressure) and the mixture is stirred for 4 h.
After purging the resulting blue solution with argon (~5 min) and
warming up to room temperature (color change to green), the
solvent is removed in vacuo and dichloromethane is added.
HRMS (ESI+): m/z calcd for C17H31N7O2CuCl [M+] 463.1524,
found 463.1525.
0.40 mm ✕ 0.25 mm ✕ 0.15 mm, triclinic, space group P1̅,
lattice constants a = 9.906(2) Å, b = 11.162(2) Å, c = 11.236(2)
Å, V = 1099.3(5) Å3, Z = 1, dcalc = 1.462 g cm−3, Mo Kα radiation
(graphite-monochromated, λ = 0.71073 Å), T = 120 K, θmax
=
31.00°. Number of reflections measured: 13069; number of
independent reflections: 10373, final R indices [I > 2(I)]: R1 =
0.0505, wR2
C34H62N14B2Cu2F8 from acetone solution, Mr = 967.68 g mol−1,
0.80 mm ✕ 0.60 mm ✕ 0.50 mm, triclinic, space group P1
lattice constants a =16.350(3) Å, b = 20.870(4) Å, c = 26.131(5)
Å, V = 8917(3) Å3, Z = 8, dcalc = 1.442 g cm−3, Mo Kα radiation
=
0.1364. Crystal data for [(1Cu)2(BF4)2]:
[5](PF6)3.
A solution of tetrakis(acetonitrile)copper(I) hexafluorophosphate
(112 mg, 299 µmol) and L1 (100 mg, 299 µmol) in acetone
(3 mL) is stirred for 1 h at room temperature. Dioxygen is
introduced via a syringe (−78 °C) and the mixture filtered via a
syringe filter. The solution is stored for 1 week in the freezer
(−80 °C). Residual dioxygen is removed by bubbling Ar (~5 min)
through the reaction solution at −78 °C. Blue crystals are grown
by ether diffusion into the solution at –18 °C and washed with
cold acetone (2 mL) and diethylether (5 mL). The crystals are
dried in vacuo to afford [5](PF6)3 as a blue powder (50 mg, 33.3
µmol) in 33% isolated yield. Elemental analysis (%) for
C45H69N12Cu3O6(F6P)3(C3H6O)1.5 (1543.21): calcd. C 36.78, H
4.80, N 10.89; found C 37.61, H 5.12, N 10.76IR (KBr):
ν = 3102 (w), 2009 (w), 2947 (m), 2900 (m), 2812 (w), 1698 (s),
1611 (m), 1588 (s), 1477 (m), 1427 (m), 1400 (m), 1358 (m),
1339 (w), 1294 (w), 1255 (w) 1236 (w), 1166 (s), 1146 (w),
1115(w), 1070 (m), 1054 (s), 1015 (w), 972 (w), 939 (w), 912 (m),
̅
,
(graphite-monochromated, λ = 0.71073 Å), T = 120 K, θmax
=
30.063°, number of reflections measured: 13050, number of
independent reflections: 8428, final R indices [I > 2(I)]: R1 =
0.0541, wR2 = 0.1792.
[L2Cu]BF4.
A
solution of tetrakis(acetonitrile)copper(I) tetrafluoroborate
(18.4 mg, 58.5 µmol) and L2 (23.4 mg, 58.5 µmol) in CH3CN
(2 mL) is stirred for a period of 1 h at room temperature. Then
the solvent is removed in vacuo, the residue is washed with Et2O
(2 x 2 mL) and the solid is dried in vacuo to afford the product as
an orange powder (25.0 mg, 51.7 µmol, 88%). 1H NMR (600
MHz, CD3CN) for the monomer: 7.72 (m, 1 H), 7.30 (m, 2 H),
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877 (m), 841 (s), 791 (m), 764 (m), 784 (w) 691 (m), 669 (w),
648 (m) 622 (m), 558 (s), 530 (w), 496 (m), 465 (w), 450 (w),
428 (w), 421 (m) cm1. UV/Vis (CH3CN), c = 4.61·10−5): lmax ( in
L mol−1 cm−1) = 218 (5.46·104), 267 (2.08·104), 334 (4.12·103),
Nonius software.[69] Multiscan absorption correction was applied
to all intensity data using the SADABS program.[ 70 ] The
structures were solved and refined using the SHELXTL software
package (Version 2014/6 and 2018/3).[71,72] Graphical handling
of the structural data during solution and refinement were
performed with XPMA and OLEX2.[73] All non-hydrogen atoms
were given anisotropic displacement parameters. Hydrogen
atoms were generally input at calculated positions and refined
with a riding model. Due to severe disorder electron density
attributed to solvent of crystallization (acetone) was removed
from the structure of [5](PF6)3 with the BYPASS procedure,[74] as
implemented in PLATON (squeeze/hybrid).[75] Partial structure
factors from the solvent masks were included in the refinement
as separate contributions to Fcalc. CCDC 1867620
(L2), CCDC 1867616 ([L1Cu)2](BF4)2) from acetonitrile solution,
CCDC 1867618 ([L1Cu)2](BF4)2) from acetone solution, CCDC
336
(3.03·103)
nm.
Crystal
data
for
[5](PF6)3:
C45H69N12Cu3O6(F6P)3(C3H6O)1.5, Mr = 1543.21 g mol−1, 0.40 mm
✕ 0.30 mm ✕ 0.15 mm, monoclinic, space group C2/c, lattice
constants a = 23.840(5) Å, b = 15.796(3) Å, c = 37.282(8) Å,
V = 13543(5) Å3, Z = 8, dcalc = 1.514 g cm−3, Mo Kα radiation
(graphite-monochromated,
λ = 0.71073 Å), T = 120 K,
θmax = 29.182°, number of reflections measured: 18224, number
of independent reflections: 14550, final R indices [I > 2(I)]:
R1 = 0.0567, wR2 = 0.1718.
Catalytic coupling of acetone to 4-hydroxy-4-methyl-2-
pentanone
A solution of tetrakis(acetonitrile)copper(I) hexafluorophosphate
(112 mg, 299 µmol) and the ligand (L1 or L2, see Table 1) in
1867617 ([5](PF6)3, CCDC 1867619 ([3]PF6)
supplementary crystallographic data for this paper. These data
can be obtained free of charge from The Cambridge
contain the
Crystallographic
Data
Centre
via
acetone (1.5 mL, 20 mmol) is stirred for 1 h at room temperature. https://www.ccdc.cam.ac.uk/data_request/cif.
Dioxygen is introduced via a syringe (1 bar overpressure) and
the mixture is stirred for 20 h. 4-Hydroxy-4-methyl-2-pentanone
and acetone are separated by distillation from the residue. 1H
and 13C NMR data are in line with those reported previously.[68]
Acknowledgements
Table 1. Yield and weighting.
The authors gratefully acknowledge continuous financial support
by the Deutsche Forschungsgemeinschaft (DFG). The authors
are grateful for the computational resources provided by the
bwForCluster JUSTUS, funded by the Ministry of Science,
Research and Arts and the Universities of the State of Baden-
Württemberg, Germany, within the framework program bwHPC-
C5. We thank Dr. J. Gross for the support with ESI-MS
spectrometry.
L1 (100 mg, 299
µmol)
L2 (117 mg, 299
µmol)
Yield diacetone 114 mg, 877 µmol,
77.9 mg, 671 µmol,
TON 2.25)
alcohol
TON 6.50).
Note: The blank experiment with ligand alone did not lead to
conversion of acetone.
Raman-measurements
Keywords: copper • dioxygen complexes • C−H activation •
oxidation • cooperative effects
The laser beam was widened with a spatial filter and then
focused on the cuvette inside the cryostat. The focus spot size
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Entry for the Table of Contents
FULL PAPER
Metal cooperativity is suggested as
the key to intramolecular ligand
hydroxylation in a dinuclear copper
complex.
F. Schön, F. Biebl, L. Greb, S.
Leingang, B. Grimm-Lebsanft,
M. Teubner, E. Kaifer, M. A
Rübhausen, H.-J. Himmel*
Page No. – Page No.
On the Metal Cooperativity
in a Dinuclear Copper-
Guanidine Complex for C−H
Bond Cleavage by Dioxygen
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