Exceptional Substrate Diversity in Oxygenation Reactions Catalyzed by a Bis(μ-oxo) Copper Complex

Article abstract of DOI:10.1002/chem.202000664

The enzyme tyrosinase contains a reactive side-on peroxo dicopper(II) center as catalytically active species in C?H oxygenation reactions. The tyrosinase activity of the isomeric bis(μ-oxo) dicopper(III) form has been discussed controversially. The synthesis of bis(μ-oxo) dicopper(III) species [Cu₂(μ-O)₂(L1)₂](X)₂ ([O1](X)₂, X=PF₆^?_, BF₄^?, OTf^?, ClO₄^?), stabilized by the new hybrid guanidine ligand 2-{2-((dimethylamino)methyl)phenyl}-1,1,3,3-tetramethylguanidine (L1), and its characterization by UV/Vis, Raman, and XAS spectroscopy, as well as cryo-UHR-ESI mass spectrometry, is described. We highlight selective oxygenation of a plethora of phenolic substrates mediated by [O1](PF₆)₂, which results in mono- and bicyclic quinones and provides an attractive strategy for designing new phenazines. The selectivity is predicted by using the Fukui function, which is hereby introduced into tyrosinase model chemistry. Our bioinspired catalysis harnesses molecular dioxygen for organic transformations and achieves a substrate diversity reaching far beyond the scope of the enzyme.

Full text of DOI:10.1002/chem.202000664

A Journal of
Accepted Article
Title: Guanidines strike back: Exceptional Substrate Diversity in
Oxygenation Reactions Catalyzed by a Bis(µ-oxo) Copper
Complex
Authors: Sonja Herres-Pawlis, Melanie Paul, Melissa Teubner,
Benjamin Grimm-Lebsanft, Christiane Golchert, Yannick
Meiners, Laura Senft, Kristina Keisers, Patricia Liebhäuser,
Thomas Rösener, Florian Biebl, Sören Buchenau, Maria
Naumova, Vadim Murzin, Roxanne Krug, Alexander
Hoffmann, Jörg Pietruszka, Ivana Ivanovic-Burmazovic, and
Michael Rübhausen
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content of this Accepted Article.
To be cited as: Chem. Eur. J. 10.1002/chem.202000664
Link to VoR: http://dx.doi.org/10.1002/chem.202000664
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Guanidines strike back: Exceptional Substrate Diversity in Oxy-
genation Reactions Catalyzed by a Bis(µ-oxo) Copper Complex
Melanie Paul[a], Melissa Teubner[a,b], Benjamin Grimm-Lebsanft[b], Christiane Golchert[a], Yannick
Meiners[a], Laura Senft[c], Kristina Keisers[a], Patricia Liebhäuser[a], Thomas Rösener[a], Florian Biebl[b],
Sören Buchenau[b], Maria Naumova[d], Vadim Murzin[d], Roxanne Krug[e], Alexander Hoffmann[a], Jörg
Pietruszka[e,f], Ivana Ivanović-Burmazović[c], Michael Rübhausen[b], Sonja Herres-Pawlis*[a]
Abstract: The enzyme tyrosinase contains a reactive side-on
peroxo dicopper(II) center as catalytically active species in C-H
oxygenation reactions. The tyrosinase activity of the isomeric
bis(µ-oxo) dicopper(III) form has been discussed controversially.
We describe the synthesis of bis(µ-oxo) dicopper(III) species
electrophilic aromatic substitution via its catechol form to the final
quinone form.[4] Although structure and reactivity of tyrosinases
were studied extensively, many details of the oxidation mecha-
nism are still under debate.[5] Recently, second shell residues at
the active site (approx. 5.5-16 Å distance to Cu ions) were con-
sidered to direct the reactivity of the enzyme.[2b,6]
[Cu2(µ-O)2(L1)2](X)2 ([O1](X)2, X = PF6 , BF4 , OTf-, ClO4 ), stabi-
lized by the novel hybrid guanidine ligand 2-{2-((dimethyla-
mino)methyl)phenyl}-1,1,3,3-tetramethylguanidine (L1), and its
characterization via UV/Vis, Raman and XAS spectroscopy as
well as cryo-UHR-ESI mass spectrometry. We highlight selective
oxygenation of a plethora of phenolic substrates mediated by
[O1](PF6)2, which results in mono- and bicyclic quinones and pro-
vides an attractive strategy for designing new phenazines. We
predict the selectivity using the Fukui function which is hereby in-
troduced into tyrosinase model chemistry. Our bioinspired cataly-
sis harnesses molecular dioxygen for organic transformations and
achieves a substrate diversity reaching far beyond the scope of
the enzyme.
-
-
-
For understanding the mechanism of activation and transfer
of O2, synthetic model systems were developed mimicking enzy-
matic properties. Some well-studied Cu/O2 species represent
μ-η2:η2-peroxo Cu(II) [P] and bis(µ-oxo) Cu(III) [O] complexes,
which exist in a dynamic equilibrium due to a small isomerization
barrier.[2b,7] In many functional tyrosinase systems, [P] cores are
found,[8] but an increasing number of examples of functional [O]
species has also been reported.[9] However, only few Tyrosinase
model systems feature catalytic oxygenation reactivity.[10] Réglier
et al. presented the first system using the imine-pyridine ligand
BiPh(impy)2,[11] followed by Casella et al. using the benzimidazole
ligand L66,[12] which both stabilize binuclear Cu catalysts. Later,
Tuczek et al. reported on the mononucleating benzimidazole lig-
and Limpy promoting catalytic conversion of 2,4-di-tert-butyl phe-
nol.[13] Over the years, Lumb et al. have focused on the chemo-
and regioselectivity of tyrosinase-like reactions using the amine
DBED giving rise to several quinones, oxidative coupling and cy-
clization products.[14] More complex phenolic substrates were ox-
ygenated by Herres-Pawlis et al. using bis(pyrazolyl)methane and
guanidine ligands.[15]
The use of dioxygen as a readily available oxidizing agent
is crucial for many biological and biomimetic oxidation processes
as well as industrial applications.[1] Natural copper enzymes such
as tyrosinase or particulate methane monooxygenase success-
fully activate molecular dioxygen.[2] Tyrosinase, in particular, is es-
sential in living organisms catalyzing phenol oxidation in melanin
biosynthesis.[3] It converts phenols, for instance L-tyrosine, via an
Herein, we report on the synthesis and characterization of
hybrid guanidine-stabilized bis(µ-oxo) complex [Cu2(µ-O)2(L1)2]2+
([O1]2+, Scheme 1) along with its high catalytic activity in oxygen-
ation and oxidation reactions of phenolic substrates and subse-
quent condensation reactions, offering a facile synthetic pathway
to new phenazines.
[a]
M. Paul, C. Golchert, Y. Meiners, K. Keisers Dr. P. Liebhäuser, Dr.
T. Rösener, Dr. A. Hoffmann, Prof. Dr. S. Herres-Pawlis
Department of Inorganic Chemistry, RWTH Aachen University
Landoltweg 1, 52074 Aachen, Germany
E-mail: sonja.herres-pawlis@ac.rwth-aachen.de
M. Teubner, Dr. B. Grimm-Lebsanft, F. Biebl, S. Buchenau, Prof. Dr.
M. Rübhausen
Department of Physics, University of Hamburg
Luruper Chaussee 149, 22761 Hamburg, Germany
L. Senft, Prof. Dr. I. Ivanović-Burmazović
[b]
[c]
Department of Chemistry and Pharmacy, Friedrich-Alexander-Uni-
versity of Erlangen-Nürnberg
Egerlandstr. 1, 91058 Erlangen, Germany
[d]
[e]
Dr. M. Naumova, Dr. V. Murzin, Deutsches Elektronen-Synchrotron
DESY, Notkestr. 85, 22607 Hamburg, Germany
Prof. Dr. J Pietruszka
Institute of Bioorganic Chemistry, Heinrich Heine University Düssel-
dorf at Forschungszentrum Jülich, 52425 Jülich, Germany
Dr. R. Krug, Prof. Dr. J. Pietruszka
Scheme 1. Synthesis of bis(µ-oxo) species [O1](PF6)2.
[f]
Guanidines feature high basicity and strong N-donor abili-
ties, enabling stabilization of metal ions with high oxidation
states.[16] For instance, TMG3tren is known to stabilize highly re-
active Cu(II) superoxo complexes.[17] By using [O1](PF6)2, it is
possible to promote selective C-H functionalization of complex
phenolic substrates. To the best of our knowledge, no activity of
Institute of Bio- and Geoscience, Forschungszentrum Jülich GmbH
IBG-1: Biotechnology, 52425 Jülich, Germany
Supporting information for this article (including experimental procedures,
spectroscopic and crystallographic data as well as computational details) is
available on the WWW under:
http://dx.doi.org/10.1002/anie.2019XXXXX.
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50000
a)
8
6
8
7
6
5
4
3
2
1
0
b)
c)
d)
[C1]PF6
45000
620
280
+
+
16O2
18O2
40000
35000
30000
4
530
556
2
591
25000
392
0
#
20000
15000
10000
5000
0
-2
-4
-6
-8
200
300
400
500
600
700
800
0
2
4
6
8
10
12
1
2
3
4
5
6
300
400
500
600
k [Å-1
]
l [nm]
ṽ [cm-1
]
R [Å]
Figure 1. a) UV/Vis spectrum of [O1](PF6)2 (0.5 mM) in THF at –90 °C, b) resonance Raman spectra of [O1](PF6)2 in THF with excitation at 420 nm (blue: 18O2, red:
16O2, green: [C1]PF6, #: solvent), c) k3-weighted Cu-K-edge EXAFS of [O1](PF6)2, d) phase-corrected Cu-K-edge Fourier transform of EXAFS of [O1](PF6)2.
tyrosinases towards complex phenolic substrates was reported
before. [O1](PF6)2 highlights a beneficial interplay of steric and
electronic factors of the ligand regarding substrate accessibility of
[Cu2O2] core leading to a remarkable extension of the substrate
scope. Using a variety of phenolic substances allows the synthe-
sis of new quinones. In a consecutive reaction, quinones can con-
dense with 1,2-phenylenediamine to phenazines, which feature
antibacterial, antimalarial and antitumor activities and are used in
dyes and pesticides.[18] We targeted to selectively obtain bent
phenazines as special benefit of the [O1](PF6)2 mediated hydrox-
ylation, since the calculation of the Fukui function of the hydrox-
ylation products indicated preferential formation of the corre-
sponding quinone.
Information) and agree well with the theoretical model. Moreover,
the edge position is in accordance with the assignment as Cu(III).
For
quantification
of
the
formation
of
[O1](PF6)2,
spectrophotometric back-titration of [O1](PF6)2 was performed
using ferrocene monocarboxylic acid (FcCOOH).[9k-l] Following
the decay of the LMCT band at 392 nm, titration of [O1](PF6)2 with
FcCOOH
revealed
>90%
formation
of
[O1](PF6)2
(Figures S18-19). To elucidate the Cu-O2 stoichiometry of
[O1](PF6)2, cryo-UHR-ESI mass spectrometry was performed
(Figure S20). The isotopic pattern and corresponding m/z values
are in accordance with the calculated spectrum of the
monocationic species [O1](PF6)+ with a 2:1 Cu-O2 ratio.
Inspired by a propylene-bridged hybrid guanidine ligand
system that showed promising phenolase activity,[9k-l] we devel-
oped a related ligand system with a more rigid aromatic backbone.
2-{2-((dimethylamino)methyl)phenyl}-1,1,3,3-tetramethylguani-
dine (L1) was synthesized in a three-step reaction and isolated in
high yield (Supporting Information). Synthesis of the colorless, air-
and moisture-sensitive Cu(I) complex [C1]PF6 was achieved by
mixing equimolar amounts of L1 and [Cu(MeCN)4]PF6 in acetoni-
trile at room temperature. Oxygenation of [C1]PF6 in THF
at -90 °C led to the formation of the khaki-colored species
[O1](PF6)2 (Scheme 1).[19] [O1](PF6)2 showed ligand-to-metal-
charge transfer (LMCT) features at 280 nm (ε = 40000 M-1 cm-1)
and 392 nm (21000 M-1 cm-1) in the UV/Vis spectrum[20] (Fig-
ure 1a), which are characteristic for bis(µ-oxo) dicopper(III) spe-
cies.[8, 21] Similar UV/Vis features were obtained using different
weakly coordinating anions (BF4 , ClO4 , OTf-) (Figure S17; Ta-
ble S3). Incorporated O2 of [O1](PF6)2 was resistant to cycles of
evacuation and purging with N2. Laser excitation at 420 nm led to
a resonance Raman spectrum with a characteristic vibration at
620 cm-1, which was attributed to the symmetrical Cu2O2 core ex-
pansion (breathing mode), thus evidencing the formation of a
bis(µ-oxo) species (Figure 1b). 16O2/18O2 isotope exchange meas-
urements in THF exhibited a shift to 591 cm-1, which is in good
agreement with theoretical calculations (Table S13). The signal at
530 cm-1 is caused by the N(amine)-Cu vibration.
Figure 2. DFT model of [O1]2+ (TPSSh/def2-TZVP, THF-PCM), selected bond
lengths [Å] and Cu···Cu vector [Å].
Thermal decomposition kinetics of [O1](PF6)2 revealed a
first-order decay at low temperatures (Figures S21-22). Half-life
times of [O1](PF6)2 in THF of 1 h at –80 °C and 5 min at –74 °C
were determined. Thermal decomposition products of [O1](PF6)2
were identified by crystallization as a dicationic µ-alkoxo-µ-hy-
droxo copper(II) complex [H1](PF6)2 with a Cu···Cu distance of
2.953(1) Å (Figure 3). Each copper atom is coordinated in a dis-
torted square-planar fashion. The average Cu-O bond length
(1.92 Å) is shorter compared to that in the mixed phenolato hy-
droxo-bridged dicopper(II) species (1.96 Å) reported by Kar-
lin et al.[22] Concomitant formation of yellow blocks was observed,
which contain the protonated ligand [(L1)H2](PF6)2.
-
-
Theoretical studies on [O1](PF6)2 were performed to investi-
gate geometry and Raman features (Figure 2). The calculations
show that the O species is favored by 10 kcal mol-1 over the P
species (Table S11). Key bond lengths around the Cu atoms were
determined by Cu-K-edge EXAFS (Figure 1c-d, Supporting
Bis(µ-hydroxo) species are commonly observed as decay
products[9,18a] and often resulted from intramolecular hydroxyla-
tion of C-H bonds in α- or β-position of N-donor groups.[23] Inter-
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estingly, [H1]2+ is the first example of a trinuclear µ-alkoxo-µ-hy-
droxo copper(II) complex cation. Only few examples of alkoxo-
hydroxo copper(II) species were reported so far.[23] Mechanistic
studies on intramolecular hydroxylation of the supporting ligand
upon warming of the bis(µ-oxo) species were proposed by Itoh,
Tolman et al., stating a mixed alkoxo-hydroxo copper(II) complex
as intermediate species to form thermodynamically stable
bis(µ-hydroxo) and bis(µ-alkoxo) complexes.[23a,24] In case of
[H1]2+, the chemoselective attack of the equatorially located me-
thyl groups of the guanidine moiety over the axially disposed ami-
nomethyl groups is favored due to geometric constraints, analo-
gously to observations made by Tolman et al.[23c,25]
Table 1. (a) Catalytic oxygenation of phenolic substrates[a] (b) subsequent
condensation of the quinone using 1,2-phenylenediamine.[b]
entry
substrate
conv.
[%]
product
yield[c] TON[d]
[%]
(quinone/phena-
zine)
1
2
>99
>99
(Q1)
[e]
[e]
[f]
[f]
(Q1)
(P1)
3
80
22
11
4
5
89
95
(P1)
(P2)
31
32
16
16
6
7
87
(P2)
(P3)
21
30
11
15
Figure 3. Molecular structure of [H1]2+ in crystals of [H1](PF6)2. H atoms except
for the H atom of µ-OH groups, counterions and solvent molecules are omitted
for clarity. Selected interatomic distances [Å] and angles [°]: Cu(1)-O(1) 1.912(2),
Cu(1)-O(2) 1.893(2), Cu(2)-O(1) 1.923(2), Cu(2)-O(2) 1.932(2), Cu(1)···Cu(2)
2.953(1), Cu(2)-N(1) 1.986(2), Cu(2)-N(4) 2.019(3), N(1)-Cu(2)-N(4) 94.9(1),
O(1)-Cu(2)-O(2) 76.8(1), Cu(2)-O(1)-Cu(1) 100.7(1), Cu(2)-Cu(1)-Cu(2’) 180.0.
>99
8
9
28
24
(Q2)
(Q3)
-
-
14[g]
12[g]
Aiming to expand the commonly used substrate scope of
simple phenols, catalytic hydroxylation activity of [O1](PF6)2 was
evaluated towards a variety of challenging phenolic substrates,
including phenols, pyridinols, naphthols, quinolinols and indolols
(Table 1, and Supporting Information), whose quinones and
phenazines are biologically relevant and difficult to synthesize.
We report on the hydroxylation of a multitude of these substrates
by [O1](PF6)2 along with transformation of the quinone into a
phenazine. Remarkably, until now, catalytic conversion of phe-
nols was mostly reported for side-on peroxo copper complexes as
catalytically active species.[11-13,15] Oxygenation reactions were
performed following a protocol established by Bulkowski and
modified by Tuczek et al. using 25 eq. of substrate and 50 eq.
NEt3 (Table 1, Reaction (a)).[13a,26] Reaction (a) was monitored by
UV/Vis spectroscopy at –90 °C for 1 h as optical spectra re-
mained constant after that time. Reactive quinones were subse-
quently converted in a one-pot step into their corresponding phen-
azines at room temperature by using 1,2-phenylenediamine (Ta-
ble 1, Reaction (b)).
10
81
(P4)
19
10
11
12
88
92
(P4)
(P5)
26
27
13
14
13
84
(P5)
31
16
[a] conditions: THF, -90 °C, 1 h. [b] conditions: THF, -90 °C, then rt, overnight.
[c] isolated yield after column chromatography. [d] based on isolated yield in
correlation with conc. of [O1](PF6)2. [e] quinone too reactive to be isolated. [f]
no extinction coefficient of the quinone reported. [g] determined after reaction
(a) via UV/Vis spectra and based on conc. of [O1](PF6)2.
When simple phenols are used, [O1](PF6)2 showed, besides
the expected hydroxylation activity, also C-O coupling chemistry
(Table S8, entries 1-4). UV/Vis spectra showed a low intensity ab-
sorption band at 510 and 530 nm (Figures S39-40). EPR meas-
urements revealed the hyperfine splitting pattern typical for a rad-
ical-free, metal-centered Cu(II) species (Figure S41), ruling out
the formation of a semiquinone species.[27]
An interesting substrate for the catalytic oxygenation is 8-
quinolinol.[15,28] While 7,8-quinolinedione (Q2) was formed with 14
turnovers (entry 8), methyl-substitution in 2-position resulted in a
TON of 12 (Q3, entry 9). However, formation of the respective
phenazine was observed in neither case (Figures S50-51), pre-
sumably due to the smaller Fukui function f+ at the corresponding
C atoms of Q2 and Q3 (Table S15). Conversion of other quino-
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linols was not reported before in Cu/O2 chemistry. 3- and 4-quin-
olinol were transformed into their quinone (absorption band at
370 nm, Figures S47-48) and isolated as quinolino[3,4-b]quinox-
aline (P2) (entries 5-6). 6-Quinolinol was oxidized into 5,6-quino-
linedione (entry 7), which showed absorption bands at 325, 340
and 370 nm (Figure S49). Pyrido[3,2-a]phenazine (P3) was iso-
lated in 15 turnovers after column chromatography and sublima-
tion, and crystallized from DMSO (see Supporting Information).
In contrast to reactions with phenols and 8-quinolinol, no
conversion of pyridinols was reported so far. When 3- and 4-pyri-
dinol (entries 1-2) are used, an intense absorption band at 375 nm,
similar to that in 3- and 4-quinolinol, was observed in both cases
within less than one minute (Figures S42-43), indicating formation
of 3,4-pyridoquinone (Q1). A fast drop in intensity illustrates high
reactivity of the quinone even at low temperatures, leading to C-O
coupled dimers (see Supporting Information).[29] Theoretical stud-
ies revealed lesser stability of 3,4-pyridoquinone compared to its
most stable 2,5-isomer.[30] However, no other study exists that re-
ports on pyridoquinones.
Table 2. Summary of calculated Fukui function (fk-) of phenolic substrates
with two possible products.
-
entry
substrate
Fukui function (fk )
C-atom position
21.14
0.74
1
3
1
1.38
15.17
2
4
2
3
23.93
0.91
5
7
19.93
1.05
4
6
4
5
2.03
11.99
5
7
Naphthoquinones are accessible from 1- and 2-naphthol in
the presence of an oxidizing agent.[31] Both naphthols were con-
verted via [O1](PF6)2 into the corresponding quinone, which re-
sulted in the formation of benzo[a]phenazine[31c] (P1) upon treat-
ment with 1,2-phenylenediamine (entries 3-4, Figures S44-45).
P1 was purified via column chromatography and isolated with a
TON of 11-16. Consistent with observations made by Krohn et al.,
no formation of the linear phenazine was observed.[31c] The con-
trol experiment using 1-methyl 2-naphthol (Table S8, entry 7)
showed no product formation as was expected (Figure S46),
since the 1-position is occupied by the methyl substituent inhibit-
ing the oxygenation process.
While related bicyclic indolols possess an easily accessible
pyrrole ring, C-H functionalization of the phenyl ring remains chal-
lenging.[32] When [O1](PF6)2 was used, 4- and 5-indolol were con-
verted into 4,5-indoledione, which was captured as pyr-
rolo[3,2-a]phenazine (P4) in 10-13 turnovers (entries 10-11, Fig-
ures S52-53). Similarly, 6- and 7-indolol (Figures S54-55) were
transformed into pyrrolo[2,3-a]phenazine (P5, TON = 14-16) and
crystallized from hexane (entries 12-13). The control experiment
revealed no oxygenation activity on 6-indolol in the absence of
supporting ligand L1 (Figure S36), thus evidencing the necessity
of the stabilizing ligand system.
While tyrosinase (from Aspergillus oryzae) oxidizes phenol
quantitatively,[34] the enzyme exhibited no reactivity towards naph-
thols, quinolinols and indolols (Table S10). Thus, the bis(µ-oxo)
species [O1](PF6)2 demonstrates an exceptional broad substrate
scope, to which the enzyme itself gave no access.
In summary, we established the synthesis of the aromatic
hybrid guanidine-stabilized bis(µ-oxo) species [O1]2+, which was
clearly evidenced by its spectroscopic properties. [O1](PF6)2 re-
vealed a moderate stability at low temperatures with a distin-
guished activity towards a large variety of phenolic substrates.
DFT calculations enabled a prognosis of the hydroxylation posi-
tion via Fukui function, which fully agreed with experimental re-
sults. The Fukui function was introduced as new predictive tool for
Cu/O2 chemistry. Moreover, our present findings clearly show ef-
ficient C-H activation of mono- and bicyclic phenolic substrates,
stating an atom-economic strategy to design new phenazines. A
bio-inspired model system such as [O1](PF6)2 indicates tyrosi-
nase-like activity of O cores and exceeds evidently the enzymati-
cally limited substrate scope. This study opens the door to future
developments on tyrosinase model systems with high relevance
to atom-economic oxygen transfer reactions with synthetic im-
portance.
The accompanying DFT calculations based on the negative
Fukui function are used to determine the location of the electro-
philic attack, which are in good accordance with the observed Acknowledgements
products (for substrates with two product possibilities, Table 1-2,
see Supporting Information). The Fukui function describes the
electron density in a frontier orbital, in this case fk denotes the
We acknowledge financial support provided by the German Re-
search Foundation (DFG), in framework of Priority Program “Re-
active Bubbly Flows” SPP 1740 (HE 5480/10-2, http://www.dfg-
spp1740.de/), Research Training Program SeleCa and further
projects (RU 773/8-1). We also acknowledge computing time and
support provided by OCuLUS Cluster at PC2 Paderborn and sup-
port at beamline P64 by Marcel Görlitz and Dr. Wolfgang Caliebe.
-
initial part for an electrophilic reaction. A large value for fk- indi-
cates the preferred site for an electrophilic attack – in this case
the tyrosinase-like hydroxylation. In all cased studied here, the
Fukui function points to the experimentally observed hydroxyla-
tion site finally yielding the bent phenazines.
It has to be highlighted that the phenazines P3, P4 and P5
are new and fully characterized.[33] Thus, the combination of tyro-
sinase-like hydroxylation reactivity with the condensation of qui-
nones with diamines allows synthetic access to a multitude of new
phenazines.
Conflict of Interest
The authors declare no conflict of interest.
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10.1002/chem.202000664
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Rev. 2016, 334, 54–66.
Keywords: copper catalysis • dioxygen activation • guanidines •
phenazines • tyrosinase
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10.1002/chem.202000664
Chemistry - A European Journal
COMMUNICATION
Entry for the Table of Contents
Layout 2:
COMMUNICATION
Melanie Paul[a], Melissa Teubner[a,b]
,
Benjamin Grimm-Lebsanft[b], Christiane
Golchert[a], Yannick Meiners[a], Laura
Senft[c], Kristina Keisers[a], Patricia
Liebhäuser[a], Thomas Rösener[a], Flo-
rian Biebl[b], Sören Buchenau[b], Maria
Naumova[d], Vadim Murzin[d], Roxanne
Krug[e], Alexander Hoffmann[a], Jörg Pie-
truszka[e,f], Ivana Ivanović-Burmazović[c],
Michael Rübhausen[b], Sonja Herres-
Pawlis*[a]
We describe the synthesis and characterization of bis(µ-oxo) dicopper(III) species
[Cu2(µ-O)2(L1)2](X)2 ([O1](X)2, X = PF6, BF4, OTf, ClO4) via UV/Vis, Raman and XAS
spectroscopy as well as cryo-UHR-ESI mass spectrometry, stabilized by an aromatic
hybrid guanidine ligand. We highlight selective oxidation of a plethora of phenolic
substrates mediated by [O1](PF6)2, that results in mono- and bicyclic quinones far
beyond the enzyme’s scope and provides an attractive strategy to design new phen-
azines.
Page No. – Page No.
Guanidines strike back: Exceptional
Substrate Diversity in Oxygenation
Reactions Catalyzed by a Bis(µ-oxo)
Copper Complex
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