Catalytic Aerobic Phenol Homo- and Cross-Coupling Reactions with Copper Complexes Bearing Redox-Active Guanidine Ligands

Article abstract of DOI:10.1002/chem.201900583

Due to their large importance in synthetic chemistry, catalytic C?C coupling reactions of phenols are currently intensively studied. Herein, new copper catalysts for the C?C coupling reaction of phenols using dioxygen as a green oxidizing reagent are reported. By using redox-active guanidine ligands, the activity as well as chemoselectivity in the cross-coupling reaction of non-complementary phenols (between an electron-rich phenol and a less nucleophilic second phenol) is significantly improved. Based on the collected data for several test reactions, a reaction mechanism is proposed.

Full text of DOI:10.1002/chem.201900583

A Journal of
Accepted Article
Title: Catalytic Aerobic Phenol Homo- and Cross-Coupling with Copper
Complexes Bearing Redox-Active Guanidine Ligands
Authors: Florian Schön, Elisabeth Kaifer, and Hans-Jörg Himmel
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Catalytic Aerobic Phenol Homo- and Cross-Coupling with Copper
Complexes Bearing Redox-Active Guanidine Ligands
Florian Schön, Elisabeth Kaifer and Hans-Jörg Himmel*[a]
Abstract: Due to their large importance in synthetic chemistry,
catalytic C-C coupling reactions of phenols are currently intensively
studied. Herein we report on new copper catalysts for the C-C
coupling of phenols using dioxygen as a green oxidizing reagent. By
using redox-active guanidine ligands, the activity as well as chemo-
selectivity in the cross-coupling of non-complementary phenols
(between an electron-rich phenol and a less nucleophilic second
phenol) is significantly improved. On the basis of the accumulated
data for several test reaction, a reaction mechanism is proposed to
explain the high chemo-selectivity.
complementary relationship (NA > NB) generally display only
inferior cross-coupling chemo-selectivity, even for a radical-
anion coupling mechanism. Waldvogel et al. presented another
concept in electrochemical cross-coupling of phenols and
anilines, providing high chemoselectivities by shifting the
oxidation potential of the phenols in dependence of the
substitution pattern in a specific range through addition of water
or methanol to the electrolyte.[22,23] Kozlowski et al. studied the
aerobic cross-coupling of phenols with
a complementary
relationship with different catalysts (i.e. Cr-salen complexes).[24]
Introduction
Modern synthetic chemistry strongly depends on the
development of strategies for the selective formation of carbon-
 9 ]
carbon bonds.[ 1
Symmetric as well as non-symmetric
biphenols, traditionally synthesized by coupling of two phenol
units, are of high relevance in several research fields such as
natural product synthesis,[10] material science,[11] drugs[12,13] as
well as the design of advanced molecular catalysts.[14] Motivated
by the efficiency and selectivity of metalloenzymes, considerable
effort has been devoted to the development of metal complexes
that mimic enzymes in mediating the selective catalytic aerobic
oxidation of phenols.[15,16]
Traditionally, non-symmetric biphenols are prepared by
transition-metal catalyzed cross-coupling of aryl-halides (Ar-
X).[17−19] Often, a number of synthesis steps is required, leading
to an unfavorable overall atom economy. In seminal work,
Pappo et al. systematically studied cross-coupling reactions of
phenols with a radical-anion coupling mechanism and grouped
the phenol cross-coupling reactions in two categories depending
on their redox potential and “global nucleophilicity” N (Scheme
1).[20,21] For practical reasons, the parameter N of a phenol was
simply defined by the authors as the HOMO energy relative to
tetrachloro-ethylene, allowing it´s straightforward determination
by standard DFT methods.[20] Obviously, for a pair of phenols A
and B with EOx(A) < EOx(B), the oxidation of phenol A to a
phenoxyl radical is thermodynamically favored. A spontaneous
radical-radical coupling of two phenoxyl radicals leads to the
undesirable homo-coupling product AA (Scheme 1). By
contrast, the cross-coupling reaction is favored in a radical-anion
Scheme 1. Flow-chart for general principles in the phenol cross-coupling.
Adapted from Pappo et al. 2015.[20]
Due to the resulting limited scope of cross-coupling reactions,
several research groups took up the challenge to disclose new
concepts for highly chemo-selective cross-coupling reactions of
phenols with a non-complementary relationship (Scheme 2).
Waldvogel et al. reported the cross-coupling of phenols at
boron-doped diamond (BDD) anodes in 1,1,1,3,3,3-
hexafluoropropan-2-ol (HFIP) as solvent.[25-29] Using this electro-
chemical approach, a variety of phenol cross-coupling reactions
was reported. The oxidation potential of phenol A needs to be
significantly lower and a one- to twofold excess of phenol B has
to be applied to achieve a high chemo-selectivity. In addition,
Waldvogel et al. used stoichiometric amounts of SeO2 as oxidant
for the cross-coupling of phenols in high yield.[ 30 ] The best
results were obtained if phenol A is applied in a fivefold excess
and HFIP as solvent. More recently, Pappo et al. reported an
iron catalyst with a tetraphenylporphyrin ligand (TPP) for
selective oxidative cross-coupling of phenols.[31] This work relied
on tBuOOH as oxidizing reagent and HFIP as solvent. This time,
phenol B was applied in threefold excess in the experiments with
highest chemo-selectivity. Very recently, Waldvogel et al. also
succeeded in the electrochemical cross-coupling of 2,6-
dimethoxyphenol with 2,6-diisopropylphenol at a BDD anode.[32]
coupling mechanism of phenols with
a
complementary
relationship (NB > NA), leading to a desired high cross-coupling
chemo-selectivity. On the other hand, phenols with a non-
[a]
F. Schön, 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/
Supporting information for this article is given via a link at the end of
the document.
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copper atoms. A number of studies [3541] has shown that the
particularly low barrier for intramolecular ligand-metal electron
transfer in guanidine-copper complexes is due to the structural
harmonization between CuII and CuI complexes caused by the -
donor properties of the guanidine ligands (see also work by
Herres-Pawlis et al. on the entatic state concept in this
context [4246]). Hence it was possible to shift electrons between
the redox-active guanidine ligand and the copper atom in a
complex by changing the counter-ions,[35] the solvent [3638] or the
Itoh et al. studied the mechanism of oxidative homo-coupling
reactions of phenols with dioxygen in the presence of copper
catalysts that initially react with dioxygen to dinuclear (side-on)
peroxo complexes (Cu2PS) or bis--oxo-complexes (Cu2O2),
sketched in Scheme 3.[33] They suggest the Cu2O2 complex to be
the active species, leading to C-C coupling products by a proton-
coupled electron transfer (PCET) from the phenol to the Cu2O2
complex, producing phenoxyl radicals which then spontaneously
dimerize.
temperature.[37,3941] An example for
a thermally induced
intramolecular electron transfer in a dinuclear copper complex
with a related bridging redox-active tetrakis-guanidine ligand is
given in Scheme 4b.[41] The high electron-donor capability of the
ligand warrants an efficient dioxygen activation or O-O bond
cleavage reaction to give Cu2O2 complexes.
Scheme 4. a) Lewis structures of the redox-active tetrakisguanidine 1 before
and after reversible two-electron oxidation. b) Valence-tautomerism with the
redox-active ligand 1,2,4,5-tetrakis(tetramethyl-guanidino)pyridine.[41]
Scheme 2. Selection of catalysts and conditions used in phenol cross-
coupling reactions in the literature and one of the catalytic reactions reported
in this work.
The advantages/peculiarities of the cross-coupling reactions
presented herein with respect to previous work are (I) the use of
dioxygen as oxidant, (II) fast reaction under mild conditions
(room temperature, 1 atm. of dioxygen), (III) use of standard
organic solvents (i. e. DCM) in place for 1,1,1,3,3,3-
hexafluoropropan-2-ol (HFIP), (IV) the use of an equimolar ratio
of both phenols and (V) a novel mechanistic option, leading to
high chemo-selectivity for phenols with a non-complementary
relationship.
Scheme 3. Cu2PS and Cu2O2 complexes.
Herein we report on the influence of redox-active ligands in new
copper catalysts for the homo-coupling reactions of 2,6-di-tert-
butylphenol and 2,4-di-tert-butylphenol. On the basis of these
results, the oxidative cross-coupling of phenols with a non-
complementary relationship is studied in detail. The oxidant,
dioxygen, is activated by copper complexes bearing the redox-
active guanidino-functionalized aromatics (GFA) 1,2,4,5-tetrakis-
(tetramethylguanidino)benzene (1) as ligand (see Scheme 4a).
Results and Discussion
Synthesis of copper complexes
47
]
The
binuclear
complexes
[1(CuBr)2] [
and
[1(CuMeCN)2](BPh4)2 (Scheme 5 and Figure 1) with the redox-
active ligand 1,2,4,5-tetrakis-(tetramethylguanidino)benzene (1)
This ligand, that is oxidized reversibly at low potential (E1/2
=
0.7 V vs. Fc+/Fc in DCM solution for the redox couple 12+/1),[34]
supplies the metal atom with extra electron-density, up to the
point of full transfer of two electrons from the ligand to the two
were
prepared
by
addition
of
CuBr
respectively
[Cu(CH3CN)3]BPh4 to the ligand in acetonitrile solutions. The
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redox-activity of the ligand should assist in the activation of
dioxygen. To elucidate the effect of redox-activity, the ligand 1,2-
coupling reaction of 2,4-di-tert-butylphenol. The reactions were
carried out in a vial with crimp cap and rubber septum under an
atmosphere of O2 (1 atm) to ensure sufficient dioxygen
bis-(tetramethylguanidino)-benzene
(2)
with
a
similar
1
coordination site, for which irreversible oxidation occurs at much
higher potentials of Eox = 0.06 V and Eox = 0.11 V vs. Fc+/Fc (see
SI), was also applied. Both mononuclear CuI complexes [2CuBr]
and [2CuMeCN]BPh4 (Scheme 5) were prepared in-situ by
availability. The yields were determined via H NMR integration
with an internal standard (hexamethylbenzene) after quenching
the reaction with a solution of NaHSO4 in water (10%) and
extraction with dichloromethane (details are found in the SI). The
variation of the catalysts (Table 1) only led to differences in the
reaction rate, but not to different reaction products. Complete
consumption of the starting material was reached with 4 mol%
[1(CuBr)2] in less than 1 h (Table 1, entry 3). With low catalyst
loadings, mainly the formation of 3 was observed. For a better
comparability, the turnover (T) at one copper atom within 1 h
reaction time was also estimated with lower catalyst loading (0.4
mol%, Table 1, entry 4).
addition
of
one
equivalents
of
CuBr
respectively
[Cu(MeCN)4]BPh4 to ligand 2. The low coordination number of
three of the copper atoms in all four complexes should favor the
formation of the initial copper-dioxygen complex. A number of
oxidative phenol coupling reactions described in the literature
employed copper(I) catalysts together with (sub-) stoichiometric
amounts of NEt3.[ 48 ] We therefore used catalytic amounts of
CuBr in combination with 0.5 eq. NEt3 for benchmarking.
Table 1. Oxidative homo-coupling of phenol S1 with different catalysts.
#
1
2
3
4
5
6
7
8
catalyst
T a)
Conversionb)
98 %
Scheme 5. Lewis structures of the complexes with 1,2,4,5-tetrakis-
(tetramethylguanidino)benzene (1) and 1,2-bis-(tetramethylguanidino)benzene
(2) ligands used in this work as catalysts in oxidative phenol coupling reactions.
8 mol% CuBr + 50 mol% NEt3
0.8 mol% CuBr + 5 mol% NEt3
4 mol% [1(CuBr)2]
1225
0
0 %
a)
b)
1250*
6875
1250*
38
100 %
55 %
0.4 mol% [1(CuBr)2]
8 mol% [2CuBr]
100 %
3 %
0.8 mol% [2CuBr]
8 mol% [2CuMeCN]BPh4
4 mol% [1(CuMeCN)2](BPh4)2
325
475
26 %
Figure 1. Illustration of the structure of the complex [1(CuMeCN)2]2+ in crystals
of [1(CuMeCN)2](BPh4)2 obtained from a CH3CN/Et2O solution (Cu atoms in
orange, N atoms in blue and C atoms in grey) from two perspectives.
Hydrogen atoms, counterions and solvent molecules were omitted for clarity.
a) View perpendicular to the aromatic plane; b) view along the aromatic plane.
Thermal ellipsoids are drawn at the 50% probability level.
38 %
a) Turnover at one copper atom after 1 h reaction time.
b) After 1 h reaction time.
* Maximum value for the chosen catalyst loading.
The benchmark catalyst CuBr/NEt3 displayed a turnover of T =
1225 (entry 1, Table 1) with 8 mol% catalyst loading, whereas a
reduction of the catalyst loading to 0.8 mol% resulted in virtually
no reaction (entry 2, Table 1). Catalyst [1(CuBr)2] with the redox-
active ligand showed a significantly higher activity with T = 6875
(entry 4, Table 1). The low catalyst loading of 0.4 mol% was
selected due to complete conversion of the starting material in
less than one hour with 4 mol% catalyst loading (entry 3, Table
Homo-coupling reaction of 2,4-di-tert-butylphenol
The oxidative homo-coupling of 2,4-di-tert-butylphenol (S1,
Table 1) is a well-known reaction, leading to biphenol 3 with
subsequent further oxidation to benzoxepine 4.[48] An additional
intramolecular reaction leads to 5 (in analogy to the already
reported formation of benzofurans in phenol coupling reactions
[49]). Therefore, the work in this article started with a comparison
of the performance of several catalysts in the oxidative homo-
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1). In direct comparison, 0.8 mol% of [2CuBr] (complete
conversion with 8 mol% catalyst loading in one hour, entry 5,
Table 1) with the virtually non-redox-active ligand 2 led to a
notably smaller turnover of T = 38 (entry 6, Table 1). For
[2CuCH3CN]BPh4, a turnover of T = 325 (entry 7, Table 1) was
obtained, which can be improved up to 475 h1 (entry 8, Table 1)
by using ([1(CuCH3CN)2](BPh4)2) with the redox-active ligand 1.
The results demonstrate that the ligands as well as the co-
ligands respectively charge of the catalyst have a great impact
on the reaction rate. Complex [1(CuBr)2] showed the highest
activity in the test reaction. The obvious inference is that the
redox-activity of ligand 1 supports the activation of dioxygen at
the copper atoms due to its electron-donating effect. With 0.4
mol% of catalyst [1(CuBr)2], a yield of 97% of 3 was measured
after 24 h, indicating no significant catalyst destruction.
Moreover, no base addition was required.
copper-dioxygen complexes is typically due to the formation of
Cu2PS complexes[50,51] that might be formed in an equilibrium
with the Cu2O2 complex (well known as key-reactive species in
the phenol coupling [33, 52 ]).In contrast to triethylamine, the
electron donating effect of the ligands 1 and 2 shifts the
equilibrium to the side of the Cu2O2 complex, forming almost no
side-products in the phenol coupling reaction. We tested the
same catalysts as for oxidative homo-coupling of S1, and
estimated again the turnover (T) in 1 h reaction time. The
catalyst CuBr/NEt3 gave a much lower turnover of T = 75 (entry
1, Table 2) with a catalyst loading of 8 mol%, compared with the
homo-coupling reaction of phenol S1 (T = 1225; entry 1, Table
1). The lower reaction rate can be rationalized by the higher
oxidation potential of S2 (E0OX = 1.62 V vs. SCE) compared with
S1 (E0OX = 1.46 V vs. SCE).[33] Complex [1(CuBr)2] exhibited a
23 times higher activity with a turnover of T = 1750 (entry 4,
Table 2) even with a lower catalyst loading of 0.4 mol%,
whereas a conversion of 14% was achieved within 1 h. A longer
reaction time of 120 h gave 52% conversion. Complete
conversion of the starting material was reached after 1 h by
rising the catalyst loading to 4% (entry 3, Table 2). The use of
([1(CuCH3CN)2](BPh4)2) reduced the activity (T = 850; entry 5,
Table 2) compared with [1(CuBr)2]. The application of complexes
with the virtually non-redox-active ligand 2 as catalysts resulted
in a lower activity, with T = 213 (entry 6, Table 2) for [2CuBr] and
T = 200 (entry 7, Table 2) for [2CuCH3CN]BPh4, highlighting the
advantage of using the redox-active ligand 1 for dioxygen
activation.
Homo-coupling reaction of 2,6-di-tert-butylphenol
Next, the oxidative homo-coupling of 2,6-di-tert-butylphenol (S2)
was examined, leading first to biphenol 7, which rapidly oxidizes
further to the para-para coupled diquinone (6, Table 2). The
advantage of this reaction is the clean conversion of S2 to only
one (main) product. According to 1H NMR and GC-MS of the
reaction solution, we suggest the formation of 2,6-di-tert-butyl-p-
benzoquinone as by-product (up to 4%) which is primarily
Table 2. Oxidative homo-coupling of phenol S2 with different catalysts.
Next the homo-coupling reaction of phenol S2 with 0.4 mol% of
the catalyst [1(CuBr)2] was repeated, but with addition of 50
mol% of a radical scavenger (TEMPO or cis-stilbene, Table 2,
entries 8 and 9). No significant decrease of the turnover (T) was
observed, indicating that no free phenoxyl radicals are formed in
the course of the reaction. On the other hand, a radical-radical
coupling mechanism with bound phenols is still compatible with
these results. This proposal is supported by the 19F NMR spectra
taken for the reaction of [1(CuBr)2] with 2,3,4,5,6-
pentafluorophenol (see SI), displaying a shift in the 19F NMR
signal relative to the free phenol, indicating the formation of a
complex between the phenol and the copper complex.
#
1
2
3
4
5
6
7
8
9
catalyst
T a)
Conversionb)
6 %
8 mol% CuBr + 50 mol% NEt3
0.8 mol% CuBr + 5 mol% NEt3
4 mol% [1(CuBr)2]
75
0
0 %
1250*
1750
850
213
200
1650
1650
100 %
14 %
Low-temperature UV/Vis experiments
0.4 mol% [1(CuBr)2]
Next, the reactivity of the complexes toward dioxygen was
studied. In first experiments, propionitrile solutions of the
complexes were cooled to −80 °C, and the changes in the
UV/Vis spectra upon addition of a pre-cooled solution of
4 mol% [1(CuMeCN)2](BPh4)2
8 mol% [2CuBr]
68 %
17 %
propionitrile, saturated with dioxygen, monitored. Figure
1
8 mol% [2CuMeCN]BPh4
0.4 mol% [1(CuBr)2] + 50 mol% TEMPO
16 %
visualizes the changes in the UV/Vis spectra upon dioxygen
addition.
13 %
Since complex [2CuMeCN]BPh4 showed the lowest reactivity in
the phenol coupling reactions, one expects this complex to
display the lowest reactivity towards dioxygen. The evolution of
an intense band at 406 nm ( = 3300 L mol1 cm1) was
observed in the UV/Vis spectra, with maximum absorbance
being reached after 290 s. The wavelength and the high
extinction coefficient are characteristic for Cu2O2 complexes, and
especially comparable to previously reported Cu2O2 complexes
0.4 mol% [1(CuBr)2]
stilbene
+
50 mol% cis-
13 %
a) Turnover at one copper atom within 1 h reaction time.
b) After 1 h reaction time.
* Maximum value for the chosen catalyst loading.
observed by using the CuBr/NEt3 catalyst (entry 1, Table 2). The
oxidation of phenols to benzoquinones (tyrosinase activity) with
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with guanidine ligands.[53,54] For prolonged reaction times the
bands vanished again, signalling decomposition of this complex
even at low temperature of −80 °C. In the case of the reaction of
complex [2CuBr] as well as both complexes with the redox-
active ligand 1 with dioxygen at 80 °C, the UV/Vis spectra gave
evidence only for decomposition products, that were responsible
for the slow evolution of absorption bands (see SI) that do not
vanish at higher temperatures. For [1(CuMeCN)2](BPh4)2 and
[1(CuBr)2] mainly absorption bands at 360 nm and 415 nm were
observed upon dioxygen addition. The absorption band at 415
nm was assigned to the twofold oxidized ligand 12+, in line with
the decline of the absorption band at 324 nm due to neutral 1.[55]
The band arises either from the free, oxidized ligand 12+ or from
the oxidized ligand in a copper (dioxygen) complex. Hence the
initially formed dioxygen complex is too reactive, even at low
temperature, to be spectroscopically studied by the applied
methods (e.g. stopped-flow UV/Vis spectroscopy, see SI).
Nevertheless, the high electron-density provided by ligand 1
should initially also lead to the formation of Cu2O2 complexes.
observed. Only in two experiments (entries 1 and 7), side-
products were formed. We started our work with the benchmark
catalyst CuBr/NEt3 which showed a quite high cross-coupling
selectivity of 58% (entry 1, Table 3), but side reactions leading to
a low cross-coupling yield of only 38%. Herein, we suggest the
formation of 2,6-di-tert-butyl-p-benzoquinone (~ 8%) as one of
the side products, being formed in larger quantities than in the
homo-coupling reaction of 2,6-di-tert-butylphenol. The complex
[2CuBr] displayed in the test reaction a cross-coupling selectivity
of 54% (entry 2, Table 3) which can be increased further to 70%
by using complex [1(CuBr)2] (entry 3, Table 3) with the redox-
active ligand. Substitution of the bromido ligands by neutral

CH3CN, requiring the presence of (weakly coordinating) BPh4
counter-ions, did not significantly change the cross-coupling
selectivity (entry 4, Table 3), while a slight improvement to 75%
cross-coupling selectivity was achieved with HFIP as solvent
(entry 5, Table 3).
Table 3. Oxidative cross-coupling reaction between S2 and S3 with different
catalysts and conditions.
2,0
1,5
1,0
0,5
0,0
0,16
0,12
0,08
0,04
0
200
400
600
800
1000
#
selectivityb)
yield (%)
/
conditionsa)
t / s
1
8 mol% CuBr + 50 mol% NEt3, 24 h, DCM, O2
8 mol% [2CuBr], 24 h, DCM, O2
58 / 38c)
54 / 54
406 nm
400
2
3
1 mol% [1(CuBr)2], 2 h, DCM, O2
70 / 70
600
800
1000
l / nm
4
1 mol% [1(CuMeCN)2](BPh4)2, 2 h, DCM, O2
1 mol% [1(CuBr)2], 24 h, HFIP, O2
2 eq. 1(PF6)2, 3 weeks, DCM
70 / 70
Figure 1. Changes in the UV/Vis spectrum in the first 900 s of the reaction
5
4
5
75 / 46d)
53 / 53
between [2CuMeCN]BPh4 (4.6·10 M) and dioxygen (6.3·10 M) in
propionitrile at 80 °C. Inset: Plot showing the change of absorbance at
406 nm with time.
6
t
7
10 eq. BuOOtBu, 36 h, MeCN, h
12 / 4c,d)
20 / 14 + 6e)
57 / 44 + 13e)
55 / 55
8
10 mol% FeCl3, 1.5 eq. tBuOOtBu, 24 h, DCM
10 mol% FeCl3, 1.5 eq. tBuOOtBu, 24 h, HFIP, 55 °C
0.5 eq. [1(CuBr)2], O2, DCM, 1 h; 2) Ar, phenols, 1 h
1 mol% [1(CuBr)2], 2 h, 2 eq. NEt3, O2
Chemo-selectivity in the cross-coupling reactions
Next, we studied the oxidative cross-coupling reaction of 2,6-di-
tert-butylphenol with 2,6-dimethoxyphenol (Table 3) in detail to
obtain further insight into the reaction mechanism. Herein, the
first step is the formation of the biphenol, which is oxidized for
prolonged reaction times to the diquinone as indicated by 1H
NMR spectroscopy. According to the literature, one could
differentiate between three reaction mechanisms for the
oxidative biaryl coupling: 1) the radical-radical coupling (A● + B●),
2) the heterolytic coupling (A+ + B), and 3) the radical-anion
coupling mechanism (A● + B).[20,24,31,56]
We systematically varied the reaction conditions to elucidate the
reaction mechanism (Table 3). For all reactions included in
Table 3, the chosen conditions led to quantitative conversion of
at least one of the phenols (phenol B). In most cases,
quantitative C-C coupling (cross- or homo-coupling) was
9
10
11
12
56 / 56
1 mol% [1(CuBr)2], 2 h, 2 eq. tetramethylguanidine,
O2
57 / 57
a) If not stated otherwise, complete conversion of phenol B was achieved under
the applied conditions.
NMR by integrating an internal standard, the cross-coupling product and the
homo-coupling product (see SI). The average of two experiments is given.
c) Formation of side-products. d) Incomplete conversion of the starting material.
e) Biphenol product.
b)
Cross-coupling selectivity was determined via 1H
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The higher cross-coupling selectivity obtained with this solvent,
which is widely applied in phenol cross-coupling reactions, is
due to three effects: 1) According to the large difference in
solvation of the coupling partners, the two crucial parameters (N
(“global nucleophilicity”) and the oxidation potential) are
differently affected, favoring the radical-anion coupling
mechanism.[22,57, 58 ] 2) Displacement of the phenol with lower
oxidation potential from the metal atom.[31] 3) Decrease of the
reaction rate for radical formation, leading to a higher preference
for a radical-anion coupling mechanism by inhibition of the
radical-radical coupling pathway.[26,59] With 1 mol% of [1(CuBr)2]
in DCM, complete conversion of the starting materials required
less than 2 h (entry 4, Table 3). By contrast, only ~60% of the
phenol had reacted after a reaction time of 24 h in HFIP (entry 5,
Table 3). We explain this result by a competitive inhibition of the
catalyst due to the coordination of HFIP to the catalyst. Indeed,
we were able to obtain crystals of [1(Cu(C6H2F6O2)2)2] (Figure 2)
suitable for X-ray diffraction after the oxygenation of a solution of
[1(CuCl)2] in HFIP, showing the coordination of deprotonated
HFIP to the copper atoms. In addition to the higher costs of
HFIP, the dramatic decrease in the reaction rate led us to resign
the use of HFIP and exploring a novel concept which is not
restricted to this solvent. The observed decrease in the reaction
rate seems to be a general problem of HFIP as indicated by high
catalyst loadings and temperatures, as well as long reaction
times in the cross-coupling of phenols in previous works (see
Scheme 2).[20,30,31]
selectivity of this radical-radical coupling process is very low,
leading to only 12% of 8 (entry 7, Table 3). The preference for
homo-coupling can easily be explained by the favored oxidation
of phenol A due to its lower oxidation potential.[20] Another route
to generate phenoxyl radicals is the use of FeCl3 as catalyst with
di-tert-butyl peroxide as oxidation agent.[20] Herein, with 10 mol%
of FeCl3 and 1.5 eq. of di-tert-butyl peroxide (entry 8, Table 3) a
low cross-coupling chemo-selectivity of 20% was obtained.
According to the literature,[20] a solvent change to HFIP leads to
a radical-anion coupling mechanism. Interestingly, a cross-
coupling selectivity of 57% was obtained under similar
conditions (entry 9, Table 3). This observation highlights the
necessity of HFIP in cross-coupling reactions, accompanied with
the search for alternative pathways. Furthermore, the very
similar value of ca. 55% in the cross-coupling selectivity
obtained with several catalysts/oxidizing agents applied in this
work, e.g. with [2CuBr], might argue for a similar coupling
mechanism, namely a radical-anion one. On the other hand, it
has to be a special version of a radical-anion coupling
mechanism due to the absence of the solvent HFIP.
The cyclovoltammogram (CV) recorded for both phenols in DCM
shows no oxidation wave in the potential window permitted by
the solvent, indicating that proton transfer is a crucial process in
the reaction sequence. Further CV studies demonstrate that
both phenols can be easily oxidized after their deprotonation
(see SI). Deprotonation of the phenols (Scheme 6) leads to very
strong nucleophiles, making the use of HFIP redundant. In the
second step phenol A is oxidized. The oxidation potential of
deprotonated phenol A (0.52 V vs. Ag/AgCl in DCM) is
significantly lower than that of deprotonated phenol B (0.63 V),
as estimated by CV measurements after addition of the strong
base tetramethylguanidine (see SI). Therefore, more of
deprotonated A than of deprotonated B is oxidized. In the third
step, the nucleophilic attack from phenolate B followed by an
oxidation leads to the cross-coupled product A-B.
Subsequently, we tested the redox-active ligand 12+, which is
also potent of phenol coupling [ 60 ] in a PCET reaction. A
quantitative reaction of 12+ with both phenols led to a value of
53% for the cross-coupling selectivity in DCM solution (entry 6,
Table 3), close to the cross-coupling selectivity of 58% for the
benchmark catalyst (entry 1, Table 3). These results clearly
show that the cross-coupling selectivity in this case is not
caused by the preferred coordination of one of the phenols to
the copper atom.
To rationalize the observed high cross-coupling selectivity and to
exclude a radical-radical coupling pathway, we tested the cross-
Scheme 6. Proposed cross-coupling pathway explaining the high chemo-
selectivity of the cross-coupling reactions.
Figure 2. Visualization of the structure of the complex [1{Cu(C6H2F6O2)2}2] in
crystals obtained from a HFIP/Et2O solution (Cu atoms in orange, N atoms in
blue, C atoms in grey, O atoms in red and F atoms in yellow). Thermal
ellipsoids are drawn at the 50% probability level. Hydrogen atoms and solvent
molecules are omitted for clarity.
We also tested if the dioxygen complex of the catalyst is the
active species or if a more stable product between dioxygen and
the copper complex is relevant for the chemo-selectivity of the
phenol cross-coupling (entry 10, Table 3). For this purpose, we
passed O2 at r.t. into a solution of [1(CuBr)2] in DCM for 1 h, and
subsequently degassed the solution with three pump-thaw
cycles. After the addition of 1 eq. of both phenols, the reaction
mixture was quenched with degassed NaHSO4 solution and a
cross-coupling selectivity of 55% (entry 10, table 3) for the
coupling selectivity for a free radical-radical coupling pathway by
generating radicals from irradiation of di-tert-butyl peroxide with
a Xenon lamp in MeCN. A hydrogen-atom-transfer (HAT)
process leads to free phenoxyl radicals, which couple
spontaneously to the dimer. The cross-coupling chemo-
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cross-coupling reaction determined by 1H NMR spectroscopy.
The lower selectivity compared with a direct conversion of the
phenols with [1(CuBr)2] and O2 (entry 3, Table 3) indeed
indicates a short-lived species responsible for the high cross-
coupling selectivity, in line with the observed formation of
unstable copper-dioxygen species. The conversion of the
phenols after degassing the solution can be explained by the
formation of stoichiometric amounts of the oxidized ligand, 12+,
from decomposition of the initially formed dioxygen complex,
and its reaction with the phenols (as reported already earlier).[60]
catalyst. Consequently, we suggest a PCET process from the
phenol to the Cu2O2 complex forming a phenoxyl radical (similar
to the conclusions of Itoh et al. for Cu2O2 complexes);[33]
however, it has to be bound to one of the Cu atoms. Together
with the proposed radical-anion coupling scenario sketched in
Scheme 6, a reaction mechanism can be formulated that is
consistent with all observations (Scheme 7). To further elaborate
on the higher cross-coupling selectivity obtained with copper
complexes with ligand 1 compared with ligand 2, we added 2 eq.
of
a
base, triethylamine (entry 11, Table 3) or
tetramethylguanidine (entry 12, Table 3) to the phenols in DCM,
followed by the addition of 1 mol% of [1(CuBr)2] and dioxygen. In
both cases, the differences in the cross-coupling selectivity of
both ligands vanished upon base addition. According to the pKa
Proposed mechanism of the phenol cross-coupling
The accumulated experimental data leave no doubt that the
initial step of the catalytic cycle is the fast reaction of the
complex [1(CuBr)2] with dioxygen. Presumably an extremely
reactive Cu2O2 complex is formed, in line with previous studies
of C-C coupling of phenols with copper catalysts.[33] Experiments
in which radical scavengers were added in the phenol coupling
reactions are inconsistent with the involvement of free radicals in
the catalytic cycle. Moreover, the high selectivity in the cross-
coupling reaction cannot be explained with a free radical-radical
coupling mechanism, as shown by the direct usage of the radical
initiator di-tert-butyl peroxide or with the catalyst FeCl3 in DCM.
Therefore, the phenoxyl radical formed upon phenol
deprotonation and oxidation has to be bound to the copper
61
]
values, triethylamine (pKa = 10.74 in H2O)[
can only
deprotonate 2,6-dimethoxyphenol (pKa = 9.98 in H2O),[ 62 ]
whereas tetramethylguanidine (pKa = 13.6 in H2O)[63] is also able
to deprotonate the less acidic 2,6-di-tert-butylphenol (pKa = 11.7
in H2O),[62] in line with the CV studies with base addition (see SI).
The obvious inference is that the mode of deprotonation of 2,6-
dimethoxyphenol plays a decisive role for the selectivity of
cross-coupling with [1(CuBr)2]. Thus, we suggest a concerted
PCET process for complexes with ligand 1, preferentially leading
to (bound) phenoxyl radicals of 2,6-dimethoxyphenol (A).
Reaction with another molecule of phenol A results in the
Scheme 7. Proposed catalytic cycle for the cross-coupling of the two phenols A and B with [1(CuBr)2] as catalyst following a radical-anion coupling pathway.
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deprotonation of phenol A, coupled with a fast oxidation (EOx(A)
< EOx(B)) or a concerned PCET, eventually yielding a copper
complex with two bound phenoxyl radicals. However, due to
their different spatial orientation, these bound phenoxyl radicals
cannot couple to the dimer. On the other hand, deprotonation of
phenol B (slow oxidation to the corresponding radical) in the
vicinity to the copper complex with bound phenoxyl radical A
initiates cross-coupling to the product A-B via a radical-anion
coupling mechanism (Scheme 7). Consequently, addition of a
base (tetramethylguanidine or triethylamine) leads to a decrease
of the cross-coupling selectivity due to the generation of
stoichiometric amounts of deprotonated phenol A, being now
available as reaction partner and yielding the homo-coupling
product. Usually, the preferred oxidation of phenol A is the prime
obstacle for the cross-coupling of non-complementary phenols.
Herein, we suggest this to be the reason for the high cross-
coupling selectivity. According to our proposed mechanism,
complementary phenols should lead to lower cross-coupling
selectivity. This will be discussed in the next section (see ross-
coupling reaction to diquinone 13 (entry 6, Table 4)).
need of HFIP as solvent. Furthermore, we tested
a
complementary pair of phenols (13[20], entry 6, table 4, N =
0.49), which showed the lowest chemo-selectivity in our study as
suggested in our mechanistic discussion (see previous section).
For 10, a subsequent Diels-Alder dimerization to 14 was
observed in the presence of traces of acids, e. g. in CDCl3
(Figure 6). The yield of the diquinones 11 and 12 was lower than
the cross-coupling selectivity of the C-C coupled products.
Table 4. Scope of the cross-coupling reaction to the diquinones 813.
selectivitya)
yield (%)
/
#
1
phenol A
phenol B
product
70 / 70
As illustrated in Scheme 8, intramolecular electron transfer (IET)
can lead to several oxidation states of the metal atoms in the
Cu2O2 complex formed from [1(CuBr)2] and O2. Due to the
instability of this complex, we were unfortunately not able to
specify its electronic structure (oxidation states of the copper
atoms or the redox-active ligand). In principle, the formation of
oligomeric species, connected through bridging dioxygen, is also
possible. However, the already quite high charge of +2 of the
monomeric units opposes an oligomerization. Furthermore, the
complex [1(CuMeCN)2](BPh4)2 should be a better precursor to
such oligomers. Since [1(CuMeCN)2](BPh4)2 displays a lower
activity than [1(CuBr)2], the formation of oligomeric appears to
be not relevant for the catalytic cycle. In addition, the initially
formed Cu2O2 complex, which is only present in catalytic
amounts, reacts more likely with a phenol which is available in
high excess, than with a second copper complex.
80 / 80
2
3
68 / 68
79 / 45
74 / 41
47 / 47
4
5
6
Scheme 8. Three out of a number of possible electronic structures with
different copper oxidation states in a Cu2O2 complex with the redox-active
ligand 1.
a)
Cross-coupling selectivity was determined via 1H NMR by integrating an
internal standard, the cross-coupling product and the homo-coupling product
(see SI). The average of two experiments is given.
Cross-coupling reactions
Finally, we studied the cross-coupling reaction of further non-
complementary phenols (entry 1-5, Table 4, N = 0.35 to 0.52,
see SI for detailed values of N and EOx) to test the scope of the
new catalytic reaction. In addition to the already known
diquinone 8 [64] we were able to synthesize the new compounds
9-12 with a high chemo-selectivity, at ambient conditions, quite
fast (2 h) with only 1 mol% catalyst (Table 4) and without the
1
According to the H NMR and 13C NMR spectra of the reaction
solution, we suggest the formation of a further C-O coupling
product, leading to additional NMR signals that occurred
alongside the signals due to the known C-C coupling products
(diquinone, biphenol).[ 65 ] This product only appeared if 2,6-
dimethylphenol is used and therefore its formation might require
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the relatively low steric demand of this phenol. However, we
were unfortunately not able to identify this by-product.
coupling reactions of phenols with non-complementary
relationship. This effect also explains the poor chemo-selectivity
observed for cross-coupling reactions between phenols with
complementary relationship, in clear difference to traditionally
employed catalysts. On the basis of these conclusions, a
catalytic cycle was suggested that is in full agreement with all
experimental results.
Finally, we elaborated on the scope of the cross-coupling
reactions with the newly developed catalyst. For 6 examples a
high chemo-selectivity was proven. The advantages of the new
catalytic system are: 1) Special solvents such as HFIP or the
addition of sub-stoichiometric amounts of a base are not
necessary. 2) Fast and efficient cross-coupling reactions of
electron-rich phenols with non-complementary relationship are
enabled with high chemo-selectivities and without side-products
at room-temperature. 3) Dioxygen is used as green and
inexpensive oxidizing reagent.
For the applied conditions, the reactions are restricted to
electron-rich phenols. Halogenated phenols, which have a
higher oxidation potential, show no conversion. We suggest this
to be a consequence of the electron-rich ligands, that provide
the copper atoms with extra electron-density. On the one hand,
this leads to a fast dioxygen activation and most importantly to a
very efficient phenol deprotonation, accelerating the reactions
(as shown by the comparison of catalysts for the homo-coupling
reactions). On the other hand, it reduces the oxidation power of
the formed Cu2O2 complex due to higher electron density at the
copper atoms (Scheme 8).
As consequence of the high electron-donation of 1, the reactions
are restricted to electron rich phenols. In ongoing work in our
group, we are expanding our experiments to redox-active
guanidine ligands with slightly higher redox-potential (see the
bisguanidine ligands in ref. 36,38,39), to achieve the optimal
balance between fast activation of dioxygen with an efficient
phenol deprotonation, and the ability to oxidize less electron-rich
phenols.
Figure 6. a) Lewis structure of 14. b) Illustration of the structure of 14 in
crystals obtained from CDCl3 solution. Thermal ellipsoids are drawn at the
50% probability level. C atoms in grey, O atoms in red, hydrogen atoms are
omitted for clarity.
Experimental Section
Experimental
details
for
the
preparation
of
[1(CuBr)2],
Conclusions
[1(CuMeCN)2](BPh4)2, homo-coupling of 2,4-di-tert-butylphenol and 2,6-
di-tert-butylphenol, cross-coupling of 813, low-temperature UV/Vis
spectroscopic studies of the catalysts [1(CuBr)2], [1(CuMeCN)2](BPh4)2,
[2CuBr] and [2CuMeCN]BPh4 with dioxygen, and cyclovoltammetric
studies of 2,6-di-tert-butylphenol and 2,6-dimethoxyphenol are provided
in the SI.
Herein, we report on the reactivity of copper(I) complexes with a
redox-active guanidine ligand (1) in the oxidative C-C homo- and
cross-coupling of phenols. The results are compared with
experiments, in which the copper complexes of the virtually non-
redox-active ligand (2) were used. As shown by homo-coupling
reactions between 2,4-di-tert-butylphenol and 2,6-di-tert-
butylphenol, a significant higher activity is observed when the
redox-active ligand (1) is used. The catalyst [1(CuBr)] showed a
remarkably high reactivity in all test experiments.
Oxidative cross-coupling experiments with two phenols with non-
complementary relationship (usually afflicted with a low chemo-
selectivity) proved the complex [1(CuBr)] to be not only very
active, but also to enable cross-coupling reactions with high
chemo-selectivity. A detailed inspection of the reaction between
2,6-di-tert-butylphenol and 2,6-dimethoxyphenol disclosed the
advantages of catalysts with the redox-active ligand (1) in
comparison to other catalysts with respect to the activity and
chemo-selectivity. Moreover, the effect of several modifications
of the reaction conditions on the activity and chemo-selectivity
was examined, allowing clear-cut conclusions concerning the
reaction mechanism. First of all the reaction follows a radical-
Acknowledgements
The authors gratefully acknowledge continuous financial support
by the Deutsche Forschungsgemeinschaft (DFG). We thank
Saskia Krieg for the support with low temperature stopped-flow
UV/Vis spectroscopy.
Keywords: cross-coupling • redox-active ligands • phenols •
guanidines • catalysis
[1]
[2]
A. De Meijere, F. Diederich, Metal-Catalysed Cross-
Coupling Reactions, 2nd edn., Wiley-VCH, 2008.
K. Tamao, N. Miyaura, Introduction to cross-coupling
reactions, Top. Curr. Chem. 2002, 219, 1–9.
anion mechanism;
a radical-radical mechanism could be
[3]
[4]
[5]
[6]
M. Beller, A. Zapf, Chem. Commun. 2005, 431–440.
L. Yin, J. Liebscher, Chem. Rev. 2007, 107, 133 –173.
Á. Molnár, Chem. Rev. 2011, 111, 2251–2320.
A. Suzuki, Angew. Chem. 2011, 123, 6854–6869;
Angew. Chem. Int. Ed. 2011, 50, 6722– 6737.
excluded. Moreover, the enhancement of the difference between
basicity and redox-activity of the initially-formed dicopper bis--
oxo complex by the electron-donating ligand 1 was found to be
the key point to anticipate the high chemo-selectivity in cross-
This article is protected by copyright. All rights reserved.

10.1002/chem.201900583
Chemistry - A European Journal
FULL PAPER
[7]
[8]
[9]
E.-I. Negishi, Angew. Chem. 2011, 123, 6870–6897;
Angew. Chem. Int. Ed. 2011, 50, 6738– 6764.
X.-H. Li, M. Baar, S. Blechert, M. Antonietti, Sci. Rep.
2013, 3, 1743.
M. Grzybowski, K. Skonieczny, H. Butenschön, D. T.
Gryko, Angew. Chem. 2013, 125, 10084–10115; Angew.
Chem. Int. Ed. 2013, 52, 99009930.
[35]
A. Ziesak, L. Steuer, E. Kaifer, N. Wagner, J. Beck, H.
Wadepohl, H.-J. Himmel, Dalton Trans. 2018, 47, 9430–
9441.
D. F. Schrempp, E. Kaifer, H.-J. Himmel, Eur. J. Inorg.
Chem. 2018, 3660–3667.
S. Wiesner, A. Wagner, E. Kaifer, H.-J. Himmel, Dalton
Trans. 2016, 45, 15828–15839.
D. F. Schrempp, E. Kaifer, H. Wadepohl, H.-J.
Himmel, Chem. Eur. J. 2016, 22, 16187–16199.
[36]
[37]
[38]
[10]
[11]
[12]
H. Musso, Angew. Chem. 1963, 20, 965-977; Angew.
Chem. Int. Ed. 1963, 2, 723−735.
[39] a) D. F. Schrempp, S. Leingang, M. Schnurr, E. Kaifer, H.
Wadepohl, H.-J. Himmel, Chem. Eur. J., 2017, 23,
13607–13611; b) D. F. Schrempp, E. Schneider, E.
Kaifer, H. Wadepohl, H.-J. Himmel, Chem. Eur. J. 2017,
23, 11636–11648.
K. Okamoto, J. Zhang, J. B. Housekeeper, S. R. Marder,
C. K. Luscombe, Macromolecules 2013, 46, 8059–8078.
F. Nussbaum, M. Brands, B. Hinzen, S. Weigand, D.
Häbich, Angew. Chem. 2006, 118, 5194–5254; Angew.
Chem. Int. Ed. 2006, 45, 5072–5129.
[40]
[41]
H.-J. Himmel, Inorg. Chim. Acta, 2018, 481, 56–68.
S. Wiesner, A. Wagner, O. Hübner, E. Kaifer, H.-J.
Himmel, Chem. Eur. J. 2015, 21, 1649416503.
B. Dicke, A. Hoffmann, H. Stanek, M. S. Rampp, B.
Grimm-Lebsanft, F. Biebl, D. Rukser, B. Maerz, D.
Göries, M. Naumova, M. Biednov, G. Neuber, A. Wetzel,
S. M. Hofmann, P. Roedig, A. Meents, J. Bielecki, J.
Andreasson, K. R. Beyerlein, H. N. Chapman, C.
Bressler, W. Zinth, M. Rübhausen, S. Herres-Pawlis, Nat.
Chem. 2018, 10, 355362.
J. Stanek, N. Sackers, F. Fink, M. Paul, L. Peters, R.
Grunzke, A. Hoffmann, S. Herres-Pawlis Chem. Eur. J.
2017, 23, 1573815745.
N. J. Vollmers, P. Müllers, A. Hoffmann, S. Herres-
Pawlis, M. Rohrmüller, W. Schmidt, U. Gerstmann, M.
Bauer, Inorg. Chem. 2016, 55, 1169411706.
A. Hoffmann, J. Stanek, B. Dicke, L. Peters, B. Grimm-
Lebsanft, A. Wetzel, A. Jesser, M. Bauer, M. Gnida, W.
Meyer-Klaucke, M. Rübhausen, S. Herres-Pawlis, Eur. J.
Inorg. Chem. 2016, 47314743.
A. Hoffmann, S. Binder, A. Jesser, R. Haase, U. Flörke,
M. Gnida, M. Salomone Stagni, W. Meyer-Klaucke, B.
Lebsanft, L. E. Grünig, S. Schneider, M. Hashemi, A.
Goos, A. Wetzel, M. Rübhausen, S. Herres-Pawlis,
Angew. Chem. 2013, 126, 305310; Angew. Chem. Int.
Ed. 2013, 53, 299304.
D. Emeljanenko, A. Peters, N. Wagner, J. Beck, E.
Kaifer, H.-J. Himmel, Eur. J. Inorg. Chem. 2010,
1839−1846.
K. V. N. Esguerra, Y. Fall, L. Petitjean, J.-P. Lumb, J.
Am. Chem. Soc. 2014, 136, 7662–7668.
B. Elser, D. Schollmeyer, S. R. Waldvogel, Faraday
Discuss., 2014, 172, 413420.
M. Rolff, J. Schottenheimer, H. Decker, F. Tuczek,
Chem. Soc. Rev. 2011, 40, 40774098.
J. N. Hamann, B. Herzigkeit, R. Juergeleit, F. Tuczek,
Coord. Chem. Rev. 2017, 334, 54-66.
J. A. Halfen, S. Mahapatra, E. C. Wilkinson, S. Kaderli,
V. G. Young Jr., L. Que Jr., A. D. Zuberbühler, W. B.
Tolman, Science 1996, 271, 13971400.
A. Hoffmann, M. Wern, T. Hoppe, M. Witte, R. Haase, P.
Liebhäuser, J. Glatthaar, S. Herres-Pawlis, S. Schindler,
Eur. J. Inorg. Chem. 2016, 4744−4751.
S. Herres-Pawlis, U. Flörke, G. Henkel, Eur. J. Inorg.
Chem. 2005, 3815−3824.
[13]
J. Magano, J. R. Dunetz, Chem. Rev. 2011, 111, 2177–
2250.
[14]
[15]
[16]
J. M. Brunel, Chem. Rev. 2005, 105, 857−989.
L. Que, W. B. Tolman, Nature 2008, 455, 333340.
J. Piera, J.-E. Bäckvall, Angew. Chem. 2008,
120, 35583567; Angew. Chem. Int. Ed. 2008, 47,
35063523.
L.-C. Campeau, K. Fagnou, Chem. Commun. 2006,
1253−1264.
J. Hassan, M. Sévignon, C. Gozzi, E. Schulz, M.
Lemaire, Chem. Rev. 2002, 102, 1359−1470.
B. Schmidt, M. Riemer, M. Karras, J. Org. Chem. 2013,
78, 8680−8688.
A. Libman, H. Shalit, Y. Vainer, S. Narute, S. Kozuch, D.
Pappo, J. Am. Chem. Soc. 2015, 137, 11453–11460.
H. Shalit, A. Dyadyuk, D. Pappo, J. Org. Chem. 2019,
84, 16771686.
B. Elser, A. Wiebe, D. Schollmeyer, K. M. Dyballa, R.
Franke, S. R. Waldvogel, Chem. Eur. J. 2015, 21,
12321–12325
[42]
[17]
[18]
[19]
[20]
[21]
[22]
[43]
[44]
[45]
[23]
[24]
[25]
S. R. Waldvogel, S. Lips, M. Selt, B. Riehl, C. J. Kampf,
Chem. Rev. 2018, 118, 67066765.
Y. E. Lee, T. Cao, C. Torruellas, M. C. Kozlowski, J. Am.
Chem. Soc. 2014, 136, 6782–6785.
[46]
B. Elsler, D. Schollmeyer, K. M. Dyballa, R. Franke, S. R.
Waldvogel, Angew. Chem. 2014, 126, 5311−5314;
Angew. Chem. Int. Ed. 2014, 53, 5210–5213.
B. Riehl, K. M. Dyballa, R. Franke, S. R. Waldvogel,
Synthesis 2017, 49, 252259.
S. Lips, B. A. Frontana-Uribe, M. Dörr, D. Schollmeyer,
R. Franke, S. R. Waldvogel, Chem. Eur. J. 2018, 24,
60576061.
A. Wiebe, S. Lips, D. Schollmeyer, R. Franke, S. R.
Waldvogel, Angew. Chem. 2017, 129, 1492014925;
Angew. Chem. Int. Ed. 2017, 56, 1472714731.
A. Wiebe, B. Riehl, S. Lips, R. Franke, S. R. Waldvogel,
Sci. Adv. 2017, 3, eaao 3920/1-7
T. Quell, N. Beiser, K. M. Dyballa, R. Franke, S. R.
Waldvogel, Eur. J. Org. Chem. 2016, 4307–4310.
H. Shalit, A. Libman, D. Pappo, J. Am. Chem. Soc. 2017,
139, 13404–13413.
B. Dahms, P. J. Kohlpainter, A. Wiebe, R. Breinbauer, D.
Schollmeyer, S. R. Waldvogel, Chem. Eur. J. 2019, 25,
27132716.
T. Osako, K. Ohkubo, M. Taki, Y. Tachi, S. Fukuzumi, S.
Itoh, J. Am. Chem. Soc. 2003, 125, 11027−11033.
B. Eberle, O. Hübner, A. Ziesak, E. Kaifer, H.-J. Himmel,
Chem. Eur. J. 2015, 21, 8578−8590.
[47]
[26]
[27]
[48]
[49]
[50]
[51]
[52]
[28]
[29]
[30]
[31]
[32]
[53]
[54]
[55]
[56]
[33]
[34]
A. Peters, E. Kaifer, H.-J. Himmel, Eur. J. Org. Chem.
2008, 5907−5914.
M. Matsushitam K. Kamata, K. Yamaguchi, N. Mizuno, J.
Am. Chem. Soc. 2005, 127, 6632–6640.
This article is protected by copyright. All rights reserved.

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FULL PAPER
[57]
[58]
A. Wiebe, D. Schollmeyer, K. M. Dyballa, R. Franke, S.
R. Waldvogel, Angew. Chem. 2016, 128, 11979–11983;
Angew. Chem. Int. Ed. 2016, 19, 11801–11805.
E. Gaster, Y. Vainer, A. Regev, S. Narute, K.
Sudheendran, A. Werbeloff, H. Shalit, D. Pappo, Angew.
Chem. 2015, 127, 42724276; Angew. Chem. Int. Ed.
2015, 54, 41984202.
[59]
[60]
L. Eberson, M. P. Hartshorn, O. Persson, F. Radner,
Chem. Commun. 1996, 2105−2111.
U. Wild, F. Schön, H.-J. Himmel, Angew. Chem. 2017,
129, 16630−16633; Angew. Chem. Int. Ed. 2017, 56,
16410−16413.
[61]
[62]
[63]
A.
G.
Grechin,
H.-J.
Buschmann,
E.
Schollmeyer, Thermochim Acta 2006, 67–72.
M. Ragnar, C. T. Lindgren, N.-O. Nilvebrant, J. Wood
Chem. Technol. 2000, 20, 277–305.
K. Kaupmees, A. Trummal, I. Leito, Croat. Chem. Acta
2014, 358–395.
[64]
[65]
K. Omura, J. Org. Chem. 1998, 63, 10031−10034.
C. Boldron, C. Aromí, G. Challa, P. Gamez, J. Reedijk,
Chem. Commun. 2005, 58085810.
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10.1002/chem.201900583
Chemistry - A European Journal
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Entry for the Table of Contents
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Herein we report on new copper
catalysts for the C-C coupling of
phenols using dioxygen as a
green oxidation reagent. By
using redox-active ligands, the
activity as well as chemo-
selectivity in the phenol cross-
F. Schön, E. Kaifer, H.-J. Himmel*
Catalytic Aerobic Phenol Homo-
and Cross-Coupling with Copper
Complexes Bearing Redox-Active
Guanidine Ligands
coupling
is
significantly
improved.
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