Spectroscopic Characterization of a Reactive [Cu2(μ-OH)2]2+ Intermediate in Cu/TEMPO Catalyzed Aerobic Alcohol Oxidation Reaction

Article abstract of DOI:10.1002/anie.202108442

Cu^I/TEMPO (TEMPO=2,2,6,6-tetramethylpiperidinyloxyl) catalyst systems are versatile catalysts for aerobic alcohol oxidation reactions to selectively yield aldehydes. However, several aspects of the mechanism are yet unresolved, mainly because o

Full text of DOI:10.1002/anie.202108442

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Accepted Article
Title: Spectroscopic Characterization of a reactive [Cu2(µ-OH)2]
intermediate in Cu/TEMPO catalyzed aerobic alcohol oxidation
reaction
Authors: Kallol Ray, Katrin Warm, Guilherme Tripodi, Erik Andris,
Stefan Mebs, Uwe Kuhlmann, Holger Dau, Peter Hildebrandt,
and Jana Roithová
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RESEARCH ARTICLE
2
+
Spectroscopic Characterization of a reactive [Cu
2
(µ-OH) ] in-
2
termediate in Cu/TEMPO catalyzed aerobic alcohol oxidation
reaction
Katrin Warm,[a] Guilherme Tripodi,[b] Erik Andris,[b] Stefan Mebs,[c] Uwe Kuhlmann,[d] Holger Dau,[c]
Peter Hildebrandt,[d] Jana Roithová,*[b] Kallol Ray*[a]
[
a]
M. Sc. K. Warm, Prof. Dr. K. Ray
Institut für Chemie
Humboldt-Universität zu Berlin
Brook-Taylor-Straße 2, 12489 Berlin, Germany
E-mail: kallol.ray@chemie.hu-berlin.de
M. Sc. G. Tripodi, Dr. E. Andris, Prof. Dr. J. Roithová
Radboud University
Heyendaalseweg 135, 6525 AJ NIJMEGEN, Netherlands
E-mail: j.roithova@science.ru.nl
Dr. S. Mebs, Prof. Dr. H. Dau
Institut für Physik
Freie Universität Berlin
Arnimallee 14, 14195 Berlin, Germany
Dr. U. Kuhlmann, Prof. Dr. P. Hildebrandt
Institut für Chemie, Fakultät II
[
[
[
b]
c]
d]
Technische Universität Berlin
Straße des 17. Juni 135, 10623 Berlin, Germany
Supporting information for this article is given via a link at the end of the document.
I
Abstract: Cu /TEMPO (TEMPO = 2,2,6,6-tetramethylpiperidine-N-
oxyl) catalyst systems are versatile catalysts for aerobic alcohol
oxidation reactions to selectively yield aldehydes. However, several
aspects of the mechanism are yet unresolved, mainly because of the
lack of identification of any reactive intermediates. Herein, we report
characterized in the catalytic cycles of different copper containing
enzymes and their synthetic model complexes.[ We now report
the generation and spectroscopic characterization of a new
1, 3]
copper-oxygen
intermediate
3
containing
a
bis(μ-
hydroxo)dicopper(II) core (H), which is formed upon dioxygen
2
+
2+
the synthesis and characterization of a dinuclear [Cu
2
L1
2
]
complex
activation at a dinuclear [Cu
2
L1
2
]
complex 1 (Scheme 1; L1 =
+
-
1
, which in presence of TEMPO can couple the catalytic 4H /4e
3,3-dimethyl-1-(1-methyl-1H-benzo[d]imidazole-2-yl)-N-(propan-
2-ylidene)butan-2-amine). Furthermore, in contrast to previous
reports, in which copper(II)-hydroxide moieties are considered as
sluggish oxidants in stoichiometric reactions[ and products of
catalyst decomposition reactions in Cu/TEMPO catalyzed aerobic
oxidation of alcohols,[ 3 is involved in the reduction of dioxygen
to water in presence of 2,2,6,6-tetramethylpiperidin-1-ol
(TEMPO-H) and also dehydrogenates aliphatic and benzyl
alcohols in presence of the 2,2,6,6-tetramethyl-1-piperidinyloxyl
(TEMPO) radical. The unique reactivity of 3 makes the 1/TEMPO
system suitable for the catalytic aerobic oxidation of alcohols to
reduction of O
2
to water to the oxidation of benzylic and aliphatic
-reduction and alcohol oxidation
alcohols. The mechanisms of the O
2
4]
reactions have been clarified by the spectroscopic detection of the
reactive intermediates in the gas and condensed phases, as well as
by kinetic studies on each step in the catalytic cycles. Bis(μ-
oxo)dicopper(III) (2) and bis(μ-hydroxo)dicopper(II) species 3 are
shown as viable reactants in oxidation catalysis. The present study
provides deep mechanistic insight into the aerobic oxidation of
alcohols that should serve as a valuable foundation for ongoing efforts
dedicated towards the understanding of transition-metal catalysts
involving redox-active organic cocatalysts.
5]
aldehydes, by consuming all four oxidizing equivalents of O
yielding H O as a byproduct.
2
and
2
Notably, combinations of a Cu(I) salt and organic aminoxyl,
such as TEMPO represent some of the most versatile and
practical catalysts for the aerobic oxidation of alcohols to
aldehydes.[5a, 6] The most widely used catalysts feature 2,2’-
bipyridine (bpy) as the ancillary ligand in combination with N-
methyl imidazole (NMI). Replacement of bpy with a pyridine-
Introduction
Copper-oxygen species are proposed as reactive intermediates
in a variety of biological and chemical oxidation reactions.[
1]
A
significant effort has been dedicated towards the understanding
of their electronic structures and reactivities, which is necessary
for obtaining detailed mechanistic insights into oxidation catalysis
and for developing new, selective catalytic reagents and
processes.[1b, 1c, 2] In the last few decades, several reactive
copper-oxygen motifs, exemplified by the structures A-G in
scheme 1, have been identified and spectroscopically
imidazole
(Py-NMI)
ligand
(2-(1-Methyl-1H-imidazol-2-
[6d]
yl)pyridine) in the above reaction has yielded comparable yields
of the aldehyde product. However, several aspects of the
mechanism remain unresolved and future studies are warranted
to gain further insights that can guide the development of new
catalytic systems. For example, although
a
mononuclear
I
+
[Cu (bpy)(NMI)] complex is proposed as an active catalyst
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1

Angewandte Chemie International Edition
10.1002/anie.202108442
RESEARCH ARTICLE
responsible for dioxygen activation, this complex is generated in
situ and has not been isolated and/or characterized. Furthermore,
1) of 1 shows a prominent signal of dimeric [Cu
334 and of monomeric [L1Cu(acetone)] at m/z 392.
2
L1
2
]2+ at m/z =
+
the
isolation
Cu (OH)
of
](CF
a
catalytically
cubane
active
tetranuclear
Complex 1 is diamagnetic (S = 0), as demonstrated by the
H NMR resonances (Figure S2) spread over a chemical shift
complex[
5a]
in
the
1
[
(bpy)
4
4
4
3
SO
3
)
4
I
Cu OTf/bpy/NMI/TEMPO catalytic system makes the proposed
bimolecular dioxygen activation mechanism ambiguous. Finally,
range of 0 to +10 ppm; the signals were shifted relative to the free
ligand, thereby confirming the binding of Cu(I) to L1. X-ray
diffraction analysis revealed a dinuclear structure of 1 (Figure S3
and scheme 1; Tables 1, S2), with L1 acting as a bridging ligand
between the two Cu(I) centers. The Cu(I) centers are two-
coordinate with almost linear N‒Cu‒N angles of 176.55(19)° and
Cu‒NBzim and Cu‒NImin distances of 1.877(4) Å, and 1.903(4) Å,
respectively. In X-ray absorption near-edge spectroscopic
(XANES) studies at the Cu K-edge (Figure 2A), 1 exhibits an edge
inflection energy of ∼8985.8 eV, with a shoulder along the rising
edge at 8983.8 eV corresponding to a 1s → 4p shakedown
transition, in accordance with the Cu(I) assignment and the linear
coordination of Cu. Analysis of the extended X-ray absorption fine
structure (EXAFS) spectra revealed 2 N scatterers at 1.91 Å and
1 Cu scatterer at 3.19 Å (Figure 2, Tables 1, S3). The good
agreement between XRD and EXAFS determined distances
(Tables 1, S2-S3) confirms that the dinuclear solid-state structure
is retained in frozen acetone solutions of 1.
a two electron reduction of O
disproportionation to H O and O
observed O
towards a direct four-electron reduction of O
The growing synthetic utility and significance of the
Cu/TEMPO catalyzed reactions and the existing mechanistic
ambiguities prompted us to undertake a thorough mechanistic
investigation. Based on the reported beneficial effect of imidazole
ligation in copper catalyzed aerobic oxidation reactions in
chemistry and biology,[1a, 7] and the suggested bimolecular
dioxygen activation mechanism[6b] in Cu/TEMPO catalyzed
2 2 2
to H O (and its subsequent
2
2
) is proposed, in spite of the
:alcohol stoichiometry of 0.5[
6b]
that may point
2
to H O.
2
2
reactions, we now employ
a well characterized dinuclear
[
CuI ]2+ complex 1 supported on a ligand L1 bearing
2
(L1)
2
benzimidazole and imino functionalities. Although 1/NMI/TEMPO
is slightly less efficient than Cu OTf/bpy/NMI/TEMPO (Table S1),
I
the high level of steric hindrance provided by L1 ensures
successful trapping of some of the reactive intermediates formed
upon dioxygen activation under catalytically relevant conditions.
This study, therefore, provides a valuable foundation for ongoing
efforts dedicated towards the understanding of transition-metal
catalysts involving redox-active organic cocatalysts.[
6c, 8]
Figure 1. ESI-MS spectra of 1 in acetone in the positive mode displaying
2
+
(m/z 334) and [L1Cu(acetone)]+ (m/z 392) (top, black); the reaction
[
2
L1 Cu
2
]
2+
product of 1 with O
2
at ‒10 °C displaying [L1
2
Cu
2
2+
(OH)
2
]
(3) at m/z 351 admixed
with signals of [L1Cu(OH)] , [L12Cu2(OH)(F)] and ([L1Cu(F)]+ (see Figure S5
+
for deconvolution) (middle, red); and the products of the addition of TEMPO-H
2
+
to a solution of 3 corresponding to copper(I) complexes [L12Cu
2
]
(m/z 334),
O)] (m/z 352), and [L1Cu(acetone)]+ (m/z 392) (bottom, blue).
+
[
L1Cu(H
2
Reaction with O
intermediates: Complex 1 reacts with O
acetonitrile at –30 °C to yield a new species 3 (Figure 3, t1/2 ≈ 5 h
20 °C in acetone) with electronic absorption maxima centered
at 345 nm (εmax = 2500 M cm ) and at 540 nm (εmax = 80 M cm
1)
. The nature of 3 was established by a variety of spectroscopic
2
and characterization of the metal-dioxygen
2
in acetone and
Scheme 1. Structures of the copper oxygen cores A-H and the dinuclear copper
complexes 1-3 (1 – XRD structure, 2,3 – DFT calculated structures; Cu: orange,
N: blue, C: grey).
@
–1
–1
–1
–
techniques. Complex 3 is silent at X-band EPR (Figure S4). ESI-
MS (Figure 1, red) shows a signal at m/z 351 corresponding to
Results and Discussion
2+
dimeric [L1
2
Cu
2
(OH)
2
] . The isotopic pattern suggests that we
Synthesis and Characterization of L1 and 1: The ligand L1
bearing benzimidazole and imino functionalities was synthesized
in a three-step reaction (Scheme S1). Metallation of L1 with
tetrakis(acetonitrile)copper(I) tetrafluoroborate yielded 1 in 63%
yield. Electrospray ionization mass spectrometry (ESI-MS; Figure
also detect monomeric [L1Cu(OH)] and [L1Cu(F)]+ and their
+
2+
dimer [L1
2
Cu
2
(OH)(F)] (see Figure S5 for the deconvolution of
–
the signals). Fluorine originates from decomposition of BF
counterions. Upon introduction of 18O into 3, its mass shifts from
4
3
51.1 to 353.1 (Figure S6), thereby demonstrating that two
18
2+
oxygen atoms from
2 2 2 2
O are incorporated into the [L1 Cu (OH) ]
2
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Angewandte Chemie International Edition
10.1002/anie.202108442
RESEARCH ARTICLE
core in 3. Upon addition of D
2
O, we observe a shift towards
2+
2 2 2
formation of [L1 Cu (OD) ]
(Figure S6).
Figure 3. UV-Vis absorption spectra of 1 (black), 2 (yellow) and 3 (blue); the
expansion of the 400 - 600 nm region is shown as an inset.
2 2 2
Cu (OH)
]2+ by
We have further investigated the structure of [L1
helium tagging infrared photodissociation (IRPD) spectroscopy
Figure 4A). This method provides IR spectra of mass-selected
ions (for more details see ref [10]). The IR spectrum of gaseous
[
9]
(
2 2 2
L1 Cu (OH)
]2+ reveals two oxygen-sensitive bands at 870 and
[
–1
–1
18
8
99 cm , which shift to 847 and 879 cm , respectively, upon O-
1
2
2 2 2
labelling. The H/ H exchange in [L1 Cu (OH)
]2+ results in a shift
–1
–1
–1
of the 899 cm band to 712 cm ; the 847 cm band also
disappears upon H/ H exchange, and is presumably shifted
below 700 cm , which is beyond the detection range of our
spectrometer.
1
2
–1
XANES of 3 in acetone provides an edge-energy of 8987.1
eV, which is blue-shifted relative to 1, and consistent with a Cu(II)
assignment (Figure 2A). Analysis (Figure 2; Tables 1, S3) of the
EXAFS spectrum shows 4 Cu‒N/O and 1 Cu‒Cu shells at 1.96 Å
and 3.01 Å, respectively, for 3, which are in the range of the Cu-
N/O and Cu-Cu distances observed in the crystallographically
Figure 2. A) X-ray absorption near edge fine structure (XANES) spectra of
solutions of 1 (black), 2 (yellow) and 3 (blue) in d -acetone and Extended X-ray
Absorption Fine Structure (EXAFS, inset; solid lines: experimental spectra,
dotted lines: simulated spectra); B) Fourier Transformation of the EXAFS
signals of 1, 2 and 3; for further details concerning bond distances and
simulation parameters table S3.
6
2+
[4a, 4c,
characterized [Cu
4d, 4f, 4g]
2
(OH)
2
]
cores in the literature (Table S4).
Taken together, all the spectroscopic studies point towards
a bis(µ-hydroxo)dicopper(II) assignment for 3, which is also
supported by density functional theoretical studies. The lowest
II
II
2+
energy structure corresponds to a [L1Cu (µ-OH)
where antiferromagnetic coupling between the SCu = 1/2 Cu(II)
centers stabilizes an open-shell S = 0 electronic configuration
Scheme 1; Figure S7). The most stable isomers A and B differ
2
Cu L1] motif,
Table 1. Selected distances [Å] for complexes 1, 2 and 3 as obtained from XRD
and XAS measurements and DFT calculations.
T
(
Cu‒NBzim
Cu‒NImin
Cu‒O
Cu‒Cu
by the benzimidazole units pointing the same or to opposite sides
of the dicopper complex. The energies of the isomers lie within 1
kcal/mol. Each of the isomers can also have other conformers
(e.g., C in Figure S7). The positions of the IR-active bands
1
2
3
XRD
EXAFS
DFT
EXAFS
DFT
1.877(4)
1.91
1.873
1.96
1.903(4)
1.91
1.891
1.96
-
-
-
3.144(1)
3.19
3.043
2.76
1.81
1.780
1.890
1.946
2.715
II
CuII core and their 18O/ O and 1H/ H
16
2
involving the Cu (µ-OH)
2
.786 [
a]
a]
1
isotopic shifts are in
a reasonable agreement with the
EXAFS
DFT
1.96
1.962
1.96
2.041
1.96
3.01
3.062
1.938
experimental values (Figure S7 and Tables 1, S6). On the basis
of the calculated frequencies and isotopic shifts (Table S6), the
1
.954 [
1
8
16
–
[
a] Asymmetric L1 coordination to copper results in a distorted Cu
2
O
2
core
experimentally observed IR bands at 877 ( O/ O shift of 23 cm
1
–1 18
16
1
2
–1
structure.
) and 899 cm ( O/ O and H/ H shifts of 20 and 187 cm ,
respectively) are assigned to symmetric and antisymmetric CuO‒
H deformation modes. For instance, the calculated frequencies
–
1
–1
18
16
for isomer B are 866 cm and 878 cm , with O/ O shifts of 20
–1
–1
2
–
cm and 18 cm , respectively. Upon H substitution the 880 cm
mode is shifted to 690 cm , in good agreement with the
1
–1
experiment. The experimentally observed Cu‒N/O distances are
also well reproduced in the calculations (Tables 1, S6).
3
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RESEARCH ARTICLE
Figure 5. A) Changes in the UV-Vis spectra of 2 (yellow) and formation of 3
(blue) upon addition of 1,4-cyclohexadiene (0.07 M) at ‒90 °C; inset shows the
time traces at the characteristic wavelengths of 2 (375 nm, yellow first-order fit)
and 3 (345 nm, blue first-order fit); B) Changes in the UV-Vis spectra of 3 (blue)
upon addition of TEMPO-H (0.05 M) at ‒50 °C yielding 1; inset shows the time-
trace at 345 nm.
Figure 4. A) IR spectra of mass-selected ions of 16O-labelled 3 (m/z 351.1,
black), 18O-labelled 3 (m/z 353.1, red) and H-labelled 3 (m/z 352.1, blue)
measured by helium-tagging IR photodissociation spectroscopy; B) rRaman
spectra of 16O-labelled 2 (black) and O-labelled 2 (red) upon 406 nm Kr+ laser
irradiation at ‒90 °C.
2
18
2
The conversion of 1 to 3 in the presence of O must involve the
initial formation of a transient Cu–dioxygen intermediate, 2,
followed by a rapid H-atom abstraction (HAA) from acetone.
Indeed, a comparison of the rates of the formation of 3 in acetone
6
and d -acetone, yields a hydrogen/deuterium kinetic isotope
effect (KIE) of 1.65 (Figure S8, Table S7), which corroborates
acetone as a H-atom donor in the reaction. Adjustment of the
reaction conditions to ensure faster formation of 2 and its slower
decay to 3, led to the eventual trapping of 2. Accordingly, the
reaction of a concentrated solution of 1 (≥2.5 mM) with O
2
at ‒
8
0 °C in d -acetone results in the development of an intense
6
–1
–1
absorption feature at 375 nm (εmax = 3700 M cm ) and a weaker
band at 465 nm (εmax = 360 M–1 cm ) (t1/2 = 10 min at ‒30°C in
–1
d
6
-acetone) corresponding to 2 (Figure 3). In presence of
substrates bearing weak O‒H (e.g. TEMPO-H) or C‒H bonds (e.g.
,4-cyclohexadiene and indene) 2 is converted to 3, with an
1
isosbestic point at 356 nm (Figures 5A, S9-11, Table S8). This
plausibly implies a single-step mechanism for the two HAA steps
required for the conversion of 2 to 3. Resonance Raman
(
rRaman) spectroscopy performed on solutions of 2 in acetone
–1
displays a ν(Cu-O) stretching vibration at 606 cm , which shifts
to 582 cm–1 upon 18O-labelling (Figure 4B). XANES of 2 shows
the presence of residual 1 in solution, which together with the lack
4
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Angewandte Chemie International Edition
10.1002/anie.202108442
RESEARCH ARTICLE
of any pre-edge in 2 removes the one sure way of assigning the
II
III
physical oxidation state of copper (Cu vs. Cu ); edge energies
are known to be an ambiguous predictor for identifying whether a
II
III [11]
given complex is Cu or Cu . EXAFS analysis of 2 reveals short
Cu‒O and Cu‒Cu distances of 1.81 Å and 2.76 Å, respectively.
III
2+
[1b, 8b, 8c]
In analogy to the well-studied [Cu
2
(µ-O)
2
]
systems,
for
which similar EXAFS, rRaman and absorption spectral signatures
III
III
were reported, we assign 2 as a [L1Cu (µ-O)
Table S5). The DFT calculated ν([Cu‒O] ) and Cu‒N/O and Cu‒
Cu distances are in reasonable agreement with the experiment
Tables 1, S6), further validating the [CuIII ]2+ assignment of
(µ-O)
. The HAA reactivity of 2 with 1,4-CHD is one order of magnitude
2
Cu L1] complex
(
2
(
2
2
2
III
2 2
(µ-O)
]2+ complexes
slower than some of the most reactive [Cu
known to date (Table S5). [
1b, 8b, 8c]
Stoichiometric Oxidation Reactions: Based on the proposed
II
+
[6a-c]
involvement of transient [Cu ‒OH] intermediates
Cu/TEMPO catalyzed aerobic oxidation of alcohols, we sought to
investigate the reactivity of the [Cu (μ-OH)
]2+ core in 3 in various
in the
2
2
oxidation reactions. In HAA reaction, the addition of TEMPO-H to
an acetone solution of 3 at 20 °C leads to the decay of the 345
nm band corresponding to 3 with the stoichiometric formation of
TEMPO• (Figure 6B, Figure S12). The first-order rate constant,
determined by pseudo-first-order fitting of the kinetic data for the
decay of 3, increases linearly with increasing TEMPO-H
concentration, thereby giving a second-order rate constant of
–1
–1
0
.12ꢀM
s
at ‒50ꢀ°C (Figure S12).
We have further monitored the reaction of 3 and TEMPO-H
by ESI-MS.[12] We have shortened the reaction time to the order
of seconds by performing the reaction in a flow setup and studied
the reaction kinetics by changing the concentration of TEMPO-H
(
Figure 6).[ The spectra show an increasing conversion of the
13]
+
dimer 3 and [L1Cu(OH)] to the copper(I) dimer 1 with the
increasing concentration of TEMPO-H (Figure 6: blue to yellow,
see also Figure S5)). The dependence of the relative ion
abundances on the concentration of TEMPO-H clearly suggests
that the monomer [L1Cu(OH)]+ reacts faster than the dimer
Figure 6. A) ESI-MS spectra at constant reaction time with varied
concentrations of TEMPO-H (indicated at the right side); B) Relative integrated
intensities of the signals corresponding to copper(II) reactants and copper(I)
products; the corresponding ions are color-coded; C) The reaction scheme
(
Figure 6B). In fact, the decreasing concentration of 3 is most
likely a result of the equilibrium reaction between 3 and the
+
[L1Cu(OH)] monomer; however, a direct reaction of 3 with
consistent with the kinetics obtained from the flow reactor
experiments.
– ESI-MS
TEMPO-H can’t be excluded. In addition, we detect intermediates
of this transformation. The [L1Cu(OH)] complex reacts with
TEMPO-H to form [L1Cu(OH)(TEMPOH)] , which eliminates H
and yields [L1Cu(TEMPO)] (in green in Figure 6). This
intermediate eliminates the TEMPO radical leading to the
regeneration of the copper(I) complex. We did not detect the
primary [L1Cu(OH)(TEMPOH)]+ intermediate, but we did detect
analogous [L1Cu(F)(TEMPOH)] (in pink). This complex can be
interpreted as
+
+
2
O
+
Catalytic Dioxygen Reduction: The direct cleavage of oxygen
by 1 to form 3 and the subsequent regeneration of 1 from 3 in
presence of a H-atom donor makes 1 an efficient catalyst for the
reduction of O
or byproduct,
significance. In a test reaction, 0.25 mol% of 1 in acetone at
0 °C was found to be able to catalytically reduce O to H O with
2
to H
2
O without forming H
2
O
2
as an intermediate
+
which
has tremendous
technological
a
“frozen” intermediate, because the large
[14]
electronegativity of F makes the elimination of HF endothermic
2
2
2
(
see also Figure S13), thereby leading to the accumulation of
a turn-over number (TON) of 250 by employing TEMPO-H as a
H-atom donor (eqn 1; Figure S14). The involvement of 2 and 3
+
[L1Cu(F)(TEMPOH)] .
[15]
could be evidenced by using the stopped-flow technique in the
reaction of 1 and O in presence of excess TEMPO-H at ‒75 °C;
2
at higher temperature the Cu(I) species is regenerated by the
reaction of 3 with TEMPO-H (Figure S11).
5
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RESEARCH ARTICLE
Stoichiometric and Catalytic Alcohol Oxidation Reactions:
Complex 3 also showed a high reactivity in the oxidation of benzyl
alcohol at 20ꢀ°C in presence of TEMPO, thereby producing
benzaldehyde quantitatively and regenerating 1 and TEMPO-H.
Addition of 100 equiv. of benzylalcohol to a solution of 3 leads to
a red-shift of the 345 nm band to 355 nm (Figure S15),
II
presumably because of the formation of the [L1Cu (µ-
II
OCH
2
Ph)(µ-OH)Cu L1] (4) in a preequilibrium step (Scheme 2),
as evident from ESI-MS (Figure S16) and EPR spectroscopy
Figure S17). Complex 4 then decays in presence of TEMPO with
(
‒1 ‒1
a second order rate constant of 0.05 M s at ‒10 °C (Figure S15).
can also dehydrogenate aliphatic alcohols like n-hexanol in
3
presence of TEMPO to the corresponding aldehydes (30% yield),
but at rates much slower than benzylalcohol (Figure S18).
Based on the demonstrated abilities of 3 to dehydrogenate
benzylalcohol in presence of TEMPO and to regenerate TEMPO
by HAA from TEMPO-H, we tested the aerobic oxidation of
benzylalcohol under catalytic conditions (eqn 2). Indeed, in
2
presence of O or air in acetone at 20 °C, 1 (2 mol%) and TEMPO
(
2 mol%) can catalytically oxidize benzyl alcohol to benzaldehyde
with a moderate TON of 25;[ however, our aliphatic model
substrate n-hexanol was only oxidized to n-hexanal
stoichiometrically. Interestingly, the addition of NMI (4 mol%)
enabled the catalytic oxidation of n-hexanol (TON = 7) and also
enhanced the catalytic efficiency of the oxidation of benzyl alcohol
15]
Scheme 2. Schematic overview of the mechanisms of catalytic alcohol
oxidation (blue) and O reduction reactions (green); the inset shows the different
2
activation mechanism suggested by Stahl et al.[6b]
O
2
(TON ≥ 50).
Conclusion
In
summary,
bis(μ-oxo)dicopper(III)
and
bis(μ-
hydroxo)dicopper(II) species have been identified and
spectroscopically characterized as reactive intermediates in
The effect of NMI addition on the reaction was evaluated under
stoichiometric conditions. An instantaneous decay of the UV-Vis
features of 3 upon addition of 5 eq NMI at ‒10 °C indicated a
substantial structural change. This was corroborated by EPR,
which showed the formation of a paramagnetic mononuclear Cu
species in 60% yield (Figure S19). Hence we conclude that NMI
not only acts as a base, as suggested previously, thereby,
1
/TEMPO catalyzed aerobic oxidation of benzylalcohol and n-
hexanol. Our study supports a mechanism, in which the catalytic
+
-
4
H /4e reduction of O
2
to water is coupled to the oxidation of
II
alcohols (Scheme 2). Although, the mechanism for 1/TEMPO
parallels the proposed bimolecular activation of
O
2
during
I
[6b]
(bpy)Cu /TEMPO catalyzed aerobic oxidation of alcohols, the
II
[5a, 6a, 6b]
assisting the formation of the Cu -alcoholate complex 4,
it
results of our study also reveal some differences in the two cases.
II
also presumably facilitates the dissociation of the [L1Cu (µ-
OH)Cu L1] dimer into the more reactive [L1Cu(OH)] monomer.
I
For example, in the (bpy)Cu /TEMPO system, based on detailed
II
2+
+
kinetic studies, an unidentified transient binuclear Cu
intermediate was proposed to convert to a mononuclear Cu -OH
species (responsible for alcohol oxidation) in presence of
2
O
2
II
TEMPO-H and H
In contrast, the two Cu centers in 1 are demonstrated to directly
2
O with the release of H
2
O
2
(Scheme 3, inset).
I
2
cleave O to form a well characterized bis(μ-oxo)dicopper(III)
intermediate 2, which undergoes HAA reactions to yield the bis(μ-
hydroxo)dicopper(II) moiety 3. Complex 3 reacts with TEMPO-H
to release water, thereby forming TEMPO, which is then used in
the dehydrogenation of alcohols. The direct cleavage of O
ensures the clean reduction of O to H O without any formation of
. Notably, the previous report[
(bpy) Cu (OH) ](CF SO may also corroborate the involvement
of similar [(bpy) Cu (OH) ](CF SO core during the
bpy/Cu /TEMPO/NMI catalyzed aerobic oxidation of alcohols; the
lower steric demand of bpy plausibly makes
(bpy) (OH) ](CF SO unstable against dimerization leading
to the precipitation of [(bpy) Cu (OH) ](CF SO
2
by 1
2
2
5a]
H
2
O
2
of the precipitation of
[
4
4
4
3
3 4
)
a
2
2
2
3
3 2
)
I
[
2
Cu
2
2
3
3 2
)
4
4
4
3
3 4
)
Acknowledgements
6
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Angewandte Chemie International Edition
10.1002/anie.202108442
RESEARCH ARTICLE
Chiavarino, M.E. Crestoni, S. Fornarini, Chem. Rev. 2020,
This work was funded by the Deutsche Forschungsgemein-schaft
1
20, 3261–3295. For the use of helium tagging IRPD
(DFG, German Research Foundation) under Germany’s
spectroscopy for characterization of reactive metal
complexes see: d) E. Andris, R. Navrátil, J. Jašík, M. Puri,
M. Costas, L. Que, Jr., J. Roithová, J. Am. Chem. Soc. 2018,
Excellence Strategy - EXC 2008 - 390540038 - UniSysCat to K.R.,
P.H., and H.D., and the Heisenberg-Professorship to K.R. and by
the European Research Council (ERC CoG No. 682275) to JR.
K.W. also thanks Einstein Foundation Berlin (ESB) - Einstein
Center of Catalysis (EC²) and ECOSTBio (COST Action CM1305)
for their support. H.D. acknowledges support by the BMBF in the
OPERANDO-XAS project. We acknowledge the Helmholtz
Zentrum Berlin (HZB) for providing experi-mental infrastructure
and allocating beamtime at beamline KMC-3 of the BESSY
synchrotron; we thank Ivo Zizak and further BESSY staff for their
support.
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7
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Angewandte Chemie International Edition
10.1002/anie.202108442
RESEARCH ARTICLE
Entry for the Table of Contents
A dinuclear Cu(I) complex 1 activates O
2
2
to form a bis(-hydroxo)dicopper(II) species, which can efficiently couple O reduction and
the oxidation of alcohols to make 1/TEMPO (TEMPO = 2,2,6,6-tetramethylpiperidine-N-oxyl) a suitable catalyst system for the aerobic
I
oxidation of alcohols to aldehydes. Notably, 1/TEMPO ensures a clean reduction of O
where the generation of H is proposed.
2
to H
2
O, in contrast to (2,2’-bipyridine)Cu /TEMPO,
2 2
O
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