Addressing Reversibility of R-NHC Coupling on Palladium: Is Nano-to-Molecular Transition Possible for the Pd/NHC System?

Article abstract of DOI:10.1021/acs.inorgchem.9b01630

It has recently been shown that palladium-catalyzed reactions with N-heterocyclic carbene (NHC) ligands involve R-NHC coupling accompanied by transformation of the molecular catalytic system into the nanoscale catalytic system. An important question appeared in this regard is whether such a change in the catalytic system is irreversible. More specifically, is the reverse nano-to-molecular transformation possible? In view of the paramount significance of this question to the area of catalyst design, we studied the capability of 2-substituted azolium salts to undergo the breakage of C-C bond and exchange substituents on the carbene carbon with corresponding aryl halides in the presence of Pd nanoparticles. The study provides important experimental evidence of possibility of the reversible R-NHC coupling. The observed behavior indicates that the nanosized metal species are capable of reverse transition to molecular species. Such an option, known for phosphine ligands, was previously unexplored for NHC ligands. The present study for the first time demonstrates bidirectional dynamic transitions between the molecular and nanostructured states in Pd/NHC systems. As a unique feature, surprisingly small activation barriers (<18 kcal/mol) and noticeable thermodynamic driving force (-5 to -7 kcal/mol) were calculated for C-C bond oxidative addition to Pd(0) centers in the studied system. The first example of NHC-mediated Pd leaching from metal nanoparticles to solution was observed and formation of Pd/NHC complex in solution was detected by ESI-MS.

Full text of DOI:10.1021/acs.inorgchem.9b01630

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Cite This: Inorg. Chem. XXXX, XXX, XXX−XXX
Addressing Reversibility of R−NHC Coupling on Palladium: Is Nano-
to-Molecular Transition Possible for the Pd/NHC System?
Ekaterina A. Denisova, Dmitry B. Eremin, Evgeniy G. Gordeev, Andrey M. Tsedilin,
and Valentine P. Ananikov*
Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, Moscow 119991, Russia
S
* Supporting Information
ABSTRACT: It has recently been shown that palladium-catalyzed
reactions with N-heterocyclic carbene (NHC) ligands involve R−
NHC coupling accompanied by transformation of the molecular
catalytic system into the nanoscale catalytic system. An important
question appeared in this regard is whether such a change in the
catalytic system is irreversible. More specifically, is the reverse nano-
to-molecular transformation possible? In view of the paramount
significance of this question to the area of catalyst design, we studied
the capability of 2-substituted azolium salts to undergo the breakage
of C−C bond and exchange substituents on the carbene carbon with corresponding aryl halides in the presence of Pd
nanoparticles. The study provides important experimental evidence of possibility of the reversible R−NHC coupling. The
observed behavior indicates that the nanosized metal species are capable of reverse transition to molecular species. Such an
option, known for phosphine ligands, was previously unexplored for NHC ligands. The present study for the first time
demonstrates bidirectional dynamic transitions between the molecular and nanostructured states in Pd/NHC systems. As a
unique feature, surprisingly small activation barriers (<18 kcal/mol) and noticeable thermodynamic driving force (−5 to −7
kcal/mol) were calculated for C−C bond oxidative addition to Pd(0) centers in the studied system. The first example of NHC-
mediated Pd leaching from metal nanoparticles to solution was observed and formation of Pd/NHC complex in solution was
detected by ESI-MS.
as a nanosized catalyst. Formation of metal NPs has been
confirmed for a variety of M/NHC systems.6 From the
mechanistic point of view it is uncertain whether this transition
is unidirectional or it can be reversed to switch the state back
from nanostructured to molecular. If R−NHC coupling is
irreversible under catalytic conditions, then the nanosized
system (right part of Scheme 1) should be considered as the
final stage of catalyst evolution in this case. Reversibility of R−
NHC coupling would allow one to adjust the mode of catalysis
(molecular vs nano) depending on the requirements of a
specific task. This question is of key importance because
completely different principles of catalyst design should be
utilized for nanoscale and molecular systems. Indeed, doing
rational catalyst design is hardly possible (or is totally
impossible) without knowledge about catalytically active
centers and without understanding possible pathways of
dynamic interconversions of catalytic species.
INTRODUCTION
■
N-heterocyclic carbenes (NHCs) are efficient ligands in
homogeneous transition-metal catalysis. They gained world-
wide recognition due to the impressive variety of compounds
of this type and the wide range of their applications.1 As
ligands, NHCs are indispensable for cross-coupling, C−H
functionalization, Mizoroki−Heck reaction, metathesis and
carbon−heteroatom bond formation,1,2 synthesis of bio-
logically active molecules, and advanced materials develop-
ment.3
The high stability of metal/NHC (M/NHC) complexes is
conventionally explained by electron-donating properties of
NHC rings enhanced by steric hindrance conferred by
substituents on nitrogen atoms.1,2,4 However, recent studies
indicate that the remarkable catalytic activity of M/NHC
complexes not only due is to their stability but also is largely
dependent on the lability of the M−NHC bond under certain
conditions.5,6
In particular, it has been shown that oxidative addition of
organic halide to a metal complex proceeds rather easily and
acts as a beginning stage for the subsequent R−NHC
coupling.7 The resulting NHC-free molecular palladium
complex is prone to agglomeration causing transition of the
molecular catalytic system into nanostructured state (arrow A
in Scheme 1). This transition is manifested by formation of
palladium nanoclusters and nanoparticles (NPs) which may act
Many reports describe the molecular-to-nanoscale con-
version where R−NHC coupling generates Pd centers
susceptible to agglomeration (arrow A in Scheme 1).6a,b,7,8
Azolium salts produced by R−NHC coupling act as efficient
stabilizers of NPs/colloidal systems.1e,6a,9 In a series of
excellent recent studies, Bullock and co-workers have shown
Received: June 3, 2019
© XXXX American Chemical Society
A
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Scheme 1. Direct Molecular-to-Nanoparticle and Reverse Nanoparticle-to-Molecular Transitions of Active Species in M/NHC
Catalysis
that Rh NPs stabilized by cyclic alkyl amino carbene (CAAC)
ligands can behave as active species in arene hydrogenation.
This hypothesis has been confirmed by a number of
experimental methods, including kinetic studies, mechanistic
studies involving a filtration test, fractional poisoning experi-
ments, XAFS measurements, STEM characterization, and
infrared spectroscopy. It was proposed that the presence of
CAAC at the surface of catalytically active particles ensures
their high reactivity.9
Scheme 2. Reaction Scheme Used for Studying C−C Bond
Breakage in the R−NHC/Pd System
In contrast, no direct nanoscale-to-molecular transitions
involving R−NHC+X− compounds (arrow B in Scheme 1) has
been described previously. The reverse process can be
considered in terms of C−C bond activation and leaching.
The effect of leaching is substantive when using phosphine
complexes of Pd,8 especially in the presence of organic halides,
in order to facilitate formation of R−Pd−X species and
removal of Pd atoms from the surface of nanoparticles.10a
Mechanistic changes, metal contamination, and sustainability
issues are important factors to be considered in the case of
leaching.10b,c
Thus, the possibility of reversible R−NHC coupling can be
associated with a particular type of leaching accompanied by
the metal-mediated C−C bond breakage (arrow B in Scheme
1). This hypothetical process, with proper refinements, may be
extremely useful in designing M/NHC catalytic systems, but
from general considerations (high activation energies of C−C
bond oxidative addition) this process cannot be regarded as
very likely. In this experimental study, C−C bond breakage in
the R−NHC coupling products is closely examined for the first
time and unique feature of this transformation is revealed.
NHC+X− reaction product (a different azolium salt) would be
impossible. Its formation, therefore, suggests the possibility of
R−NHC bond breakage by Pd clusters (Scheme 2). Being the
key step toward the nano-to-molecular transformation of the
studied system under catalytic conditions, this reaction models
the process reverse to R−NHC coupling (Scheme 1B).
Observation of Palladium Nanoparticles. Formation of
palladium nanoparticles (Pd NPs) from palladium acetate in
DMF has been described previously.11 We performed this
process in order to characterize Pd NPs in DMF before using
them in the experiment (Figure 1). The samples were prepared
by heating of Pd(OAc)2 solution in DMF for 1 h at 140°C.
Concerning the temperature range, formation of Pd nano-
particles can be also observed at lower temperatures (75−100
°C; Supporting Information, Figure S24). According to the
transmission electron microscopy (TEM) images, Pd NPs are
formed efficiently under these conditions. Higher magnifica-
tions images (Figure 1, parts c and d) allow to distinguish
overlaps of the atomic layers in palladium nanoparticles.
Computational Proof of Thermodynamic Driving
Force of the Process. Quantum chemical modeling of the
energy profile involving R−NHC coupling and the reverse
process of R−NHC oxidative addition has been performed for
the model system (Figure 2). Remarkably, the C−C bond in
the starting complex I can be broken via overcoming of
RESULTS AND DISCUSSION
■
Experimental examination of C−C bond breakage in the R−
NHC coupling product was carried out in accordance with
Scheme 2. In DMF, palladium acetate undergoes chemical
reduction leading to formation of metal clusters and nano-
particles. Upon the addition of azolium salt R−NHC+X− to the
system, the metal particles are stabilized against agglomeration
and precipitation. We propose that NHC-capped Pd NPs
become capable of transformation into molecular palladium
complex R−Pd−NHC after C−C bond breakage. This
complex can be trapped by reaction with organic halides R′-
X leading to formation of a different product. It is worth noting
that the resulting azolium salt R′−NHC+X− can also act as a
stabilizer for Pd NPs. Indeed, without breakage of C-C bond in
the starting azolium salt R−NHC+X− formation of the R′−
B
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energy difference of ΔEI→III = −9.1 to −16.7 kcal/mol
(ΔGI→III = −10.6 to −15.4 kcal/mol). A further gain in energy
occurs upon transition from complex III to complex IV, as a
result of substitution of methyl group with phenyl group. It
should be noted that the energy gain upon replacement of Me
with Ph is almost the same for different NHC ligands: ΔE
(kcal/mol) = −5.2 (BIMe), −5.5 (IPr), −5.6 (IMe), and −6.3
(IMes).
Subsequent Ph−NHC coupling leads to product VI via the
transition state V-TS, with ΔE‡
= 18.0−23.1 kcal/mol
IV→V‑TS
(ΔG‡
= 17.9−22.1 kcal/mol) for the studied NHC
IV→V‑TS
ligands. However, it can be noted that the activation energy of
the R−NHC coupling (IV → V-TS for the Ph−NHC coupling
and III → II-TS for the Me−NHC coupling) increases in the
following order IMes > IPr > IMe ∼ BIMe. This pattern may
be related to the strength of the metal−ligand bond and the
influence of steric hindrance.
Figure 1. TEM images for Pd NPs forming from Pd(OAc)2 in DMF
at 140 °C. Scale bars: 100 nm (a), 50 μm (b); 20 μm (c and d).
The product VI is more stable than the starting complex I
(ΔE = −9.3 to −15.0 kcal/mol; ΔG = −7.9 to −13.1 kcal/mol
for the studied complexes). Thus, the replacement of alkyl
substituent with phenyl substituent in the studied R−NHC/Pd
system is thermodynamically favorable for all NHC ligands
under consideration. It should be noted that activation
energies of R−NHC coupling for different R are very similar,
relatively small energy barrier of ΔE‡
= 9.9 kcal/mol
I→II‑TS
(ΔG‡
= 8.5 kcal/mol; NHC = BIMe).
I→II‑TS
The lowest activation energy of the Me-NHC oxidative
addition is observed for NHC = IMe, whereas the highest
activation energy (ΔE‡ = 11.4; ΔG‡ = 11.2 kcal/mol) is
inherent in the process with the IPr as the NHC ligand.
However, the differences in potential barriers of the methyl
group transfer are small (ΔΔE‡ = 3.5 kcal/mol), since the
methyl group is characterized by a small spatial volume and,
apparently, relatively weak interacts with NHC ligands of even
a large volume. The reaction for complexes with all NHC
ligands is thermodynamically favored, for example with the
e.g. ΔE‡
ΔE‡
= 19.0−24.7 kcal/mol for R = Me and
III→II‑TS
= 18.0−23.1 kcal/mol for R′ = Ph (ΔG‡ = 19.1−
IV→V‑TS
24.2 and 17.9−22.1 kcal/mol, respectively for the studied
NHC systems).
Thus, the theoretical calculations reveal thermodynamic
driving force for the alkyl/aryl substitution in the studied R−
NHC system. The observed stabilization may be explained by a
more efficient Pd−Ar interaction as compared with a Pd−Alk
Figure 2. Calculated energy profile with total energies (ΔE, kcal/mol) and Gibbs energies (ΔG, kcal/mol, in parentheses) for each stage at the
PBE1PBE/6-311G(d)&def2TZVP D3BJ level (Alk = Me; NHC = BIMe, IMe, IMes, IPr). Scrambling stage is shown formally to compare relative
energies (mechanistic pathways are discussed in detail later).
C
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interaction (IV vs III), as well as by contribution of a larger
bond energy of Ar−NHC as compared to Alk-NHC (VI vs I).
It should be noted that in this section we only model the
overall thermodynamic driving force. More detailed computa-
tional consideration of different reaction channels will be given
in subsequent sections, and its relation to experimental findings
will be thoroughly addressed.
Analytical Assessment of the R−NHC Transformation
on Pd by Mass Spectrometry and Nuclear Magnetic
Resonance. For experimental study, the corresponding
system was chosen as a suitable model for studying the
reaction of R−NHC with Pd by electrospray ionization high-
resolution mass spectrometry (ESI-MS) and nuclear magnetic
resonance spectroscopy (NMR) (Scheme 3). The interaction
Scheme 3. Model Reaction Used for Studying Interactions
of R−NHC species with Pd by Mass Spectrometry and
NMR Spectroscopy and Calculated Bond Energies
Figure 3. Normalized mass spectra of the reaction mixtures with
different Pd sources after 24 h (0.1 mmol 1a, 0.2 mmol PhI, 1 equiv of
[Pd], DMF, 140 °C).
in the upfield region at δ 3.89 ppm (Figure 4). This signal
corresponds to the N-Me groups of Ph-substituted azolium salt
of Me-substituted starting material 1a with iodobenzene was
studied in the presence of equimolar amount of palladium from
different sources. As a result of the studied reaction, Ph-
substituted product 2a was formed (Scheme 3). According to
the theoretical calculations discussed above, the exchange
process leading to substitution of methyl group with phenyl
group should be energetically favored (Figure 2). Regarding
the final products, the calculations have shown that the NHC−
Ph bond is by 13.3 kcal/mol stronger as compared to the
NHC-Me bond (Scheme 3). Formation of the target product,
1,3-dimethyl-2-phenyl-1H-benzimidazol-3-ium iodide (2a),
was monitored by ESI-MS (Figure 3). Signal intensities for
molecular cations of azolium salts 1a and 2a (m/z 161 and 223
respectively) were measured at the moment the reaction was
launched and after 24 h.
At the beginning of the reaction, no traces of the product
were detected for all of the experiments, which excluded the
possibility of in-source formation of 2a. The maximal intensity
of signal for molecular ion 2a was achieved in the reaction with
Pd(OAc)2. It should be noted that the use of triethylamine as a
base suppressed formation of the m/z 223 molecular ion in all
cases. The possibility of this reaction to take place with other
metals was also tested under similar conditions. The reaction
proceeded well in the presence of copper salts, with lower
reactivity in the presence of nickel salts and did not proceed in
the presence of cobalt salts (Supporting Information, Table
S4).
Figure 4. 1H NMR spectra of the reaction mixtures with different Pd
sources after 24 h (0.1 mmol 1a, 0.2 mmol PhI, 1 equiv of [Pd],
DMF, 140 °C).
2a. The control experiments confirmed participation of Pd in
the reaction (no corresponding transformation was observed in
the absence of Pd).
1
Kinetics of the R−NHC exchange was studied by H NMR
monitoring (Figure 5) using Pd(OAc)2 as a source of
palladium. Within 1 h after beginning of the reaction, at 25%
conversion of the starting 1a, the yield of 2a was about 20%.
After 24 h of the reaction, the product yield reached a plateau
of 31%, whereas conversion of 1a at this point was close to
44%, which suggests the presence of side reactions that also
consume the azolium salt. Accordingly, toluene, iodomethane,
and biphenyl (the product of iodobenzene homocoupling)
were detected in the reaction mixture by GC-MS. The product
2a was isolated from the mixture in 20% yield by flash
chromatography. Kinetic curves, with built in C = f(t), ln C =
f(t), 1/C = f(t), and 1/C2 = f(t) coordinates on the basis of
experimental data, are nonlinear.
Quantitative identification of the reaction product formation
was carried out by NMR for the three most efficient systems
selected on the basis of the results of mass spectrometry:
Pd(OAc)2, Pd(OAc)2/PPh3, and Pd(acac)2. In all three cases,
the 1H NMR spectra recorded after 24 h contained new signal
D
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yl)-1H-imidazol-3-ium iodide (1c) (Table 1, entries 10 and
11).
Possible Mechanism of R,R′−NHC Exchange. For a
better insight into the mechanism, a potential energy surface
was calculated for the studied system. The mechanism of the
process, resulting in the exchange of organic substituents on
the carbene carbon, was analyzed at PBE1PBE/6-311G(d)
&def2TZVP D3BJ level. As long as palladium acetate is
invariably reduced under the action of DMF, Pd(0) species 4
were chosen as a starting point (Figure 6). Complex 4
coordinates the initial azolium salt 1a and forms a prereaction
complex 5. This stage is exothermic (ΔE4→5 = −15.4 kcal/
mol) even though the iodide ion remains in the outer sphere of
the complex and is not coordinated directly to the palladium
atom (Figure 6). The next stage, oxidative addition of the
1
Figure 5. H NMR monitoring of R,R′−NHC coupling (1a, PhI, 1
equiv of Pd(OAc)2, DMF, 140 °C).
azolium salt via transition state 6-TS, is exothermic (ΔE5→7
=
=
−24.6 kcal/mol) and has a low activation energy (ΔE‡
Thus, the computationally predicted possibility of sub-
stitution of the methyl group (−CH3) at the carbon in the
second position of benzimidazolium ring by phenyl group
(−Ph) has been confirmed experimentally. It is evident
therefore that the C−C bond in the R−NHC molecular
framework can be broken in the presence of Pd nanoparticles.
Reversible R,R′−NHC Coupling under Various Con-
ditions. Reversibility of R−NHC coupling was evaluated for a
range of conditions (Table 1) and the following trends can be
5→6‑TS
16.0 kcal/mol). In product 7, coordination sphere of palladium
atom contains the methyl group, the NHC-ligand and two
DMF molecules, whereas the iodide-ion is located in the outer
sphere and coordinated by a single H-bond to a formamide
hydrogen of DMF. Subsequent rearrangement of complex 7,
associated with the elimination of one DMF molecule and the
transfer of iodide-ion to coordination sphere of palladium, is
accompanied by a small increase in energy ΔE7→8 = 4.4 kcal/
mol. The next step, oxidative addition of aryl halide (PhI) via
transition state 9-TS, yields octahedral Pd(IV) complex 10.
Activation energy for this step, ΔE‡8→9‑TS= 16.5 kcal/mol, is
similar to activation energy for the first oxidative addition of
azolium salt. In screening for the most stable isomer of
complex 10, the isomer with phenyl group and NHC-ligand in
trans was found to be relatively unstable; it undergoes
rearrangement into a significantly more stable complex 10b
with phenyl group and NHC-ligand in the cis-position (Figures
6, S35). Subsequent transformation may involve either of two
channels. The first of them is reductive elimination of MeI
molecule via transition state 11-TS with activation energy
Table 1. Proceeding of R−NHC Coupling Observed under
Various Conditions
variable parameter
1H NMR
a
b
ESI-MS
2 signal
yield of 2
b
no.
(%)
1
2
3
4
5
6
7
8
9
ArX
(p-OMe)C6H4I
(p-NO2)C6H4I
PhBr
PhCl
1:1
high
small
high
trace
high
high
trace
trace
44
12
16
0
43
31
<1
1
1a to PhI ratio
ΔE‡
= 18.6 kcal/mol. Transition state 11-TS
1:2
10b→11‑TS
promotes the transfer of methyl group from palladium onto
iodine, whereas DMF molecule essentially loses its bonding
with the metal atom. Complex 12, the formation of which is
exothermic (ΔE10b→12 = −12.4 kcal/mol), has square planar
geometry with MeI molecule coordinated to the metal.
The alternative reaction channel, Ph−NHC coupling,
involves transition state 13-TS with activation energy
Pd(OAc)2 loading
5 mol %
10 mol %
50 mol %
1b
average
average
average
20
56
34
10
11
azolium salt
1c
a
ESI-MS, I = I[NHC‑Ph]+/I[NHC‑Me]+, where 0.1 < I < 0.3, small; 0.3 < I
b
< 0.5, average; and I > 1, high. After 24 h of heating.
ΔE‡
= 25.7 kcal/mol leading to product 14 where
10b→13‑TS
the Ph−NHC fragment is detached from the metal atom.
Formation of complex 14 is strongly exothermic (ΔE10b→14
−31.3 kcal/mol). Whereas subsequent elimination of the MeI
molecule is kinetically unfavorable (ΔE‡
= 39.3 kcal/
=
mentioned. The use of aryl halides with electron-donating
substituents favors the target product formation (Table 1,
entry 1), whereas the use of aryl halides with electron-
withdrawing substituents is disadvantageous for the process
(Table 1, entry 2). The observed yields correlate with
Hammett parameters. The use of aryl bromides results in
reduced yields of 2a (Table 1, entry 3), whereas nonactivated
aryl chlorides are totally nonreactive in the R−NHC exchange
(Table 1, entry 4). The proportion of starting reagents has no
significant influence on the reaction (Table 1, entries 5 and 6).
Reduced loads of palladium result in substantial decrease in the
yields of the final product (Table 1, entries 7−9). The scope of
reversible R−NHC coupling also includes imidazolium salts
with bulky substituents on nitrogen, e.g., 1,3-dimesityl-1H-
imidazol-3-ium iodide (1b) and 1,3-bis(2,6-diisopropylphen-
14→15‑TS
mol). Despite the fact that in products 12 and 14 the
palladium atom is in a similar square planar environment of
ligands (organic substituent, two iodine atoms and a neutral
ligand molecule: NHC in 12 or DMF in 14) the energy of
complex 14 is by 18.9 kcal/mol lower than the energy of
complex 12. Thus, assuming the formation of Pd(IV) complex
as a key intermediate, it can be suggested that both processes,
MeI elimination and Ph−NHC coupling, are in principle
accessible. Formation of MeI is possible at lower temperatures
but involves formation of less favorable intermediate, whereas
the direct Ph−NHC coupling requires higher temperatures,
but results in the most stable reaction product in the studied
system (14).
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Figure 6. Calculated potential energy profile of the Me-NHC/Ph−NHC exchange reaction at PBE1PBE/6-311G(d)&def2TZVP D3BJ level (see
Supporting Information for a description of the model system).
It should be noted that a number of different pathways were
analyzed in the present study by theoretical calculations
(Supporting Information, section 5). The route of oxidative
addition via dipalladium complex was found less probable
(Supporting Information, Scheme S1 and discussion therein).
The transfer of methyl group between palladium atoms in
binuclear complex is characterized by a high activation energy
of 41.7 kcal/mol (Figures S28−S30). Formation of Pd(IV)
complex through addition of Me-NHC+I− salt to Pd(II)
complex is also kinetically unlikely. The Me-NHC oxidative
addition step with Pd(IV) complex formation has rather high
activation energy of 63.3 kcal/mol (Figures S31−S33). In
addition, the R,R′−NHC coupling mechanism involving MeI
elimination was considered; however, it is also characterized by
a high potential barrier of 46.2 kcal/mol (Figures S36−S38).
Thus, the most probable mechanism for R,R′-exchange
combines oxidative addition of Me-NHC+I− to Pd(0) complex
with subsequent oxidative addition of PhI leading to formation
of Pd(IV) complex (Figure 6).
Of course, the theoretical study represents only a model of
the metal center and involves certain simplifications. The real
experimental system is much more complex (i.e., in the
structure of metal center, colloidal organization, etc.).
Nevertheless, in spite of model character, the calculations
performed are in good agreement with the experimental
findings. Computational modeling provides rational pathway
for the R,R′−NHC exchange process. It is important to
emphasize that the computed energy surface is consistent with
the formation of MeI observed experimentally.
R,R′−NHC Coupling and Leaching Involving Pd NPs.
Pd NPs were first isolated in neat form (Figure S25,
Supporting Information) and then used in the reaction.
Under the same experimental conditions (Scheme 3), R,R′−
NHC coupling was carried out using presynthesized palladium
F
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nanoparticles and 1a. After 24 h the product 2a was detected
in the reaction mixture by ESI-MS (m/z 223) and H NMR
reaction of 2-substituted azolium salts with aryl halides of
various nature in the presence of palladium leads to substituent
exchange on the carbene carbon atom. The reaction is tolerant
to modified substrates and conditions.
1
(signal at δ 3.89 ppm). The reaction was also performed with
azolium salts 1b and 1c, where the formation of corresponding
products 2b and 2c was detected by ESI-MS. Although the
activity of isolated nanoparticles may be lower compared to the
nanoparticles formed in situ (partial deactivation and
agglomeration may occur during isolation), the obtained
results clearly indicated the possibility of the studied reaction
involving Pd NPs.
Detailed ESI-MS study of the reaction mixture revealed Pd-
containing complex in solution upon the reaction of Pd NPs
with 1a. Plausible structure includes two NHC moieties and
one Pd atom. The number of Pd atoms can be clearly
established according to simulation of the isotopic distribution
(Figure 7) and the presence of NHC moieties was confirmed
Computational study indicates that the trapping process
preferentially proceeds via Pd(IV) complex formed stepwise by
double oxidative addition of the starting azolium salt and aryl
halide. The organic substituent exchange is possible when the
groups were present simultaneously in coordination sphere of
the metal. Thus, Pd(IV) complex encompassing both methyl
and phenyl substituents is an important intermediate of the
process. Decomposition of the Pd(IV) complex may proceed
in two ways; both are accompanied by elimination of a MeI
molecule detected experimentally. Decomposition of the
Pd(IV) complex may begin with the Ph−NHC coupling
followed by MeI elimination. However, this channel leads to a
very stable intermediate which makes the subsequent
elimination of organic halide kinetically unfavorable. The
alternative decomposition channel of the Pd(IV) complex with
MeI elimination followed by Ph−NHC coupling is more likely
as it is not accompanied by formation of a kinetically blocked
intermediate. In both cases, regardless of the reaction channel,
the overall pathway is shifted toward Ph−NHC coupling
product which has lower energy as compared to the Pd(II)
alkyl complex.
Using presynthesized Pd NPs reversibility of R,R′−NHC
coupling was experimentally demonstrated. Leaching of NHC-
containing Pd complex from the surface of Pd nanoparticle was
observed upon reaction with azlolium salts, which provides an
evidence for the nano-to-molecular transformation in the
studied system.
NHCs are well-known ligands for transition metal catalysis.
Metal systems with NHC ligands can switch their state from
molecular (represented by metal complexes) to nanoscale
(represented by metal clusters and nanoparticles). Such
transitions have been commonly associated with decomposi-
tion of M/NHC catalysts via R−NHC coupling. However, the
possibility of reverse transition (by C−C bond activation in
R−NHC+X− azolium salts) has not been studied for the M/
NHC systems. This article provides the first demonstration of
possibility of such reverse transition which may well provide a
key to construction of dynamic cocktail-type Pd/NHC
systems.
Indeed, understanding mechanistic pathways associated with
R−NHC coupling is required for rational catalyst design, as
discussed above (see Introduction). Typically, it is assumed
that C−C bond oxidative addition to metal centers is an
endothermic process accompanied by overcoming of high
activation barriers. Here, we demonstrate that oxidative
addition of C−C bond in the R−NHC+X− species has
surprisingly small activation barriers and the process is
noticeably exothermic (I → II-TS → III and VI → V-TS →
IV, Scheme 2). This unique feature provides the necessary
basement for the studied transformation of Pd-active species.
Moreover, the findings go far beyond the studied system and
open possibilities for catalytic C−C bond activations (usually
rather difficult to achieve) in the revealed molecular frame-
work.
Figure 7. ESI-(+)MS spectrum of the detected Pd-containing ion,
formed as a result of interaction of salt 1a with Pd NPs after 10 min
(3 μmol 1a, Pd NPs prepared from 3 μmol of Pd(OAc)2, DMF, 140
°C). Experimental spectrum is shown in black, and the theoretical
simulation is shown in red.12
by MS2 experiment (Figure S23, Supporting Information). A
possible structure of the ion was proposed according to
quantum chemical modeling (Figure S39). Appearance of Pd-
NHC framework in the mononuclear metal complex provides
the evidence of C−C bond breakage in 1a salt under the
influence of Pd NPs. These findings further support the
hypothesis shown in Scheme 1B.
To the best of our knowledge, this is the first example of
metal leaching from Pd NPs initiated by NHC ligand core.
Transfer of metal atoms from Pd nanoparticles to solution and
formation of Pd/NHC complex can be proposed on the bases
of the experiment.
CONCLUSIONS
■
The present study reports experimental evidence of Pd
insertion into C−C bond in a chemical system with R−
NHC+ molecular framework. The results indicate plausibility
of breaking of the C−C bond in R−NHC+X− azolium salt
under studied conditions, which is a key requirement for
reversibility of the R−NHC coupling process. A model
EXPERIMENTAL SECTION
■
1
General Considerations. H and 13C{1H} NMR spectra were
recorded on a Bruker Fourier 300HD instrument at 300 MHz for 1H
1
and at 75 MHz for 13C{1H}. H and 13C{1H} chemical shifts are
G
DOI: 10.1021/acs.inorgchem.9b01630
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
given in ppm relative to the residual peak of the solvent for the proton
spectra (δ 2.75 ppm, δ 2.92 ppm, δ 8.03 ppm for DMF-d7 and δ 2.50
ppm for DMSO-d6) and for the carbon spectra (δ 163.2 ppm, δ 34.9
ppm, δ 29.8 ppm for DMF-d7 and δ 39.52 ppm for DMSO-d6). GC-
MS measurements were carried out on Agilent 7890 gas chromato-
graph with Agilent 5970 mass-selective detector. Measurements were
performed in scan range from m/z 80 to m/z 300 mode with
ionization energy set at 70 eV, source temperature set at 230 °C and
transfer capillary temperature set at 300 °C. Separation was carried
out on Agilent HP-5MS fused silica capillary column (30 m length;
250 μm I.D.; 0.25 μm film thickness, (5% phenyl)-methylpolysilox-
ane) using He (5.0 grade, NII KM) as carrier gas at flow of 0.5 mL/
min. The temperature program was started at 40 °C and held for 3
min, then increased at a rate of 5 °C/min to 60 °C, and then
increased at a rate of 25 °C/min to 160 °C and held for 1 min.
Injection port temperature was set at 300 °C and was operated in split
mode at 15:1 ratio with sample injection volume of 10 μL. The
spectra were processed using the Bruker Data Analysis 4.0 software
package with NIST 14 spectra database.
High-resolution mass spectra were registered on Bruker maXis Q-
TOF instrument equipped with electrospray ionization (ESI) ion
source. The measurements were performed in positive mode with HV
capillary at 4.5 kV, spray shield offset at −0.5 kV, and scan range of
m/z 50−1200. External calibration was performed using low-
concentration tuning mix solution (Agilent Technologies). Direct
syringe injection was used for all analyzed solutions in MeCN at flow
rate of 5 μL/min. Nitrogen was used as both nebulizer gas at 1 bar
and dry gas at 4.0 L/min, 200 °C. Nitrogen (6.0 grade, NII KM) was
used as collision gas for MS2 experiments. MS2 spectrum was acquired
at 0.08 Hz and precursor was isolated with a width of 7 Da. Collision
energies were set to 20 eV, data was acquired for 1 min in the range
100−1500 m/z. All recorded spectra were processed using Bruker
Data Analysis 4.0 software package.
argon atmosphere. The reaction mixture was then cooled down to
room temperature, solvent was removed, and the desired product
(2a) was isolated by column chromatography, using dichloro-
methane/methanol (v/v, 100/1−20/1) as eluent. Yield: 0.263 g
(75%). 1H NMR (300 MHz, DMSO-d6), δ, ppm: 8.13−8.16 (m, 2H),
7.91−7.93 (m, 2H), 7.75−7.85 (m, 5H), 3.90 (s, 6H). 13C{1H} NMR
(75 MHz, DMSO-d6), δ, ppm: 150.3, 132.9, 131.7, 130.8, 129.4,
126.6, 121.0, 113.4, 32.8. ESI-MS: [M − I]+ calcd for [C15H15N2]+,
m/z 223.1230; found, m/z 223.1227 (Δ = 1.3 ppm). Anal. Calcd for
C15H15IN2: C, 51.45; H, 4.32; N, 8.00. Found: C, 51.38; H, 4.27; N,
7.94.
General Procedure for Analytical Assessment of the
Oxidative Addition of R−NHC to Metal by Mass Spectrometry
and NMR and Quantitative Isolation of the R−NHC Coupling
Product. A screw-top tube equipped with magnetic stir bar was
charged with 2-methylation azolium salt (0.1 mmol) in 500 μL of
DMF; the inside of the tube was thoroughly flushed with argon, then
ArX (0.2 mmol) and metal source (0.1 mmol) were added. The
reaction mixture was thoroughly flushed with argon, sealed, and
heated at 140 °C under continuous magnetic stirring. After 24 h, the
reaction was stopped and the mixture was analyzed by mass-
1
spectrometry and H NMR. Product 2a was quantitatively isolated
from the reaction mixture by flash chromatography after evaporation
of the solvent. The mixture was passed through a column (h = 3 cm, d
= 2.5 cm) packed with alumina (Brockmann II, neutr.), with gradient
elution using DCM−MeOH (100/1 to 20/1, v/v). The pure product
was obtained as colorless crystals (yield 20%). The structure was
1
confirmed by H NMR (300 MHz, DMSO-d6), δ, ppm: 8.12−8.15
(m, 2H), 7.91−7.93 (m, 2H), 7.75−7.85 (m, 5H), 3.89 (s, 6H).
13C{1H} NMR (75 MHz, DMSO-d6), δ, ppm: 150.3, 132.9, 131.7,
130.8, 129.4, 126.6, 121.0, 113.4, 32.8. ESI-MS: [M − I]+ calcd for
[C15H15N2]+, m/z 223.1230; found, m/z 223.1230 (Δ = 0.2 ppm).
Anal. Calcd for C15H15IN2: C, 51.45; H, 4.32; N, 8.00. Found: C,
51.38; H, 4.27; N, 7.94.
All synthetic manipulations were conducted under argon
atmosphere using standard Schlenk techniques. Dry solvents were
used for all operations. Column chromatography was conducted on
Al2O3 (Brockmann II, neutr.). Glassware was dried at 120 °C in an
oven for at least 3 h.
Synthesis of Compounds 1b and 1c. In a 25 mL round-bottom
flask with magnetic stir bar, 1,3-bis(2,6-diisopropylphenyl)-imidazo-
lium chloride17 (0.001 mol, 0.42 g) or 1,3-dimesityl-1H-imidazol-3-
ium chloride17 (0.001 mol, 0.34 g) in THF solution (5 mL) was
cooled to −78 °C. n-BuLi (0.483 mL, 1.14 mmol, 1.6 M solution in
hexanes) was added dropwise to get a white suspension. The reaction
mixture was stirred for 10 min. The resulting clear solution was
warmed to room temperature and stirred for another 5 min, and then
MeI (0.0011 mmol, 0.09 mL) was added at −78 °C. A white
precipitate was isolated by filtration and then washed with water and
hexane and dried. The desired products (1b and 1c) were isolated as
colorless solids.
1,2,3-Trimethyl-1H-benzimidazol-3-ium iodide,13 1,3-dimethyl-2-
phenyl-1H-benzimidazol-3-ium iodide,14 1,3-dimesityl-2-methyl-1H-
imidazol-3-ium iodide,15 1,3-bis(2,6-diisopropylphenyl)-2-methyl-1H-
imidazol-3-ium,15 and 1,3-dimethyl-1H-benzimidazol-3-ium iodide16
were synthesized as described in the literature. All other chemicals
were purchased from commercial sources.
1,2,3-Trimethyl-1H-benzimidazol-3-ium iodide (1a). Phenyl-
enediamine (0.019 mol, 2.0 g) and acetic acid (0.062 mol, 3.53 mL)
were placed in a 25 mL round-bottom flask with magnetic stir bar.
Reaction mixture was refluxed for 2 h. Then, ice and KOH were
added up to pH 10, and a light-purple solid was filtered out and was
purified by recrystallization from water. Isolated as a light-yellow
needle-shaped crystals, 2-methylbenzimidazole (1.72 g, yield 70%)
was used in the next step. 2-Methylbenzimidazole (0.005 mol, 0.66 g),
12 mL of benzene, and MeI (0.015 mol, 0.93 mL) were added to
solution of Na (0.005 mol, 0.12 g) in 2 mL of ethanol under constant
stirring and refluxed for 18 h. The reaction mixture was then cooled to
the room temperature, and the solvent was removed. The crude
product was purified by recrystallization from 95% ethanol. The
desired product (1a) was isolated as colorless needle-shaped crystals
(1.15 g, 80% yield). 1H NMR (300 MHz, DMSO-d6), δ, ppm: 7.97−
8.00 (m, 2H), 7.62−7.65 (m, 2H), 4.00 (s, 6H), 2.88 (s, 3H).
13C{1H} NMR (75 MHz, DMSO-d6) δ ppm: 152.2, 131.3, 125.8,
112.7, 31.7, 10.6. ESI-MS: [M − I]+ calcd for [C10H13N2]+, m/z
161.1073; found, m/z 161.1076 (Δ = 1.9 ppm). Anal. Calcd for
C10H13IN2: C, 41.69; H, 4.55; N, 9.72. Found: C, 41.66; H, 4.56; N,
9.65.
1,3-Dimesityl-2-methyl-1H-imidazol-3-ium iodide (1b). Yield:
0.280 g (63%). 1H NMR (300 MHz, DMF-d7), δ, ppm: 8.31 (s,
2H), 7.29 (s, 4H), 2.42 (s, 6H), 2.39 (s, 3H), 2.17 (s, 12H). 13C{1H}
NMR (75 MHz, DMF-d7), δ, ppm: 149.0, 146.3, 141.6, 135.1, 130.1,
124.4, 20.7, 16.9, 9.5. ESI-MS: [M − I]+ calcd for [C22H27N2]+, m/z
319.2169; found, m/z 319.2166 (Δ = 0.9 ppm).
1,3-Bis(2,6-diisopropylphenyl)-2-methyl-1H-imidazol-3-ium (1c).
1
Yield: 0.269 g (51%). H NMR (300 MHz, DMF-d7), δ, ppm: 8.62
(d, J = 3.7 Hz, 2H), 7.83−7.76 (m, 2H), 7.65 (dd, J = 7.8, 3.7 Hz,
4H), 2.46−2.36 (m, 4H), 2.34 (s, 3H), 1.37−1.25 (m, 24H). 13C{1H}
NMR (75 MHz, DMSO-d6), δ, ppm: 150.1, 147.0, 145.5, 132.6,
129.9, 125.6, 24.9, 24.1, 22.8, 22.3, 10.6. ESI-MS: [M − I]+ calcd for
[C28H39N2]+, m/z 403.3108; found, m/z 403.3111 (Δ = 0.7 ppm).
Anal. Calcd for C28H39IN2: C, 63.39; H, 7.41; N, 5.28. Found: C,
63.37; H, 7.49; N, 5.36.
Computational Details. Reagents, products, intermediates, and
transition states 4−16 were fully optimized by PBE1PBE18 with basis
sets 6-311G(d)19 for H, C, N, and O and def2TZVP20 for Pd and I.
The dispersion was accounted for by using Grimme D3BJ empirical
corrections.21
1,3-Dimethyl-2-phenyl-1H-benzimidazol-3-ium iodide (2a).
1,3-Dimethyl-1H-benzimidazolium iodide16 (0.001 mol, 274.0 mg),
phenyl iodide (0.002 mol, 408.0 mg), Cu2O (29.0 mg, 20 mol %), and
NaOAc (0.001 mol, 82.0 mg) in DMF solution (5 mL) were placed in
a Schlenk tube and kept at 120 °C for 24 h under constant stirring in
Several benchmark studies have shown that the PBE1PBE (aka
PBE0) method is reliable and accurate for modeling reactions
involving late transition metals, including palladium. In particular, it
was shown that for model reactions of C−C, C−Hal, and C−H
H
DOI: 10.1021/acs.inorgchem.9b01630
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
oxidative addition to the Pd center, the root-mean-square (RMSD)
deviation for this method is only 0.8 kcal/mol when compared with
the CCSD(T) method.22 For a larger range of oxidative addition
reactions (C−H, C−C, O−H, B−H, N−H, C−Cl) to the Pd center,
it was shown that the most accurate method is the PBE1PBE D3, for
which the mean absolute deviation (MAD) is 1.1 kcal/mol.23
Vibrational spectra were calculated for all optimized molecules to
determine the types of stationary points on the potential energy
surface. All computations were performed in the Gaussian 16 software
package.24
Properties of N-Heterocyclic Carbenes. Chem. Soc. Rev. 2013, 42,
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.inorg-
chem.9b01630.
S.; Glorius, F. Surveying Sterically Demanding N-Heterocyclic
Carbene Ligands with Restricted Flexibility for Palladium-Catalyzed
Cross-Coupling Reactions. Acc. Chem. Res. 2008, 41, 1523−1533.
(f) Samojłowicz, C.; Bieniek, M.; Grela, K. Ruthenium-Based Olefin
Metathesis Catalysts Bearing N-Heterocyclic Carbene Ligands. Chem.
Rev. 2009, 109, 3708−3742. (g) Lin, J. C. Y.; Huang, R. T. W.; Lee,
C. S.; Bhattacharyya, A.; Hwang, W. S.; Lin, I. J. B. Coinage Metal−N-
Heterocyclic Carbene Complexes. Chem. Rev. 2009, 109, 3561−3598.
(h) Vougioukalakis, G. C.; Grubbs, R. H. Ruthenium-Based
Heterocyclic Carbene-Coordinated Olefin Metathesis Catalysts.
■
S
Additional experimental data, NMR spectra, ESI-MS
data, TEM images, and a detailed description of
theoretical calculations (PDF)
̈
Chem. Rev. 2010, 110, 1746−1787. (i) Droge, T.; Glorius, F. The
AUTHOR INFORMATION
Corresponding Author
*E-mail (V.P.A.): val@ioc.ac.ru.
ORCID
Ekaterina A. Denisova: 0000-0003-4818-2942
Dmitry B. Eremin: 0000-0003-2946-5293
Evgeniy G. Gordeev: 0000-0002-0545-5720
Andrey M. Tsedilin: 0000-0001-6483-0327
Valentine P. Ananikov: 0000-0002-6447-557X
Measure of All Rings − N-Heterocyclic Carbenes. Angew. Chem., Int.
Ed. 2010, 49, 6940−6952. (j) Johansson Seechurn, C. C. C.; Kitching,
M. O.; Colacot, T. J.; Snieckus, V. Palladium-Catalyzed Cross-
Coupling: a Historical Contextual Perspective to the 2010 Nobel
Prize. Angew. Chem., Int. Ed. 2012, 51, 5062−5085. (k) Li, H.;
Johansson Seechurn, C. C. C.; Colacot, T. J. Development of
Preformed Pd Catalysts for Cross-Coupling Reactions, Beyond the
2010 Nobel Prize. ACS Catal. 2012, 2, 1147−1164. (l) Wang, F.; Liu,
L.-J.; Wang, W.; Li, S.; Shi, M. Chiral NHC−Metal-Based Asymmetric
Catalysis. Coord. Chem. Rev. 2012, 256, 804−853. (m) Gildner, P. G.;
Colacot, T. J. Reactions of the 21st Century: Two Decades of
Innovative Catalyst Design for Palladium-Catalyzed Cross-Couplings.
Organometallics 2015, 34, 5497−5508.
■
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
■
This research was supported by the Russian Science
Foundation (RSF) Grant 17-13-01526. The authors also
thank Alexey S. Galushko for microscopy services.
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DOI: 10.1021/acs.inorgchem.9b01630
Inorg. Chem. XXXX, XXX, XXX−XXX