Ionic Pd/NHC Catalytic System Enables Recoverable Homogeneous Catalysis: Mechanistic Study and Application in the Mizoroki–Heck Reaction

Article abstract of DOI:10.1002/chem.201903221

N-Heterocyclic carbene (NHC) ligands are ubiquitously utilized in catalysis. A common catalyst design model assumes strong M–NHC binding in this metal–ligand framework. In contrast to this common assumption, we demonstrate here that lability and controlled cleavage of the M?NHC bond (rather than its stabilization) could be more important for high-performance catalysis at low catalyst concentrations. The present study reveals a dynamic stabilization mechanism with labile metal–NHC binding and [PdX₃]^?[NHC-R]⁺ ion pair formation. Access to reactive anionic palladium intermediates formed by dissociation of the NHC ligands and plausible stabilization of the molecular catalyst in solution by interaction with the [NHC-R]⁺ azolium ion is of particular importance for an efficient and recyclable catalyst. These ionic Pd/NHC complexes allowed for the first time the recycling of the complex in a well-defined form with isolation at each cycle. Computational investigation of the reaction mechanism confirms a facile formation of NHC-free anionic Pd in polar media through either Ph–NHC coupling or reversible H–NHC coupling. The present study formulates novel ideas for M/NHC catalyst design.

Full text of DOI:10.1002/chem.201903221

A Journal of
Accepted Article
Title: Ionic Pd/NHC Catalytic System Enables Recoverable
Homogeneous Catalysis. Mechanistic Study and Application in
the Mizoroki-Heck Reaction
Authors: Dmitry Eremin, Ekaterina Denisova, Alexander Kostyukovich,
Jonathan Martens, Giel Berden, Jos Oomens, Victor
Khrustalev, Victor Chernyshev, and Valentine P. Ananikov
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To be cited as: Chem. Eur. J. 10.1002/chem.201903221
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Ionic Pd/NHC Catalytic System Enables Recoverable
Homogeneous Catalysis. Mechanistic Study and Application in
the Mizoroki-Heck Reaction
Dmitry B. Eremin,[a] Ekaterina A. Denisova,[a] Alexander Yu. Kostyukovich,[a] Jonathan Martens,[b]
Giel Berden,[b] Jos Oomens,[b] Victor N. Khrustalev,[c,d] Victor M. Chernyshev,[a,e]
Valentine P. Ananikov*[a]
Abstract: N-Heterocyclic carbene ligands (NHC) are ubiquitously
utilized in catalysis. A common catalyst design model assumes
strong M-NHC binding in this metal-ligand framework. In contrast to
this common assumption, we demonstrate here that lability and
controlled cleavage of the M-NHC bond (rather than its stabilization)
could be more important for high-performance catalysis at low
functional frameworks and stimuli-responsive molecular
architectures, in addition to many other well-established
applications, are highlights of the recently emerging areas that
utilize the Mizoroki-Heck reaction, where aryl halides (1)
transform mono-substituted olefins (2) into disubstituted alkenes
(3) (Figure 1a).[3] Great practical potential of the Mizoroki-Heck
reaction was confirmed by implementation of molecular,[4]
nanoparticle,[5] anionic[3d, 6] and hybrid radical[7] catalytic systems.
Palladium complexes with NHC ligands constitute versatile
catalysts for the Mizoroki-Heck reaction as well as for other
catalytic transformations. Although numerous efforts towards re-
usability of Pd/NHC complexes have been attempted, the
establishment of well-defined recyclable complexes remains a
problem.[8] More generally speaking, development of the
recyclability concept for Pd/NHC complexes is a cutting edge
challenge.
As is common for many homogeneously operating complexes,
the Mizoroki-Heck reaction catalyzed by Pd/NHC starts with
precatalyst activation, followed by catalyst turnover, which
generally involves proposed intermediates of oxidative addition,
coordination, migratory insertion, β-H-elimination and reductive
elimination (Figure 1b). At some stage of the reaction, a Pd/NHC
catalyst inevitably changes and the loss of initial molecular
precatalyst usually leads to catalyst deactivation.[9] Indeed, in the
vast majority of catalytic reactions M/NHC complexes are of
single use, and re-cycling is not possible due to decomposition
during the reaction. A comparative thin-layer chromatography
(TLC) analysis of Pd/NHC complex transformation serves as an
illustration. Lane I on a TLC plate (Figure 1c) corresponds to a
pure Pd/NHC complex eluted in DCM and the spot can be
characterized with a specific retention factor. Lane II on the TLC
plate (Figure 1c) corresponds to the initial mixture before the
reaction. Evidently, the Pd/NHC complex can easily be found
just before the Mizoroki-Heck reaction (Figure 1c). However,
after the reaction has completed (Lane III), there are no spots
which can be attributed to the molecular form of Pd/NHC
complex.
catalyst concentrations. The present study reveals
a dynamic
stabilization mechanism with labile metal-NHC binding and [PdX3]–
[NHC-R]+ ion pair formation. Access to reactive anionic palladium
intermediates formed by dissociation of the NHC ligands and
plausible stabilization of the molecular catalyst in solution by
interaction with the [NHC-R]+ azolium cation is of particular
importance for an efficient and recyclable catalyst. These ionic
Pd/NHC complexes allowed for the first time the recycling of the
complex in
a well-defined form with isolation at each cycle.
Computational investigation of the reaction mechanism confirms a
facile formation of NHC-free anionic Pd in polar media via either Ph-
NHC coupling or reversible H-NHC coupling. The present study
formulates novel ideas for M/NHC catalyst design.
Introduction
M/NHC catalytic systems have been firmly established for
carrying out a variety of C–C bond formation reactions in
modern organic synthesis.[1] The development of olefin arylation
processes has led to diverse and efficient modifications
ubiquitously applied in research and industry.[2] Furthermore,
easily available starting materials and the efficient preparation of
drugs, dyes, organic electronic and photonic materials, smart
[a]
Dr. Dmitry B. Eremin, Ekaterina A. Denisova, Dr. Alexander Yu.
Kostyukovich, Prof. Dr. Victor M. Chernyshev, Prof. Dr. Valentine P.
Ananikov*
Zelinsky Institute of Organic Chemistry
Russian Academy of Sciences
Leninsky Pr. 47, Moscow 119991, Russia
E-mail: val@ioc.ac.ru
TLC here is used as a representative visual illustration. Similar
behavior of Pd/NHC complexes may be observed by other
analytical techniques (NMR, MS, etc.) as a result of the
transformation of Pd/NHC framework. Commonly, this leads to
the conclusion that either the complexes were deactivated
through decomposition (with possible formation of Pd-black,
especially at higher concentrations of palladium) or the mode of
operation of the catalyst shifts to nano-catalysis (Figure 1d).[9-10]
Here, we point our attention to the remaining spot at the start of
Lane III (Figure 1c). After careful analysis we have surprisingly
found that the typically assumed picture is incorrect
[b]
Dr. Jonathan Martens, Dr. Giel Berden, Prof. Dr. Jos Oomens
Radboud University, Institute for Molecules and Materials, FELIX
Laboratory
Toernooiveld 7c, 6525 ED, Nijmegen, The Netherlands
Prof. Dr. Victor N. Khrustalev
National Research Center «Kurchatov Institute»
Acad. Kurchatov Sq. 1, Moscow, 123182, Russia
Prof. Dr. Victor N. Khrustalev
Peoples’ Friendship University of Russia (RUDN University)
Miklukho-Maklay St. 6, Moscow, 117198, Russia
Prof. Dr. Victor M. Chernyshev
[c]
[d]
[e]
Platov South-Russian State Polytechnic University (NPI)
Prosveschenya 132, Novocherkassk 346428, Russia
Supporting information for this article is given via a link at the end of
the document.
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Figure 1. Pd complex transformations in catalytic reactions. (a) Mizoroki-Heck reaction; (b) general Mizoroki-Heck reaction mechanism for Pd/NHC catalytic
system; (c) TLC analysis of Pd precatalyst in pure form, before and after the Mizoroki-Heck reaction; Pd/NHC catalyst life-path: (d) at higher concentrations; (e) at
lower concentrations.
for the studied system. We show here that the spot at the start of
Lane III contains soluble ionic Pd species that may still possess
catalytic activity. Moreover, in less concentrated solutions (below
10–4 M), formation of nanoparticles is suppressed in favor of
ionic complex formation.
connection between Ph-NHC coupling and catalyst performance,
including the recycling of the ionic Pd/NHC complex in a well-
defined form.
Here, we report the discovery of an unexpected shift of the
molecular Pd/NHC catalyst to an ionic Pd complex during the
catalyst life-path under Mizoroki-Heck reaction conditions
(Figure 1e). The discovered ionic [NHC-R]+[PdX3]– species are
stable and highly active in the Mizoroki-Heck reaction in dilute
solutions (Figure 1e). Efforts to rationalize performance of the
catalytic system have motivated mechanistic studies to
understand the off-NHC pathway reactions that stimulate the
catalyst turnover. Our investigations reveal an unexpected
pathway of catalyst transformation that illuminates the
Results and Discussion
Catalytic reactions with relatively large Pd loadings (>1 mol%)
have been investigated in detail previously.[3, 9-11] We performed
transmission electron microscopy (TEM) analysis and confirmed
the formation of metal-containing particles/nanoparticles in the
Mizoroki-Heck reaction under study (2.5×10–4 – 7.5×10–3 M).
With relatively large Pd loadings (> 10–3 M), the known
molecular-to-nano transformation of Pd species takes place
(Figure 1d). However, different observations were made for a
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high-performance process with smaller metal loadings (0.1 – 0.5
mol %; 10–4 – 10–3 M) in diluted mixtures, where the full power of
the Pd/NHC system in solution-state catalysis is manifested.
To reveal transformation of metal species, a mass spectrometric
evaluation of the mixtures under native reaction conditions was
performed. To trace the formation of active species, electrospray
ionization mass spectrometry (ESI-MS) with time-of-flight (TOF)
or Fourier transform ion-cyclotron resonance (FT/ICR) detection
was utilized with a soft ionization approach. [12]
signals was confirmed by isotopic pattern simulations and DFT
quantum-chemical calculations.
Good activation properties of methanol[14] allowed easy detection
of 9 in this solvent. However, dimethylformamide (DMF) is more
commonly used for the Mizoroki-Heck reaction.[2-3] Direct MS
analysis of 4a in DMF in negative ion mode confirmed the
presence of 7 and 9 but with much lower intensities, which was
in agreement with the soft activation properties of this solvent,[15]
as compared with MeOH. The positive ion mode MS confirmed
the formation of the corresponding azolium salt 8. Switching to
DMF-d7 led to a clear mass shift by +1 Da, showing the
formation of deuterated species.
First, transformation of initial Pd complexes was studied.
Solutions of the palladium precursor (NHC)PdX2Py (4; see
Scheme S1 for detailed structures) in methanol were subjected
to ESI-MS (Figure 2a, R = H), revealing several palladium
complexes corresponding to the activation process. A plausible
mechanism of the precatalyst activation involves coordination of
MeOH (5, (NHC)PdX2(MeOH)) followed by rearrangement 6 (β-
H-elimination like). As a result, the NHC-containing palladium
hydride 7 ([(NHC)PdX2H]–) is formed, followed by elimination of
the NHC ligand and formation of [PdX2H]– (9), as is evident from
the ESI-MS data. The initial complex 4 and all proposed
intermediates (5, 7, 8 ([NHC-H]+), and 9) were detected in the
mass spectra. The experiment was performed for different
halogen ligands X = I, Br, and Cl (4a, 4b, and 4c; Figure 2).
Moreover, the formation of product 9 from complex 7 was
confirmed by a collision-induced dissociation (CID) experiment
carried out on a FTICR-MS. Indeed, decomposition of 7 led to
direct formation of 9 and expulsion of a free carbene ligand as a
neutral. The proposed mechanism was confirmed by
experiments with deuterium-labeled solvents. Application of
CD3OD and CD3OH resulted in formation of [PdI2D]– (9D), while
reaction in CH3OD produced [PdI2H]–, indicating that the methyl
group (rather than the hydroxy group) of methanol was the
source of the hydride ligand.
Infrared ion spectroscopy (IRIS), which combines mass
spectrometry with infrared (IR) spectroscopy, was employed
here to determine the gas-phase structures of ions generated in
the mass spectrometer. This method has recently been shown
to be able to determine the structures of otherwise elusive
reaction intermediates.[13] In addition to the m/z and MS/MS
fragmentation spectra, IRIS provides an infrared fingerprint of
mass selected ions trapped in the ion trap mass
spectrometer. In order to provide additional confirmation of the
structures of the [PdX2H]– (Xꢀ =ꢀ I, Br) ions, we used IRIS in the
2000 – 2500 cm–1 region to characterize their gas-phase
structures. These IR spectra (Figure S47) show a highly specific
and diagnostic vibrational band attributed to a Pd-H stretching
vibration, thus confirming the presence of a Pd-H bond in these
ions. The position of this Pd-H band at ca. 2200 cm–1 is in a
region of the infrared spectrum that should otherwise be empty
and closely matches to the position of the calculated IR band.
This allows us to correlate the molecular structure of the
[PdX2H]– ions to those calculated by density functional theory
(DFT).
Other reductants commonly applied as bases in Mizoroki-Heck
catalytic systems are amines.[11c] Solution of Et3N in DMF-d7
strongly promoted the formation of 9, and not of 9D, while the
NHC-bound
7
reduced to the noise level. Even
[Et2(N=CH)CH3I2]– was detected at trace levels as an
intermediate of hydride transfer. Although olefins are known to
act as metal reductants as well,[3e] the use of butyl acrylate
appeared to be less efficient as compared with DMF-d7.
Interestingly, palladium hydrides are often implicated in catalyst
activation[15-16] or in the catalytic cycle after β-H-elimination,[17]
although direct identification of these intermediates under
catalytic conditions remains a challenge. In organometallic
transformations, only palladium hydride complexes stabilized by
appropriate ligands (i.e., phosphine ligands) have been isolated
and characterized.[17f] Here, we report for the first time the
detection of unstabilized palladium hydride.
The second possibility to switch the catalytic system from neutral
to ionic form is Ar-NHC coupling from oxidative addition
18]
intermediates (Figure 2a, R = Ar).[10,
We have conducted
analysis of 4a (6.6 µmol) transformations under Mizoroki-Heck
catalytic conditions. Three parallel arylations of butyl acrylate
(2a) with PhI (1a) (1.5 mmol), catalyzed by 4a, were stopped at
23%, 62% and 99% butyl cinnamate (3a) yields (Figure 2b).
Palladium complexes were isolated from the reaction mixtures
and analyzed using a suite of experimental methods: 1H NMR
spectroscopy, 1H NOE, {1H-13C}HMBC, 1H DOSY NMR, EDX
spectroscopy, LC-UV/Vis-MS, and ESI-(+/–)MS. The isolated
residue consisted of KI (confirmed by UV-Vis, and ESI-MS),
palladium iodide (confirmed by EDX spectroscopy, and ESI-MS)
and two ionic species: [NHC-Ph]+ and, plausibly, [NHC-PdI3]–
(confirmed by NMR, LC, and ESI-MS). Upon crystallization, the
structure of ionic complex 10 was confirmed by single-crystal X-
ray analysis. Thus, the ionic species were quantitatively formed
in
a real synthetic-scale experiment, which indicates a
mechanistic picture involving counterion stabilization by
dissociated NHC ligands transformed to azolium salts, while no
palladium nanoparticles were observed by electron microscopy.
The appearance of [NHC-PdI3]–[NHC-Ph]+ ionic complex 10
([NHC-Ph]+ – 10a, [NHC-PdI3]– – 10b) in the reaction mixture
was confirmed by independent synthesis from μ-iodo-palladium
dimer complex 12 and 2-phenyl-1,3-dimethylbenzimidazolium
salt 13 (Figure 2c). 1H DOSY NMR has shown that the cation
and anion behave as a single unit in non-polar solvents (CD2Cl2)
or could be separated in a polar solvent (DMSO-d6). The identity
of the crystal structure was confirmed by X-ray analysis, along
with
To evaluate the scope of possible organometallic compounds,
11 different Pd/NHC complexes were studied, and 9 was
detected in all cases. The corresponding Pd hydrides, [PdI2H]–,
[PdBr2H]– and [PdCl2H]–, were clearly detected in the ESI-MS
spectra recorded in negative-ion mode. The experiments were
reproduced several times, and the nature of the observed
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Figure 2. Pd/NHC activation and its transformation into ionic Pd/NHC complex in Mizoroki-Heck reaction. (a) Formation of active ionic species: (R = H)
ESI-MS established mechanism of [PdX2H]– formation from (NHC)PdX2Py complexes, (R = Ar) proposed transformation pathway of molecular Pd/NHC into ionic
form via R-NHC coupling; (b) ionic Pd salt isolated from Mizoroki-Heck reaction mixture with 0.44 mol.% of 4a, and its crystal structure, 1H NMR and ESI-(+/–)MS;
(c) independent synthesis of ionic Pd/NHC salt and confirmation of its structure by 1H DOSY NMR, ESI-MS and IRIS analysis.
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well-correlated ESI-MS and NMR spectra. It is worth noting that
4a, 12, and 13 are significantly less soluble in DCM, DMF, or
DMSO.
in quasi-equilibrium with 11, which can be crystallized as a dimer
11’ from the reaction mixture when using 10 as a precatalyst
(Figure 3b). The presence of complexes 9, 10b, 11, 14, 15 and
cations 8a and 10a have been confirmed by ESI-MS.
Complexes 16 and 17 have not been detected by ESI-MS, but
these organometallic species probably decompose under the
ESI-MS conditions.[12] To test the proposed mechanism, the
reaction was performed using a deuterium-labeled 2a-D in
regular non-deuterated solvent. In this case, coordination of
deuterated 2a-D, followed by insertion and β-D-elimination, is
predicted to result in formation of [PdX2D]–. The formation of
deuterated product 9a-D was confirmed by NMR and GC-MS,
and the observed kinetic isotope effect (k = 3.1 measured by
NMR) was consistent with the mechanism dependent on the
reduction as the rate-limiting step.
Under these conditions, possibility of Pd nanoparticle formation
was analyzed; however, no solid species were found in the
reaction mixtures by TEM analysis. Meanwhile, metal-containing
nanoparticles were observed for 4a in more concentrated
solutions. Indeed, similar processes have been described in the
literature.[3, 9-11]
The data indicate formation of NHC-free metal species with
dynamic stabilization due to the counterion effect of the organic
cation in the form of azolium salts: [PdX3]–[NHC-R]+ (R = H or
Ph). These results are consistent with the proposed precatalyst
activation mechanism and supported by successful isolation of
complex 10 from the Mizoroki-Heck reaction mixture.
Additional
characterization
of
the
conducted
ionic
using
complex
IRIS.
[NHC-Ph]+[(NHC)PdI3]– (10) was
Excellent agreement between the experimental and DFT-
predicted IR spectra was obtained for the anionic [BIMePdI3]–
species (Figure 2с and S46) and the [NHC-Ph]+ cation (Figure
S45) further confirming our assignment to the calculated
structures.
The initial complex 4a appeared to possess the same activity as
12, whereas using 10 as a precatalyst was even more efficient
giving a quantitative yield after 2 hours (at a 37.5 µmol level).
Furthermore, no visible catalyst degradation was observed when
using ionic Pd/NHC salt 10 as a precatalyst. Encouraged by the
catalytic activity of ionic Pd complex 10, which was initially
obtained due to lability of Pd-NHC bond via Ph-NHC coupling,
we studied the Mizoroki-Heck reaction mechanism by ESI-MS of
the undiluted reaction mixture (starting materials at ~10–2 M, 4a
as a precatalyst at a ~10–5 M concentration). The reaction was
carried out in DMF and online monitoring was performed using a
special pressurized sample infusion balloon interface recently
developed by McIndoe and co-workers.[19]
At the initial point, monitoring was started by heating the reaction
mixture without the palladium complex. After 3 min, the solution
containing the catalyst precursor was introduced through a
septum. The first Pd-containing signal appearing in the spectra
corresponded to [(NHC)PdI3]–, which quickly reached the
maximum intensity and then decreased. Over the next minute,
two more Pd-containing signals were detected corresponding to
[PdI2Ph]–, an NHC-free intermediate of oxidative addition, and
palladium hydride 9. Moreover, the rates of [PdI2Ph]– and
[PdI2H]– were linearly dependent, which confirms their
involvement in the same reaction. Remarkably, despite the low
concentration, a characteristic rise-descending curve[20] was
detected for the palladium hydride [PdI2H]– signal, confirming the
reliable nature of this reaction intermediate. Notably, no NHC-
containing intermediates of the Mizoroki-Heck catalytic cycle
were detected during the process. The reaction was monitored
for 130 min, and the formation of a butyl cinnamate product was
confirmed by gas chromatography-mass spectrometry (GC-MS)
and NMR. Replacement of DMF with DMF-d7 did not change the
observed picture. No H/D scrambling occurred during the
reaction as DMF contributes in the Pd activation only in cases as
described above. Similarly, no Pd/NHC intermediates were
detected under varying solvent, base, precatalyst, and
temperature conditions.
Encouraged by the fact that the ionic Pd complex is active,
stable and operates homogeneously, we studied the possibility
of recycling 10 in the Mizoroki-Heck reaction in comparison with
the initial complex 4a (Figure 3c). To achieve full conversion of
1a into 3a, the reactions were heated for 3 hours with 10 as a
precatalyst and for 4 hours with 4a as a precatalyst. After the
reaction completion, remaining Pd species were isolated,
dissolved in DCM and analyzed by TLC. For both of the tested
Pd complexes, no neutral complexes were detected and only the
ionic complex stood rooted at the start. The ionic complex was
successfully re-used for 5 cycles with constant activity and no
visible degradation (Figure 3d). After the 5th cycle, the remaining
Pd species were studied by NMR and MS and no Pd-NHC
species were found. Crystallization from DCM afforded another
anionic complex 11’ [Pd2I6]2–[NHC-Ph]+ , which was confirmed
2
by single crystal X-ray analysis. TLC analysis of the catalyst
solution in DCM after each cycle confirmed the presence of ionic
species only (Figure 3e). If a solution of any precatalyst after
Mizoroki-Heck reaction is filtered through a short pad of silica,
the residue is inactive in the second cycle already. The
separated crude mixture containing 11’ was stored for 3 weeks
under air without additional purification and re-used again. A
less than 1.5-fold decrease was observed in the initial reaction
rate of the 6th cycle, the isolated product yield after 3 hours was
80% (Figure 3d). Thus, anionic Pd complexes with NHC-Ph+
cations represent a class of highly stable recyclable catalysts of
the Mizoroki-Heck reaction, which, to the best of our knowledge,
has not been reported before.
The proposed mechanism is as follows (Figure 3a). The NHC-
free ionic pair 14 ([PdI]–[NHC-R]+) is formed directly from 4a, or
10, or 12 via Ph-NHC or H-NHC coupling or via solvent
activation through 5. Then, cationic species like [NHC-R]+ play a
stabilization role while anionic Pd undergoes oxidative addition
with Ph-I (1) giving 15, followed by coordination of olefin 2 giving
16, followed by migratory insertion. Products 3 and 9 are formed
subsequently via β-H-elimination from 17. A base assisted
reduction of 9 leads to 14, closing the cycle. At this stage, 14 is
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Figure 3. Ionic Pd/NHC-catalyzed Mizoroki-Heck reaction with counterion stabilization: Mechanism, Recycling and Scope. (a) Anionic mechanism of
Mizoroki-Heck reaction studied by ESI-MS, GC-MS, NMR, deuterium labeling experiments and single crystal X-ray analysis; (b) crystal structure of off-cycle ionic
Pd/NHC complex isolated after the reaction; (c) reaction studied for recycling of ionic Pd/NHC complex; (d) reaction profiles for the recycling, cycle 6 was
performed after 3 weeks of the isolated catalyst storage; (e) model TLC analysis of ionic Pd/NHC complex catalyst upon recycling after cycles 1 and 5. (f)
Reaction scope with the halogen X = I, Br, or Cl in Ar-X and corresponding yields indicated under each product. The yields were determined by 1H NMR and
confirmed by GC. Reaction conditions: 1 (5 × 10–2 M), 2 (1.2 eq), K2CO3 (1.6 eq.), TBAX (1 eq.), 10 (1 mol%), DMF, 100 °C. a3 h; b4 h; c6 h; d24 h; e120 °C, 48 h.
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Following the mechanistic and recycling studies, a reaction
scope for Mizoroki-Heck reaction was evaluated for ionic media
in diluted mixtures (Figure 3f). Introducing electron-withdrawing
groups into Ar-X resulted in high product yields (3b-h), even for
p-chlorobenzaldehyde 1e. Steric hindrance in 1d provided only
65% yield of 3d in 24 h; however, the reaction was selective,
and no side products were detected. Condensed aromatic
bromides reacted efficiently, and 3i-k were obtained in
quantitative yields. Electron donating substituents in Ar-X
appeared to react efficiently as could be seen for 3l-q. Alkyl
substituents also did not affect the product outcomes (3r-t).
Even o-iodotoluene reacted smoothly, and the yield of 3s was
not affected by steric bulkiness of the methyl group. Several
esters and a nitryl of acrylic acid were also tested in the reaction
affording 3u-x in yields from good to excellent; however, p-tolyl
bromides appeared to give lower yields than p-tolyl iodides.
Encouraged by the results of catalytic studies, we calculated and
analyzed the potential energy surface (PES) of the Mizoroki-
Heck reaction catalyzed by Pd/NHC system. In order to compare
molecular and anionic modes, we followed catalytic paths for the
commonly assumed complexes with the retained Pd-NHC bond
(ΔG35→15 = –25.6 and ΔG‡35→TS36 = 9.3 kcal/mol) as compared
with the [NHC-Ph]+ addition reaction (ΔG35→21 = 9.5 and
ΔG‡35→TS33 = 22.9 kcal/mol). It is also worth noting that the ratio
of the rates of the two processes under consideration also
depends on the ratio of the concentrations of iodobenzene and
the corresponding azolium salt in the reaction mixture. As the
azolium salt is present in the reaction mixture in catalytic
amounts, the rate of the corresponding oxidative addition
reaction is low.
The other possibility for anionic species formation is H-NHC
coupling
28→48.
This
process
is
endergonic
(ΔG28→48 = 4.4 kcal/mol) and has a very low activation energy
ΔG‡28→TS47 = 6.3 kcal/mol. In the case of H-NHC coupling,
thermodynamic equilibrium between anionic and neutral
systems is also determined by two processes of oxidative
addition of PhI (ΔG35→15 = –25.6 and ΔG‡35→TS36 = 9.3 kcal/mol)
and [NHC-H]+ (ΔG35→28 = 3.2 and ΔG‡35→TS47 = 9.5 kcal/mol). As
can be seen from the energetic parameters of these processes,
the equilibrium completely shifted towards the anionic system.
Note that the addition of [NHC-H]+ cation to the Pd complex
35→28 is more advantageous and proceeds more facile as
compared to the oxidative addition of [NHC-Ph]+ 35→21. This
indicates that azolium cations with aryl substituents should
predominate in the reaction mixture.
–
as opposed to the anionic PdX3 species with cationic NHC-R+
partners formed directly from a single Pd-NHC precursor (Figure
4).
The PESs calculated for two different reaction pathways are
similar. In each case the base-assisted reduction is the rate-
determining step, being additionally dependent on the nature of
the base. The activation barrier ΔG‡ (ΔH‡) for this step in the
case of the anionic channel (21.3 (29.8) kcal/mol) is only slightly
lower than for the NHC-bound Pd (23.6 (29.7) kcal/mol). These
values indicate comparable probabilities of the considered
pathways and fit with the experimentally observed behavior of
the ionic complex, albeit that NHC-bound intermediates were not
detected in this study.
Conclusion
We report the development of a recyclability concept for Pd/NHC
complexes, powered by the lability of M-NHC framework and full
utilization of dynamic stabilization mode. The present idea
abandons commonly assumed attempts to strengthen M-NHC
bond, instead, the novel point is to reach a stable and recyclable
form of the catalyst. Remarkably, the concept is powerful for
high performance processes with low concentrations of Pd
catalysts.
ESI-TOF and ESI-FT/ICR mass spectrometry experiments
enabled the detection of intermediates in Pd/NHC activation and
in the Mizoroki-Heck reaction, including the elusive [PdX2H]–, the
existence of which had been suggested previously. IRIS of
[PdX2H]– unambiguously confirmed formation of hydride species.
The nature of the palladium intermediates was confirmed by
deuterium labelling experiments. The products of Pd/NHC
transformations into ionic species were studied by a variety of
analytical techniques. The results confirmed the possibility of
Pd-NHC bond breaking without the loss of catalytic activity.
The observed ionic palladium complex could be easily isolated
from the reaction mixture after the reaction was completed and
used as a well-defined catalyst precursor. The obtained ionic
[NHC-PdI3]–[NHC-Ph]+ complex was highly active and recyclable
Activation barriers for the other steps of the mechanism, namely,
oxidative addition, migratory insertion, and β-H-elimination, are
significantly lower – in the range of 4.2 – 13.4 (4.7 – 14.2)
kcal/mol for both catalytic cycles. The main difference between
neutral and ionic mechanisms is attributed to the steps of
oxidative addition and β-H-elimination. The oxidative addition
barrier ΔG‡
for the ionic complex is nearly two times
35→TS36
higher than ΔG‡19→TS20 for the neutral complex: 9.3 (8.9) kcal/mol
vs 4.2 (4.7) kcal/mol. The situation is opposite for β-H-
elimination: ΔG‡39→TS40 = 6.8 (7.5) kcal/mol vs ΔG‡24→TS25 = 13.4
(14.2) kcal/mol.
As mentioned above, there are two possibilities to shift the
catalytic system from the neutral Pd-NHC system to the ionic
system with NHC-free Pd: Ph-NHC coupling and H-NHC
coupling. The Ph-NHC coupling 21→34 is favorable
(ΔG21→34 = –6.8 kcal/mol) and has low activation energy
ΔG‡21→TS33 = 13.4 kcal/mol. Since this process does not have
thermodynamic and kinetic prohibitions, the content of the
anionic species in the reaction mixture is determined by the
equilibrium between anionic and neutral catalytic systems. For
complexes 34 and 35, two ways of oxidative addition are
possible: (1) addition of iodobenzene and formation of anionic
species (35→15); (2) addition of [NHC-Ph]+ cation and formation
of the Pd-NHC neutral system (35→21). The addition of
iodobenzene (Figure 4) is a more advantageous process
–
in Mizoroki-Heck reaction. From cycle to cycle, the NHC-PdI3
anion loses an NHC ligand, producing monomeric PdI3 in
–
solution (represented as Pd2I62– in solid state). Thus, a dual role
of the Pd/NHC complexes is proposed: (1) Pd/NHC complexes
act as a source of highly active catalysts with NHC-free anionic
palladium species and (2) the [NHC-R+] cations, formed upon
dissociation of the NHC ligand (R = H, Ar), stabilize the metal
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Figure 4. Potential energy surface for Mizoroki-Heck reaction catalyzed by Pd/NHC complexes. Magenta path – neutral intermediates with Pd-NHC (NHC = 1,3-dimethyl-1H-benzimidazol-2-ylidene) bond; blue path –
anionic Pd intermediates formed after NHC-Ph coupling; green path – anionic Pd intermediates formed after NHC-H coupling. Computations performed at PBE1PBE//6-31+G(d,p)/def2-TZVP SMD level of theory with DMF as a
solvent; the numbers correspond to relative free Gibbs energy values.
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The authors are grateful to Dr. Alexander V. Astakhov for the
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Conflict of interest
The authors declare no conflict of interest.
Keywords: Mizoroki-Heck reaction • NHC-complexes • Dynamic
catalysis • Mass spectrometry • Electrospray ionization
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Entry for the Table of Contents
Layout 1:
RESEARCH ARTICLE
Reactive ionic palladium complex
forms due to dissociation of the NHC
ligand and subsequent stabilization by
the interaction with the [NHC-R]+
azolium cations, thus providing a
powerful concept of ionic recyclable
catalyst.
D. B. Eremin, E. A. Denisova,
A. Yu. Kostyukovich, J. Martens,
G. Berden, J. Oomens, V. N. Khrustalev,
V. M. Chernyshev, V. P. Ananikov*
Page No. – Page No.
Ionic Pd/NHC Catalytic System
Enables Recoverable Homoge-neous
Catalysis. Mechanistic Study and
Application in the Mizoroki-Heck
Reaction
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