C–H Bond Activation by a Ruthenium(II) β-Diketonate Complex: A Mechanistic Study

Article abstract of DOI:10.1002/ejoc.201800787

Ruthenium(II)-catalysed C–H bond activation of arenes containing a functional directing group depends on the ligand coordinated to ruthenium(II). In this study, 2-phenylpyridine C–H activation catalysed by a “piano-stool“ ruthenium(II) complex containing a fluorinated β-diketonate ligand was examined by ESI-MS in combination with CID experiments. [Ru(β-diketonate)(^CTPhPy)Cl]⁺ was identified as an active intermediate, and its collisional activation leads to C–H activation. CID analysis indicates proton transfer from the phenylpyridine to the chlorine anion, showing HCl elimination, while the β-diketonate ligand is retained in the complex together with the activated phenylpyridine. Furthermore, DFT calculations were performed for the neutral analogue [Ru(β-diketonate)(PhPy)Cl] to identify all ruthenium intermediates along the C–H activation reaction pathway. The results suggest that the most stable structure of [Ru(β-diketonate)(PhPy)Cl] has pre-activated 2-phenylpyridine with a partly developed Ru–H bond. Further, we show that K₂CO₃ is not directly involved in the C–H activation step and it serves in the reaction as a base.

Full text of DOI:10.1002/ejoc.201800787

A Journal of
Accepted Article
Title: C-H Bond Activation by a Ruthenium(II) β-diketonate Complex: A
Mechanistic Study
Authors: Anamarija Bris, Iztok Turel, and Jana Roithová
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201800787
Link to VoR: http://dx.doi.org/10.1002/ejoc.201800787
Supported by

10.1002/ejoc.201800787
European Journal of Organic Chemistry
FULL PAPER
C-H Bond Activation by a Ruthenium(II) β-diketonate Complex:
A Mechanistic Study
Anamarija Briš,[a] Iztok Turel,[b] and Jana Roithová*[a,c]
Abstract: Ruthenium(II)-catalysed C-H bond activation of arenes
containing a functional directing group depends on the ligand
coordinated to ruthenium(II). In this study, 2-phenylpyridine C-H
Today, researchers agree that ruthenium(II)-catalysed C-H
activation of arenes containing a functional directing group
occurs via metalacycle formation. However, metalacycle
formation proceeds in different pathways, depending on the
ligand coordinated to ruthenium(II) and/or on the additives used.
For example, Özdemir et al.[8] preformed DFT calculations for 2-
phenylpyridine C-H activation by NHC-ruthenium(II) complex
and carbonate. They showed that the first step of the C-H
activation reaction occurs via proton abstraction by carbonate in
activation catalysed by
containing a fluorinated β-diketonate ligand was examined by ESI-
MS in combination with CID experiments. [Ru(β-
a “piano-stool” ruthenium(II) complex
diketonate)(CTPhPy)Cl]+ was identified as an active intermediate, and
its collisional activation leads to C-H activation. CID analysis
indicates proton transfer from the phenylpyridine to the chlorine
anion, showing HCl elimination, while the β-diketonate ligand is
retained in the complex together with the activated phenylpyridine.
Furthermore, DFT calculations were performed for the neutral
analogue [Ru(β-diketonate)(PhPy)Cl] to identify all ruthenium
intermediates along the C-H activation reaction pathway. The results
suggest that the most stable structure of [Ru(β-diketonate)(PhPy)Cl]
has pre-activated 2-phenylpyridine with a partly developed Ru-H
bond. Further, we show that K2CO3 is not directly involved in the C-H
activation step and it serves in the reaction as a base.
the
negatively
charged
(Figure
ruthenium
1a, PhPy
complex
2-
[(NHC)RuCl2(PhPy)(HCO3)]-
=
phenylpyridine).[9] In addition, mass spectrometry studies of C-H
activation with ruthenium(II) carboxylates showed that
carboxylates accept a proton from the activated C-H bond.
Subsequent DFT calculations suggested that the carboxylate
ligand is directly involved in the C-H activation step, which
proceeds via a six-membered transition state (Figure 1b).[10] Zell
et al.[ 11 ] and Graux et al.[ 12 ] performed experiments with
ruthenium(II) phosphinous acid complexes highlighting the
importance of phosphinoate in C-H activation (Figure 1c), and
the suggested mechanism is similar to that involving
carboxylates.
Introduction
In recent years, breakthroughs in the development of direct
C-C bond formation via C-H activation have enabled us to
reduce the number of synthetic steps.[1] Among the transition
[ 2 ]
metal complexes used,
ruthenium complexes stand out
because they are relatively inexpensive, non-toxic, and stable in
air and water.[3] Although Murai, et al.[4] used ruthenium(0) in
their pioneering experiments, ruthenium(II) complexes are now
intensively used,[ 5 ] particularly [RuCl2(arene)]2. Initially, the
[6]
[RuCl2(arene)]2 complex was mostly used with either PPh3 or
Figure 1. Transition states for the ruthenium(II) catalysed C-H activation of a
carboxylic acid[ 7 ] addition for C-H activation. Subsequently,
[RuCl2(arene)]2 was used as precursor of easily prepared
ruthenium(II) catalysts for C-H activation/functionalisation
reactions, whose regioselectivity can be modulated by changing
their chelating ligand.
2-phenylpyridine with
a different ligand coordinated to ruthenium: a)
imidazolium salt and carbonate,[8] b) carboxylate[10] and c) phosphinoate[12]
.
Here, we study C-H activation by the ruthenium(II) catalyst
[Ru(CYM)(β-diketonate)Cl] (Figure 2) with electrospray
ionisation mass spectrometry. It has been shown that various
[Ru(CYM)(β-diketonate)Cl] complexes are efficient catalysts for
ortho arylation via C−H activation.[13] In the selected catalyst,
[a]
[b]
[c]
A. Briš, J. Roithová
Department of Organic Chemistry
Faculty of Science, Charles University
Hlavova 2030/8, 128 43 Prague, Czech Republic
I. Turel
Faculty of Chemistry and Chemical Technology
University of Ljubljana
ruthenium(II) is η6-coordinated to p-cymene (CYM), to
a
fluorinated β-diketonate ligand and to Cl- (Figure 2). This study
aimed to assess the role of β-diketonate in 2-phenylpyridine C-H
activation. In principle, the β-diketonate ligand could accept the
proton from a C-H activated bond in a mechanism similar to
those reported for ruthenium carboxylates.[10]
Večna pot 113, SI-1000 Ljubljana, Slovenia
J. Roithová
Institute for Molecules and Materials, Radboud University,
Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands
E-mail: jana.roithova@ru.nl
We note that besides the catalytic activity, these
complexes also exhibit strong anticancer effects.[14] Interestingly,
also cycloruthenated compounds obtained by a C–H activation
reaction exerted strong anticancer effects.[15] In general, design
of organometallic catalysts that can also be used in therapy is a
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800787
European Journal of Organic Chemistry
FULL PAPER
hot research topic in last years.[16] Frequently, it is difficult to
determine the mechanisms of actions of metal complexes that
act as catalysts but even harder of those that act as drugs. It is
therefore of a big importance to study such processes in detail.
2-phenylpyridine (Figure 4a). The primary fragment [Ru(CYM)(β-
diketonate)]+ (m/z 485) can associate with a molecule of
acetonitrile present as background gas in the mass
spectrometer; accordingly, we also observe [Ru(CYM)(β-
diketonate)(CH3CN)]+ (m/z 526) in the CID spectrum. However,
no [(β-diketonate)H] elimination is observed, thus suggesting
that C-H activation does not proceed within the gaseous
[Ru(CYM)(β-diketonate)(PhPy)]+ reaction complex; otherwise, C-
H activation would have been evident as the elimination of
neutral [(β-diketonate)H]. We can estimate the binding energy of
2-phenylpyridine to the ruthenium center from energy-resolved
CID experiments (Figure 4b)[ 17 ],[ 18 ],[ 19 ] because the collision
energy scale of our ion trap instrument can be calibrated (Figure
S5 in the Supporting Information).[18] We assessed the
appearance energy for the loss of PhPy as 1.6 ± 0.1 eV by linear
extrapolation of the 2-phenylpyridine appearance curve (Figure
4b). This energy is the lower limit of the energy that would be
necessary for C-H activation of 2-phenylpyridine within
[Ru(CYM)(β-diketonate)(PhPy)]+ and for the subsequent [(β-
diketonate)H] elimination.
Figure 2. Structure of the ruthenium(II) catalyst.
Results and Discussion
In the ESI-MS spectrum of the reaction mixture, we also
Ruthenium(II)[5] catalysed C-H bond activation and
functionalisation reactions are usually performed in N-methyl-2-
pyrrolidone, but this solvent is unsuitable for ESI-MS
experiments. Therefore, we have performed the experiments in
acetonitrile because previous studies have shown that aprotic
polar solvents are generally suitable for direct C-H activation of
phenylpyridines.[6]
observed
a
metalacycle species with C-H-activated 2-
phenylpyridine, [Ru(CYM)(PhPy-H)]+ (m/z 390, Figure 3).[ 20 ]
Detection of these ions shows that the C-H activation reaction
proceeds in the reaction mixture. Unfortunately, we only observe
the product of C-H activation, but no intermediate in which we
could study the reaction itself. We have also tried an analogous
reaction with K2CO3 addition (reaction mixture B in Supporting
information). No expected intermediates with a coordinated
carbonate anion were found, neither in the positive- nor in the
negative-ion mode mass spectra.
Electrospray ionisation (ESI) of acetonitrile solution of the
[Ru(CYM)(β-diketonate)Cl]
catalyst
yields
[Ru(CYM)(β-
diketonate)]+ ions (m/z 485 in the ESI-MS spectrum, Figure S4 in
the Supporting information). We also observe adducts of these
ions with acetonitrile, [Ru(CYM)(β-diketonate)(CH3CN)]+ (m/z
526). 2-phenylpyridine (PhPy) addition to the acetonitrile solution
of the ruthenium(II) catalyst (reaction mixture
A in the
Supporting information) forms a new complex with m/z 640. The
mass of the complex suggests that its composition is
[Ru(CYM)(β-diketonate)(PhPy)]+ (Figure 3).
Figure 3. ESI-MS spectrum of the ruthenium(II) catalyst and 2-phenylpyridine
in acetonitrile. The inset compares the experimental and the simulated isotope
pattern for m/z 640.
Figure 4. a) CID spectrum and b) breakdown diagram as a function of the
collision energy of the mass selected ion [Ru(CYM)(β-diketonate)(PhPy)]+.
Collision-induced dissociation (CID) of the [Ru(CYM)(β-
diketonate)(PhPy)]+ complex exclusively eliminates the neutral
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800787
European Journal of Organic Chemistry
FULL PAPER
Scheme 1. Synthetic procedure for the preparation of imidazolium-based charge-tagged phenylpyridine.
Most likely, the intermediates are negatively charged or
neutral, rather than positively charged, thus explaining why no
reaction complex showing C-H activation reaction is observed in
the positive-ion mode mass spectra. However, we have not
detected negatively charged intermediates either (Figure S6 in
the Supporting Information). Therefore, we probed the reactivity
of neutral complexes using the charge-tagging method. The
charge-tagging strategy[ 21 ] relies on the introduction of a
permanently charged group in a remote position of the substrate
or catalyst. The charge-tag group should not interfere with the
reaction site or with the reaction in general. Thus, the only
function of the charge-tag group should be to make “neutral
intermediates” visible for mass spectrometry. To this end, we
phenylpyridine on top. Collisional activation of this complex
exclusively eliminates the charge-tagged substrate (Figure 6a).
Again, we observed no C-H activation. The binding energy of
charge-tagged
2-phenylpyridine
in
[Ru(CYM)(β-
diketonate)(CTPhPy)Cl]+ was estimated from energy resolved
CID as 1.0 ± 0.1 eV (Figure 6b). Hence, the binding energy of
the substrate in [Ru(CYM)(β-diketonate)(CTPhPy)Cl]+ is lower
than the binding energy of neutral 2-phenylpyridine in
[Ru(CYM)(β-diketonate)(PhPy)]+. This can be rationalised by the
presence of the chlorine anion in the complex. It means that still
after the elimination of CTPhPy, the 18e‾ sphere around
ruthenium is conserved. Conversely, the fragmentation of
[Ru(CYM)(β-diketonate)(PhPy)]+ leads to
a
coordinatively
have
phenylpyridine
prepared
imidazolium-based
charge-tagged
1 and Supporting
2-
unsaturated ruthenium complex. We do not expect a large effect
of the charge tag on the binding energy between phenylpyridine
and ruthenium, because the positively charged group is
separated by two methylene groups from the pyridine ring.
(
CTPhPy; see Scheme
Information for further details). The charge-tagged 2-
phenylpyridine was used as the reactant in our subsequent
studies of ruthenium(II) β-diketonate-assisted C-H activation.
Figure 5. ESI-MS spectrum of the ruthenium(II) catalyst and charge-tagged
phenylpyridine in acetonitrile.
A signal of the charge-tagged phenylpyridine dominates
the ESI-MS spectrum of the ruthenium catalyst and CTPhPy in
acetonitrile solution (Figure 5, reaction mixture C in Supporting
information). All ruthenium complexes are detected at much
lower intensity. The most abundant signal originates from the
ruthenium catalyst itself. In addition, we observe three signals of
complexes containing the ruthenium catalyst and the charge-
tagged 2-phenylpyridine: [Ru(β-diketonate)((CTPhPy)-H)]+ (m/z
614), [Ru(β-diketonate)(CTPhPy)Cl]+ (m/z 650) and [Ru(CYM)(β-
diketonate)(CTPhPy)Cl]+ (m/z 784).
The [Ru(β-diketonate)(CTPhPy-H)]+ complex is the product
of C-H activation. Its presence suggests that the charge-tagged
phenylpyridine is undergoing C-H activation. The remaining two
complexes can be the reaction intermediates through which C-H
activation reaction proceeds. The larger complex [Ru(CYM)(β-
diketonate)(CTPhPy)Cl]+ (m/z 784) retains all ligands of the
original ruthenium catalyst and bears the charge-tagged
Figure 6. a) CID spectrum and b) energy-resolved CID of the mass-selected
ion [Ru(CYM)(β-diketonate)(CTPhPy)Cl]+.
The last detected complex [Ru(β-diketonate)(CTPhPy)Cl]+
results from elimination of the p-cymene ligand from the
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800787
European Journal of Organic Chemistry
FULL PAPER
ruthenium catalyst. Such ruthenium(II) complexes with an O,O-
ligand and cleaved-off p-cymene ring have already been
identified as active intermediates.[22] Indeed, collisional activation
of this complex leads to the desired C-H activation (Figure 7b)
as the main fragmentation channel. The proton from the
phenylpyridine substrate is transferred to the chlorine anion that
eliminates as HCl, while the β-diketonate ligand is retained in the
complex together with the activated phenylpyridine (Figure 7a).
However, the appearance energy of HCl loss is 2.1 ± 0.1 eV
(Figure 7c), which is too high for C-H activation.
energy. Instead, this appearance energy corresponded to the
energy required for the elimination of neutral acetic acid from the
ruthenium complex, which was higher than the energy demand
of the C-H activation step.
The C-H activation reactions are performed in the
presence of excess K2CO3. Carbonate could potentially also
play a role in the C-H activation step as suggested previously.[8]
We have probed the reaction in the presence of K2CO3 (reaction
mixture D in the Supporting information) and we did not detect
any intermediates with a carbonate anion (Figure S8 in the
Supporting Information). The ESI-MS spectra of the reaction
mixtures containing the ruthenium catalyst and CTPhPy with and
without K2CO3 show an identical pattern (cf. Figure 5 and Figure
S8). This suggests that the role of carbonate is limited to the role
of a base that is required to neutralize the Brønsted acid
produced during the reaction.
To further exclude the active role of carbonate in the C-H
activation
reaction,
we
have
repeated
the
C-H
activation/coupling reaction reported for the [Ru(CYM)(β-
diketonate)Cl] catalyst with N,N-diisopropylethylamine (DIPEA)
instead of K2CO3 as a base (Scheme 2, see the Supporting
Information for more details).[13] DIPEA is a bulky amine that is
not expected to be directly involved in the C-H activation
reaction step. The conversion of 2-phenylpyridine to the arylated
products and the ratio of mono to diarylated products were in
agreement with the previously published data for the reaction in
the presence of K2CO3.[13] The conversion was about the same
(~ 70%) and the ratio of mono to diarylated products was 80 to
20 in the reaction with DIPEA compared to the 93 to 7 in the
reaction with K2CO3 (see Scheme 2). This result clearly shows
that the role of K2CO3 is analogous to the role of DIPEA that is
the role of a base.
Scheme 2. Ruthenium catalysed C-C coupling in the presence of K2CO3 or
N,N-diisopropylethylamine (DIPEA) as base.
Ultimately, the key question is: what is the role of the β-
diketonate ligand? Does the diketonate mediate C-H activation
in a similar, concerted mechanism, as reported for carboxylates,
or is the mechanism different? We have performed exploratory
DFT calculations for neutral [Ru(β-diketonate)(PhPy)Cl].[23] This
complex is analogous to the charge-tagged complex [Ru(β-
diketonate)(CTPhPy)Cl]+ that showed C-H activation. The
calculations suggest that the most stable structure of [Ru(β-
diketonate)(PhPy)Cl] contains a pre-activated 2-phenylpyridine
molecule (B in Figure 8). The next step can proceed either
through a ruthenium(IV) intermediate or through direct transfer
of the hydrogen atom to the chlorine atom or to one of the
oxygen atoms of the diketonate ligand (the more stable
structures are found upon transfer to the oxygen next to the
phenyl ring). DFT calculations provided several ruthenium(IV)
intermediates (the most stable intermediate is shown in Figure
Figure 7. a) Structural representation of the species involved in C-H activation,
b) CID spectrum and c) breakdown diagram as a function of the collision
energy of the mass-selected ion [Ru(β-diketonate)(CTPhPy)Cl]+. The black
marks represent the sum of all other fragments with higher appearance
energies, the loss of CTPhPy and (β-diketonate)H from the main fragment, and
CTPhPy.
We have previously reported an analogous C-H activation
reaction with a ruthenium acetate complex.[10] However, the
appearance energy for the elimination of acetic acid formed by
2-phenylpyridine C-H activation did not match the C-H activation
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800787
European Journal of Organic Chemistry
FULL PAPER
Figure 8. DFT-localized ruthenium complexes along the C-H activation reaction pathway (method: M06L/6-31+G*:
SDD on Ru). The ball-and-stick models show the optimized geometries of the most stable isomers of the given
complexes.
8), but the geometry of the pre-activated complex suggests that
the hydrogen atom could also be directly transferred to the
chlorine atom or to one of the oxygen atoms of the diketonate
ligand. However, we were unable to localise transition states for
this system; therefore, we cannot differentiate the two
mechanistic pathways: (1) direct H-transfer in the ruthenium(II)
complex or (2) formation of the ruthenium(IV) intermediate. In
any case, the ruthenium atom is actively involved in the
hydrogen transfer.
The activated hydrogen atom can be bound to the chlorine
atom or to the diketonate ligand. The latter is energetically more
favourable (by 60 kJ mol-1) than the former. However, the
elimination of the protonated diketonate is drastically
energetically demanding because of the formation of the highly
coordinatively unsaturated [Ru(PhPy-H))Cl] product. Such a
process would not occur in solution. Instead, the proton would
be transferred to a base (K2CO3 or DIPEA as shown in Scheme
2). In the gas phase, we experimentally observed the elimination
of HCl that corresponds to a higher-energy demanding C-H
activation pathway, but the final elimination of HCl is the
preferred fragmentation pathway.
Formation of such complexes is therefore not likely. The
exchange of the β-diketonate by HCO3‾ is endothermic by only 8
kJ mol-1. Such exchange is therefore also not likely. Moreover, if
such complex would be formed and would mediate the C-H
activation reaction, then all [RuCl2(arene)]2 type catalysts in the
presence of K2CO3 should be efficient in the C-H activation
reactions. This is not true. It was shown that ruthenium has to
have an additional electron-rich ligand to be efficient in the C-H
activation reaction.[7] The role of carbonate is therefore limited to
deprotonation of β-diketonate in the product complexes such as
D in Figure 8.
In conclusion, the DFT study suggests that the β-
diketonate is not directly involved in the C-H activation, in
contrast to C-H activation in carboxylates. Instead, β-diketonate
remains bidentally coordinated to the ruthenium atom throughout
the reaction pathway. The C-H activation step is assisted by the
ruthenium atom, which forms either a partial Ru-H bond or
undergoes full oxidative addition, thereby generating a fully
developed Ru-H bond.
Finally, we have also probed a possible involvement of
carbonate computationally. The exchange of Cl‾ by HCO3‾ in the
complexes A and B is endothermic by 36 kJ mol-1 and 30 kJ mol-
1, respectively (Figure S10 in the Supporting Information).
Conclusions
No ruthenium(II)-assisted C-H activation was observed in
positively charged complexes bearing β-diketonate in combined
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800787
European Journal of Organic Chemistry
FULL PAPER
ESI-MS and CID experiments. Instead, we consistently identify
the elimination of intact 2-phenylpyridine as the energetically
favoured reaction pathway. Therefore, we concluded that the C-
H activation most likely proceeds in neutral complexes, and we
have continued our studies using the charge-tagging method.
For this purpose, we have synthesised imidazolium-based
charge-tagged 2-phenylpyridine for further analysis of
ruthenium(II)-β-diketonate-assisted C-H activation. We have
observed C-H activation in the [Ru(β-diketonate)(CTPhPy)Cl]+
complex as HCl elimination. Further, we have excluded the role
of carbonate in the C-H activation step by control experiments.
DFT analysis of the C-H activation reaction in neutral
[Ru(β-diketonate)(PhPy)Cl] suggested that the β-diketonate
ligand remains bidentally coordinated to ruthenium throughout
the reaction pathway. The most stable structure of [Ru(β-
diketonate)(PhPy)Cl] contains pre-activated 2-phenylpyridine
with a partly developed Ru-H bond. The C-H activation can
proceed directly via ruthenium-assisted H-transfer to the β-
diketonate or via the ruthenium(IV) intermediate. The
experimentally observed hydrogen transfer to the chlorine anion
results from the gas-phase-favoured fragmentation pathway.
thank to the Management Committee of the COST Action
CA15106 (C-H Activation in Organic Synthesis – CHAOS) for a
Short Term Scientific Mission grant. The authors also thank to
Dr. Carlos V. Melo for proofreading the manuscript. We further
thank Fernando Bonin Okasaki for preliminary experiments.
Keywords: Ruthenium • Mass spectrometry • C-H activation •
Collision-induced dissociation • Charge-tagging method
[1]
[2]
Q. Zhao, T. Poisson, X. Pannecoucke, T. Besset, Synthesis 2017, 49,
4808-4826.
L. Ping, D. S. Chung, J. Bouffard, S.-G. Lee, Chem. Soc. Rev. 2017, 46,
4299-4328.
[3]
[4]
P. Nareddy, F. Jordan, M. Szostak, ACS Catal. 2017, 7, 5721-5745.
S. Murai, F. Kakiuchi, S. Sekine, Y. Tanaka, A. Kamatani, M. Sonoda,
N. Chatani, Nature 1993, 366, 529-531.
[5]
[6]
[7]
P. B. Arockiam, C. Bruneau, P. H. Dixneuf, Chem. Rev. 2012, 112,
5879-5918.
S. Oi, S. Fukita, N. Hirata, N. Watanuki, S. Miyano, Y. Inoue, Org. Lett.
2001, 3, 2579-2581.
a) L. Ackermann, R. Vicente, A. Althammer, Org. Lett. 2008, 10, 2299-
2302; b) L. Ackermann, R. Vicente, H. K. Potukuchi, V. Pirovano, Org.
Lett. 2010, 12, 5032-5035.
[8]
[9]
I. Özdemir, S. Demir, B. Çetinkaya, C. Gourlaouen, F. Maseras, C.
Bruneau, P. H. Dixneuf, J. Am. Chem. Soc. 2008, 130, 1156-1157.
Also see: C. Shan, X. Luo, X. Qi, S. Liu, Y. Li, Y. Lan, Organometallics
2016, 35, 1440−1445.
Experimental Section
The synthesis of the ruthenium(II) catalyst has been previously
reported.13 ESI-MS spectra were acquired with
[10] A. Gray, A. Tsybizova, J. Roithová, Chem. Sci. 2015, 6, 5544-5553.
[11] D. Zell, S. Warratz, D. Gelman, S. J. Garden, L. Ackermann, Chem. Eur.
J. 2016, 22, 1248-1252.
a linear ion trap
instrument LTQ equipped with an electrospray ionisation source. The
ions of interest were generated from the acetonitrile solution of the
ruthenium(II) catalyst, 2-phenylpyridine or imidazolium-based charge-
tagged phenylpyridine, both with and without potassium carbonate. The
details for the preparation of the reaction mixtures are included in
Supporting information. The electrospray voltage was 4.5 kV, and the
capillary was heated to 300°C. The sheath gas, flow rate and voltages of
capillary and lenses were optimised to maximise the signal of the
required ions. Energy-resolved CID experiments were performed using a
Finnigan LCQ Deca mass spectrometer equipped with an electrospray
ionisation source. For mass-selected ions, the excitation period was 30
ms and the trapping parameter was qz= 0.25. The Schröder’s calibration
method was used to calibrate the collision energy and to determine the
appearance energies.17 The calibration was performed by correlating the
[12] L. V. Graux, M. Giorgi, G. Buono, H. Clavier, Dalton Trans. 2016, 45,
6491-6502.
[13] S. Seršen, J. Kljun, F. Poꢀgan, B. ꢁtefane, I. Turel, Organometallics
2013, 32, 609-616.
[14] S. Seršen, J. Kljun, K. Kryeziu, R. Panchuk, B. Alte, W. Körner, P.
Heffeter, W. Berger, I. Turel, J. Med. Chem. 2015, 58, 3984 – 3996.
[15] Ch. Gaiddon, M. Pfeffer, Eur. J. Inorg. Chem. 2017, 1639–1654.
[16] a) A. L. Noffke, A. Habtemariam, A. M. Pizarro, P. J. Sadler, Chem.
Commun. 2012, 48, 5219–5246. b) J. J. Soldevila-Barreda, I. Romero-
Canelo, A. Habtemariam, P. J. Sadler, Nat. Commun. 2015, 6, 6582; c)
M. Tomas-Gamasa, M. Martinez-Calvo, J. R. Couceiro, J. L.
Mascarenas, Nat. Commun. 2016, 7, 12538.
[17] E. L. Zins, C. Pepe, D. Schröder, J. Mass Spectrom. 2010, 45, 1253-
1260.
[18] J. E. Carpenter, C. P. McNary, A. Furin, A. F. Sweeney, P. B.
Armentrout, J. Am. Soc. Mass Spectrom. 2017, 28, 1876-1888.
[19] a) G. Yassaghi, L. Jašíková, J. Roithová, Int. J. Mass Spectrom. 2016,
407, 92-100; b) J. Schulz, E. Shcherbachenko, J. Roithová,
Organometallics 2015, 34, 3979-3987; c) A. ꢁkríba, J. Schulz, J.
Roithová, Organometallics, 2014, 33, 6868-6878; d) J. Schulz, L.
Jašíková, A. ꢁkríba, J. Roithová, J. Am. Chem. Soc., 2014, 136, 11513-
11523; e) J. Hꢂvl, J. Roithová, Org. Lett. 2014, 16, 200-203.
[20] A. D. Dwivedi, C. Binnani, D. Tyagi, K. S. Rawat, P.-Z. Li, Y. Zhao, S. M.
Mobin, B. Pathak, S. K. Singh, Inorg. Chem. 2016, 55, 6739-6749.
[21] a) F. Coelho, M. N. Eberlin, Angew. Chem. Int. Ed. 2011, 50, 5261-
5263; b) C. Iacobucci, S. Reale, J.-F. Gal, F. De Angelis, Angew. Chem.
Int. Ed. 2015, 54, 3065-3068.
experimental appearance energies of
a
set of substituted
benzylpyridiunium ions [RBnPy]+ with the values determined by
Carpenter et al (Figure S5 in the Supporting Information).18 The values of
the appearance energies are given with the experimental uncertainties of
different measurements.
The DFT calculations were performed using the M06L functional[24],the
SDD basis set for ruthenium and the 6-31+G* basis set for the remaining
atoms, as implemented in the Gaussian program package.[25] All complexes
were fully optimized, and the minima were assessed by frequency calculations
(none of the second derivatives were imaginary). The geometries of the
optimized complexes can be found in Supporting Information.
[22] A. D. Dwivedi, C. Binnani, D. Tyagi, K. S. Rawat, P.-Z. Li, Y. Zhao, S. M.
Mobin, B. Pathak, S. K. Singh, Inorg. Chem. 2016, 55, 6739-6749.
[23] For a recent theoretical study on this type of ruthenium complexes see:
Z. Sochorová Vokáčová, I. Turel, J. V. Burda, J. Mol. Model. 2018, 24,
98.
Acknowledgements
[24] Y. Zhao, D. G. Truhlar, J. Chem. Phys. 2006, 125, 194101: 1-18.
[25] Gaussian 09, Revision D.01, M. J. Frisch, G. W. Trucks, H. B. Schlegel,
G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone,
G. A. Petersson, H. Nakatsuji, X. Li, M. Caricato, A. Marenich, J. Bloino,
This work was supported by the European Research Council
(ERC CoG IsoMS No. 682275) and by Charles University
Research Centre program No. UNCE/SCI/014. The authors
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800787
European Journal of Organic Chemistry
FULL PAPER
B. G. Janesko, R. Gomperts, B. Mennucci, H. P. Hratchian, J. V. Ortiz,
A. F. Izmaylov, J. L. Sonnenberg, D. Williams-Young, F. Ding, F.
Lipparini, F. Egidi, J. Goings, B. Peng, A. Petrone, T. Henderson, D.
Ranasinghe, V. G. Zakrzewski, J. Gao, N. Rega, G. Zheng, W. Liang,
M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T.
Nakajima, Y. Honda, O. Kitao, H. Nakai, T. Vreven, K. Throssell, J. A.
Montgomery, Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J. Heyd, E.
Brothers, K. N. Kudin, V. N. Staroverov, T. Keith, R. Kobayashi, J.
Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J.
Tomasi, M. Cossi, J. M. Millam, M. Klene, C. Adamo, R. Cammi, J. W.
Ochterski, R. L. Martin, K. Morokuma, O. Farkas, J. B. Foresman, D. J.
Fox, Gaussian, Inc., Wallingford CT, 2016.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800787
European Journal of Organic Chemistry
FULL PAPER
Entry for the Table of Contents (Please choose one layout)
Layout 1:
FULL PAPER
2-phenylpyridine C-H activation
catalysed by a ruthenium(II) β-
diketonate complex was studied by
ESI-MS and CID. We have identified
[Ru(β-diketonate)(CTPhPy)Cl]+ as an
active intermediate, and its collisional
activation leads to C-H activation.
DFT calculations were performed to
identify all ruthenium intermediates
along the C-H activation reaction
pathway.
C-H activation
Anamarija Briš, Iztok Turel, Jana
Roithová*
Page No. – Page No.
C-H Bond Activation by a
Ruthenium(II) β-diketonate
Complex: A Mechanistic Study
This article is protected by copyright. All rights reserved.