A Gentler Touch: Synthesis of Modern Ruthenium Olefin Metathesis Catalysts Sustained by Mechanical Force

Article abstract of DOI:10.1002/cctc.201901444

Mechanochemical synthesis of nine contemporary ruthenium catalysts used for olefin metathesis is described, being the first reported example of formation of Ru carbene organometallic complexes in solid state. Three key organometallic transformations commonly used in the synthesis of the second and third generations of Ru catalysts in solution—phosphine ligand (PCy₃) exchange with in situ formed N-heterocyclic carbene (NHC) ligand, PCy₃ to pyridine ligand replacement, and benzylidene ligands interchange—were proved to work under mechanochemical conditions, affording the targets in high purity. Mechanochemical approach not only requires less amounts of organic solvent (null for synthesis, only for purification) and is scalable, but also allows for transformations that were reported impossible in the solution phase.

Full text of DOI:10.1002/cctc.201901444

Full Papers
DOI: 10.1002/cctc.201901444
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A Gentler Touch: Synthesis of Modern Ruthenium Olefin
Metathesis Catalysts Sustained by Mechanical Force
Nirmalya Mukherjee,[a] Anna Marczyk,[a] Grzegorz Szczepaniak,[a] Adrian Sytniczuk,[a]
Anna Kajetanowicz,[a] and Karol Grela*[a]
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Mechanochemical synthesis of nine contemporary ruthenium
catalysts used for olefin metathesis is described, being the first
reported example of formation of Ru carbene organometallic
complexes in solid state. Three key organometallic transforma-
tions commonly used in the synthesis of the second and third
generations of Ru catalysts in solution—phosphine ligand
(PCy3) exchange with in situ formed N-heterocyclic carbene
(NHC) ligand, PCy3 to pyridine ligand replacement, and
benzylidene ligands interchange—were proved to work under
mechanochemical conditions, affording the targets in high
purity. Mechanochemical approach not only requires less
amounts of organic solvent (null for synthesis, only for
purification) and is scalable, but also allows for transformations
that were reported impossible in the solution phase.
Introduction
(c) Route 3: Exchange reaction in which a PCy3 ligand is
replaced with a pyridine ligand to obtain third generation
Ru catalysts (Figure 1).
Catalytic olefin metathesis evolved into a powerful and versatile
methodology for the assembly of carbon-carbon bonds.[1–2] So-
called second and third generation ruthenium metathesis
catalysts bearing the privileged N-heterocyclic carbene (NHC)
ligands, are currently finding their first applications in pharma-
ceutical production.[3] Industrially, the biggest application (by
volume) utilizing olefin metathesis is located in polymers and
composites area.[4] For this purpose a highly specialized class of
so-called latent metathesis catalysts has been developed.[5–7]
Recent advances expanding the potential of the free carbenes
(particularly cyclic (alkyl)(amino) carbenes (CAAC))[8–9] as ligands
for Ru, made another large-scale application of metathesis
finally possible—a biomass transformation via ethenolysis.[10–11]
At the same time, the most popular benzylidene, indenylidene
and Hoveyda-Grubbs complexes continue to dominate current
academic research.[1–3] The second and third generation cata-
lysts are typically accessed via ligand exchange reactions
utilizing easily obtainable Ru complexes as starting materials.
The most frequently used routes can be classified as follows:
(a) Route 1: Exchange reaction in which a PCy3 ligand is
replaced with a carbene ligand (NHC or CAAC; Figure 1)
All these transformations (with a partial exception of Route
3, where the excess of a liquid pyridine serves as the solvent)[12]
have been made always in solutions, utilizing organic solvents,
such as toluene, dichloromethane (DCM) or hexane to dissolve
the reagents.[1–2] In addition to obvious practical inconvenience
(handling of anhydrous solvents under inert atmosphere), in
some cases these routes (Figure 1) suffer also from loses of
product due to its partial solubility, decomposition during
isolation and contamination with various impurities, which is
discussed in detail below.
At the same time, mechanochemistry and, more specifically,
ball-milling is becoming an increasingly valuable technique for
solvent-free (or at least partially solvent free) and environ-
mentally friendly synthesis of organic compounds (catalysed
and uncatalysed).[13–15] The metal-catalysed organic syntheses
under mechanochemical conditions include also one report on
olefin metathesis reactions in
a
ball-mill.[16] On contrary,
examples of organometallic complexes assembled by mecha-
nochemistry are less populated, however, recently a number of
elegant contributions have been published on synthesis of
simple NHC complexes of Pd, Cu and Au[17–22] as well as on the
synthesis of NHC ligand precursors.[23]
(b) Route 2: Alkylidene ligand metathesis-exchange, where a
Ru complex (usually benzylidene or indenylidene one)
reacts in a stoichiometric metathesis reaction with a
corresponding styrene derivative (Figure 1).
However, according to our knowledge, a mechanochemical
approach to synthesis of sophisticated multi-ligand carbene-
alkylidene complexes of ruthenium has never been reported.
The reason for this can be associated to the relative fragility of
these complexes and their sensitivity to heat resulted during
grinding. During the key study on mechanochemical olefin
metathesis it was reported that Ru catalysts were unstable
when steel jar and balls were used.[16] On the other hand,
problems related to synthesis of these complexes in solution
are also known. For example, oxygen, moisture, Brønsted bases
and some other reagents or solvents used during the solution
phase synthesis pose threats to quality of the obtained complex
(see below for a more detailed discussion). Fogg has proven
[a] Dr. N. Mukherjee, A. Marczyk, Dr. G. Szczepaniak, Dr. A. Sytniczuk,
Dr. A. Kajetanowicz, Prof. K. Grela
Faculty of Chemistry, Biological and Chemical Research Centre
University of Warsaw
Żwirki i Wigury 101
Warsaw 02-089 (Poland)
E-mail: karol.grela@gmail.com
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/cctc.201901444
This manuscript is part of the Special Issue on New Concepts in Homo-
geneous Catalysis.
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Figure 1. Modern Ru metathesis catalysts and key transformations in their preparation. Outside the circle are selected second (marked blue) and third
generation catalysts (Gru-III and Gru-III’, marked green), inside the circle are common precursors, incl. first generation catalysts Hov-I, Gru-I, Ind-I (marked
red). Circle represents three key transformations in second and third generation catalysts synthesis.
that various batches of commercial catalysts can contain Ru Results and Discussion
nanoparticles that can cause unwanted side reactions.[24]
Therefore, we decided to check the utility of the mecha-
nochemical methods in preparation of advanced second and
third generation Ru metathesis catalysts. Here we report the
success of this approach, illustrated with synthesis of nine
contemporary catalysts, some of them being already the classics
(Hov-II, Ind-II, Ind-II’), two being activated analogues of robust
Hoveyda-Grubbs system (Gre-II, Est-II), and third generation
complex Gru-III and Gru-III’. In addition, two specialized
complexes designed for industrially important transformations
—ring opening metathesis polymerization (Lat-II) and ethenol-
ysis (Ber-II)—were targeted, due to their increasing commercial
potential.
Mechanochemical synthesis of Hoveyda-Grubbs catalysts
Hov-II (PCy3!NHC exchange reaction). Proof-of-concept and
optimization. Second generation catalysts can be economically
accessed from the corresponding inexpensive first-generation
complexes via Route 1, in which a PCy3 is replaced with an NHC
ligand. Classically, this route relies on in situ generation of free
carbenes, via treatment of various imidazolinium salts with a
strong base such as t-BuOK, LiHMDS, potassium t-amylate (t-
AmOK), etc. This method is deceptively simple experimentally,
and utilizes inexpensive imidazolinium salts, however a long list
of warnings and failures related to it was reported in literature,
forcing chemists to look for alternatives.[25–31] The catalytic
activity of the resulted second generation Ru complex can be
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Scheme 1. Mechanochemical synthesis of Hoveyda-Grubbs catalyst Hov-II. General concept and optimization variables. LiHMDS=lithium 1,1,1,3,3,3-
hexamethyldisilazane.
Table 1. Optimization of Hov-II catalyst preparation by PCy3 to NHC exchange.[a]
Entry
Grinding Auxiliary
Jar
Additive (1.5 equiv.)
Frequency [Hz]
Time [min]
Isolated Yield [%]
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2
3
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8
NaCl
agate
agate
agate
steel
steel
steel
steel
steel
steel
steel
steel
steel
steel
steel
steel
none
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120
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90
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15
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40
56
59
18
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67
none
none
none
none
none
NaCl
celite
none
none
none
none
none
toluene
CH2Cl2
none
CuCl[b]
CuCl
CuCl
CuCl
CuCl
CuCl
tartaric acid
citric acid
benzoic acid
NH4Cl
CHCl3
CuCl
CuCl
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[a] Reaction conditions: jar charged under argon with SIMes×HCl (1.2 equiv.), Hov-I (1 equiv.), LiHMDS (1.1 equiv.), grinding auxiliary (100 wt.% for solids;
°
25 μL for liquids), additive (1.5 equiv.). The temperature of the vessel at the end of milling was not exceeding 37 C, [b] 1.2 equiv.
reduced or even spoiled completely by traces of unreacted
imidazolinium salts or alkali metal base, and various other
contaminants, including dangerous Ru-hydrides, formed during
the process, or during the work-up upon action of methanol or
water added to quench the excess of base.[31] The in situ
generated free NHC is sensitive to water and CO2, so
unintended exposure to air must be avoided during the
reaction course. On the other hand, high crystalline nature of
the popular imidazolinium salts and possibility of drying them
and storing over long periods of time is a valuable aid to the
reproducibility. Therefore, despite all difficulties discussed so
diligently by Fogg,[31] we decided to choose the imidazolinium
salt SIMes×HCl as the model NHC precursor due to its low cost
and easy synthesis.
To check if the concept of free carbene generation and
ligand exchange in solid state is doable, a set of initial reactions
(Scheme 1) was conducted in a Retsch MM400 mill, using
0.15 mmol reaction scale in a 10 mL steel milling jar charged
under argon, milled at 28 Hz using one stainless steel ball
(12 mm diameter) and NaCl as grinding auxiliary. Different
bases (t-AmOK, t-BuOK, Cs2CO3, K2CO3, KHMDS, LiHMDS) were
screened to convert SIMes×HCl into free SIMes that can react
with solid Hov-I present in the same jar. The best result (around
15% of yield) was obtained in the case of LiHMDS. In order to
improve the yield, different jar materials (steel, agate, Teflon),
grinding auxiliaries (none, Al2O3, NaCl, and liquids), number of
balls and milling frequencies (25–30 Hz) were tested. In an
agate jar at 28 Hz the yield was improved to 43%, the value
that allowed us to demonstrate the validity of our proof-of-
concept, but not high enough to be competitive with classical
“in solution” synthesis. It is well known that formation of Hov-II
can be inhibited by the interaction of PCy3 ligand, and therefore
the synthesis of this complex is commonly driven by addition of
various phosphine scavengers, such as solid CuCl,[32] various
exchange resins,[30,31,33] or even CHCl3.[34]
In our screening we tested, therefore, various additives
starting from previously optimized conditions (Table 1, en-
tries 1–2) and applying modifications in due course. Surpris-
ingly, conventional steel jars gave best results,[35] and we found
that shorter milling time and higher frequency give better
results. The best PCy3-scavenger was undoubtedly CuCl (en-
try 5), however, interesting results were found with citric and
tartaric acid, never tested before in the context of second
generation catalyst preparation (entries 9–10). Promising was
ammonium chloride (NH4Cl, entry 12), unfortunately observed
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corrosion of the stainless steel jar surface discouraged us from
further trials. (Similar effect was exhibited by KHSO4, see SI).
Benzoic, p-toluenesulfonic and camphorsulfonic acids as
well as liquid auxiliaries (as in the liquid assisted grinding
technique)[36] gave lower yields of Hov-II (Table 1).
of the double bond, was chosen to check if the catalyst
produced by us is free from traces of hazardous ruthenium by-
products. We were, therefore, pleased to see that in both
reactions the catalytic profiles exhibited by the mechanochemi-
cally obtained catalyst matched or even slightly outperformed
in activity the commercial sample. Importantly, despite the RCM
of diene 3 was conducted at relatively high temperature, no
other products than 4 were observed. The lack of CÀ C double
bond isomerization observed for both 0.1 mol% and 500 ppm
loadings suggests that no traces of ruthenium hydrides nor
other impurities that can deviate the reaction course were
present in the sample of Hov-II prepared by grinding.
Mechanochemical synthesis of other modern catalysts via
PCy3!NHC and CAAC exchange reaction. Having proven the
possibility of NHC generation and exchange under mechano-
chemical conditions, we attempted to check the scope and
limitations of this method by preparing other advanced second
generation catalysts. First, we studied phosphine to SIMes and
IMes ligands exchange in popular Ind-I complex (Scheme 2a).
We were pleased to find that the milling sequence we have
developed previously, works also in this case, and afforded,
after filtration through SiO2 and evaporation of the solvent, the
ex-Evonik Catmetium® RF catalyst (Ind-II’) in 64% yield and
excellent purity (Scheme 2a). While the originally reported
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Under the optimized conditions we used CuCl (added after
15 minutes of milling to avoid formation of NHCÀ Cu complex),
a steel jar with two balls and 30 minutes of total milling time at
30 Hz, to afford cleanly Hov-II as a green powder in 82%
isolated yield (Scheme 1, Table 1 entry 6), after the usual SiO2
filtration and crystallization (the same conditions were tested
also in a larger scale without silica gel use, vide infra). In
comparison, the original route gave Hov-II in 85% yield after
work-up and purification.[37] This complex was virtually pure by
analytical techniques (see SI). To finally check if the activity
profile of such obtained Hov-II can match the activity of the
commercial catalyst (from Sigma-Aldrich) two model ring-
closing metathesis (RCM) tests were conducted utilising the
catalysts at loading of 0.1 mol% (see ESI) and 500 ppm (Fig-
ure 2). The first target (1) is a standard benchmark RCM
substrate, recommended by Grubbs,[38] while the second diene
(3), being more susceptible to a RuÀ H promoted isomerization
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Figure 2. Testing the catalytic activity of mechanochemically prepared
Hoveyda-Grubbs complex. Top: Model RCM reaction of 1 (500 ppm catalyst
loading). Bottom: Model RCM reaction of 2 (500 ppm catalyst loading).
Conversion by GC against an internal standard. Comm.=Commercial
catalyst; Synth.=catalyst synthesized mechanochemically. Lines are visual
aid only.
Scheme 2. Mechanochemical synthesis of other Ru catalysts via PCy3 with
NHC (or CAAC) exchange. a) Synthesis of Umicore Grubbs M2 (Ind-II) and
Evonik Catmetium® RF catalyst (Ind-II’); b) Synthesis of Bertrand-Grubbs
CAAC complex Ber-II; c) Preparation of nitro-catalyst Gre-II.
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method in an anhydrous hexane solution was giving Ind-II’ in
79%, so in 15% higher yield,[39] we think that simplicity of the
milling method that does not require drying the solvent, is in
part balancing this. Repeating the same procedure with SIMes×
HCl gave the saturated analogue Ind-II in similar isolated yield
(Scheme 2a).
Bertrand-Grubbs complex (Ber-II) is an important catalyst in
the context of ethenolysis of bio-sourced unsaturated fatty
acids.[8–10] Therefore, we were pleased to see that under
previously established conditions CAAC×HCl can be deproto-
nated to form the free cyclic (alkyl)(amino) carbene that reacts
in the same milling chamber with solid Hov-I to yield the
ethenolysis catalyst Ber-II in 65% yield (Scheme 2b).
In order to compare the activity of catalysts obtained in a
ball mill with the classically made Ber-II, a model ethenolysis
reaction of ethyl oleate 5 was made (Scheme 3). Importantly,
this experiment exhibited the same activity and selectivityof the
mechanochemically made complex (for details see SI).
The above described PCy3 to NHC and CAAC ligand
exchange reactions were successful, but one can point out that
the yields obtained by us were only comparable (Scheme 1) or
even slightly lower (Scheme 2a–b) than those obtained in
classical reactions in solution. To check if the milling method
can really bring a new opportunity into some “problematic” Ru
catalysts syntheses, we decided to try a direct ligand exchange
between Gre-I and the SIMes ligand. Direct synthesis of the
nitro-activated catalyst Gre-II from its first generation precursor
was tried by us in the solution many times, but without
success,[40] probably because of low stability of Gre-I under
strongly basic conditions required for in situ generation of the
free NHC ligand. Therefore, we were pleased to see that in the
solid state 36% of Gre-II can be obtained by a direct metalation
of SIMes (Scheme 2c).
Mechanochemical synthesis of Ru catalysts via alkylidene
metathesis-exchange. The second most popular method for
synthesis of advanced ruthenium benzylidene metathesis
catalysts is based on alkylidene ligands metathesis-exchange
process.[41] In this method a 2nd generation complex (e.g. Gru-II
or Ind-II) reacts with a corresponding styrene derivative, under-
going a cross metathesis-alkylidene ligands exchange reaction.
Such reactions are very well optimized in a solution, leading to
many useful catalysts in a laboratory and semi-preparative scale.
Analogously, we decided to check if the same reaction can be
made under mechanochemical conditions (Scheme 4).
As we found, the EWG-activated complex Gre-II can be
straightforwardly obtained without a solvent in almost quanti-
tative yield (94%, Scheme 4a). It shall be noted that the same
reaction in solution gives slightly lower yield (76%). To check
the activity of the mechanochemically made EWG-activated
catalyst Gre-II we used it in a challenging RCM macrocyclisation
of 13 leading to a macrocyclic musk 14,[42] and were pleased to
find that it shows the same activity as the commercial Apeiron-
Synthesis catalyst (Scheme 5).
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Scheme 3. Ethenolysis of ethyl oleate 5 utilising commercial (comm.) and
mechanochemically (synth.) prepared Ber-II. Conv.=100À [(final moles of
5)×100/(initial moles of 5); Sel.=100×(moles of 6+7)/([moles of 6+7)
+(2×moles of 8+9)].
Similarly, the chelating-ether modified complex Est-II,
utilized in BILN 2061 hepatitis C antiviral agent production,[43]
Scheme 4. Mechanochemical synthesis of Ru catalysts via alkylidene metathesis-exchange. a) Synthesis of Apeiron Nitro Catalyst (Gre-II) b) Synthesis of an 18-
electron bis-chelated catalyst (Est-II); c) Preparation of Apeiron LatMet polymerization catalyst (Lat-II).
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catalysts from solid pyridine derivatives, such as 4-dimeth-
ylaminopyridine (DMAP) must be done in an organic solvent.[47]
To illustrate the applicability of mechanochemical methods in
synthesis of this type of complexes, we obtained catalyst Gru-
III’, disclosed in the patent literature.[47] As we checked, milling
of a mixture of solid Gru-II and DMAP (two steel balls) led to
formation of Gru-III’ in 87% yield (Scheme 6 bottom).
Outlook, larger scale experiment and green chemistry
context. Experiments described herewith show that despite
some initial fears, diverse types of advanced Ru alkylidene
complexes can be obtained mechanochemically, in steel. Three
prototypical methods of assembling the 2nd generation Ru
metathesis catalysts were tested (NHC metalation; benzylidene
ligands metathesis; neutral ligands exchange) and all of them
seem to be operational at milling conditions. The yields
obtained were in some cases lower, in some cases higher as
compared with classical methods, however, importantly, at least
in two cases (Gre-II, Lat-II) we have shown that the reactions
that are problematic in a solution proceed better under
mechanochemical conditions. We can only speculate that this is
because of different stability of reactive species, such as NHC
free carbenes or Gre-I, in the solid form. This observation is also
of practical importance and can have some consequences in
synthesis of specialized Ru-complexes.
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Scheme 5. RCM of diene 13 utilising commercial (comm.) and mechano-
chemically (synth.) prepared Gre-II.
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was obtained using ball milling in the yield comparable to the
one reported previously in a solution (71%).[44]
Next, we decided to check if the mechanochemistry can
bring some additional value to synthesis of a latent catalyst for
olefin metathesis polymerization reactions. A ruthenium pheno-
late complex Lat-II, a commercially available catalysts for
ROMP,[5] is typically synthesized from Gru-II precursor and 2-
propenylphenol in a presence of PCy3 used to bind HCl formed
in the reaction.[45,46] As the use of the costly and air-sensitive
cycloalkyl phosphine is not advantageous practically, we were
looking for a more economical and simpler method, utilizing
the easily available and inexpensive sodium salt 12 (Scheme 4c).
Interestingly, while the same reaction in a solution was giving
only 18% isolated yield (see SI) and suffered from low
reproducibility, under mechanochemical conditions complex
Lat-II was formed in a satisfactory yield of 59%.
Mechanochemical synthesis of a third generation catalysts
via PCy3!pyridine exchange. To test yet another type of
exchange in the coordination sphere of Ru, we attempted to
obtain a so-called third generation catalyst Gru-III, bearing
pyridine ligands instead of phosphines. Interestingly, this
valuable polymerization catalyst is prepared in solvent free
conditions, because the excess of a liquid pyridine used in the
exchange reaction can act as the solvent.[12] Using mild
mechanochemical conditions (one Telfon ball and low fre-
quency), we were able to obtain the popular Gru-III under
conditions that can be related to the liquid assisted grinding[47]
(Scheme 6 top). In contrast, synthesis of other III-generation
In addition, the scalability of mechanochemical methods
was preliminary tested by us by repeating the synthesis of Hov-
II in 0.5 g scale without the use of column chromatography
(Scheme 7). We were pleased to see that the reaction
proceeded in this scale without problems, and despite the
product was purified only by crystallization, without use of silica
gel purification, it was obtained in good yield and in high purity
(see SI).
Excluding—even in part[48]—of solvents during the synthesis
of sophisticated organometallic complexes, such as the modern
Ru catalysts, is advantageous from the practical point of view,
as the solvents must be rigorously dried and degassed before
use, which is costly, and if not done correctly leads to non-
Scheme 7. Mechanochemical synthesis of Hov-II without using column
chromatography. Grey box shows the solvent-free part of the preparation;
operations marked in blue were made in air with standard not-dried
solvents. Scale of synthesis: 0.5 g. For details see SI.
Scheme 6. Mechanochemical synthesis of Ru third generation catalyst Gru-III
and Gru-III’ via PCy3!pyridine exchange.
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reproducible results.[31] Minimizing the use of solvents is also
important from the green chemistry point of view. Using the
preparation of Gre-II from Ind-II (Scheme 4a) as the practical
example, we conducted calculations of green chemistry
metrics.[49] We found that Reaction Mass Efficiency (RME) and
especially the Environmental (E) factor were better in the case
of mechanochemical synthesis of Gre-II (see SI for details).
The benefit of metathesis catalysts production by milling of
solid reagents, as compared to classical conditions in a solution
is, however, the most visible when so-called Ecoscale score[50] is
considered. Ecoscale gives a score from 0 to 100 taking into
account variables such as cost, safety, technical set-up, energy
and purification. According to the definition, the Ecoscale is
calculated by assigning a value of 100 to an ideal reaction and
then subtracting penalty points for non-ideal conditions. As we
calculated, the Ecoscale score for the preparation of Gre-II by
mechanochemical methods is 54, while the same reaction
conducted in a solution gives only 32 points, which shall be
considered as less favourable in a modern chemical synthesis.[49]
As the key NHC-precursors used by us can also be obtained
under mechanochemical conditions,[23] this renders the addi-
tional advantage of the presented methodology.
green crystals were filtered off on a Büchner funnel with glass frit
and, washed twice with small portions of methanol (2–3 mL). The
resulted crystals were dried under vacuum to afford Hoveyda-
Grubbs 2nd generation catalyst Hov-II (382 mg, isolated yield 72%).
1H NMR (400 MHz, CD2Cl2) δ 16.51 (s, 1H), 7.57-7.53 (m, 1H), 7.08 (s,
4H), 6.98-6.89 (m, 2H), 6.84 (d, J=8 Hz, 1H), 4.89 (sept, J=8 Hz, 1H),
4.15 (s, 4H), 2.44 (s, 12H), 2.41 (s, 6H), 1.22 ppm (d, J=4 Hz, 6H); 13C
NMR (101 MHz, CD2Cl2) δ 296.1 (d, J=16.2 Hz), 211.3, 152.5, 145.7,
139.4, 129.9, 129.8, 122.8, 122.7, 113.5, 75.7, 52.1, 21.4, 21.3,
19.7 ppm. The spectra correspond to those described in the
literature.[37]
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Mechanochemical synthesis of Gre-II from Ind-II. A dry 10 mL
stainless steel ball mill jar was equipped with two stainless steel
balls (12 mm) and placed under inert atmosphere. The jar was
charged with 1-isopropoxy-4-nitro-2-propenylbenzene (1.2 equiv.,
21.2 mg), complex Ind-II (1 equiv., 75.9 mg) and CuCl (1.5 equiv.,
12 mg) and subjected for milling at 30 Hz frequency for 30 minutes.
After this point forth, all manipulations were carried out in air. The
green solid mass was extracted with ethyl acetate (12-15 mL),
concentrated in vacuo, and the resulting material was purified by
filtering through a column of silica. Elution with n-hexane/EtOAc
(8:2 v/v) removed the desired compound as a green band. Removal
of the solvent, the green residue was then dissolved in a 1:3 v/v
mixture of CH2Cl2 and methanol at ambient temperature. After
concentration of this solution to ca. one-fourth of the initial volume
at room temperature using a rotary evaporator green crystals were
precipitated. The rest of the methanol was decanted, and the
product was washed with n-hexane (2×1.5 mL) and dried in a
rotary evaporator and then on the vacuum pump (50.5 mg, 94%).
Conclusions
To sum up, the mechanochemical methodology can be seen as
a valuable addition to the existing solution-based preparation
methods of selected 2nd generation Ru metathesis catalysts,[51]
affording the expected targets in high purity and activity fully
comparable to the same catalysts obtained in solution. Not only
does it reduce the amount of solvent used for synthesis, but it
can also expedite catalyst production relative to traditional
Note: Authors contributions: NM made majority of ball-mill
experiments, except Gru-III synthesis; AM participated in early
experiments; AS made comparative metathesis experiments
and obtained Gru-III; GS initiated this research, AK and KG
supervised it and wrote manuscript.
methods.[52] We believe that this technique will gain more Acknowledgements
importance for synthesis of advanced organometallic com-
plexes, especially in the context of its very recent recognition
by IUPAC as one of top ten chemistry innovations that will
change the world.[53,54]
The authors are grateful to the „Catalysis for the Twenty-First
Century Chemical Industry” project carried out within the TEAM-
TECH programme of the Foundation for Polish Science co-financed
by the European Union under the European Regional Develop-
ment Fund. The study was carried out at the Biological and
Chemical Research Centre, University of Warsaw, established
within the project co-financed by European Union from the
European Regional Development Fund under the Operational
Programme Innovative Economy, 2007–2013.
Experimental Section
Mechanochemical preparation of Hov-II: A dry 10 mL stainless
steel ball mill jar was equipped with two stainless steel balls
(12 mm) and placed under inert atmosphere. The jar was charged
with SIMes×HCl (1.2 equiv., 350 mg), Ru 1st generation complex
(Hov-I) (1 equiv., 511 mg) and lithium bis(trimethylsilyl)amide
(1.1 equiv., 161 mg) and subjected for milling at 30 Hz frequency
for 15 minutes. Then solid CuCl (1.5 equiv., 128 mg) was added in
one portion to the same reaction jar and further subjected to ball
milling for 30 min at 30 Hz. After this point forth, all manipulations
were carried out in air. The dark brown-green solid mass was
extracted with ethyl acetate (25–30 mL). The solution was filtrated
through a Büchner funnel with glass frit filled with neutral Celite.
Then the filtrate was evaporated to dryness under reduced
pressure. The dark brown residue was then dissolved in 1:10 v/v
mixture of CH2Cl2 and methanol (16 mL) at ambient temperature.
After concentration of one fourth of the initial volume using a
rotary evaporator (without immersion in a water bath, the flask
should be covered by frost) green crystals were precipitated. The
Conflict of Interest
The authors declare no conflict of interest.
Keywords: green chemistry · mechanochemistry · NHC ligands ·
olefin metathesis · organometallic complexes
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[52] Authors are grateful to the Referees for suggesting us preparing Gru-III
and testing the catalysts obtained by milling in a number of challenging
metathesis transformations and for other valuable comments.
[53] F. Gomollón-Bel, Chem. Int. 2019, 41, 12–17.
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[29] Imidazolinium bicarbonate salts (not to be mistaken with NHC-CO2
adducts mentioned above) seem to be promising in situ NHC
precursors, despite they have to be obtained with a special ion-
Manuscript received: August 7, 2019
Revised manuscript received: September 23, 2019
Version of record online: ■■■, ■■■■
ChemCatChem 2019, 11, 1–9
www.chemcatchem.org
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FULL PAPERS
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Dr. N. Mukherjee, A. Marczyk, Dr. G.
Szczepaniak, Dr. A. Sytniczuk, Dr. A.
Kajetanowicz, Prof. K. Grela*
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A Gentler Touch: Synthesis of
Modern Ruthenium Olefin Meta-
thesis Catalysts Sustained by Me-
chanical Force
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The first solid state synthesis of
phosphine ligand (PCy3) exchange
with in situ formed N-heterocyclic
carbene (NHC) ligand, PCy3 to
pyridine ligand replacement, and
benzylidene ligands interchange—
work efficiently under mechanochem-
ical conditions.
ruthenium carbene organometallic
complexes used asolefin metathesis
catalysts is described. It was shown
that three key organometallic trans-
formations commonly used in the
synthesis of the second and third gen-
erations of Ru catalysts in solution—