Cu(0), O2 and mechanical forces: a saving combination for efficient production of Cu-NHC complexes

Article abstract of DOI:10.1039/c6sc03182j

Mechanical forces induced by ball-milling agitation enabled the highly efficient and widely applicable synthesis of Cu-carbene complexes from N,N-diaryl-imidazolium salts and metallic copper. The required amount of gaseous dioxygen and insoluble copper could be reduced down to stoichiometric quantities, while reaction rates clearly outperformed those obtained in solution. Utilisation of Cu(0) as the copper source enabled the application of this approach to a wide array of N,N-diaryl-imidazolium salts (Cl^-, BF₄^- and PF₆^-) that transferred their counter anion directly to the organometallic complexes. Cu-NHC complexes could be produced in excellent yields, including utilisation of highly challenging substrates. In addition, five unprecedented organometallic complexes are reported.

Full text of DOI:10.1039/c6sc03182j

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Cu(0), O2 and mechanical forces: a saving
combination for efficient production of Cu–NHC
complexes†
Cite this: DOI: 10.1039/c6sc03182j
*
*
Audrey Beillard, Thomas-Xavier Metro, Xavier Bantreil, Jean Martinez
´
*
and Frederic Lamaty
´ ´
Mechanical forces induced by ball-milling agitation enabled the highly efficient and widely applicable
synthesis of Cu–carbene complexes from N,N-diaryl-imidazolium salts and metallic copper. The
required amount of gaseous dioxygen and insoluble copper could be reduced down to stoichiometric
quantities, while reaction rates clearly outperformed those obtained in solution. Utilisation of Cu(0) as
the copper source enabled the application of this approach to a wide array of N,N-diaryl-imidazolium
Received 19th July 2016
Accepted 16th September 2016
salts (Clꢀ, BF4 and PF6ꢀ) that transferred their counter anion directly to the organometallic complexes.
ꢀ
DOI: 10.1039/c6sc03182j
Cu–NHC complexes could be produced in excellent yields, including utilisation of highly challenging
substrates. In addition, five unprecedented organometallic complexes are reported.
www.rsc.org/chemicalscience
on the outstanding efficacy of using ball-mills to react mate-
rials with high physical state heterogeneity. Used as catalysts
in a wide range of reactions,27–31 Cu–NHC complexes are
Introduction
The application of mechanical forces to solvent-free or solvent-
less reaction mixtures through the use of ball-mills offers many
advantages over traditional solvent-based strategies,1–5 espe-
cially when using poorly soluble, undissolved or insoluble
reactants such as metals.6–16 Yet, these examples are limited to
reactions between solid chemicals with liquid or so solid
reagents. In addition, the use of ball-mills to promote reactions
involving solid reactants with gaseous reagents has been
described previously.17,18 Yet, the ball-milling efficiency in
reacting chemicals with a high physical state heterogeneity (so
material, gas, liquid and solid) has been explored only scarcely.
In 2015, the reduction of organic molecules (so material) in
the presence of H2 (gas), generated by mechano-mediated
reduction of water (liquid) with zero-valent chromium (solid),
was reported.19 In the same year, a study described the mech-
anochemical Rh(III)-catalyzed C–H bond functionalization of
acetanilides (so material) in the presence of alkyl acrylates
(liquid) and a large excess of molecular oxygen (gas) as the
terminal oxidant.20
generally synthesised by deprotonation of imidazolium
precursors with a strong base followed by reaction with Cu(I).
Although interesting, a less frequent alternative is the use of
metallic Cu(0) as the copper source. This route enables the
transfer of the imidazolium counter anion directly to the Cu–
NHC complexes,32–36 thereby providing easier access to a wider
range of copper complexes. Unfortunately, these solvent-
based reaction conditions require a large excess of insoluble
Cu(0) and long reaction times.
Results and discussion
When IMes$HCl was treated with 5 equivalents of Cu(0) under
magnetic stirring in reuxing water (Fig. 1), only 19% conver-
sion was obtained aer 8 h of reaction. On the other hand, 80%
of IMes$HCl was converted into [CuCl(IMes)] when mixed with
5 equivalents of Cu(0) in a planetary ball-mill (pbm) agitated at
450 rpm for 8 h, without external heating. When adding small
amounts of water as a grinding assistant (0.3 mL per mg of
reactants), complete conversion could be reached aer only 3
h.37 These ball-milling conditions were so efficient that only 1.0
equivalent of insoluble Cu(0) was enough to obtain >95%
conversion aer 8 h (Fig. 1). This impressive increase in the
reaction rate could be explained by the highly concentrated
reaction media, along with the highly efficient mixing that
prevented mass transfer limitations. Indeed, no conversion
could be observed when this reaction was performed with small
amounts of water (0.3 mL per mg of reactants) and placed under
reux with magnetic stirring (Fig. 1). Though reactions
Continuing our efforts to provide the community of chemists
with more efficient ways to produce high value molecules,7,21–26 we
describe herein the mechanosynthesis of Cu–NHC complexes
(NHC ¼ N-heterocyclic carbene). This study includes details
´
´
Institut des Biomolecules Max Mousseron (IBMM), UMR 5247, CNRS, Universite de
`
Montpellier, ENSCM, Campus Triolet, Place Eugene Bataillon, 34095 Montpellier
cedex 5, France. E-mail: thomas-xavier.metro@umontpellier.fr; xavier.bantreil@
umontpellier.fr; frederic.lamaty@umontpellier.fr
† Electronic supplementary information (ESI) available: Operating procedures
and characterization data. See DOI: 10.1039/c6sc03182j
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isolated efficiently within a few hours. The 4,5-dimethyl-
substituted imidazolium derivatives IMesMe$HCl and IPr-
Me$HCl, which are known to be less reactive, could also be
converted to the corresponding copper complexes in excellent
yields with the ball-milling approach. Besides, the previously
unreported [CuCl(SIMesMe)] complex was also isolated in
excellent yield by applying these reaction conditions.
The role of dioxygen in the course of the reaction was next
investigated (Fig. 2). When IMes$HCl was treated with 5
equivalents of Cu(0) under inert atmosphere (N2) in a hermeti-
cally closed reactor, no conversion into [CuCl(IMes)] could be
detected, thus conrming the participation of atmospheric O2
to the overall process. According to eqn (1) (Fig. 2), 1 mmole of
O2 could react with 4 mmoles of imidazolium. The reaction was
thus repeated under ambient atmosphere with 0.62 mmoles of
IMes$HCl and 3.08 mmoles of Cu(0) in a 12 mL reactor for
which the free volume contained 79.6 mmoles (0.52 equivalent)
of O2 under these conditions.39,40 Conversion of IMes$HCl into
[CuCl(IMes)] reached a maximum at 29%, thereby conrming
that with these conditions, the reaction was limited by the
amount of O2 present in the reactor.39 When the same reaction
was performed with the amount of O2 ranging from 0.20 to 1.27
equivalents,39 the conversion and yield were highly proportional
to the amount of O2 (Fig. 2). Gratifyingly, quasi-stoichiometric
amounts of O2 (1.27 equiv.) were sufficient to convert 100% of
IMes$HCl, furnishing [CuCl(IMes)] in 83% yield (Table 1, entry
1). These results showed the impressive capacity of ball-milling
to convert high proportions of a gaseous reactant spread among
chemicals of high physical state heterogeneity (gas, solid and
so material). To the best of our knowledge, such efficacy in
lowering the required quantity of a gaseous reactant in a reac-
tion performed in a ball-mill has never been reported before.
In 2012, Mack reported the critical importance of the bro-
moalkane physical state when it was used as an alkylating agent of
cyclohexanone in a ball-mill.41 Indeed, it was observed in this
situation that gaseous bromoalkanes were less reactive than the
liquid ones. In most reports, a different situation is observed, the
Fig.
1 Comparison of reaction conditions for the formation of
[CuCl(IMes)]. Mes ¼ mesityl; BM ¼ ball-milling; MS ¼ magnetic stirring.
performed in reuxing water were limited to 100 ꢁC, it is known
that under peculiar conditions, the temperature inside a ball-
mill can reach much higher levels.38 In our case, the tempera-
ture of the reaction mixture aer 6 h milling did not exceed 35
ꢁC, in complete accordance with what was previously observed
by us and by other research groups using similar milling
conditions.38
Conditions involving 2 equivalents of Cu(0) and water as the
grinding assistant were selected for further transformations,
since the full conversion of IMes$HCl could be reached in only 5
h
(Scheme 1). Several [CuCl(NHC)] complexes, featuring
unsaturated IMes, IPr and saturated SIMes and SIPr, could be
Scheme 1 Mechanosynthesis of various [CuCl(NHC)] complexes from
Cu(0). [a] Benzonitrile was used in place of H2O. [b] Previously unre- Fig. 2 Conversion and yield as a function of O2 equivalents for the
ported complex. [c] 5 equiv. of Cu(0) were used.
reaction of Cu(0), O2 and IMes$HCl performed in a ball-mill.
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Table
1 Mechanosynthesis of [CuCl(NHC)] complexes with 1.27
derivatives in hydrosilylation and 1,3-dipolar cycloaddition
reactions.42–44 Unfortunately, these complexes could not be ob-
tained when IMes$HBF4 and IMes$HPF6 were ball-milled with
Cu(0), with or without water (Table 2, entries 1 and 2). Yet, ball-
milling of these substrates in the presence of 1.1 equivalents of
NaOH furnished [Cu(IMes)2]BF4 and [Cu(IMes)2]PF6 in 79% and
87% yield, respectively (Table 2, entry 3). The necessity of using
a stronger base could be explained by the weaker hydrogen
bonds between the proton at C2 and the BF4ꢀ and PF6ꢀ counter
anions than in Clꢀ salts, leading to a lower acidity of this
proton.30,45 To our delight, the previously unreported
[Cu(IMesMe)2]BF4 and [Cu(IMesMe)2]PF6 could be produced in
excellent yields, showing the particularly high efficiency and
wide applicability of this approach (Table 2, entry 4). Besides,
the highly encumbered 1,3-bis-(2,6-diisopropylphenyl)-imida-
zolium derivatives reacted efficiently under these conditions,
yet a stronger base, KHMDS, had to be employed in most cases
to obtain acceptable conversion in a reasonable amount of time.
By using KHMDS, two additional unprecedented complexes,
[Cu(IPrMe)2]BF4 and [Cu(IPrMe)2]PF6, could be produced in
satisfying yields (Table 2, entry 6).
equivalents of dioxygen
Entry
Product
Time (h)
Yield (%)
1
2
3
4
[CuCl(IMes)]
[CuCl(SIMes)]
[CuCl(IPr)]
6
8
8
8
83
91
76
69
[CuCl(SIPr)]
gaseous nature of a reagent is not an obstacle for its reactivity.17–20
In our case, gaseous O2 is even close to being completely
consumed. Although composed of reactants of high physical state
heterogeneity, the reaction mixture was homogeneous at the
macroscopic scale, as indicated by identical conversions of three
samples withdrawn in three different locations inside the reactor.
To conrm that such conditions with a low amount of dioxygen
were general, [CuCl(SIMes)], [CuCl(IPr)] and [CuCl(SIPr)] were
synthesised in good to excellent yields by using only 1.27 equiva-
lents of O2 (Table 1). Notably, the yields obtained under these
conditions were very similar to those where the amount of
dioxygen was not precisely controlled.
We next turned our attention to the less studied, poorly
reactive and thus more challenging tetrauoroborate and hex-
auorophosphate imidazolium salts to produce their corre-
sponding cationic [Cu(NHC)2]+ homoleptic complexes that have
previously shown superior catalytic activities than their neutral
Conclusions
In conclusion, these results have demonstrated the particularly
high efficiency of ball-milling for the production of Cu–carbene
complexes from N,N-diaryl imidazolium salts, dioxygen and
metallic copper. It was shown for the rst time that ball-milling
enabled drastic reduction in the amount of gaseous reactant
required down to the stoichiometric scale, without hampering
conversion and yield. In addition, the rates of reaction clearly
outperformed those obtained in traditional solvent-based
Table 2 Mechanosynthesis of [Cu(NHC)2]BF4 and [Cu(NHC)2]PF6 complexes
Y ¼ BF4
t (h)
Y ¼ PF6
t (h)
Entry
Substrate
Cu(0) (equiv.)
Additive (1.1 equiv.)
Yield (%)
Yield (%)
1
2
3
4
5
IMes$HY
3
2
3
3
5
5
5
None
6
6
3
6
6
—
8
0
0
6
6
6
6
—
6
6
0
0
H2Oa
NaOH
NaOH
NaOH
KHMDS
KHMDSc
79
91b
85
—
72b
87
97b
—
89
78b,d
IMesMe$HY
IPr$HY
6
IPrMe$HY
a
b
c
d
0.3 mL of water per mg of reactants. Previously unreported complexes. 5 equiv. were used. Obtained as a mixture of two structures, one of
which is identied as being [Cu(IPrMe)2]PF6.
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conditions. Besides, ve previously unreported Cu–NHC
complexes could be isolated by using this approach. In an era of
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