Functionalised [(NHC)Pd(allyl)Cl] complexes: Synthesis, immobilisation and application in cross-coupling and dehalogenation reactions

Article abstract of DOI:10.1016/j.catcom.2016.09.006

A novel NHC–palladium(II) (NHC?=?N-heterocyclic carbene) complex and its immobilised version have been prepared and fully characterised. Optimisation studies led to good catalytic activities in Suzuki-Miyaura cross coupling and chloroarene dehalogenation reactions. Furthermore, the unexpected palladium-mediated transfer hydrogenation of a carbonyl compound is reported.

Full text of DOI:10.1016/j.catcom.2016.09.006

Catalysis Communications 87 (2016) 78–81
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Short communication
Functionalised [(NHC)Pd(allyl)Cl] complexes: Synthesis, immobilisation
and application in cross-coupling and dehalogenation reactions
⁎
John-Michael Collinson, James D.E.T. Wilton-Ely, Silvia Díez-González
Department of Chemistry, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 August 2016
Received in revised form 4 September 2016
Accepted 6 September 2016
Available online 09 September 2016
A novel NHC–palladium(II) (NHC = N-heterocyclic carbene) complex and its immobilised version have been
prepared and fully characterised. Optimisation studies led to good catalytic activities in Suzuki-Miyaura cross
coupling and chloroarene dehalogenation reactions. Furthermore, the unexpected palladium-mediated transfer
hydrogenation of a carbonyl compound is reported.
© 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://
creativecommons.org/licenses/by/4.0/).
Keywords:
Cross-coupling
Dehalogenation
N-Heterocyclic carbene
Palladium complexes
Transfer hydrogenation
1. Introduction
complex on silica-coated nanoparticles. This strategy minimises chang-
es around the metal centre during the catalytic reactions, often linked to
Cross-coupling reactions represent one of the major success stories
of transition metal catalysis, and have unarguably changed the way
chemists envision retrosynthetic analysis of their targets, particularly
in the case of biaryl compounds. Despite the interest in alternative
metals, palladium derivatives remain the catalyst of choice for most ap-
plications [1]. Ligandless, or PPh3-based systems are well established in
the literature, however, sterically demanding, strongly σ-donating li-
gands have been crucial for the development of extremely performing
catalysts. Hence, it is not surprising that, together with alkene metathe-
sis, cross-coupling reactions are the most popular application of N-het-
erocyclic carbenes as ligands. Following pioneering work by Herrmann
in 1995 [2], a variety of [(NHC)Pd] architectures have been reported in
the literature [3,4]. Among these, palladium(II) allyl complexes
attracted our attention since they are easily accessible, moisture- and
oxygen-stable and have shown excellent catalytic activities in different
cross-coupling reactions [5]. It was hypothesised that the immobilisa-
tion of such species on magnetic nanoparticles would combine the
high activity of palladium–NHC catalysts with the facile separation
and recyclability of a heterogeneous catalyst [6]. Indeed, our recent re-
search led to the development of a highly performing supported
copper(I) catalyst for the azide-alkyne cycloaddition reaction [7]. It
was therefore anticipated that a modified NHC bearing a hydroxyl sub-
stituent on the backbone would allow the immobilisation of a palladium
the loss in performance observed for complexes attached to surfaces
through the N-substituents of the NHC [8].
2. Results and discussion
2.1. Preparation of the catalysts
The 4-hydroxyimidazolium salt 1∙HCl used in this work was synthe-
sised [9] and the corresponding [(NHC)Pd(allyl)] complex was pre-
pared by treating 1∙HCl with an slight excess of LiHMDS at 0 °C,
followed by addition of [Pd(η3-C3H5)Cl]2. [(1)Pd(allyl)Cl] was then iso-
lated as a light green solid in good yield (Scheme 1). This complex was
stable in air and could be stored for months at room temperature. When
other bases were used (i.e. KOt-Bu or NaOt-Bu), no NHC complexation
was observed even at high temperatures. Instead, a zwitterionic deriva-
tive was isolated as the only reaction product (Scheme 1).
In contrast to 1⋅HCl, the 1H NMR spectrum of [(1)Pd(allyl)Cl] notably
displayed two distinctive roofed doublets at 4.52 and 4.38 ppm, attrib-
uted to the CH2 protons on the backbone and indicating that this com-
plex was isolated in its keto form. The signals due to the allyl ligand
appeared between 4.84 and 1.52 ppm, in accordance with the spectra
of other reported [(NHC)Pd(allyl)Cl] complexes [10]. [(1)Pd(allyl)Cl]
was further characterised using 13C{1H} NMR, IR spectroscopies and
HRMS. Unfortunately, all attempts to grow crystals suitable for X-ray
crystallography failed.
⁎
Corresponding author.
In order to develop an immobilised catalyst, magnetic nanoparticles
(Fe3O4) were prepared following established literature procedures [11,
E-mail addresses: j.wilton-ely@imperial.ac.uk (J.D.E.T. Wilton-Ely),
s.diez-gonzalez@imperial.ac.uk (S. Díez-González).
http://dx.doi.org/10.1016/j.catcom.2016.09.006
1566-7367/© 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

J.-M. Collinson et al. / Catalysis Communications 87 (2016) 78–81
79
time, Table 1, entry 1). Since milder reaction conditions are likely to fa-
cilitate the recovery and recycling of any supported catalyst, the base
loading was then reduced to 1.1 equiv. Even though a loss in conversion
was observed, using KOt-Bu instead of its sodium analogue, led again to
a good conversion of 78% (Table 1, entries 2 and 3). No significant
changes were observed using isopropanol, a significantly greener sol-
vent than dioxane. While complete conversion was obtained under
these conditions at a higher temperature of 80 °C, only 22% of 2a formed
at room temperature. Using the relatively mild conditions of entry 4,
Imm[(1)Pd(allyl)Cl] was compared to its untethered analogue
[(1)Pd(allyl)Cl], as well as [(IPr)Pd(allyl)Cl] (Table 1, entries 7 and 8).
In both cases, higher conversions were obtained of around 90%. Most
importantly, novel [(1)Pd(allyl)Cl] displayed a catalytic activity compa-
rable to previously reported [(IPr)Pd(allyl)Cl].
Scheme 1. Synthesis of [(1)Pd(allyl)Cl].
12,13,14]. The immobilisation of [(1)Pd(allyl)Cl] on these was carried
out with 4 Å MS in refluxing toluene. It was anticipated that the resident
silanol groups on the silica coating magnetic particles would bind to the
backbone of the NHC complex in its enol tautomer, due to the (mildly)
acidic nature of the silica coating. The resulting material was centrifuged
and washed with dichloromethane to remove any remaining unat-
tached species and then dried overnight under vacuum to give
Imm[(1)Pd(allyl)Cl].
The immobilised complex was first characterised by inductively
coupled plasma analysis (ICP) that indicated a metal loading of
0.57 μmolPd/mg. This is lower than the theoretical maximum loading
(0.83 μmolPd/mg), but in accordance with the reaction mass balance
(Scheme 2) [14]. Transmission electron microscopy (TEM) images
showed nanoparticles of 45.5 ( 2.2) nm in diameter with a magnetic
core (Scheme 2). TEM also confirmed the absence of palladium nano-
particles in the prepared material with palladium only detected on the
surface of the nanoparticles. Furthermore, energy dispersive X-ray spec-
troscopy (EDS) analysis of Imm[(1)Pd(allyl)Cl] detected Pd and Cl from
the original palladium complex, as well as the Fe and Si from the nano-
particles [14].
In an attempt to further increase the yield while keeping the temper-
ature at 60 °C, alternative bases were tested. Gratifyingly, KOH and
NaOH led to high conversions under otherwise identical conditions
(Table 1, entries 9 and 10), demonstrating that simple, inexpensive
bases could be used. Overall, NaOH and i-PrOH were selected as optimal
pairing for these cross-coupling reactions at 60 °C. When the model re-
action was carried out under optimised conditions using 4-
chlorotoluene instead of the bromo derivative, an average conversion
of 40% was obtained either at 60 or 80 °C. Importantly, all these reac-
tions were carried out in technical grade solvents and without any pre-
cautions to exclude oxygen or moisture from the reaction mixtures.
Next, after a first run of the model reaction, the catalyst was separat-
ed using a magnet and dried. Its metal content was determined by ICP in
order to carry out the second run with the same 1 mol% palladium load-
ing (Scheme 3). However, the reaction conversion dropped to 20% after
only recycling once.
Unsurprisingly, the TEM analysis of the recycled material clearly
showed that palladium nanoparticles (≈10 nm in diameter) had
formed during the first catalytic run [14], and no iron oxide/silica core
shell nanoparticles could be detected. These observations show that,
in contrast to our earlier work on cycloaddition reactions [7], this cata-
lyst reported is not robust enough under the reaction conditions to re-
sist the loss of its structural integrity and forms palladium
nanoparticles. Nevertheless, this result also supports ligated Pd–NHC
species as the active species in these Suzuki-Miyaura couplings, instead
of the palladium nanoparticles formed during the reaction. The genera-
tion of palladium nanoparticles is indeed a recurring issue in catalytic
applications. Depending on the system, such nanoparticles can either
be the actual active species [16,17], or mainly inactive degradation
products, as in this case.
2.2. Suzuki-Miyaura cross-coupling reactions
The prepared systems were then tested in Suzuki-Miyaura cross-
couplings, using 4-bromotoluene and phenylboronic acid (1.05 equiv)
as model substrates. This reaction was first carried out using conditions
reported previously for the parent [(NHC)Pd(allyl)Cl] complexes: 3
equiv NaOt-Bu in dioxane at 60 °C [15]. With
1 mol% of
Imm[(1)Pd(allyl)Cl], a conversion of 84%, similar to the reported 91%
with [(IPr)Pd(allyl)Cl], was observed after 18 h (non-optimised reaction
In the light of these results, the scope of the reaction was next ex-
plored using [(1)Pd(allyl)Cl] only, since it had displayed a slightly
higher activity during the optimisation. A range of biaryl derivatives
was successfully isolated in analytically pure form after column chroma-
tography (Scheme 4). Ortho-substituents and functional groups such as
ethers and aldehydes were successfully tolerated by this catalytic sys-
tem. Only in the case of a 2-pyridyl substrate was low conversion into
cross-coupled product observed.
Biaryl 2b was analysed by ICP to determine metal contamination
both before and after column chromatography. While the crude product
obtained after work-up contained 87.6% of the palladium used in the re-
action, after column chromatography no palladium could be detected.
As
a
comparison, the same product 2b obtained using
Imm[(1)Pd(allyl)Cl] contained only 8.9% of the original palladium,
which could again be entirely removed during the purification step.
2.3. Dehalogenation reactions
[(NHC)Pd(allyl)Cl] complexes have also been applied
dehalogenation reactions [15]. Often regarded as undesired side-reac-
tions, the metal-catalysed reduction of halogenated organic
Scheme 2. Immobilisation of [(1)Pd(allyl)Cl] and resulting TEM image.

80
J.-M. Collinson et al. / Catalysis Communications 87 (2016) 78–81
Table 1
Optimisation studies.
Entry
Base
Solvent
T (°C)
Conv (%)a
1
2
3
4
5
6
7
8
9
NaOt-Bu
NaOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOt-Bu
KOH
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
60
60
60
60
80
RT
60
60
60
60
84b
60
78
76
N95
22
91c
93d
87
10
NaOH
90
a
1H NMR conversions are the average of at least two independent experiments.
Reaction carried out with 3 equiv of base.
Reaction carried out in the presence of 1 mol% of [(1)Pd(allyl)Cl].
Reaction carried out in the presence of 1 mol% of [(IPr)Pd(allyl)Cl].
b
c
d
compounds, particularly arenes, is of substantial importance due to
their high toxicity to the environment [18].
3. Conclusions
Dehalogenation reactions were explored under the same reaction
conditions optimised for the cross-coupling experiments, and the
crude reaction product(s) were analysed by GC–MS. Even if they were
not suitable for cross-coupling reactions, it was interesting to note
that chloroarenes readily reacted in the presence of [(1)Pd(allyl)Cl].
All reactions depicted in Table 2 proceeded very cleanly and no by-prod-
uct formation was observed in any of them. An ortho-substituent did not
prove problematic in the case of 2-chloronaphthalene, however a much
lower conversion was observed in the case of 2-chloroanisole (Table 2,
entries 2 and 3). Quite surprisingly a similar conversion was obtained
with para-chlorobenzonitrile (16% at 60 °C or 35% at 80 °C, Table 2,
entry 4). In contrast, 2-chlorothiophene was dehalogenated with an ex-
cellent conversion under identical conditions (Table 2, entry 5).
From 3,5-dichloroanisole, a mixture of mono- and bis-dehalogenated
products was obtained (Table 2, entry 6). More surprising was the out-
come of the reaction of 2,6-dichlorobenzaldehyde, where two reaction
products were identified, both being benzylic alcohols formed by a trans-
fer hydrogenation reaction (Table 2, entry 7) [19]. This was unexpected
since this reactivity is well-established with other metals such as rutheni-
um or iridium, while the palladium-mediated transfer hydrogenation of
carbonyl derivatives remains largely unexplored [20,21].
A novel [(NHC)Pd(allyl)Cl] complex, bearing an NHC with a modi-
fied backbone was prepared and fully characterised. This complex
displayed very similar reactivity to commercially available
[(IPr)Pd(allyl)Cl] in Suzuki and dehalogenation reactions under rela-
tively milder and greener reaction conditions (1 mol% [Pd], 1.1 equiv
NaOH, i-PrOH, 60 °C). An immobilised version of [(1)Pd(allyl)Cl] on sil-
ica-coated magnetic nanoparticles also performed well in initial runs,
but could not be reused under such reaction conditions. This might be
due to the pernicious effect of the base on the silica linker, or to the gen-
eration of H2 under catalytic conditions. Indeed, the transfer hydrogena-
tion of a benzaldehyde derivative was observed. Such reactivity is
largely underdeveloped for palladium and it is currently under
investigation.
Acknowledgements
This work was supported by Imperial College London and EPSRC. We
thank GlaxoSmithKline (GSK) for supplying the boronic acids used for
products 2b, 2d and 2e.
Importantly, when boronic acids are present dehalogenated prod-
ucts formed only as traces, if at all. Also, no reduction of the formyl
group in 2e was observed, which indicates that the boronic acid readily
reacts with the base, inhibiting the significant formation of any other re-
action product. These results also support the hypothesis that
[(1)Pd(allyl)Cl] is not a suitable cross-coupling pre-catalyst for
chloroarenes, unlike parent [(IPr)Pd(allyl)Cl] [15] due to an adverse
electronic effect of the functionalised backbone on either the
transmetallation, or reductive elimination steps.
Scheme 4. [(1)Pd(allyl)Cl]-mediated Suzuki-Miyaura cross coupling reactions. Isolated
yields are the average of at least two independent experiments. 1H NMR conversions are
shown in brackets for reactions that did not reach completion.
Scheme 3. Recycling experiments with Imm[(1)Pd(allyl)Cl]. Conversions determined by 1
NMR spectroscopy are the average of at least two independent experiments.
H

J.-M. Collinson et al. / Catalysis Communications 87 (2016) 78–81
81
Table 2
[(1)Pd(allyl)Cl]-mediated dehalogenation reactions of chloroarenes.
Entry
1
Chloroarene
Product(s)
Conv (%)a
N95
2
94
3
4
19
35b
5
6
94
16 + 12
7
71 + 29
a
1H NMR conversions are the average of at least two independent experiments.
Reaction carried out at 80 °C.
b
complexes (NHC
1629–1635.
= N-heterocyclic carbene), Organometallics 23 (2004)
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