Reusable and highly active supported copper(i)-NHC catalysts for Click chemistry

Article abstract of DOI:10.1039/c3cc44371j

Immobilised [Cu(NHC)] catalysts are reported for the preparation of 1,2,3-triazoles. In addition to showing outstanding catalytic activity, the catalyst systems are easy to prepare and can be recycled many times.

Full text of DOI:10.1039/c3cc44371j

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Reusable and highly active supported copper(I)–NHC
catalysts for Click chemistry†
Cite this: DOI: 10.1039/c3cc44371j
´
John-Michael Collinson, James D. E. T. Wilton-Ely* and Silvia D´ıez-Gonzalez*
Received 10th June 2013,
Accepted 26th June 2013
DOI: 10.1039/c3cc44371j
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Immobilised [Cu(NHC)] catalysts are reported for the preparation of centre, as significantly diminished catalytic activities are often
1,2,3-triazoles. In addition to showing outstanding catalytic activity, the reported for catalysts attached to surfaces via the substituent on
catalyst systems are easy to prepare and can be recycled many times.
the N atoms of the NHC ligand.10
Following the reported synthetic route for the preparation of
The copper-mediated cycloaddition reaction of azides and alkynes is a 4-hydroxyimidazol-2-ium salts bearing aromatic groups on the nitrogen
recent example of how metal catalysis can have an impact on a wide atoms,9c the known adamantylformamidine 1 was prepared.11 How-
range of scientific disciplines.1 It has been thrust into the spotlight by ever, under acylation conditions 1 decomposed to give 2 as the sole
its use as a proof of concept for the Click philosophy postulated by isolated product (Scheme 1).12 This reactivity might be attributed to the
Sharpless.2 The reported applications for this cycloaddition reaction fragility of alkyl formamidines when compared to their aryl analogues.13
are numerous and diverse, but the development of true Click Thus, construction of the ligand was commenced instead from the
transformations still relies on the significant efforts being devoted backbone. The preparation of the ligand OHIAdÁHBF4 5ÁHBF4 was then
to improve the understanding of the mechanism(s) involved,3 as well accomplished in three simple steps from adamantyl amine, starting
as on the development of ligand-modified systems.4 Among the with its acylation by chloroacetyl chloride, followed by amine alkylation
families of ligands reported for this reaction, N-heterocyclic carbenes (Scheme 1). Subsequent cyclisation with triethyl orthoformate led to the
(NHCs)5 are prominent as they produce highly robust catalysts isolation of 5ÁHBF4. Gratifyingly, it was found that all these reactions
capable of conferring outstanding catalytic activity on the copper could be run in air with no need for purification on silica gel.
centre, often at extremely low catalytic loadings.6
It is important to note that, for known 4-hydroxyimidazolium
The immobilisation of metals on nanoparticles allows the prop- ligands (and their 4-amino analogues),14 the enol tautomer is so
erties and flexibility of a metal–ligand unit to be harnessed while favourable that no 4-oxo-1,3-diarylimidazolium derivatives are
exploiting the advantages of attachment to a surface.7 An enhanced observed. In contrast, the H NMR spectrum of 5ÁHBF4 showed
1
Click catalyst for the cycloaddition of azides and alkynes could thus two singlets at 6.16 and 4.10 ppm, attributed to the enol and keto
be achieved by a system that combines the exceptional activity of tautomers, respectively. The integration of these signals indicated
copper–NHC systems with the easy separation and recyclability of a a 1 : 1 equilibrium between both forms of OHIAdÁHBF4.
heterogeneous catalyst.8 In this quest, it was decided to use
[CuI(IAd)] (IAd = 1,3-di(adamantyl)imidazol-2-ylidene) as the starting
point due to its superior reactivity when compared to other neutral
[Cu(NHC)] complexes.6d Thus, it was anticipated that an analogue of
the IAd ligand could be immobilised on silica through a hydroxyl
substituent on the NHC backbone. Precedents in the literature for
such architectures (sometimes referred to as switchable carbenes)
include copper(I) complexes.9 More importantly, the modification of
the ligand backbone minimises the changes around the metal
Department of Chemistry, Imperial College London, South Kensington Campus,
London SW7 2AZ, UK. E-mail: j.wilton-ely@imperial.ac.uk,
s.diez-gonzalez@imperial.ac.uk; Fax: +44 (0)20 7594 5804;
Tel: +44 (0)20 7594 9718, +44 (0)20 7594 9699
† Electronic supplementary information (ESI) available: Experimental details and
information on characterisation of the materials described. See DOI: 10.1039/
Scheme 1 Synthesis of OHIAdÁHBF4, 5ÁHBF4.
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The new azolium salt was then immobilised on three
different carrier materials, namely silica flakes, silica nano-
particles and magnetite/silica nanoparticles. This was achieved
by reaction of these supports with 5ÁHBF4 in hot DMF in the
presence of molecular sieves. The anchored ligands were then
treated with CuI under otherwise identical conditions to those
reported for the preparation of [CuI(IAd)] to give the corres-
ponding supported [CuI(5)] complexes (Scheme 2).
Transmission Electron Microscopy (TEM) revealed that the silica
nanoparticles, Si-NP[CuI(5)], possessed an average diameter of
150.4 (Æ5.3) nm, while those with a magnetite core, Fe O /Si[CuI(5)],
were 47.7 (Æ3.8) nm in size. All three functionalised silica materials
showed the presence of copper, as determined by Energy Dispersive
X-Ray Spectroscopy (EDS). Infrared spectroscopy provided limited
information due to the small proportion of surface units compared
to the bulk material of the nanoparticles. Initially, mass balance
calculations were used to determine the loading of copper surface
units on the nanoparticles but this was replaced by Inductively
3
4
Scheme 3 Recyclability of supported catalysts. 1H NMR conversions are the
average of at least two independent experiments.
Coupled Plasma (ICP) analysis to provide the mmolCu per mg the scope of the reaction (Table 1). When incomplete conversions
loading for the materials. were observed, either a slightly higher copper loading (0.5 mol%)
With the supported copper complexes in hand, the influence of the or a small increase in the reaction temperature (40 1C) allowed the
support on the catalytic activity was examined, along with the recycling expected triazoles to be formed quantitatively.
efficiency of each system. Hence, the three prepared catalysts were
Overall, a variety of triazoles 7 was isolated in excellent yields and
applied to the model reaction of benzyl azide 6a and phenylacetylene high purity after simple extraction and decantation/filtration, regard-
on water at room temperature (Scheme 3). In the first cycle, all catalysts less of the substitution on either the starting azide 6 or alkyne.
led to the quantitative formation of triazole 7a after overnight reactions Several functional groups (e.g., alcohol, amine, halogen) were well
with only 1 mol% [Cu]. After dissolving the formed triazoles in EtOAc, tolerated by benzylic, aromatic or aliphatic azides. Increasing the
the reaction mixtures were centrifuged, and the catalysts were collected steric profile of either of the cycloaddition partners did not diminish
by filtration or using a magnet, washed, dried under vacuum and the catalytic activity (Table 1, entries 3 and 8).
The performance of Fe O /Si[CuI(5)] was also compared to the
3
4
reused in a new cycle. The catalyst supported on silica flakes lost its
catalytic activity by the fifth cycle, whereas the copper-functionalised parent [CuI(IAd)], probably one of the best reported catalysts for this
silica nanoparticles led to diminished conversions after only 3 cycles (53 particular cycloaddition. Both complexes led to complete conversion
and 68% conversion, respectively). However, the copper complex to 7a (model reaction, see Scheme 3) with only 0.25 mol% [Cu] at
anchored on coated magnetic nanoparticles displayed optimal activity room temperature. In order to probe the relative activity further,
for at least nine cycles before deactivation (91, 82 and 20% conversions another pair of cycloaddition partners was chosen that did not lead
for cycles 9 to 11). The improved recyclability observed for Fe O /Si[CuI(5)] to complete conversion with the supported catalyst under such
3
4
is attributed to its facile manipulation and recovery by simple decanta- reaction conditions (Scheme 4, see also Table 1, entry 4). Using
either [CuI(IAd)] or Fe O /Si[CuI(5)] produced 7d at a comparable level
3
4
tion in the presence of a hand-held magnet.
To highlight the essential role of the NHC ligand, silica flakes of conversion, suggesting that the catalytic activity of Fe O /Si[CuI(5)] is
3
4
were treated with CuI in the absence of the NHC ligand, resulting not affected significantly by its immobilised nature.
in a yield for 7a of only 56% under otherwise identical reaction
conditions. This result clearly showed that the observed catalytic still contained all the starting copper loading, even after acid
activity can be attributed to supported NHC–copper species. hydrolysis, whereas the same analysis of 7h produced using
ICP analysis of 7h formed using [CuI(IAd)] showed that it
Optimisation studies revealed that Fe O /Si[CuI(5)] performed Fe O /Si[CuI(5)] showed extremely low copper contamination
equally well in the model reaction with only 0.25 mol% copper (around 3% of the original metal loading). TEM and EDS
loading and this finding was used in the further investigation of analysis of the used Cu–silica–magnetite catalyst demonstrated
no discernible change of structure and showed no evidence of
3
4
3 4
formation of copper nanoparticles.
In conclusion, a supported copper(I) catalyst has been developed
that combines high recyclability with the remarkable activity of
[Cu(NHC)] systems in the cycloaddition reaction of azides and
alkynes. Importantly, in terms of its wider utility, the new system
does not require a lengthy or complicated synthetic sequence
for its preparation. The activity of the supported catalyst is
comparable to its homogeneous analogue while permitting the
reuse of the catalyst up to ten times after simple decantation in
Scheme 2 Preparation of supported catalysts. Mass balances are reported.
the presence of a hand-held magnet.
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Fe O
3 4
Table 1
/Si[CuI(5)]-catalysed triazole formation
Entry
1
Triazole
[Cu]/mol%, T/1C
Yielda/%
92
Scheme 4 Comparison of copper catalysts.
0.25, RT
Imperial College and EPSRC are gratefully acknowledged for
financial support of this work.
0.25, RT
0.5, RT
0.25, 40 1C
40b
80
83
2
3
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