Catalysts by the meter: Rapid screening approach of N-heterocyclic carbene ligand based catalysts

Article abstract of DOI:10.1039/c0cc02306j

Here, we demonstrate a versatile screening platform for NHC ligand based catalysts by coating fused-silica micro capillaries with a bonded 1,3-bismesityl-2-imidazolidinylidene ligand. Such micro capillaries can be efficiently converted into (pre)-catalyst

Full text of DOI:10.1039/c0cc02306j

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Catalysts by the meter: rapid screening approach of N-heterocyclic
carbene ligand based catalystswz
Carolin Lang, Ute Gartner and Oliver Trapp*
¨
Received 1st July 2010, Accepted 24th August 2010
DOI: 10.1039/c0cc02306j
Here, we demonstrate a versatile screening platform for NHC
ligand based catalysts by coating fused-silica micro capillaries
with a bonded 1,3-bismesityl-2-imidazolidinylidene ligand. Such
micro capillaries can be efficiently converted into (pre)-catalysts
from various organometallic precursors by solid-phase chemistry
techniques and can be quantitatively screened using on-column
reaction chromatography.
1–3
N-Heterocyclic carbenes (NHCs) are highly versatile ligands
and are of major focus in the development of highly active
4
–7
catalysts
in a broad range of reactions with superior
properties in regard to stability and use in various reaction
8
,9
10
media and conditions. NHCs have been immobilized on a
variety of soluble and insoluble polymers and inorganic
1
1–13
14,15
materials, i.e. on silica.
Advantages of immobilization
are the recyclability of catalysts, easy removal from reaction
mixtures, and minimisation of leaching of expensive catalysts,
which is of great importance for the practicability of catalysts
in industrial applications.
Fig. 1 Strategy utilizing immobilised NHC ligands in fused-silica
micro capillaries to create NHC ligand based catalysts (here Ru and
Au catalysts) for high-throughput investigations by on-column
reaction chromatography.
Here, we present a novel strategy utilizing the permanent
immobilisation of NHC pre-ligands on the inner surface of
fused-silica micro capillaries (id 250 mm) with a defined film
thickness (between 50 to 1000 nm) of the polymeric matrix.
Such NHC pre-ligand modified fused-silica capillaries can
be converted to NHC ligands and with suitable organometallic
precursors to pre-catalysts utilizing all advantages of solid-phase
organic chemistry, i.e. high reagent concentrations, simple
removal of non-reacted reagents, and analytical techniques
at the same time (cf. Fig. 1).
To immobilise the prototype of NHC ligands, a 1,3-
bismesityl-2-imidazolidinylidene ligand, we considered
a
1
0
similar strategy used by Blechert et al. to modify the back-
bone of the 2-imidazolidinylidene moiety via an ether function,
which allows us to introduce terminal alkene chains, which can
react under benign conditions in a hydrosilylation with
hydridopolysiloxanes. Polysiloxanes are ideal polymeric
supports, because solvent properties can be easily tuned, they
are inert, are commonly used as stationary phases in gas
Reactions can be directly monitored by implementing
such capillaries in chromatographic systems. Furthermore,
the integration of catalysis and analysis by on-column
chromatography allows rapid and precise high-throughput
measurements of kinetic and thermodynamic data, which
recently was made possible by the derivation of mathematical
2
7
chromatography, and can show positive effects in catalysis.
All three investigated pathways are starting with 1,3-
bismesityl-2-imidazolidinylidene, which is converted into the
allylether in 91% yield, but can be also converted into ligand
precursors with various spacer lengths. A total spacer length of
˚
about 5 to 10 A is ideal, because intramolecular interactions of
1
6
functions to access kinetic parameters from such experiments.
These data are important to tune reaction conditions and to
the ligand with the polymer backbone caused by gauche
2
conformations of the linker are reduced and there is still
8
1
7–21
understand reactions on a molecular level.
On the other
2
sufficient flexibility of the ligand. Similar to the strategy
9
hand this approach can be also switched to a preparative
2
1
developed by Blechert et al. in pathway A (cf. Scheme 1)
0
2–25
micro reactor mode
by continuous feeding of reagents
1
0
1
-(allyloxy)-N,N -dimesityl-2,3-diamino-propane 2 was cyclised
7,26
into the catalytically active capillary.
with triethyl orthoformate to give the imidazolium salt 3 in
6% yield, which was consecutively immobilized to 4 by
9
hydrosilylation using the Karstedt catalyst under ultrasonication.
Pt is removed by treatment with activated charcoal. In the next
step the carbene is formed by treatment with potassium tert-
butoxide followed by a reaction with Grubbs 1st generation
Ruprecht-Karls-Universita¨t Heidelberg, Organisch-Chemisches Institut,
Im Neuenheimer Feld 270, 69120 Heidelberg, Germany.
E-mail: trapp@oci.uni-heidelberg.de; Fax: +49 (0) 6221 544904;
Tel: +49 (0) 6221 548470
w This article is part of the ‘Emerging Investigators’ themed issue for
ChemComm.
30
catalyst to form the bonded Grubbs 2nd generation catalyst
5. However, we found that the polymer supported catalyst 5
z Electronic supplementary information (ESI) available: Experimental
details and further characterisation data. See DOI: 10.1039/c0cc02306j
prepared by pathway A was very sensitive to decomposition
This journal is c The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 391–393 391

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modified capillaries 9 are characterised by excellent long term
stability and easy activation to the carbene, to form together
with organometallic precursors, NHC ligand based catalysts
by the meter, which is successfully demonstrated in the next
steps. Heating modified capillaries 9 in a water bath to 60 1C
results in the formation of the immobilized free carbene which
reacts with Grubbs 1st generation catalyst by ligand exchange
to give permanently bonded polymeric Grubbs 2nd generation
catalyst capillary 10. Here, we utilize several advantages,
which include solid-phase chemistry at high reagent concen-
trations, excess of reagents, easy removal of reagents by
flushing the capillary with solvents, and requiring only short
capillary pieces to synthesize the desired catalytically active
column under defined and reproducible conditions. Furthermore,
capillaries compatible to chromatographic separation columns
offer the possibility of in situ reaction monitoring by installing
capillary column 9 between a pre-separation column for
thermal equilibration, followed by a separation column
connected to EI GC/MS. This approach has also the
advantage that the system can be simply checked against
catalytic activity of the sample injector and separation
columns by performing measurements with and without the
catalytically active capillary. For the here studied reactions
and reaction conditions no catalytic activity of the injector or
separation capillary was observed. Heating the capillary from
Scheme 1 (a) 3-Bromo-prop-1-ene, NaH, THF, 24 h, 64 1C.
b) NH BF , HC(OEt) (c) Hydridomethyldimethylpolysiloxane,
Karstedt catalyst, THF, ultrasonication for h. (d) KOtBu,
THF, rt, h, (Cy P) Cl Ru (Q CHPh), toluene, 80 1C, h.
e) Hydridomethyldimethylpolysiloxane, Karstedt catalyst, THF
ultrasonication for 3 h. (f) Pentafluorobenzaldehyde, AcOH, 24 h.
g) (Cy P) RuCl CHPh, toluene, 80 1C, h. (h) Pentafluoro-
P) RuCl CHPh,
(
4
4
3
.
3
1
3
2
2
4
(
(
3
2
2
4
benzaldehyde, AcOH, n-pentane, 60 1C. (i) (Cy
n-pentane, 60 1C.
3
2
2
which could be explained by the combination of free base and
remaining Si–H groups in the polysiloxane, which are necessary
for a permanent bonding of the polymer to glass surfaces via
condensation with surface silanol-groups. Therefore the
strategy was changed to a base free route in pathways B and
C (cf. Scheme 1). In pathway B the diamine 2 is first
immobilized via hydrosilylation to hydridomethyldimethyl-
polysiloxane to form polymer 6, which was monitored by
ꢀ
1
40 to 80 1C with a heating rate of 4 K min results in the
observation of a broad peak (w E 2 min) with a characteristic
h
EI MS fragmentation pattern (m/z = 168 (100%) and 99
(50%)) for pentafluorobenzene. Permanently bonded polymeric
Grubbs 2nd generation catalyst capillaries 10 show some
remarkable properties in comparison to Grubbs 2nd generation
catalyst dissolved in poly(dimethylsiloxane) and coated onto
1
H-NMR spectroscopy (cf. Fig. S6 in the ESIz). The bonded
diamine 6 is then cyclised with pentafluorobenzaldehyde to the
3
immobilised 2-(pentafluorophenyl)imidazolidine 7.
1,32
17
The
the inner surface of fused-silica capillaries. These capillaries
advantage is that the bonded carbene can be thermally generated,
which can be immediately converted to form the bonded
Grubbs 2nd generation catalyst 5 by ligand exchange against
the tricyclohexylphosphine ligand. The formation of the
bonded Grubbs 2nd generation catalyst was monitored by
are moisture and air insensitive, can be installed several times
over weeks without any loss of activity or leaching (detected
by MS), and are stable even at elevated temperatures of 105 1C
for several hours.
Injection of N,N-diallyltrifluoroacetamide at 50 1C and
80 kPa leads to the formation of N-trifluoroacetamide-3-
pyrroline in 61.0% yield, considering a response factor of
3
1
P-NMR spectroscopy (cf. Fig. S7 in the ESIz). In contrast to
the polymeric Grubbs 2nd generation catalyst 5 obtained via
pathway A this material is stable, which can be attributed to
the absence of base. Coating of the inner surface of fused silica
capillaries with the catalytically active polymer 5 turned out to
be highly challenging, because of the large active glass surface
(
high surface to volume ratio) and the immobilization of the
polymer to the surface which affords higher temperatures.
Therefore the optimized reaction conditions were transferred
at a very early stage to the fused-silica capillary as solid-phase
reaction vessel in pathway C (cf. Scheme 1). Polymeric diamine 6
was coated onto the inner surface of a fused-silica capillary
(id 250 mm) with a film thickness of 250 nm. The polymer
film was then immobilized onto the glass surface by heating
the capillary to 180 1C (40 1C for 5 min, then heating up
ꢀ
1
Fig. 2 On-column reaction gas chromatographic experiments using
to 180 1C for 10 min at a heating rate of 0.5 K min ) under
slow nitrogen flow. This polymer is highly reactive and is
permanently bonded to the glass surface via Si–O–Si bonds.
(
a) a 10 cm permanently bonded polymeric Grubbs 2nd generation
catalyst capillary 10 to achieve on-column ring closing metathesis of
N,N-diallyltrifluoroacetamide to N-trifluoroacetamide-3-pyrroline at
The permanently bonded polymeric diamine
8 is then
50 1C, and (b) a 10 cm permanently bonded polymeric 1,3-bis(2,4,6-
trimethylphenyl)imidazol-2-ylidene gold(I) chloride to hydrogenate
converted with pentafluorobenzaldehyde to the permanently
bonded polymeric 2-(pentafluorophenyl)imidazolidine 9. Surface
nitrobenzene to aniline at 95 1C.
3
92 Chem. Commun., 2011, 47, 391–393
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ꢀ1
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1
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¨
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¨
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4
9,41
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2
2
2
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#
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ꢀ
1
9
1.5 kJ mol
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.
3
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easily converted to catalytically active separation columns
using solid phase chemistry strategies. This has been successfully
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the capillary surface and generating free carbene ligands
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Generous financial support by the Deutsche Forschungsge-
meinschaft (DFG) for an Emmy Noether grant (TR 542/3)
and the SFB 623 ‘Molecular Catalysts: Structure and
Functional Design’ is gratefully acknowledged.
4
This journal is c The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 391–393 393