Catalytic Transfer of Magnetism Using a Neutral Iridium Phenoxide Complex

Article abstract of DOI:10.1021/acs.organomet.5b00311

A novel neutral iridium carbene complex Ir(κC,O-L₁)(COD) (1) [where COD = cyclooctadiene and L₁ = 3-(2-methylene-4-nitrophenolate)-1-(2,4,6-trimethylphenyl)imidazolylidene] with a pendant alkoxide ligand has been prepared and characterized. It contains a strong Ir-O bond, and X-ray analysis reveals a distorted square planar structure. NMR spectroscopy reveals dynamic solution-state behavior commensurate with rapid seven-membered ring flipping. In CD₂Cl₂ solution, under hydrogen at low temperature, this complex dominates, although it exists in equilibrium with a reactive iridium dihydride cyclooctadiene complex. 1 reacts with pyridine and H₂ to form neutral Ir(H)₂(κC,O-L₁)(py)₂, which also exists in two conformers that differ according to the orientation of the seven-membered metallocycle, and while its Ir-O bond remains intact, the complex undergoes both pyridine and H₂ exchange. As a consequence, when placed under para-hydrogen, efficient polarization transfer catalysis (PTC) is observed via the signal amplification by reversible exchange (SABRE) approach. Due to the neutral character of this catalyst, good hyperpolarization activity is shown in a wide range of solvents for a number of substrates. These observations reflect a dramatic improvement in solvent tolerance of SABRE over that reported for the best PTC precursor IrCl(IMes)(COD). For THF, the associated ¹H NMR signal enhancement for the ortho proton signal of pyridine shows an increase of 600-fold at 298 K. The level of signal enhancement can be increased further through warming or varying the magnetic field experienced by the sample at the point of catalytic magnetization transfer. (Chemical Equation Presented).

Full text of DOI:10.1021/acs.organomet.5b00311

Article
pubs.acs.org/Organometallics
Catalytic Transfer of Magnetism Using a Neutral Iridium Phenoxide
Complex
Amy J. Ruddlesden,† Ryan E. Mewis,†,§ Gary G. R. Green,‡ Adrian C. Whitwood,†
and Simon B. Duckett*,†
†Department of Chemistry, University of York, Heslington, York, YO10 5DD U.K.
‡York Neuroimaging Centre, The BiocentreYork, Science Park, Heslington, York, YO10 5NY U.K.
S
* Supporting Information
ABSTRACT: A novel neutral iridium carbene complex Ir(κC,O-
L1)(COD) (1) [where COD = cyclooctadiene and L1 = 3-(2-
methylene-4-nitrophenolate)-1-(2,4,6-trimethylphenyl)imidazolylidene]
with a pendant alkoxide ligand has been prepared and characterized. It
contains a strong Ir−O bond, and X-ray analysis reveals a distorted
square planar structure. NMR spectroscopy reveals dynamic solution-
state behavior commensurate with rapid seven-membered ring flipping.
In CD2Cl2 solution, under hydrogen at low temperature, this complex
dominates, although it exists in equilibrium with a reactive iridium
dihydride cyclooctadiene complex. 1 reacts with pyridine and H2 to form
neutral Ir(H)2(κC,O-L1)(py)2, which also exists in two conformers that
differ according to the orientation of the seven-membered metallocycle, and while its Ir−O bond remains intact, the complex
undergoes both pyridine and H2 exchange. As a consequence, when placed under para-hydrogen, efficient polarization transfer
catalysis (PTC) is observed via the signal amplification by reversible exchange (SABRE) approach. Due to the neutral character
of this catalyst, good hyperpolarization activity is shown in a wide range of solvents for a number of substrates. These
observations reflect a dramatic improvement in solvent tolerance of SABRE over that reported for the best PTC precursor
1
IrCl(IMes)(COD). For THF, the associated H NMR signal enhancement for the ortho proton signal of pyridine shows an
increase of 600-fold at 298 K. The level of signal enhancement can be increased further through warming or varying the magnetic
field experienced by the sample at the point of catalytic magnetization transfer.
niazid,20 pyrazinamide,20 pyrazole,10 and acetonitrile.13 The
magnetic field experienced by the catalyst at the point of
INTRODUCTION
■
The underlying sensitivity problem in NMR has led to the
polarization transfer is instrumental in determining the
development and utilization of hyperpolarization methods to
amplitude and identity of the created magnetic states.18 The
address this issue.1−3 Para-hydrogen-induced polarization4
use of NHC ligands in the catalyst dramatically increased the
(PHIP) is one such method, which produces non-Boltzmann
enhancement levels relative to those with PCy3.14,15,20,21 These
spin populations by the incorporation of para-hydrogen (p-H2),
charged systems contain three analyte molecules and are
efficient SABRE catalysts in polar solvents such as methanol,
with benzene being less effective. In this class of catalyst,
SABRE transfer proceeds into the two analyte molecules that
are trans to hydride ligands. It is ligand exchange, a secondary
process, that results in visible hyperpolarization in the analyte
molecule in solution.
a nuclear singlet, into unsaturated molecules.5,6 This chemical
transformation results in increased signal intensity in the
corresponding NMR spectra of reaction product nuclei
originating from, or coupled to, those that were p-H2-derived
nuclei.7,8
Unlike classical PHIP methods, SABRE (signal amplification
by reversible exchange)9 does not involve incorporation of p-H2
An alternative catalyst system has been reported that is based
into the analyte that is to be polarized. Polarization is instead
transferred via a J-coupling that exists between hydride ligands
on [Ir(H)2(IMes)(PCy3)(analyte)2]Cl.13 Now the exemplified
analytes are pyridine and acetonitrile. The mixed analyte-
containing catalyst, [Ir(H)2(IMes)(PCy3)(pyridine)-
(CH3CN)]Cl, which is also charged, proved most effective
that are derived from p-H2 and those of the spin-1/2 analyte
nuclei in the polarization transfer catalyst.9 These catalysts most
commonly take the form of cationic iridium complexes, which
possess either phosphine10−13 or N-heterocyclic carbene
for SABRE even though it contains a pair of chemically and
(NHC) ligands.14,15 One of the most successful catalysts to
magnetically inequivalent hydride ligands. These results
confirmed that it is possible to block the two axial coordination
date is based upon [Ir(H)2(IMes)(analyte)3]Cl, and it contains
magnetically inequivalent but chemically equivalent hydride
ligands.15 This complex has proved active for a wide range of
analytes, which include pyridine,15,16 nicotinamide,17−19 iso-
Received: April 14, 2015
© XXXX American Chemical Society
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sites in the SABRE catalyst with nonlabile ligands without
suppressing activity, while retaining a charged system. Species
such as [Ir(H)2(IMes)(PCy3)(pyridine)2]Cl with magnetically
inequivalent but chemically equivalent hydride ligands, while
being directly related to [Ir(H)2(IMes)(analyte)3]Cl, proved
less effective due to poor ligand exchange. Herein we present
data dealing with the use of a neutral iridium catalyst containing
a cis-spanning bidentate NHC to mediate polarization transfer
from p-H2 to pyridine and nicotinamide. The use of the chelate
effect to promote and control catalysis is well exemplified by
phosphines,22 bipyridyl,23 pincer,24,25 and pincer carbene
ligands.26−29 We seek to retain a carbene functionality while
adding a hard anionic oxygen ligand and have selected
phenolate because it has found wide use in many inorganic
systems.30−32 Many iridium aliphatic alkoxide systems exist,
although these can readily undergo β-hydride elimination.33,34
In comparison, phenolate ligands are more stable due to the π-
interaction and lack of β-protons. A related system has been
shown to act as a hydrogenation catalyst with no elimination of
the phenol.35 Here we employ a phenolate-substituted NHC
that can coordinate to the same face of the metal to make
Ir(κC,O-L1)(COD) (1) [where COD = cyclooctadiene and L1
= 3-(2-methylene-4-nitrophenolate)-1-(2,4,6-trimethylphenyl)-
imidazolylidene] in order to achieve this and demonstrate good
activity in nonpolar solvents while retaining optimal catalytic
behavior.
singlet at δ ∼7.03, but upon cooling its rotation is hindered and
two singlets separate from it, which resonate at δ 7.06 and 6.96.
Line-shape analysis38,39 of this behavior enabled the activation
enthalpy for mesityl group rotation, ΔH⧧ to be estimated as
,
65.5
3.1 kJ mol−1, with the corresponding value for ΔS⧧
being +28.0 10.9 J K−1 mol−1. These ΔH⧧ and ΔS⧧ values are
commensurate with those expected for an intramolecular ring
rotation40,41 (see Supporting Information (SI) for the raw
data). We note that similar coalescence effects are also observed
when 1 is present in a THF-d8 solution in accordance with a
process where there is little charge separation.40
In a separate dynamic process, the two proton resonances of
the CH2 linker are also broadened, in this case into the baseline
at 298 K. At 253 K these protons provide two distinct doublets
at δ 6.60 and 4.79 that share a common coupling of 13.97 Hz.
This behavior is a consequence of the fact that the two CH2
protons are diastereotopic, due to their differing exo and endo
orientations. They become equivalent by inversion of the
conformation of the seven-membered ring through ring-flip and
alkoxide lone pair inversion.42 The complexity of the associated
NMR spectral changes and the large chemical shift difference
that exists between these resonances preclude the quantitative
analytical assessment of this process through line-shape
analysis.
The structure of 1 was further confirmed by X-ray diffraction.
Figure 1 shows the corresponding ORTEP plot, determined at
RESULTS AND DISCUSSION
■
Synthesis and Characterization. The synthesis of
Ir(κC,O-L1)(COD) (1) via a transmetalation reaction was
achieved according to Scheme 1. Occhipinti et al. have
Scheme 1. Reaction Scheme for the Formation of Ir(κC,O-
36
37a
L1)(COD), 1, from AgL1 and [Ir(COD)Cl]2
Figure 1. ORTEP plot of 1. Hydrogens have been omitted for clarity.
Selected bond lengths (Å) and angles (deg): Ir1−O1, 2.067(3); Ir1−
C8, 2.049(4); Ir1−C20, 2.111(5); Ir1−C21, 2.101(5); Ir1−C24,
2.185(4); Ir1−C25, 2.183(4); C20−C21, 1.444(7); C24−C25,
1.393(7); C8−Ir1−O1, 92.88(14).
110 K. The crystals employed for this analysis were grown by
the slow diffusion of hexane into a dichloromethane solution of
1. The crystal exhibited both pseudomerohedral and multi-
crystal twinning; see see experimental procedures X-ray section
for further details. The structure has a distorted square planar
geometry around iridium, where the corresponding bond angles
are close to 90°. 1 can be compared to two related Ir(I)
complexes, Ir(IMes)(COD)(OSiMe3), containing a siloxide
ligand,43 and [Ir(IMes)(COD)(py)]Cl, containing a pyridine
ligand.44 These complexes also proved to adopt distorted
square planar arrangements. 1 has an Ir−O bond length of
2.067(3) Å, which compares well to the value of 2.020(4) Å
reported for Ir(IMes)(COD)(OSiMe3). For [Ir(IMes)(COD)-
(py)]Cl the Ir−N bond length is 2.0954(17) Å. The CC
bond of COD, which lies trans to the phenoxide in 1, is the
longest of the series and hence the weakest (1.444(7) Å,
compared to 1.407(5) Å for Ir(IMes)(COD)(OSiMe3) and
1.399(3) Å for [Ir(IMes)(COD)(py)]Cl). Consequently, the
phenoxide ligand in 1 must be the most electron-donating
ligand of this series, and its iridium metal center must therefore
a
Reagents and conditions: (i) Ag2O, THF, toluene, reflux, 3 h; (ii)
[Ir(COD)Cl]2, THF, rt, 18 h.
previously reported the synthesis of the silver carbene complex
AgL1 and attached it to ruthenium. Here we use a similar
36
route to make 1. Notably, the precursor, L1HBr in Scheme 1,
shows a broad infrared (IR) signal at ∼3000 cm−1 for a
phenolic O−H stretch as well as signals at 1339 and 1279 cm−1
for the O−H bend and C−OH stretching mode, respectively.36
Complex 1 was prepared in 96% yield, and its structure
confirmed by NMR, X-ray, and mass spectrometry. A peak is
present in the IR spectrum of 1 at 1293 cm−1 due to a C−OIr
stretch.
Comparison of the NMR data for 1 at 298 K in CD2Cl2 with
that at 253 K revealed that its proton chemical shifts are
strongly temperature dependent. At 298 K, the two aromatic
proton resonances for the mesityl group appear as a broad
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be the most electron rich. Due to this increase in electron
density at iridium, the oxidative addition of H2 to 1 will be
disfavored due to repulsion between it and the electron density
provided by the ligands in the five-coordinate transition state.45
The bond angle in 1 that exists between C(carbene)−Ir−O is
92.88(14)° and smaller than that of C(carbene)−Ir−N
(94.45(7)°) in [Ir(IMes)(COD)(py)]Cl. This change is a
consequence of the chelate effect, which acts here to restrict the
bond angle, but when the freely orientating complex Ir(IMes)-
(COD)(OSiMe3) is compared, the C(carbene)−Ir−OSi angle is
now compressed to 88.2(2)°. Therefore, steric interactions
must play a role in determining the shape of these complexes.
Reactivity of 1 toward H2 or Pyridine. Upon addition of
p-H2 at 3 bar pressure to a CD2Cl2 solution of 1 at 253 K, an
immediate reaction is observed to take place and the formation
of a new dihydride complex (2) is indicated (see Scheme 2).
The very broad hydride and hydrogen signals that are seen in
the associated H NMR spectra confirm that the interconver-
1
sion between 1 and 2 is rapid; upon heating this sample to 303
K, the hydride resonances broaden into the baseline of the
NMR spectrum. The H2/Ir−H exchange process that is
indicated by this observation provides a route to destroy the
p-H2 that is present in solution because the relaxation times of
metal hydride ligands are relatively short.47,48 Therefore,
despite PHIP being observed when a sample at 243 K is
removed from the magnet, shaken, and then returned to the
magnet for measurement, this effect does not last. Furthermore,
at 298 K, this pair of hydride signals shows very small levels of
PHIP and appears only transiently, thereby confirming that the
p-H2 present in solution is consumed very rapidly. We note that
significant signal averaging is necessary to observe the hydride
resonances of 2 with normal, thermally equilibrated NMR
polarization.
Scheme 2. Formation of Dihydride 2 from 1
In the corresponding low-temperature spectrum, a second
pair of very weak hydride signals is observed at 243 K that also
exhibit PHIP. These signals are observed only after a
considerable number of scans under conditions where the
magnetism of the molecules is thermally equilibrated. These
new hydride ligand signals appear with just ca. 6% of the
intensity of those for 2 and are hence too weak to allow the
associated product to be characterized. They are likely,
however, to arise from a minor isomer of 2 that differs from
the main isomer according to the conformation of the seven-
membered ring. These signals do not appear in the
corresponding high-temperature NMR spectrum, presumably
due to dynamic averaging between the rapidly interconverting
isomers.
This species yields a pair of PHIP polarized hydride resonances
at δ −10.84 and −21.51 in the corresponding 1H NMR
spectrum, where the chemical shift values are diagnostic of sites
that lie trans to alkene and alkoxide, respectively. We note that
similar spectral changes have been reported when H2 adds to
[Ir(COD)(NCCH3)(PMe3)]BF4 to form [Ir(H)2(COD)-
(NCCH3)(PMe3)]BF4.46 The product of the reaction with 1
is Ir(H)2(κC,O-L1)(COD) (2), and it exists in equilibrium with
1, where a steady state of just 5% conversion is achieved under
these conditions.
Upon adding pyridine to a CD2Cl2 solution of 1, the slow
1
displacement of COD is indicated in the resulting H NMR
spectrum. However, no clearly identifiable reaction product is
observed in this spectrum and decomposition occurs. After 6
days of reaction with pyridine, the subsequent addition of H2 to
Scheme 3. Formation of Ir(H)2(κC,O-L1)(py)2, 3, from 1 with the Vacant Site Represented through the Shaded Orbital and the
Purple and Magenta Hydride Ligand Labels Detailing the Hydride Interchange Processes
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the resulting solution leads to the formation of a new dihydride
species in 60% yield after a further 3 days of activation.
Formation of 3 from 1 upon Addition of Pyridine and
H2. In contrast, 1 reacts very slowly and cleanly with H2 when it
is located in a freshly prepared CD2Cl2 solution containing
pyridine at 298 K to form the same reaction product. We have
identified this product as neutral Ir(H)2(κC,O-L1)(py)2, 3 (see
Scheme 3), through a series of observations that we now
describe. We note that after 24 h 40% conversion of a 1.6 ×
10−5 mol solution of 1 with an 8-fold excess of pyridine under 3
bar of pressure of H2 to 3 is achieved; this reaction goes to
completion on a longer time scale.
The infrared spectrum of 3 contains a noteworthy C−OIr
stretch at 1274 cm−1 and no evidence for either an OH or OD
stretch. The corresponding stretch in 1, an Ir(I) complex, is
1293 cm−1, which suggests that the Ir(III)−alkoxide bond in 3
is strengthened. Furthermore, starting material 1 possesses a
strong yellow-orange color when in solution, and this is
retained upon activation with pyridine and H2. UV−vis analysis
of 1 in CH2Cl2 reveals the complex yields an absorption band at
405.5 nm with a molar extinction coefficient, ε, of 21 060 dm3
mol−1 cm−1. Similar analysis of the activated complex, 3, reveals
an absorption band at the slightly higher energy of 398.6 nm
with a reduced ε value of 10 975 dm3 mol−1 cm−1. Interestingly,
when the related complex [Ir(H)2(IMes)(pyridine)3]Cl is
monitored in methanol, no equivalent transition is present,
the most prominent feature being a broad blue-shifted band at
341.0 nm with an ε of 3413 dm3 mol−1 cm−1. The large molar
absorptivity values exhibited by 3 are consistent with its intense
color and the detection of a charge transfer band.
conformer is observed. The rate of this process is 4.00 0.08
s−1, and the pair of exchanging hydride ligands remain trans to
their original partner throughout. Probing the reverse step, by
selective irradiation of HA′, enabled the rate of transfer of HA′
into HA to be quantified as 19.80 0.33 s−1. This means that
the equilibrium constant connecting 3A′ and 3A is 4.95, and we
note that it matches that determined by integration.
Exchange of these two hydride ligands into free H2 or into a
site that is trans to nitrogen is not observed at 233 K. The latter
process, which corresponds to that of isomer interconversion, is
however evident at 298 K alongside that of H2 loss, as shown in
Scheme 3. In fact, the H2 loss process proved to be inhibited by
the addition of pyridine, while the process of hydride site
interchange was unaffected.
1
When the corresponding H EXSY measurement procedure
was used to monitor pyridine exchange in 3, only loss of the
equatorial ligand was observed, in a process that followed
saturation kinetics. These observations confirm that the loss of
pyridine from 3 is therefore dissociative. Furthermore, the
resulting 16-electron intermediate must have a trigonal
bipyramidal shape or undergo very rapid hydride site
interchange, to equilibrate hydrides HA and HB. This is
reflected in the fact that the hydride ligand exchange process is
unaffected by added pyridine. It can also be concluded that H2
loss from 3 must therefore proceed after pyridine loss (see
Table 1). These deductions are supported by the fact that the
Table 1. Summary of the Specified Ligand Loss Rates from 3
a
as a Function of Pyridine Concentration in CD2Cl2
no. of py equiv by NMR ratio
rate of py loss/s−1
rate of H2 loss/s−1
As expected, COD is released during the formation of 3, and
it proved to be hydrogenated on a slower time scale, first to
form COE and then COA [where COE = cyclooctene and
COA = cyclooctane] according to NMR analysis. The
substitution of COD for pyridine in a related cyclometalated
square planar palladium system has been reported,49 as has the
hydrogenation of COD in a series of related systems.50−52
Neutral 3 forms according to Scheme 3, and the alternative
zwitterionic Ir−O bond cleaved product [Ir(H)2(κC-L1-O−)-
(py)3]+ is not observed. At 298 K, the 1H NMR spectrum of 3
contains two distinct hydride ligands, which yield a broad
singlet at δ −21.80 for the trans pyridine site (HA) and a sharp
doublet at δ −28.90 for the trans oxygen site (HB). Further
analysis of these NMR spectra of 3 revealed that, upon cooling
to 223 K, each hydride signal pair separates into two sets of
hydride resonances, at δ −21.40 (HA) and −29.80 (HB) and at
δ −22.60 (HA′) and −29.00 (HB′), respectively, with relative
intensity 83:17. The two pairs of hydride resonances share
common −8.9 and −7.3 Hz couplings, respectively, and are due
to two conformers, 3A and 3A′, which result from differing
orientations of the seven-membered metallocycle. A 15N-
HMQC 2D NMR measurement completed at 233 K located
two signals at δ 258.4 and 240.7 for the equatorial and axial
pyridine ligands of the major isomer 3A, respectively. Given that
the chemical shift of free pyridine is 303 ppm, and the
difference between it and the bound signal has been suggested
to be indicative of bond strength, the ligand trans to the
carbene is more strongly bound.53 Full characterization data for
3A at 233 K in CD2Cl2 is presented in the SI.
15
25
30
50
0.28 0.03
0.28 0.03
0.31 0.01
0.28 0.03
0.078 0.003
0.071 0.003
0.053 0.002
0.042 0.002
a
Data confirm pyridine loss is dissociative and that both hydride site
interchange and H2 loss occur after this step.
rate of H2 loss for a solution containing a 50-fold excess of
pyridine was 0.042
pyridine loss rate was 0.28
exchange mechanism based on the transient formation of the
0.002 s−1, while the corresponding
0.03 s−1. In addition, a H2
55,56
related complex IrCl(H)2(η2-H2)(PPri3)2
has been de-
scribed previously. We note that these measurements were
relatively straightforward to complete in CD2Cl2, as no H/D
exchange is evident on the time scales of these measurements.
When examined in MeOD-d4, 1 still reacts with H2 and
pyridine to form 3 in an analogous way to that described in
CD2Cl2. The hydride ligand resonances of 3 appear at δ −21.62
and −29.22 in this solvent and are hence very similar in value to
those in CD2Cl2. In this case, 100% conversion of a 7.9 × 10−6
mol solution of 1 is observed after just 24 h, and thus the
activation of 1 is much more facile in this polar protic solvent
when compared to CD2Cl2. At 243 K, H/D exchange between
the hydrides and the solvent is not observed. However, at 270
K, deuterium exchange from the solvent into the hydride
resonances of 3 proceeds with an experimentally determined
rate constant of 4.24 × 10−5 6 × 10−7 s−1, and both HD and
MeOH-d3 are formed. At 298 K, the rate constant for H/D
exchange increases to 8.19 × 10−4 8 × 10−6 s−1.
Ligand Exchange Pathways in Ir(H)2(κC,O-L1)(py)2, 3.
When the hydride resonance for HA of 3 in CD2Cl2 is
selectively irradiated in an EXSY54 experiment at 233 K,
magnetization transfer into only the HA′ signal of the second
In order to examine the pyridine and H2 exchange processes
more reliably, the solvent MeOH-d3 was employed. At 298 K, a
sample containing 15 equiv of pyridine enabled the observation
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that the hydride ligand trans to the oxygen donor proved to
exchange into H2 with an experimentally determined rate
constant of 0.54 0.03 s−1, a ΔH⧧ of 67.5 7 kJ mol−1, and a
solvents after 2 and 24 days, respectively. The hydride ligand
that is trans to oxygen in 3 always gives rise to a sharp doublet
1
in these H NMR spectra, while the resonance for the hydride
ΔS⧧ of −17.3
25 J K−1 mol−1. In contrast, pyridine
ligand that lies trans to pyridine is considerably broader. This
suggests that pyridine loss is possible in accordance with the
observations we described earlier in the article.
dissociation at 298 K occurs with a rate constant of 1.33 0.23
s−1, a ΔH⧧ of 71.1 3 kJ mol−1, and a ΔS⧧ of 2.4 12 J K−1
mol−1. In MeOH-d3, H2 loss therefore proceeds at a slower rate
than pyridine loss, and upon increasing the number of
equivalents of pyridine, the rate of H2 loss is decreased, while
the rate of pyridine loss remains constant. This is again
consistent with the mechanism shown in Scheme 3 and shows
that the exchange process remains dissociative in methanol. A
mechanism for such a H/D exchange process in a closely
related system has been proposed by Brookhart et al.57,58
Reaction of 3 with p-H2. Upon addition of p-H2 to a
CD2Cl2 solution of 1 at 298 K, a single pair of PHIP-enhanced
hydride signals are observed that are indicative of 3.59 The
enhanced signal at δ −28.90 that is due to the HB hydride
ligand of 3 and that lies trans to oxygen has a line-width at half-
height of 14.6 Hz, and signal integration confirms a signal
enhancement of 346-fold relative to that seen in the normal
trace. Its partner appears at δ −21.40 with a half-height width of
45.1 Hz. When the same measurement is made at 268 K or
below, neither the hydride resonances of 3A or 3A′ show PHIP
in accordance with the suppression of their exchange with the
free H2 pool.
When a sample containing 0.05 M pyridine and 15 mol % 1
in CD2Cl2 is examined in this way, after polarization transfer in
a 6.5 × 10−3 T field, strong SABRE is visible in the NMR
signals observed for free pyridine that is present in solution.
This effect manifests itself clearly in the resulting single-scan 1H
NMR measurement as a 141-fold-enhanced ortho pyridine
proton resonance when compared to the corresponding signal
without polarization transfer. We note that complex 3 is
detected as the sole inorganic reaction product in these
solutions for periods out to 24 days and that no deuterium
exchange with the solvent is evident.
3 also forms cleanly in both benzene-d6 and THF-d8
solutions, where it is again stable for extended periods of
time. We observed, however, that the slow reaction means that
significant time is necessary for full activation. When a benzene-
d6 system is examined for SABRE, after 2 days of activation, a
121-fold signal enhancement is seen for the same ortho pyridine
proton signal under similar conditions. In THF-d8 the
analogous level of signal gain reduces to 98-fold for a similar
sample under similar conditions. Despite this drop in SABRE
efficiency in THF-d8, these observations in CD2Cl2, benzene-d6,
and THF-d8 confirm our original hypothesis that neutral 3 is a
good SABRE catalyst in a variety of low-polarity solvents. When
the same systems are examined after 24 days the signal
enhancements for the ortho protons of pyridine in these
samples have now increased to a maximum of 346-fold, 561-
fold, and 600-fold for CD2Cl2, benzene-d6, and THF-d8,
respectively. This information confirms that while the catalyst
takes longer to fully form in these less polar solvents, it delivers
good activity.
In order to test for the formation of zwitterionic [Ir(H)2(κC-
L1-O−)(py)3]+, we have also examined the formation of 3 when
a 1:1 mixture of d5- and h5-pyridine is employed. Under these
conditions no new PHIP-enhanced hydride ligand signals are
seen even though related studies on [Ir(H)2(IMes)(pyridine)3]
2
Cl would suggest that the presence of the H-label is sufficient
to break hydride ligand symmetry and thereby enable it to
exhibit PHIP. For these reasons we conclude that the Ir−O
bond in 3 is retained throughout these measurements in
CD2Cl2. Analogous results are observed when the solvent is
changed to methanol-d4, so again the Ir−O bond is retained.
Solvent Effects on SABRE Catalysis by 3. Evidence for
When the solvent is changed to polar protic methanol or
ethanol, different behavior is observed. In MeOD-d4 for a
sample containing 0.1 M pyridine and 5 mol % 1, the initial
levels of SABRE that were observed in the 1H NMR resonances
of pyridine are small (∼6 fold for the ortho 1H resonances) after
shaking in a polarization transfer field (PTF) of 6.5 × 10−3 T at
40 °C. However, when the same sample is tested 72 h later, the
signal enhancement levels are far greater (178-, 96-, and 52-fold
1
the SABRE effect is also seen in many of the H NMR signals
that are observed in these NMR spectra. The simplest
experimental procedure to view the SABRE effect involves
taking an NMR tube under an atmosphere of p-H2 and shaking
it for a set time period in a known magnetic field before rapidly
making an NMR observation. We now describe the results of
this process in the solvents CD2Cl2, benzene-d6, THF-d8,
methanol-d4, and ethanol-d6. We discuss the catalyst activation
process and highlight the species that are formed. Table 2
details the performance of 1 under SABRE in the indicated
1
observed for ortho, meta, and para H resonances of pyridine,
respectively). A typical trace is shown in Figure 2. These data
confirm our earlier observation that 1 takes a significant time to
fully activate. However, upon longer time scales, the level of
delivered polarization falls as the pyridine substrate becomes
2H-labeled; 50% deuteration of the ortho proton signal for
pyridine was observed after 24 days in methanol-d4. The
analogous deuterium exchange process is seen in ethanol-d6,
but it now proceeds more slowly in accordance with the slower
formation of 3; no deuterium exchange is seen in the nonprotic
solvents.
1
Table 2. Pyridine H NMR Signal Enhancements Produced
for a Series of 0.05 M Pyridine and 15 mol % 1 Solutions at
298 K Using 3 bar of p-H2 after an Activation Period of 48 h
and 24 days
1
pyridine H NMR SABRE signal enhancements (fold)
In order to demonstrate that the polarization transfer to
pyridine observed in these systems arises from SABRE rather
than one-proton PHIP,60 a d5-pyridine-containing solution was
also examined. These measurements were completed after
shaking the sample in a PTF of 6.5 × 10−3 T and involved the
48 h
24 days
deuterated solvent
ortho
meta
para
ortho
meta
para
benzene
THF
121
98
93
61
56
49
65
36
82
561
600
346
282
29
469
442
212
145
24
253
265
159
142
18
1
DCM
141
86
105
35
application of a 45° excitation pulse. The H NMR signal for
ethanol
methanol
residual d4-pyridine was shown to polarize, delivering an in-
phase emission peak at δ 8.56, which rapidly decayed to
185
130
E
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Organometallics
Article
IrCl(IMes)(COD), 4.65,15 When activated with pyridine and
H2, 4 has been reported to form [Ir(H)2(IMes)(py)3]Cl, which
then enables polarization transfer. The route to H2 addition to
4 is via the formation of [Ir(IMes)(COD)(py)]Cl, which
actually adds H2 faster than the precursor IrCl(IMes)(COD).
In contrast, 1 takes a significant time to activate due to the
analogous indirect reaction pathway being no longer available
because of the strong Ir−O bond.
Table 3 displays a series of enhancement data that results
from the SABRE of the substrates pyridine and nicotinamide in
MeOD-d4 as a function of temperature and transfer field using
both 4 and 1. It is clear from this table that 4 is the superior
room-temperature catalyst, delivering in some instances 30
times more signal intensity when compared to that produced by
1. For 1, the signal enhancement seen for bulk nicotinamide
proton HA increases by a factor of ∼5 on going from 2 × 10−4
T to 6.5 × 10−3 T at 30 °C and a factor of ∼6 at 60 °C. This
compares with a drop in signal intensity when 4 is employed at
the higher temperatures. Now, under transfer at 6.5 × 10−3 T,
proton HA of nicotinamide shows better enhancement at 30 °C
rather than 60 °C. These investigations on nicotinamide were
conducted because of the recent publications that investigate
the biological implications of hyperpolarizing nicotinamide in a
move toward developing imaging applications that utilize the
SABRE technique.17−19,21
1
Figure 2. H NMR spectra of a sample containing 0.05 M pyridine
and 15 mol % 1 in MeOD-d4 after (A) thermal equilibrium at high
field and (B) polarization transfer from p-H2 at 6.5 × 10−3 T, using a
45° pulse. Pyridine and hydride species are labeled.
thermal magnetization over a time course of ∼30 s. If this signal
was to be enhanced through the one-proton PHIP effect, it
should remain enhanced over this period. For this reason we
conclude here that SABRE is the only polarization transfer
pathway operating.61,62
The magnetization transfer process was also probed by
OPSY (only para-hydrogen spectroscopy63,64). This pulse
sequence enables the detection of signals that are derived
directly from either p-H2 or nuclei that have received
polarization from it. Two representative 1H NMR spectra
that were recorded after shaking in a PTF of 2 × 10−4 T at 0 or
60 °C, respectively, are shown in Figure 3. It can be readily seen
The effect of temperature is also clearly illustrated in Figure
4. The continued improvement in the activity of 1 with an
increase in temperature is associated with an increase in ligand
dissociation rate.15 In contrast, the rate of ligand exchange with
4 actually becomes too rapid for good catalysis upon exceeding
1
30 °C. A full comparison of temperature-dependent H NMR
enhancements for pyridine and nicotinamide in MeOD-d4 as
polarized by 1 and 4 is detailed in the SI.
Further optimization was achieved by altering the PTF. This
study was completed using a polarizer equipped with a
vertically aligned coil that is capable of producing a well-
defined vertical field between 0.5 × 10−4 and 1.5 × 10−2 T in
steps of 0.5 × 10−4 T.15,18 The four hyperpolarized 1H
resonances of nicotinamide resulting from polarization in set
fields between −1.5 × 10−2 and +2.5 × 10−3 T are illustrated in
Figure 5. The maximum signal enhancement proved to be
delivered by 1 when the PTF lies between −6.5 × 10−3 and
−7.5 × 10−3 T for sites HA, HB, and HC, and their signals all
appear in emission. The corresponding meta proton (HC)
resonance undergoes two phase changes on moving from −1.5
× 10−2 T to −1.25 × 10−2 T and from −6.5 × 10−3 T to −5.0 ×
10−3 T, respectively, and shows relatively weak signal
amplification levels. Related observations have been reported
for pyridine with 4, and the profiles are remarkably similar even
though the two catalysts are very different in nature.13
1
Figure 3. H OPSY-dq NMR spectra of a sample containing 0.1 M
pyridine and 5 mol % 1 in MeOD-d4 after polarization transfer from p-
H2 at 2 × 10−4 T and 60 °C (A) or 0 °C (B).
Two other substrates that have been shown to polarize using
4 for SABRE in methanol are quinoline66 and nicotine.21 We
have therefore examined these substrates using 1 in benzene, as
this is one of the most efficient solvent systems for this neutral
catalyst. Both compounds show enhanced signals, with
polarization transfer to nicotine being more efficient than
quinoline. Nicotine exhibits a total proton enhancement of 360-
fold across the four aromatic proton sites, with quinoline
showing a 54-fold increase across six of its proton sites. This
shows that the use of specially designed catalysts in nonpolar
solvents could prove very important for identifying low-
concentration analytes in solution via the SABRE approach.
from these NMR spectra that greater polarization transfer is
evident at 60 °C and that polarization transfer via SABRE into
free pyridine occurs. The two NMR spectra are presented in
magnitude mode, and the signals for pyridine and the hydride
resonances of 3 dominate, which confirms that they receive
visible polarization from p-H2.
SABRE Catalysis Optimization Using 3. In order to
optimize the efficiency of polarization transfer in methanol
from p-H2 to substrates using 1, a number of conditions have
been investigated. These include varying the temperature, the
PTF, and the catalyst. The most widely used catalyst to date is
F
DOI: 10.1021/acs.organomet.5b00311
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Article
Table 3. Signal Enhancements Obtained for Each of the Listed 1H Resonances of Pyridine and Nicotinamide after Polarization
a
Transfer in Fields of Either 2 × 10−4 T or 6.5 × 10−3 T Using Catalyst 1 or 4 in MeOD-d4
polarization transfer at 2 × 10−4
T
polarization transfer at 6.5 × 10−3
T
1
4
1
4
1H resonance
30 °C
60 °C
30 °C
616
188
247
147
74
60 °C
269
35
30 °C
116
70
60 °C
254
158
66
30 °C
677
182
295
469
306
64
60 °C
474
212
205
393
242
55
pyridine HA, HE
pyridine HB, HD
pyridine HC
44
20
10
4
72
20
20
7
113
117
59
28
nicotinamide HA
nicotinamide HB
nicotinamide HC
nicotinamide HD
20
40
2
2
15
33
2
4
99
54
6
18
3
5
107
85
20
40
364
293
a
For proton assignments see the SI.
would be expected to be stable. The pyridine and H2 ligand loss
processes enable the incorporation of p-H2 into 3 and thereby
facilitate its action as a good SABRE catalyst.
In methanol, the formation of 3 proceeds cleanly with no
evidence being observed for zwitterionic [Ir(H)2(κC-L1-O−)-
(py)2(CD3OD)]+ or [Ir(H)2(κC-L1-O−)(py)3]+ in solution.
The ligand exchange rates for substrate dissociation and H2 loss
have been determined in MeOH-d3, and both increase with
temperature. The H2 loss process has been suggested to
proceed via Ir(H)2(H2)(κC,O-L1)(py) as shown in Scheme 3.
The associated activation parameters for the H2 loss process,
ΔH⧧ and ΔS⧧, are 67.5 7 kJ mol−1 and −17.3 25 J K−1
mol−1, respectively. In contrast, pyridine dissociation, which
precedes H2 loss, occurs with a ΔH⧧ of 71.1 3 kJ mol−1 and a
ΔS⧧ of 2.4 12 J K−1 mol−1. The entropy term for this latter
reaction is smaller than expected for a dissociative exchange
pathway and may reflect an early transition state or a reduction
in the conformational freedom of the seven-membered ring.
Nevertheless, when 3 is monitored for activity as a
polarization transfer catalyst, good levels of hyperpolarization
are seen in a range of substrates when utilizing the low-polarity
solvents CD2Cl2, benzene-d6, and THF-d8, which find wide-
spread use in NMR spectroscopy. For example, in THF, the
ortho proton of the substrate pyridine shows an impressive 600-
fold enhancement, which equates to a 2% polarization level.
Furthermore, the level of PTC was found to be PTF
dependent, and in methanol, the best single-spin polarization
resulted from transfer at a field strength of between −6.5 ×
10−3 and −7.5 × 10−3 T. When PTC by 3 in methanol is
compared to that achieved by [Ir(H)2(IMes)(py)3]Cl, while
lower catalyst efficiency is observed, the enhancement levels are
still commensurate with significant time savings in both NMR
and MRI measurements. Superior catalysis is, however, found
in benzene using 1, and similar signal enhancements are seen in
dichloromethane albeit with a catalyst species present that is
different from that described previously for 4.
Figure 4. Normalized enhancement of the HA 1H NMR resonance of
nicotinamide after polarization transfer at 6.5 × 10−3 T using either 1
▲
●
(red ) or 4 (blue ).
CONCLUSIONS
■
The iridium precatalyst Ir(κC,O-L1)(COD) (1), which contains
a phenolate-substituted NHC, has been synthesized and shown
to act as a SABRE catalyst precursor in the five solvents
dichloromethane, benzene, tetrahydrofuran, methanol, and
ethanol. This overcomes the current low-polarity-solvent
limitations shown by existing SABRE catalysts. 1 contains
strong Ir−O and Ir−NHC bonds, which are preserved in all of
these solvents, and the chelate effect acts to create a seven-
membered metallocycle that adopts two interconverting
conformations in solution because of the non-planarity of the
Ir−O−C bond. In addition, the square planar catalyst precursor
1 exhibits a strong charge transfer transition at 398 nm.
We have shown that 1 and H2 exist in equilibrium with
dihydride 2 at low temperature in CD2Cl2 solution. The
hydride resonances of this product exhibit PHIP in the
1
associated H NMR spectra. 2 is an example of an unusual
M(H)2(alkene) intermediate, for which other related com-
plexes have been implicated in hydrogenation catalysis in many
systems.67,68 Upon warming 1 in the presence of pyridine and
H2 in the five described solvents, slow conversion into neutral
3, Ir(H)2(κC,O-L1)(py)2, is observed. The stepwise hydro-
genation of COD, first into COE and then COA, is also evident
upon studying this reaction at 298 K.
Neutral 3 has been shown to undergo the dissociative loss of
pyridine, according to Scheme 3, prior to H2 exchange, but no
evidence for the reductive elimination of the cis IrO and IrH
groups is observed even though the corresponding alcohol
The range of substrates exemplified includes pyridine,
quinoline, and nicotine in order to demonstrate the wider
utility of this catalyst in nonpolar solvents. We note that catalyst
activation takes on average 5 days in these relatively nonpolar
solvents, but over 500-fold ortho proton enhancement values
for pyridine result. These enhancement levels can be improved
further still by warming and using an optimized PTF. We
therefore expect derivatives of this neutral catalyst to
dramatically widen the applicability of SABRE for NMR
measurements in the future, and we are now seeking to prepare
G
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Article
Figure 5. 1H NMR field plots showing the signal intensity of the four 1H (A-HA, B-HD, C-HB, D-HC) resonances of nicotinamide over the range of
−1.5 × 10−2 to +2.5 × 10−3 T.
structure solution was the direct methods,70 within SHELXS.
a precatalyst such as Ir(κC,O-L1)(COE)2, which may activate
Refinement by full-matrix least-squares used the SHELXL algorithm
within OLEX2. All non-hydrogen atoms were refined anisotropically.
Hydrogen atoms were placed using a “riding model” and included in
the refinement at calculated positions.
rapidly while retaining both the air stability and efficiency of 1.
EXPERIMENTAL PROCEDURES
■
Methods and Equipment. All experimental procedures were
performed under an atmosphere of either dinitrogen or argon, using
standard Schlenk line techniques or an MBraun Unilab glovebox,
unless otherwise stated. General solvents for synthetic chemistry were
dried using an Innovative Technology anhydrous solvent engineering
system or were distilled from an appropriate drying agent under N2 as
necessary. Deuterated solvents (methanol-d4, methanol-d3, CDCl3,
CD2Cl2, benzene-d6, THF-d8) were obtained from Sigma-Aldrich and
Cambridge Isotope Laboratories (ethanol-d6) and used as supplied.
NMR measurements were made on a Bruker Avance III Series 400
MHz NMR spectrometer (1H at 400.13 MHz, 13C at 100 MHz) and a
500 MHz NMR spectrometer (1H at 500.13 MHz, 13C at 125.77
MHz). NMR samples were made up in Young’s tap equipped 5 mm
NMR tubes. Para-hydrogen (p-H2) was prepared by cooling hydrogen
gas over charcoal in a copper block at 30 K. COSY, HMQC, and
EXSY54 pulse sequences were used as previously described. Polar-
ization transfer experiments are described in the SI.
The crystal exhibited both merohedral and multicrystal twinning.
Only one form of twinning can be modeled. Modeling the merohedral
twinning gave a statistically better result than the multicrystal twin
model. For the merohedral twinning, a twin matrix of −1 0 0 0 −1 0 0
0 1 was used with a BASF of 0.0863(5). This left a large residual
density of 8 e Å−3 presumably due to the alternative site of iridium
from the multicrystal twinning. This was accounted for by adding a
partially occupied iridium with a refined occupancy of 0.0418(12); all
other atoms from this minor form were too weak to be modeled.
Inclusion of the partial iridium gave a significant improvement in the
structure quality (R1 [I ≥ 2σ(I)] from 4.22 to 3.45%, wR2 [All data]
from 10.06 to 7.01%, residual density from 8.08 to 1.81 e Å−3).
Synthesis of 1-(2,4,6-trimethylphenyl)-1H-imidazole.71 Gla-
cial acetic acid (10 mL), aqueous formaldehyde (3 mL, 37 wt %, 40
mmol), and aqueous glyoxal (4.6 mL, 40 wt %, 40 mmol) were added
to a round-bottom flask and heated at 70 °C. A solution of glacial
acetic acid (10 mL), ammonium acetate (3.08 g, 40 mmol, in 2 mL of
water), and mesitylamine (5.6 mL, 40 mmol) was added dropwise to
the flask over a period of 30 min. The resulting solution was
continuously stirred and heated for 18 h. The reaction mixture was
cooled to room temperature and was added dropwise to a stirred
solution of sodium hydrogen carbonate (29.4 g in 300 mL of water).
The product formed a precipitate, which was filtered off and washed
with water before being allowed to air-dry. The brown solid was
dissolved in the minimal amount of ethyl acetate and placed in a
freezer overnight, whereupon the required product crystallized and
X-ray. Single crystals of C27H30Ir1.04N3O3 (1) were grown from
slow diffusion of hexane into a DCM solution of 1. A suitable crystal
was selected, and diffraction data were collected at 110 K on an Oxford
Diffraction SuperNova diffractometer with Cu Kα radiation (λ =
1.541 84 Å) using an EOS CCD camera. The crystal was cooled with
an Oxford Instruments Cryojet. Diffractometer control, data
collection, initial unit cell determination, frame integration, and unit
cell refinement were carried out with “Crysalis” (CrysAlisPro, Oxford
Diffraction Ltd., version 1.171.34.40). Face-indexed absorption
corrections were applied using spherical harmonics, implemented in
the SCALE3 ABSPACK scaling algorithm (empirical absorption
correction using spherical harmonics, within CrysAlisPro software,
Oxford Diffraction Ltd., version 1.171.34.40). OLEX269 was used for
overall structure solution, refinement, and preparation of computer
graphics and publication data. Within OLEX2, the algorithm used for
1
was isolated via filtration (4.36 g, yield 59%): H NMR [CDCl3, 400
MHz] δ 7.44 (s, 1H, CHimidazole), 7.24 (s, 1H, CHimidazole), 6.98 (s, 2H,
2 × CHmesityl), 6.90 (s, 1H, CHimidazole), 2.35 (s, 3H, CH3), 2.00 (s, 6H,
2 × CH3); 13C{1H} NMR [CDCl3] δ 138.8, 137.5, 135.4, 133.4, 129.5,
H
DOI: 10.1021/acs.organomet.5b00311
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Organometallics
Article
129.0, 120.1, 21.0 (CH3), 17.3 (2 × CH3); MS [ESI] m/z 187.0 (M +
H)+.
(CH2), 28.9 (CH2), 28.4 (CH2), 21.0 (CH3), 18.7 (CH3), 17.6
(CH3); MS [ESI] m/z 636.19. Anal. Calcd for C27H30N3O3Ir (Mr =
636.77): C, 50.93; H, 4.75; N, 6.60. Found: C, 50.64; H, 4.52; N, 6.14.
Synthesis of 3-(2-Methylene-4-nitrophenol)-1-(2,4,6-
trimethylphenyl)imidazolium Bromide, L1HBr.36 1-(2,4,6-Trime-
thylphenyl)-1H-imidazole (0.61 g, 3.3 mmol) and 2-hydroxy-5-
nitrobenzyl bromide (0.76 g, 3.3 mmol) were dissolved in toluene
(8 mL). The resulting mixture was refluxed for 18 h, and then the
solution was cooled to room temperature. The precipitate was
collected via vacuum filtration and was washed with diethyl ether (1.25
g, yield 91%): 1H NMR [DMSO, 400 MHz] δ 11.81 (s, 1H, OH), 9.55
ASSOCIATED CONTENT
■
S
* Supporting Information
Experimental details, exchange rate data, activation parameters,
crystal structure data, UV−vis and IR analysis, SABRE analysis
1
of pyridine in different solvents, H and 13C hyperpolarized
4
(s, 1H, CHimidazole), 8.39 (d, 1H, J(HH) = 2.55 Hz, CHaromatic), 8.22
spectra of nicotinamide and pyridine, and enhancement vs
temperature graphs. The Supporting Information is available
free of charge on the ACS Publications website at DOI:
10.1021/acs.organomet.5b00311.
4
3
(dd, 1H, J(HH) = 2.55 Hz, J(HH) = 9.04 Hz, CHaromatic), 8.05 (s,
1H, CHimidazole), 7.94 (s, 1H, CHimidazole), 7.15 (s, 2H, 2 × CHmesityl),
7.09 (d, 1H, 3J(HH) = 9.04 Hz, CHaromatic), 5.53 (s, 2H, CH2), 2.33 (s,
3H, CH3), 2.01 (s, 6H, 2 × CH3); 13C{1H} NMR [DMSO, 500 MHz]
δ 163.3 (Caromatic), 141.2 (Caromatic), 140.3 (Caromatic), 139.1
(CHimidazole), 135.2 (Caromatic), 132.0 (Caromatic), 130.1 (2 × CHmesityl),
128.1 (CHaromatic), 127.9 (CHaromatic), 125.0 (CHimidazole), 124.1
(CHimidazole), 122.2 (Caromatic), 116.7 (CHaromatic), 49.2 (CH2), 21.5
(CH3), 17.7 (2 × CH3); MS [ESI] m/z 338.1 (M − Br)+.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: simon.duckett@york.ac.uk. Tel: 01904 322564.
Synthesis of Silver(II) 3-(2-Methylene-4-nitrophenolate)-1-
(2,4,6-trimethylphenyl)imidazolylidene, AgL1.36 L1 (500 mg, 1.2
mmol), silver(I) oxide (569.4 mg, 2.5 mmol), and 4 Å molecular sieves
(1.12 g) were added to a Schlenk flask under a nitrogen atmosphere.
Dried THF (8.5 mL) and toluene (8.5 mL) were added to the flask,
and the reaction mixture was stirred at reflux for 3 h. Once cooled to
room temperature, the mixture was diluted with dichloromethane (80
mL), filtered through a pad of Celite, and washed through with
dichloromethane (2 × 5 mL). The solvent was removed under
Present Address
§Ryan E. Mewis is now a Lecturer in Inorganic Chemistry at
Manchester Metropolitan University.
Author Contributions
The manuscript was written through contributions of all
authors. All authors have given approval to the final version of
the manuscript.
1
Notes
pressure to produce a yellow solid (0.45 g, yield 85%): H NMR
[CDCl3, 400 MHz] δ 8.16 (s br, 1H, CHaromatic), 7.78 (s br, 1H,
CHaromatic), 7.38 (s br, 1H, CHaromatic), 7.01 (s br, 2H, 2 × CHmesityl),
6.99 (s br, 1H, CHaromatic), 5.84 (s br, 1H, CHaromatic), 5.27 (s br, 2H,
CH2), 2.42 (s, 3H, CH3), 1.96 (s br, 6H, 2 × CH3); 13C{1H} NMR
[CDCl3] δ 174.7, 139.6, 137.2, 135.2, 134.5, 129.2 (2 × CHmesityl),
127.2 (CHaromatic), 126.8 (CHaromatic), 124.4, 122.2, 121.9 (CHaromatic),
121.5 (CHaromatic), 50.3 (CH2), 21.4 (CH3), 17.9 (2 × CH3); MS
[ESI] m/z 783 (Ag dimer, protonated phenol groups).
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We acknowledge the Nuffield Foundation for an undergraduate
bursary for A.J.R. (URB/39689), Bruker Biospin, the University
of York, the EPSRC (grant no. EP/G009546/1), and the
Wellcome Trust and Wolfson Foundation (092506 and
098335) for their generous funding.
Synthesis of Iridium(I) (3-(2-Methylene-4-nitrophenolate)-1-
(2,4,6-trimethylphenyl)imidazolylidene) (Cyclooctadiene), 1.37
AgL1 (170 mg, 0.38 mmol) and [Ir(COD)Cl]2 (129 mg, 0.19 mmol)
were added to a Schlenk flask, which was evacuated and filled with
nitrogen. Dry THF (12 mL) was added to the flask, and the reaction
mixture was stirred overnight at room temperature. The mixture was
diluted with DCM, filtered through a pad of Celite, and then purified
by column chromatography (silica, DCM/acetone, 80:20). It was
evaporated to dryness to produce an orange-brown powder (0.23 g,
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