Iridium(III) hydrido N-heterocyclic carbene-phosphine complexes as catalysts in magnetization transfer reactions

Article abstract of DOI:10.1021/ic401783c

The hyperpolarization (HP) method signal amplification by reversible exchange (SABRE) uses para-hydrogen to sensitize substrate detection by NMR. The catalyst systems [Ir(H)₂(IMes)(MeCN)₂(R)]BF₄ and [Ir(H)₂(IMes)(py)₂(R)]BF₄ [py = pyridine; R = PCy₃ or PPh₃; IMes = 1,3-bis(2,4,6-trimethylphenyl) imidazol-2-ylidene], which contain both an electron-donating N-heterocyclic carbene and a phosphine, are used here to catalyze SABRE. They react with acetonitrile and pyridine to produce [Ir(H)₂(NCMe)(py)(IMes)(PPh ₃)]BF₄ and [Ir(H)₂(NCMe)(py)(IMes)(PCy ₃)]BF₄, complexes that undergo ligand exchange on a time scale commensurate with observation of the SABRE effect, which is illustrated here by the observation of both pyridine and acetonitrile HP. In this study, the required symmetry breaking that underpins SABRE is provided for by the use of chemical inequivalence rather than the previously reported magnetic inequivalence. As a consequence, we show that the ligand sphere of the polarization transfer catalyst itself becomes hyperpolarized and hence that the high-sensitivity detection of a number of reaction intermediates is possible. These species include [Ir(H)₂(NCMe)(py)(IMes)(PPh₃)] BF₄, [Ir(H)₂(MeOH)(py)(IMes)(PPh₃)]BF ₄, and [Ir(H)₂(NCMe)(py)₂(PPh ₃)]BF₄. Studies are also described that employ the deuterium-labeled substrates CD₃CN and C₅D₅N, and the labeled ligands P(C₆D₅)₃ and IMes-d₂₂, to demonstrate that dramatically improved levels of HP can be achieved as a consequence of reducing proton dilution and hence polarization wastage. By a combination of these studies with experiments in which the magnetic field experienced by the sample at the point of polarization transfer is varied, confirmation of the resonance assignments is achieved. Furthermore, when [Ir(H)₂(pyridine-h₅)(pyridine-d₅)(IMes) (PPh₃)]BF₄ is examined, its hydride ligand signals are shown to become visible through para-hydrogen-induced polarization rather than SABRE.

Full text of DOI:10.1021/ic401783c

Article
pubs.acs.org/IC
Iridium(III) Hydrido N‑Heterocyclic Carbene−Phosphine Complexes
as Catalysts in Magnetization Transfer Reactions
Marianna Fekete, Oliver Bayfield, Simon B. Duckett,* Sam Hart, Ryan E. Mewis, Natalie Pridmore,
Peter J. Rayner, and Adrian Whitwood
Department of Chemistry, Centre for Hyperpolarization in Magnetic Resonance, University of York, York Science Park, York, YO10
5NY, U.K.
S
* Supporting Information
ABSTRACT: The hyperpolarization (HP) method signal
amplification by reversible exchange (SABRE) uses para-
hydrogen to sensitize substrate detection by NMR. The catalyst
systems [Ir(H)2(IMes)(MeCN)2(R)]BF4 and [Ir(H)2(IMes)-
(py)2(R)]BF4 [py = pyridine; R = PCy3 or PPh3; IMes = 1,3-
bis(2,4,6-trimethylphenyl)imidazol-2-ylidene], which contain
both an electron-donating N-heterocyclic carbene and a
phosphine, are used here to catalyze SABRE. They react with
acetonitrile and pyridine to produce [Ir(H)2(NCMe)(py)-
(IMes)(PPh3)]BF4 and [Ir(H)2(NCMe)(py)(IMes)(PCy3)]-
BF4, complexes that undergo ligand exchange on a time scale commensurate with observation of the SABRE effect, which is
illustrated here by the observation of both pyridine and acetonitrile HP. In this study, the required symmetry breaking that
underpins SABRE is provided for by the use of chemical inequivalence rather than the previously reported magnetic
inequivalence. As a consequence, we show that the ligand sphere of the polarization transfer catalyst itself becomes
hyperpolarized and hence that the high-sensitivity detection of a number of reaction intermediates is possible. These species
include [Ir(H)2(NCMe)(py)(IMes)(PPh3)]BF4, [Ir(H)2(MeOH)(py)(IMes)(PPh3)]BF4, and [Ir(H)2(NCMe)(py)2(PPh3)]-
BF4. Studies are also described that employ the deuterium-labeled substrates CD3CN and C5D5N, and the labeled ligands
P(C6D5)3 and IMes-d22, to demonstrate that dramatically improved levels of HP can be achieved as a consequence of reducing
proton dilution and hence polarization wastage. By a combination of these studies with experiments in which the magnetic field
experienced by the sample at the point of polarization transfer is varied, confirmation of the resonance assignments is achieved.
Furthermore, when [Ir(H)2(pyridine-h5)(pyridine-d5)(IMes)(PPh3)]BF4 is examined, its hydride ligand signals are shown to
become visible through para-hydrogen-induced polarization rather than SABRE.
recently, Koptyug et al. have used the same methods to follow a
number of heterogeneous reactions.13−15
INTRODUCTION
■
Hyperpolarization (HP) methods are being used to improve
the sensitivity of NMR and magnetic resonance imaging to
substrate detection.1 Signal amplification by reversible exchange
(SABRE) corresponds to one such method in which the
nuclear spin order from para-hydrogen (p-H2) is used to
sensitize a substrate. In this case, the process does not involve a
change in the chemical structure of the hyperpolarized
substrate, as demonstrated in the more traditional p-H2-
induced polarization (PHIP) technique pioneered by Weite-
kamp and Eisenberg.2−4 In PHIP, detection of a product that
contains two nuclei that were originally located in a single p-H2
molecule is achieved and therefore a simultaneous change in
the chemical identity is required. Nonetheless, this approach is
very powerful, and detection of the true reaction intermediates
has been achieved,5−7 the development of NMR theoretical
approaches facilitated,8,9 and the monitoring of hydrogenation
products in organic transformation enabled.10,11 The latter
situation has led to significant interest in PHIP as a tool for the
in vivo monitoring of living systems.12 Furthermore, more
In SABRE, while the HP feedstock is still p-H2, a catalyst is
now used as a scaffold to temporarily bind both H2 and the
substrate.16,17 Consequently, after ligand dissociation, there is
no change in the chemical identity of the hyperpolarized
species. Earlier studies used [Ir(COD)(PCy3)(py)]BF4, which
contains the sterically bulky electron-donating phosphine PCy3
as a suitable catalyst.17 More recently, greater HP efficiency has
been demonstrated for the related 1,3-bis(2,4,6-
trimethylphenyl)imidazol-2-ylidene (IMes) complex, [Ir-
(COD)(IMes)Cl].18 Recent reviews illustrate the context of
both SABRE and PHIP.19,20
The iridium−phosphine system [Ir(COD)(PCy3)(py)]+ is
known as Crabtree’s catalyst and is usually associated with a
role as either a hydrogenation or deuterium-transfer catalyst.21
Evidence obtained through studies of the effect of the ligand
electronic parameters by Tolman,22 computation,23 and
Received: July 16, 2013
© XXXX American Chemical Society
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calorimetric analysis of the bond strengths24 has revealed that
N-heterocyclic carbenes (NHCs) are more electron-donating
than phosphines.25 Furthermore, the work of Nolan and Buriak
has shown that the stability and activity of Crabtree’s catalyst
can be improved with such ligands.26 They achieve this by
combining a bulky NHC, such as IMes, with an appreciably
encumbered phosphine (PPh3, PBn3, PMe2Ph, and PnBu3) to
deliver the most robust and effective deuterium exchange
catalyst.27
EXPERIMENTAL SECTION
■
[Ir(COD)(PCy3)(py)]PF6 (1) was obtained from Strem. [Ir(COD)-
{CO(CH3)2}(IMes)]BF4 (2), [Ir(H)2(NCMe)2(IMes)(phosphine)]-
BF4 (3a and 4a), [Ir(H)2(py)2(IMes)(PPh3)]BF4 (3b), and [Ir-
(H)2(NCMe)(py)(IMes)(PPh3)]BF4 (3c) were prepared based on
published literature methods, as described in the Supporting
Information.37 All NMR measurements were recorded on a Bruker
Avance III series 400 or 500 MHz system. Samples were now typically
dissolved in 3 mL of methanol-d4 (5 mM) and contained pyridine (5
or 20-fold excess). Single crystals of both 3c and 5 were grown from a
benzene solution and analyzed on an Oxford Diffraction SuperNova
diffractometer. The crystals were kept at 110.00(10) K during data
collection.
Upon reaction of [Ir(COD)(PCy3)(py)]BF4 with pyridine
and p-H2, [Ir(H)2(PCy3)(py)3]BF4 formed and proved to
function very effectively as a SABRE catalyst.17 Indeed,
measurements under SABRE with its counterpart [Ir-
(H)2(IMes)(py)3]Cl yielded proton signal intensity gains in
free pyridine of greater than 3000-fold.18 These complexes
completed the HP transfer step in a low magnetic field in order
to facilitate the interactions necessary for spin-order transfer.8 A
growing number of studies have used the SABRE effect.28−34
Both of these systems are examples of catalysts in which it is
magnetic inequivalence in the equatorial plane that provides the
necessary symmetry breaking that activates the two nuclei that
were originally located within p-H2 and now reside on the metal
as a pair of dihydride ligands. Hence while these systems
contain three potential polarization acceptors in the form of
pyridine, only the two that are trans to hydride fulfill this role
and, consequently, the effective spin system involved in transfer
is made up of just 2 hydride and 10 pyridine protons. We aim
here to show that it is possible to improve on the efficiency of
this polarization transfer catalyst by sharing the p-H2 spin order
with fewer protons. While this has already been demonstrated
by using deuterated substrates,18,35 a redesign of the catalyst to
include fewer exchangeable ligand sites offers another route to
achieving this goal. In this paper, we describe how the
combination of an electron-donating NHC and a phosphine
produces a new set of high-activity catalysts for SABRE. The
phosphines employed are PCy3 and PPh3, and they provide
access to the well-defined complexes [Ir(H)2(IMes)-
(MeCN)2(PPh3)]BF4 and [Ir(H)2(IMes)(MeCN)2(PCy3)]-
BF4. The molecules that are hyperpolarized in this study
correspond to pyridine and acetonitrile. It has previously been
suggested that the HP efficiency of the SABRE catalyst is linked
to both the lifetime of the metal complex and the strength of
the magnetic field where polarization transfer occurs.8 These
concepts are further tested here by using a flow-polarization
apparatus that has been previously described.18,36 In particular,
we explore the ligand-exchange processes and demonstrate how
a number of new species are detectable, including character-
ization of a C−H bond activation product that acts as a resting
state within the SABRE process. In this case, it is products of
the type [Ir(H)2(NCMe)(py)(IMes)(PR3)]BF4 that are
dominant in the catalyst medium. The effect of the magnetic
field experienced by the catalyst at the point of polarization
transfer (the polarization transfer field, or PTF) is monitored
experimentally and shown to vary with the identity of the
catalyst and detected substrate. We also demonstrate how
breaking of the original p-H2 molecule symmetry through the
chemical shift difference in the dihydride product [Ir-
(H)2(NCMe)(py)(IMes)(PR3)]BF4 enables the wide transfer
of HP within the parent complex and hence their detection as
examples of hyperpolarized reaction intermediates.
[Ir(H)2(NCMe)2(IMes)(PPh3)]BF4 (3a). 1H NMR (400 MHz,
CDCl3, 298 K): δ −21.45 (d, 2H, JHP = 17.27 Hz), 1.65 (s, 6H,
NCCH3), 2.11 (s, 12H, CH3 of IMes), 2.38 (s, 6H, CH3), 6.95−7.34
(m, 21H, CH, PPh3, IMes). 13C{1H} NMR (101 MHz, CDCl3, 298
K): δ 1.0 (NCCH3), 17.9, 21.2 (CH3), 117.83 (NCMe), 122.2, 122.6
(NCH), 127.9, 128.9, 129.6 (d, CH, JCP = 11.3 Hz), 129.8, 132.7,
133.1 (CH), 133.9, 134.4 6 (d, CH, JCP = 11.0 Hz), 135.9, 137.6, 138.8
(−C), 164.1 (d, NCN, JCP = 114.7 Hz). 31P{1H} NMR (162 MHz,
CDCl3, 298 K): δ 18.96. 11B NMR (160 MHz, CD3CN, 298 K): δ
−1.40 (11BF4, 81%), −1.42 (10BF4, 19%). 19F NMR (470 MHz,
CD3CN, 298 K): δ −152.89 (10BF4, 19%), −152.94 (11BF4, 81%). ESI
MS: 802.29 [M+ − NCMe].
Compound 3b. 1H NMR (400 MHz, methanol-d4, 296 K): δ
−22.74 (d, 2H, JHP = 18.4 Hz), 1.97 (s, 12H, CH3 of IMes), 2.31 (s,
6H, CH3), 6.75−7.29 (m, 27H, CH, PPh3, IMes, py), 7.55 (t, 2H, JHH
1
1
= 7.2 Hz, para H py), 7.55 (d, 4H, JHH = 4.5 Hz, ortho H py).
13C{1H} NMR (101 MHz, methanol-d4, 298 K): δ 17.9, 21.2 (CH3),
122.0, 122.3 (NCH), 123.6 (CH, py), 127.8, 128.7, 129.5 (d, CH, JCP
=
11.3 Hz), 129.7, 132.5, 133.1 (CH), 133.9, 134.4, (d, CH, JCP = 11.0
Hz), 135.7 (CH, py), 135.9, 137.6, 138.8 (−C), 149.7 (−C, py),
164.1 (d, NCN, JCP = 114.7 Hz). 31P{1H} NMR (162 MHz, methanol-
d4, 298 K): δ 22.1. ESI MS: 840.31 [M+ − py].
Compound 3c. This complex was prepared in situ in an NMR
tube by adding 5 equiv of acetonitrile to a solution of 3b or 5 equiv of
1
pyridine to a solution of 3a. H NMR (500 MHz, acetonitrile-d3, 298
K): δ −22.30 (dd, 1H, trans to pyridine, JHH = 7.21 Hz, JHP = 19.44
Hz), −21.10 (dd, 1H, trans to NCCH3, JHH = 7.21 Hz, JHP = 16.09
Hz), 1.52 (s, 3H, coordinated NCCH3), 1.80 (s, 6H, CH3), 2.00 (s,
free NCCH3), 2.15 (s, 6H, 2 × −CH3), 2.36 (s, 6H, 2 × −CH3), 6.81
(d, 1H, −CH, JHH = 0.77 Hz), 6.97 (d, 1H, CH, JHH = 0.77 Hz),
7.05−7.49 (m, 21H, CH, PPh3, IMes), 7.78 (t, 1H, para 1H pyridine),
1
8.72 (d, 2H, ortho H pyridine. 31P{1H} NMR (161 MHz, CD3CN,
298 K): δ 22.98. 11B NMR (160 MHz, CD3CN, 298 K): δ −1.05. 19
F
NMR (470 MHz, CD3CN, 298 K): δ −154.69 (10BF4, 19%), −154.74
(11BF4, 81%). 15N NMR (40.54 MHz, CDCl3, 263 K): δ 177.8
(coordinated NCCH3), 195.8 (NCN, IMes), 238.1 (coordinated
pyridine).
[Ir(H)2(NCMe)2(IMes)(PCy3)]BF4 (4a). 1H NMR (400 MHz,
methanol-d4, 296 K): δ −22.24 (d, 2H, JHP = 18.7 Hz), 1.32−1.96
(m, 30H CH2 of PCy3), 2.16 (s, 6H, CH3 of acetonitrile), 2.21 (s, 12H,
CH3 of IMes), 2.38 (3H, m, CH of PCy3), 7.08 (m, 2H, CH, IMes.
13C{1H} NMR (101 MHz, CDCl3, 298 K): δ 1.4 (NCCH3), 16.0, 19.8
(CH3), 25.8, 26.2, 27.0, 28.4, 30.5, 32.8, 33.1 (CH2), 118.8 (NCMe),
122.5, 125.1 (NCH), 128.5 (CH), 135.8, 137.9, 138.5 (−C), 173.9
(d, NCN, JCP = 118.0 Hz). 31P{1H} NMR (162 MHz, methanol-d4,
296 K): δ 18.24. ESI MS: 779.40 [M+ − 2NCMe].
NMR Data for [Ir(H)2(py)2(IMes)(PCy3)]BF4 (4b). 1H NMR (400
MHz, methanol-d4, 296 K): δ −23.83 (d, 2H, JHP = 18.7 Hz), 1.32−
1.96 (m, 30H, CH2 of PCy3), 2.19 (s, 12H, CH3 of IMes), 2.41 (s, 6H,
CH3 of IMes), 7.21 (s, 4H, CH, IMes), 7.66 (t, 2H, meta 1H pyridine),
1
8.01 (s, 2H, CH, IMes), 8.18 (t, 1H, para H pyridine), 8.95 (d, 2H,
ortho 1H pyridine). 31P{1H} NMR (162 MHz, methanol-d4, 298 K): δ
21.9.
NMR Data for [Ir(H)2(NCMe)(py)(IMes)(PCy3)]BF4 (4c). 1H
NMR (400 MHz, methanol-d4, 296 K): δ −23.42 (dd, 1H, JHP = Hz),
−21.98 (dd, 1H, JHP = Hz), 1.13−1.73 (m, 30H, CH2 of PCy3), 1.83
B
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Scheme 1. Equilibration of 3a or 3b with Pyridine and Acetonitrile Leading to 3c as the Dominant Product
a H−15N HMQC NMR spectrum is recorded for this system
(in CDCl3), where the 15N label is present at natural
abundance, as shown in Figure 2, a different set of connections
1
(s, 6H, CH3 of IMes), 2.15 (s, 6H, CH3 of IMes), 2.19 (s, 3H, CH3,
acetonitrile), 2.38 (s, 6H, CH3 of IMes), 6.90 (s, 2H, −CH, IMes),
1
7.07 (s, 2H, −CH, IMes), 7.16 (t, 2H, JHH = 6.3 Hz, meta H
pyridine), 7.18 (s, 2H, −CH, IMes), 7.81 (t, 1H, JHH = 8.3 Hz,
1
1
ortho H pyridine), 8.23 (d, 2H, JHH = 4.3 Hz, para H pyridine).
31P{1H} NMR (162 MHz, methanol-d4, 298 K): δ 22.73.
RESULTS AND DISCUSSION
■
Complexes 3a, 3b, and 4a were prepared and characterized by
multinuclear NMR spectroscopy. Key resonances are listed in
the Experimental Section. The hydride ligands in these species
appear as simple phosphorus-coupled doublets at δ −21.40,
−22.70 and −22.24, in methanol-d4 at 298 K and at δ −21.45,
−22.80, and −22.42 in CDCl3. These resonances are used to
monitor the chemical evolution of these systems as they react
with pyridine and acetonitrile. Two control samples were
prepared to do this. The first sample contained 3a in methanol-
d4 and 5 equiv of pyridine and 3 bar of H2. The second
contained 3b in CDCl3 and 1 equiv of NCMe and 3 bar of H2.
In both cases, the hydride signals of 3a or 3b were replaced by a
common species that yielded a pair of coupled hydride ligand
signals at δ −21.02 and −22.18. This product, 3c, is the sole
product in both reactions and confirms that 3c is
thermodynamically more stable than either 3a or 3b, as
illustrated by Scheme 1 and Figure 1.
Figure 2. 2D 1H−15N HMQC NMR spectrum of unlabeled 3c
recorded at 263 K in CDCl3, with the resulting 15N data providing
diagnostic information on the ligand arrangement, as discussed in the
text (relative expansions in the boxed areas are indicated).
become visible. Now the hydride signal that appears at lower
field connects with a coordinated acetonitrile 15N signal at δ
177.8 through a 15.3 Hz JH15N splitting; it also connects to its
CH3 partner at δ 1.48. The second, higher field, hydride signal
at δ −22.18 possesses a JHN splitting of 18.5 Hz and is located
trans to pyridine. The 15N resonance of the associated
coordinated pyridine ligand of 3c appears at δ 239.1 in this
NMR spectrum. In addition to these two connections, the δ
6.99 (JHN = 10.6 Hz) signal of the −CHCH− protons in the
imidazolium ring of the IMes ligand shows a strong correlation
peak to a third 15N signal at δ 195.7 in this experiment. These
measurements therefore locate key 15N ligand resonances in 3c
and give a high level of confidence in our product assignment;
we note that these measurements were achieved in only a few
hours without 15N labeling. The characterization of 3c was
further confirmed by X-ray crystallography at 110 K. Figure 3
shows the corresponding ORTEP for 3c, while Table 1 lists key
bond lengths and angles.
Characterization of 4c. A series of related studies were
then undertaken on the PCy3 analogues of 3. These studies
revealed that, upon dissolution of 4a in methanol-d4 and the
addition of 5 equiv of pyridine and 3 bar of H2, 4c was formed
in a manner similar to that of 3c. NMR data for 4a−4c are
presented in the Experimental Section.
It is well-known that species such as 3c and 4c can undergo
C−H activation of an o-methyl group of the mesityl ring after
ligand loss. Aldridge and co-workers38 reported such an
observation in the solid-state chemistry of Ir(IMes)(IMes′)-
(H)Cl, while Torres et al.37 demonstrated that [Ir(H)2(IMes)-
Figure 1. Hydride region of two 1H NMR spectra used to illustrate the
conversion of 3a into 3c upon the addition of pyridine. These traces
were recorded at 273 K in CDCl3.
The peak integrals for these two hydride resonances of 3c
exhibit the expected 1:1 ratio, and we note that a coordinated
NCMe signal appears at δ 1.48. In 3c, the methyl substituents
of the IMes ligand appear as three distinct sets, each of six
protons, in accordance with rapid rotation about the metal−
carbene and N−C bonds (see the Experimental Section). The
hydride ligand resonances of 3c are also well-resolved and
connect, according to nuclear Overhauser effect methods, with
proton signals at δ 6.99 and 1.48, which are attributed to bound
pyridine and CH3CN ligands, respectively. These connections
arise because of through-space interactions and confirm the cis-
ligand arrangement that is shown in Figure 1. In contrast, when
C
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Figure 3. ORTEP diagrams of the cations 3c and 5 as determined by X-ray diffraction.
Table 1. Bond Distance (Å) and Angles (deg) for Complexes
3c and 5
Kinetics of Ligand Exchange in 3c and 4c. It should be
clear that the dominant species present in these solutions is 3c
or 4c. A series of H-selective EXSY NMR experiments were
1
3c
5
therefore performed in order to probe the ligand-exchange
processes undergone by 3c and 4c. These data are presented in
the Supporting Information (section 4), but our findings are
summarized here. In the first instance, 3c was observed to
undergo magnetization transfer between free and bound
pyridine, free and bound acetonitrile, and the two hydride
sites, as illustrated in Scheme 2. When the experimentally
observed rate of transfer of magnetization from bound pyridine
into free pyridine was monitored as a function of the pyridine
concentration, saturation behavior indicative of a dissociative
process was evident at high pyridine concentrations. The
limiting rate constant for magnetization transfer into free
pyridine was determined to be 1.15 0.1 s−1. However, when a
similar sample was examined, where the initial concentrations
of 3c and pyridine were 0.0152 and 0.0342 M, respectively, the
rate of magnetization transfer into free pyridine reduced to zero
with increase in the acetonitrile concentration. This informa-
tion suggests that it is actually acetonitrile dissociation that
accounts for the observed pyridine magnetization transfer.
Hence, this process happens by secondary ligand exchange
through unstable 3b as indicated in Scheme 2 rather than the
direct dissociation of pyridine. This deduction was confirmed
when the effect of the acetonitrile concentration on the rate of
transfer of bound to free acetonitrile was explored. Now
exchange rate saturation was again seen, but the maximum rate
constant for ligand loss proved to be 1.95 0.1 s−1. This value
is twice that of the limiting pyridine rate, a link that is expected
if 3b were to be involved because once formed there is now an
equal probability of losing the magnetically labeled pyridine or
the freshly bound pyridine ligand. Furthermore, the observed
rate constant for hydride site interchange is smaller than this
and is affected by the ligand excess, in accordance with the 16-
electron reaction intermediate retaining unique hydride ligand
identities as expected.39
Ir−P1
Ir−H1
Ir−C1
Ir−C4
Ir−N3
Ir−N4
2.2832(9)
1.603
2.3347(9)
1.604
2.068(4)
2.046(3)
2.101(3)
2.090(3)
2.154(3)
2.160(3)
2.107 (5)
C1−Ir−P1
C4−Ir−P1
C1−Ir−C4
N3−Ir−N4
N3−Ir−H1
N4−Ir−H1
N3−Ir−C1
N4−Ir−C4
P1−Ir−N3
P1−Ir−N4
168.29(11)
165.48(10)
94.00(10)
80.24(13)
85.55(11)
91.6(2)
176.58
175.85
179.16
93.96(13)
97.54(14)
94.14(7)
90.67(11)
94.82(12)
92.06(12)01
91.41(8)
100.54(8)
(NCMe)2(PiPr3)]PF6 forms [IrH(IMes′)(NCMe)2(PiPr3)]PF6
upon treatment with ethylene. In this case, upon exposure of
the cyclometalated complex to H2, the dihydride is re-formed.
We were therefore not surprised when a sample of 4a that was
placed under N2 underwent H2 reductive elimination to form a
new product. This species proved to correspond to [IrH-
(IMes′)(NCMe)2(PCy3)]BF4 (5). Isolation of complex 5 led
to the collection of X-ray-quality crystals, which yielded the
structure shown in Figure 3. The Ir−phosphine bond lengths in
5 and the related complex [IrH(IMes′)(NCMe)2(PiPr3)]PF6
are 2.3347(9) and 2.3367(17) Å and hence indistinguishable. In
contrast, the corresponding IrC1 bond lengths are slightly
different at 2.046(3) vs 1.973(7) Å, in accordance with the
greater electron-donating power of PCy3 vs PiPr3. The
corresponding Tolman cone angles change from 170° to
160° for these ligands. The difference in the phosphine steric
bulk changes the structure such that in 5 the equatorial N−Ir−
C and N−Ir−H bond angles are larger than those for
[IrH(IMes′)(NCMe)2(PiPr3)]PF6.
In contrast, when 4c is examined, a limiting reaction rate is
again reached as both the pyridine and acetonitrile concen-
trations are increased. However, now the limiting rate constant
for pyridine loss is 3.1 0.1 s−1, while that for acetonitrile loss
is half that, at 1.4
0.1 s−1. Hence, for 4c, the mechanism
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Scheme 2. Magnetization Transfer Pathways Revealed through EXSY Examination of 3 (R = Ph) or 4 (R = Cy) with Pyridine
a
and Acetonitrile as a Function of the Reagent Concentration
a
The color scheme shows how labeled magnetization can propagate through the system, based on the indicated dissociative reactions. Solvation of
the intermediates is to be expected, and distinct hydride ligand sites are retained in these complexes.
seems to be inverted, with the main ligand loss process
corresponding to loss of pyridine. Consequently, trapping with
acetonitrile now leads to 4a, where two identical equatorial
ligands reside. The temperature dependence of the observed
magnetization transfer rates between the bound and free
ligands is detailed in the Supporting Information.
It is interesting to note that when the hydride ligands of 3c
are probed by EXSY spectroscopy, no exchange into free H2 is
observed. This situation marks a significant difference in
behavior from that previously reported for 1 and 2, where H2
loss is relatively facile. These data therefore suggest that 3c and
4c are suitable as SABRE catalysts because they undergo ligand
exchange on the NMR time scale. We now describe a series of
SABRE-type measurements that are designed to explore this
hypothesis.
Figure 4. (a) One-scan 1H NMR spectrum showing the hyper-
Using 3 and 4 as SABRE Catalysts. In order to monitor
polarized pyridine signals produced under SABRE with 4. (b) Thermal
these complexes under SABRE conditions rather than PHIP, a
control spectrum illustrating the scale of signal enhancement.
flow apparatus that has been previously described was
employed.36 This equipment allows for the automated
of the meta resonance of pyridine as a function of the catalyst
identity.
Surprisingly, the level of proton signal enhancement
observed using 4c is comparable to that found for 2 even
collection of hyperpolarized NMR data. A series of identical
solutions were prepared, containing the same amount of
specified catalyst (1, 2, 3a, 3b, and 4a) and a 20-fold excess of
1
pyridine. The total H NMR signal enhancement of the three
though the ligand-exchange rates are slower. Additionally, the
proton sites of pyridine was then plotted as a function of the
level of signal enhancement seen in the proton signals of
strength of the PTF. Table 2 summarizes these data, while
acetonitrile, phosphine, and IMes ligands of 4c is substantial,
1
Figure 4 illustrates a typical H NMR spectrum of the organic
albeit at a lower level than that of pyridine. We further note that
region to demonstrate the impact of SABRE and Figure 5
when 3c and 4c are employed as magnetization transfer
shows the corresponding PTF plot for the signal amplification
catalysts, transfer into the protons of NCMe is observed. The
level of enhancement seen for the acetonitrile protons in these
systems reaches a maximum with a PTF of 20 G, as shown in
Figure 6.
Table 2. Total Pyridine Proton Signal Enhancement (Metal
Concentration 5.5 mM; 20-Fold Excess of Pyridine)
Measured in Conjunction with the Described SABRE−Flow
Apparatus for the Indicated PTF with the Corresponding
Exploring the Reactions of 3c and 4c by PHIP. This
involved taking a solution of 3a, with added pyridine, under p-
Experimentally Determined Rate of Ligand Loss
1
H2, and collecting a H NMR spectrum at 298 K using a 45°
excitation pulse. Now strong PHIP was seen for the signals that
catalyst precursor field/G absolute value ligand loss rate constant (s−1
)
arise from the two hydride ligands of 3c, as shown in Figure 7.
No signals for either 3a or 3b were visible in this NMR
spectrum, and these data are consistent with the previous
section, which detailed how 3c is the thermodynamic product
of the reaction. These NMR spectra, however, do reveal the
presence of a further minor reaction product that is not readily
1
40/90
110
130
646
405
372
685
0.46
6.26
1.94
1.94
3.1
2
3a
3b
4
140
130
130
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visible without PHIP. This product appears as a pair of
mutually coupled hydride signals at δ −11.89 (ddd, JHH = 4.8,
JPcisH = 23.6, and JPtransH = 133.8 Hz) and δ −20.45 (multiplet,
JHH = 4.5, JPcisH = 16.0, and JPcisH = 11.3 Hz), which possess
couplings to two inequivalent 31P centers. These centers were
located at δ 2.87 (trans to the hydride resonating at δ −11.89)
and 6.30 (cis to both hydrides) in the corresponding 2D
1H−31P NMR correlation. The corresponding 1H−15N HMQC
NMR experiment revealed that the hydride signal at δ −20.45
connected with an acetonitrile 15N signal at δ 196.7 through a
trans coupling. These results confirm that this additional
species is the ligand redistribution product [Ir(H)2(NCMe)-
(IMes)(PPh3)2]BF4 (6), with a cis−cis hydride and phosphine
ligand arrangement.
Exploring the Reactions of 3c and 4c by SABRE. When
an analogous sample was examined using the flow apparatus,
after a p-H2 exposure time of 30 s, the SABRE effect was
observed in some of the resonances of 3c and 6. For example,
the signal for the o-phenyl proton of the phosphine ligand of 3c
now appears as an emission peak, a triplet at δ 7.05, which
simplifies upon 31P decoupling into the expected doublet. A
weaker signal at δ 6.99 is visible for an o-phenyl proton of the
phosphine in 6. The signal intensities seen for these
hyperpolarized ligand resonances proved to vary with the
PTF used for SABRE and, in this case, were maximized when
set to 50 and 90 G, respectively. The o-pyridine proton signal
for 3c can also be seen as a SABRE-enhanced signal at δ 7.78 in
these measurements. Upon examination of the region around δ
2.0, hyperpolarized signals are also detected at δ 2.05, 1.54, and
1.32 for free CH3CN and bound CH3CN in 3c and 6,
respectively. These resonances proved to have maximum
intensity when the PTF was 20 G. Additionally, when the
PTF field was increased to 140 G, signals for the corresponding
methyl protons of the IMes ligands in 3c and 6 were enhanced;
they appear at δ 1.88, 2.13, and 2.39 for 3c and at δ 2.36 and
3.05 for 6. These observations have therefore demonstrated
that the SABRE effect can be used to observe key resonances in
these complexes at high sensitivity. They also reveal that the
PTF can be used to select key resonances.
Figure 5. Plot showing how the PTF controls both the degree of
pyridine meta proton signal enhancement and the phase of the signal
for transfer in a methanol-d4 solution using 2 (blue), 1 (red), 3c
(purple), and 4c (green) SABRE catalysts when 1 equiv of NCMe and
20 equiv of pyridine are present in solution.
Exploring the Reactions of 3c by SABRE While
Employing a Range of Deuterated Ligands. We have
built further on these SABRE studies by reexamining these
reactions in conjunction with deuterium labeling, with the aim
of making the ligand resonances even more intense. For
example, when pyridine-d5, rather than pyridine-h5, is used, the
SABRE-enhanced signals seen for the o-phenylphosphine
protons of 3c and 6 proved to be reduced in intensity by
around 80%. In contrast, the corresponding signals for the
CH3CN ligands of 3c and 6 were, however, now 20% stronger,
with the methyl resonances of their IMes groups showing an 8
fold increase under optimum conditions rather than the 4-fold
seen in the experiments with pyridine-h5. The signal enhance-
ments for the hydride ligand signals of 3c were also increased
by 20% over those seen with pyridine-h5. The effects of
deuteration are therefore substantial and confirm that, by a
reduction in the number of protons in the spin system, the
signal enhancement can be focused onto the remaining
resonances. For the phosphine, however, the opposite is true,
and hence we can deduce that its signals are actually enhanced
via transfer from the protons of pyridine.
Figure 6. Plot showing the PTF dependence on the absolute signal
■
enhancement observed for the protons of ( ) acetonitrile (11-fold
○
excess) and ( ) pyridine (31-fold excess), produced in a methanol-d4
solution using the SABRE catalyst 3c at 291 K.
1
Figure 7. H NMR spectrum of the hydride region of a methanol-d4
Interestingly, when a mixture of pyridine-h5 and pyridine-d5
is employed, the hydride ligands of 3b now become visible as
strongly PHIP-enhanced signals. These hydride resonances are
solution of 3c under p-H2, revealing the pairs of hydride resonances for
3c (major) and 6 (minor).
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strongly amplified by virtue of the creation of a small chemical
shift difference between them; the result of this process is the
creation of two AB-type hydride resonances. Consequently,
when a 45° excitation pulse is employed, these signals
dominate, although the signals for 3c and 6 are still visible.
Under SABRE conditions, enhanced signals for 3b are also
visible at δ 7.09 (the o-phenyl proton of the phosphine), at δ
7.98 (the o-pyridine proton), and at δ 2.16 for its IMes ligand in
this experiment.
yield pairs of hydride signals at δ −20.56 (dd, JHH = 6.1 Hz, JPH
= 12.9 Hz) and −22.54 (dd, JHH = 5.8, JPH = 18.6 Hz) (3d) and
at δ −20.81 (dd, JPH = 18 Hz) and δ −21.88 (dd, JPH = 17 Hz)
(3e). They are therefore both monophosphine-containing.
Species 3d was assigned as [Ir(H)2(MeOH)(py)(IMes)-
(PPh3)]+ on the basis of a series of multinuclear NMR
1
observations. It is worth noting, in the corresponding H−1H
COSY experiment, the hydride signal of 3d at δ −20.56
coupled with a hydride signal at δ −22.54 and a −CH3 proton
signal of a bound methanol-h4 ligand at δ 2.99. In the
Furthermore, when PPh3-d15 is employed instead of PPh3-
h15, the hydride ligand signals of 3c and 6 appear to be 27%
larger and 26% smaller, respectively. One further benefit of
1
corresponding H−31P HMQC NMR experiment, a 31P signal
at δ 6.54 was seen for 3d. In contrast, 3e is [Ir(H)2(NCMe)-
(py)2(PPh3)]+, and while its NMR signals are too weak for full
characterization, a proton signal of the axial pyridine ligand was
located at δ 9.04. In both of the newly detected complexes, 3d
and 3e, it is the chemical shift of the hydride ligands that
secures their identity.
1
deuteration is that the H resonances of the bound pyridine-h5
ligands in these species can now be clearly seen because there is
no longer any overlap with what would be PPh3-h15 resonances.
The important aspects of this behavior are illustrated in Figure
8. We note, however, that separation of these signals can also be
These unusual deductions are supported by Figure 9 where
part a shows the one-scan 1H NMR spectrum that was recorded
after 30 s of bubbling of p-H2 through a methanol-d4 solution of
3c at a PTF of 130 G. In the hydride region of this spectrum,
PHIP-enhanced signals are seen for 3a, 3d, 3e, and 6. In
contrast, the organic region shows polarized and diagnostic
proton signals for bound PPh3, the −CH3 groups of the IMes
ligands, the pyridine ligands, and the NCMe ligands in these
1
species. When the corresponding H OPSY NMR spectrum
(Figure 9b) was collected, the corresponding p-H2-enhanced
signals now appear very clearly, while those of 3a are
suppressed, as expected, because of its high symmetry. Figure
9c shows the corresponding normal 32-scan 1H NMR spectrum
that was recorded under true Boltzmann conditions for
comparison. These observations are therefore fully consistent
with the expected redistribution of ligands in solution that allow
the formation of an array of low-concentration species that are
not readily detectable by normal NMR methods.
1
Figure 8. Plot of variation of the NCMe H signal intensity versus
CONCLUSIONS
■
PTF when a 3c-derived catalyst system is employed in conjunction
with the specified deuterium labeling. A total of 3 mL of a methanol-d4
solution of 3c (5.5 mM) with an 11-fold excess of NCMe and a 31-
fold excess of pyridine relative to metal was employed in these room
temperature measurements.
This study has revealed that when 3a, 3b, and 4a are exposed to
a solution containing H2, pyridine, and acetonitrile, the
dominant products are 3c and 4c. The ligand-exchange
pathways of 3c and 4c were explored using EXSY methods.
These studies revealed that 3c undergoes preferential
acetonitrile loss, while for 4c, pyridine is lost preferentially.
These processes are dissociative in nature and show the
expected saturation behavior at high ligand concentrations. We
further note that when a solution of 4a is left under N2, the CH
bond activation product 5 is obtained.
Utilization of 3c and 4c as SABRE catalysts has also revealed
that substantial enhancements in both pyridine and acetonitrile
can be achieved. In this case, it is the chemical and magnetic
inequivalence of the hydride ligands that provides the route to
SABRE activity. This is reflected in these systems by both the
axial and equatorial ligands seeing different hydride couplings
and hence receiving SABRE transfer. The efficiency of the HP
of free pyridine by 4a is comparable with that of Ir(COD)-
{CO(CH3)2}(IMes)]BF4. We note that in the case of 4a the
spin polarization derived from p-H2 is now shared with just 7
in-plane protons, while in 2, it is 12. Consequently, we confirm
that one route to maximize the SABRE effect is to introduce
fewer protons into the complex at the point of magnetization
sharing. This effect overcomes its slower ligand-exchange rate
compared to 2. We also note that while 3 is better at polarizing
acetonitrile, the reverse is true for 4, with pyridine being
achieved by varying the PTF and, consequently, either route
can be used to confirm the resonance assignment. This means
that even if deuteration is not chemically viable, character-
ization is still possible.
We have also studied the effect of deuteration on the
polarization of free NCMe. When pyridine-d5 was used instead
of pyridine-h5, the enhancement level of the NCMe protons is
25 times higher. Furthermore, if a IMes-d22 ligand is used, this
increases further to an absolute enhancement of 49-fold. When
both IMes-d22 and pyridine-d5 are employed, the enhancement
level rises yet further to 117-fold. These data are illustrated in
Figure 8 and therefore demonstrate that it is possible to
produce a viable NCMe HP transfer catalyst. We note that the
cyanide function plays a role in many important drugs such as
AstraZeneca’s Anastrozole, which is marketed as Arimidex.40
We further note that when p-H2 is used to examine the
original solution of 3a in the presence of a very small amount of
pyridine (0.1-fold based on iridium) with methanol-h4 (120-
fold) in methanol-d4, while weak signals for 3a dominate,
PHIP-enhanced signals are seen for both 3c and 6 in addition
to those of two further products. These additional products
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Figure 9. (a) 1H NMR signals from hyperpolarized pyridine, PPh3, the −CH3 groups of IMes ligands, and the NCMe ligands that are detected as a
consequence of SABRE. The enhanced signals in the hydride region are detected through PHIP. This NMR spectrum is the result of bubbling p-H2
through a methanol-d4 solution of 3c at 130 G for 30 s prior to transfer into the NMR probe for observation. (b) Corresponding one-scan 1H OPSY
NMR spectrum of this sample. (c) Corresponding 32-scan 1H NMR spectrum, recorded when the sample magnetization yields signals of an intensity
that reflects the normal Boltzmann distribution rather than the HP conditions. The sample consisted of 3 mL of methanol-d4 solution of 3c (5.5
mM) and a 20-fold excess of pyridine.
optimally polarized. This observation is consistent with the
change in the ligand-exchange mechanism, where 3 dissociates
acetonitrile and 4 pyridine.
consequence of the small chemical shift difference that exists
between them and further illustrates how magnetic symmetry
underpins both SABRE and PHIP observations.
We have also shown that it is possible to detect
hyperpolarized signals that are diagnostic of the ligands
surrounding the metal centers through SABRE. In this case,
[Ir(H)2(MeOH)(py)(IMes)(PPh3)]BF4 (3d) and [Ir-
(H)2(NCMe)(py)2(PPh3)]BF4 (3e) were detected as a direct
result of this process. These observations therefore illustrate a
new route to using p-H2-derived magnetization to characterize
reaction intermediates. Two concepts have been explored here
to aid this process. In the first, the effect of the magnetic field
experienced by the sample at the point of polarization transfer
has been examined and is related to the efficiency of ligand HP.
These data revealed that it is possible to differentiate signals in
the same NMR region by collecting a series of 1H NMR spectra
at different PTF values. We have also completed an extensive
array of deuterium-labeling studies. These have confirmed that
it is possible by reducing the extent of magnetization sharing to
dramatically increase the level of transfer into the remaining 1H
sites in the catalyst system. This has been used not only to
increase the level of pyridine and acetonitrile polarization but to
aid in the characterization of the reaction intermediates 3d and
3e. We further note that when 3b is formed as the isotopomer
[Ir(H)2(h5-pyridine)(d5-pyridine)(IMes)(PPh3)]BF4, the cor-
responding hydride ligand signals now become visible through
PHIP rather than the SABRE effect. This is a direct
Consequently, these measurements established that SABRE
can be used to probe the NMR signature of the ligand sphere
surrounding such hyperpolarized complexes. By utilizing the
PTF to change the intensity of nearly overlapping resonances, it
is possible to clearly distinguish them. We hope these examples
help to illustrate a novel route to monitor reactivity. The results
presented here also reveal how important it is to consider the
role of all species present in solution when quantifying and
explaining the appearance of SABRE-derived spectra.
ASSOCIATED CONTENT
■
S
* Supporting Information
X-ray crystallographic data in CIF format and experimental
details. This material is available free of charge via the Internet
at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: simon.duckett@york.ac.uk.
Author Contributions
All authors have given approval to the final version of the
manuscript.
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(24) Huang, J. K.; Schanz, H. J.; Stevens, E. D.; Nolan, S. P.
Organometallics 1999, 18, 2370.
(25) Chianese, A. R.; Li, X. W.; Janzen, M. C.; Faller, J. W.; Crabtree,
R. H. Organometallics 2003, 22, 1663.
(26) Vazquez-Serrano, L. D.; Owens, B. T.; Buriak, J. M. Inorg. Chim.
Acta 2006, 359, 2786.
Funding
The authors thank Bruker Biospin UK for the p-H2 polarizer
used in this work. The EPSRC (Grant EP/G009546/1),
Wellcome Trust (Grants 092506 and 098335), and University
of York are also thanked for supporting this work.
Notes
(27) Brown, J. A.; Irvine, S.; Kennedy, A. R.; Kerr, W. J.; Andersson,
S.; Nilsson, G. N. Chem. Commun. 2008, 1115.
The authors declare no competing financial interest.
(28) Borowiak, R.; Schwaderlapp, N.; Huethe, F.; Lickert, T.; Fischer,
E.; Baer, S.; Hennig, J.; von Elverfeldt, D.; Hoevener, J.-B. Magn. Reson.
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Tessari, M.; Feiters, M. C.; Blumich, B.; Rutjes, F. P. J. T. Chem.
Commun. 2013, 49, 7388.
ACKNOWLEDGMENTS
■
The Spanish MEC Consolider Ingenio 2010-ORFEO-
CSD2007-00006 research programme is thanked. We thank
Prof G. Green for helpful discussions and M. Buchner for help
with the 19F and 11B NMR measurements.
(30) Duecker, E. B.; Kuhn, L. T.; Muennemann, K.; Griesinger, C. J.
Magn. Reson. 2012, 214, 159.
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