Iridium(I) Complexes with Anionic N-Heterocyclic Carbene Ligands as Catalysts for H/D Exchange in Nonpolar Media

Article abstract of DOI:10.1002/adsc.202000438

A series of neutral iridium(I) complexes of the general type [(WCA?NHC)]IrL(COD)] (COD=1,5-cyclooctadiene; L=phosphine, pyridine), bearing anionic N-heterocyclic carbenes (WCA?NHC) with a weakly coordinating anionic (WCA) borate moiety, were prepared by a

Full text of DOI:10.1002/adsc.202000438

Title: Iridium(I) Complexes with Anionic N-Heterocyclic Carbene
Ligands as Catalysts for H/D Exchange in Nonpolar Media
Authors: Marvin Koneczny, Luong Phong Ho, Alexandre Nasr,
Matthias Freytag, Peter Jones, and Matthias Tamm
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.202000438
Link to VoR: https://doi.org/10.1002/adsc.202000438

Advanced Synthesis & Catalysis
10.1002/adsc.202000438
Very Important Publication
FULL PAPER
DOI: 10.1002/adsc.202((will be filled in by the editorial staff))
Iridium(I) Complexes with Anionic N-Heterocyclic Carbene
Ligands as Catalysts for H/D Exchange in Nonpolar Media
a
a
a
a
Marvin Koneczny, Luong Phong Ho, Alexandre Nasr, Matthias Freytag, Peter G.
a
a
Jones, and Matthias Tamm *
a
Institut für Anorganische und Analytische Chemie, Technische Universität Braunschweig, 38106 Braunschweig,
Hagenring 30 (Germany).
E-mail: m.tamm@tu-bs.de
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
Abstract. A series of neutral iridium(I) complexes of the complexes as catalysts for H/D exchange was investigated,
general type [(WCA-NHC)]IrL(COD)] (COD
cyclooctadiene; L = phosphine, pyridine), bearing anionic N- deuteration in nonpolar solvents such as cyclohexane.
heterocyclic carbenes (WCA-NHC) with weakly
= 1,5- revealing their suitability for promoting efficient
a
coordinating anionic (WCA) borate moiety, were prepared
by addition of phosphines and pyridine to [(WCA- Keywords: Hydrogen Isotope Exchange; Deuterium;
NHC)]Ir(COD)], in which the available coordination site is Iridium Catalysis; N-Heterocyclic Carbenes; Weakly
stabilized by intramolecular metal-arene interaction (-face Coordinating Anions
donation). The solvent and substrate scope of the neutral
Crabtree’s catalyst [(COD)Ir(PCy
3
)(py)]PF
6
(I,
Introduction
COD = 1,5-cyclooctadiene, Cy = cyclohexyl, py =
[7]
pyridine) is a well-established and effective HIE
[8]
Hydrogen isotope exchange (HIE) is commonly used
to label molecules by introducing heavier isotopes of
hydrogen (deuterium or tritium) through C-H
functionalization.[ Though numerous heterogeneous
or homogeneous methods for HIE have been
described, [ selective ortho-directed HIE catalyzed
by iridium(I) complexes has become particularly
iridium catalyst (Figure 1) that is commercially
[9]
available and widely used to date. By replacing the
pyridine ligand with an N-heterocyclic carbene
(NHC), Kerr introduced highly efficient, air- and
1-3]
moisture-stable
[(IMes)Ir(PR )(COD)]X (IMes
trimethylphenyl)imidazolin-2-ylidene; PR
catalysts
of
the
1,3-bis(2,4,6-
= PPh
, etc.), which are able to introduce
type
1,3,4]
3
=
3
3
,
[5]
[10]
prominent (Scheme 1). This process has distinct
advantages over the classic preparation of labelled
compounds, since it is possible to label the desired
molecule after its synthesis under mild conditions
with commercially available catalysts. The use of gas
PBn
3
, PPhMe
2
hydrogen isotopes into a large variety of substrates,
for example primary sulfonamides, ketones, amides,
[
10-13,14]
esters and heterocycles.
of the “flagship” catalyst [(IMes)Ir(PPh
(IIa) had a substantial influence on the catalytic
Counterion variations
3
)(COD)]PF
6
(
D
2
or T ) as an isotope source is especially
2
advantageous for tritiation reactions, since it is
readily available in high isotopic purity (>99%), and
the preparation of alternative tritiated precursors
requires special care because of their radioactive
nature.[
activity,
with
the
tetrakis[3,5-
bis(trifluoromethyl)phenyl]borate (BArF24) complex
IIb showing a superior solubility profile and
[13]
applicable solvent scope in HIE processes.
In
6]
addition to these cationic species, neutral complexes
of the type [(NHC)IrCl(COD)] were also succesfully
[15]
employed. Similar anion effects were observed for
the iridium(I) catalysts III supported by P,N ligands,
which were developed in the course of our work with
[16]
highly basic imidazolin-2-imine ligands.
Hence,
the BArF24 derivative IIIb showed remarkable
performance in H/D exchange with a broad range of
aromatic substrates, including ketones, amides, esters,
heterocycles and nitro compounds, and also promoted
H/D exchange in
Scheme 1. General iridium-catalyzed HIE reaction. DG =
directing group.
1
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Advanced Synthesis & Catalysis
10.1002/adsc.202000438
solvent scope of the complexes IV and their
derivatives [(WCA-NHC)IrL(COD)] (1–4) in ortho-
directed H/D exchange reactions.
Results and Discussion
Synthesis and Characterization. The complex
[
(WCA-IMes)Ir(COD)] (IVa, WCA = B(C
6
F ) ,
5
3
IMes = 1,3-bis(2,4,6-trimethylphenyl)imidazolin-2-
ylidene) was treated with the phosphines PPh
PPh Me, PPhMe , and PMe in tetrahydrofuran
THF). Simple addition and formation of the
complexes [(WCA-IMes)IrL(COD)] was observed
only for L = PPh (1) and L = PPh Me (2), whereas
the reaction with the smaller, more electron-rich
phosphines PPhMe and PMe afforded cyclooctenyl
complexes of the composition [(WCA-IMes-
COE)IrL ] by COD insertion into the Ir–Ccarbene bond.
These complexes exhibit three P NMR signals, and
for L = PMe , the molecular structure could be
3
,
2
2
3
(
3
2
2
3
3
3
1
3
established by X-ray diffraction analysis, revealing a
distorted trigonal-bipyramidal coordination sphere;
see the Supporting Information for the crystal
structure of [(WCA-IMes-COE)Ir(PMe
3
)
3
]·CH
2
Cl .
2
Similar insertion reactions have been observed for
[24]
indenyl complexes of the type [(Ind)Ir(COD)].
The complexes 1 (L = PPh ) and 2 (L = PPh Me)
3
2
Figure 1. Selected examples of iridium complexes active
in HIE; Mes = 1,3,5-trimethylphenyl, Dipp = 2,6-
diisopropylphenyl.
were isolated as red-orange powders in 83% and 80%
3
1
yield (Figure 1). The P NMR spectra exhibit
singlets at 16.1 ppm (1) and 0.4 ppm (2), while the
1
3
C NMR spectra of 1 and 2 show doublets at 171.8
2
2
aromatic Boc-protected anilines, benzylamines and
methoxy derivatives.[ Moreover, HIE reactions with
ppm ( J = 7.5 Hz) and 176.4 ppm ( J = 8.1 Hz),
CP
CP
17]
respectively. These chemical shifts fall in the
expected range in comparison with Kerr’s catalysts
such as IIa and are in accordance with the expected
cis arrangement of the carbene and phosphine
[18]
sulfonamides, N-oxides, phosphonamides
and
phenylacetic acid esters and amides were
accomplished.[
19]
[10]
Anionic N-heterocyclic carbenes that bear a
weakly coordinating anion (WCA) are another class
ligands. Addition of pyridine to a THF solution of
IVa afforded the pyridine complex 3 as a yellow
powder in moderate yield (50%). 3 gave rise to
[20]
of ligands introduced by our group, which were
used for the preparation of homogeneous WCA-NHC
1
13
similar H and C NMR signals for the WCA-IMes
and COD ligands; e.g., the carbene carbon atom
resonates at 175.8 ppm. Similar addition reactions
with the sterically more demanding complex [(WCA-
IDipp)Ir(COD)] (IVb, WCA = B(C F ) , IDipp = 1,3-
gold(I),[ iridium(I)
21]
[22]
and palladium(II)
[23]
(pre-
)
catalysts. The iridium(I) systems IV can be regarded
as carbene analogues of Crabtree’s catalyst I, with
their overall neutral charge allowing olefin
6
5 3
hydrogenations in nonpolar media.[
22]
Notably,
bis(2,6-diisopropyllphenyl)imidazolin-2-ylidene)
intramolecular -face donation is an important
proved successful only for L = PPhMe , and the
2
feature of complexes IV, and stabilizes
a
resulting complex 4 was isolated as a red-orange
solid in 67% yield (Figure 1). Like compounds 1–3,
coordination site that is potentially available for the
introduction of donor ligands. Accordingly, the
reaction of complexes IV with phosphines should
afford neutral congeners of Kerr’s catalysts II, which
could be used in nonpolar solvents. In contrast, most
HIE reactions with cationic iridium(I) complexes are
performed in chlorinated solvents such as
dichloromethane, which is considered unfavourable
because of its associated hazards, including suspected
1
the low symmetry (C ) of 4 leads to complicated H
1
1
3
and C NMR spectra, and hindered rotation around
the B–C F bonds creates additional complexity. The
6 5
3
1
P NMR signal is found at –16.5 ppm.
The molecular structures of 1·Et O, 3·CH Cl and
2
2
2
4·2CH Cl were determined by X-ray diffraction
2
2
analyses (Figure 2, Table 1), revealing that the
iridium atom exhibits in all cases a slightly distorted
square-planar coordination sphere with C1–Ir1–P/N
angles of 98.5(1)° (1), 88.7(1)° (3) and 94.0(1)° (4).
The Ir–C1 and Ir–P1 bond lengths in the phosphine
complexes
[11]
carcinogenicity and high vaporisability.
To the best of our knowledge, no catalyst suitable
for HIE in nonpolar solvents such as cyclohexane or
n-hexane has been described to date, and in this
contribution, we wish to present the application and
2
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Advanced Synthesis & Catalysis
10.1002/adsc.202000438
Figure 2. Molecular structures of the iridium complexes in 1·Et
2
O, 3·CH
Cl
2 2
and 4·2CH
Cl
2 2
. Thermal ellipsoids drawn at
5
0% probability. Co-crystallized solvent and hydrogen atoms were omitted for clarity. For selected bond lengths and
angles, see Table 1.
1
/4 are 2.090(2)/2.131(3) Å and 2.368(1)/2.333(1) Å
incorporation was determined by 1H NMR
spectroscopy (see the Supporting Information for
details). Initial screenings revealed that the WCA-
IMes complex IVa does not promote deuteration of
acetophenone, presumably because of its significantly
lower stability in comparison with the air-stable
and fall in the ranges established for related cationic
complexes of type II,[
10,13]
indicating that the overall
neutral nature of the WCA-NHC complexes does not
affect the structural parameters significantly. The
pyridine complex 3 shows a slightly shorter Ir–C1
bond length of 2.077(2) Å and an Ir–N3 bond length
of 2.104(2) Å, which are in good agreement with the
values established for similar cationic NHC
complexes, e.g., Ir–C = 2.076(4) and Ir–N = 2.103(4)
[22]
WCA-IDipp complex IVb. Complex 4 gave only
very low deuterium incorporation (6%–17%), which
corresponds to Kerr’s finding that all attempts to
form HIE catalysts containing a phosphine and the
[25]
[15]
in [(IDipp)Ir(py)(COD)]BF
4
,
whereas the Ir–N
sterically more encumbered carbene IDipp failed.
bond in Crabtree’s catalyst I is slightly shorter at
Therefore, compounds IVa and 4 were excluded from
further screening, which was performed with IVb and
.089(2) Å. [
26]
2
1
–3 (Figure 1).
Table 1. Table Caption. Selected bond lengths (Å) and
angles (°) of compounds 1, 3 and 4.
The results of the solvent screening are
summarized in Figure 3. In dichloromethane (DCM),
high degrees of deuteration were found for all four
catalysts (90%–95%). In contrast, only IVb
performed well in tetrahydrofuran (THF), which
agrees with the observation that THF represents a
1
3
4
Ir–Ccarbene
Ir–P/N
2.090(2)
2.368(1)
2.077(2)
2.103(2)
2.131(3)
2.333(1)
[13]
C1–Ir1–P/N 98.5(1)
88.7(1)
94.0(1)
challenging solvent for Kerr-type catalysts.
Complex 3 gave inconclusive results, presumably
because of the lability of the pyridine ligand in THF
solution. Methyl tert-butyl ether (MTBE) is used in
Catalytic Studies. Since weakly coordinating
anions (WCA) are known to improve the solubility
and therefore the activity of ionic complexes in
[11]
industry as a safer alternative to diethyl ether, and
complexes IVb and 2 performed well with ca. 95%
deuterium incorporation, whereas only mediocre
performance was found for 1 and 3. Notably, almost
quantitative deuteration (96%) was achieved with 1
and 2 even in cyclohexane and n-hexane, which
confirms our initial hypothesis that the WCA-NHC
complexes act as neutral analogues of Kerr’s catalysts
II for HIE in nonpolar solvents. A slightly lower
degree of deuteration was found for IVb in n-hexane,
while the pyridine complex 3 again proved inferior.
For a better understanding of the activity of the
new catalysts in cyclohexane, deuteration of
acetophenone (5) was studied with a reduced catalyst
loading of 0.5 mol%. The reaction mixtures were
solvents of low polarity,[
13,27]
we aimed at
investigating the influence of the solvent on H/D
exchange. Acetophenone (5) was employed as a
common substrate for screening H/D exchange
reactions, with 5 mol% of the catalyst in each solvent.
The catalysts and substrates were handled in air and
treated with commercially available HPLC grade
solvents. All H/D exchange reactions were carried
out in a 12-vial reactor equipped with a 3-way
stopcock connected to a vacuum line and a balloon
filled with deuterium gas. To start the deuteration, the
atmosphere in the vials was exchanged several times
with deuterium gas. After a reaction time of 16 h, the
solvent was reduced to a minimum and the residue
filtered through a short silica column. Deuterium
3
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Advanced Synthesis & Catalysis
10.1002/adsc.202000438
Figure 3. Solvent screening of H/D exchange with acetophenone (5, 0.083 mmol). The reactions were set up under
ambient conditions with commercially available HPLC grade solvents; 5 mol% catalyst loading, 16 h reaction time at
room temperature under 1 atm D
2
gas. Total amount of solvent used: 1 mL (DCM, THF, MTBE), 2 mL (cyclohexane), 4
mL (n-hexane). Results are reported as an average of two runs. [a] = No conclusive results could be obtained.
prepared under inert conditions to avoid catalyst
decomposition. Remarkably, deuterium incorporation
dropped significantly only for catalyst 1, whereas
almost the same level of deuteration was reached
with IVb and 2 even after shortening the reaction
time from 16 h to 90 min (Figure 4). These results
indicate that the extremely high level of catalytic
activity reported for cationic Kerr-type catalysts can
be attained by neutral WCA-NHC complexes even in
the nonpolar solvent cyclohexane.
highly active in n-hexane, we opted for a screening in
cyclohexane, since some commonly used substrates
are poorly soluble in n-hexane, e.g., ethyl 4-
dimethylaminobenzoate (8). 2-Phenylpyridine (6) is
often used to assess the tolerance of HIE catalysts
towards N-heterocycles as directing groups. A high
level of deuterium incorporation (94%) was realised
with complex 1, which is in the range reported for
Kerr’s catalysts. The lower degree observed for
IVb and 2 can probably be ascribed to stronger
binding of the substrate to the sterically less
encumbered catalysts.
[10]
To test whether the new complexes can accept a
nitro group as a directing group, deuteration of 4-
nitroanisole (7) was investigated. Thereby, the ether
group might act as a second directing group via a
four-membered metallacyclic intermediate (4-mmi)
in contrast to the generally preferred 5-mmi
[12,17]
mechanism.
Deuterium
was
selectively
incorporated in ortho-position to the nitro group with
high (98% for 1 and 2) or moderate (62% for IVb)
deuterium levels. Likewise, exclusive ortho-
deuteration was found next to the ester group in ethyl
4
-dimethylaminobenzoate
(8),
with
IVb
outperforming the IMes complexes 1 and 2. Pyrrole 9
and indole 10 were also tested, since general methods
Figure 4. Screening of H/D exchange with acetophenone
(
5, 0.083 mmol) at 0.5 mol% catalyst loading in
for labelling Boc-protected (Boc
butyloxycarbonyl) anilines are still rare.
only IVb achieved good levels of deuterium
incorporation up to 93%. The ferrocene-based diester
=
tert-
Again,
[17]
cyclohexane (2 mL). Results are reported as an average of
two runs.
To assess the substrate scope of the new iridium
catalysts for H/D exchange reactions in nonpolar
solvents, a series of selected substrates was screened
in the presence of IVb, 1 and 2 with 5 mol% catalyst
loading under the same conditions as described above
1
1 was chosen as another unusual substrate, with a
high degree of deuteration (95%) being observed only
[28]
in the presence of IVb.
Another remarkable feature of catalyst IVb is the
tolerance of anilines and benzylamines, as
demonstrated by the efficient deuteration of 1-
(
Figure 5). Even though our complexes proved to be
4
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Advanced Synthesis & Catalysis
10.1002/adsc.202000438
naphthylamine (12), 4-dimethylaminobenzylamine
(13) and 1-naphthylmethylamine (14), since primary
Figure 5. Substrate screening of H/D exchange in cyclohexane with various substrates (0.083 mmol of each substrate);
mol% catalyst loading, 16 h reaction time at room temperature under 1 atm D gas. Total amount of solvent used: 1 mL
5, 6), 5 mL (7 – 11, 13), 6 mL (12, 15), 10 mL (14). Values in square brackets denote the degree of deuteration [%] in the
5
2
(
1
2
3
1
2
indicated position (D); multiple deuteration sites are assigned in the order [D ]/[D ]/[D ] (14) and [D ]/[D ] (15); % values
indicate isolated yields. Results are reported as an average of two runs. * Almost quantitative yield of material containing
solvent impurities.
amino groups generally coordinate strongly to the versus 41%). The observation that only IVb is
iridium atom and thus lead to deactivation of the capable of labelling in positions consistent with the
catalyst.[
8,17,29]
Deuteration of 1-naphthylamine (12) formation of six-membered metallacycles can be
can be achieved adequately with all three catalysts, ascribed to a higher tendency to accommodate these
whereas the benzylamines 13 and 14 were efficiently larger rings in comparison with the sterically more
deuterated only in the presence of IVb. Moreover, congested carbene-phosphine complexes 1 and 2.
1
IVb enables efficient labelling of 14 in both the D -
2
(
83%) and D -position (87%), which indicates that
this catalyst is able to promote deuteration via five- Conclusion
(
5-mmi)
and
six-membered
metallacyclic
[
19,30,31]
intermediates (6-mmi).
To confirm this ability, We have described a new class of stable iridium(I)
2
-phenylacetophenone (15) was chosen as a final complexes with anionic N-heterocyclic carbenes that
substrate to . As expected, given the results obtained contain a weakly coordination anionic borate moiety
for the deuteration of acetophenone (5, vide supra), and have investigated their ability to promote H/D
all three catalysts lead to high degrees of deuteration exchange in nonpolar media. Phosphine introduction
via a 5-mmi, whereas labeling via a 6-mmi is only into the previously reported hydrogenation catalysts
observed for IVb, albeit to a smaller extent (91% [(WCA-NHC)Ir(COD)] (IV) affords neutral carbene-
5
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Advanced Synthesis & Catalysis
10.1002/adsc.202000438
Deutsche Forschungsgemeinschaft (DFG) through grant TA
phosphine complexes, with [(WCA-IMes)IrL(COD)]
1
89/9-2.
(
1, L = PPh
3
; 2, L = PPh Me) demonstrating a similar
2
level of catalytic activity to that reported for
established cationic Kerr-type HIE catalysts. Because
of the overall neutral charge of the new complexes,
efficient deuteration could be achieved even in
nonpolar solvents such as cyclohexane. Moreover, the
well-established hydrogenation catalyst [(WCA-
IDipp)Ir(COD)] (IVb) proved to be particularly
useful for deuterium incorporation into a wide scope
of substrates, including primary and Boc-protected
anilines, and its sterically less congested nature
creates a higher tendency to promote H/D exchange
involving not only the preferred five-membered, but
also six-membered metallacycles.
References
[
[
[
[
1] J. Atzrodt, V. Derdau, T. Fey, J. Zimmermann, Angew.
Chem. Int. Ed. 2007, 46, 7744.
2] J. Atzrodt, V. Derdau, W. J. Kerr, M. Reid, Angew.
Chem. Int. Ed. 2018, 57, 1758.
3] J. Atzrodt, V. Derdau, W. J. Kerr, M. Reid, Angew.
Chem. Int. Ed. 2018, 57, 3022.
4] a) J. Atzrodt, V. Derdau, J. Label Compd.
Radiopharm. 2010, 53, 674; b) D. Hesk, C. F. Lavey,
P. McNamara, J. Label Compd. Radiopharm. 2010, 53,
7
22; c) M. Valero, V. Derdau, J. Label Compd.
Radiopharm. 2019, in press.
[
[
5] a) J. R. Heys, J. Label Compd. Radiopharm. 2007, 50,
Experimental Section
7
70; b) G. N. Nilsson, W. J. Kerr, J. Label Compd.
Radiopharm. 2010, 53, 662; c) R. Salter, J. Label
Compd. Radiopharm. 2010, 53, 645; d) W. J. Kerr, G.
J. Knox, L. C. Paterson, J. Label Compd. Radiopharm.
Full experimental procedures, including the synthesis and
characterization of compounds 1–4 can be found in the
Supporting Information.
2
020, in press, 1.
6] a) J. J. Katz in Encyclopedia of chemical technology
Eds.: R. E. Kirk, D. F. Othmer), Wiley, New York,
Labelling reactions: General remarks. All labelling
experiments were carried out in a Radleys carousel reactor
and HPLC grade solvents without further purification.
Exceptions are experiments with low catalyst loading (0.5
mol%) and naphthylmethylamine 14 (air-sensitive), which
were prepared under standard Schlenk conditions with
purified solvents. Deuterium incorporation was determined
(
NY, 2003, p. 566; b) R. Voges, J. R. Heys, T.
Moenius, Preparation of compounds labeled with
tritium and carbon-14, Wiley, Chichester, United
Kingdom, 2009; c) W. J. S. Lockley, A. McEwen, R.
Cooke, J. Label Compd. Radiopharm. 2012, 55, 235;
d) E. M. Isin, C. S. Elmore, G. N. Nilsson, R. A.
Thompson, L. Weidolf, Chem. Res. Toxicol. 2012, 25,
532.
1
by H NMR spectra via correlation of the respective
integrals of the undeuterated starting material versus the
deuterated product. Both integrals of the starting material
and product were calibrated against a peak corresponding
to a position not expected to be labelled (see equation 1 in
the Supporting Information). All degrees of deuteration
were determined by the average of two reactions.
[
[
7] R. Crabtree, Acc. Chem. Res. 1979, 12, 331.
8] G. J. Ellames, J. S. Gibson, J. M. Herbert, A. H.
McNeill, Tetrahedron 2001, 57, 9487.
9] M. Valero, A. Mishra, J. Blass, R. Weck, V. Derdau,
ChemistryOpen 2019, 8, 1183.
General screening procedure. A stock solution of the
substrate is prepared by dissolving 0.083 mmol of the
substance per reaction in a specific amount of solvent (0.5–
[
[
5
mL). After transfer of the substrate, the corresponding
catalyst (0.00415 mmol IVb = 5.0 mg, 1 = 5.7 mg, 2 = 5.5
mg, 3 = 4.9 mg, 5 mol%) is added as a solution to the
Radleys Reactor (0.5–5 mL). The reactor caps are closed,
and the atmosphere is exchanged four times with deuterium
10] J. A. Brown, S. Irvine, A. R. Kennedy, W. J. Kerr, S.
Andersson, G. N. Nilsson, Chem. Commun. 2008,
1
115.
gas via a balloon. With tightly closed caps, the reaction is [11] A. R. Cochrane, C. Idziak, W. J. Kerr, B. Mondal, L.
stirred for 16 h at room temperature. To terminate the
C. Paterson, T. Tuttle, S. Andersson, G. N. Nilsson,
Org. Biomol. Chem. 2014, 12, 3598.
deuteration process, the atmosphere is exchanged twice
with argon prior to careful removal of the corresponding
solvent in vacuo. For volatile substrates, the solvent is [12] J. A. Brown, A. R. Cochrane, S. Irvine, W. J. Kerr, B.
reduced to a minimum before work-up. Details of the
work-up procedures and solvent amounts are available in
the Supporting Information.
Mondal, J. A. Parkinson, L. C. Paterson, M. Reid, T.
Tuttle, S. Andersson et al., Adv. Synth. Catal. 2014,
3
56, 3551.
[
[
13] A. R. Kennedy, W. J. Kerr, R. Moir, M. Reid, Org.
Biomol. Chem. 2014, 12, 7927.
Crystal structures. CCDC 1995319 (1·Et
2
O), CCDC
1
1
995320 (3∙CH
2
Cl
2
), CCDC 1995321 (4∙2 CH
]·CH
2
Cl
2
), CCDC
), and
Cl
995322 ([(WCA-IMes-COE)Ir(PMe
3
)
3
Cl
2 2
14] a) W. J. Kerr, R. J. Mudd, L. C. Paterson, J. A. Brown,
Chem. Eur. J. 2014, 20, 14604; b) P. Cross, J. Herbert,
W. Kerr, A. McNeill, L. Paterson, Synlett 2015, 27,
111; c) J. Atzrodt, V. Derdau, W. J. Kerr, M. Reid, P.
Rojahn, R. Weck, Tetrahedron 2015, 71, 1924; d) J.
Devlin, W. J. Kerr, D. M. Lindsay, T. J. D. McCabe,
M. Reid, T. Tuttle, Molecules 2015, 20, 11676; e) W.
J. Kerr, M. Reid, T. Tuttle, ACS Catal. 2015, 5, 402; f)
W. J. Kerr, D. M. Lindsay, M. Reid, J. Atzrodt, V.
Derdau, P. Rojahn, R. Weck, Chem. Commun. 2016,
CCDC 1995323 ([(WCA-IMes)Ir(14)(COD)]·CH
2
2
)
contain the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The
Cambridge
Crystallographic
Data
Centre
via
www.ccdc.cam.ac.uk/data_request/cif.
Acknowledgements
The authors wish to acknowledge helpful discussions with Dr.
Volker Derdau (Sanofi-Aventis), Daniel Becker and Dr. Kristof
Jess. L. P. Ho thanks the Fonds der Chemischen Industrie (FCI)
for a Chemiefonds fellowship. This work was supported by the
5
2, 6669; g) W. J. Kerr, R. J. Mudd, P. K. Owens, M.
Reid, J. A. Brown, S. Campos, J. Label Compd.
Radiopharm. 2016, 59, 601; h) W. J. Kerr, M. Reid, T.
6
This article is protected by copyright. All rights reserved.

Advanced Synthesis & Catalysis
10.1002/adsc.202000438
Tuttle, Angew. Chem. Int. Ed. 2017, 56, 7808; i) W. J.
Kerr, D. M. Lindsay, P. K. Owens, M. Reid, T. Tuttle,
S. Campos, ACS Catal. 2017, 7, 7182; j) W. J. Kerr, R.
J. Mudd, M. Reid, J. Atzrodt, V. Derdau, ACS Catal.
2
018, 8, 10895.
[
15] A. R. Cochrane, S. Irvine, W. J. Kerr, M. Reid, S.
Andersson, G. N. Nilsson, J. Label Compd.
Radiopharm. 2013, 56, 451.
[
[
16] X. Wu, M. Tamm, Coord. Chem. Rev. 2014, 260, 116.
17]K. Jess, V. Derdau, R. Weck, J. Atzrodt, M. Freytag, P.
G. Jones, M. Tamm, Adv. Synth. Catal. 2017, 359, 629.
18] M. Valero, A. Burhop, K. Jess, R. Weck, M. Tamm, J.
Atzrodt, V. Derdau, J. Label Compd. Radiopharm.
[
[
2
018, 61, 380.
19] M. Valero, D. Becker, K. Jess, R. Weck, J. Atzrodt, T.
Bannenberg, V. Derdau, M. Tamm, Chem. Eur. J.
2
019, 25, 6517.
20] A. Nasr, A. Winkler, M. Tamm, Coord. Chem. Rev.
016, 316, 68.
[
[
2
21] S. Kronig, E. Theuergarten, C. G. Daniliuc, P. G.
Jones, M. Tamm, Angew. Chem. Int. Ed. 2012, 51,
3
240.
[
22] E. L. Kolychev, S. Kronig, K. Brandhorst, M. Freytag,
P. G. Jones, M. Tamm, J. Am. Chem. Soc. 2013, 135,
1
2448.
[
[
23] A. Winkler, K. Brandhorst, M. Freytag, P. G. Jones,
M. Tamm, Organometallics 2016, 35, 1160.
24] a) J. S. Merola, R. T. Kacmarcik, Organometallics
1
989, 8, 778; b) J. F. Frazier, F. E. Anderson, R. Clark,
J. S. Merola, Inorg. Chim. Acta 1994, 222, 135.
25] J. Fawcett, D. A. J. Harding, E. G. Hope, K. Singh, G.
A. Solan, Dalton Trans. 2010, 39, 10781.
26] H. M. Lee, T. Jiang, E. D. Stevens, S. P. Nolan,
Organometallics 2001, 20, 1255.
27] I. M. Riddlestone, A. Kraft, J. Schaefer, I. Krossing,
Angew. Chem. Int. Ed. 2018, 57, 13982.
28] A. R. Petrov, K. Jess, M. Freytag, P. G. Jones, M.
Tamm, Organometallics 2013, 32, 5946.
[
[
[
[
[
29] a) M. Valero, D. Bouzouita, A. Palazzolo, J. Atzrodt,
C. Dugave, S. Tricard, S. Feuillastre, G. Pieters, B.
Chaudret, V. Derdau, Angew. Chem. Int. Ed. 2020, 59,
3
517; b) M. J. Hickey, J. R. Jones, L. P. Kingston, W.
J.S. Lockley, A. N. Mather, B. M. McAuley, D. J.
Wilkinson, Tetrahedron Lett. 2003, 44, 3959.
30] A.Y.L. Shu, W. Chen, J. R. Heys, J. Organomet.
Chem. 1996, 524, 87.
31] The inability of 1 to achieve deuteration of 14 can be
tentatively ascribed to catalyst deactivation by
phosphine substitution and strong coordination of the
amine substrate as evidenced by isolation of the
complex [(WCA-IMes)Ir(14)(COD)]; see the
Supporting Information for the crystal structure of
[
[
[
2 2
(WCA-IMes)Ir(14)(COD)]·CH Cl .
7
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Advanced Synthesis & Catalysis
10.1002/adsc.202000438
FULL PAPER
Iridium(I) Complexes with Anionic N-
Heterocyclic Carbene Ligands as Catalysts for
H/D Exchange in Nonpolar Media
Adv. Synth. Catal. Year, Volume, Page – Page
Marvin Koneczny, Luong Phong Ho, Alexandre
Nasr, Matthias Freytag, Peter G. Jones, and
Matthias Tamm*
8
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