Enhanced Catalytic Activity of Iridium(III) Complexes by Facile Modification of C,N-Bidentate Chelating Pyridylideneamide Ligands

Article abstract of DOI:10.1021/acs.inorgchem.7b01654

A set of aryl-substituted pyridylideneamide (PYA) ligands with variable donor properties owing to a pronounced zwitterionic and a neutral diene-type resonance structure were used as electronically flexible ligands at a pentamethylcyclopentadienyl (Cp) iridium center. The straightforward synthesis of this type of ligand allows for an easy incorporation of donor substituents such as methoxy groups in different positions of the phenyl ring of the C,N-bidentate chelating PYA. These modifications considerably enhance the catalytic activity of the coordinated iridium center toward the catalytic aerobic transfer hydrogenation of carbonyls and imines as well as the hydrosilylation of phenylacetylene. Moreover, these PYA iridium complexes catalyze the base-free transfer hydrogenation of aldehydes, and to a lesser extent also of ketones. Under standard transfer hydrogenation conditions including base, aldehydes are rapidly oxidized to carboxylic acids rather than reduced to the corresponding alcohol, as is observed under base-free conditions.

Full text of DOI:10.1021/acs.inorgchem.7b01654

Article
pubs.acs.org/IC
Enhanced Catalytic Activity of Iridium(III) Complexes by Facile
Modification of C,N-Bidentate Chelating Pyridylideneamide Ligands
Miquel Navarro,† Christene A. Smith,†,‡ and Martin Albrecht*,†
†Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, CH-3012 Bern, Switzerland
S
* Supporting Information
ABSTRACT: A set of aryl-substituted pyridylideneamide (PYA)
ligands with variable donor properties owing to a pronounced
zwitterionic and a neutral diene-type resonance structure were
used as electronically flexible ligands at a pentamethylcyclopenta-
dienyl (Cp*) iridium center. The straightforward synthesis of this
type of ligand allows for an easy incorporation of donor
substituents such as methoxy groups in different positions of
the phenyl ring of the C,N-bidentate chelating PYA. These modifications considerably enhance the catalytic activity of the
coordinated iridium center toward the catalytic aerobic transfer hydrogenation of carbonyls and imines as well as the
hydrosilylation of phenylacetylene. Moreover, these PYA iridium complexes catalyze the base-free transfer hydrogenation of
aldehydes, and to a lesser extent also of ketones. Under standard transfer hydrogenation conditions including base, aldehydes are
rapidly oxidized to carboxylic acids rather than reduced to the corresponding alcohol, as is observed under base-free conditions.
INTRODUCTION
■
Classic spectator ligands like phosphines, amines, or halides
typically feature static bonding characteristics such as π-donor
or π-acceptor properties, which can be more or less
pronounced depending on the metal center to which they are
coordinating. Such ligands traditionally stabilize a specific metal
Figure 1. (a) Generic representation of PYE (E = H2) and PYA (E =
O) and their limiting neutral (A) and zwitterionic (B) resonance
configuration; e.g., strong π acceptors preferably bind to low-
valent, electron-rich metal centers.1 More recently, non-
innocent ligands that can significantly modulate their donor
properties have become increasingly popular as a powerful class
of ligands for a variety of homogeneous catalytic applications
because the modular ligation alleviates the constrain of static
ligands, which stabilize predominantly one specific config-
uration.2 For example, Shvo’s cyclopentadienone system or
Noyori’s diamine ligand can change from L-type neutral
coordination to anionic X-type metal bonding during a catalytic
cycle.3 Similar L/X-type ambiguous ligand systems have been
developed based on pyridines, guanidines, and related func-
tional groups.4 This ligand flexibility allows for facilitating both
oxidative addition and reductive elimination processes on a
putative catalytic cycle, properties that are highly attractive for
the design of efficient catalysts, and offering opportunities also
for materials science. Such dynamic bonding may, in fact, be
one of the key features of N-heterocyclic carbenes (NHCs) that
underpins their beneficial role in homogeneous catalysis
through adoption of either a more neutral carbenic bonding
(L-type) or a zwitterionic (X-type) bonding mode during
catalytic transformations.5−7
structures. (b) PYA ligand containing a chelating aryl group (C).
resonance forms comprised of a diene heterocycle and a
neutral imine donor site with minimal charge separation (A)
and a zwitterionic form (B) that features an anionic amide
donor site and aromatic stabilization of the pyridinium residue.8
PYA coordination to transition metals has been pioneered by
Johnson and Douthwaite,9 and we have recently demonstrated
the adaptiveness of PYAs in response to the external
environment such as the solvent polarity.10 Complexes with
PYA or PYE ligands have shown high catalytic activity in
different redox transformations including C−F bond activatio-
n,9a C−H bond stannylation,11 water oxidation,10b and transfer
hydrogenation,10a,12 which warrants further investigation of
PYAs as ancillary ligands to catalytically active metal centers.
A major advantage of PYA ligands is their straightforward
synthesis, which allows modifications to be introduced easily for
fine-tuning the electronic and steric properties as a method to
improve the catalytic activity.13 Here, we applied this concept
for facile catalyst tailoring by incorporating donor substituents
in different positions of the phenyl ring of the C,N-bidentate
chelating PYA ligand C (Figure 1). These modifications greatly
enhance the catalytic activity of the coordinated iridium center.
Similar to NHCs, pyridylideneamines (PYEs) and pyridyli-
deneamides (PYAs) are electronically highly flexible nitrogen-
donor sites that can coordinate to the metal center as a π-acidic
imine or as a π-basic pyridinium amide (Figure 1). Their
electronic flexibility is represented by the two limiting
Received: June 28, 2017
© XXXX American Chemical Society
A
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Scheme 1. Synthesis of the IrCp*PYA-Type Complexes
Table 1. Selected Bond Lengths (Å) and Angles (deg) of the IrPYA Complexes 4
a
b
4a
4b
4c
4d
4e
Ir−C
Ir−N
average Cα−Cβ
average Cβ−Cγ
Ir−Cp
2.045(2)
2.120(2)
1.371(5)
1.410(5)
1.8316(11)
2.033(4)
2.095(3)
1.366(13)
1.407(12)
1.827(4)
2.053(7)
2.119(6)
1.356(14)
1.416(14)
1.829(3)
2.055(17)
2.096(14)
1.38(3)
2.047(3)
2.122(2)
1.366(6)
1.407(6)
1.8221(12)
1.40(3)
1.826(8)
centroid
C−Ir−N
C−Ir−Cl
N−Ir−Cl
78.12(9)
89.59(7)
85.67(6)
77.89(16)
89.92(12)
87.61(10)
78.0(3)
89.9(2)
76.6(6)
87.5(5)
87.3(4)
77.73(10)
89.65(8)
89.48(7)
86.07(17)
a
b
Data from ref 10b. Data for one of the two independent molecules in the unit cell; the average Cα−Cβ and Cβ−Cγ were calculated from both
molecules.
compounds 3a−3e and hence independent of, and electroni-
cally decoupled from, the aryl substitution pattern. The free
bases are stable toward air and moisture and have been
characterized also by elemental analysis.
RESULTS AND DISCUSSION
■
Synthesis. A set of PYA iridium complexes were prepared
starting from differently substituted benzoyl chlorides in four
straightforward synthetic steps (Scheme 1).10b Accordingly,
benzoyl chlorides with one, two, or three aromatic OMe
substituents were reacted with 4-aminopyridine to yield the
corresponding amides 1a−1e. Formation of the products was
indicated by the diagnostic low-field singlet around 10.5 ppm in
the 1H NMR spectrum due to the amide NH proton.
Subsequent alkylation with MeI occurred selectively and
exclusively at the pyridine nitrogen, even in the presence of a
large excess of alkylating agent, and afforded the pyridinium
amide salt 2 in excellent yield.14 All salts showed the
characteristic [M − I]+ signal in high-resolution mass
spectrometry (HR-MS). Alkylation was further supported by
1H NMR spectroscopy, which revealed a new singlet for the
NCH3 group (δH = 4.2) as well as a 0.3 to 0.5 ppm downfield
shift of the pyridinium proton signals compared to the
analogous resonances of the neutral pyridine resonances in 1.
Amide deprotonation was accomplished with simple bases such
as NaOH in a straightforward CH2Cl2/H2O extraction and
afforded the free ligands 3a−3e in good yield (64−84%). In
The reaction of the free ligands with [IrCp*Cl2]2 in the
presence of NaOAc as an auxiliary ligand15 induced cyclo-
metalation and afforded the iridium complexes 4a−4e in good
yield (70−78%) as air-stable complexes that were purified by
standard column chromatography on silica. Cyclometalation
was confirmed for all complexes by the loss of one proton
signal in the aromatic region of the 1H NMR spectrum.
Moreover, the m-OCH3 groups in 4d and 4e appeared as two
distinct singlets due to the reduced symmetry upon cyclo-
metalation.16 The 13C resonance of the amide carbonyl
appeared at lower field than that in the precursor compound,
in agreement with coordination of the amide to the metal
center.17 While the methyl group of the Cp* ligand resonates at
almost identical frequency in all five complexes [δH = 1.50
( 2); δC = 9.2 ( 1)], the ring carbon resonances are
deshielded if the aryl ring contains methoxy substituents (δCp
= 82.3 for complex 4a versus 87.4 ( 2) for complexes 4b−4e).
This difference suggests a direct electronic influence of the
aromatic substituents on the electronic configuration of the
IrCp* unit.
1
addition to the disappearance of the amide proton, the H
NMR spectra of the free-base complexes also revealed a
substantial upfield shift of about 0.8 ppm for the heterocyclic
proton resonances.8 In contrast, the aryl proton signals are
barely affected, indicating that the pyridylidene system is
involved in stabilizing the amide but not the (methoxy)aryl
unit. Moreover, the heterocyclic proton shifts are identical in all
The structures of all complexes were unequivocally
confirmed by single-crystal X-ray diffraction analysis. The
molecular structures show the classical three-legged piano-stool
geometry with the iridium center in a pseudotetrahedral
geometry. Bond lengths and angles around the iridium center
B
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Figure 2. ORTEP representation of complexes 4b−4e (50% probability; hydrogen atoms and cocrystallized solvent molecules omitted for clarity).
are identical within standard deviations for all complexes (Table
1). We note that the pyridyl Cα−Cβ bonds are consistently
shorter (average 1.37 Å) compared to the Cβ−Cγ bonds (1.41
Å), confirming considerable contribution of the neutral diene-
type resonance structure in the solid state (cf. Figure 2), in
agreement with previous studies.10,12 The essentially identical
Cα−Cβ bond distances for all five complexes corroborate the
conclusions deduced from NMR spectroscopy that the aryl
substitution pattern does not perturb the electronic config-
uration of the heterocycle. This disconnection is remarkable
because the electron-donating properties of the methoxy
groups are expected to enhance the electron density at the
iridium center and hence enhance the iridium-to-imine back-
bonding. Such interactions would favor the contribution of
diene-type resonance structures with increasing numbers of
methoxy substituents. However, no such trend is indicated by
the data for complexes 4a−4e, and the diene structure is
equally pronounced, e.g., for complexes 4b and 4e containing
one and three OMe substituents, respectively.
neutral resonance form (A in Figure 1), while bond and torsion
angle analysis suggests a predominance of the resonance form B
(Figure 1).
Catalytic Transfer Hydrogenation. The effect of ligand
modification in these PYA ligands was probed in iridium-
catalyzed transfer hydrogenation of ketones.18 Initially,
benzophenone was used as a model substrate to compare the
activities of all of the complexes. Under standard transfer
hydrogenation conditions using iPrOH as both the dihydrogen
source and solvent and KOH as the base (100:10:1 substrate/
base/catalyst), the unsubstituted complex 4a displayed modest
activity, reaching essentially full conversion within 24 h at 1 mol
% loading (Table 2). This performance is a considerable
improvement compared to that of [IrCp*Cl2]2 as a benchmark
complex, which only reached 39% conversion under identical
conditions. No significant difference in the catalytic activity was
observed upon exchange of the spectator ligand from an
anionic chloride (4a) to neutral acetonitrile (MeCN; 5a) or
dimethyl sulfoxide (DMSO; 6a; entries 1−3), suggesting that
Closer inspection of the bonding situation around the
iridium-bound nitrogen nucleus indicates a dihedral angle of
about 35° between the pyridine heterocycle and the amide
functionality [determined as the Cβ−Cγ−N−C(O) torsion
angle, Table S1], which minimizes the overlap of the π electron
density between these two systems. This tilting is in agreement
with the negligible contribution of a zwitterionic form with an
oxo anion, as deduced from IR data recorded on related
complexes.12 These data showed no perturbation of the NC(
O) amide unit upon solvent modification, while the
pyridylidene amide moiety was strongly affected. The sum of
the three bond angles around the iridium-bound nitrogen is
exactly 360°, confirming sp2 hybridization of this nucleus. The
torsion angles between the carbonyl unit of the amide and the
N−Ir bond are very close to 180°, while the torsion angle
between the N−Ir bond and the pyridyl Cγ−Cβ bond is very
similar to the dihedral angle of the pyridyl ring with the N−
C(O) bond vector. These data indicate that, in the solid
state, π electron overlap of the Ir−N bond is stronger with the
carbonyl unit than with the pyridyl heterocycle, which is twisted
out of the nitrogen sp2 plane. As a consequence, the PYA ligand
shows ambiguous characteristics: the partial CC double-
bond localization points to a significant contribution of the
Table 2. Transfer Hydrogenation of Benzophenone with
PYA Iridium Complexes 4−6
a
b
conversion/%
entry
catalyst
2 h
4 h
24 h
1
2
3
4
5
6
7
8
4a
5a
6a
7
27
28
13
99
96
99
4
99
2
99
4b
77
30
93
2
n.d.
c
4c
99
d
4d
99
n.d.
30
4e
4
[IrCp*Cl2]2
n.d.
n.d.
37
a
General conditions: benzophenone (1.0 mmol), KOH (50 μL, 2 M in
H2O, 0.1 mmol), anisole (1.0 mmol), iridium complex (0.01 mmol),
b
iPrOH (5 mL), reflux temperature. Determined by 1H NMR
spectroscopy (error 3%) with anisole as the internal standard; n.d. =
c
d
not determined. After 5 h. After 3 h.
C
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a
Table 3. Catalytic Transfer Hydrogenation of Different Ketones
a
General conditions: substrate (1.0 mmol), complex 4d (0.01 mmol), KOH (50 μL, 2 M in H2O, 0.1 mmol), anisole (1.0 mmol), iPrOH (5 mL),
b
1
reflux temperature. Yields determined by H NMR spectroscopy (error 3%) with anisole as the internal standard. 65% yield.
the ancillary ligand is not bound to the metal center during the
catalytic transformation. The lower conversion of complex 6a at
the initial stages of the reaction is probably due to the higher
stability of the Ir−SDMSO bond compared to the Ir−Cl and Ir−
NMeCN bonds in complexes 4a and 5a, respectively.10b The
catalytic activity of the complex is markedly improved when
electron-donating methoxy substituents are available on the
ligand scaffold. Thus, complexes 4b and 4c, both containing
one methoxy substituent, showed substantially higher catalytic
activity and achieved full conversion in 4 and 5 h, respectively
(entries 4 and 5). The incorporation of a second methoxy
group enhances the catalytic activity even further, and complex
4d reaches 93% conversion after 2 h and essentially full
conversion within 3 h (entry 6), corresponding to about a 10-
fold improvement of the catalytic activity compared to the
parent complex 4a.19 While this trend suggests that an electron-
rich iridium(III) center is beneficial for catalytic turnover, a
subtle balance is operational. When a third methoxy group is
added to the ligand as in complex 4e, the catalytic activity does
not increase further but drops even below the performance of
the unsubstituted complex 4a and reaches a low 30%
conversion after 24 h (entry 7). This different behavior
suggests that another step in the catalytic cycle is substantially
affected by the presence of three substituents on the aryl ligand.
The radical change in the activity of 4e in comparison to that of
4b−4d is surprising, and while we do not have mechanistic
evidence to rationalize this activity change, an electronic effect
seems unlikely.20 Mesomeric stabilization does not appear to be
particularly significant for controlling the catalytic activity
because the activities of the complexes with methoxy
substituents ortho/para or meta to the iridium center are
very similar (4d vs 4b). Likewise, inductive effects are not
substantially altering the catalytic activity, as demonstrated by
the moderate increase of activity upon the introduction of one
versus two methoxy groups to the ligand scaffold. It is therefore
difficult to conceive that electronic factors induced by the third
methoxy group of 4e lead to an almost complete shutdown of
the catalytic activity. More likely, the presence of ortho-
positioned methoxy groups influences the orientation of the
OMe group ortho to the iridium-bound carbon. Therefore, we
tentatively attribute the low activity of 4e to a buttressing effect
of the vicinal methoxy group,21 which is caused by excessive
substitution of the arene and which results in efficient shielding
of the iridium coordination sphere. According to this model,
the additional OMe substituent in 4e compared to 4d inhibits a
flexible arrangement of the vicinal methoxy group and hence
hinders substrate coordination, which significantly abates
catalytic turnover. Irrespective of these mechanistic consequen-
ces, the different activities of complexes 4a−4e and the poor
activity of the PYA-free [IrCp*Cl2]2 iridium complex (entry 8)
underpin the efficacy of ligand aryl substitution as a
methodology to tailor and optimize the catalytic activities of
these PYA iridium complexes.
On the basis of its better catalytic activity, complex 4d was
used as the catalyst precursor for a set of different substrates
(Table 3). Cyclohexanone as an aliphatic ketone was fully
converted within 2 h (entry 1).22 Likewise, acetophenone was
transfer hydrogenated to 1-phenylethanol at a slightly slower
rate and within 3 h. Aromatic substituents on acetophenone
displayed the expected effect, with electron-withdrawing
substituents increasing the electrophilicity of the carbonyl
group and hence facilitating reduction, while electron-donating
substituents had the opposite effect (entries 2−4).18 Along
these lines, transfer hydrogenation of acetylpyridine proceeded
D
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significantly faster than that of (substituted) acetophenones and
reached maximum conversion in just 1 h (entries 5−7). The
conversion rate is dependent on the isomer, viz., 2-, 3-, or 4-
acetylpyridine (see conversion at 0.5 h, entries 5−7); however,
complete conversion at 1 h suggests a purely electronic role of
the pyridyl unit in this reaction. In particular 2-acetylpyridine is
for most catalysts a challenging target because both the
substrate and the alcohol product are potentially chelating
ligands that tend to poison the catalyst.23 The smooth
transformation of this substrate tentatively suggests the
presence of only one labile coordination site at the iridium
center in the catalytic species originating from these bidentate
PYA complexes and therefore lends indirect support to the
strong chelation of the PYA ligand.
(entries 2 and 3). We note that while the introduction of a third
methoxy substituent on the aryl group deactivated the iridium
center for catalytic ketone transfer hydrogenation, no such
effect was observed for imine reduction, and complex 4e
performed equally well when compared with the related
complexes 4a−4d in imine transfer hydrogenation (entry 5).
On the basis of these catalyst screening results, the iridium
complex 4b was used as the catalyst precursor for transfer
hydrogenation of different imines (Table 5). Functionalized
imines showed the same trends as those established for ketones,
with electron-withdrawing substituents accelerating hydrogen
transfer and electron-donating groups slowing it down (entries
1 and 2).18 Interestingly, ketimines were not converted at all
(entry 3), suggesting either a critical role of the α proton of the
imine or steric constraints that hamper or even prevent
substrate binding. In contrast to analogous carbonyl substrates,
aliphatic and benzylic aldimines are poor substrates and need
longer reaction times to reach substantial conversion (entries
4−6).
Further mechanistic insight was gained from a transfer
hydrogenation experiment in heptadeuterated iPrOH,
(CD3)2CDOH, as a selective HD donor, and benzophenone
as the acceptor. The diphenylmethanol obtained from this
reaction was completely deuterated at the carbinol position
1
with less than 5% hydrogen incorporation according to H
Base-Free Transfer Hydrogenation. Because of the
potentially zwitterionic resonance structure and hence
ambiguous donor properties of the PYA ligand in these iridium
complexes 4a−4e, we investigated transfer hydrogenation of
more challenging substrates such as aldehydes.18 The iridium
complex 4d was used as the catalyst precursor for the reduction
of benzaldehyde under base-assisted standard conditions
(refluxing iPrOH, 1 mol % catalyst loading, and 10 mol %
KOH; Scheme 2). Essentially, full conversion of the substrate
was achieved within less than 5 min [turnover frequency
(TOF) > 1200 h−1]; however, the yield of benzyl alcohol was
only 50%. Isolation of the products revealed benzoic acid and
benzoate as the second products, as expected from the
Cannizzaro reaction.26 However, no esters were formed
under these reaction conditions.27 Identical results were
obtained when the catalyst loading was lowered to 0.01 mol
%, but in this case, longer reaction times of up to 30 min were
needed to reach maximum conversion. To establish the role of
complex 4d in this reaction, blank reactions in the presence of
base but in the absence of complex 4d were carried out, and
they indeed showed the formation of benzyl alcohol and
benzoic acid, although at a significantly slower rate. The metal-
free reaction reached 25% conversion after 5 min and 65% after
30 min. In contrast, the 4d-catalyzed reaction was complete
within 5 min (at 1 mol % loading) and at 30 min at 0.01 mol %
4d, suggesting a catalytic effect of the iridium complex.
Moreover, the alcohol/acid product ratio was always 1:2, as
opposed to the 1:1 ratio observed in runs in the presence of 4d.
When catalytic runs with 4d were performed under an
anaerobic argon atmosphere, the ratio of products was
unaffected and remained at a 1:1 mixture of alcohol and acid.
The rates and product ratio indicate that complex 4d is
accelerating the Cannizzaro reaction by about an order of
magnitude and that the complex itself favors the reductive
process and formation of the benzyl alcohol. These
observations prompted us to investigate the hydrogen transfer
activity of complex 4d under base-free reaction conditions.
When the metal-catalyzed reaction with benzaldehyde was
performed in neat iPrOH and without the addition of any base,
aldehyde conversion was much slower, yet it reached 85%
within 24 h. In contrast to the base-mediated reaction, the base-
free procedure was completely selective and afforded
exclusively benzyl alcohol as the product of transfer hydro-
genation. Base-free transfer hydrogenation has been suggested
NMR spectroscopy. The selective transfer of the deuterium
atom from the carbon site of the hydrogen donor (iPrOH-d7)
to the carbonyl carbon of the substrate is in agreement with a
monohydride mechanism for the transfer hydrogenation
reaction.18b,24 This mechanism requires only one labile
coordination site and therefore corroborates the model
deduced above.
Because pyridyl moieties were tolerated by the catalytically
active species without significant compromises of the turnover
rates (cf. Table 3, entries 5−7), imines were investigated as
substrates for transfer hydrogenation. The model substrate N-
benzylideneaniline was almost fully hydrogenated to N-
benzylaniline after 4 h using iridium complexes 4a−4e under
the same standard conditions (Table 4). The longer reaction
Table 4. Transfer Hydrogenation of N-Benzylideneaniline
a
with PYA Iridium Complexes 4a−4e
b
conversion/%
entry
catalyst
1 h
2 h
4 h
1
2
3
4
5
4a
4b
4c
4d
4e
30
34
31
31
34
49
54
50
48
53
87
94
92
86
80
a
General conditions: N-benzylideneaniline (1.0 mmol), KOH (50 μL,
2 M in H2O, 0.1 mmol), hexamethylbenzene (1.0 mmol), iridium
complex (0.01 mmol), iPrOH (5 mL), reflux temperature.
b
Determined by 1H NMR spectroscopy (error 3%) with
hexamethylbenzene as the internal standard.
time required to reach quantitative yields is in line with the
expected lower activity of imines compared to ketones.22b,25
The catalytic activity for imine hydrogenation is not
significantly affected by the different electronic properties of
the PYA ligands, and all complexes display similar conversion
rates (entries 1−5). However, catalysts 4b and 4c, both
containing only one methoxy group, are slightly more active
catalyst precursors and reach >90% conversion after 4 h
E
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a
Table 5. Catalytic Transfer Hydrogenation of Different Imines
a
General conditions: imine (1.0 mmol), complex 4b (0.01 mmol), KOH (50 μL, 2 M in H2O, 0.1 mmol), hexamethylbenzene (0.16 mmol), iPrOH
b
1
(5 mL), reflux temperature. Determined by H NMR spectroscopy (error 3%) with hexamethylbenzene as the internal standard; n.d. = not
determined. After 3 h.
c
Scheme 2. Catalytic Transformation of Benzaldehyde in Different Conditions
as an attractive methodology for the reduction of ketones and
aldehydes because most alkali-metal bases traditionally used in
transfer hydrogenation are corrosive and irreversibly alter the
catalyst.28 Stimulated by this activity, transfer hydrogenation of
different substrates was tested under base-free conditions
(Table 6). Substituted benzaldehydes are less active than the
model substrate and did not give quantitative yields (entries 2
and 3). 4-Cyanobenzaldehyde is only moderately active,
although we note that the nitrile group is not hydrogenated
during the process and that the complex demonstrates excellent
selectivity toward the carbonyl group (entry 4). In contrast to
the ketone analogue in the base-assisted transfer hydrogenation,
2-pyridinecarboxaldehyde and aliphatic aldehydes are unsuit-
able substrates for transfer hydrogenation with no strong base
added (entries 5 and 6). While aliphatic aldehydes may be too
bulky to coordinate to the metal center under base-free
conditions (entry 6), such conditions may favor pyridine
coordination to the iridium center, which prevents conversion
of heterocyclic substrates. In support of this model, conversion
of benzaldehyde does not proceed in the presence of
substoichiometric quantities of pyridine (<5% conversion
after 2 h and 20% conversion after 24 h, compared to 59%
and 85%, respectively, in the absence of pyridine). Hence, the
presence of potentially coordinating functional groups in the
substrate poisons the catalyst, which points to a distinctly
different mechanism in comparison to the base-catalyzed
reaction. In contrast, ketones such as acetophenone and
benzophenone were essentially fully converted to the
corresponding alcohol in 24 h. These considerably longer
reaction times compared to the base-assisted transfer hydro-
genation (3 h; cf. Table 3, entry 2) suggest a different
mechanistic pathway for the base-free reaction compared to the
KOH-mediated hydrogen transfer. We suggest that the base-
catalyzed transfer hydrogenation conditions rapidly lead to the
formation of the Ir−H species (i.e., the chlorides in complexes
4a−4e are rapidly exchanged for hydrides), and hydrogenation
then follows through insertion of the carbonyl group into the
Ir−H bond. In contrast, under base-free conditions, iPrOH
coordination to the metal center must occur to provide the
potentially ligand-assisteddehydrogenation, and this coordi-
nation is unfavorable in the presence of stronger coordinating
substrates such as the pyridyl unit in pyridylcarboxylate. The
high conversions of benzaldehyde derivatives with complexes
4a−4e suggest promising opportunities for base-free catalytic
reactions using PYA ligands.
Catalytic Hydrosilylation of Phenylacetylene. Similar
to transfer hydrogenation, hydrosilylation typically requires the
transient formation of a metal hydride intermediate.29
Prompted by the support established for a monohydride
mechanism in transfer hydrogenation, we were therefore
interested in evaluating the PYA complexes as catalyst
precursors for the hydrosilylation of terminal alkynes. Three
isomeric vinylsilane derivatives are usually obtained in this
reaction, namely, β(Z)- and β(E)-vinylsilane as the products
F
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Article
a
Table 6. Base-Free Transfer Hydrogenation of Aldehydes and Ketones
a
General conditions: aldehyde or ketone (1.0 mmol), complex 4e (0.01 mmol), hexamethylbenzene (0.16 mmol), iPrOH (5 mL), reflux
b
1
temperature. Determined by H NMR spectroscopy (error 3%) with hexamethylbenzene as the internal standard.
a
Table 7. Hydrosilylation of Phenylacetylene with PYA Iridium(III) Complexes
selectivity
entry
complex
4a
T (°C)
time (h)
conv (%)
β(Z)
90
β(E)
α
styrene
1
26
26
26
26
26
26
40
40
40
40
40
40
2
78
4
3
3
2
4b
2
89
95
2
2
1
3
4c
2
75
92
2
2
4
4
4d
2
94
95
1
3
1
5
4e
2
68
95
1
3
1
6
[IrCp*Cl2]2
4a
0.5/2
1
95/99
99
92/91
93
3/4
3
3/3
2
2/2
2
7
8
4b
0.25
0.33
0.33
0.5
0.25/2
99
93
2
3
2
9
4c
99
94
2
3
1
10
11
12
4d
99
95
1
3
1
4e
99
95
1
3
1
[IrCp*Cl2]2
99/99
95/91
1/4
3/3
1/2
a
General conditions: phenylacetylene (0.18 mmol), triethylsilane (0.19 mmol), hexamethylbenzene (0.02 mmol), and catalyst (0.0018 mmol, 1 mol
1
%) in either CH2Cl2 (26 °C) or CHCl3 (40 °C). Conversion and selectivities were measured by H NMR spectroscopy (error 3%) with
hexamethylbenzene as the internal standard.
from anti-Markovnikov addition and 2-silyl-1-alkene (α isomer)
from Markovnikov addition (Table 7). In addition, the
formation of the dehydrogenative silylation product, i.e., the
corresponding silylacetylene as well as the unsubstituted alkene
G
DOI: 10.1021/acs.inorgchem.7b01654
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Inorganic Chemistry
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due to desilylation, has also been observed in this reaction, in
particular when sterically demanding alkynes or silanes were
used.29b Hence, control of the regio- and stereoselectivity of
this reaction remains a key issue. Numerous hydrosilylation
studies have been performed using platinum group metal
catalysts, in particular, with platinum,30 ruthenium(II),31
iridium(I), or rhodium(I).32 However, only a few examples
were reported starting from an iridium(III) complex as the
catalyst precursor.33
Hence, complexes 4a−4e were investigated as catalyst
precursors for the hydrosilylation of phenylacetylene in the
presence of a small excess of Et3SiH as the silylating agent. A
high catalytic efficiency was observed when the reaction was
performed in CD2Cl2 at room temperature using a 1 mol %
catalyst loading, reaching essentially quantitative conversion in
2 h (Table 7). The reaction proceeds with excellent selectivity
(>90%) toward the β(Z) isomer with only trace amounts of
styrene, β(E), and α isomers (entries 1−5).34 Because
formation of the β(E) isomer is typically a postcatalytic
process,35 we assume that isomerization is suppressed by the
presence of the PYA ligand, which prevents coordination of the
β(Z) isomer to the iridium center as a first step en route to
formation of the Z isomer.
Similar to transfer hydrogenation, the methoxy substitution
pattern requires optimization rather than maximization to reach
the highest catalytic activity. The best performance was
observed with catalyst precursors 4b and 4d containing one
and two methoxy substituents, respectively, although the
differences are not very pronounced. Complexes 4a and 4e
are the least active, presumably for reasons similar to those
discussed for transfer hydrogenation (see above); i.e., 4a lacks
the activating methoxy substituents, while for 4e, substrate
coordination and activation may be hindered for steric reasons.
In contrast to previous studies using [IrCp*Cl2]2 as the catalyst
precursor,35 no isomerization toward the β(E) isomer was
detected, presumably because of the constrained space around
the catalytically active metal center imposed by the rigid
chelation of the C,N-bidentate PYA ligand. This model is in
agreement with the reactivity pattern observed in transfer
hydrogenation, viz., moderate conversion of pyridyl ketones
and poor conversion of sterically demanding (e.g., open-chain
aliphatic) substrates. Moreover, this selectivity underpins the
relevance of the PYA ligand because simple [IrCp*Cl2]2
catalyzes the hydrosilylation faster but leads to a gradual
increase in isomerization after completion of the reaction
(entries 6 and 12), consistent with previous reports.35 When
the reaction temperature for hydrosilylation was raised to 40
°C, both the activity and selectivity toward the β(Z) isomer
increased (entries 7−11). When using complex 4b, full
conversion and 93% selectivity were noted after 15 min of
reaction (entry 8). Complex 4d required only slightly longer to
reach the same conversion (20 min) and produced the β(Z)
isomer in 95% selectivity (entry 10). These preliminary
investigations therefore suggest a high potential for these
PYA iridium complexes for the selective transformation of
acetylenes. While less pronounced than in transfer hydro-
genation, tailoring of the aryl unit of the PYA ligand in
complexes 4a−4e provides an efficient methodology to
optimize the catalyst activity.
prepared. The incorporation of one, two, or three methoxy
groups in the phenyl ring was achieved without affecting the
ease of ligand preparation or subsequent cyclometalation with
iridium(III). Spectroscopic and crystallographic analyses
indicate no structural distortion imparted by the methoxy
groups, and therefore this methodology allows for the
electronic parameters at the metal center to be tailored
selectively. Such tailoring was demonstrated in transfer
hydrogenation and hydrosilylation catalysis, which revealed a
delicate balance and a nonlinear correlation between the
number of donor groups and the catalytic activity. These results
emphasize the importance of synthetic strategies for subtle
ligand modifications in order to optimize the catalytic
performance. The scanning of different substrates in transfer
hydrogenation and hydrosilylation suggests that the bidentate
PYA ligand remains coordinated to the Ir(Cp*) fragment and
imparts a sterically constrained catalytic center, which has direct
consequences on the catalyst activity and selectivity. Specifi-
cally, steric constraints prevent the coordination and conversion
of bulky substrates, disfavor isomerization processes, and hence
increase the selectivity in hydrosilylation, and finally they put
limitations on the substituent incorporation to the phenyl unit
of the PYA ligand. In addition, this work demonstrates that
PYA ligands, still largely underexplored, offer vast synthetic
opportunities for modifications, and together with their flexible
donor structure, they constitute an attractive class of ligands for
transition-metal catalysis. In particular, we have developed a
protocol for base-free transfer hydrogenation of aldehydes,
which under classic conditions with a base rapidly dispropor-
tionate to give large amounts of carboxylic acids instead.
EXPERIMENTAL PART
■
General Information. The metal precursor salt [IrCp*Cl2]2,36
compounds 1a, 2a, and 3a and iridium complexes 4a, 5a, and 6a were
all synthesized as reported in the literature.10b All other reagents were
commercially available and were used as received. Unless specified
otherwise, NMR spectra were recorded at 25 °C on Bruker
spectrometers operating at 300 or 400 MHz (1H NMR) and 100
MHz (13C NMR). Chemical shifts (δ in ppm and coupling constants J
in Hz) were referenced to residual solvent signals (1H and 13C).
Assignments are based on homo- and heteronuclear shift correlation
spectroscopy. The purity of the bulk samples of the complexes has
been established by NMR spectroscopy and by elemental analysis,
which were performed at the Microanalytic Laboratory, University of
Bern, using a Thermo Scientific Flash 2000 CHNS-O elemental
analyzer. The residual solvent was confirmed by NMR spectroscopy
and also by X-ray structure determinations. HR-MS was carried out
with a Thermo Scientific LTQ Orbitrap XL (ESI-TOF) spectrometer.
General Procedure for the Formation of Amides 1b−1e. A
solution of acyl chloride (11 mmol) in tetrahydrofuran (THF; 10 mL)
was added dropwise at 0 °C into a solution of 4-aminopyridine (1.19
mL, 10 mmol) and NEt3 (1.50 mL, 11 mmol) in THF (30 mL), which
resulted in the formation of an immediate white precipitate. The
reaction was slowly warmed to room temperature and stirred for 3 h.
The formed precipitate was removed by filtration and washed with
THF (50 mL). All filtrates were collected and the volatiles removed in
vacuo to give a white solid, which was purified via column
chromatography (SiO2; 95:5 CH2Cl2/MeOH). All solvents were
removed to yield the product as white solids.
Compound 1b. This compound was prepared according to the
general procedure from 2-methoxybenzoyl chloride (1.877 g, 11
mmol). Yield: 1.750 g, 77%. 1H NMR (300 MHz, DMSO-d6): δ 10.55
3
3
(s, 1H, NH), 8.48 (d, JHH = 6.5 Hz, 2H, CHpyr), 7.78 (d, JHH = 6.5
Hz, 2H, CHpyr), 7.58−7.44 (m, 3H, CHPh), 7.23−7.17 (m, 1H, CHPh),
3.84 (s, 3H, OCH3). 13C{1H} NMR (100 MHz, DMSO-d6): δ 166.2
(CO), 159.2 (CPh), 150.3 (CHpyr), 145.8 (Cpyr), 135.6 (CPh), 129.7
CONCLUSIONS
A new family of Ir(C^N)Cp*-type complexes containing
methoxy-substituted PYA ligands has been successfully
■
H
DOI: 10.1021/acs.inorgchem.7b01654
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Inorganic Chemistry
Article
(CHPh), 120.0 (CHPh), 117.8 (CHPh), 114.0 (CHpyr), 113.1 (CHPh),
55.4 (OCH3). HR-MS. Calcd for C13H13N2O2 ([M + H]+): m/z
229.0977. Calcd: m/z 229.0960. Elem. anal. Calcd for C13H13N2O2: C,
68.41; H, 5.30; N, 12.27. Found: C, 67.64; H, 5.00; N, 12.32.
Compound 1c. This compound was prepared according to the
general procedure from 4-methoxybenzoyl chloride (1.877 g, 11
mmol). Yield: 1.990 g, 87%. 1H NMR (300 MHz, DMSO-d6): δ 10.42
(s, 1H, NH), 8.46 (d, JHH = 6.4 Hz, 2H, CHpyr), 7.97 (d, JHH = 8.8
Hz, 2H, CHPh), 7.78 (d, 3JHH = 6.4 Hz, 2H, CHpyr), 7.09 (d, 3JHH = 8.9
Hz, 2H, CHPh), 3.85 (s, 3H, OCH3). 13C{1H} NMR (100 MHz,
DMSO-d6): δ 165.7 (CO), 162.3 (CPh), 150.2 (CHpyr), 146.1 (Cpyr),
129.9 (CHPh), 126.2 (CPh), 113.9 (CHpyr), 113.7 (CHPh), 55.5
(OCH3). HR-MS. Calcd for C13H14N2O2 ([M + H]+): m/z 229.0977.
Calcd m/z 229.0962. Elem. anal. Calcd for C13H13N2O2: C, 68.41; H,
5.30; N, 12.27. Found: C, 68.21; H, 4.89; N, 12.20.
7.0 Hz, 2H, CHpyr), 8.27 (d, 3JHH = 7.0 Hz, 2H, CHpyr), 7.16 (d, 4JHH
=
4
2.2 Hz, 2H, CHPh), 6.85 (t, JHH = 2.2 Hz, 1H, CHPh), 4.21 (s, 3H,
NCH3), 3.86 (s, 6H, OCH3). 13C{1H} NMR (100 MHz, DMSO-d6):
δ 166.8 (CO), 160.6 (CPh), 151.8 (Cpyr), 145.9 (CHpyr), 138.9 (CPh),
115.5 (CHpyr), 106.3 (CHPh), 104.5 (CHPh), 55.7 (OCH3), 46.4
(NCH3). HR-MS. Calcd for C15H17N2O3 ([M − I]+): m/z 273.1234.
Found; m/z 273.1228. Elem. anal. Calcd for C15H17N2O3I: C, 45.02;
H, 4.28; N, 7.00. Found: C, 44.80; H, 4.08; N, 7.13.
3
3
Compound 2e. Compound 2e was prepared according to the
general procedure from 1e (577 mg, 2.0 mmol). Yield: 792 mg, 92%.
1H NMR (300 MHz, DMSO-d6): δ 11.36 (s, 1H, NH), 8.80 (d, 3JHH
=
3
7.0 Hz, 2H, CHpyr), 8.26 (d, JHH = 7.0 Hz, 2H, CHpyr), 7.34 (s, 2H,
CHPh), 4.22 (s, 3H, NCH3), 3.90 (s, 6H, OCH3), 3.78 (s, 3H, OCH3).
13C{1H} NMR (100 MHz, DMSO-d6): δ 166.6 (CO), 152.8 (CPh),
151.9 (Cpyr), 145.9 (CHpyr), 141.7 (CPh), 127.9 (CPh), 115.5 (CHpyr),
106.2 (CHPh), 60.2 (OCH3), 56.3 (OCH3), 46.4 (NCH3). HR-MS.
Calcd for C16H19N2O4 ([M − I]+): m/z 303.1339. Found: m/z
303.1328. Elem. anal. Calcd for C16H19N2O4I: C, 44.67; H, 4.45; N,
6.51. Found: C, 44.58; H, 4.12; N, 6.66.
General Procedure for Synthesis of the Pyridylidene Amides
3b−3e. A suspension of the pyridinium salt 2 (1.0 mmol) in CH2Cl2
(10 mL) was placed in a separating funnel. Aqueous NaOH (15 mL,
2M) was added. After vigorous mixing, the organic phase was
collected. The aqueous layer was extracted with CH2Cl2 (3 × 15 mL),
and the combined organic layers were dried over anhydrous Na2SO4
and filtered. All volatiles were removed, thus giving free ligand 3 as
white-yellow solids, which were purified by recrystallization from
pentane.
Compound 1d. This compound was prepared according to the
general procedure from 3,5-dimethoxybenzoyl chloride (2.206 g, 11
mmol). Yield: 2.207 g, 85%. 1H NMR (300 MHz, DMSO-d6): δ 10.50
3
3
(s, 1H, NH), 8.48 (d, JHH = 6.4 Hz, 2H, CHpyr), 7.77 (d, JHH = 6.4
Hz, 2H, CHpyr), 7.10 (d, 4JHH = 2.4 Hz, 2H, CHPh), 6.76 (t, 4JHH = 2.3
Hz, 1H, CHPh), 3.83 (s, 6H, OCH3). 13C{1H} NMR (100 MHz,
DMSO-d6): δ 166.0 (CO), 160.4 (CPh), 150.3 (CHpyr), 145.8 (Cpyr),
136.2 (CPh), 114.7 (CHpyr), 105.8 (CHPh), 103.7 (CHPh), 55.6
(OCH3). HR-MS. Calcd for C14H15N2O3 ([M + H]+): m/z 259.1083.
Calcd: m/z 259.1071. Elem. anal. Calcd for C14H14N2O3: C, 65.11; H,
5.46; N, 10.85. Found: C, 65.01; H, 5.10; N, 10.75.
Compound 1e. This compound was prepared according to the
general procedure from 3,4,5-dimethoxybenzoyl chloride (2.537 g, 11
mmol). Yield: 2.134 g, 74%. 1H NMR (300 MHz, DMSO-d6): δ 10.45
Compound 3b. Compound 3b was synthesized following the
3
3
(s, 1H, NH), 8.50 (d, JHH = 6.4 Hz, 2H, CHpyr), 7.76 (d, JHH = 6.4
Hz, 2H, CHpyr), 7.29 (s, 2H, CHPh), 3.89 (s, 6H, OCH3), 3.75 (s, 3H,
OCH3). 13C{1H} NMR (100 MHz, DMSO-d6): δ 165.8 (CO), 152.7
(s, CPh), 150.3 (CHpyr), 145.9 (Cpyr), 140.8 (CPh), 129.3 (CPh), 114.1
(CHpyr), 105.6 (CHPh), 60.1 (OCH3), 56.2 (OCH3). HR-MS. Calcd
for C14H17N2O4 ([M + H]+): m/z 289.1188. Calcd: m/z 289.1176.
Elem. anal. Calcd for C15H16N2O4·0.25H2O: C, 61.53; H, 5.68; N,
9.57. Found: C, 61.51; H, 5.37; N, 9.24.
general procedure from compound 2b (370 mg, 1.0 mmol). Yield: 160
1
3
mg, 66%. H NMR (300 MHz, DMSO-d6): δ 7.91 (d, JHH = 7.5 Hz,
3
4
2H, CHpyr), 7.38 (dd, JHH = 7.5 Hz, JHH = 1.8 Hz, 1H, CHPh), 7.31
(d, 3JHH = 7.5 Hz, 2H, CHpyr), 7.28−7.23 (m, 1H, CHPh), 6.97 (d, 3JHH
= 8.0 Hz, 1H, CHPh), 6.88 (t, 3JHH = 7.4 Hz, 1H, CHPh), 3.80 (s, 3H,
NCH3), 3.72 (s, 3H, OCH3). 13C{1H} NMR (100 MHz, DMSO-d6):
δ 176.3 (CO), 163.0 (Cpyr), 156.4 (CPh), 141.7 (CHpyr), 132.5 (CPh),
129.0 (CHPh), 128.7 (CHPh), 119.6 (CHPh), 117.1 (CHpyr), 111.9
(CHPh), 56.1 (OCH3), 46.4 (NCH3). HR-MS. Calcd for C14H15N2O2
([M + H]+): m/z 243.1134. Found: m/z 243.1122. Elem. anal. Calcd
for C14H14N2O2: C, 69.41; H, 5.82; N, 11.56. Found: C, 69.65; H,
5.42; N, 11.22.
General Procedure for the Formation of Pyridinium Salts 2.
Compound 1 (2.0 mmol) was dissolved in MeCN (15 mL) in a
pressure tube. MeI (187 μL, 3.0 mmol) was added, and the reaction
was stirred for 18 h at 80 °C. The solution was cooled to room
temperature and concentrated to 5 mL. Et2O (50 mL) was added,
affording compound 2 as a yellow solid, which was collected by
filtration.
Compound 2b. Compound 2b was prepared according to the
general procedure from 1b. Yield: 715 mg, 97%. 1H NMR (300 MHz,
DMSO-d6): δ 11.43 (s, 1H, NH), 8.78 (d, 3JHH = 7.3 Hz, 2H, CHpyr),
8.21 (d, 3JHH = 7.3 Hz, 2H, CHpyr), 7.68−7.55 (m, 2H, CHPh), 7.26 (d,
3JHH = 8.3 Hz, 1H, CHPh), 7.13 (t, 3JHH = 7.6 Hz, 1H, CHPh), 4.21 (s,
3H, NCH3), 3.91 (s, 3H, OCH3). 13C{1H} NMR (100 MHz, DMSO-
d6): δ 166.8 (CO), 156.7 (CPh), 151.2 (Cpyr), 146.3 (CHpyr), 133.5
(CHPh), 129.8 (CHPh), 123.3 (CPh), 120.6 (CHPh), 115.0 (CHpyr),
112.3 (CHPh), 56.1 (OCH3), 46.4 (NCH3). HR-MS. Calcd for
C14H15N2O2 ([M − I]+): m/z 243.1128. Found: m/z 243.1124. Elem.
anal. Calcd for C14H15N2O2I: C, 45.42; H, 4.08; N, 7.57. Found: C,
45.15; H, 3.75; N, 7.66.
Compound 3c. Compound 3c was synthesized following the
general procedure from compound 2c (370 mg, 1.0 mmol). Yield: 155
1
3
mg, 64%. H NMR (300 MHz, DMSO-d6): δ 8.07 (d, JHH = 8.8 Hz,
2H, CHPh), 7.90 (d, 3JHH = 7.4 Hz, 2H, CHpyr), 7.40 (d, 3JHH = 7.4 Hz,
2H, CHpyr), 6.91 (d, 3JHH = 8.8 Hz, 2H, CHpyr), 3.80 (s, 3H, NCH3),
3.79 (s, 3H, OCH3). 13C{1H} NMR (100 MHz, DMSO-d6): δ 173.8
(CO), 163.8 (CPh), 161.0 (Cpyr), 141.6 (CHpyr), 132.4 (CPh), 130.6
(CHPh), 117.4 (CHpyr), 112.8 (CHPh), 55.2 (OCH3), 43.7 (NCH3).
HR-MS. Calcd for C14H15N2O2 ([M + H]+): m/z 243.1134. Found:
m/z 243.1121. Elem. anal. Calcd for C14H14N2O2: C, 69.41; H, 5.82;
N, 11.56. Found: C, 68.66; H, 5.27; N, 12.00.
Compound 3d. Compound 3d was synthesized following the
general procedure from compound 2d (400 mg, 1.0 mmol). Yield: 233
1
3
mg, 86%. H NMR (300 MHz, DMSO-d6): δ 7.98 (d, JHH = 7.5 Hz,
2H, CHpyr), 7.47 (d, 3JHH = 7.5 Hz, 2H, CHpyr), 7.31 (d, 4JHH = 2.4 Hz,
4
Compound 2c. Compound 2c was prepared according to the
2H, CHPh), 6.56 (t, JHH = 2.4 Hz, 1H, CHPh), 3.84 (s, 3H, NCH3),
3.77 (s, 6H, OCH3). 13C{1H} NMR (100 MHz, DMSO-d6): δ 173.2
(CO), 164.0 (Cpyr), 159.8 (CPh), 142.3 (CHpyr), 141.9 (CPh), 117.8
(CHpyr), 106.4 (CHPh), 102.4 (CHPh), 55.1 (OCH3), 43.8 (NCH3).
HR-MS. Calcd for C15H17N2O3 ([M + H]+): m/z 273.1239. Found:
m/z 273.1220. Elem. anal. Calcd for C15H16N2O3: C, 66.16; H, 5.92;
N, 10.29. Found: C, 65.75; H, 5.50; N, 10.75.
general procedure from 1c (456 mg, 2.0 mmol). Yield: 646 mg, 87%.
1H NMR (300 MHz, DMSO-d6): δ 11.33 (s, 1H, NH), 8.76 (d, 3JHH
=
=
7.2 Hz, 2H, CHpyr), 8.26 (d, 3JHH = 7.2 Hz, 2H, CHpyr), 8.03 (d, 3JHH
3
8.8 Hz, 2H, CHPh), 7.14 (d, JHH = 8.8 Hz, 2H, CHPh), 4.19 (s, 3H,
NCH3), 3.87 (s, 6H, OCH3). 13C{1H} NMR (100 MHz, DMSO-d6):
δ 166.3 (CO), 163.2 (CPh), 152.1 (Cpyr), 145.7 (CHpyr), 130.5
(CHPh), 124.7 (CPh), 115.5 (CHpyr), 114.0 (CHPh), 56.0 (OCH3),
46.4 (NCH3). HR-MS. Calcd for C14H15N2O2 ([M − I]+): m/z
243.1128. Found; m/z 243.1117. Elem. anal. Calcd for C14H15N2O2I:
C, 45.42; H, 4.08; N, 7.57. Found: C, 45.10; H, 3.78; N, 7.68.
Compound 2d. Compound 2d was prepared according to the
general procedure from 1d (517 mg, 2.0 mmol). Yield: 735 mg, 92%.
Compound 3e. Compound 3e was synthesized following the
general procedure from compound 2e (430 mg, 1.0 mmol). Yield: 252
1
3
mg, 84%. H NMR (300 MHz, DMSO-d6): δ 7.96 (d, JHH = 7.1 Hz,
3
2H, CHpyr), 7.48 (s, 2H, CHPh), 7.45 (d, JHH = 7.5 Hz, 2H, CHpyr),
3.83 (s, 3H, NCH3), 3.82 (s, 6H, OCH3), 3.71 (s, 3H, OCH3).
13C{1H} NMR (100 MHz, DMSO-d6): δ 173.2 (CO), 164.0 (Cpyr),
152.0 (CPh), 141.8 (CHpyr), 139.5 (CPh), 135.4 (CPh), 117.7 (CHpyr),
1H NMR (300 MHz, DMSO-d6): δ 11.43 (s, 1H, NH), 8.79 (d, 3JHH
=
I
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Article
106.0 (CHPh), 60.0 (OCH3), 55.7 (OCH3), 43.8 (NCH3). HR-MS.
Calcd for C16H19N2O4 ([M + H]+): m/z 303.1345. Found: m/z
303.1327. Elem. anal. Calcd for C16H18N2O4: C, 63.56; H, 6.00; N,
9.27. Found: C, 63.90; H, 5.87; N, 10.89.
mL) were taken at set times and dissolved in CD3OD, acetone-d6, or
CDCl3. The reaction mixtures were analyzed by H NMR spectros-
copy. Conversions and yields were determined relative to anisole or
hexamethylbenzene.
1
General Procedure for the Synthesis of Complexes 4b−4e.
Compound 3 (0.4 mmol), [IrCp*Cl2]2 (120 mg, 0.15 mmol), and
NaOAc (33 mg, 0.4 mmol) were dissolved in CH2Cl2 and stirred at
room temperature for 18 h. All volatiles were removed under reduced
pressure, and the crude solid was purified by column chromatography
(SiO2; 98:2 CH2Cl2/MeOH), thus yielding 4 as orange solids.
Compound 4b. Compound 4b was prepared according to the
general procedure from 3b (97 mg, 0.40 mmol). Yield: 139 mg, 77%.
General Procedure for Base-Free Catalytic Transfer Hydro-
genation. In a one-neck round-bottom flask open to air, a mixture of
catalyst precursor (0.01 mmol), hexamethylbenzene (27 mg, 0.16
mmol) as internal standard and substrate (1.0 mmol) was refluxed in
iPrOH (5 mL). Aliquots (ca. 0.1 mL) were taken at set times and
dissolved in CDCl3. The reaction mixtures were analyzed by 1H NMR
spectroscopy. Conversions and yields were determined relative to
anisole or hexamethylbenzene.
3
1H NMR (400 MHz, CDCl3): δ 8.27 (d, JHH = 7.1 Hz, 2H, CHpyr),
General Procedure for Hydrosilylation of Phenylacetylene.
Phenylacetylene (20 μL, 0.18 mmol), triethylsilane (30 μL, 0.19
mmol), and hexamethylbenzene (3.2 mg, 0.02 mmol) were dissolved
in CD2Cl2 or CDCl3 (0.5 mL) in an NMR tube under a normal
atmosphere of air. The catalyst (1.8 μmol, 1 mol %) was added, and
7.47 (d, 3JHH = 7.4 Hz, 2H, CHpyr), 7.31 (d, 3JHH = 7.3 Hz, 1H, CHPh),
7.14 (t, 3JHH = 7.8 Hz, 1H, CHPh), 6.49 (d, 3JHH = 7.8 Hz, 1H, CHPh),
3.89 (s, 3H, OCH3), 3.53 (s, 3H, NCH3), 1.47 (s, 15H, Cp*CH3).
13C{1H} NMR (100 MHz, CDCl3): δ 182.3 (CO), 163.2 (CPh), 161.6
(Cpyr), 160.3 (CPh), 140.6 (CHpyr), 132.7 (CHPh), 129.4 (CHPh),
127.5 (CPh), 120.6 (CHpyr), 105.1 (CHPh), 87.5 (CCp*), 55.3 (OCH3),
44.8 (NCH3), 9.2 (CH3Cp*). HR-MS. Calcd for C24H29IrN2O2 ([M
− Cl]+): m/z 605.1541. Found: 605.1522. Elem anal. Calcd for
C24H29ClIrN2O2: C, 47.71; H, 4.67; N, 4.64. Found: C, 47.67; H, 4.52;
N, 4.61.
1
the reaction was followed by H NMR spectroscopy at fixed times at
either 26 or 40 °C.
Crystal Structure Determinations. Suitable crystals of 4b−4e
were mounted in air at ambient conditions and measured on an
Oxford Diffraction SuperNova area-detector diffractometer at T =
173(2) K using mirror optics monochromated Mo Kα radiation (λ =
0.71073 Å) and filtered aluminum.37 Data reduction was performed
using the CrysAlisPro program.38 The intensities were corrected for
Lorentz and polarization effects, and an absorption correction based
on the multiscan method using SCALE3 ABSPACK in CrysAlisPro was
applied. The structures were solved by direct methods using
SHELXT,39 and all non-hydrogen atoms were refined anisotropically.
All hydrogen atoms were placed in geometrically calculated positions
and refined using a riding model, with each hydrogen atom assigned a
fixed isotropic displacement parameter (1.2Ueq of its parent atom and
1.5Ueq for the methyl groups). Structures were refined on F2 using full-
matrix least-squares procedures. The weighting schemes were based on
counting statistics and included a factor to downweight the intense
reflections. All calculations were performed using the SHELXL-2014
program.39
Compound 4c. This compound was prepared according to the
general procedure from 3c (97 mg, 0.40 mmol. Yield: 140 mg, 78%.
3
1H NMR (400 MHz, CDCl3): δ 8.29 (d, JHH = 7.0 Hz, 2H, CHpyr),
7.58 (d, 3JHH = 8.4 Hz, 1H, CHPh), 7.51 (d, 3JHH = 7.3 Hz, 2H, CHpyr),
7.27 (d, 4JHH = 2.5 Hz, 1H, CHPh), 6.53 (dd, 3JHH = 8.4 Hz, 4JHH = 2.5
Hz, 1H, CHPh), 3.88 (s, 3H, OCH3), 3.47 (s, 3H, NCH3), 1.47 (s,
15H, Cp*CH3). 13C{1H} NMR (100 MHz, CDCl3): δ 182.7 (CO),
162.4 (CPh), 162.2 (CPh), 161.7 (Cpyr), 140.9 (CHpyr), 134.4 (CPh),
129.6 (CHPh), 121.1 (CHpyr), 119.8 (CHPh), 109.4 (CHPh), 87.3
(CCp*), 55.2 (OCH3), 45.3 (NCH3), 9.2 (CH3Cp*). HR-MS. Calcd
for C24H29IrN2O2 ([M − Cl]+): m/z 605.1541. Found: m/z 605.1493.
Elem anal. Calcd for C24H29ClIrN2O2·0.25CH2Cl2: C, 46.50; H, 4.75;
N, 4.47. Found: C, 46.31; H, 4.39; N, 4.47.
Compound 4d. The title compound was prepared according to the
general procedure from 3d (109 mg, 0.40 mmol). Yield: 162 mg, 75%.
The asymmetric unit of compound 4b contained two independent
complex molecules and two molecules of the solvent. Careful checking
did not reveal any obvious symmetry operation relating the two
independent molecules. All investigated crystals of 4c were system-
atically affected by an intergrowth nonmerohedral twinning. The data
were therefore integrated and refined using reflections of both
components, and each measured structure factor was fitted to the sum
of all contributing components (HKLF5 option in SHELX). For the
3
1H NMR (400 MHz, CDCl3): δ 8.35 (d, JHH = 7.0 Hz, 2H, CHpyr),
7.51 (d, 3JHH = 7.5 Hz, 2H, CHpyr) 6.89 (d, 4JHH = 2.4 Hz, 1H, CHPh),
4
6.47 (d, JHH = 2.4 Hz, 1H, CHPh), 3.83 (s, 3H, OCH3), 3.80 (s, 3H,
OCH3), 3.47 (s, 3H, NCH3), 1.47 (s, 15H, Cp*CH3). 13C{1H} NMR
(100 MHz, CDCl3): δ 183.5 (CO), 163.1 (CPh), 161.7 (Cpyr), 157.4
(CPh), 142.0 (CPh), 141.0 (CHpyr), 139.0 (CPh), 120.9 (CHpyr), 103.6
(CHPh), 103.2 (CHPh), 87.3 (CCp*), 56.0 (OCH3), 55.6 (OCH3), 45.6
(NCH3), 9.2 (CH3Cp*). HR-MS. Calcd for C25H30IrN2O3 ([M −
Cl]+): m/z 599.1886. Found: m/z 599.1859. Elem anal. Calcd for
C25H30ClIrN2O3: C, 47.35; H, 4.77; N, 4.42. Found: C, 47.92; H, 4.60;
N, 4.38.
1
2
sample selected for structural analysis, compositions of /3 and /3
were refined (although other samples gave other ratios). All mounted
crystals of 4d were systematically affected by weak diffraction at high
resolution, diffuse scattering, and spurious peaks at non-Bragg
positions possibly, indicating the presence of many twin components.
For this reason, the quality indices of the refinement are poorer and
large residuals in the vicinity of the iridium atom are found, which
could not be associated with a structural disorder. Further details are
given in Tables S2−S5. Crystallographic data for all four structures
have been deposited with the Cambridge Crystallographic Data Centre
as supplementary publication numbers 1530958 (4b), 1530960 (4c),
1530961 (4d), and 1530959 (4e).
Compound 4e. Compound 4e was prepared according to the
general procedure from 3e (121 mg, 0.40 mmol). Yield: 139 mg, 70%.
3
1H NMR (400 MHz, CDCl3): δ 8.39 (d, JHH = 7.0 Hz, 2H, CHpyr),
3
7.52 (d, JHH = 7.3 Hz, 2H, CHpyr) 7.14 (s, 1H, CHPh), 3.98 (s, 3H,
OCH3), 3.88 (s, 3H, OCH3), 3.87 (s, 3H, OCH3), 3.58 (s, 3H,
NCH3), 1.52 (s, 15H, Cp*CH3). 13C{1H} NMR (100 MHz, CDCl3):
δ 183.4 (CO), 161.5 (Cpyr), 156.4 (CPh), 150.1 (CPh), 146.8 (CPh),
140.6 (CHpyr), 136.3 (CPh), 120.9 (CHpyr), 108.3 (CHPh), 87.6 (CCp*),
62.0 (OCH3), 60.8 (OCH3), 56.2 (OCH3), 45.0 (NCH3), 9.3
(CH3Cp*). HR-MS. Calcd for C26H32IrN2O4 ([M − Cl]+): m/z
629.1991. Found: m/z 666.19744. Elem anal. Calcd for
C26H32ClIrN2O4: C, 47.02; H, 4.86; N, 4.22. Found: C, 47.11; H,
4.59; N, 4.17.
General Procedure for Base-Assisted Catalytic Transfer
Hydrogenation. A mixture of the catalyst precursor (0.01 mmol),
anisole (110 μL, 1 mmol), or hexamethylbenzene (27 mg, 0.16 mmol)
as the internal standard and KOH (2 M solution in H2O, 50 μL, 0.1
mmol) in iPrOH (5 mL) was mixed in a one-neck round-bottomed
flask in air (or argon if specified) and heated to reflux for 15 min.
Then, substrate (1.0 mmol) was rapidly added, and aliquots (ca. 0.1
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.inorg-
chem.7b01654.
Time−conversion profiles for catalytic experiments,
crystallographic details, and NMR spectra of all
compounds (PDF)
J
DOI: 10.1021/acs.inorgchem.7b01654
Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
(5) For selected classic NHC reviews, see: (a) Hahn, F. E.; Jahnke,
M. C. Heterocyclic Carbenes: Synthesis and Coordination Chemistry.
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Accession Codes
CCDC 1530958−1530961 contain the supplementary crystal-
lographic data for this paper. These data can be obtained free of
charge via www.ccdc.cam.ac.uk/data_request/cif, or by email-
ing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Author
*E-mail: martin.albrecht@dcb.unibe.ch.
■
ORCID
Martin Albrecht: 0000-0001-7403-2329
Present Address
‡C.A.S.: Department of Chemistry, Queen’s University, 90
Bader Lane, Kingston, Ontario, Canada.
(7) For low π-acidic properties of NHCs, see: (a) Back, O.; Henry-
Ellinger, M.; Martin, C. D.; Martin, D.; Bertrand, G. 31P NMR
Chemical Shifts of Carbene−Phosphinidene Adducts as an Indicator
of the π-Accepting Properties of Carbenes. Angew. Chem., Int. Ed.
2013, 52, 2939−2943. (b) Vummaleti, S. V. C.; Nelson, D. J.; Poater,
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
́ ́
A.; Gomez-Suarez, A.; Cordes, D. B.; Slawin, A. M. Z.; Nolan, S. P.;
We acknowledge generous financial support from the European
Research Council (Grant CoG 615653) and from the Swiss
National Science Foundation (Grant 200021_162868 and
R’equip Projects 206021_128724 and 206021_170755).
C.A.S. thanks the Natural Science and Engineering Research
Council of Canada, the Water Sumner Foundation, and
Queen’s University. We thank the group of Chemical
Crystallography of the University of Bern for X-ray analysis
of all reported structures.
Cavallo, L. What can NMR spectroscopy of selenoureas and
phosphinidenes teach us about the π-accepting abilities of N-
heterocyclic carbenes? Chem. Sci. 2015, 6, 1895−1904. (c) Jacobsen,
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