Salt-promoted catalytic methanol carbonylation using iridium pincer-crown ether complexes

Article abstract of DOI:10.1039/c8cy00328a

Iridium complexes of pincer ligands containing aza-crown ether macrocycles are precatalysts for methanol carbonylation. Eleven different pincer complexes were examined in the presence of various potential external promoters under standard reaction conditi

Full text of DOI:10.1039/c8cy00328a

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Salt-promoted catalytic methanol carbonylation
using iridium pincer-crown ether complexes†
Cite this: DOI: 10.1039/c8cy00328a
a
a
a
Lauren C. Gregor, Javier Grajeda, Peter S. White,
b
a
Andrew J. Vetter and Alexander J. M. Miller
*
Iridium complexes of pincer ligands containing aza-crown ether macrocycles are precatalysts for methanol
carbonylation. Eleven different pincer complexes were examined in the presence of various potential exter-
nal promoters under standard reaction conditions of 0.1 M CH
5 bar CO and heated to 150 °C for 3 hours. Methyl acetate is the major product under these conditions,
with turnover numbers (TONs) for all acetyl-containing products ranging from 265 to 1950 based on the
choice of metal salt (with LiCl and HfCl giving highest TON) or tetrabutylammonium salts. While the pin-
3
I and 0.34 mM catalyst in methanol under
2
Received 14th February 2018,
Accepted 13th May 2018
4
cer-crown ether complexes remain intact under conditions of low temperature and pressure, the
precatalysts convert to new active species derived from pincer ligand methanolysis in high pressure reac-
tors with excess methyl iodide.
DOI: 10.1039/c8cy00328a
rsc.li/catalysis
and is regenerated in a parallel catalytic cycle by the reaction
of HI with CH OH. Rhodium-catalyzed (Monsanto-type) pro-
3
Introduction
Carbon monoxide is a fundamental building block of the
chemical industry. The transition metal-catalyzed carbonyla-
cesses utilize iodide salts (e.g. LiI) as promoters to control
catalyst speciation, accelerate oxidative addition, and enable
catalysis in low-water conditions (<4 wt%) that mitigate com-
1
tion of methanol (CH
3
OH), eqn (1), produces ∼8 million tons
1
,3
per year of acetic acid (AcOH), much of which is converted to
vinyl acetate monomers that are widely used in polymer
peting water gas shift (WGS) reactivity.
Iridium-catalyzed (Cativa-type) processes also utilize pro-
moters, most commonly iodide abstractors that prevent the
precipitation of inactive iodide species and produce electro-
philic carbonyl complexes that undergo rapid migratory in-
2–4
synthesis.
Current industrial methods using homogeneous
rhodium or iridium iodocarbonyl catalysts achieve >99%
selectivity for acetyl-containing products at 150–200 °C and
3,5
3
3
0–60 bar CO, when paired with the right promoters. Along
sertion. The ∼3-fold rate enhancement afforded by addition
with acetic acid, methyl acetate (CH OAc) is a commonly ob-
of RuIJCO) I is sufficient to warrant inclusion of this precious
3
4 2
served co-product formed either by reaction of acetyl iodide
metal additive in industrial processes; simple inorganic salts,
(
AcI) with the solvent or by acid-catalyzed esterification of
such as CdI
2
and InI
recently reported heterogeneous catalyst
consisting of iridium supported on a carbon surface showed
3
, give about 1.8 fold rate enhance-
6
1,3,4
acetic acid in the solvent. As is clear from eqn (2) (K
5
=
ments.
A
eq
8
7
.2), AcOH will be favored at high conversion of CH OH.
3
9
3
roughly 3-fold promotion by LaI . Free iodide ions from salts
CH OH + CO ⇌ AcOH
(1)
(2)
such as LiI and [TBA][I] (TBA = tetra-n-butylammonium) typi-
cally poison leading Ir systems.
We are designing catalyst systems that can hold cationic
species in close proximity to the transition metal active
3
4
CH
3
OH + AcOH ⇌ CH
3
OAc + H
2
O
1
0–12
Promoters are critical in both Rh- and Ir-catalyzed pro-
cesses. In both systems, methyl iodide (CH I) facilitates for-
mation of metallomethyl intermediates by oxidative addition
site,
carbonylation.
steps of oxidative addition and migratory insertion with irid-
motivating studies of cation-accelerated methanol
1
3
3
We recently investigated the elementary
1
2
ium pincer-crown ether complexes, which feature a strongly
donating phenylphosphinite backbone and an aza-crown-ether
group.
ligand for controllable catalysis,
cations in close proximity to the metal center.
a
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel
14,15
Hill, North Carolina 27599-3290, USA. E-mail: ajmm@email.unc.edu
The macrocycle can either act as a hemilabile
b
Eastman Chemical Company, Kingsport, Tennessee 37660, USA
10,16
or act to hold Lewis acidic
†
Electronic supplementary information (ESI) available: NMR spectra, detailed
1
2,17,18
The rate
analysis of catalysis products, crystallographic details. Crystallographic data is
deposited in the CCDC: 1584277–1584278. For ESI and crystallographic data in
CIF or other electronic format see DOI: 10.1039/c8cy00328a
of C–C bond-forming migratory insertion at pincer-crown ether
iridium methyl complexes was enhanced by lithium and
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12
lanthanum salts in acetonitrile solvent. The rate enhance-
ment was ascribed in part to halide abstraction (14-fold rate in-
crease), and in part to carbonyl complex activation (a further
2
-fold rate increase with strongly Lewis acidic LaIJOTf) , where
3
12
OTf is trifluoromethanesulfonate or triflate).
Molecular iridium methanol carbonylation catalysts beyond
the industrially used anionic complex [IrIJCO) I ] are rare.
−
2,19–21
2
2
A few iridium catalysts of bidentate and tridentate phosphine
ligands, including some pincer structures, have appeared in re-
22–24
cent patent literature.
We report herein salt-responsive
methanol carbonylation using iridium pincer-crown ether com-
plexes as precatalysts. The reactivity of iridium complexes
supported by pincer ligands bearing either aza-15-crown-5 or
aza-18-crown-6 macrocycles in the presence of various salt pro-
moters has been assessed under various conditions.
Scheme
2
Synthesis of aza-18-crown-6-containing iridium pincer
complexes.
Results and discussion
Synthesis and characterization of iridium carbonyl pincer
complexes
1
8c6
18c6
IridiumIJI) carbonyl complexes and iridiumIJIII) methylcarbonyl
complexes were targeted as precatalysts because these types
of intermediates are typically invoked in methanol carbonyla-
tion. The four iridium complexes containing aza-15-crown-5
1
. The molecular structure of 1
(Fig. 1A) features
pseudo-octahedral geometry around Ir, with
hydridochloride geometry analogous to 1
a
trans-
1
5c5 25
.
1
8c6
t
Dehydrohalogenation of 1
with KO Bu in benzene af-
1
2,25
18c6
iPr
18c6
macrocycles shown in Scheme 1 were previously reported.
fords the IrIJI) carbonyl complex ( NCOP )IrIJCO) (2
good yield (Scheme 2). Bright yellow crystals suitable for
X-ray diffraction were obtained by evaporation of an Et O so-
(Fig. 1B) fea-
tures a square-planar geometry. The spectroscopic and struc-
) in
Iridium complexes containing larger aza-18-crown-6 macro-
cycles were prepared with the goal of supporting stronger cat-
2
2
6–28
18c6
18c6
ion-crown interactions.
Nickel complexes of the aza-18-
lution of 2
. The molecular structure of 2
crown-6-containing ligand were recently synthesized in our
lab and found to support stronger interactions with alkali
1
8c6
tural features of 2
reported 15-crown-5 analogue.
Addition of CH I to a bright yellow CH
carbonyl complex 2
pale yellow. The H NMR spectrum of the isolated product is
are nearly identical to the previously
1
7
25
metal cations.
Metallation with iridium was readily accomplished by
3
2
2
Cl solution of IrIJI)
1
8c6
iPr
29
18c6
refluxing ( NCOP )H with IrIJp-toluidine)IJCO) IJCl) in tolu-
resulted in the color rapidly fading to
2
1
8c6
iPr
18c6
1
ene, affording ( NCOP )IrIJH)IJCO)IJCl) (1
) in 81% yield
(
Scheme 2). Light brown crystals suitable for X-ray diffraction
similar to that of the previously reported IrIJIII) complex
1
5c5 12
1
2
were obtained by slow evaporation of an Et O solution of
3
.
Upfield doublets in the H (δ 0.77 JPH = 2.2 Hz) and
2
1
3
1
2
C{ H} (δ −18.5, J = 5.5 Hz) NMR spectra are attributed to
PH
an iridium methyl ligand weakly coupled to phosphorus in
the methylcarbonyl iodide complex ( NCOP )IrIJCH )IJCO)-
3
1
8c6
iPr
1
8c6
IJI) (3
, Scheme 3).
Development of catalytic methanol carbonylation conditions
Initial benchmarking of iridium pincer complexes was
performed in a six-vessel multireactor in methanol solvent
containing 0.5 M CH I and 0.34 mM catalyst at 150 °C and
3
2
5 bar CO for 3 h (Scheme 4). After the reaction, two layers
t
were observed in the reactor. tert-Butanol ( BuOH) was
added to serve both as an internal standard and as an emul-
sifying agent that led to homogeneous, miscible solutions
1
ready for quantitative H NMR spectroscopic analysis. CH
3
-
OAc and AcOH are observed in all cases, along with the typi-
cal volatile side product dimethyl ether (DME, b.p. = −24
3
0
°
3
C). The formation of CH OAc and DME occurs with re-
lease of water (Fig. S21†), and NMR analysis indicates for-
Scheme 1 Pincer aza-15-crown-5 ether complexes.
mation of a water/methanol layer and an organic layer
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Scheme 4 General catalytic conditions for methanol carbonylation.
1
8c6
and 2
were investigated alongside IrIJIII) methylcarbon-
1
5c5
18c6
yliodide complexes (3
methyl complex [( NCOP )IrIJCH
and 3
) and the cationic IrIJIII)
1
5c5
iPr
F
15c5
F
3
)IJCO)]ijBAr
4
] (4
, Ar is
3,5-bisIJtrifluoromethyl)phenyl). Based on our prior observa-
tion that pincer-crown ether IrIJI) carbonyl complexes can be
protonated to form IrIJIII) hydrides in the presence of water
2
5
15c5
and Lewis acids, the IrIJIII) hydridocarbonyl complexes (1
and 1
1
8c6
) were also investigated.
Two trends are observed: (i) the low-valent IrIJI) complexes
1
5c5
18c6
(
2
and 2
) produce more acetyl-containing products
than the IrIJIII) complexes and (ii) the complexes containing
the larger aza-18-crown-6 macrocycle outperform those with
the smaller aza-15-crown-5 complexes in the absence of salts.
The hydridocarbonyl complexes are comparable in catalytic
activity to the other species investigated, showing that hy-
dride species that might be catalytic intermediates are capa-
1
8c6
iPr
ble of entering the cycle. Precatalyst ( NCOP )IrIJCO)
1
8c6
(
2
3
) was the top performer, producing CH OAc with a turn-
over number (TON) of 1110 and AcOH with a TON of 390; the
turnover frequency (TOF) for producing acetyls over this 3 h
−
1
span was 500 h . Furthermore, recent studies show that aza-
8-crown-6-containing complexes bind alkali metal cations
1
1
7
stronger than the aza-15-crown-5 analogues. We therefore
utilized ( NCOP )IrIJCO) (2
1
8c6
Fig. 1 Structural representations of 1
(A) and one of the two
18c6
iPr
18c6
1
8c6
) for initial catalyst optimiza-
independent molecules in the asymmetric unit of
2
(B) with
tion and additive studies.
ellipsoids drawn at 50% probability level. Hydrogen atoms are omitted
for clarity. Selected distances (Å) and angles (deg) for A: Ir1–Cl1
1
8c6
The temperature, CO pressure, concentration of 2
, and
2
.5070IJ13), Ir1–P1 2.2288IJ13), Ir1–C1 2.030(6), Ir1–N1 2.224(5), Ir–C2
concentration of methyl iodide were varied. The TON in-
creased with increasing temperature up to 150 °C, after
which a decrease was observed. The TON increased in a lin-
ear fashion both with increasing catalyst loading and with
increasing CO pressure (Fig. 2, top and Fig. S23 and S24†).
Two operating regimes are apparent for different levels of
1
.933(6); P1–Ir1–N1 157.68IJ14), P1–Ir1–Cl1 97.86(5). B: Ir2–P2 2.2007(8),
Ir2–C3 2.028(3), Ir2–N2 2.198(2), Ir2–C4 1.877(3); P2–Ir2–N2 156.44, C3–
Ir2–C4 178.77IJ12).
composed of methyl acetate and methyl iodide. The volatility
of DME precluded any quantification of the amount pro-
duced; because this reaction is not a carbonylation, it does
not affect the desired quantification of acetyl-containing
products.
CH
M) the rate of catalysis increases linearly with increasing
CH I concentration; in the high concentration regime (> 0.2
3
I (Fig. 2, bottom): in the low concentration regime (< 0.2
3
Seven Ir pincer-crown ether complexes were assessed as
1
5c5
summarized in Table 1. The IrIJI) carbonyl complexes 2
Table 1 Catalyst screening of different iridium carbonyl pincer–crown
ether complexesa
b
Iridium catalyst
3
TON CH OAc
TON AcOH
Total TON
1
1
1
1
1
1
1
5c5
5c5
5c5
5c5
8c6
8c6
8c6
1
2
3
4
1
2
3
590
750
460
500
680
1110
510
200
240
190
200
370
390
210
790
990
650
700
1050
1500
720
a
3
Conditions: 25 bar CO, 0.34 mM iridium catalyst, 0.5 M CH I, 150
b
Scheme
complex 3
3
Synthesis of aza-18-crown-6 iridium methylcarbonyl
.
°C for 3 h. Standard deviation ±75 estimated based on averages of
1
8c6
multiple trials.
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Fig. 3 Effect of metal and ammonium salt on turnover number of
CH
carbonylation by (
reactions containing 3.4 mM [TBA]ijOTf]. Conditions: 150 °C, 25 bar
CO, 3 h, 0.1 M CH I, 0.34 mM Ir catalyst, 0.34 mM Lewis acid.
3
OAc (blue) and AcOH (orange) produced in methanol
18c6
iPr
18c6
NCOP )IrIJCO) (2
). Purple bars are data from
3
3
catalytic conditions (0.5 M CH I) produced only a slight ex-
cess of CH OAc (∼2.5 : 1 CH OAc : AcOH).
3
3
3 3
In light of LaI and GaI causing a decrease in catalytic
activity (Fig. 3) and previous observations that these iridium
pincer carbonyl complexes favor the soft/soft acid/base
Fig. 2 Turnover of products, defined as the total turnover number
−
25,31,32
(
TON) for both methyl acetate and acetic acid, during methanol
match between Ir and I ,
we considered the possibility
18c6
iPr
18c6
carbonylation catalyzed by (
NCOP )IrIJCO) (2
) at 150 °C for 3
that iodide might poison the catalyst. However, when the
reaction was run with a 10-fold excess of tetrabutylam-
monium iodide ([TBA][I]) relative to catalyst, rather than any
inhibition, a 1.5-fold improvement in TON was observed
hours, varying CO pressure with 0.5 M CH
concentration at 25 bar CO (bottom).
3
I (top) and varying CH
3
I
(
Table S2†). We hypothesize that the ammonium salt is a
3
3,34
M) a strong inhibitory effect is observed, probably due to cat-
alyst decomposition. The amount of CH I used in catalytic
phase transfer mediator.
Given that separated layers
3
were observed in the reactor at the conclusion of catalytic
trials (see above), the tetraalkylammonium salt could help
avoid mass transport complications that arise from a bi-
phasic reaction medium.
Tetrabutylammonium triflate ([TBA]ijOTf]) was chosen for
subsequent studies because it contains a weakly coordinat-
ing anion. Including [TBA][OTf] in catalytic runs containing
Lewis acid salts results in an additional increase in acetyl
containing products (Fig. 3, purple bars). Some of the best-
trials was therefore reduced from 0.5 M to 0.1 M for subse-
quent studies, while maintaining the previously established
conditions under 25 bar CO and at 150 °C for 3 h. Under
these conditions, the catalytic activity was maintained in the
−
1
range of 200–300 h over a 12 h period (Fig. S26†).
Catalytic methanol carbonylation in the presence of
promoters
4
performing metal salts (e.g. HfCl and LiCl) improved fur-
The influence of various metal salts on the activity of
ther in the presence of [TBA]ijOTf]. The salt CeIJOTf) was in-
3
1
8c6
iPr
18c6
(
NCOP )IrIJCO) (2
) was assessed under low CH I con-
hibitory in the absence of [TBA][OTf] (factor of 0.81), but
was markedly improved in the presence of the ammonium
salt (factor of 1.26). The system with the highest turnover
3
ditions (150 °C, 25 bar CO, 3 h, 0.34 mM Ir catalyst, 0.1 M
CH I). The results with equimolar amounts of metal salt and
3
catalyst are shown in Fig. 3 (also see Table S1†). The greatest
rate enhancements were observed for KCl and LiCl, which in-
creased total TON by factors of 1.18 and 1.21, respectively.
4
numbers included HfCl and [TBA][OTf] (TON = 1580),
which featured a promotion factor of 1.61. A related catalyst
containing a methoxy group ortho to the phosphinite donor
was targeted in order to prevent unwanted cyclometallation
at alternate positions, which has been observed under cer-
The LiCl-promoted reaction produced predominantly CH OAc
3
(TON = 1150), with only small amounts of AcOH (TON = 40).
2
5
In general, the reactions at lower CH I loading selectively
tain conditions in related complexes. The new methoxy-
substituted aza-18-crown-6-decorated ligand (Scheme 5) was
3
generate CH OAc (∼30 : 1 CH OAc : AcOH), whereas the initial
3
3
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Scheme 6 Additional iridium pincer carbonyl complexes utilized in
this study.
Scheme
complexes.
5 Synthesis of methoxy-substituted iridium pincer
MeO-18c6
produced less acetyl-containing products than 2
in
the absence of salt additives, but exhibited significant rate
enhancement with LiCl (Fig. 5 and Table S5†). A full 2-fold
rate enhancement was observed in conjunction with tetra-
butylammonium chloride, as the TON approached 2000. It is
accessed by reductive amination of iso-vanillin using so-
dium triacetoxyborohydride in the presence of aza-18-crown-
i
6
, followed by phosphination with NEt
3
and Pr
2
PCl. Subse-
noteworthy that LiCl is the only metal salt that significantly
MeO-15c5
quent metallation and dehydrohalogenation were achieved
using procedures analogous to those used for the parent
promotes carbonylation with 2
, given that prior bind-
+
ing affinity studies showed selective Li complexation by
complexes appended with this small macrocycle.
1
8c6
18c6
17
17
complexes 1
and 2
(Scheme 5).
was tested for methanol carbonylation
activity with a variety of metal and ammonium salts (Fig. 4
MeO-18c6
Complex 2
To probe the necessity of the pendent crown ether group,
we utilized a crown-ether-free analogue containing a diethyl-
amino group (Scheme 6). The iridiumIJI) carbonyl complex,
MeO-18c6
and Table S4†). In the absence of additives, 2
pro-
Et
iPr
Et
duced more CH OAc than the analogous unsubstituted com-
( NCOP )IrIJCO) (2 ) was synthesized according to the previ-
3
1
8c6
25
Et
plex 2
. Although a high TON is obtained in the absence of
ously published procedure. As shown in Table 2, 2 ex-
hibits up to 1.16-fold rate enhancement in the presence of
salts. Activity similar to the optimized conditions for
macrocycle-containing precatalysts is achieved when free or-
ganic 12-crown-4 is added, suggesting that intramolecular
cation-crown interactions are not essential for the observed
promotive effects.
additives (1500 total TON), this catalyst was not greatly pro-
moted by salt additives.
To probe the role of cation-crown ether interactions in ca-
talysis, the analogous methoxy-substituted catalyst bearing
MeO-15c5
iPr
the smaller aza-15-crown-5 macrocycle, (
IJCO) (2
NCOP )Ir-
MeO-15c5
12
MeO-15c5
, Scheme 6), was examined. Catalyst 2
Fig. 4 Effect of metal and tetrabutylammonium salt on turnover
number of CH OAc (blue) and AcOH (orange) produced in methanol
carbonylation by (
C, 25 bar CO, 3 h, 0.1 M CH
Fig. 5 Effect of metal and tetrabutylammonium salt on turnover
3
number of CH
carbonylation by (
°C, 25 bar CO, 3 h, 0.1 M CH
ammonium salt, and 0.34 mM metal salt.
3
OAc (blue) and AcOH (orange) produced in methanol
MeO-18c6
iPr
MeO-18c6
MeO-15c5
iPr
MeO-15c5
NCOP )IrIJCO) (2
). Conditions: 150
NCOP )IrIJCO) (2
). Conditions: 150
°
3
I, 0.34 mM Ir catalyst, 3.4 mM
3
I, 0.34 mM Ir catalyst, 3.4 mM
ammonium salt, and 0.34 mM metal salt.
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Table 2 Methanol carbonylation with a macrocycle-free catalysta
b
c
Iridium catalyst
Ammonium Salt
Metal Salt
3
TON CH OAc
TON AcOH
Total TON
Promotion factor
Et
Et
Et
Et
iPr
Et
(
(
(
(
NCOP )IrIJCO) (2 )
—
—
—
1300
1510
1390
1630
40
50
40
60
1340
1560
1430
1690
—
iPr
Et
NCOP )IrIJCO) (2 )
HfCl
HfCl
HfCl
4
4
4
1.16
1.07
1.26
iPr
Et
NCOP )IrIJCO) (2 )
[TBA][OTf]
[TBA][OTf]
iPr
Et
NCOP )IrIJCO) (2 )
+ 12-crown-4
a
b
Standard conditions of 150 °C, 25 bar CO, 3 h, 0.1 M CH
3
I and 0.34 mM Ir catalyst. 10 equivalents of ammonium salt (3.4 mM) relative to
c
iridium. 1 equivalent of free 12-crown-4 and Lewis acid (0.34 mM) relative to iridium.
−
Probing catalyst stability
2 2
difficult to conclusively rule out [IrIJCO) I ] as an active cata-
lyst formed in situ, given that under our optimized conditions
After typical catalytic runs in the high-pressure reactors,
solvents were removed and the crude material was
−
[
IrIJCO) I ] is slightly more active (TON = 1870); in addition
2
2
to the evidence above, it is also noteworthy that the pincer
dissolved in CD OD to probe the nature of any iridium-
3
−
3
1
1
precatalysts are promoted by [TBA][I] while [IrIJCO) I ] is not
(Table S6†).
2
2
containing products by P{ H} NMR spectroscopy. Two or
3
8
3
1
three prominent P resonances were observed between 75
and 90 ppm in most cases (Fig. S27†). Similar products
were observed under a range of conditions and with vari-
ous catalysts.
To test whether the species formed during the reaction
were still catalytically active, a recycling experiment was
18c6
iPr
18c6
performed with ( NCOP )IrIJCO) (2
). After a run at 130
°
C (0.34 mM Ir catalyst, 0.1 M CH I, 25 bar CO, 3 h), the reac-
3
The identity of the phosphorus-containing species formed
tion vessels were returned to the glovebox and the solvents
were removed under vacuum. The resulting yellow solids
were returned to a reactor with new methanol and CH I, and
3
during catalysis remains unclear. We considered the possibil-
−
ity of a phosphine adduct derived from [IrIJCO)
2
I
2
] , but addi-
1
8c6
iPr
31
1
tion of free ( NCOP )H ( P{ H} δ 150) to [PPN]ijIrIJCO) I ]
2
2
a second catalytic run was carried out. In the initial 3 h reac-
tion time, a total of 200 turnovers of acetyls was observed.
When the isolated catalyst residues were used as the catalyst
for a second 3 h run, 300 total turnovers were observed. In
parallel, a second reactor was run for 6 h without disturbance
for comparison, resulting in 475 total turnovers and
confirming that the unknown species are active catalysts.
(
3
PPN = bisIJtriphenylphosphine)iminium) in CD CN resulted
31
1
in clean conversion to a species ( P{ H} NMR δ 124) that is
not observed during or after catalysis (Fig. S28†). We also
considered pincer ligand dissociation and subsequent degra-
dation in the CH
3
I/CH
3
OH solution. Dissolving the free
15c5
iPr
ligand ( NCOP )H in CD OD led to the appearance of new
3
3
1
1
P{ H} NMR signals at 158 and 62 ppm assigned to
i
i
P Pr
2 3 2
IJOCD ) and Pr PIJO)D, respectively (Fig. S29†). Subse-
quent addition of excess CH I to this mixture led to a new
signal at 109 ppm tentatively assigned to [P Pr IJOCD )IJCH )] .
2 3 3
3
i
+
Catalytic methanol carbonylation at low temperature and
pressure
These species were not observed at the conclusion of Ir-
containing carbonylation reactions, but they could act as
monodentate ligands on Ir during turnover. To test this, a
carbonylation reaction was carried out at high Ir loading and
To monitor the product distribution and catalyst state in situ
over time, methanol carbonylation was performed in NMR
tubes at 70 °C and 1 atm pressure CO. Tubes were charged
3
1
18c6
MeO-18c6
the Ir-containing products were analyzed by P NMR and IR
spectroscopy as well as mass spectrometry (MS). Negative
with 2.5 mM catalyst (2
or 2
) and 25 equiv. of
CH I in CH OH (ensuring protio products for easy analysis
3
1
3
i
−
mode electrospray MS ions included [IrIJ Pr
2
PIJO)H)IJI)
2
IJH
2
O)
2
] ,
by H NMR). The reaction progress was monitored periodi-
i
−
−
1
[
IrIJP Pr IJOCH ))IJI) IJCO)] , and [IrIJCO) IJI) ] (Fig. S31†). The IR
cally over 40 h by H NMR spectroscopy (the headspace was
2
3
2
2
2
spectra are consistent with monocarbonyl species (single
refilled with CO gas twice during this time). Product analysis
was performed using H NMR spectroscopy after an external
−
1
1
broad feature at 2060 cm , Fig. S32†), suggesting that
−
2
[
IrIJCO) IJI) ] is not present in high concentration. These ex-
lock on a separate tube containing CD OD. The low signal-to-
2
2
3
periments suggest that the catalyst undergoes thermal pincer
ligand decoordination (presumably initiated by reductive
elimination of the ligand-derived arene from an Ir hydride
intermediate) followed by methanolysis to form monodentate
3
noise ratio due to the large CH OH peak prevents direct inte-
1
gration of the catalyst in H NMR spectra, so the concentra-
tion of iridium was confirmed using ICP-MS.
1
8c6
Catalyst 2
3
gave 3.3 turnovers of CH OAc after 40 h in
i
i
35–37
2 3 2
complexes of P Pr IJOCH ) and Pr PIJO)H.
Examples of
the absence of salts under these mild conditions. The rate of
monodentate phosphines in iridium-catalyzed methanol car-
bonylation are notably lacking, but monodentate phosphite
ligands have been shown to accelerate migratory insertion in
CH OAc production increased in the presence of LiOTf
3
(TON = 5.3) and LaIJOTf)
high-pressure multireactor experiments, 2
3
(TON = 7.2). As observed in the
MeO-18c6
exhibited
−
19
[
MeIrIJCO) IJI) ] . The anionic nature of the catalyst and the
higher activity initially (TON = 14.3 without salts), but did
not experience significant promotion effects (TON = 18.2 with
LiOTf, TON = 16.0 with LaIJOTf) ).
3
2
3
presence of the Lewis basic methoxy substituents on phos-
phorus may contribute to observed cation effects. It is still
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1
8c6
Even under these mild conditions, the precatalysts 2
an iridium acetyl and without any decomposition of the Ir
pincer-crown ether complex under these conditions. The in
situ experiments show that the intact pincer-crown ether
complexes can carry out all of the required steps for metha-
nol carbonylation.
MeO-18c6
and 2
precatalyst 2
convert to new species during the reaction. The
, which lacks a blocking group on the back-
bone, evolved into fewer species over 40 h, including major
1
8c6
3
1
P
resonances in the region of the cyclometallated
iridiumIJIII) complexes (δ 144 and 139, Fig. S34†). Precatalyst
MeO-18c6
2
, on the other hand, showed no evidence of cyclo-
Conclusions
3
1
metallated pincer ligands, only a bevy of P resonances in
the range 60 to 125 ppm.
Iridium pincer-crown ether complexes are precatalysts for
methanol carbonylation, producing methyl acetate as the ma-
jor product under the employed reaction conditions. A com-
plex bearing an aza-18-crown-6 macrocycle was significantly
Probing catalyst intermediates in CD
3
OD
promoted by several metal-containing salts. The biggest rate
1
3
To study the migratory insertion process directly, the C-la-
3+
enhancements are observed for LiCl and HfCl , whereas La
1
5c5
iPr
13
15c5 13
4
beled methyl complex ( NCOP )IrIJ CH
3
)IJCO)IJI) (3 - C,
3+
and Ce salts were generally inhibitory. Interestingly, non-
1
2
available from a prior study ) was heated at 70 °C under 1
metal tetrabutyl ammonium salts are also strong promoters
for this catalyst system, perhaps due to a role in phase trans-
fer catalysis.
1
3
atm CO in CD OD and monitored by H NMR spectroscopy.
15c5 13
1
The methyl resonance of 3 - C ( H NMR δ 0.81) disap-
pears over 40 hours with concomitant appearance of reso-
nances assigned to partially-deuterated methyl acetate,
A comparative catalyst study provides some insight into the
factors influencing reactivity. Incorporating a methoxy substit-
uent in the backbone improves performance. The size of the
macrocycle could be studied with these methoxy-containing
species, and the activity of the precatalyst with the smaller
aza-15-crown-5 macrocycle was doubled in the presence of
LiCl. This result may reflect a strong cation-crown interac-
tion, but further trends in cation binding are not apparent.
Using a pincer ligand with a non-macrocyclic dialkylamine
donor revealed that similar salt promotion effects can be ob-
served in conjunction with external macrocycles. These find-
ings indicate that intramolecular cation-crown interactions
are not essential for promoting catalysis, which is a promis-
ing finding for practical catalyst development.
Studies to probe the reaction mechanism and the fate of
the catalyst under various conditions were carried out. Under
low temperature, low pressure conditions, the pincer-crown
ether complexes remain intact and are well-defined; upon
moving to high pressure reactors with excess methyl iodide,
the precatalysts convert to new active species tentatively
assigned as complexes of simple monodentate phosphines
derived from pincer ligand methanolysis. These studies speak
to the challenge of designing molecular iridium catalysts
with complex ligands that are robust enough to withstand
the forcing conditions of methanol carbonylation. While the
precatalysts decompose under the reaction conditions, the
resulting solutions retain their activity in recycling experi-
ments and are promoted by certain salts, providing guidance
for future catalyst design.
13
1
13
CH
3 3
C(O)OCD ( H NMR δ 2.02, C NMR δ 173.4, 51.5,
2
0.5). An analogous experiment in CH OH solution with a
3
CD
16.6, JPH = 19.6 Hz) that enables identification of the major
iridium product as the previously reported hydridocarbonyl
3
OD capillary revealed a prominent hydride resonance (δ
2
−
1
5c5
iPr
25
iodide complex ( NCOP )IrIJH)IJCO)IJI) (Scheme 7). With
nearly full conversion after 4 h, the reaction in CH OH
proceeded significantly faster than the reaction in CD OD.
3
3
These findings stand in contrast to prior observations in
acetonitrile, wherein methyl complexes undergo migratory
insertion to form a stable acetyliridium species that does not
1
2
eliminate free acetyls. In methanol, free methyl acetate is
produced on a similar timescale, and no acetyl intermediates
are observed. This stoichiometric carbonylation is noteworthy
because methyl acetate is produced without intermediacy of
Experimental section
General considerations
All manipulations were carried out using standard Schlenk or
glovebox techniques under a N atmosphere. Under standard
2
glovebox operating conditions, pentane, diethyl ether, ben-
zene, toluene, and tetrahydrofuran were used without purg-
ing, such that traces of those solvents were present in the
Scheme 7 Stoichiometric formation of methyl acetate under mild
conditions.
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1
31
13
atmosphere and in the solvent bottles. H, P, and C spec-
tra were recorded on 400, 500 or 600 MHz spectrometers at
least squares minimization. A two-component twinning
1
8c6
model was used in the refinement of 1
.
2
98 K. NMR solvents were purchased from Cambridge Iso-
1
8c6
iPr
18c6
topes Laboratories, Inc.
dichloromethane-d2 (CD Cl )
degassed three times before drying by passage through a
small column of activated alumina. H and C chemical
shifts are reported in ppm relative to residual protio solvent
Methanol-d4
(CD OD) and
3
Synthesis of (
A Schlenk flask was charged with 0.380 g (0.749 mmol) of
IrIJp-toluidine)IJCO) IJCl) suspended in 10 mL of toluene. The
NCOP )IrIJH)IJCO)IJCl) (1
)
were
freeze–pump–thaw
2
2
1
13
2
iPr
1
8c6
ligand, ( NCOP )H (0.360 g, 0.972 mmol) was dissolved in
0 mL of toluene and added to the Ir precursor suspension
to yield a yellow solution. The mixture was refluxed under N
for 15 h, at which point it was allowed to cool and the tolu-
ene was removed under vacuum. The resulting brown residue
was washed with pentane (3 × 4 mL) and extracted with ben-
zene (5 mL). The orange/brown benzene solution was evapo-
rated under vacuum to yield a brown oil. The oil was
dissolved in minimal benzene (<0.5 mL), layered with penta-
ne and placed in the freezer (−30 °C) overnight to recrystal-
lize, yielding a brown analytically pure solid (0.450 g, 81%
yield). H NMR (600 MHz, CD
Ar–H), 6.79 (d, J = 7.4 Hz, 1H, Ar–H), 6.70 (d, J = 7.9 Hz, 1H,
Ar–H), 4.71 (d, J = 13.8 Hz, 1H, ArCH N), 4.37 (m, 1H, crown-
CH ), 4.17 (dd, J = 13.9, 3.6 Hz, 1H, ArCH N), 3.99 (m, 1H,
crown-CH ), 3.84 (m, 3H, crown-CH ), 3.62 (m, 18H, crown-
), 3.27 (m, 1H, crown-CH
m, 1H, CHIJCH
1
3
1
resonances. P chemical shifts are reported relative to 85%
2
H PO
external standard (δ 0). The compounds
3
4
1
5c5
iPr
10
18c6
iPr
17
39
(
NCOP )H,
(
(
NCOP )H,
NCOP )IrIJH)IJCO)IJCl) (1
IrIJp-toluidine)IJCO) Cl,
2
3
8
15c5
iPr
15c5 25
15c5
[PPN]ijIrIJCO)
2 2
I ],
),
(
-
iPr
15c5 25 15c5
iPr
15c5 12
NCOP )IrIJCO) (2
),
(
NCOP )IrIJCH )IJCO)IJI) (3
),
3
15c5
iPr
Et 25
F
15c5 12
Et
iPr
[(
NCOP )IrIJCH )IJCO)]ijBAr ] (4
)
and ( NCOP )Ir-
3
4
IJCO) (2 ) were synthesized according to literature proce-
dures. All other reagents were commercially available and
used without further purification. Elemental analyses were
performed by Robertson Microlit Labs (Ledgewood, NJ). In-
frared spectroscopy was carried out with a Thermo Scientific
Nicolet iS5 FT-IR equipped with Quest Single Reflection ATR
Accessory. High temperature and pressure catalysis was
performed with a Parr Series 5000 Multiple Reactor System
operated by a Parr 4871 Process Controller equipped with six
reactors with internal stirring. Each reactor is individually
pressure and temperature controlled with maximum operat-
ing limits of 3000 psi (200 bar) and 300 °C. Each reactor is
monitored by computer software SpecView 32. Mass spectro-
1
Cl
2 2
): δ 6.91 (t, J = 7.7 Hz, 1H,
2
2
2
2
2
CH
2
2
3 2
), 2.90 (m, 1H, CHIJCH ) ), 2.44
(
3
)
2
), 1.30 (m, 6H, CHIJCH
3 2
) ), 1.12 (dd, J = 19.3,
7
.0 Hz, 3H, CHIJCH ) ), 1.03 (dd, J = 16.2, 6.9 Hz, 3H,
3
2
1
3
1
CHIJCH
)
3 2
), −19.09 (d, J = 20.8 Hz, 1H, Ir–H). C{ H} NMR
Cl ): δ 181.36 (d, J = 3.9 Hz, Ir–CO), 161.61 (d,
J = 2.5 Hz, C ), 149.10 (d, J = 2.4 Hz, C ), 148.77 (d, J = 4.9
(
151 MHz, CD
2
2
metry was carried out with
a LTQ FT (ICR 7 T)
Ar
Ar
(ThermoFisher, Bremen, Germany) mass spectrometer. Mea-
Hz, CAr), 126.06 (s, CAr), 117.40 (s, CAr), 108.88 (d, J = 12.4 Hz,
Ar), 71.71 (s, ArCH N), 71.26–70.37 (m, crown-CH ), 68.30 (s,
crown-CH ), 63.58 (s, crown-CH ), 59.97 (d, J = 2.4 Hz, crown-
surements were made on complexes dissolved in either meth-
anol or acetonitrile. Samples were introduced via a micro-
C
2
2
−
1
2
2
electrospray source at a flow rate of 3 μL min . Xcalibur
ThermoFisher, Bremen, Germany) was used to analyze the
CH
2
), 32.44 (d, J = 33.5 Hz, CHIJCH
)
3 2
), 29.25 (d, J = 42.3 Hz,
), 18.10 (s,
(
CHIJCH )
3 2
), 18.67 (d, J = 5.5 Hz, CHIJCH )
3 2
data. Molecular formula assignments were determined with
Molecular Formula Calculator (v 1.2.3). All observed species
were singly charged, as verified by unit m/z separation be-
CHIJCH ) ), 17.68 (d, J = 3.5 Hz, CHIJCH ) ), 15.97 (s,
3
2
3 2
3
1
1
CHIJCH
(
3
)
2
). P{ H} NMR (162 MHz, CD
2
Cl
2
): δ 153.12. IR
−
1
−1
solid, cm ): ν(CO) 2016 cm . Anal. calcd for
1
2
tween mass spectral peaks corresponding to the C and
C H ClIrNO P: C, 42.13; H, 5.98; N, 1.89. Found: C, 42.18;
13
12
26 44
7
C Cc-1 isotope for each elemental composition. Samples for
ICP-MS were prepared using 2% nitric acid diluted with 18.2
+
18c6
+
H, 5.54, N; 2.01. HRMS (ESI ) m/z: [1 -Cl] calcd for
44IrNO P 706.24846; found 706.24754.
26
C H
7
−
1
MΩ cm water. Samples were analyzed with an Element XR
inductively coupled plasma (ThermoFisher, Bremen, Ger-
many) mass spectrometer (ICP-MS). Samples were introduced
via a peristaltic pump connected to an Elemental Scientific
SC autosampler (Omaha, Nebraska). Iridium 193 was moni-
tored in low resolution mode for 30 s for each sample (∼300
scans). Optimized gas flows and instrument voltages were
cross-checked against calibration solutions prior to all data
collections events. Method mass offsets were adjusted as
needed to accommodate the center most section of the peaks
of interest. ICP-MS data was analyzed using Thermo Show
and Run software in the Element software suite. Single crys-
tal X-ray diffraction data was collected on a Bruker APEX-II
CCD diffractometer at 100 K with Cu Kα radiation (λ =
1
8c6
iPr
18c6
Synthesis of (
NCOP )IrIJCO) (2
)
A 20 mL scintillation vial was charged with 0.25 g (0.337
1
8c6
iPr
mmol) of ( NCOP )IrIJH)IJCO)IJCl) and 0.056 g (0.499 mmol)
t
of KO Bu. The solids were dissolved in 8 mL benzene and
allowed to stir for 2 h, after which benzene was removed un-
der vacuum. The dark brown residue was stirred in 20 mL of
pentane for 48 h yielding a bright yellow solution. The solu-
tion was filtered removing insoluble brown solids and penta-
ne was removed in vacuo to yield a bright yellow analytically
pure solid (0.185 g, 66% yield). H NMR (600 MHz, CD
6.81 (t, J = 7.6 Hz, 1H, Ar–H), 6.75 (d, J = 7.3 Hz, 1H, Ar–H),
6.65 (d, J = 7.8 Hz, 1H, Ar–H), 4.51 (s, 2H, ArCH N), 4.40
(ddd, J = 11.1, 7.1, 4.1 Hz, 2H, crown-CH
10.5, 5.6, 4.3 Hz, 2H, crown-CH ), 3.73 (m, 2H, crown-CH ),
1
2
Cl
2
): δ
2
4
0
1
.54175 Å). Using Olex2, the structures were solved with the
2
), 3.99 (ddd, J =
4
1
olex2.solve structure solution program using Charge Flip-
2
2
4
2
ping and refined with the XL refinement program using
3.67–3.56 (m, 18H, crown-CH ), 2.25 (m, J = 6.7 Hz, 2H,
2
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CHIJCH ) ), 1.17 (d, J = 7.1 Hz, 6H, CHIJCH ) ), 1.14 (dd, J =
60/40 CH Cl /EtOAc mobile phase until TLC showed no
3
2
3 2
2
2
1
3
1
7
.1, 2.4 Hz, 6H, CHIJCH ) ). C{ H} NMR (151 MHz, CD Cl ):
remaining traces of alcohol. The product was then eluted
with an 85/10/5 CH Cl /NEt /CH OH mobile phase. Fractions
3
2
2
2
δ 198.45 (d, J = 2.7 Hz, Ir–CO), 166.96 (d, J = 7.8 Hz, CAr),
65.72 (d, J = 6.1 Hz, C ), 154.55 (d, J = 2.4 Hz, C ), 127.05
2
2
3
3
1
containing the product were combined and the solvent was
removed to provide an off-white oil which was dried over
Ar
Ar
(
s, C ), 114.94 (s, C ), 107.10 (d, J = 12.4 Hz, C ), 72.78 (s,
Ar Ar Ar
ArCH
2
N), 71.00 (s, crown-CH
2
), 70.90 (s, crown-CH
2
), 70.88 (s,
2 5
P O overnight to yield analytically pure material (0.748, 70%
yield). H NMR (600 MHz, CD Cl ) δ 7.02 (d, J = 2.0 Hz, 1H,
2 2
1
crown-CH ), 70.84 (s, crown-CH ), 70.37 (s, crown-CH ), 63.72
2
2
2
(
3
d, J = 2.2 Hz, crown-CH ), 31.45 (d, J = 37.6 Hz, CHIJCH )),
Ar–H), 6.78 (d, J = 8.2 Hz, 1H, Ar–H), 6.73 (dd, J = 8.2, 2.0 Hz,
1H, Ar–H), 3.84 (s, 3H, Ar–OCH ), 3.66–3.61 (m, 8H, crown-
CH ), 3.61–3.57 (m, 4H, crown-CH ), 3.57–3.52 (m, 10H,
2
3
0.07 (s, CHIJCH
3
)), 18.37 (d, J = 4.8 Hz, CHIJCH
3
)), 17.63 (s,
3
3
1
1
CHIJCH )). P{ H} NMR (162 MHz, CD Cl ): δ 170.80. IR
3
2
2
2
2
−
1
−1
(solid, cm ): ν(CO) 1920 cm . Anal. calcd for C H IrNO P:
overlapping crown-CH and ArCH N), 2.68 (t, J = 5.7 Hz, 4H).
2
6
43
7
2
2
1
3
1
C, 44.31; H, 6.15; N, 1.99. Found: C, 44.58; H, 6.02; N, 1.86.
C{ H} NMR (151 MHz, CD
Cl
2 2
) δ 146.14 (CAr), 145.97 (CAr),
1
33.81 (C ), 119.96 (C ), 115.61 (C ), 110.84 (C ), 71.12
Ar Ar Ar Ar
1
8c6
iPr
18c6
(
crown-CH ), 70.86 (crown-CH ), 70.78 (crown-CH ), 70.51
Synthesis of (
NCOP )IrIJCH )IJCO)IJI) (3
)
2
2
2
3
(
(
6
crown-CH
2
), 70.13 (crown-CH
2
), 59.53 (crown-CH
2
), 56.28
A 20 mL scintillation vial was charged with 42 mg (0.059
Ar–OCH ), 54.57 (ArCH N). Anal. calcd. for C H NO : C,
3 2 20 33 7
0.13; H, 8.33; N, 3.51. Found: C 60.07; H, 8.36, N, 3.59.
1
8c6
iPr
mmol) of ( NCOP )IrIJCO) in 5 mL of CH Cl . To this solu-
2
2
3
tion, 5.5 μL (0.089 mmol) CH I was added via syringe and
+
+
HRMS (ESI ) m/z: [phenol
4
20 7
+ H] calcd for C H34NO
the bright yellow color turns to a pale yellow within minutes.
The solution was allowed to stir for 2 h at room temperature,
then the solvent was removed under vacuum yielding a pale
yellow oil. The oil was triturated with pentane (3 × 1 mL) to
yield a fluffy off-white solid (45.4 mg, 90% yield, 95% purity
00.23298; found 400.23177.
MeO-18c6
iPr
Synthesis of (
NCOP )H
In a glovebox, a 20 mL scintillation vial was charged with
0.281 g (0.703 mmol) of 5-(aza-18-crown-6)-2-methoxy phenol
and 10 mL of THF. To the clear, colorless solution, 109 μL of
triethylamine was added dropwise via a syringe while stirring.
The mixture was allowed to stir for 15 minutes at room tem-
1
based on multinuclear NMR spectroscopy). H NMR (400
2 2
MHz, CD Cl ) δ 6.92 (t, J = 7.6 Hz, 1H, Ar–H), 6.83 (m, 2H,
Ar–H), 4.87 (d, J = 13.6 Hz, 1H, ArCH N), 4.36 (dd, J = 13.7,
2
3
.8 Hz, 1H, ArCH
2
N), 4.22 (m, 1H, crown-CH
2
), 4.05 (m, 1H,
crown-CH ), 3.85 (m, 2H, crown-CH
2
2
), 3.78 (m, 2H, crown-
perature. In a separate vial, 112 μL of diisopropyl-
CH ), 3.70–3.56 (m, 18H, crown-CH ), 3.15 (m, 1H, crown-
chlorophosphine was dissolved in 2 mL of THF. The phos-
phine solution was slowly added dropwise to vial containing
the phenol/amine mixture. The resulting mixture was allowed
to stir for 4 h, during which time a white precipitate formed.
The solvents were removed under vacuum leaving a mixture
of an oil and white solids. The oil was extracted with ether (2
× 5 mL) and filtered. The ether was removed under vacuum
2
2
CH
2
), 2.96 (dp, J = 14.0, 7.2 Hz, 1H, CHIJCH
3
)
2
), 2.80 (m, 1H,
), 1.30 (dd,
J = 14.3, 7.1 Hz, 3H, CHIJCH ) ), 1.20 (dd, J = 19.5, 7.3 Hz, 3H,
3 2 3 2
CHIJCH ) ), 1.41 (dd, J = 15.4, 7.4 Hz, 6H, CHIJCH )
3
2
1
3
1
CHIJCH
MHz, CD
.5 Hz, C ), 147.96 (C ), 125.70 (C ), 117.56 (C ), 109.58 (d,
)
3 2
), 0.77 (d, J = 2.2 Hz, 3H, Ir–CH
3
). C{ H} NMR (151
2
Cl ) δ 180.42 (s, Ir–CO), 159.79 (CAr), 152.08 (d, J =
2
5
Ar
Ar
Ar
Ar
J = 11.8 Hz, CAr), 70.85 (ArCH
2
N), 70.76–69.67 (m, overlapping
), 59.48 (crown-CH ), 54.77
to yield an analytically pure colorless oil (0.273 g, 75% yield).
H NMR (600 MHz, CD Cl ) δ 7.12 (s, 1H, Ar–H), 6.88 (dd, J =
2 2
1
crown-CH ), 67.32 (crown-CH
2
2
2
(
crown-CH ), 29.69 (CHIJCH ) ), 25.78 (d, J = 38.6 Hz,
8.1, 2.0 Hz, 1H, Ar–H), 6.79 (d, J = 8.2 Hz, 1H, Ar–H), 3.79 (s,
2H, ArCH N), 3.57 (m, 23H, overlapping crown-CH and Ar–
OCH ), 2.71 (t, J = 5.9 Hz, 4H, crown-CH ), 1.92 (m, 2H,
2
3 2
CHIJCH
3 2
)
), 18.68 (CHIJCH
3
)
2
), 18.35 (CHIJCH
)
3 2
), 16.20 (d, J =
), −18.57 (d,
J = 5.5 Hz, Ir–CH ). P{ H} NMR (243 MHz, CD Cl ) δ 135.36.
2
2
4
.0 Hz, CHIJCH
3
)
2
), 16.11 (d, J = 4.9 Hz, CHIJCH
3
)
2
3
2
31
1
CHIJCH ) ), 1.19 (dd, J = 10.7, 7.0 Hz, 6H, CHIJCH ) ), 1.09 (dd,
3
2
2
3 2
3 2
−
1
−1
+
18c6
+
13
1
IR (solid, cm ): ν(CO) 2009 cm . HRMS (ESI ) m/z: [3 -I]
calcd for C27 46IrNO P 720.26356; found 720.26394.
3 2
J = 15.6, 7.2 Hz, 6H, CHIJCH ) ). C{ H} NMR (151 MHz,
H
7
2 2
CD Cl ) δ 149.82 (CAr), 148.61 (d, J = 8.0 Hz, CAr), 132.75 (CAr),
1
7
5
22.63 (C ), 120.47 (d, J = 14.7 Hz, C ), 112.28 (C ), 71.21–
Ar Ar Ar
0.07 (m, overlapping crown-CH
2
, ArCH
2
3
N, and Ar–OCH ),
Synthesis of 5-(aza-18-crown-6 methyl)-2-methoxy phenol
2 2
9.71 (crown-CH ), 56.16 (crown-CH ), 28.84 (d, J = 18.4 Hz,
A 200 mL Schlenk flask was charged with 0.830 g (5.56
mmol) 3-hydroxy-4-methoxybenzaldehyde, 0.720 g (2.73 mmol)
CHIJCH ) ), 17.91 (d, J = 20.3 Hz, CHIJCH ) ), 17.21 (d, J = 8.9
Hz, CHIJCH
C H46NO P: C, 60.56; H, 8.99; N, 2.72. Found: C 60.64; H,
26 7
3
2
3 2
3
1
1
3 2
) ).
P{ H} NMR
δ
150.0 Anal. calcd. for
1
-aza-15-crown-5, and 35 mL THF. The mixture was allowed
to stir for 1 h and then 1.3 g (6.13 mmol) sodium triacetoxy-
borohydride was added portion-wise over 24 hours. The reac-
tion was stirred for an additional 24 h and then quenched
+
MeO-18c6
iPr
+
8.82, N, 2.87. HRMS (ESI ) m/z: [(
NCOP )H + H ]
calcd for C26H47NO P 516.30846; found 516.30697.
7
with aqueous saturated NaHCO . The product was extracted
3
MeO-18c6
iPr
MeO-18c6
Synthesis of (
NCOP )IrIJH)IJCO)IJCl) (1
)
into 4 × 25 mL of CH Cl and the solvent of the combined ex-
2
2
tracts was removed. The crude product was purified using a
short silica plug. Unreacted aldehyde and the directly re-
duced byproduct 3-hydroxymethylphenol were eluted with a
A Schlenk flask was charged with 0.238 g (0.462 mmol) of
MeO-18c6
iPr
(
NCOP )H, 0.180
g
(0.461 mmol) of IrIJp-
toluidine)IJCO) Cl and 50 mL of toluene. The mixture was
2
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refluxed under N for 16 h, at which point the mixture was
C ), 115.82 (C ), 111.87 (C ), 72.25 (Ar–OCH ), 71.05
2
Ar
Ar
Ar
3
allowed to cool and the toluene removed under vacuum leav-
ing a brown residue. The residue was washed with pentane
(crown-CH ), 70.95 (crown-CH ), 70.89 (crown-CH ), 70.86
2
2
2
(crown-CH
2
2
), 70.46 (ArCH N), 63.57 (d, J = 2.5 Hz, crown-
(3 × 2 mL) and extracted with benzene (6 mL). The resulting
CH ), 56.73 (crown-CH ), 31.70 (d, J = 37.4 Hz, CHIJCH ) ),
2 2 3 2
brown benzene solution was evaporated under vacuum to
yield a brown oil. The brown oil was recrystallized by slow
evaporation from ether to give analytically pure light brown
30.10 (CHIJCH ) ), 18.48 (d, J = 4.9 Hz, CHIJCH ) ), 17.79
3 2 3 2
3
1
1
(CHIJCH
3
)
2
). P{ H} NMR (162 MHz, CD
2
Cl
2
) δ 173.16. IR
−
1
−1
+
(solid, cm ): ν(CO) 1910 cm . HRMS (ESI ) m/z:
1
MeO-18c6
+
crystals (0.338 g, 98% yield). H NMR (600 MHz, CD Cl ) δ
[2
736.26212.
+ H] calcd for C H NO P 736.25957; found
27 4 8
2
2
6
4
4
.77 (d, J = 8.0 Hz, 1H, Ar–H), 6.54 (d, J = 8.0 Hz, 1H, Ar–H),
.66 (d, J = 13.5 Hz, 1H, ArCH N), 4.35 (m, 1H, crown-CH ),
2
2
.10 (dd, J = 13.5, 3.6 Hz, 1H, ArCH N), 3.98 (m, 1H, crown-
2
Catalysis using series 5000 Parr multireactor system
CH
2 3
), 3.90–3.73 (m, 6H, overlapping Ar–OCH and crown-
CAUTION: When working with CO gas, especially under high
pressures, the use of CO monitors is recommended. These ex-
periments were conducted with a personal monitor worn on
the researcher's lab coat at all times and an additional moni-
tor placed near the regulator of the CO cylinder. All catalytic
CH ), 3.75–3.45 (m, 20H, crown-CH ), 3.25 (m, 1H, crown-
2
2
CH ), 2.89 (dp, J = 14.7, 7.3 Hz, 1H, CHIJCH ) ), 2.48 (dp, J =
2
3 2
1
1
3.8, 6.9 Hz, 1H, CHIJCH
2.0, 7.2 Hz, 6H, CHIJCH ) ), 1.12 (dd, J = 19.4, 7.0 Hz, 3H,
3 2
) ), 1.31 (overlapping dd, J = 20.6,
3
2
CHIJCH ) ), 1.03 (dd, J = 16.2, 6.9 Hz, 3H, CHIJCH ) ), −19.05
3
2
3 2
3
loadings were performed in a glovebox with degassed CH -
13
1
(
1
1
d, J = 20.8 Hz, 1H, Ir–H). C{ H} NMR (151 MHz, CD
2
Cl
81.16 (d, J = 4.0 Hz, Ir–CO), 149.92 (dd, J = 5.0, 3.4 Hz, CAr),
49.57 (d, J = 3.4 Hz, CAr), 144.13 (d, J = 13.1 Hz, CAr), 140.51
2
) δ
OH. A stock solution of the desired iridium catalyst was pre-
pared in methanol such that 2 mL were added to each reactor
to reach the desired catalyst concentration of 0.34 mM. For
(d, J = 2.3 Hz, CAr), 118.05 (CAr), 110.03 (CAr), 71.70 (Ar–
1
8c6
iPr
example, 14.4 mg ( NCOP )IrIJCO) was dissolved in 12 mL
OCH ), 71.17 (ArCH N), 70.91 (crown-CH ), 70.86 (crown-
CH
CH
3
2
2
of CH OH and 2 mL of this stock solution as added of the six
3
2
2
), 70.80 (crown-CH
), 70.62 (crown-CH
2
2
), 70.74 (crown-CH
), 70.61 (crown-CH
2
2
), 70.71 (crown-
), 70.41 (crown-
3
reactors. Next, CH I was added to the reactor followed by a
stock solution of the appropriate Lewis acid or ammonium
salt. Additional methanol was added to reach a final volume
of 10 mL. The reactor and vessel heads were secured in the
CH ), 68.23 (d, J = 1.9 Hz, crown-CH ), 63.36 (crown-CH ),
2
2
2
5
9.88 (d, J = 2.3 Hz, crown-CH
2
), 56.46 (crown-CH
2
), 32.69 (d,
J = 33.2 Hz CHIJCH
3 2 3 2
) ), 29.47 (dd, J = 42.3, 1.9 Hz CHIJCH ) ),
2
box under N atmosphere, and the sealed reactors were re-
1
8.57 (d, J = 5.8 Hz, CHIJCH ) ), 18.32 (d, J = 1.7 Hz,
3
2
moved and connected to the multireactor system. The reactor
manifold was purged with CO and each vessel was subjected
to three pressurization–venting cycles (approximately 10 bar)
CHIJCH
3 2
)
), 17.69 (d, J = 3.2 Hz, CHIJCH
)
3 2
), 16.08 (d, J = 1.5
). P{ H} NMR (162 MHz, CD Cl ) δ 155.16. IR
solid, cm ): ν(CO) 2010 cm . Anal. calcd. for
31
1
Hz, CHIJCH
(
3
)
2
2
2
−
1
−1
to ensure full replacement of the N headspace with CO. The
2
C
27
H
46ClIrNO
H, 5.81; N, 2.20. HRMS (ESI ) m/z: [1
C H NO P 736.25957; found 736.25822.
8
P: C, 42.05; H, 6.01; N, 1.82. Found: C, 41.87;
vessels were then pressurized as desired and the temperature
was set utilizing the SpecView 32 software. The t = 0 of the re-
action was chosen as the time when the reactor vessels
reached their set temperature. After the given reaction time,
the vessels were allowed to cool to room temperature, then
placed further cooled in an ice bath before venting the
remaining CO slowly. Once vented, an internal NMR stan-
dard was added directly to the reaction vessel via syringe as
+
MeO-18c6
+
− Cl] calcd for
2
7
46
8
MeO-18c6
iPr
MeO-18c6
Synthesis of (
NCOP )IrIJCO) (2
)
A 20 mL scintillation vial was charged with 0.110 g (0.142
mmol) of (
MeO-18c6
iPr
NCOP )IrIJH)IJCO)IJCl) and 5 mL of benzene.
t
After 0.025 g (0.223 mmol) of KO Bu was added, the mixture
was allowed to stir for 2 h, resulting in a color change from
bright yellow to dark brown. Benzene was removed under
vacuum and the dark brown residue was stirred in 20 mL of
pentane for 48 h, yielding a bright yellow solution. The solu-
tion was filtered, removing the insoluble brown solids, and
pentane was removed in vacuo to yield a bright yellow solid
2
00 μL of a 90 : 10 t-butanol : methanol (v/v) solution. A ∼500
μL aliquot was removed and placed in an NMR tube fitted
1
with a CD
ing a delay time of 10 seconds per scan and the concentra-
tion of CH OAc and AcOH was determined by integration rel-
3
OD capillary. H NMR spectra were obtained utiliz-
3
ative to t-butanol. Turnover number (TON) values were
calculated as the moles of product (CH OAc or AcOH) divided
3
(0.042 g, 40% yield, 98% purity based on multinuclear NMR
by the moles of precatalyst added to the reactor. Turnover fre-
quency (TOF) values are TON divided by the reaction time
1
2 2
spectroscopy). H NMR (600 MHz, CD Cl ) δ 6.75 (d, J = 8.0
Hz, 1H, Ar–H), 6.46 (d, J = 8.0 Hz, 1H, Ar–H), 4.45 (s, 2H,
ArCH N), 4.40 (m, 2H, crown-CH ), 3.98 (m, 2H, crown-CH ),
(
for reactions at low conversion, typically 3 h).
2
2
2
3
.78 (s, 3H, Ar–OCH
3
), 3.72 (m, 2H, crown-CH
2
), 3.67–3.56
Low-loading NMR catalysis reactions
(m, 18H, crown-CH ), 2.28 (h, J = 7.0 Hz, 2H, CHIJCH ) ), 1.18
2 3 2
18c6
iPr
MeO-
(d, J = 7.1 Hz, 6H, CHIJCH ) ), 1.16 (dd, J = 7.0, 3.7 Hz, 6H,
Stock solutions of either
(
NCOP )IrIJCO) or
(
3
2
1
3
1
18c6
iPr
3 2 2 2
CHIJCH ) ). C{ H} NMR (151 MHz, CD Cl ) δ 198.19 (d, J =
NCOP )IrIJCO) were prepared along with stock solutions
2
.5 Hz, Ir–CO), 168.42 (d, J = 7.6 Hz, C ), 153.40 (d, J = 7.4
of Lewis acids. To each J. Young NMR tube the desired
amount of iridium catalyst or Lewis acid solution was added
Ar
Hz, C ), 145.94 (d, J = 2.7 Hz, C ), 142.98 (d, J = 13.8 Hz,
Ar
Ar
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along with 10 μL (3.23 mmol) of CH I and 50 μL of a 0.474 M
12 L. C. Gregor, J. Grajeda, M. R. Kita, P. S. White, A. J. Vetter and
A. J. M. Miller, Organometallics, 2016, 35, 3074–3086.
13 G. L. Williams, C. M. Parks, C. R. Smith, H. Adams, A. Haynes,
A. J. H. M. Meijer, G. J. Sunley and S. Gaemers, Organometallics,
2011, 30, 6166–6179.
14 C. J. Pedersen, Angew. Chem., Int. Ed. Engl., 1988, 27, 1021–1027.
15 R. M. Izatt, J. S. Bradshaw, S. A. Nielsen, J. D. Lamb, J. J.
Christensen and D. Sen, Chem. Rev., 1985, 85, 271–339.
16 M. R. Kita and A. J. M. Miller, Angew. Chem., Int. Ed., 2017, 56,
5498–5502.
3
solution of 1,1,2,2-tetrachloroethane (TCE) in CH OH as an
3
internal standard. The volume was adjusted to 500 μL total
volume with additional CH OH. The NMR tubes were
3
degassed by cooling the tube in a liquid nitrogen/hexane
bath (approx. −90 °C) and applying dynamic vacuum. The J.
Young NMR tubes were sealed and allowed to fully warm to
room temperature under static vacuum. After the degassed
tube warmed to room temperature, 1 atm CO was admitted.
The reactions were heated to 70 °C in an oil bath and moni-
1
tored by H NMR spectroscopy. “No-D” NMR spectra were
17 J. B. Smith, S. H. Kerr, P. S. White and A. J. M. Miller,
Organometallics, 2017, 36, 3094–3103.
obtained by first locking and shimming on a NMR tube of
5
00 μL pure CD OD. Next, the reaction sample (in CH OH)
18 A. J. M. Miller, Dalton Trans., 2017, 46, 11987–12000.
19 A. Haynes, J. M. Pearson, P. W. Vickers, J. P. H. H. Charmant
and P. M. Maitlis, Inorg. Chim. Acta, 1998, 270, 382–391.
3
3
was injected into the instrument for data acquisition (delay
time of 10 seconds).
2
0 R. Churlaud, U. Frey, F. Metz and A. E. Merbach, Inorg. Chem.,
2000, 39, 304–307.
Conflicts of interest
2
1 R. Churlaud, U. Frey, F. Metz and A. E. Merbach, Inorg. Chem.,
There are no conflicts to declare.
2000, 39, 4137–4142.
2
2
2
2 S. Gaemers and J. G. Sunley, US7276626, 2007.
3 S. Gaemers and J. G. Sunley, US7368597B2, 2008.
4 E. L. Carrington-Smith, D. J. Law, P. G. Pringle and J. G. Sunley,
US2010/0324332A1, 2010.
Acknowledgements
We gratefully acknowledge funding from Eastman Chemical
Company. J. G. acknowledges support from a NSF Graduate
Research Fellowship (DGE-1144081) and UNC-CH Graduate
School Dissertation Completion Fellowship. The authors
thank Dr. Steven T. Perri, Dr. Joseph Zoeller, Dr. Nathan M.
West, and Dr. Jim Ponasik for their helpful discussions. Dr.
Brandi M. Ehrmann assisted with mass spectrometry and Dr.
Marc ter Horst assisted with NMR spectroscopy.
2
2
2
2
2
5 J. Grajeda, M. R. Kita, L. C. Gregor, P. S. White and A. J. M.
Miller, Organometallics, 2016, 35, 306–316.
6 R. M. Izatt, K. Pawlak, J. S. Bradshaw and R. L. Bruening, Chem.
Rev., 1991, 91, 1721–2085.
7 R. M. Izatt, K. Pawlak, J. S. Bradshaw and R. L. Bruening, Chem.
Rev., 1995, 95, 2529–2586.
8 P. Di Bernardo, A. Melchior, M. Tolazzi and P. L. Zanonato,
Coord. Chem. Rev., 2012, 256, 328–351.
9 D. Roberto, E. Cariati, R. Psaro and R. Ugo, Organometallics,
1994, 13, 4227–4231.
References
1
A. Haynes, in Comprehensive Inorganic Chemistry II, Elsevier,
013, pp. 1–24.
2
30 J. R. Zoeller, Org. Process Res. Dev., 2016, 20, 1016–1025.
31 R. G. Pearson, J. Am. Chem. Soc., 1963, 85, 3533–3539.
32 R. G. Pearson, J. Chem. Educ., 1968, 45, 581–587.
33 K. Maruoka, Pure Appl. Chem., 2012, 84, 1575–1585.
34 J. Novacek and M. Waser, Eur. J. Org. Chem., 2013, 2013,
637–648.
2
A. Haynes, P. M. Maitlis, G. E. Morris, G. J. Sunley, H. Adams,
P. W. Badger, C. M. Bowers, D. B. Cook, P. I. P. Elliott, T.
Ghaffar, H. Green, T. R. Griffin, M. Payne, J. M. Pearson, M. J.
Taylor, P. W. Vickers and R. J. Watt, J. Am. Chem. Soc.,
2004, 126, 2847–2861.
3
A. Haynes and S. Sheffield, in Catalytic Carbonylation Reactions.
Topics in Organometallic Chemistry, ed. M. Beller, 2006, vol. 18,
pp. 179–205.
A. Haynes, Adv. Catal., 2010, 53, 1–45.
G. J. Sunley and D. J. Watson, Catal. Today, 2000, 58, 293–307.
Y. Liu, E. Lotero and J. Goodwin Jr., J. Catal., 2006, 242,
35 L. Xiao-Liang, D. Michos, R. H. Crabtree and M. B. Hall, Inorg.
Chim. Acta, 1992, 198–200, 429–435.
36 A. M. Z. Slawin, M. B. Smith and J. D. Woollins, J. Chem. Soc.,
Dalton Trans., 1996, 1283–1293.
37 A. M. Z. Slawin, M. B. Smith and J. D. Woollins, J. Chem. Soc.,
Dalton Trans., 1996, 4575–4581.
4
5
6
2
78–286.
38 V. J. Scott, L. M. Henling, M. W. Day, J. E. Bercaw and J. A.
Labinger, Organometallics, 2009, 28, 4229–4230.
39 D. Roberto, E. Cariati, R. Psaro and R. Ugo, Organometallics,
1994, 13, 4227–4231.
7
8
9
B. Bessling, J.-M. Löning, A. Ohligschläger, G. Schembecker and
K. Sundmacher, Chem. Eng. Technol., 1998, 21, 393.
S. Lux, T. Winkler and M. Siebenhofer, Ind. Eng. Chem. Res.,
2
010, 49, 10274–10278.
40 O. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard and
H. Puschmann, J. Appl. Crystallogr., 2009, 42, 339–341.
41 L. J. Bourhis, O. V. Dolomanov, R. J. Gildea, J. A. K. Howard and
H. Puschmann, Acta Crystallogr., Sect. A: Found. Adv., 2015, 71,
59–75.
J. H. Kwak, R. Dagle, G. C. Tustin, J. R. Zoeller, L. F. Allard and
Y. Wang, J. Phys. Chem. Lett., 2014, 5, 566–572.
1
0 M. R. Kita and A. J. M. Miller, J. Am. Chem. Soc., 2014, 136,
4519–14529.
1 J. B. Smith and A. J. M. Miller, Organometallics, 2015, 34,
669–4677.
1
1
42 G. M. Sheldrick, Acta Crystallogr., Sect. A: Found. Crystallogr.,
2007, 64, 112–122.
4
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