Decarbonylative ether dissection by iridium pincer complexes

Article abstract of DOI:10.1039/d0sc03736b

A unique chain-rupturing transformation that converts an ether functionality into two hydrocarbyl units and carbon monoxide is reported, mediated by iridium(i) complexes supported by aminophenylphosphinite (NCOP) pincer ligands. The decarbonylation, which involves the cleavage of one C-C bond, one C-O bond, and two C-H bonds, along with formation of two new C-H bonds, was serendipitously discovered upon dehydrochlorination of an iridium(iii) complex containing an aza-18-crown-6 ether macrocycle. Intramolecular cleavage of macrocyclic and acyclic ethers was also found in analogous complexes featuring aza-15-crown-5 ether or bis(2-methoxyethyl)amino groups. Intermolecular decarbonylation of cyclic and linear ethers was observed when diethylaminophenylphosphinite iridium(i) dinitrogen or norbornene complexes were employed. Mechanistic studies reveal the nature of key intermediates along a pathway involving initial iridium(i)-mediated double C-H bond activation. This journal is

Full text of DOI:10.1039/d0sc03736b

View Article Online
View Journal
Chemical
Science
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: C. Yoo, H. M.
Dodge, A. Farquhar, K. E. Gardner and A. J. M. Miller, Chem. Sci., 2020, DOI: 10.1039/D0SC03736B.
Volume
Number
9
1
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
7
January 2018
Pages 1-268
Chemical
Science
Accepted Manuscripts are published online shortly after acceptance,
before technical editing, formatting and proof reading. Using this free
service, authors can make their results available to the community, in
citable form, before we publish the edited article. We will replace this
Accepted Manuscript with the edited and formatted Advance Article as
soon as it is available.
rsc.li/chemical-science
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes to the
text and/or graphics, which may alter content. The journal’s standard
Terms & Conditions and the Ethical guidelines still apply. In no event
shall the Royal Society of Chemistry be held responsible for any errors
or omissions in this Accepted Manuscript or any consequences arising
from the use of any information it contains.
ISSN 2041-6539
EDGE ARTICLE
Xinjing Tang et al.
Caged circular siRNAs for photomodulation of gene
expression in cells and mice
rsc.li/chemical-science

Page 1 of 9
PleaseCdhoemnoictaal dScjuiesntcmeargins
View Article Online
DOI: 10.1039/D0SC03736B
EDGE ARTICLE
Decarbonylative Ether Dissection by Iridium Pincer Complexes
Changho Yoo, Henry M. Dodge, Alexandra H. Farquhar, Kristen E. Gardner, and Alexander J. M.
Miller*
Received 00th January 20xx,
Accepted 00th January 20xx
A unique chain-rupturing transformation that converts an ether functionality into two hydrocarbyl units and carbon
monoxide is reported, mediated by iridium(I) complexes supported by aminophenylphosphinite (NCOP) pincer ligands. The
decarbonylation, which involves the cleavage of one C–C bond, one C–O bond, and two C–H bonds, along with formation of
two new C–H bonds, was serendipitously discovered upon dehydrochlorination of an iridium(III) complex containing an aza-
18-crown-6 ether macrocycle. Intramolecular cleavage of macrocyclic and acyclic ethers was also found in analogous
complexes featuring aza-15-crown-5 and bis(2-methoxyethyl)amino groups. Intermolecular decarbonylation of cyclic and
linear ethers was observed when diethylaminophenylphosphinite iridium(I) dinitrogen or norbornene complexes were
employed. Mechanistic studies reveal the nature of key intermediates along a pathway involving initial iridium(I)-mediated
double C–H bond activation.
DOI: 10.1039/x0xx00000x
intermediate, (PNP)Ir=C(H)(OtBu), that undergoes isobutene
elimination.
Introduction
Decarbonylation reactions, which release carbon monoxide
(CO) from organic compounds, are widely utilized in organic
synthesis, biomass valorization, and on-demand carbon
monoxide reagent generation.1–7 The emergence of catalytic
decarbonylation methodologies can be traced back to seminal
discoveries of stoichiometric transformations. In 1965, Tsuji and
Ohno reported that a rhodium complex can effect the
stoichiometric decarbonylation of aldehydes to form rhodium
carbonyl complexes (Scheme 1).8 Subsequent development of
catalytic decarbonylation reactions has enabled a range of
synthetic methods that utilize aldehydes as precursors to
alkanes and alkenes, as cross-coupling reaction partners, and as
reagents in transfer hydroformylation.1,3,4,9,10 In 1980,
Yamamoto and coworkers reported the stoichiometric
decarbonylation of esters by nickel complexes, forming nickel
carbonyl complexes and alcohols.11 This reaction has also
subsequently been developed into impressive catalytic
reactions, including cross-coupling with ester precursors and
biomass upgrading reactions.1–3,5 Decarbonylation reactions are
dominated by organic carbonyl substrates; CO release from
other organic compounds is rare (and often still proceeds via
carbonyl intermediates, as in alcohol decarbonylation initiated
by dehydrogenation to form an aldehyde).6,7
Scheme 1. Leading examples of transition metal-mediated decarbonylation.
Tsuji and Ohno, 1965
PPh3
Ph3P Rh Cl
PPh3
PPh3
OC Rh Cl
PPh3
O
C
+
RH + PPh3
+
R
H
Yamamoto, 1980
PPh3
Ni
O
C
Ni(COD)2
+
3 PPh3
+
+
ArOH
H
+ C2H4
Ar
PPh3
OC
O
PPh3
Grubbs, 2008
PiPr2
H
PiPr2
O
N
O
Ir
+
N
Ir CO
+
+ H2
H3C
H
PiPr2
–
P
iPr2
H
This work
PiPr2
O
PiPr2
MeO
MeO
H2
C
Ir
NEt2
L
Ir CO
NEt2
R1
H
R2
+
H
+
R2
+
R1
O
Here we present a unique ether decarbonylation reaction
that selectively dissects a wide range of ethers, cleaving two C–
H bonds, one C–C bond, and one C–O bond, and forming two
new C–H bonds to furnish CO and two saturated hydrocarbyl
groups. Intramolecular decarbonylation of crown ether groups
is described first, followed by extensions to intermolecular
reactions. Mechanistic studies provide insight into key
intermediates and implicate amine hemilability in controlling
the reaction pathway.
Despite the prevalence of ether functionalities in synthetic
intermediates and in biomass, only one example of ether
decarbonylation has been reported. Romero, Whited, and
Grubbs found that a pincer iridium complex reacted with
MeOtBu to generate a carbonyl complex, isobutene, and H2
(Scheme 1).12 The stoichiometric reaction is initiated by double
C–H bond activation of MeOtBu to generate H2 and a carbene
Results and discussion
Intramolecular ether decarbonylation. Preliminary
evidence for decarbonylation reactivity was discovered
serendipitously while attempting to prepare an iridium(I)
complex with
a pincer-crown ether ligand. The yellow
a. Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill,
North Carolina 27599-3290, United States
Email: ajmm@email.unc.edu
Electronic Supplementary Information (ESI) available: CDC 2014654, 2014655,
2014656, 2014657. For experimental details, characterization data, and
crystallographic details, see DOI: 10.1039/x0xx00000x
Please do not adjust margins

PleaseCdhoemnoictaal dScjuiesntcmeargins
Page 2 of 9
ARTICLE
Chemical Science
iridium(III) precursor (MeO-18c6NCOP)Ir(H)(Cl) (118c6, Figure 1) was combination of multidimensional NMR experiments, including
View Article Online
1
1
1
13
1
13
DOI: 10.1039/D0SC03736B
obtained from the reaction of the known pincer-crown ether
H- H COSY, H- C HSQC and H- C HMBC (Figure S38-40, ESI).
ligand
(
MeO-18c6NCOP)H13 and [Ir(COD)Cl]2. All of the The presence of a carbonyl ligand provided an additional
spectroscopic data for 118c6 aligned with expectations for a surprise, revealed by inspection of 13C NMR spectra (δ 198.75)
hydridochloride complex with a single crown ether oxygen and infrared (IR) spectra (nCO = 1931 cm–1). On the basis of the
donating to complete an octahedral coordination environment. combined spectroscopic data, along with electrospray
The solid-state structure elucidated from an X-ray diffraction ionization mass spectrometry (ESI-MS) data, the product was
study confirmed the expected tetradentate (k
4) pincer ligand assigned as an iridium(I) carbonyl with the ligand crown ether
binding mode, with one crown ether oxygen bound trans to the decarbonylated (218c6, Figure 1B). 218c6 was isolated in 90% yield
hydride ligand (Figure 1A). The bond distances and angles are in a preparative-scale experiment.
essentially indistinguishable from the previously characterized
15-crown-5-containing variant.14
To probe the generality of this reaction, other iridium
complexes containing pendent ethers were examined. The
Base-promoted dehydrochlorination was attempted in known aza-15-crown-5 complex (MeO-15c5NCOP)Ir(H)(Cl) (115c5
)
pursuit of an iridium(I) complex, inspired by similar procedures was prepared as previously described.19 Dehydrochlorination of
developed for other pincer iridium complexes.12,15–17 Addition 115c5 with NaHMDS at 80 °C also resulted in intramolecular
of NaHMDS to a yellow solution of 118c6 in C6D6 at ambient decarbonylation (Figure 1), producing an iridium(I) carbonyl
temperature resulted in an immediate color change to brown species with activated crown ether moiety (215c5), which was
and the appearance of multiple species in the 31P NMR isolated in 68% yield and was spectroscopically almost identical
spectrum. After heating the mixture at 80 °C for 1 h, however, to the 18-crown-6-derived variant.
the solution turned yellow and only a single resonance was
apparent in the 31P NMR spectrum, δ 171.32.
An acyclic ligand variant containing
methoxyethyl)amine fragment was accessed by reductive
The absence of a hydride resonance in the 1H NMR spectrum amination of iso-vanillin followed by phosphination withiPr2PCl.
a
bis(2-
MeO-
and a ca. 30 ppm upfield shift of the phosphinite resonance Subsequent metalation with [Ir(COD)Cl]2 afforded
(
relative to 118c6 (from δ 143.67 to δ 171.32) in the 31P NMR BMENCOP)Ir(H)(Cl) (1BME). The crystallographically determined
spectrum provided an early indication that the product was an solid-state structure of 1BME shows the expected k4 binding
iridium(I) complex.13,18 We initially vetted the spectroscopic mode, with one methoxy group ligating iridium (Figure 2A). The
data against the possibility of iridium(I) complexes with either distances and angles around the iridium center are very similar
(a) a tetradentate pincer-crown ether ligand containing one to those of 118c6, but an overlay of 118c6 and 1BME reveals subtle
crown ether oxygen bound, (k4
tridentate pincer-crown ether ligand with N2 completing the the macrocycle providing
square planar coordination sphere, (k3 MeO-18c6NCOP)Ir(N2). environment around the metal center (Figure S69 in the SI).
However, neither of these structures could be explained by the In contrast to the perfectly selective decarbonylative
-
MeO-18c6NCOP)Ir, or (b) a shifts in the chloride ligand and isopropyl groups consistent with
a
more sterically crowded
-
NMR data. In particular, a distinctive triplet (δ 1.09) and singlet macrocycle dissection in the pincer-crown ether complexes,
(δ 2.90) were present in the 1H NMR spectrum, while the crown treatment of 1BME with base followed by heating at 80 °C
ether region did not account for all of the expected protons produced two products in a 7:3 ratio (Figure 2). The major
(Figure 1D). The new triplet and singlet were assigned as species (3BME) contains an ethylamine, as characterized by a
unexpected –OCH2CH3 and –NCH3 groups, respectively, using a
H
O
N
MeO
O
N
MeO
PiPr2
PiPr2
(B)
NaHMDS
(A)
Ir Cl
Ir
C
β
O
O
C6D6
80 ºC, 1 hr
O
O
H1
O
CH2-H
δ
α
H-CH2
O
δ
ε
n
C
α
β
H2
O
ε
118c6 (n = 2)
15c5 (n = 1)
218c6 (n = 2, 90% yield)
215c5 (n = 1, 68% yield)
P1
O
1
n
C6
Ir1
O3
(C)
N1
Cl1
β
α
δ
β
α
ε
ε
δ
α
δ
(D)
ε
5
4
3
2
1
-31
1H (ppm)
Figure 1. (A) Structural representation of 118c6 with ellipsoids drawn at 50% probability level. (B) Decarbonylation of 118c6 and 115c5. (C) Partial 1H NMR spectrum of
118c6. (D) Partial 1H NMR spectrum of 218c6
2 | Chem. Sci., 2020, 00, 1-3
.
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 9
Chemical Science
Please do not adjust margins
Chemical Science
ARTICLE
View Article Online
DOI: 10.1039/D0SC03736B
PiPr2
O
N
MeO
+
H2
Ir
CO
δ
(A)
(B)
H
α
PiPr2
O
PiPr2
β
O
N
O
MeO
MeO
H1
3BME
(73% yield)
NaHMDS
O
Ir
Ir
Ir Cl
δ
C6D6
RT
3 hr
C6D6
80 °C
1 hr
P1
α
β
N
PiPr2
O
C6
N1
O
MeO
δ
O
Ir1
α
O
β
+
CH4
δ
Cl1
CO
β
1BME
N
α
O4
2BME
(27% yield)
O
Figure 2. (A) Structural representation of 1BME with ellipsoids drawn at 50% probability level. (B) Decarbonylation of 1BME
.
triplet (δ 1.30) and quartet (δ 3.17) that are correlated in 1H-1H
The reaction of acyclic variant 1BME with NaHMDS in C6D6
COSY experiments. This reaction could be balanced by loss of was monitored over time in a sealed NMR tube at room
H2, which was detected by analyzing headspace using gas temperature. After 5 h, 1BME was converted to a single new
1
chromatography (GC). Although peak overlaps prevented full species, which did not have any hydride resonances in the H
1
characterization, the minor species (2BME) is tentatively assigned NMR spectra. The H NMR spectrum reflects an asymmetric
as the decarbonylation product containing a methylamine geometry consistent with one methoxy group bound to the
-
group. Both H2 and CH4 were observed in solution as byproducts iridium center, (k4 MeO-BMENCOP)Ir (Figure 2). The geminal
in these sealed NMR tube experiments.
protons in the methoxyethyl groups are diastereotopic with
Mechanistic Studies. The new ether decarbonylation chemical shift differences in the range of 0.03-0.61 ppm,
reaction ruptures the crown ether ring by cleavage of two C–H consistent with a constrained geometry in close proximity to the
bonds, one C–C bond, and one C–O bond, as well as formation metal center (Figure S54-58).20 A strong correlation between
of two C–H bonds. The formerly macrocyclic aza-crown ether is the phosphorus and one (and only one) methyl of a
thus transformed into a linear poly(ether) with a methylamine methoxyethyl group in a 1H-31P HMBC experiment provides
terminus bound to an iridium carbonyl. To our knowledge, the additional evidence for ether ligation (Figure S57). NOESY data
formation of two saturated hydrocarbyl end groups by ether revealed a slow chemical exchange process between two
decarbonylation is an unprecedented transformation.
methoxyethyl groups (Tmix = 320 ms, 298 K, Figure S58), and
Initial insight into the reaction mechanism can be gleaned dipole-dipole coupling between the isopropyl protons and the
from the identity of the product, which reflects the bonds that methoxy protons of one amine substituent. This intermediate
have been broken and formed. In both macrocyclic complexes was stable at room temperature for 2 days. Heating this
118c6 and 115c6, the Ca–Cβ bond of the macrocycle (Figure 1) is intermediate at 80 °C for 1 h gave carbonyl complexes 2BME and
selectively activated (among multiple possible sites) to produce 3BME
.
a methylamine-containing product. The ethylamine-containing
The different intermediates detected in these experiments
product 3BME (Figure 2) would derive from decarbonylation of are consistent with initial formation of a reactive iridium(I)
the methoxy end group and release of H2 as a byproduct, with species that undergoes C–H bond activation prior to
the CO carbon derived from the
d
position in 1BME. The overall decarbonylation. The presence of multiple C–H bond activation
bond-breaking and bond-forming events involved in the products in initial spectra, which eventually funnel to a single
formation of minor product 2BME are analogous to the crown decarbonylation product, suggests rapid equilibria between C–
ether-containing reactions, with Ca–Cβ bond cleavage leading to H activation products at 80 °C. We hypothesize that the
the formation of CH4, which was present in 1H NMR spectra. The geometric constraints in the macrocyclic ligand lead to faster C–
difference in products for macrocyclic and acyclic ethers is H bond activation than the acyclic variant.
striking, with exclusive formation of N-methyl products for
Based on an initial C–H bond activation, we considered two
macrocyclic NCOP complexes and predominant formation of N- mechanisms for the decarbonylation reaction, shown in Scheme
ethyl products for the acyclic variants. The differing selectivity 2. Both mechanisms start with C–H bond activation to form an
could be due to the presence of a methoxy group only in the alkyl hydride intermediate. In the first mechanism (Path A), the
acyclic case, or perhaps due to the different steric profiles (c.f. alkyl intermediate undergoes α-hydrogen migration to generate
X-ray overlay in Figure S69).
an alkoxycarbene, followed by hydride transfer to the alkoxy
Further mechanistic insight was gleaned from in situ group on the carbene to generate a free hydrocarbyl-containing
monitoring to probe for reaction intermediates. Treating 118c6 organic product and an acyl iridium complex. Alkyl migration
with NaHMDS gave rise to four resonances in the hydride region would then produce a carbonyl alkyl hydride complex that
1
of H NMR spectra, which persisted over the course of 10 h at undergoes reductive elimination to furnish the final products. In
room temperature. After heating at 80 °C for 1 h, all the hydride the second mechanism (Path B), the initial alkyl intermediate
species disappeared, replaced by the carbonyl complex 218c6
.
undergoes
a-alkoxy migration followed by β-hydride
The complex with the smaller macrocycle, 115c5, followed an elimination to generate an aldehyde, which would then
essentially identical course. These results are consistent with undergo decarbonylation.
initial C–H bond activation.
This journal is © The Royal Society of Chemistry 20xx
Chem. Sci., 2020, 00, 1-3 | 3
Please do not adjust margins

PleaseCdhoemnoictaal dScjuiesntcmeargins
Page 4 of 9
ARTICLE
Chemical Science
View Article Online
DOI: 10.1039/D0SC03736B
Scheme 2. Possible mechanism for decarbonylation.
CH2R2
CO
deinsertion
H
H
R1
(NCOP)Ir
CO
α-Hydrogen
Red.
Elim.
Hydride
transfer
OCH2R2
R1
O
O
migration
(NCOP)Ir
C
(NCOP)Ir
C
(NCOP)Ir
C
H
(NCOP)Ir CO
– R2CH2H
– R1H
R1
R1
H
H
H
Path A
alkyl
migration
Red.
Elim.
H
O
R2
C-H
2 activation
(κ2-NCOP)Ir
C
CH
OCH2R2
– R2CH2H
R2H2C
R1
(NCOP)Ir
O
H
(NCOP)Ir
H
CH2
R1
R1
H
R2
R2
H
+
C
O
Path B
H
H
OCH2R2
H
H
R2
C
Aldehyde
decarbonylation
α-Alkoxy
migration
1,2-Hydride
migration
β-Hydride
elimination
Red.
Elim.
R2
O
(NCOP)Ir
H
H
(NCOP)Ir CO
(NCOP)Ir
C
(NCOP)Ir CH2R1
(NCOP)Ir
(NCOP)Ir
O
C
OCH2R1
– R1CH2H
– R2H
R1
H
Nonproductive
C-H activations
H
CH2R1
The two possible pathways of Scheme 2 are considered decarbonylation reactions, an analogous diethylamino-NCOP
based on the closest literature analogues that could be ligand was utilized in order to isolate iridium(I) species without
identified. The most relevant reaction sequence was reported ligand activation. Metalation of the known diethylamine-
by Grubbs and coworkers, Scheme 3A, where initial C–H bond containing ligand, (EtNCOP)H,41 with [Ir(COD)Cl]2 was initially
activation of the methyl group of MeOtBu is followed by α- attempted, but this gave multiple species, presumably due to
hydrogen elimination to form a carbene.12,21–28 The (PNP)Ir the undesired metallation ortho to the phosphinite. The new
system rapidly generated H2 after C–H activation and
elimination, leaving coordinatively
unsaturated procedure similar that employed in the synthesis of (MeO-
alkoxycarbene, Ir=C(H)(OtBu), that generated isobutene BMENCOP)H and metallated to form [(MeO-EtNCOP)Ir(H)(Cl)]2 (1Et).
a
-H methoxy-substituted ligand (MeO-EtNCOP)H was prepared by a
a
through
d
-hydride elimination.12
The hydride resonance (δ –38.94 in C6D6) in the 1H NMR
spectrum is slightly downfield of other square pyramidal iridium
hydridochloride complexes possessing a vacant coordination
site trans to the hydride.12,42–47 Complex 1Et is poorly soluble in
CH2Cl2 and benzene, but highly soluble nature in coordinating
solvents (THF and MeCN), which suggested that 1Et might adopt
a dimeric structure in the absence of coordinating solvents. An
, grown from
CH2Cl2/pentane, revealed a diiridium complex with two bridging
chloride ligands each sitting trans to hydride.
Dehydrochlorination of 1Et by NaHMDS under N2 cleanly
generated a new iridium complex. The hydride resonance
completely disappeared in 1H NMR spectra and the phosphinite
resonance was shifted ca. 20 ppm upfield relative to 1Et (from δ
143.67 to δ 163.66), indicating formation of the iridium(I)
species. The same reaction under Ar resulted in formation of
multiple unidentified hydride species, raising the possibility of
Scheme 3. Iridium(I)-mediated ether activation via C–H activation
(A) α-Hydrogen migration
α-hydrogen
migration
δ-hydride
elimination
CO
deinsertion
O
OtBu
H
H
(PNP)Ir CO
H
O
H
O
H
tBu
(PNP)Ir
(PNP)Ir
(PNP)Ir
(PNP)Ir
- H2
–
H
(B) α-Alkoxy migration
α-alkoxy
migration
1,2-Hydride
migration
O
OPh
OPh
X-ray diffraction study of crystals of 1Et
Ph
(PCP)Ir
(PCP)Ir
(PCP)Ir CH2
H
(PCP)Ir OPh
CH3
H
(C) β-Alkoxy migration
O
Ph
R
Ph
β-alkoxy
migration
O
OPh
(PCP)Ir
H
R
R
(PCP)Ir
(PCP)Ir
(PCP)Ir OPh
H
–
R
H
iPr2P
Ir
iPr2 P
Ir
PiPr2
PiPr2
N
(PNP)Ir
=
(PCP)Ir =
Alkoxy migration also occurs in iridium-mediated net C–O
oxidative addition reactions of ethers.29–36 As shown in Scheme
3B and 3C, the reactions developed by the Goldman group
undergo initial C–H bond activation, but alkoxide elimination
occurs (either α- or β-elimination depending on the site of C–H
activation) preferentially to α-hydrogen elimination for the
(PCP)Ir system.28,34–40 Although decarbonylation was not
observed in the examples of Scheme 3B and 3C, these phenyl
N2 coordination. The ion peaks observed by ESI-MS revealed the
1
N2-bridged dimer [(MeO-EtNCOP)Ir]2(μ-N2) (
4
, Figure 3). The H
NMR spectrum of 4 is consistent with C2-type symmetry and the
presence of a bridging N2 ligand in the solid state was confirmed
by resonance Raman spectroscopy (νNN = 2017 cm–1). No
solution IR stretch corresponding to a terminal N2 complex was
observed. The bridging N2 ligand in
to similar pincer iridium(I) N2 complex [(PCP)Ir]2(μ-N2) (1979
cm–1).48 Complex
was isolated in 56% yield and can be stored
4 is less activated compared
ether substrates could not undergo the b-hydride elimination as
an alkyl ether would in Path B in Scheme 2.
4
as a solid under N2, but underwent 60% decomposition after 15
days at room temperature in C6D6.
The particular elimination process that follows formation of
the alkyl intermediate seems to control the selectivity between
decarbonylation, dehydrogenation, or C–O oxidative addition
pathways. Additional studies to distinguish between the
pathways of Scheme 2 are presented in intermolecular
reactions below.
Isolation of iridium(I) dinitrogen and norbornene
complexes. With the goal of exploring intermolecular
4 | Chem. Sci., 2020, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 9
Chemical Science
Please do not adjust margins
Chemical Science
ARTICLE
View Article Online
DOI: 10.1039/D0SC03736B
(B)
(A)
(C)
NaHMDS
N2
PiPr2
N
PiPr2
Et2N
O
MeO
O
MeO
H1
Ir1
CO
Ir
NEt2
N
Ir
Ir CO
H
P1
C6
N1
toluene
RT, 1hr
PiPr2
C6D6
O
MeO
iPr2P
O
P1
Ir1
OMe
Cl1
NEt2
Et2
C20
C19
Ir Cl
N
6Et
4
0.5
N
Et2
Cl Ir
P
C6
PiPr2
NaHMDS
norbornene
O
MeO
OMe
O
CO
C6D6
iPr2
H
Cl1’
Ir
N1
toluene
RT, 1hr
1Et
NEt2
5
Figure 3. (A) Structural representation of 1Et and (B) 5 with ellipsoids drawn at 50% probability level. (C) Synthesis of iridium(I) complexes.
Seeking
dehydrochlorination of 1Et was performed in the presence of dinitrogen complex
norbornene. The norbornene adduct (MeO-EtNCOP)Ir(NBE) (
heating benzene solutions at 80 °C for 24 h in Teflon-sealed
Figure 3) was isolated in 90% yield. The bound norbornene NMR tubes. Table 1 summarizes the results. In each case,
ligand was clearly indicated by NMR spectroscopic data and X- carbonyl complex was observed, with the yield varying as a
ray diffraction study (Figure 3). Complex is somewhat more function of ether identity and concentration. The yield of
stable than , undergoing just 15% decomposition after 15 days carbonyl complex
was measured by quantitative 31P NMR
a
more thermally stable iridium(I) synthon, Intermolecular Ether Decarbonylation. The reactivity of
4
with various ethers was explored by
5,
6
5
4
6
at room temperature in C6D6. Both N2 and norbornene ligands spectroscopy using triphenyl phosphate as an internal standard.
can be replaced upon addition of CO to give (MeO-EtNCOP)Ir(CO) The organic products were analyzed by NMR spectroscopy and
(
6) quantitatively.
headspace GC.
The activation of macrocyclic ethers resulted in formation of
linear poly(ether) products and the corresponding Ir carbonyl
complex 6. Di- and tetra(ethylene glycol) ethyl methyl ether
Table 1. Intermolecular ether decarbonylation by 4.
were obtained from the decarbonylation of 12-crown-4 and 18-
crown-6, respectively. The yield of poly(ether) product was
similar to that of (MeO-EtNCOP)Ir(CO), as expected.
PiPr2
O
MeO
PiPr2
N
Et2N
Ir
O
MeO
H2
C
1/2
Ir
N
+
R2
Ir CO
+
R1
H
+
R2
H
R1
O
C6D6
80 °C, 24 hr
iPr2P
O
OMe
NEt2
NEt2
4
6
Intermolecular reactions of linear ethers produced two
Ether/
4
6
Organic
product
Organic
yielde
n.q.f
37%g
n.q.
23%g
n.q.
n.q.
saturated hydrocarbyl coproducts. Treating glyme with
4
Ether
Ratioa
yieldcd
produced carbonyl complex along with methane and dimethyl
6
O
1
10
1
10
10
530b
10
5%
42%
3%
26%
2%
10%
7%
18%
67%
5%
ether. Grubbs and coworkers only reported ether
decarbonylation of MeOtBu, so this substrate is an important
point of comparison. The prior study converted MeOtBu to
isobutene and a dihydridocarbonyl complex.12 In contrast,
O
18-crown-6
12-crown-4
4
O
O
2
O
complex
carbonyl complex
comprehensive studies of other substrates, the MeOtBu
experiment effectively rules out -alkoxide migration and
suggests that Path B of Scheme 2 is not operative. An -alkoxide
migration would produce tert-butoxide intermediate
4
reacts with MeOtBu to produce isobutane, H2, and
Although low yields precluded
O
+
CH4
O
6.
8%h
O
100
450b
10
15%h
67%h
n.q.
+
H2
a
a
O
Not detected
Not detected
a
530b
15%
n.q.
incapable of β-hydrogen elimination. The fact that the reaction
still produces an iridium carbonyl product suggests that a
pathway featuring a-hydrogen migration is likely operative, as
shown in Path A in Scheme 2. The extreme steric congestion of
a putative IrV-tBu complex that would be formed by alkyl
migration suggests that the hydride transfer route of Path A
may be more likely.
Even simple ethers like Et2O and THF can be decarbonylated
by 4, albeit in low yield (Table 1). Although double C–H bond
activation of THF is commonly observed at iridium
complexes,25,26,37–40,49 no stable alkoxycarbene species was
observed in the THF reactions.
O
680b
10
2%
n.q.
n.q.
O
O
n
21%
O
O
n-1
(Mn ~ 250 Da)
a Amount of ether relative to one iridium center. b The substrate was used as
a solvent. c Yield of
6 4 used.
obtained from quantitative 31P NMR relative to
d >99% of
4
was consumed for all cases. e Yield of organic product relative to
f
g
4
used. not quantified due to low yield of
quantitative 13C NMR. h Yield of (HC(CH3)3) obtained from quantitative 1H
NMR.
6
.
Yield obtained from
Considering current interest in polymer degradation and
recycling, we also tested the poly(ether) substrate
This journal is © The Royal Society of Chemistry 20xx
Chem. Sci., 2020, 00, 1-3 | 5
Please do not adjust margins

PleaseCdhoemnoictaal dScjuiesntcmeargins
Page 6 of 9
ARTICLE
Chemical Science
with norbornene complex (MeO-EtNCOP)Ir(NBE) (
4 5). We VhieywpoArttihcleesOinzleinde
poly(ethylene glycol), PEG (Table 1). The reaction of
methyl-terminated PEG (Mn ~ 250 Da) resulted in 21% yield of that the improved thermal stability of norbornene adduct
iridium carbonyl . The PEG sample employed was dominated relative to (60% decomposition vs. complete decomposition
DOI: 10.1039/D0SC03736B
5
6
4
by pentamer, hexamer and heptamer peaks observed by in 6 h at 80 °C) would lead to higher yields of the desired
atmospheric pressure chemical ionization mass spectroscopy. products. The results are summarized in Table 2. While complex
No trimer or tetramer peaks were apparent initially. After
treatment with complex , however, new peaks for trimer and in a similar fashion to
tetramer appeared in the mass spectrum, indicating successful were observed during glyme and diethyl ether activation.
5
decarbonylates the macrocycles 18-crown-6 and 12-crown-4
4
4, higher yields of carbonyl complex
6
decarbonylation (Figure S62 in the SI).
A complex with a pincer ligand of renowned stability,
[(PCP)Ir]2(μ-N2) (
),48 was also examined. (PCP)Ir platforms
7
Table 2. Intermolecular ether decarbonylation using Ir(I) pincer complexes.
exhibit exceptional stability at high temperatures, as
established in studies of alkane dehydrogenation,50 and we
observed no significant decomposition after 5 days at 80 °C in
the presence of Et2O. Furthermore, (PCP)Ir complexes facilitate
H2
C
[Ir]
[Ir] CO
R1
H
+
R2
H
+
+
R2
R1
O
C6D6
80 °C, 24 hr
MeO
PiPr2
PiPr2
N
Et2N
Ir
tBu
Ir
PtBu2
N
2P
O
O
MeO
Ir
net C–O oxidative addition of a range of substrates34–36
although there are no reports of ether decarbonylation with this
system. Surprisingly, reactions of complex with 18-crown-6,
—
Ir
NEt2
N
Ir
PtBu2
N
iPr2
P
O
P
tBu2
OMe
NEt2
4
5
7
7
12-crown-4, and glyme produced (PCP)Ir(CO) in poor yield
(Table 2). There was no detectable conversion with Et2O. Even
in cases where (PCP)Ir(CO) was formed, only trace amounts of
decarbonylated organic product (<1% yield) were detected. The
diphosphine-based pincer complex is thus essentially unable to
carry out the chemistry observed for the aminophosphinite-
based complexes, despite excellent stability.
The distinct reactivity of (NCOP)Ir and (PCP)Ir complexes
suggests a possible role of amine hemilability in determining the
selectivity of ether decarbonylation. In the intramolecular
reactions, amine dissociation seems inevitable in order to
accommodate appropriate conformations for C–H bond
activation and subsequent elimination reactions. In
intermolecular reactions, amine dissociation could facilitate
alkyl migration (lower route of Path A in Scheme 2) or provide
flexibility needed for the bulky alkoxy(alkyl)carbene complex to
achieve the appropriate conformation for hydride transfer
(upper route of Path A in Scheme 2). However, influences of
steric (isopropyl/ethyl vs. tert-butyl) or electronic differences of
the pincer ligands cannot be completely ruled out.51
Conversion
of SM
Yield of
carbonyl
Yield of
organic
Ir
4
substrate
18-crown-6
(10 eq.a)
12-crown-4
(10 eq.a)
Glyme
>99%
>99%
>99%
>99%
>99%
>99%
>99%
>99%
35%
42%
26%
10%
15%
42%
27%
39%
34%
12%
3%
37%
23%
-
(530 eq.ab)
Et2O
-
(530 eq.ab)
18-crown-6
(10 eq.a)
12-crown-4
(10 eq.a)
Glyme
49%
23%
5
7
-
(530 eq.ab)
Et2O
-
(530 eq.ab)
18-crown-6
(10 eq.a)
12-crown-4
(10 eq.a)
Glyme
trace
67%
trace
76%
11%
<1%
-
-
(530 eq.ab)
Et2O
The studies comparing different iridium precursors provide
some insight into the low yields of the intermolecular reactions.
<1%
(530 eq.ab)
With complexes
4 and 5, the yield is limited by background
Amount of ether relative to one iridium center. b The substrate was used as a
solvent. Yield of (L)Ir(CO) obtained from quantitative 31P NMR relative to
used. Consumption of the iridium compound from quantitative 31P NMR
relative to the initial amount of the iridium compound used. e Yield obtained
from quantitative 13C NMR.
a
decomposition of the iridium complexes. With complex
6,
c
4
stability is achieved but the desired reaction is not observed.
These results guide research towards new ligand motifs that
include hemilabile amine donors with improved stability.
The formation of stable carbonyl adducts represents
another limitation that must be overcome to achieve catalysis.
Importantly, the stabilization conferred by CO binding to iridium
is not required to drive the decarbonylation reactions. The ether
decarbonylation reactions of Scheme 4 are estimated to be
exergonic under standard conditions (Table S1 and S2, ESI).
Methods to promote CO discoordination52 or tandem reactions
that consume CO6,7,10 could be explored in future work aimed at
achieving catalytic turnover. Considering the broad utility of
decarbonylation methods based on aldehydes, esters, and
alcohols, new catalytic ether decarbonylation reactions could
find utility in distinct biomass conversion schemes, in cross-
coupling of ethers, and other applications.1–7
d
The yield of the carbonyl complex generally increased with
increasing concentration of substrate (Table 1). We
hypothesized that the higher concentrations of substrate
promoted productive reactivity, outcompeting background
degradation of the complex (complete decomposition observed
after heating at 80 °C for 6 h in the absence of substrate).
Considering that the poor stability of
4 under the reaction
conditions was likely a primary contributor to the low yields for
intermolecular reactions, we explored different iridium
precursors.
In an attempt to improve the yield of decarbonylation, we
tested intermolecular reactions between ethers and the
6 | Chem. Sci., 2020, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 7 of 9
Chemical Science
Please do not adjust margins
Chemical Science
ARTICLE
thank Andrew M. Camp for assistance with NMR spectroscopy.
View Article Online
DOI: 10.1039/D0SC03736B
We acknowledge Dr. Chun-Hsing (Josh) Chen, Director of the
Department of Chemistry X-ray Core Laboratory, and Quinton J.
Bruch for assistance with crystallography.
Scheme 4. Thermodynamics of ether decarbonylation53–56
O
CO + CH4 + C2H6
∆Gº298K = –29 kcal/mol
O
CO + H2
+
∆Gº298K = –9.1 kcal/mol
Notes and references
1
X. Zhang, F. Jordan and M. Szostak, Org. Chem. Front.,
2018, 5, 2515–2521.
2
L. Guo and M. Rueping, Acc. Chem. Res., 2018, 51, 1185–
1195.
Conclusions
3
L. Guo and M. Rueping, Chem. - A Eur. J., 2018, 24, 7794–
7809.
A. Modak and D. Maiti, Org. Biomol. Chem., 2016, 14, 21–
35.
G. J. S. Dawes, E. L. Scott, J. Le Nôtre, J. P. M. Sanders and J.
H. Bitter, Green Chem., 2015, 17, 3231–3250.
L. Wu, Q. Liu, R. Jackstell and M. Beller, Angew. Chemie Int.
Ed., 2014, 53, 6310–6320.
T. Morimoto and K. Kakiuchi, Angew. Chemie Int. Ed., 2004,
43, 5580–5588.
J. Tsuji and K. Ohno, Tetrahedron Lett., 1965, 6, 3969–
3971.
S. Kusumoto, T. Tatsuki and K. Nozaki, Angew. Chemie - Int.
Ed., 2015, 54, 8458–8461.
S. K. Murphy, J.-W. Park, F. A. Cruz and V. M. Dong, Science
(80-. )., 2015, 347, 56–60.
T. Yamamoto, J. Ishizu, T. Kohara, S. Komiya and A.
Yamamoto, J. Am. Chem. Soc., 1980, 102, 3758–3764.
P. E. Romero, M. T. Whited and R. H. Grubbs,
Organometallics, 2008, 27, 3422–3429.
The decarbonylative cleavage of ethers into CO and
hydrocarbyl fragments is mediated by iridium(I) pincer
complexes. The reaction features an extraordinary number of
bond-breaking (two C–H bonds, one C–C bond, and one C–O
bond) and bond-forming (two C–H bonds) events.
4
5
Intramolecular
ether
activation
was
discovered
6
serendipitously while studying pincer-crown ether complexes.
These reactions proceed in excellent yield and high selectivity,
with a change in the site of decarbonylation observed for acyclic
pendent ethers relative to the macrocyclic variants. Using a
diethylamine-based pincer ligand enabled an intermolecular
variant of the reaction, where the pincer ligand remains intact
while reacting with free ethers.
Mechanistic studies revealed initial C–H bond activation by
an iridium(I) species. The efficient decarbonylation of MeOtBu
rules out the α-alkoxy migration pathway and suggests the α-
hydrogen migration is the operative pathway. The conversion
with a PCP iridium(I) complex was much lower than that of
NCOP complexes, confirming the importance of ligand design in
conferring the desired reactivity and suggesting a possible role
of amine hemilability.
7
8
9
10
11
12
13
14
15
16
17
18
L. C. Gregor, J. Grajeda, P. S. White, A. J. Vetter and A. J. M.
Miller, Catal. Sci. Technol., 2018, 8, 3133–3143.
M. R. Kita and A. J. M. Miller, J. Am. Chem. Soc., 2014, 136,
14519–14529.
M. Gupta, C. Hagen, R. J. Flesher, W. C. Kaska and C. M.
Jensen, Chem. Commun., 1996, 36, 2083–2084.
I. Göttker-Schnetmann, P. S. White and M. Brookhart,
Organometallics, 2004, 23, 1766–1776.
Collectively, these results raise hopes of future development
of a suitable ligand that can promote the desired reaction while
maintaining suitable thermal stability to release the CO ligand
and achieve turnover.
Conflicts of interest
There are no conflicts to declare
Y. Wang, C. Qin, X. Jia, X. Leng and Z. Huang, Angew.
Chemie - Int. Ed., 2017, 56, 1614–1618.
L. C. Gregor, J. Grajeda, M. R. Kita, P. S. White, A. J. Vetter
and A. J. M. Miller, Organometallics, 2016, 35, 3074–3086.
H. M. Dodge, M. R. Kita and A. J. M. Miller, submitted.
A. M. Camp, M. R. Kita, J. Grajeda, P. S. White, D. A. Dickie
and A. J. M. Miller, Inorg. Chem., 2017, 56, 11141–11150.
E. Carmona, M. Paneque, L. L. Santos and V. Salazar, Coord.
Chem. Rev., 2005, 249, 1729–1735.
M. L. Poveda, L. L. Santos, A. G. Petronilho, M. Paneque, E.
Carmona, E. Álvarez and K. Mereiter, Organometallics,
2007, 26, 1231–1240.
M. T. Whited and R. H. Grubbs, Organometallics, 2009, 28,
161–166.
M. T. Whited and R. H. Grubbs, Acc. Chem. Res., 2009, 42,
1607–1616.
S. Conejero, M. Paneque, M. L. Poveda, L. L. Santos and E.
Carmona, Acc. Chem. Res., 2010, 43, 572–580.
Acknowledgements
19
20
This work was primarily supported by Eastman Chemical Co.
Ligand synthesis efforts were supported by the National Science
Foundation under CAREER award CHE-1553802. The mass
spectrometry instrumentation was supported by the National
Science Foundation under Grant No. CHE-1726291. The NMR
spectroscopy instrumentation was supported by the National
Science Foundation under Grant No. CHE-1828183. Kyle
Brennaman assisted with resonance Raman spectroscopy
performed in the AMPED EFRC Instrumentation Facility
established by the Alliance for Molecular PhotoElectrode Design
for Solar Fuels, an Energy Frontier Research Center (EFRC)
funded by the U.S. Department of Energy, Office of Science,
Office of Basic Energy Sciences under Award DE-SC0001011. We
21
22
23
24
25
This journal is © The Royal Society of Chemistry 20xx
Chem. Sci., 2020, 00, 1-3 | 7
Please do not adjust margins

PleaseCdhoemnoictaal dScjuiesntcmeargins
Page 8 of 9
ARTICLE
Chemical Science
26
27
H. Werner, Angew. Chemie - Int. Ed., 2010, 49, 4714–4728.
K. I. Goldberg and D. M. Heinekey, Organometallics, 2016,
35, 3546–3556.
B. Sheludko, M. T. Cunningham, A. S. Goldman and F. E.
Celik, ACS Catal., 2018, 8, 7828–7841.
B. A. Younglove and J. F. Ely, J. Phys. Chem. Ref. Data, 1987,
16, 577–798.
C. H. Barron, J. C. Chaty, R. A. Gonzalez and J. W. Eldridge,
J. Chem. Eng. Data, 1962, 7, 394–397.
J. G. Aston, R. M. Kennedy and S. C. Schumann, J. Am.
Chem. Soc., 1940, 62, 2059–2063.
David R. Lide, Ed., CRC handbook of chemistry and physics,
CRC Press, Florida, 84th Ed., 2003.
View Article Online
DOI: 10.1039/D0SC03736B
N. J. Brookes, M. T. Whited, A. Ariafard, R. Stranger, R. H.
Grubbs and B. F. Yates, Organometallics, 2010, 29, 4239–
4250.
J. E. V. Valpuesta, E. Álvarez, J. Lõpez-Serrano, C. Maya and
E. Carmona, Chem. - A Eur. J., 2012, 18, 13149–13159.
L. E. Doyle, W. E. Piers and D. W. Bi, Dalt. Trans., 2017, 46,
4346–4354.
S. Sung and R. D. Young, Dalt. Trans., 2017, 46, 15407–
15414.
L. E. Doyle, W. E. Piers and J. Borau-Garcia, J. Am. Chem.
Soc., 2015, 137, 2187–2190.
S. Sung, T. Joachim, T. Krämer and R. D. Young,
Organometallics, 2017, 36, 3117–3124.
P. Cui and V. M. Iluc, Chem. Sci., 2015, 6, 7343–7354.
M. C. Haibach, N. Lease and A. S. Goldman, Angew. Chemie
- Int. Ed., 2014, 53, 10160–10163.
52
53
54
55
56
28
29
30
31
32
33
34
35
36
S. Kundu, J. Choi, D. Y. Wang, Y. Choliy, T. J. Emge, K. Krogh-
Jespersen and A. S. Goldman, J. Am. Chem. Soc., 2013, 135,
5127–5143.
Y. Choliy, T. J. Emge, X. Zhang, J. Choi, A. S. Goldman and K.
Krogh-Jespersen, J. Am. Chem. Soc., 2009, 131, 15627–
15629.
37
38
39
Y. Zhang and N. D. Schley, Chem. Commun., 2017, 53,
2130–2133.
N. Grüger, H. Wadepohl and L. H. Gade, Eur. J. Inorg.
Chem., 2013, 2013, 5358–5365.
M. T. Whited, Y. Zhu, S. D. Timpa, C.-H. Chen, B. M.
Foxman, O. V. Ozerov and R. H. Grubbs, Organometallics,
2009, 28, 4560–4570.
40
41
42
J. Meiners, A. Friedrich, E. Herdtweck and S. Schneider,
Organometallics, 2009, 28, 6331–6338.
D. M. Spasyuk, D. Zargarian and A. Van Der Est,
Organometallics, 2009, 28, 6531–6540.
R. B. Leveson-Gower, P. B. Webb, D. B. Cordes, A. M. Z.
Slawin, D. M. Smith, R. P. Tooze and J. Liu, Organometallics,
2018, 37, 30–39.
43
A. J. Nawara-Hultzsch, J. D. Hackenberg, B. Punji, C.
Supplee, T. J. Emge, B. C. Bailey, R. R. Schrock, M.
Brookhart and A. S. Goldman, ACS Catal., 2013, 3, 2505–
2514.
44
45
46
47
48
49
I. Göttker-Schnetmann, P. White and M. Brookhart, J. Am.
Chem. Soc., 2004, 126, 1804–1811.
B. Punji, T. J. Emge and A. S. Goldman, Organometallics,
2010, 29, 2702–2709.
I. Göttker-Schnetmann, P. S. White and M. Brookhart,
Organometallics, 2004, 23, 1766–1776.
Y. Wang, C. Qin, X. Jia, X. Leng and Z. Huang, Angew.
Chemie Int. Ed., 2017, 56, 1614–1618.
R. Ghosh, M. Kanzelberger, T. J. Emge, G. S. Hall and A. S.
Goldman, Organometallics, 2006, 25, 5668–5671.
N. J. Brookes, M. T. Whited, A. Ariafard, R. Stranger, R. H.
Grubbs and B. F. Yates, Organometallics, 2010, 29, 4239–
4250.
50
51
J. Choi, A. H. R. MacArthur, M. Brookhart and A. S.
Goldman, Chem. Rev., 2011, 111, 1761–1779.
J. M. Goldberg, S. D. T. Cherry, L. M. Guard, W. Kaminsky,
8 | Chem. Sci., 2020, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 9 of 9
Chemical Science
View Article Online
DOI: 10.1039/D0SC03736B
TOC Graphic and Synopsis
A unique chain-rupturing transformation that converts an ether functionality into two
hydrocarbyl units and carbon monoxide is reported.