Mechanistic Insights into C-H Borylation of Arenes with Organoiridium Catalysts Embedded in a Microporous Metal-Organic Framework

Article abstract of DOI:10.1021/acs.organomet.9b00874

Organometallic iridium catalysts can be used in conjunction with bispinacolatodiboron (B₂Pin₂) to effect the borylation of a variety of substrates such as arenes, alkanes, heteroarenes, and oxygenates. Recently, efforts have also focused on integrating these catalysts into porous supports, such as metal-organic frameworks (MOFs). While the mechanism of homogeneous borylation systems has been thoroughly investigated experimentally and computationally, analogous studies in MOF-supported iridium catalysts have not been conducted. Herein, we report the mechanistic investigation of a phenanthroline-iridium catalyst immobilized in the organic linker of Universitetet i Oslo (UiO)-67 (Zr₆O₄(OH)₄(BPDC)₄(PhenDC)₂, BPDC = biphenyl-4,4′-dicarboxylate, PhenDC = 1,10-phenanthroline-4,4′-dicarboxylate). By using benzene as a model substrate, variable time normalization analysis (VTNA) of the kinetic data suggested a rate law consistent with zero-order in B₂Pin₂, and first-order in arene. A primary kinetic isotope effect (KIE) in the time course of benzene-d₆ borylation also provided complementary information about the role of the arene in the rate-determining step of the reaction. Characterization by techniques such as X-ray absorption spectroscopy (XAS) confirmed the presence of Ir(III), while pair distribution function (PDF) analysis suggested structures containing an Ir-Cl bond, further substantiated by X-ray photoelectron spectroscopy (XPS). Analysis of postcatalysis materials by inductively coupled plasma-optical emission spectroscopy (ICP-OES) revealed low boron accumulation, which may indicate an absence of boron in the resting state of the catalyst. Finally, in comparing borylation of benzene and toluene, a slight selectivity for benzene is observed, which is similar to the analogous homogeneous reaction, indicating the influence of substrate sterics on reactivity.

Full text of DOI:10.1021/acs.organomet.9b00874

pubs.acs.org/Organometallics
Article
Mechanistic Insights into C−H Borylation of Arenes with
Organoiridium Catalysts Embedded in a Microporous Metal−
Organic Framework
Zoha H. Syed, Zhihengyu Chen, Karam B. Idrees, Timothy A. Goetjen, Evan C. Wegener, Xuan Zhang,
Karena W. Chapman, David M. Kaphan,* Massimiliano Delferro,* and Omar K. Farha*
Cite This: https://dx.doi.org/10.1021/acs.organomet.9b00874
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: Organometallic iridium catalysts can be used in conjunction with
bispinacolatodiboron (B2Pin2) to effect the borylation of a variety of substrates such
as arenes, alkanes, heteroarenes, and oxygenates. Recently, efforts have also focused
on integrating these catalysts into porous supports, such as metal−organic
frameworks (MOFs). While the mechanism of homogeneous borylation systems
has been thoroughly investigated experimentally and computationally, analogous
studies in MOF-supported iridium catalysts have not been conducted. Herein, we
report the mechanistic investigation of a phenanthroline-iridium catalyst
immobilized in the organic linker of Universitetet i Oslo (UiO)-67
(Zr6O4(OH)4(BPDC)4(PhenDC)2, BPDC = biphenyl-4,4′-dicarboxylate, PhenDC
= 1,10-phenanthroline-4,4′-dicarboxylate). By using benzene as a model substrate,
variable time normalization analysis (VTNA) of the kinetic data suggested a rate
law consistent with zero-order in B2Pin2, and first-order in arene. A primary kinetic
isotope effect (KIE) in the time course of benzene-d6 borylation also provided complementary information about the role of the
arene in the rate-determining step of the reaction. Characterization by techniques such as X-ray absorption spectroscopy (XAS)
confirmed the presence of Ir(III), while pair distribution function (PDF) analysis suggested structures containing an Ir−Cl bond,
further substantiated by X-ray photoelectron spectroscopy (XPS). Analysis of postcatalysis materials by inductively coupled plasma−
optical emission spectroscopy (ICP-OES) revealed low boron accumulation, which may indicate an absence of boron in the resting
state of the catalyst. Finally, in comparing borylation of benzene and toluene, a slight selectivity for benzene is observed, which is
similar to the analogous homogeneous reaction, indicating the influence of substrate sterics on reactivity.
comparison to their previously reported Cp*Ir systems.3,8
Hartwig, Miyaura, Ishiyama, and co-workers later reported the
borylation of arenes using combinations of dimeric iridium(I)
INTRODUCTION
■
The functionalization of C−H bonds in abundant, natural
feedstocks remains a pervasive challenge in the petrochemical
and pharmaceutical industries.1,2 For further derivatization,
precursors, such as [Ir(COD)X]2 (where COD = 1,5-
cyclooctadiene and X = Cl or OMe), and bidentate nitrogen
donor ligands such as 2,2′-bipyridine (bpy) or 4,4′-ditertbutyl-
2,2′-bipyridine (dtbpy) (Figure 1B).9,10 In the presence of
bispinacolatodiboron (B2Pin2) or HBPin, arenes and hetero-
arenes2−5,9−18 could be used to form arylboronate esters with
turnover numbers as high as 24 000, ranging from room
temperature to 80 °C.3,9,19
installation of reactive moieties is often required for
subsequent transformation to commodity chemicals.1,2 An
example of such is the catalytic incorporation of C−B bonds to
hydrocarbons, forming products such as boronic esters or
boronates, that can serve as useful synthons for a variety of
reactions such as cross-coupling, conjugate addition, and
oxidative amination.3−5
In particular, borylation methodologies catalyzed by iridium-
based catalysts have shown promise.3−5 Smith and co-workers
first reported the borylation of aryl substrates using a
Cp*Ir(PMe3)(H)(BPin) (17 mol %, Cp* = pentamethylcy-
clopentadienyl, BPin = pinacolboryl) catalyst (Figure 1A).6−8
Monoborylated benzene (phenylboronic acid pinacol ester,
PhBPin) was formed in 53% yield after 120 h at 150 °C using
pinacolborane (HBPin) as the borylating agent. Smith and co-
workers expanded their investigation to phosphine-ligated
iridium catalysts as well, which showed enhanced activity in
Since the report of these seminal examples, investigation has
continued into optimization of borylation systems through
Special Issue: Organometallic Chemistry at Various
Length Scales
Received: December 27, 2019
https://dx.doi.org/10.1021/acs.organomet.9b00874
© XXXX American Chemical Society
Organometallics XXXX, XXX, XXX−XXX
A

Organometallics
pubs.acs.org/Organometallics
Article
are known for their high porosity, crystallinity, and diverse
structural features. Moreover, MOF-supported catalysts offer
an opportunity to study structure-activity relationships in a
single-site heterogeneous catalyst system.40 Indeed, the
successful incorporation of organoiridium-based borylation
catalysts has occurred in MOFs for borylation of substrates
such as arenes and methane.34,35,37,39−41 In particular, we
recently reported the incorporation of 1,10-phenanthroline
into a UiO-67-type framework, which generated a mixed linker
MOF comprised of 4,4′-biphenyldicarboxylate (BPDC) and
1,10-phenanthroline-4,4′-dicarboxylate (PhenDC) (UiO-67-
mix) (Figure 2).40 Upon metalation with [Ir(COD)Cl]2 and
subsequent oxidation in ambient atmosphere, a single-site
Ir(III) catalyst was generated (Figure 2, vide infra) that proved
to be competent for the chemoselective monoborylation of
methane, likely due to tailored pore size and aperture.40
As catalytic competency for borylation has been widely
demonstrated with organometallic iridium catalysts, interest
has grown in the mechanism of these processes. In the
molecular, N,N-ligand/Ir(I) systems, Hartwig and others,
through extensive kinetic study and structural character-
ization,4,5,7,11,14,19,20,22,25,27,42−47 proposed the catalytic cycle
depicted in Scheme 1. A five coordinate Ir(III)trisboryl active
Figure 1. Homogeneous, organoiridium catalysts for borylation. (A)
Smith and co-workers, Cp*Ir(PMe3)(H)(BPin) for borylation of
arenes. (B) Ishiyama, Miyaura, Hartwig, and co-workers (dtbpy)Ir-
(BPin)3(COE), active for borylation of arenes upon dissociation of
COE. (C) Smith, Baik, Mindiola, and co-workers, proposed active
catalyst for methane borylation, studied computationally.
ligand modification and expansion to other classes of
substrates, beyond arenes.2−4,11,20−30 In particular, efforts
have expanded to functionalizing light alkanes such as
methane, which is particularly difficult due to the chemical
inertness of the C−H bonds. Sanford and co-workers
contemporaneously with Smith, Baik, and Mindiola and co-
workers reported the borylation of methane using iridium
catalysts in combination with ligands such as 1,10-phenanthro-
line derivatives (Figure 1C).26,27 At 150 °C and high pressures
of methane in the presence of B2Pin2, a mixture of
monoborylated and diborylated products could be ob-
tained.26,27
Scheme 1. Proposed Ir(III)/Ir(V) Catalytic Cycle for
Homogeneous Borylation of Hydrocarbons with an N,N-
Bidentate Ligand Scaffold
To improve the chemoselectivity and efficiency of borylation
reactions, efforts have begun and continued toward the
immobilization of efficient molecular catalysts into porous
supports.31−40 In such a scenario, the molecular, architectural
features of the support can impart a shape selective effect, thus
using size exclusion to improve selectivity for one product over
another. Moreover, grafting of an organometallic fragment
onto a heterogeneous support may generate single site catalysts
with enhanced activity, likely due to decreased catalyst
deactivation. One class of inorganometallic materials that can
be used for this application is metal−organic frameworks
(MOFs). Featuring inorganic nodes and organic linkers, they
Figure 2. Structure of mixed-linker MOF UiO-67-mix, comprised of biphenyl-4,4′-dicarboxylate (BPDC) and 1,10-phenanthroline-4,4′-
dicarboxylate (PhenDC) organic linkers bound to Zr-based cluster nodes. Octahedral pore is shown for clarity, and ligands other than
phenanthroline have been omitted from the inner coordination sphere of the iridium center for clarity.
B
https://dx.doi.org/10.1021/acs.organomet.9b00874
Organometallics XXXX, XXX, XXX−XXX

Organometallics
pubs.acs.org/Organometallics
Article
intermediate, which is generated from dissociation of COE
(COE = cyclooctene) from the metal center, can activate the
arene substrate through oxidative addition or σ-bond meta-
thesis, with the former being more likely (Scheme 1). This
seven-coordinate Ir(V) adduct is then proposed to undergo
isomerization, followed by reductive elimination of the PhBPin
product (Scheme 1). The Ir(III)trisboryl is then regenerated
following reaction with B2Pin2 (Scheme 1). This has also been
supported computationally23,25,27,45,47 and is hypothesized to
be the mechanistic pathway with other organometallic iridium
complexes as well.27,34
Computational investigation of the borylation mechanism in
an Ir catalyst immobilized in a MOF has also been carried out.
Gagliardi and co-workers studied the mechanism of methane
borylation with UiO-67-mix-Ir to gain insight into the origin of
the chemoselectivity that was observed.48 It was found that the
Ir center inside the MOF had similar reactivity to the
homogeneous analogues, proceeding through an iridium-
trisboryl intermediate. The selectivity for monoborylated
methane originated from a larger barrier of diffusion (24.7
kcal/mol) for the diborylated product, which is 14.2 kcal/mol
higher than that for monoborylated methane. In addition, the
rate-determining step was found to be isomerization of the
seven coordinate Ir(V) rather than C−H bond cleavage via
oxidative addition as in the homogeneous reaction.48
The kinetic and mechanistic implications of MOF
immobilization of iridium borylation catalysts, however, have
not been thoroughly investigated, experimentally. Herein, we
examine the mechanism of borylation with UiO-67-mix-Ir
catalysts. Using benzene as a model substrate, for ease of
handling and higher activity, kinetic data was collected, and
catalyst speciation was studied. Vapor-phase sorption studies
were used to gain insight into affinity of the Ir catalyst for
benzene. Time course profiles revealed an induction period in
benzene borylation, which is effected by the concentration and
nature of arene that is present. A comparison of benzene and
toluene borylation indicated similar substrate selectivity to the
corresponding homogeneous reaction. Characterization of
UiO-67-mix-Ir postcatalysis also showed low boron content
present in the material, which may indicate little boron
accumulation in the catalyst in its resting state, representing a
departure from previously reported homogeneous systems.
Information for characterization).49 Exposure of 2 to ambient
atmosphere results in a color change from blue to orange,
generating the Ir(III) material, UiO-67-mix-Ir(III) (3), which
had previously shown competency for chemoselective methane
borylation.40 Following washing and soaks in acetone over-
night to remove residual water and activation under high
vacuum at 150 °C overnight, the N2 isotherm for 3 showed a
decrease in surface area from 2430 m2/g to 1550 m2/g, with a
corresponding decrease in quantity of N2 adsorbed (Figure S4
and S8), though the pore width distribution remained
relatively unchanged, centered at ∼1.0 nm. Powder X-ray
diffraction (PXRD) patterns confirmed crystallinity and phase
purity was maintained after postsynthetic metalation and
thermal activation (Figure S5 and S9). Inductively coupled
plasma-optical emission spectroscopy (ICP-OES) confirmed Ir
loading onto the MOFapproximately two Ir atoms per Zr6
node were present (∼13 wt % Ir, Table S2), which
corresponded to the approximately two PhenDC linkers per
Zr6 node.
While structural elucidation by single crystal X-ray
diffractometry of 2 and 3 was precluded due to the disordered
nature of the mixed-linker MOF, X-ray pair distribution
function (PDF)/difference envelope density (DED) analyses
(dPDF, Figure 3A), X-ray absorption spectroscopy (XAS), and
DRIFTS were used to probe the ligand environment around
the as-prepared iridium materials.
High resolution X-ray powder diffraction patterns were
collected for the native MOF 1, and the Ir(I) and Ir(III)
metalated MOFs, 2 and 3 respectively, after which PDF/DED
analyses were conducted. In all three samples, crystallinity was
maintained (Figure S3). DED analysis revealed electron
density centered around the linkers of samples 2 and 3,
consistent with Ir chelated by the phenanthroline linkers and
was localized to the octahedral pore of 1 as opposed to the
tetrahedral pore based on PDF/DED analysis, on average
(Figure S40−S43). PDF analysis confirmed the integrity of the
UiO-67 framework in all samples, though slight distortion of
the Zr6 node was observed after postsynthetic modification of
the native MOF.
A comparison between 3 and authentic samples of
[Ir(COD)Cl]2 and (phen)Ir(COD)(Cl)49(a molecular ana-
logue to the proposed structure of 2, where Cl− is in the inner
coordination sphere) by X-ray absorption near edge structure
(XANES) indicates changes to the local coordination of
iridium upon metalation and air exposure. The increased white
line intensity suggests the presence of Ir(III) in 3 (Figure S19)
and the EXAFS are consistent with the first coordination
sphere consisting of light-scattering atoms (i.e., C, N, or O)
(fitting results in Table S8), both consistent with previously
reported results of 3.40
Upon conducting differential pair distribution function
(dPDF) analysis, with 1 as a reference, local information
regarding the guest iridium and its interactions with the
frameworks in 2 and 3 could be obtained. Three atom−atom
distances in particular were observed in various magnitudes,
centered at ∼2.1, ∼2.4, and ∼3.0 Å (Figure 3A). On the basis
of previous structural characterization of organometallic
phenanthroline-iridium complexes, the distance at 2.1 Å
could be assigned to bonds such as Ir−N, Ir−O, or Ir−C
(consistent with EXAFS) and 3.0 Å to longer range
interactions such as that between Ir and aromatic carbon
atoms on the phenanthroline backbone (Figure 3A). A
distance at 2.4 Å is consistent with the presence of Ir−Cl in
RESULTS AND DISCUSSION
■
Synthesis and Characterization of UiO-67-mix and
UiO-67-mix-Ir Materials. UiO-67-mix (1) was synthesized
according to our reported sample preparation40 (for
spectroscopic characterization confirming catalyst integrity,
see the Supporting Information, pages S15−4140 for further
discussion and characterization). The MOF was then
metalated with iridium via solvothermal deposition in MOFs
(SIM) at room temperature under inert atmosphere, using a
modification of the previously reported preparation (see the
Supporting Information for further discussion).40 Upon
addition of [Ir(COD)Cl]2 and anhydrous tetrahydrofuran
(THF), the off-white MOF turned green (Figure S1),
consistent with chelation of the Ir(I) precursor by the 1,10-
phenanthroline linker.49 Upon shaking overnight, to facilitate
mass transport, under inert argon atmosphere, the suspension
changed from green to blue (Figure S1), likely due to the
coordination of Cl− to the Ir center, as observed by Colacot
and co-workers with homogeneous (phen)Ir complexes49 (vide
infra), forming UiO-67-mix-Ir(I) (2, see the Supporting
C
https://dx.doi.org/10.1021/acs.organomet.9b00874
Organometallics XXXX, XXX, XXX−XXX

Organometallics
pubs.acs.org/Organometallics
Article
MOF organic linkers along with new aliphatic C−H stretches
around 2850 cm−1 are observed, consistent with coordination
of COD to the iridium center of 2. After oxidation to Ir(III), 3
retains aliphatic C−H stretches, suggesting COD is still bound
to the metal center (Figure 3B). Thus, through a combination
of the aforementioned techniques, precatalyst structures can be
proposed for 2 and 3. The Ir(I) analogue 2 likely contains an
inner sphere chloride bound to the Ir center as well as COD,
forming a five coordinate 18 electron complex analogous to
homogeneous phenanthroline-iridium species formed in THF
using [Ir(COD)Cl]2 as the metalating agent with 1,10-
phenanthroline.49 Upon oxidation to Ir(III), retention of
COD ligand on the Ir center may be consistent with formation
of a cationic six coordinate 18 electron complex such as that in
Figure 3, in which there is coordination of X-type ligands such
as hydroxide or chloride, likely resulting in a mixture of species
inside the MOF.
Benzene Affinity in UiO-67-mix-Ir via Vapor Sorption
and Catalytic Benzene Borylation. To demonstrate the
viability of benzene as a borylation substrate and explore its
potential interactions with the Ir center, vapor-phase sorption
data were collected for native MOF 1 and UiO-67-mix-Ir(III)
3. The adsorption isotherms for benzene were collected for 1
and 3 at 338 K to probe interaction of the vapor source with
the material similar to reaction conditions and determine
propensity for adsorption (Figure 4). The adsorption is at ∼7
mmol/g for 1 and ∼3 mmol/g for 3 at about 20 mmHg partial
pressure of benzenethe disparity between uptake likely due
to the decrease in pore volume upon metalation of 1 with Ir
(Figure 4A). A steeper uptake of benzene is observed at low
pressure (<3 mmHg) for 3 in comparison to 1, which is
indicative of a relatively higher affinity of 3 with benzene in
comparison to the native MOF (Figure 4B).
To investigate the reversibility of adsorption, a second cycle
of benzene sorption was conducted, following reactivation of
the samples at 338 K under vacuum. Similar adsorption
isotherms are obtained, with steeper uptake observed once
again at low pressure (<3 mmHg) for 3 in comparison to 1
(Figure S46−S47). The steep uptake may suggest a strong but
reversible interaction between benzene and the metalated
MOF.
Having observed this affinity for benzene by 3, catalytic
studies of benzene borylation with B2Pin2 as the limiting
reagent were subsequently pursued (Scheme 2). In the
borylation of benzene, 2 equiv of PhBPin can be formed per
mole of B2Pin2 in a one-pot reaction, liberating H2. The first
equivalent of PhBPin can be formed from borylation of
benzene with B2Pin2, forming product and HBPin (Figure
S48). The second equivalent of PhBPin can form through
concomitant borylation with in situ generated HBPin, which
can also be consumed over the course of the reaction, forming
dihydrogen (H2). This manifests as low HBPin accumulation
over the course of the reaction. Indeed, in using HBPin as a
borylating agent in place of B2Pin2, PhBPin could be formed
(for further discussion, see the Supporting Information, page
S44).
Figure 3. Characterization of 1, 2, 3, and 4 by X-ray PDF and
DRIFTS for investigation of catalyst structure. (A) dPDF patterns
showing the presence of Ir N/C/O bonds and an Ir−Cl bond, which
could be present in 2 and 3. (B) DRIFTS spectra of Ir-metalated
samples 2−4 in comparison to native MOF 1 (not commonly scaled)
showing the growth of aliphatic C−H stretches likely associated with
COD ligand. A proposed structure for 2 may include an inner sphere
chloride bound to Ir with COD, generating an 18 electron Ir(I)
adduct inside the MOF. Upon exposure to ambient atmosphere to
form 3, oxidation/hydrolysis can occur, leading to coordination of
hydroxyl groups. The presence of COD by DRIFTS may suggest a
cationic Ir(III) 18 electron complex being formed inside the MOF as
a mixture of species with or without inner sphere chloride. A chloride
ion in the outer coordination sphere for structure 3 has been omitted
for clarity.
samples 2 and 3 (Figure 3A), which is not observed in EXAFS
fittings, likely due to the overlap of multiple scattering paths in
the first coordination sphere. The presence of Ir−Cl in 2 and 3
was further confirmed by X-ray photoelectron spectroscopy
(XPS), where peaks in the Cl 2p region were observed at
binding energies consistent with metal-chloride bonds being
present in the samples (Figure S25−S33).50
Diffuse reflectance infrared Fourier transform spectroscopy
(DRIFTS) was also used for structural elucidation of 2 and 3
(Figure 3B). Upon metalating native MOF 1 with [Ir(COD)-
Cl]2, the retention of aromatic stretches associated with the
To minimize variation, all reaction kinetics experiments were
conducted using the same batch of catalyst (see the Supporting
Information, page S9 and S48, for discussion of batch to batch
variation in catalyst performance). In a stirred reaction with
benzene (1.93 M) and B2Pin2 (0.073 M) in the presence of 3
(40 mg, 12 mol % catalyst loading, catalyst loading = mmol Ir/
mmol B2Pin2 as a percentage) and cyclohexane solvent,
D
https://dx.doi.org/10.1021/acs.organomet.9b00874
Organometallics XXXX, XXX, XXX−XXX

Organometallics
pubs.acs.org/Organometallics
Article
absence of catalyst showed no benzene borylation (see the
Supporting Information, page S45−S46). Through monitoring
of the reaction over time by gas chromatography-flame
ionization detection (GC-FID), in the presence of hexadecane
as an internal standard, an induction period was revealed in the
first ∼60 min of reaction after which it reached quantitative
conversion of starting material (Figure 5A,B). Upon decreasing
the concentration of benzene while holding concentration of
B2Pin2 constant, an apparent elongation of the induction
period was observed, with little PhBPin observed after 280 min
using the lowest concentration of 0.22 M benzene (Figure
5C,D). When comparing two concentrations of B2Pin2 (Figure
5E,F), a slight inhibitory effect that elongates the induction
period at higher concentration is observed compared to lower
concentration as reaction with 0.037 M B2Pin2 appears to
reach quantitative conversion faster than that which is using
0.146 M. If activation of the arene is requisite for induction,
increased concentration of B2Pin2 relative to benzene may lead
to competition of pore occupation between the two substrates,
which could result in elongation of the induction period.
Alternatively, the arene could be involved in turnover after
induction, at which point pore blockage by B2Pin2 can occur.
In either mechanistic scenario, B2Pin2 may have an inhibitory
effect.
To further interrogate kinetic dependence on concentration
in the region most influenced by induction, variable time
normalization analysis (VTNA) was performed (Figure
6).51−53 This analysis was first conducted on a series of
experiments designed to assess rate dependence on concen-
tration of catalyst. Upon variation of the catalyst loading from
20 mg to 40 mg to 80 mg, VTNA revealed a change in catalyst
order graduallythe reaction remained first-order in catalyst
in the first ∼50 min (Figure 6A,B) after which deviation from
first-order behavior began to occur. This suggests the
development of mass transport limitations over time during
the reaction, which is believed to occur through adhesion of
catalyst to the walls of the reaction vessel, leading to uneven
mixing which generally coincided with the onset of mass
transfer effects. Bearing this in mind, visual kinetic analysis was
performed on profiles with variable concentrations of benzene
and B2Pin2, with deviations to partial order rate dependence
likely taking place due to mass transport. VTNA of a plot of
varying concentration of benzene (Figure 6C) began showing
overlap when fit to a first-order rate dependence on the
concentration of benzene, though optimal overlap is observed
when fit to a 0.75 order rate dependence (Figure 6D). As
VTNA is designed to extract information on rate dependence
of the reaction, it is likely borylation occurs first-order in arene
after induction; however, an alternative interpretation of these
data is that the generation of the active catalyst is first order in
arene and the subsequent catalytic turnover is zero-order in
arene. The latter interpretation cannot be discounted based on
these data. In contrast, visual fit was achieved in varying B2Pin2
concentration plots near zero-order (Figure 6E), with optimal
fit occurring in fits of −0.1 order (Figure 6F), precluding a
positive rate dependence on B2Pin2. As with benzene, deviation
to a partial order in B2Pin2 is also observed over time, which is
likely due to mass transport. A slight inhibitory effect of B2Pin2
is also observed in this reaction, notably at earlier time points
in the region of induction, and thus a negative order in B2Pin2
is in accord with this observation. The borylation reaction is
likely zero-order in B2Pin2 after induction. The observation of
this zero rate dependence, however, precludes it from being
Figure 4. Benzene vapor sorption of 1 and 3 at 338 K with (A)
showing overall uptake and (B) showing low pressure region (<3
mmHg) where a sharp uptake of benzene is observed with 3 in
comparison to 1. See the Supporting Information for discussion of
conditions.
Scheme 2. Benzene Borylation with 3 to Form PhBPin
borylation of benzene to PhBPin (selective for monobor-
ylation) was observed in quantitative conversion of B2Pin2 over
the course of 280 min at 80 °C (∼16 turnovers, turnover =
mmol PhBPin/mmol Ir) (Figure 5). In analyzing the mass
balance of the reaction (see the Supporting Information, pages
S48−51), fluctuations from 100% are likely due to
accumulation of HBPin and/or physisorption of reactants
and products within the porous material. A hot filtration test
confirmed the heterogeneity of the reaction and ICP-OES
analysis of the postcatalysis material showed retention of Ir
loading. In addition, control borylation experiments in the
E
https://dx.doi.org/10.1021/acs.organomet.9b00874
Organometallics XXXX, XXX, XXX−XXX

Organometallics
pubs.acs.org/Organometallics
Article
Figure 5. Benzene borylation monitored over time by GC-FID at 80 °C stirring at 1000 rpm in cyclohexane solvent, (A) variation of catalyst
loading monitored over time with 0.073 M [B2Pin2] and 1.93 M [benzene], (B) early reaction time region of catalyst loading rate dependence, (C)
variation of benzene concentration monitored over time with 0.073 M [B2Pin2] and 40 mg catalyst, (D) early reaction time region of benzene
concentration rate dependence, (E) variation of B2Pin2 concentration monitored over time with 0.48 M [benzene] and 40 mg catalyst, (F) early
reaction time region of B2Pin2 concentration rate dependence.
involved in the chemical transformation at the Ir center to
generate the active catalyst during the induction period. Thus,
consistent with these observations is a rate law that is first-
order in iridium and arene and close to zero-order with a slight
inhibitory effect in B2Pin2. This rate law bears resemblance to
the previously reported homogeneous rate law for arene
borylation,19 though the observed kinetic effects may also be
associated with generation of the active catalyst. Nonetheless,
the aforementioned kinetic data implicates the arene in the
rate-determining step of the reaction.
To further explore the role of arene, the borylation reaction
was conducted with benzene-d6 to probe for isotope effects
(Scheme 3A,B). In monitoring the reaction over time by GC-
FID (Figure 7), the reaction progresses with a significantly
decreased initial rate. Comparison of the two kinetic profiles
shows a deviation in rates, consistent with a primary kinetic
isotope effect (KIE) in benzene (Figure 7). This may be
indicative of rate-limiting C−H bond cleavage during this
period. This is either in formation of the active catalyst or the
reaction following activation. The presence of this isotope
effect agrees with both of these mechanistic scenarios. This
isotope effect is a departure from previously reported
conclusions in which isomerization of an Ir(V) intermediate
was implicated in the rate-limiting step.48
4A,B, H2 omitted from reaction scheme for clarity). In
replacing benzene with toluene for borylation (Scheme 4A), a
similar total concentration of borylated toluene is produced
(Table 1, entries 1 and 2) with quantitative conversion of
B2Pin2. Borylation of toluene at the para- and meta- positions is
observed in relatively equimolar amounts, with only trace
amounts of the ortho- product observed. This is consistent with
the regioselectivity observed in Hartwig’s homogeneous Ir
borylation systems, which is driven by sterics of the substrate.9
To determine if there is selectivity present for one substrate
over another, a competition experiment of benzene and
toluene borylation was conducted (Scheme 4B). Borylation of
both substrates was observed with a 3:1 selectivity for benzene
borylation over toluene borylation, with similar regioselectivity
of toluene borylation observed to a reaction in the absence of
benzene (Table 1, entry 3). This selectivity for benzene
borylation over toluene borylation is similar to that which is
observed in the analogous homogeneous reaction (Table 1,
entry 4). We hypothesize this selectivity for benzene borylation
over toluene borylation may be dictated by the sterics of the
substrate, an effect that is intrinsic to the phenanthroline-
iridium borylation system.
To determine if size selectivity was operant within this
system, t-butylbenzene was next used in a borylation reaction
instead of benzene and B2Pin2 conversion was analyzed at the
conclusion of the reaction (see the Supporting Information,
The borylation of toluene was next investigated in order to
study the effect of arene identity on the reaction (Scheme
F
https://dx.doi.org/10.1021/acs.organomet.9b00874
Organometallics XXXX, XXX, XXX−XXX

Organometallics
pubs.acs.org/Organometallics
Article
Figure 6. VTNA of benzene borylation monitored over time by GC-FID at 80 °C stirring at 1000 rpm in cyclohexane solvent, (A) VTNA of
catalyst loading rate dependence, (B) early reaction time region of catalyst loading rate dependence VTNA, (C) VTNA of benzene concentration
rate dependence, (D) early reaction time region of benzene concentration rate dependence VTNA, (E) VTNA of B2Pin2 concentration rate
dependence, (F) early reaction time region of B2Pin2 concentration rate dependence VTNA.
Scheme 3. Benzene vs Benzene-d6 Borylation with 3 to
Determine Kinetic Isotope Effect from Two Parallel
Reactions
Figure 7. Investigation of the isotopic dependence of benzene
borylation by comparing time profiles of benzene borylation to
benzene-d6 borylation monitored over time by GC-FID at 80 °C
stirring at 1000 rpm in cyclohexane solvent. Error bars represent the
standard deviation of the reactions; for low values, the error bars may
be behind the graphical marker, thus they are also included in the
page S67, for further discussion). A change in B2Pin2
concentration was not observed in the reaction of t-
butylbenzene after 3 h in comparison to that which is
observed with benzene (Table S22), in addition to no
borylated products being detected. This suggests substrates
larger than toluene are sterically constrained from accessing the
Supporting Information.
active sites located in the pores of the MOF, leading to a low
turnover frequency and/or delayed catalyst activation.
Characterization of Postcatalysis Materials and
Mechanistic Hypotheses. To gain insight into the potential
G
https://dx.doi.org/10.1021/acs.organomet.9b00874
Organometallics XXXX, XXX, XXX−XXX

Organometallics
pubs.acs.org/Organometallics
Article
organometallic iridium species in the octahedral pore of the
MOF, having uniform iridium-trisboryl structures for all of
them would likely create too much steric congestion for
borylation to take place within the pores of the MOF. Thus,
this suggests a lack of a boryl species in the catalyst resting
state, lack of uniformity in active site structures for the catalyst,
or a combination thereof. The residual levels of boron may also
be due to physisorbed borylated compounds that were not
removed after washing, which could preclude a boron-
containing species being operant in the catalysis.
Scheme 4. Benzene vs Toluene Borylation with 3 to
Determine Substrate Selectivity
To further probe post-catalysis structure, the material was
analyzed by XAS as well as PDF/DED. Negligible changes
were observed in the EXAFS and XANES regions of the post-
catalysis material in comparison to 3. DED analysis of 4 was
also similar to 3, demonstrating a lack of movement of Ir
within the sample (Figure S44). PDF analysis revealed slight
Zr node distortion within the sample; however, no significant
changes were observed to the UiO-67 framework. Following
dPDF analysis, the same peaks observed in 3 were also
observed in 4, though in different magnitudes (Figure 3A).
Interestingly, an Ir−Cl bond was still present in 4, (Figure 3A)
which was substantiated by the presence of Cl in the Cl 2p
region probed by XPS. Analysis of the post-catalysis material
by DRIFTS (Figure 3B) yielded a similar spectrum to 3, with
aromatic and aliphatic C−H stretches retained in the sample.
In order to probe the induction period further, a post-
borylation sample was resubjected to reaction conditions and
monitored over time (see the Supporting Information, page
S68, for further discussion). A similar induction period was
observed, followed by catalytic turnover with a greater
maximum instantaneous rate than that observed with the
pristine material. Similarly, when a quantity of HBPin was
added to a borylation reaction with B2Pin2 at the start of the
reaction, the reaction rate was observed to be marginally faster
however an induction period still remained (Figure S49).
This may be consistent with a mechanistic scenario in which
the induction period can stem from a combination of chemical
conversion to generate the catalytically active species and/or
the buildup of sufficient reactant concentration within the
pores of the MOF in order for the reaction to proceed.
Following the induction period, two mechanistic hypotheses
emerge. Likely the resting state of the catalyst remains Ir(III)
as evidenced by similar XANES spectra of 3 and 4. A low B/Ir
ratio may suggest active site nonuniformity, in which case an
Ir-trisboryl could be generated in low concentrations and
proceed through the Ir(III)/Ir(V) cycle that has been
proposed by others.4 Alternatively, this may imply that a
species such as Ir-monoboryl is being generated that can also
access the Ir(III)/Ir(V) cycle, proceeding through the same
elementary reaction steps as the Ir-trisboryl complex. Further
investigation will be required to interrogate this.
resting state of 3, the post-catalysis material (4) was
characterized after isolation from the reaction mixture through
centrifugation/decantation and washes with pentane without
exposure to air (see the Supporting Information for further
discussion). Analysis of the supernatant of the borylation
reaction to generate 4 by GC-FID confirmed it had reached
completion. Analysis of 4 by N2 sorption, following activation
under high vacuum at 25 °C, showed a BET surface area of
1050 m2/g with a slight decrease in the pore volume. PXRD
patterns showed crystallinity was retained in the catalyst post-
borylation and phase purity was also maintained.
ICP-OES analysis was used to assess quantity of boron in
the post-catalysis material. This would give insight into the
presence of potential Ir-boryl species in postcatalysis materials,
as what was observed in analogous homogeneous reactions.
Following acid digestion of 3 in a quartz reaction vessel, to
assess the “base-line” boron levels in as-prepared samples, a
ratio of ∼0.17 B/Ir was obtained, which may occur from
presence of adventitious boron from borosilicate vessels and/
or tools used prior to digestion (see the Supporting
Information, page S26 for further discussion). Analysis of 4
by ICP-OES after subtracting baseline boron quantity results in
a ratio of ∼0.42 B/Ir, showing an increase in boron from
baseline levels, but an overall lack of accumulation of boron in
the post-catalysis sample. If a uniform amount of Ir-boryl was
formed in this material, as what was observed in the molecular
case, a ratio greater than 1 for B/Ir would be expected, with a
theoretical ratio of 3 B/Ir for Ir-trisboryl. The native MOF is
capable of encapsulating one iridium-trisboryl species in the
octahedral pore as computationally modeled by Gagliardi and
co-workers.48 As there are approximately three to four
a
Table 1. Borylation of Benzene and Toluene in Cyclohexane Solvent Reveals Differences in Substrate Selectivity
entry
[benzene] (M)
[toluene] (M)
[PhBpin] (M)
[p-TolBpin] (M)
[m-TolBpin] (M)
[o-TolBpin] (M)
1
2
3
1.86
−
1.86
−
0.138
−
0.0946
−
−
−
1.84
1.84
1.84
0.0496
0.01476
0.00922
0.0687
0.0225
0.0192
0.00279
0.000622
0
b
4
1.86
0.0823
a
Conditions: 13 mg catalyst, 0.070 M B2Pin2, 80 °C, stirring 1000 rpm, 280 min, after which the reaction is quantified by GC-FID (internal
b
standard = hexadecane, 0.067 M). 2.61 mg [Ir(COD)Cl]2 (0.0039 mmol), 1.4 mg 1,10-phenanthroline (0.0078 mmol), 0.070 M B2Pin2, 80 °C,
stirring 1000 rpm, 280 min, after which the reaction is quantified by GC-FID (internal standard = hexadecane, 0.067 M).
H
https://dx.doi.org/10.1021/acs.organomet.9b00874
Organometallics XXXX, XXX, XXX−XXX

Organometallics
pubs.acs.org/Organometallics
Article
Omar K. Farha − Department of Chemistry and International
Institute of Nanotechnology, Northwestern University, Evanston,
Illinois 60208, United States; orcid.org/0000-0002-9904-
9845; Email: o-farha@u.northwestern.edu
CONCLUSIONS
■
The immobilization of molecular iridium borylation catalysts
into supports such as MOFs has led to improvements in
chemoselectivity.31,32,34−37,40,41 While a great deal of mecha-
nistic work has occurred with homogeneous organoiridium
borylation systems, the mechanistic implications of conducting
borylation in the pores of a microporous material have not
been fully explored experimentally. We have investigated the
mechanistic aspects of a phenanthroline-ligated Ir catalyst
immobilized in UiO-67 to gain insight into intrinsic features of
this borylation reaction. Characterization of the precatalyst
structure before and after oxidation revealed information
regarding ligand environment, notably the presence of an Ir−
Cl bond by X-ray PDF/DED analysis. Affinity of the iridium−
metalated MOF catalyst for aryl substrates such as benzene was
demonstrated via benzene vapor sorption. An induction period
was revealed in time course profiles of benzene borylation,
which was perturbed through variation in amount of arene that
was present in the system, and mass transport effects were
found to greatly effect reaction rate over time. Overall, a rate
law zero-order in B2Pin2 and first-order in arene is consistent
with the presented kinetic observations; however, this behavior
may also be ascribed, in part, to activation of the catalyst.
Monitoring borylation of benzene-d6 revealed a primary kinetic
isotope effect in the profile, while borylation of toluene
demonstrated the competency of the catalyst to borylate
alternative aryl substrates with slightly greater selectivity for
benzene over toluene. Borylation of more sterically encum-
bered substrates such as t-butylbenzene was found to be
challenging, which may indicate a size exclusion effect.
Characterization of materials after catalysis also showed a
deficiency of boron present, indicating a lack of accumulation
which is a deviation from previously observed homogeneous
behavior.
Authors
Zoha H. Syed − Department of Chemistry and International
Institute of Nanotechnology, Northwestern University, Evanston,
Illinois 60208, United States; Chemical Sciences and
Engineering Division, Argonne National Laboratory, Lemont,
Illinois 60439, United States; orcid.org/0000-0002-0074-
2253
Zhihengyu Chen − Department of Chemistry, Stony Brook
University, Stony Brook, New York 11764, United States
Karam B. Idrees − Department of Chemistry and International
Institute of Nanotechnology, Northwestern University, Evanston,
Illinois 60208, United States; orcid.org/0000-0002-9603-
3952
Timothy A. Goetjen − Department of Chemistry and
International Institute of Nanotechnology, Northwestern
University, Evanston, Illinois 60208, United States;
orcid.org/0000-0001-8023-9107
Evan C. Wegener − Chemical Sciences and Engineering
Division, Argonne National Laboratory, Lemont, Illinois 60439,
United States
Xuan Zhang − Department of Chemistry and International
Institute of Nanotechnology, Northwestern University, Evanston,
Illinois 60208, United States; orcid.org/0000-0001-8214-
7265
Karena W. Chapman − Department of Chemistry, Stony Brook
University, Stony Brook, New York 11764, United States;
orcid.org/0000-0002-8725-5633
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.organomet.9b00874
A preliminary understanding of the dynamics of this MOF-
based borylation system and catalyst speciation has been
established. Through efforts such as studying larger substrates
than benzene and further experimentation regarding mitigation
of the induction period and mass transport effects of this
reaction, further experimental insight may be gained to
establish a catalytic cycle for this process, in particular
highlighting deviations from well-understood homogeneous
systems.
Funding
This work was supported by the Inorganometallic Design
Center, an Energy Frontier Research Center (EFRC) funded
by the U.S. Department of Energy (DOE), Office of Science,
Basic Energy Sciences (DE-SC0012702). This material is
based upon work supported by the National Science
Foundation Graduate Research Fellowship under Grant No.
(DGE-1842165) (Z.H.S.). Use of the Advanced Photon
Source (APS) at Argonne National Laboratory is funded by
the U.S. DOE under contract DE-AC-02-06CH11357.
MRCAT operations are supported by the U.S. DOE and the
MRCAT member institutions. X-ray pair distribution function
(PDF) and differential envelope density (DED) analyses were
obtained at 11-ID-B at the APS at Argonne National
Laboratory. This work made use of the IMSERC at
Northwestern University, which has received support from
the Soft and Hybrid Nanotechnology Experimental (SHyNE)
Resource (NSF ECCS-1542205), the State of Illinois, and the
International Institute for Nanotechnology (IIN). For NMR
work on the Au400, this work made use of the IMSERC at
Northwestern University, which has received support from the
NSF (CHE-1048773); Soft and Hybrid Nanotechnology
Experimental (SHyNE) Resources (NSF ECCS-1542205);
the State of Illinois and International Institute for Nano-
technology (IIN). This work also made use of the Keck-II
facility of Northwestern University’s NUANCE Center, which
has received support from the Soft and Hybrid Nano-
technology Experimental (SHyNE) Resource (NSF ECCS-
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.organomet.9b00874.
Experimental materials and methods, synthetic proce-
dures, characterization of materials (PDF)
AUTHOR INFORMATION
■
Corresponding Authors
David M. Kaphan − Chemical Sciences and Engineering
Division, Argonne National Laboratory, Lemont, Illinois 60439,
United States; orcid.org/0000-0001-5293-7784;
Email: kaphand@anl.gov
Massimiliano Delferro − Chemical Sciences and Engineering
Division, Argonne National Laboratory, Lemont, Illinois 60439,
United States; orcid.org/0000-0002-4443-165X;
Email: delferro@anl.gov
I
https://dx.doi.org/10.1021/acs.organomet.9b00874
Organometallics XXXX, XXX, XXX−XXX

Organometallics
pubs.acs.org/Organometallics
Article
(13) Larsen, M. A.; Wilson, C. V.; Hartwig, J. F. Iridium-Catalyzed
Borylation of Primary Benzylic C-H Bonds without a Directing
Group: Scope, Mechanism, and Origins of Selectivity. J. Am. Chem.
Soc. 2015, 137 (26), 8633−8643.
(14) Oeschger, R. J.; Larsen, M. A.; Bismuto, A.; Hartwig, J. F.
Origin of the Difference in Reactivity between Ir Catalysts for the
Borylation of C-H Bonds. J. Am. Chem. Soc. 2019, 141 (41), 16479−
16485.
(15) Takagi, J.; Sato, K.; Hartwig, J. F.; Ishiyama, T.; Miyaura, N.
Iridium-Catalyzed C-H Coupling Reaction of Heteroaromatic
Compounds with Bis(Pinacolato)Diboron: Regioselective Synthesis
of Heteroarylboronates. Tetrahedron Lett. 2002, 43 (32), 5649−5651.
(16) Ishiyama, T.; Nobuta, Y.; Hartwig, J. F.; Miyaura, N. Room
Temperature Borylation of Arenes and Heteroarenes Using
Stoichiometric Amounts of Pinacolborane Catalyzed by Iridium
Complexes in an Inert SolventElectronic Supplementary Information
(ESI) Available: Experimental Procedures and Spectral Analyses of P.
Chem. Commun. 2003, No. 23, 2924.
(17) Ishiyama, T.; Takagi, J.; Yonekawa, Y.; Hartwig, J. F.; Miyaura,
N. Iridium-Catalyzed Direct Borylation of Five-Membered Hetero-
arenes by Bis(Pinacolato)Diboron: Regioselective, Stoichiometric,
and Room Temperature Reactions. Adv. Synth. Catal. 2003, 345
(910), 1103−1106.
(18) Boebel, T. A.; Hartwig, J. F. Silyl-Directed, Iridium-Catalyzed
Ortho-Borylation of Arenes. A One-Pot Ortho-Borylation of Phenols,
Arylamines, and Alkylarenes. J. Am. Chem. Soc. 2008, 130 (24),
7534−7535.
(19) Boller, T. M.; Murphy, J. M.; Hapke, M.; Ishiyama, T.; Miyaura,
N.; Hartwig, J. F. Mechanism of the Mild Functionalization of Arenes
by Diboron Reagents Catalyzed by Iridium Complexes. Intermediacy
and Chemistry of Bipyridine-Ligated Iridium Trisboryl Complexes. J.
Am. Chem. Soc. 2005, 127 (41), 14263−14278.
(20) Vanchura, B. A., II; Preshlock, S. M.; Roosen, P. C.; Kallepalli,
V. A.; Staples, R. J.; Maleczka, R. E., Jr.; Singleton, D. A.; Smith, M. R.,
III Electronic Effects in Iridium C-H Borylations: Insights from
Unencumbered Substrates and Variation of Boryl Ligand Substitu-
ents. Chem. Commun. 2010, 46 (41), 7724−7726.
(21) Ji, L.; Fucke, K.; Bose, S. K.; Marder, T. B. Iridium-Catalyzed
Borylation of Pyrene: Irreversibility and the Influence of Ligand on
Selectivity. J. Org. Chem. 2015, 80 (1), 661−665.
(22) Jover, J.; Maseras, F. Mechanistic Investigation of Iridium-
Catalyzed C-H Borylation of Methyl Benzoate: Ligand Effects in
Regioselectivity and Activity. Organometallics 2016, 35 (18), 3221−
3226.
(23) Chattopadhyay, B.; Dannatt, J. E.; Andujar-De Sanctis, I. L.;
Gore, K. A.; Maleczka, R. E.; Singleton, D. A.; Smith, M. R. Ir-
Catalyzed Ortho-Borylation of Phenols Directed by Substrate-Ligand
Electrostatic Interactions: A Combined Experimental/in Silico
Strategy for Optimizing Weak Interactions. J. Am. Chem. Soc. 2017,
139 (23), 7864−7871.
(24) Montero Bastidas, J. R.; Oleskey, T. J.; Miller, S. L.; Smith, M.
R.; Maleczka, R. E. Para-Selective, Iridium-Catalyzed C-H Borylations
of Sulfated Phenols, Benzyl Alcohols, and Anilines Directed by Ion-
Pair Electrostatic Interactions. J. Am. Chem. Soc. 2019, 141 (39),
15483−15487.
(25) Zatsepin, P.; Sorsche, D.; Ahn, S.; Baik, M.-H.; Mindiola, D. J.
Catalytic Borylation of Methane: Combining Computational and
High-Throughput Screening Approaches to Discover a New Catalyst.
Alkane Functionalization 2018, 337−369.
1542205); the MRSEC program (NSF DMR-1720139) at the
Materials Research Center; the International Institute for
Nanotechnology (IIN); the Keck Foundation; and the State of
Illinois, through the IIN. In addition, this work made use of the
EPIC facility of Northwestern University’s NUANCE Center,
which has received support from the Soft and Hybrid
Nanotechnology Experimental (SHyNE) Resource (NSF
ECCS-1542205); the MRSEC program (NSF DMR-
1720139) at the Materials Research Center; the International
Institute for Nanotechnology (IIN); the Keck Foundation; and
the State of Illinois, through the IIN. Metal analysis was
performed at the Northwestern University Quantitative
Bioelement Imaging Center. Molecular graphics and analyses
were performed with UCSF Chimera, developed by the
Resource for Biocomputing, Visualization, and Informatics at
the University of California, San Francisco, with support from
NIH P41-GM103311.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors thank Dr. Magali S. Ferrandon for initial kinetics
protocol optimization and GC method development, Dr.
Xingjie Wang for initial XPS measurements, Ms. Rebecca
Sponenburg for microwave digestion of MOF samples for ICP-
OES analysis to quantify boron, and Dr. Timur Islamoglu and
Dr. Zhijie Chen for helpful discussions.
REFERENCES
■
(1) Labinger, J. A.; Bercaw, J. E. Understanding and Exploiting C-H
Bond Activation. Nature 2002, 417, 507−514.
(2) Hartwig, J. F. Evolution of C-H Bond Functionalization from
Methane to Methodology. J. Am. Chem. Soc. 2016, 138, 2−24.
(3) Mkhalid, I. A. I.; Barnard, J. H.; Marder, T. B.; Murphy, J. M.;
Hartwig, J. F. C-H Activation for the Construction of C-B Bonds.
Chem. Rev. 2010, 110 (2), 890−931.
(4) Hartwig, J. F. Borylation and Silylation of C-H Bonds: A
Platform for Diverse C-H Bond Functionalizations. Acc. Chem. Res.
2012, 45 (6), 864−873.
(5) Xu, L.; Wang, G.; Zhang, S.; Wang, H.; Wang, L.; Liu, L.; Jiao, J.;
Li, P. Recent Advances in Catalytic C−H Borylation Reactions.
Tetrahedron 2017, 73, 7123−7157.
(6) Iverson, C. N.; Smith, M. R. Stoichiometric and Catalytic B-C
Bond Formation from Unactivated Hydrocarbons and Boranes [1]. J.
Am. Chem. Soc. 1999, 121, 7696−7697.
(7) Cho, J. Y.; Iverson, C. N.; Smith, M. R. Steric and Chelate
Directing Effects in Aromatic Borylation [3]. J. Am. Chem. Soc. 2000,
122 (51), 12868−12869.
(8) Cho, J. Y.; Tse, M. K.; Holmes, D.; Maleczka, R. E.; Smith, M. R.
Remarkably Selective Iridium Catalysts for the Elaboration of
Aromatic C-H Bonds. Science (Washington, DC, U. S.) 2002, 295
(5553), 305−308.
(9) Ishiyama, T.; Takagi, J.; Ishida, K.; Miyaura, N.; Anastasi, N. R.;
Hartwig, J. F. Mild Iridium-Catalyzed Borylation of Arenes. High
Turnover Numbers, Room Temperature Reactions, and Isolation of a
Potential Intermediate. J. Am. Chem. Soc. 2002, 124 (3), 390−391.
(10) Ishiyama, T.; Takagi, J.; Hartwig, J. F.; Miyaura, N. A
Stoichiometric Aromatic C-H Borylation Catalyzed by Iridium(I)/
2,2′-Bipyridine Complexes at Room Temperature. Angew. Chem., Int.
Ed. 2002, 41 (16), 3056−3058.
(11) Hartwig, J. F. Regioselectivity of the Borylation of Alkanes and
Arenes. Chem. Soc. Rev. 2011, 40, 1992−2002.
(12) Larsen, M. A.; Hartwig, J. F. Iridium-Catalyzed C-H Borylation
of Heteroarenes: Scope, Regioselectivity, Application to Late-Stage
Functionalization, and Mechanism. J. Am. Chem. Soc. 2014, 136 (11),
4287−4299.
(26) Cook, A. K.; Schimler, S. D.; Matzger, A. J.; Sanford, M. S.
Catalyst-Controlled Selectivity in the C-H Borylation of Methane and
Ethane. Science (Washington, DC, U. S.) 2016, 351 (6280), 1421−
1424.
́
(27) Smith, K. T.; Berritt, S.; Gonzalez-Moreiras, M.; Ahn, S.; Smith,
M. R.; Baik, M. H.; Mindiola, D. J. Catalytic Borylation of Methane.
Science (Washington, DC, U. S.) 2016, 351 (6280), 1424−1427.
(28) Preshlock, S. M.; Ghaffari, B.; Maligres, P. E.; Krska, S. W.;
Maleczka, R. E.; Smith, M. R. High-Throughput Optimization of Ir-
J
https://dx.doi.org/10.1021/acs.organomet.9b00874
Organometallics XXXX, XXX, XXX−XXX

Organometallics
pubs.acs.org/Organometallics
Article
Catalyzed C-H Borylation: A Tutorial for Practical Applications. J.
Am. Chem. Soc. 2013, 135 (20), 7572−7582.
Mechanism for the Para-C-H Borylation of Arenes. Organometallics
2017, 36 (11), 2107−2115.
(45) Zhong, R. L.; Sakaki, S. Sp3 C-H Borylation Catalyzed by
Iridium(III) Triboryl Complex: Comprehensive Theoretical Study of
Reactivity, Regioselectivity, and Prediction of Excellent Ligand. J. Am.
Chem. Soc. 2019, 141 (25), 9854−9866.
(46) Tamura, H.; Yamazaki, H.; Sato, H.; Sakaki, S. Iridium-
Catalyzed Borylation of Benzene with Diboron. Theoretical
Elucidation of Catalytic Cycle Including Unusual Iridium(V)
Intermediate. J. Am. Chem. Soc. 2003, 125 (51), 16114−16126.
(47) Ahn, S.; Sorsche, D.; Berritt, S.; Gau, M. R.; Mindiola, D. J.;
Baik, M. H. Rational Design of a Catalyst for the Selective
Monoborylation of Methane. ACS Catal. 2018, 8 (11), 10021−10031.
(48) Yang, B.; Wu, X. P.; Gagliardi, L.; Truhlar, D. G. Methane
Functionalization by an Ir(III) Catalyst Supported on a Metal−
Organic Framework: An Alternative Explanation of Steric Confine-
ment Effects. Theor. Chem. Acc. 2019, DOI: 10.1007/s00214-019-
2498-y.
(29) Liskey, C. W.; Hartwig, J. F. Iridium-Catalyzed Borylation of
Secondary C-H Bonds in Cyclic Ethers. J. Am. Chem. Soc. 2012, 134
(30), 12422−12425.
(30) Coventry, D. N.; Batsanov, A. S.; Goeta, A. E.; Howard, J. A.
K.; Marder, T. B.; Perutz, R. N. Selective Ir-Catalysed Borylation of
Polycyclic Aromatic Hydrocarbons: Structures of Naphthalene-2,6-
Bis(Boronate), Pyrene-2,7-Bis(Boronate) and Perylene-2,5,8,11-
Tetra(Boronate) Esters. Chem. Commun. 2005, No. 16, 2172−2174.
(31) Chen, Q.; Dong, A.; Wang, D.; Qiu, L.; Ma, C.; Yuan, Y.; Zhao,
Y.; Jia, N.; Guo, Z.; Wang, N. Efficient and Selective Methane
Borylation Through Pore Size Tuning of Hybrid Porous Organic-
Polymer-Based Iridium Catalysts. Angew. Chem., Int. Ed. 2019, 58
(31), 10671−10676.
(32) Tahir, N.; Muniz-Miranda, F.; Everaert, J.; Tack, P.;
Heugebaert, T.; Leus, K.; Vincze, L.; Stevens, C. V.; Van
Speybroeck, V.; Van Der Voort, P. Immobilization of Ir(I) Complex
on Covalent Triazine Frameworks for C−H Borylation Reactions: A
Combined Experimental and Computational Study. J. Catal. 2019,
371, 135−143.
(49) Seechurn, C. C. C. J.; Sivakumar, V.; Satoskar, D.; Colacot, T. J.
Iridium-Catalyzed C-H Borylation of Heterocycles Using an Over-
looked 1,10-Phenanthroline Ligand: Reinventing the Catalytic
Activity by Understanding the Solvent-Assisted Neutral to Cationic
Switch. Organometallics 2014, 33 (13), 3514−3522.
́
(33) Coperet, C.; Comas-Vives, A.; Conley, M. P.; Estes, D. P.;
́
Fedorov, A.; Mougel, V.; Nagae, H.; Nunez-Zarur, F.; Zhizhko, P. A.
(50) Freakley, S. J.; Ruiz-Esquius, J.; Morgan, D. J. The X-Ray
Photoelectron Spectra of Ir, IrO2 and IrCl3 Revisited. Surf. Interface
Anal. 2017, 49 (8), 794−799.
Surface Organometallic and Coordination Chemistry toward Single-
Site Heterogeneous Catalysts: Strategies, Methods, Structures, and
Activities. Chem. Rev. 2016, 116, 323−421.
́
(51) Bures, J. Variable Time Normalization Analysis: General
(34) Feng, X.; Song, Y.; Li, Z.; Kaufmann, M.; Pi, Y.; Chen, J. S.; Xu,
Z.; Li, Z.; Wang, C.; Lin, W. Metal-Organic Framework Stabilizes a
Low-Coordinate Iridium Complex for Catalytic Methane Borylation.
J. Am. Chem. Soc. 2019, 141 (28), 11196−11203.
Graphical Elucidation of Reaction Orders from Concentration
Profiles. Angew. Chem., Int. Ed. 2016, 55 (52), 16084−16087.
(52) Blackmond, D. G. Reaction Progress Kinetic Analysis: A
Powerful Methodology for Mechanistic Studies of Complex Catalytic
Reactions. Angew. Chem., Int. Ed. 2005, 44, 4302−4320.
(53) Blackmond, D. G. Kinetic Profiling of Catalytic Organic
Reactions as a Mechanistic Tool. J. Am. Chem. Soc. 2015, 137,
10852−10866.
(35) Gonzalez, M. I.; Bloch, E. D.; Mason, J. A.; Teat, S. J.; Long, J.
R. Single-Crystal-to-Single-Crystal Metalation of a Metal-Organic
Framework: A Route toward Structurally Well-Defined Catalysts.
Inorg. Chem. 2015, 54 (6), 2995−3005.
(36) Mamlouk, H.; Suriboot, J.; Manyam, P. K.; Alyazidi, A.;
Bergbreiter, D. E.; Madrahimov, S. T. Highly Active, Separable and
Recyclable Bipyridine Iridium Catalysts for C-H Borylation Reactions.
Catal. Sci. Technol. 2018, 8 (1), 124−127.
(37) Manna, K.; Zhang, T.; Lin, W. Postsynthetic Metalation of
Bipyridyl-Containing Metal-Organic Frameworks for Highly Efficient
Catalytic Organic Transformations. J. Am. Chem. Soc. 2014, 136 (18),
6566−6569.
(38) Kimura, A.; Hayama, H.; Hasegawa, J. Y.; Nageh, H.; Wang, Y.;
Naga, N.; Nishida, M.; Nakano, T. Recyclable and Efficient
Polyurethane-Ir Catalysts for Direct Borylation of Aromatic
Compounds. Polym. Chem. 2017, 8 (47), 7406−7415.
(39) Manna, K.; Zhang, T.; Greene, F. X.; Lin, W. Bipyridine- and
Phenanthroline-Based Metal-Organic Frameworks for Highly Efficient
and Tandem Catalytic Organic Transformations via Directed C-H
Activation. J. Am. Chem. Soc. 2015, 137 (7), 2665−2673.
(40) Zhang, X.; Huang, Z.; Ferrandon, M.; Yang, D.; Robison, L.; Li,
P.; Wang, T. C.; Delferro, M.; Farha, O. K. Catalytic Chemoselective
Functionalization of Methane in a Metal-Organic Framework. Nat.
Catal. 2018, 1 (5), 356−362.
(41) Dhakshinamoorthy, A.; Asiri, A. M.; Garcia, H. Formation of C-
C and C-Heteroatom Bonds by C-H Activation by Metal Organic
Frameworks as Catalysts or Supports. ACS Catal. 2019, 9 (2), 1081−
1102.
(42) Nguyen, P.; Blom, H. P.; Westcott, S. A.; Taylor, N. J.; Marder,
T. B. Synthesis and Structures of the First Transition-Metal
Tris(Boryl) Complexes: (H6-Arene)Ir(BO2C6H4)3. J. Am. Chem.
Soc. 1993, 115 (20), 9329−9330.
(43) Chotana, G. A.; Vanchura, B. A., II; Tse, M. K.; Staples, R. J.;
Maleczka, R. E., Jr.; Smith, M. R., III Getting the Sterics Just Right: A
Five-Coordinate Iridium Trisboryl Complex That Reacts with C-H
Bonds at Room Temperature. Chem. Commun. 2009, No. 38, 5731−
5733.
(44) Zhu, L.; Qi, X.; Li, Y.; Duan, M.; Zou, L.; Bai, R.; Lan, Y.
Ir(III)/Ir(V) or Ir(I)/Ir(III) Catalytic Cycle? Steric-Effect-Controlled
K
https://dx.doi.org/10.1021/acs.organomet.9b00874
Organometallics XXXX, XXX, XXX−XXX