Probing Substrate Diffusion in Interstitial MOF Chemistry with Kinetic Isotope Effects

Article abstract of DOI:10.1002/anie.201713244

Metal–organic frameworks (MOFs) have garnered substantial interest as platforms for site-isolated catalysis. Efficient diffusion of small-molecule substrates to interstitial lattice-confined catalyst sites is critical to leveraging unique opportunities of

Full text of DOI:10.1002/anie.201713244

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Accepted Article
Title: Probing Substrate Diffusion in Interstitial MOF Chemistry with
Kinetic Isotope Effects
Authors: Chen-Hao Wang, Anuvab Das, Wen-Yang Gao, and David C
Powers
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Angewandte Chemie International Edition
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COMMUNICATION
Probing Substrate Diffusion in Interstitial MOF Chemistry with
Kinetic Isotope Effects
ꢀ
Chen-Hao Wang, Anuvab Das, Wen-Yang Gao, and David C. Powers*
Abstract: Metal-organic frameworks (MOFs) have garnered
substantial interest as platforms for site-isolated catalysis. Efficient
diffusion of small molecule substrates to interstitial lattice-confined
catalyst sites is critical to leveraging unique opportunities of these
materials as catalysts. Understanding the rate of substrate diffusion
in MOFs is challenging and few in situ chemical tools are available to
evaluate substrate diffusion during interstitial MOF chemistry. Here,
we demonstrate nitrogen-atom transfer (NAT) from a lattice-confined
Ru
comparison of the intramolecular deuterium kinetic isotope effect
KIE), determined for amination of a partially deuterated substrate,
2
nitride to toluene to generate benzylamine. We use a
(
Figure 1. Active-site confinement of intermediate Q in the active site of
sMMO is critical to intermolecular C–H oxidation in biology. Substrate flux to,
and product egress from, the active site are carefully controlled by
conformationally gated diffusion. For many substrates, comparison of the
intramolecular deuterium kinetic isotope effect (KIE), determined for oxidation
of partially deuterated substrates, with the intermolecular KIE, determined by
with the intermolecular KIE, determined by competitive amination of
a mixture of perdeuterated and undeuterated substrates, to establish
the relative rates of substrate diffusion and interstitial chemistry. We
anticipate the developed KIE-based experiments will contribute to
the development of porous materials for group-transfer catalysis.
competitive oxidation of
a mixture of perdeuterated and undeuterated
substrates, indicates that conformationally gated substrate diffusion is
turnover limiting. The sMMO image is reprinted from reference 2.
Reactive metal–ligand (M–L) multiply bonded complexes
are
critical
intermediates
in
many
biological
C–H
functionalization reactions. Intermediate Q, a diiron(IV) bis-µ-oxo
complex embedded in the active site of soluble methane
monooxygenase (sMMO), is responsible for partial oxidation of
decomposition reactions, such as ligand oxidation chemistry,
bimolecular dimerization, and solvent oxidation reactions, which
prevent utilization of these reactive structures for intermolecular
1
methane to methanol in methanotrophic bacteria (Figure 1).
7
C–H functionalization reactions. For example, diruthenium
Soluble MMO achieves selective partial methane oxidation by
conformationally gated substrate diffusion to, and product
nitride 2 participates in facile intramolecular C–H amination of
2
proximal ligand-based C–H bonds to afford amido complex 3
egress from, the enzyme active site. Analysis of kinetic isotope
8
(
Figure 2a). Metal-organic frameworks (MOFs), which are
effects (KIEs), which measure the impact of isotopic substitution
on reaction rates, can provide direct evidence of
conformationally gated diffusion. For example, sMMO catalyzed
porous materials based on metal ions and organic linking groups,
have been advanced as catalysis platforms based on catalyst
site isolation and because the pore space provides an
opportunity to co-localize substrates in proximity to catalyst
C–H hydroxylation often exhibits large intramolecular KIEs (i.e.
3
k
k
H
/k
/k
D
= 4.2, measured using partially deuterated ethane, where
9
sites. In order to leverage many of the unique opportunities of
H
D
is the ratio of the rates of C–H and C–D functionalization)
4
MOFs in catalysis, substrates must diffuse to interstitial lattice-
confined catalyst sites. While in many cases indirect evidence is
available for the impact of diffusion on substrate
but negligible intermolecular KIEs (i.e. k
H
/k
D
= 1.0, measured
5
using mixtures of perdeuterated and undeuterated substrates).
The combination of large intramolecular KIEs and small
intermolecular isotope effects has been interpreted to indicate
that while C–H cleavage is involved in hydroxylation, diffusional
barriers, which are not sensitive to isotopic substitution, are rate
determining. Similar experimental data indicate that substrate
access to compound I, the oxoiron intermediate in cytochrome
10
functionalization,
experimental tools to directly evaluate
substrate diffusion through porous materials during interstitial
chemistry are lacking.
We were attracted to the hypothesis that confinement of
2
Ru nitride intermediates that are isoelectronic to 2 within porous
6
coordination lattices could enable intermolecular C–H amination.
Development of amination via lattice-confined carboxylate-
P450s, can also be diffusionally limited.
In the absence of a protein superstructure, reactive M–L
multiply bonded complexes can participate in a variety of
supported Ru
principles: 1) M–M cooperation in a Ru
would provide access to highly reactive M–L multiply bonded
2
sites was guided by the following design
2
nitride intermediate
11
intermediates, 2) unlike the formamidinate ligands that are
used to stabilize 2, carboxylate ligands would not present ligand-
based C–H bonds in proximity to reactive M–L multiple bonds,
[*]
C.-H. Wang, A. Das, Dr. W.-Y. Gao, Prof. Dr. D. C. Powers
Department of Chemistry
Texas A&M University
12
3
) confinement of reactive intermediates as structural elements
3255 TAMU, College Station, TX USA
E-mail: david.powers@chem.tamu.edu
of a MOF lattice would suppress bimolecular nitride coupling
13
reactions, and 4) material porosity could co-localize substrate
in proximity to the reactive Ru nitride to facilitate intermolecular
Supporting information for this article is given via a link at the end of
the document.
2
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Angewandte Chemie International Edition
10.1002/anie.201713244
COMMUNICATION
experimental and computed PXRD patterns). Elemental analysis
of [Ru
the Ru
material (empirical formula: [Ru
6
btc
4 3
Cl ] indicates a 2:1 mixture of Cl and OH ligands on
2
sites, which is consistent with previous reports of this
1
4a
6
btc
4
Cl
2
OH]).
N
2
sorption
2
experiments indicate a BET surface area of 746 m /g (Langmuir
2
surface area of 1056 m /g, Figure 3c (black)), which is in good
2
agreement with the literature (BET surface area = 704 m /g and
2
14a
Langmuir surface area = 891 m /g).
-for-Cl exchange is accomplished by soaking
Cl in an aqueous N,N-dimethylformamide (DMF)
solution of NaN Exchange of chloride in preference to
hydroxide at Ru lattice sites is evidenced by elemental analysis,
which is consistent with [Ru btc
formulation, and may arise from the relative bond dissociation
N
3
[
Ru
6
btc
4
3
]
3
.
2
a
6
4 3
Cl0.26(N )1.44(OH)1.3]
18
energies of Ru–Cl and Ru–OH bonds. In an alternative
synthetic route, a material with empirical formula [Ru btc (N
was accessed by treatment of [Ru btc Cl ] first with trimethylsilyl
triflate (TMSOTf) in CH Cl followed by NaN in an aqueous
6
4
3 3
) ]
6
4
3
2
2
3
DMF solution. The azide-exchanged materials obtained from
these two procedures displayed identical amination chemistry
(
vide infra). Prior to subsequent use, the extent of azide
exchange in each batch was assessed by elemental analysis.
The IR spectrum of [Ru btc (N ] displays an isotope-sensitive
signal at 2048 cm , which shifts to 2031 cm
2
Figure 2. (a) Molecular Ru nitride 2 participates in facile C–H amination of
proximal ligand-based C–H bonds. This chemistry exemplifies a challenge
that is frequently encountered in leveraging reactive M–L multiple bonds for
intermolecular C–H functionalization. (b) Lattice confinement of reactive
intermediates within porous materials can enable intermolecular group
6
-1
4
3 3
)
-1
in
1
5
15
[
Ru
6
btc
4
( NN
2
)
3
] (prepared using Na NN
2
, Figure 3d). Ligand
transfer chemistry. Here we disclose toluene amination at a Ru
Similar to sMMO, slow substrate diffusion, as evidenced by the disparity of
intra- and intermolecular KIEs, is operative in this system.
2
MOF node.
exchange is accompanied by a bathochromic shift of the solid-
state UV-vis absorption features, which is similar to UV-vis
spectral changes observed in N
synthesis of compound (Figure S3). [Ru
isomorphous to [Ru btc based on PXRD (Figure 3b).
Extensive soaking of [Ru (N ] in MeOH followed by CH Cl
3
-for-Cl ligand exchange in the
1
6
btc (N is
4
3 3
) ]
6
4
Cl
3
]
nitrogen-atom transfer (NAT). Here, we report the intermolecular
6
btc
4
3
)
3
2
2
2
amination of toluene at a Ru nitride intermediate confined as
allowed for low-temperature activation of this material and
part of a MOF lattice (Figure 2b). Further, using the relative
magnitudes of intra- and intermolecular KIEs for toluene
amination, we demonstrate that substrate diffusion in the
developed porous material is slower than C–H amination. We
anticipate the developed kinetic tools will be useful to the
ongoing development of catalysis with porous materials.
2
determination of a BET surface area of 619 m /g (Figure 3c (red),
see Figure S4 and Table S1 for additional discussion of the
activation of [Ru
6 4 3 3
btc (N ) ]). For comparison, activation of
[
Ru btc Cl ] under identical low-temperature conditions yielded a
6
4
3
2
BET surface area of 662 m /g (Figure 3c (blue)). X-ray
absorption near edge structure (XANES) and magnetometry
We initiated our examination of the potential for lattice-
confined intermolecular group transfer chemistry with
data collected for [Ru
sites in [Ru btc Cl ] are maintained following ion exchange
Figures S5 and S6, respectively).
To investigate potential group-transfer chemistry, we
introduced toluene (PhCH ; bond dissociation energy (BDE) of
6 4 3 3 2
btc (N ) ] indicate that the S=3/2 Ru [II,III]
6
4
3
[
Ru
6 4 3 2
btc Cl ], a porous MOF comprised of Ru [II,III] nodes and
(
3
-
14
1
,3,5-benzene tricarboxylate (btc ) linkers.
[Ru
networks display
a 3-dimensional channel structure and feature three distinct pore
6 4 3
btc Cl ] is
15
isomorphous with Cu
3
btc
2
(HKUST-1).
3 2
M btc
3
19
PhCH
Ru btc
material (PhCH
2
–H is 90 kcal/mol ) into the porous material by soaking
(N ] in PhCH for 6 h. Heating the PhCH -impregnated
@[Ru btc (N ]) to 100 °C resulted in the
16
environments. The smallest pore displays an 8.1 Å M-to-M
separation and is accessed via a 4.0 Å aperture (M–M distance
minus van der Waals radii of Ru). The two larger pores feature
M-to-M separation greater than 11.4 Å and are accessed by a
[
6
4
3
)
3
3
3
3
6
4
3 3
)
-1
disappearance of the azide stretching mode (2048 cm ) in the
IR spectrum (Figure S7). Following acidic work-up, benzylamine
7
.3 Å aperture (M–M distance minus van der Waals radii of Ru).
was observed in 32% yield based on available Ru
speculate that the low yield may be due to inefficient substrate
diffusion to all available Ru sites, for example, due to size
exclusion from the smallest pores in M The generated
2 3
N sites. We
In situ X-ray diffraction studies have demonstrated that while
17
small guests, such as methanol (kinetic diameter: 3.7 Å ), can
access all three pores, larger guests, such as toluene (kinetic
2
N
3
16
3
btc
2
.
1
7
diameter: 5.9 Å ) only access the two larger pores (for
benzylamine was characterized by gas chromatography (GC)
1
6
additional discussion of M
Solvothermal combination of Ru
O and AcOH at 160 °C affords [Ru
Powder X-ray diffraction (PXRD) of the as-synthesized material
indicates that the obtained network is isostructural to Cu btc
HKUST-1, Figure 3b, see Figure S2 for comparison of
3
btc
2
structures, see Figure S1).
(OAc) Cl and H
btc Cl ] (Figure 3a).
1
co-injection (Figure S8), H NMR (Figure S9), and electrospray
2
4
3
btc in
ionization-mass spectrometry (ESI-MS; m/z
=
108.0805,
); Figure S10). Based on
PXRD (Figure S11) and gas sorption (Figure S12) analyses of
the spent Ru -based material, framework crystallinity and
porosity are maintained following thermolysis.
1
4a
H
2
6
4
3
+
2 3
calculated m/z = 108.0808 (PhCH NH
3
2
2
(
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Angewandte Chemie International Edition
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COMMUNICATION
Figure 3. (a) Synthesis of [Ru
Ru btc Cl ], which are isostructural to Cu
activated at 25 °C (adsorption (l), desorption (¡)), and for [Ru
6
btc
4
(N
3
)
3
] and use as a platform for intermolecular nitrogen-atom transfer chemistry. (b) PXRD patterns of [Ru
btc . (c) N sorption isotherms for [Ru btc Cl ] activated at 150 °C (adsorption (l), desorption (¡)), for [Ru
btc (N ] activated at 25 °C (adsorption (l), desorption (¡)). (d) IR spectra of [Ru
6
btc
4
(N
3
)
3
] and
btc Cl
3
btc Cl ],
[
6
4
3
3
2
2
6
4
3
6
4
3
]
6
4
3
)
3
6
4
1
5
[
6 4 3 3 6 4 2 3
Ru btc (N ) ], and [Ru btc ( NN ) ].
To confirm that intermolecular amination of toluene had
occurred, we carried out a series of isotope labeling experiments. Formation of Ru
First, using -toluene resulted in the observation of vis spectroscopies (Figures S13, S14, and S15, respectively),
benzylamine (m/z = 115.1246, calculated m/z = 115.1247 and the structure of Ru (OBz) was confirmed by X-ray
diffraction. We hypothesized that the evolution of N proceeds
via azide binding, extrusion of one equivalent of N to generate a
reactive nitride, and subsequent nitride coupling to generate an
additional 0.5 equivalents of N . Consistent with this hypothesis,
analysis of the N evolved upon treatment of Ru (OBz) BF with
(Figure S16).
-forming reaction from
with concurrent evolution of N
2
(detected by GC, Figure 4).
1
2
(OBz) was indicated by H NMR, IR, and UV-
4
d
8
7
d -
2
4
+
(
C
6
D
5
CD
2
1
NH
3
)). Second, amination of toluene using
2
5
14
15
[
Ru
6
btc
4
( NN
2
)
3
]
led to
a
1:1 mixture of
N- and
N-
2
1
5
benzylamine, which is expected because NN
2
could bind via
either the labeled or the unlabeled terminus (ESI-MS data is
summarized in Figure S10). Control experiments in which the
2
2
2
4
4
1
5
30
NaN
3
soaking solution was decanted and heated in the presence
Na NN
Formation of
mono-labeled NN
2
revealed substantial formation of
N
2
3
0
of toluene resulted in no benzylamine, which confirms the
observed amination chemistry proceeds in the solid state.
Observation of benzylamine and the described isotope-labeling
experiments confirm the viability of intermolecular group transfer
2 2
N implies a bimolecular N
1
5
–
30
2
0
. In contrast to the evolution of
N
2
from
3
Ru
2
(OBz)
4
BF
4
, no
btc
N was detected in the headspace following
2
1
5
treatment of Ru
6
4
Cl
3
with Na NN
2
.
chemistry with the developed Ru
Cyclohexane and benzene do not participate in amination
with [Ru btc (N ], which may be due to the C–H bond strength
of these substrates (BDE: C
2
-based materials.
To gain insight into the selectivity for benzylic versus
aromatic C–H amination, we have pursued a series of kinetic
6
4
3
)
3
isotope effect (KIE) experiments (Figure 5). Amination of d
1
-
20
6
H
11–H, 96 kcal/mol;
kcal/mol ). Ortho-xylene is a competent substrate for amination
~5% yield). Meta- and para-xylene do not participate in
amination, which we hypothesize may be due to restricted
diffusion into the porous Ru material (vide infra).
Unlike lattice-isolated Ru [II,III] sites, analogous Ru
C
6
H
5
–H, 113
toluene proceeds with an intramolecular k /k = 7.86(3) at 100
H
D
1
9
H D
°C (Figure 5a; based on the Arrhenius equation, a k /k ~ 13.2
(
Cl
O
O
O
O
2
Ph
O
NaN3
PhCH3, 23 ºC
Ph
O
Ru
Ru
O
O
Ru
Ru
O
O
2
2
[II,III]
Ph
Ph
O
O
O
O
Ph
Ph
carboxylate complexes do not participate in toluene amination
chemistry. We have carefully examined the reaction chemistry of
-NaCl
-1.5 N2
O
O
Ph
Ph
Ru
the dichotomy between lattice-isolated and homogeneous
catalysts (OBz = benzoate). Treatment of Ru (OBz) Cl, or the
more soluble analog Ru (OBz) BF , with NaN resulted in rapid
one-electron reduction to generate Ru [II,II] complex Ru (OBz)
2 2 4 3
[II,III] complex Ru (OBz) Cl with NaN to better understand
Figure 4. In contrast to lattice confined Ru
Ru azide sites (i.e. [Ru btc (N ]), molecular site analogs participate in rapid
reductive decomposition reactions. Treatment of Ru (OBz) Cl with NaN
results in rapid reduction of the Ru2 core to generate Ru (OBz) with
2
tetracarboxylates, which support
2
6
4
3 3
)
2
4
2
4
3
2
4
4
3
2
4
2
2
4
2
concurrent evolution of N .
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Angewandte Chemie International Edition
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COMMUNICATION
(a)
D
H
NH2
N3
O
O
1
. [Ru6btc4(N3)3]
00 ºC
O
O
1
O
O
Ru
D
NH2
+
NaCl
NaN3
O
O
2
. HCl, H2O;
NaOH
Ru
-N2
a.
b.
d1-toluene
kH / kD = 7.86(3)
Cl
N
O
O
O
O
Ru
O
O
(
b)
O
O
Ru
O
O
D
D
NH2
O
O
O
O
1
. [Ru6btc4(N3)3]
00 ºC
O
Me
Ru
O
Ru
1
NH2
D8/H8
D5
+
2
. HCl, H2O;
NaOH
H
O
R
d.
N
c.
CH3
NH2
O
O
HCl
O
O
Ru
1:1 Mixture of
kH / kD = 1.02(2)
O
O
O
H8- and d8-toluene
Ru
Figure 5. (a) The intramolecular KIE, measured with d
1
-toluene, indicates
that substantial C–H cleavage is involved in the C–H amination transition
state. (b) The intermolecular KIE, measured with a 1:1 mixture of H - and d
toluene, indicates that substrate diffusion is slow relative to amination.
Figure 6.
A synthetic cycle for toluene amination. In single turnover
8
8
-
experiments, each of the steps in the amination cycle has been demonstrated.
Based on the relative magnitudes of intra- and intermolecular KIEs, lack of
catalyst turnover is ascribed to restricted diffusion of substrates within
[Ru btc (N ) ].
would be expected at 25 °C). In contrast, amination of an
equimolar mixture of toluene and d -toluene at 100 °C afforded
an intermolecular /k 1.02(2) (Figure 5b). In these
6
4
3 3
8
k
H
D
=
Inspired by intra- and intermolecular KIE studies that have
experiments, benzylamine isotopomers were quantified by ESI-
MS; data are collected in Figures S17 and S18. Control
been used to elucidate the importance of conformationally gated
substrate diffusion in enzymatic C–H oxidation chemistry, we
have evaluated the relative magnitudes of intra- and
intermolecular KIEs (Figure 5) to probe the role of substrate
diffusion during the amination of toluene. The measured
intramolecular KIE value (7.86(3)) is above the classical limit for
experiments using DCl to liberate benzylamine from our Ru
2
material confirmed that the determined KIEs are not influenced
by the acidic work-up.
The stoichiometric reactions described here constitute
demonstration of a synthetic cycle for nitrogen-atom transfer to
21
H/D isotope effects and is consistent with significant C–H/D
C–H bonds (Figure 6). Lattice-confined Ru
generated by ion exchange into [Ru btc Cl ] (step a, Figure 6).
evolution from Ru sites provides access to a reactive
2
N
3
sites were
cleavage in the NAT transition state and the contribution of
quantum mechanical tunneling. These data suggest that
amination proceeds via initial H-atom abstraction, which is
consistent with the observed selectivity for benzylic C–H
functionalization. The measured intermolecular KIE (1.02(2))
indicates that C–H bond cleavage is not involved in the product-
6
4
3
N
2
2 3
N
nitride equivalent (step b, Figure 6) that is unable to participate
in nitride dimerization, a process which is facile at molecular site
analogs (Figure 4). Insertion of the lattice-confined nitride into a
C–H bond of pore-localized toluene is believed to generate a
benzylamido intermediate (step c, Figure 6). Subsequent
protonation liberates benzylamine (step d). The observed
8
determining step in the amination of mixture of toluene and d -
toluene. Based on the relative magnitudes of intra- and
intermolecular KIEs, lack of catalyst turnover is ascribed to
amination of toluene at Ru
2
sites confined within a MOF lattice
nitrides would
6 4 3 3
restricted diffusion of substrates within [Ru btc (N ) ]. The
confirms the hypothesis that lattice-confined Ru
2
relative lack of discrimination between H and D reflected in the
absence of an intermolecular KIE indicates that selection
between H and D is not possible under these reaction conditions
participate in intermolecular C–H amination chemistry with pore-
confined hydrocarbon substrates.
Given the demonstration of intermolecular NAT chemistry,
and that substrate diffusion in [Ru
C–H amination.
6 4 3 3
btc (N ) ] is slow relative to
2
and the observation that the crystallinity and porosity of the Ru -
based material are maintained following thermolysis, one could
envision achieving amination catalysis if appropriate sources of
protons and azide were available to regenerate the lattice-
In summary, we have demonstrated lattice confinement of
reactive Ru nitride intermediates as strategy for
intermolecular NAT chemistry. Site isolation of reactive Ru
nitride intermediates 1) prevents bimolecular nitride coupling,
which is facile at homogeneous Ru tetracarboxylate complexes
and 2) provides platform for intermolecular C–H
2
a
2
2 2
confined Ru azide from a Ru amido intermediate (steps d and
a, Figure 6). Despite extensive experimentation, we have not
identified conditions to achieve NAT catalysis. Because each of
the steps in the synthetic cycle illustrated in Figure 6 has been
demonstrated in stoichiometric reactions, we speculated that
2
a
functionalization reactions that are challenging to achieve in the
homogeneous milieu. The developed intermolecular C–H
amination provides a venue to directly evaluate the impact of
substrate diffusion on interstitial substrate functionalization.
Comparison of intra- and intermolecular KIEs reveals that while
substantial C–H cleavage is involved in the C–H amination
transition state, substrate diffusion through the microporous
network is slow relative to amination chemistry. We believe the
2
restricted diffusion of substrates and reagents in the Ru network
may be responsible for the lack of observed catalyst turnover.
Consistent with this hypothesis, prolonged pre-soaking of
toluene into [Ru
amination chemistry. Further, using IR spectroscopy, we
determined that exchange of toluene with d -toluene in Ru btc
6 4 3 3
btc (N ) ] was required in order to observe
8
3
2
-
based materials is slow, and requires several hours for complete
exchange (Figure S19).
presented KIE analysis represents
a useful new tool in
understanding the impact of substrate diffusion on interstitial
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Angewandte Chemie International Edition
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COMMUNICATION
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Probing Substrate Diffusion in
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