Palladium nanoparticles encapsulated in a metal-organic framework as efficient heterogeneous catalysts for direct C2 arylation of indoles

Article abstract of DOI:10.1002/chem.201101705

Highly dispersed palladium nanoparticles (Pd NPs) encapsulated in the mesoporous cages of the metal-organic framework (MOF) MIL-101(Cr) have been prepared by using the wetness impregnation method. The Pd NPs were characterized by powder X-ray diffraction (PXRD), N₂ adsorption, transmission electron microscopy, inductively coupled plasma atomic emission spectroscopy (ICP-AES), and X-ray photoelectron spectroscopy (XPS). The particles size ((2.6 ± 0.5) nm) of the obtained Pd NPs was in good agreement with the cage diameters (2.9 and 3.4 nm) of the MOF. The resulting Pd/MIL-101(Cr) catalyst exhibited extremely high catalytic activities in the direct C2 arylation of substituted indoles by using only 0.1 mol-% of the Pd catalyst. Moreover, the catalyst is easily recoverable and can be reused several times without leaching into solution and loss of activity. The combination of the highly dispersible Pd NPs within the accessible mesoporous cages and the favorable adsorption of the aryl halides on MIL-101 are suspected to be the main reasons for the observed high activities of the Pd/MIL-101(Cr) catalyst in the direct C2 arylation of indoles. MOF-encapsulated catalyst: Highly dispersed palladium nanoparticles encapsulated in the mesoporous metal-organic framework (MOF) MIL-101(Cr) exhibited high catalytic activities for the direct C2 arylation of substituted indoles with a range of substituted iodobenzenes (see figure) by only using a very low amount of the Pd catalyst (0.1 mol-%). The catalyst is easily recovered and can be reused several times without leaching into solution and loss of activity.

Full text of DOI:10.1002/chem.201101705

DOI: 10.1002/chem.201101705
Palladium Nanoparticles Encapsulated in a Metal–Organic Framework as
Efficient Heterogeneous Catalysts for Direct C2 Arylation of Indoles
Yuanbiao Huang, Zujin Lin, and Rong Cao*[a]
Abstract: Highly dispersed palladium
nanoparticles (Pd NPs) encapsulated in
the mesoporous cages of the metal–or-
ganic framework (MOF) MIL-101(Cr)
have been prepared by using the wet-
ness impregnation method. The Pd
NPs were characterized by powder X-
ray diffraction (PXRD), N2 adsorption,
transmission electron microscopy, in-
ductively coupled plasma atomic emis-
sion spectroscopy (ICP-AES), and X-
ray photoelectron spectroscopy (XPS).
The particles size ((2.6Æ0.5) nm) of
the obtained Pd NPs was in good
agreement with the cage diameters (2.9
and 3.4 nm) of the MOF. The resulting
Pd/MIL-101(Cr) catalyst exhibited ex-
tremely high catalytic activities in the
direct C2 arylation of substituted in-
doles by using only 0.1 mol% of the Pd
catalyst. Moreover, the catalyst is
easily recoverable and can be reused
several times without leaching into so-
lution and loss of activity. The combi-
nation of the highly dispersible Pd NPs
within the accessible mesoporous cages
and the favorable adsorption of the
aryl halides on MIL-101 are suspected
to be the main reasons for the ob-
served high activities of the Pd/MIL-
101(Cr) catalyst in the direct C2 aryla-
tion of indoles.
À
Keywords: C H activation · heter-
ogeneous catalysis · indoles · metal–
organic framework · nanoparticles ·
palladium
Introduction
surface coordination sites.[9] Unfortunately, these metallic
nanoparticles are unstable with respect to agglomeration to
the bulk. In most cases, this aggregation generally leads to
the loss of the catalytic properties.[9a] Therefore, suitable sta-
bilizers and/or supports for nanoparticle catalysts are gener-
ally required.
Metal–organic frameworks (MOFs) have been emerging
as very promising functional materials for gas storage, sepa-
ration, heterogeneous catalysis, sensing, and drug delivery
due to their high surface area, porosity, and chemical tuna-
bility.[10,11] These unique features make MOFs very attractive
in heterogeneous catalysis. However, the MOFs used for
catalysis should have high thermal and chemical stability.
Additionally, the catalytic active sites of the most MOFs are
not easy accessible for substrates due to the lack of big
pores.[11] So far, only a handful of MOF materials have been
reported to be used as catalysts for organic catalysis[11] and
even fewer of them as host matrices to support metal nano-
particles (NPs) as catalysts for heterogeneous cataly-
sis.[11e,12–15] To the best of our knowledge, up to now, there
are no reports of employing MOFs as supports for metal
The C2-arylated indole substructure is one of the most im-
portant building blocks of biologically active and functional
molecules.[1] Although palladium-catalyzed cross-coupling
reactions provide an efficient approach to these compounds,
such protocols require functionalized indoles and activated
arenes.[1,2] From a sustainable chemistry viewpoint, direct
À
À
transformation of a C H bond into a C C bond is an effi-
cient and environmentally friendly way for the synthesis of
such compounds. Recently, great efforts have been devoted
À
to palladium-catalyzed direct C2 H arylations of indoles
with activated arenes.[3–7] However, unfortunately the expen-
sive palladium catalyst in such a homogeneous form can not
be recovered and is difficult to separate from the products.
Although heterogeneous palladium catalysts have been de-
veloped for their easy separation and feasibility of catalyst
recycling, up to now, there are only few reports describing
À
the direct C2 H arylation of indoles by using heterogeneous
palladium catalysts.[8]
Today, metal nanoparticles show great potential applica-
tion in catalysis because of a great ratio of atoms remaining
at the large surface area and the density of the unsaturated
À
NPs in the direct C H arylation of indoles.
MIL-101(Cr) (Cr
3A
N
N
A
synthesized by Fꢀrey et al.,[16] is an excellent MOF material
due to its extra high specific surface area, its pore volume,
and its high thermal (up to 3008C) and chemical stability to
water and common organic solvents. It has two types of
mesoporous cages (2.9 and 3.4 nm) accessible through mi-
croporous windows (1.2 and 1.4 nm). The combination of
these outstanding features makes it an interesting candidate
for adsorption[17] and catalysis.[12a–g,13h,18] The mesoporous
[a] Dr. Y. Huang, Dr. Z. Lin, Prof. R. Cao
State Key Laboratory of Structural Chemistry
Fujian Institute of Research on the Structure of Matter
Chinese Academy of Science
155 Yangqiao West Road Fuzhou Fujian 335002 (P. R. China)
Fax : (+86)591-83796710
E-mail: rcao@fjirsm.ac.cn
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201101705.
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Chem. Eur. J. 2011, 17, 12706 – 12712

FULL PAPER
cages can be used to confine the metal nanoparticles and to
restrict their growth, which are pertinent features for their
applications in heterogeneous catalysis.[12a–g] Furthermore,
the mesoporous cages and large microporous windows may
allow the large reactant molecules to reach the active site in
the pores and the large product molecules to leave from the
active sites easily. Herein, we choose MIL-101(Cr) to sup-
À
port Pd NPs as a highly active catalyst for the direct C H
arylation of indoles.
Results and Discussion
Preparation and characterization of Pd NPs: MIL-101(Cr)
was synthesized according to the literature.[16] For completed
removal of the unreacted terephthalic acid in the pores, the
as synthesized blue-green samples were solvothermally
treated with DMF, aqueous NH4F solution, and EtOH, re-
spectively. The X-ray powder diffraction (PXRD) patterns
of the resulting solid are coincident with the simulated ones,
confirming the formation of MIL-101(Cr) (Figure 1). Nitro-
&
Figure 2. Nitrogen sorption isotherms at 77.3 K for MIL-101(Cr) ( =ad-
~
~
sorption, & =desorption) and Pd/MIL-101(Cr) ( =adsorption, =de-
sorption).
using the Nano Mersurer 1.2 version software.[12a] However,
although the impregnated MIL-101(Cr) samples containing
palladium salts have been repeatedly washed till the filtrate
became colorless, few nanoparticles still remain outside the
pores due to the electrostatic interactions between the MIL-
101(Cr) and palladium.[12e] The decrease in surface area and
pore size indicate that the cavities of MIL-101(Cr) may be
occupied by palladium NPs and/or blocked by palladium
NPs that are located at the surface (Figure 2 and Table 1).[12]
X-ray photoelectron spectroscopy (XPS) (Figure 4) and
EDS data (Figure 3) indicate that Pd0 and CrIII coexist in
the Pd/MIL-101(Cr) materials. In the XPS traces, the 3d5/2
and 3d3/2 peaks of Pd0 appear at 336.2 and 341.4 eV and no
obvious peak of Pd2+ is observed, which indicates that most
of the palladium is in the reduced form.[12r]
Catalysis of C2-arylation of indoles: It is well known that
À
the activation of C H bonds is very important for organic
Figure 1. Powder XRD patterns of MIL-101 samples: a) MIL-101, simu-
lated; b) MIL-101, activated; c) Pd/MIL-101, before reaction; d) Pd/MIL-
101, after five runs of catalysis.
synthesis.[3–7] The C2 H arylation of N-methylindoles cata-
À
lyzed by Pd
(OAc)2 in homogeneous catalysis is sensitive to
the reaction conditions, such as solvent and/or base. Herein,
N-methylindole and iodobenzene were employed as the sub-
strates for the screening of optimized reaction conditions for
gen adsorption measurements showed a high specific surface
area of the obtained porous material (SBET =3447.7 m2 gÀ1,
Figure 2), which is in agreement with the previously report-
ed data.[16] The supported Pd NP catalyst, denoted as Pd/
MIL-101(Cr), was prepared through solution infiltraion of
À
direct C2 H arylation over Pd/MIL-101(Cr). It is notewor-
thy that almost no C3-arylation product is formed in the fol-
À
lowing cases. Our initial efforts towards the direct C2 H ar-
ylation of N-methylindoles in DMF were focused on the
base (Table 2, entries 1–5). It should be noted that the reac-
tion can not proceed without addition of a base (Table 2,
entry 6). It became apparent that the organic base NEt3 is
not a suitable base for this reaction (Table 2, entry 1). A
series of inorganic bases has been investigated. The coupling
reactions gave moderate yields in the presence of KOAc
and Cs2CO3 (Table 2, entries 3, 4). Interestingly, the results
show that cesium acetate is the optimum reagent (85%
yield, Table 2, entry 5), which indicates that both the cation
(Cs+) and anion (OAcÀ) play an essential role.[3]
activated MIL-101(Cr) with PdACHTNUGTRNEUNG(NO3)2 as precursor, followed
by treatment with H2 at 2008C for 4 h. PXRD patterns
(Figure 1) show that the frameworks of MIL-101(Cr) do not
change after the Pd loading (ca. 0.5 wt%). The characteris-
tic peak of Pd (111) at 2q=40.18 is indistinguishable due to
the low Pd loading amount and the small well-dispersed Pd
NPs.[12] TEM images (Figure 3) of Pd/MIL-101(Cr) indicate
that most of the dispersed Pd NPs are successfully encapsu-
lated in the cages of the MIL-101(Cr), with a mean diameter
of (2.6Æ0.5) nm (Figure 3), based on TEM observation by
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R. Cao et al.
Figure 4. XPS spectrum of a Pd/MIL-101(Cr) sample.
Table 2. Optimization of direct arylation of N-methylindole with PhI.[a]
Entry Catalyst
(Pd [mol%])
Solvent Base
T
Yield
G
E
A
ACHTUNGTRENNUNG
1
2
3
4
Pd/MIL-101(Cr) (0.1)
Pd/MIL-101(Cr) (0.1)
Pd/MIL-101(Cr) (0.1)
Pd/MIL-101(Cr) (0.1)
Pd/MIL-101(Cr) (0.1)
Pd/MIL-101(Cr) (0.1)
Pd/MIL-101(Cr) (0.1)
Pd/MIL-101(Cr) (0.1)
Pd/MIL-101(Cr) (0.1)
Pd/MIL-101(Cr) (0.1)
Pd/MIL-101(Cr) (0.1)
MIL-101(Cr)
DMF
DMF
DMF
DMF
DMF
DMF
xylene
NEt3
120 trace
120 24
120 41
120 38
120 85
Na2CO3
KOAc[c]
Cs2CO3
CsOAc
–
5
6[d]
7
120
0
CsOAc
120 trace
120 37
120 82
25 trace
75 26
8
9
NMP[e] CsOAc
DMA[f] CsOAc
DMF
DMF
DMF
10
11
12
13
14
15
16
17
18[h]
19[i]
20[j]
21[k]
22
23
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
120
0
Pd/MIL-101(Cr) (0.05) DMF
120 31
120 78
Pd/MIL-101(Cr) (0.5)
Pd/MIL-101(Cr) (1)
Pd/MIL-101(Cr) (5)
DMF
DMF
DMF
120 64 (18)[g]
120 45 (32)[g]
120 31
Figure 3. a,b) TEM and HRTEM images of Pd/MIL-101(Cr) (0.56wt%
Pd) before the reaction and c) after five catalytic cycles. d) Size distribu-
tion of Pd NPs. The inset of a) shows the energy-dispersive X-ray spec-
troscopy (EDS) pattern.
Pd/MIL-101(Cr) (0.01) DMF
Pd/MIL-101(Cr) (0.1)
Pd/MIL-101(Cr) (0.1)
Pd/MIL-101(Cr) (0.1)
Pd/MIL-101(Cr) (0.1)
Pd/C (0.5)
DMF
DMF
DMF
DMF
DMF
DMF
120 trace
120 21
120 22
120 57
120 trace (22)[g]
120 25 (11)
Table 1. Surface area measurements for MIL-101(Cr) and Pd/MIL-
101(Cr) (0.56 wt% Pd).
[l]
Pd/MIL-53(Al)-NH2
AHCTUNGTERG(NNUN 0.5)
Sample
BET
Langmuir
surface
Pore
volume
Pore
size
[nm]
[a] Conditions: N-methylindole (1 mmol), iodobenzene (1.2 mmol), t=
24 h, under air. [b] Yield of isolated product based on N-methylindole.
[c] Ac=acetate. [d] No base was added. [e] NMP=N-methyl-2-pyrroli-
done. [f] DMA=dimethylacetamide. [g] Biphenyl was formed as byprod-
uct. [h] t=3 h. [i] t=6 h. [j] The MIL-101(Cr) catalyst was removed after
6 h. The filtrate was kept on stirring for 24 h. [k] t=12 h. [l] Pd/MIL-
surface
area
A
]
A
]
ACHTUNGTRENNUNG ]
[m2 gÀ1
MIL-101(Cr)
Pd/MIL-101(Cr)
3447.7
2245.6
5713.5
3800.9
1.88
1.31
2.20
2.18
53(Al)-NH2 =Al(OH)ACTHNUTRGNE[UNG H2N-BDC], H2N-BDC=2-aminoterephthalic acid.
The influence of the solvents was then examined. Xylene
was found to be ineffective in promoting the reaction
(Table 2, entry 7). NMP was also less effective and gave
moderate yield (Table 2, entry 8). It was found that the rate
of the coupling reaction was significantly improved and the
best yields were obtained in DMF or DMA (Table 2, en-
tries 5 and 9). The temperature also affects the rate of the
reaction. The substrates can not be activated at room tem-
perature (Table 2, entry 10). At 758C only a low yield was
obtained (Table 2, entry 11). To obtain good yields, a higher
temperature (1208C) was required (Table 2, entry 5), which
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Palladium Nanoparticles for Direct C2 Arylation of Indoles
is similar to the corresponding homogeneous reaction cata-
FULL PAPER
Table 3. Direct arylation of N-methylindole with various aryl halides.[a]
lyzed by PdACHTUNGTRENNUNG
(OAc)2.[3]
As shown in Table 2, the amount of catalyst is also very
important for this reaction. The reaction does not take place
in the presence of only MIL-101(Cr). The use of 0.05 mol%
Pd catalyst gave only 31% yield (Table 2, entry 13). It is
very interesting that N-methylindole can be activated effec-
tively by only 0.1 mol% Pd catalyst, which gave a very high
yield (86%, Table 2, entry 5). In contrast, higher catalyst
loadings (up to 0.5 mol%) are generally required in the ho-
mogeneous catalyst system.[3–7] It should be noted that in
most cases only traces of the byproduct biphenyl were ob-
tained from the palladium-catalyzed Ullmann coupling reac-
tion of iodobenzene.[3c,12a] However, increasing the amount
of the catalyst (starting from 0.5 mol% Pd) led to a steady
decrease of the yield of the desired product, but an increase
of the yield of the byproduct biphenyl (Table 2, entries 14–
16). This observation indicates that the Ullmann coupling
reaction represents a key competitive process of the direct
C2 arylation of N-methylindoles. Consequently, a decrease
of the catalyst amount can favor the production of the de-
sired product and suppress the formation of biphenyl, which
requires a bimolecular transmetalation of the aryl–palladium
species.[3c] The influence of the reaction time was also exam-
ined. Considering the slow diffusion of the reactants to
reach accessible metal sites in the pores and the low catalyst
loading, a long reaction time (about 24 h) was necessary to
obtain good yields of the desired product. It is worthy
Entry
1
X
I
R3
H
Product
Yield [%][b]
85
2[c]
3[d]
4
Br
Cl
I
H
H
31
21
89
4-CN
5
I
3-CN
83
6
7
8
9
I
I
I
I
4-CF3
4-COOEt
4-Me
88
86
84
74
4-OMe
10
I
I
3-OMe
2-OMe
71
49
noting that reactions catalyzed by PdACTHNUTRGENUG(N OAc)2 also need pro-
11[e]
longed reaction time (24 h) to give good yields.[3]
For comparison, different supported palladium catalysts
have been examined under the same conditions. A commer-
cial Pd/C catalyst (5 wt% Pd) only gave traces of the C2-ar-
ylation product and 22% of the byproduct biphenyl
(Table 2, entry 22). A low activity was also observed for our
previous palladium-supported MIL-53(Al)-NH2 catalyst
(Table 2, entry 23), which exhibits high activity for the
Suzuki reaction.[19] The high activity of Pd/MIL-101(Cr), as
compared to Pd/C and Pd/MIL-53(Al)-NH2, may be as-
cribed to the larger surface area and accessible mesoporous
cages of MIL-101, which may ensure the high dispersion of
the palladium active sites and facilitate the diffusion of the
reactants and the large product molecules in the pores.[12a]
Moreover, it can not be excluded that the enhanced surface
Lewis acidity of MIL-101(Cr) may favor the adsorption of
the aryl halides, and thus enhance the activity.[12a,b]
[a] Conditions: N-methylindole (1 mmol), substituted iodobenzene
(1.2 mmol), CsOAc (2 mmol), cat. (0.1 mol% Pd), DMF (3 mL), 1208C,
24 h, under air. [b] Yield of isolated product. [c] Bromobenzene
(2 mmol), 1508C, 48 h. [d] Chlorobenzene (2 mmol),1508C, 48 h. [e] 2-
Methoxyl-iodobenzene (2 mmol), 5% of the C3-arylation product were
obtained, based on GC-MS.
of substituted iodobenzenes, bearing electron-withdrawing
groups (CN, CF3, and COOEt), with N-methylindole, giving
excellent yields (Table 3, entries 4–7). Electron-rich func-
tional groups in para and meta position to the iodine are
also well tolerated in these reactions. Reactions between N-
methylindole and a variety of iodobenzenes substituted with
electron-donating groups (4-Me, 3-OMe, and 4-OMe) gave
the C2-arylation products in good yields (Table 3, entries 8–
10). Notably, the sterically hindered 2-iodoanisole, bearing
an electron-donating group, also proceeded smoothly, af-
fording the corresponding C2-arylation product in moderate
yield (Table 3, entry 11). It should be noted that only traces
of the C3-arylation product were obtained for the above-
mentioned, substituted iodobenzenes, except for 2-iodoani-
sole (about 5% of the C3-arylation product were obtained,
due to the sterically hindrance).[3]
We next examined the scope of the reactions with a varie-
ty of substituted aryl halides (Table 3). Due to the high
À
À
bond energy of the C Br and C Cl bonds, the activation of
bromobenzene and chlorobenzene is difficult. Therefore, the
reaction of bromobenzene/chlorobenzene with N-methylin-
dole required harsh conditions and extended reaction time.
Unfortunately, even at 1508C after 48 h low yields were ob-
tained for the reaction of bromobenzene/chlorobenzene
with N-methylindole (Table 3, entries 2 and 3), which is sim-
Subsequently, the influence of the substituent group at
the indole on the direct arylation reactions was also exam-
ined. It was found that the process catalyzed by Pd NPs is
ilar to the Pd
the reactions proceeded extraordinarily well with a variety
ACHTUNGTRENNUNG
(OAc)2-catalyzed reactions.[3–7] Interestingly,
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R. Cao et al.
able to transfer most aryl substituents on the indole to form
the C2 regioisomer with excellent selectivity and in good
replacing the benzene ring of N-methylindole with a pyri-
dine group did not affect the yield (Table 4, entry 10).
À
yields (except for the free N H indole; in this case about
4% of the C3-arylation product were obtained). As shown
in Table 4, the substituent on the indole nitrogen atom dra-
It is known that one of the disadvantages of supported Pd
catalysts is the leaching of palladium into solution, resulting
in the contamination of the product with metal and the loss
of the activity of the supported Pd catalysts.[20] For these rea-
sons, leaching of the metal from the Pd/MIL-101(Cr) cata-
lyst has been examined. After the workup, inductively cou-
pled plasma atomic emission spectroscopy (ICP-AES) anal-
ysis showed that the amount of Pd leaching into the reaction
mixture was very low (0.4 ppm), which satisfies specifica-
tions required by the pharmaceutical industry regarding the
final purity of the products (c(Pd)<2 ppm).[20] The result
may be attributed to the fact that the escape of the nanopar-
ticles from the mesoporous cages (2.9 and 3.4 nm) is difficult
through the microporous windows (1.2 and 1.4 nm). There
was also no detectable leaching of chromium to the reaction
mixtures because of the high stability of MIL-101(Cr)
(c(Cr)<0.1 ppm for drinking water),[18a] so the support will
not contaminate the environment. If the catalyst was re-
moved after 20% of conversion (after 6 h) and the resulting
filtrate was monitored under identical reaction condition for
another 24 h; no further conversion was detected (Table 2,
entry 20). Advantages of the Pd/MIL-101(Cr) catalyst are
the fact that the catalytic reactions can be conveniently car-
ried out in air and that the separation of the catalyst can be
achieved easily by centrifugation. After being recycled for
five runs of the reaction of N-methylindole and iodoben-
zene, the Pd catalyst still exhibits a remarkable activity (the
yield decreased only for 4%) (Figure 5). The PXRD study
showed that the crystalline structure of the catalyst is mostly
retained after five catalytic cycles (Figure 1). The TEM
image of the reused catalyst revealed that the size of the Pd
NPs is very similar to that before the reaction (Figure 2).
This may be ascribed to the fact that the Pd NPs are con-
fined in the mesoporous cages and their growth is thus re-
Table 4. Direct arylation of various indoles with PhI.[a]
Entry
1
Indole
Product
Yield [%][b]
85
2[c]
18[c]
91
3
4
5
0
67
6
7
8
84
85
71
9
78
81
10
[a] Conditions: indole (1 mmol), PhI (1.2 mmol), CsOAc (2 mmol), cat.
(0.1 mol% Pd), DMF (3 mL), 1208C, 24 h. [b] Yield of isolated product.
[c] Crude yield based on GC-MS, about 4% of the C3-arylation product
were obtained.
matically influences the reaction. The N-methylindole is
À
more reactive than the free N H indole (Table 4, entries 1
and 2). Interestingly, the use of N-(n-butyl)indole gave a
higher yield than N-methylindole (Table 4, entry 3). In con-
trast, N-acetylindole was inactive in the reaction. The N-
methylindole derivative, which contains an electron-rich
substituent on the 5-position of the benzene segment
(Table 4, entry 6) exhibited a higher yield than the deriva-
tive with an electron-withdrawing group (Table 4, entry 9).
Notably, the substituents at the different positions of the
benzene segment obviously affect the yield of the products
(Table 4, entries 5–8). The N-methylindole derivatives,
which contain a methoxy substituent at the 5- or 6-position
of the benzene segment gave higher yields than the ones
bearing the substituents at the 4- or 7-position. Interestingly,
Figure 5. Catalytic activity of the recycle experimental of N-methylindole
and iodobenzene at 1208C for 24 h. Every experiment was repeated
twice and the yields are the average of the two experiments. The error
was within 3%.
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Chem. Eur. J. 2011, 17, 12706 – 12712

Palladium Nanoparticles for Direct C2 Arylation of Indoles
FULL PAPER
stricted. These results indicate that the reaction proceeds in
a heterogeneous fashion.[12–15]
Acknowledgements
We acknowledge the financial support from 973 Program
(2011CB932504, 2007CB815303), NSFC (2103128, 20731005 and
91022007), Fujian Key Laboratory of Nanomaterials (2006L2005), the
Key Project from CAS and FJIRSM (SZD07002).
Conclusion
In conclusion, we have developed a highly efficient hetero-
geneous catalyst system for the direct C2 arylation of in-
doles by using Pd NPs encapsulated in the mesoporous
MOF MIL-101(Cr). The direct C2 arylation of indoles by
using only 0.1 mol% Pd as catalyst afforded the desired
products in good yields. Furthermore, the catalyst is easily
recoverable and can be reused several times without leach-
ing and loss of activity.
[1] a) N. K. Garg, R. Sarpong, B. M. Stolz, J. Am. Chem. Soc. 2002, 124,
13179–13184; b) S. Cacchi, G. Fabrizi, Chem. Rev. 2005, 105, 2873–
2920.
[2] a) C. G. Hartung, A. Fecher, B. Chapell, V. Snieckus, Org. Lett.
2003, 5, 1899; b) X. Cai, V. Snieckus, Org. Lett. 2004, 6, 2293; c) Z.
Zhao, A. Jaworski, I. Piel, V. Sniekus, Org. Lett. 2008, 10, 2617–
2620; d) M. Miyasaka, A. Fukushima, T. Satoh, K. Hirano, M.
Miura, Chem. Eur. J. 2009, 15, 3674–3677.
[3] a) B. S. Lane, M. A. Brown, D. Sames, J. Am. Chem. Soc. 2005, 127,
8050–8057; b) X. Wang, D. V. Gribkov, D. Sames, J. Org. Chem.
2007, 72, 1476–1479; c) B. S. Lane, D. Sames, Org. Lett. 2004, 6,
2897–2900; d) B. B. Tourꢀ, B. S. Lane, D. Sames, Org. Lett. 2006, 8,
1979–1982; e) B. Sezen, D. Sames, J. Am. Chem. Soc. 2003, 125,
5274–5275.
[4] a) N. Lebrasseur, I. Larrosa, J. Am. Chem. Soc. 2008, 130, 2926–
2927; b) J. Cornella, P. Lu, I. Larrosa, Org. Lett. 2009, 11, 5506–
5509.
[5] a) S. Potavathri, K. C. Pereira, S. I. Gorelsky, A. Pike, A. P. LeBris,
B. DeBoef, J. Am. Chem. Soc. 2010, 132, 14676–14681; b) J. Zhao,
Y. Zhang, K. Cheng, J. Org. Chem. 2008, 73, 7428–7431; c) E. T.
Nadres, A. Lazareva, O. Daugulis, J. Org. Chem. 2011, 76, 471–483;
d) L. Joucla, N. Batail, L. Djakovitch, Adv. Synth. Catal. 2010, 352,
2929–2936; e) D. R. Stuart, K. Fagnou, Science 2007, 316, 1172; f) F.
Bellina, S. Cauteruccio, R. Rossi, Eur. J. Org. Chem. 2006, 1379–
1382; g) S. Kirchberg, R. Frçhlich, A. Studer, Angew. Chem. 2009,
121, 4299–4302; Angew. Chem. Int. Ed. 2009, 48, 4235–4238; h) L.
Joucla, L. Djakovitch, Adv. Synth. Catal. 2009, 351, 673; i) G. Cusati,
L. Djakovitch, Tetrahedron Lett. 2008, 49, 2499.
[6] a) X. Chen, K. M. Engle, D. H. Wang, J. Q. Yu, Angew. Chem. 2009,
121, 5196–5217; Angew. Chem. Int. Ed. 2009, 48, 5094–5115;
b) N. R. Deprez, D. Kalyani, A. Krause, M. S. Sanford, J. Am.
Chem. Soc. 2006, 128, 4972–4973; c) Z. Liang, B. Yao, Y. Zhang,
Org. Lett. 2010, 12, 3185–3187; d) N. S. Nandurkar, M. J. Bhanusha-
li, M. D. Bhor, B. M. Bhanage, Tetrahedron Lett. 2008, 49, 1045–
1048; e) F. Jafarpour, S. Rahiminejadan, H. Hazrati, J. Org. Chem.
2010, 75, 3109–3112; f) D. R. Stuart, E. Villemure, K. Fagnou, J.
Am. Chem. Soc. 2007, 129, 12072.
[7] a) Y. Li, W. H. Wang, S. D. Yang, B. J. Li, C. Feng, Z. J. Shi, Chem.
Commun. 2010, 46, 4553–4555; b) S. D. Yang, C. L. Sun, Z. Fang,
B. J. Li, Y. Z. Li, Z. J. Shi, Angew. Chem. 2008, 120, 1495–1498;
Angew. Chem. Int. Ed. 2008, 47, 1473–1476.
[8] L. Wang, W. B. Yi, C. Cai, Chem. Commun. 2011, 47, 806–808.
[9] a) A. Roucoux, J. Schulz, H. Patin, Chem. Rev. 2002, 102, 3757–
3778; b) R. Schlçgl, S. B. A. Hamid, Angew. Chem. 2004, 116, 1656;
Angew. Chem. Int. Ed. 2004, 43, 1628–1637; c) N. Yan, C. Xiao, Y.
Kou, Chem. Soc. Rev. 2010, 39, 1179–1218; d) N. R. Shiju, V. V. Gu-
liants, Appl. Catal. A 2009, 356, 1–17; e) E. Moreno-MaÇas, R.
Pleixats, Acc. Chem. Res. 2003, 36, 638–643; f) M. C. Daniel, D.
Astruc, Chem. Rev. 2004, 104, 293–346; g) L. Yin, J. Liebscher,
Chem. Rev. 2007, 107, 133–173.
Experimental Section
[21]
Materials: MIL-101(Cr)[16] and MIL-53(Al)-NH2 were synthesized ac-
cording to the literatures. The as synthesized MIL-101(Cr) was activated
by solvothermal treatment with DMF (1508C for 12 h), aqueous NH4F
solution (0.1m, 708C for 12 h), and EtOH (1208C for 12 h), respectively.
The obtained blue-green MIL-101(Cr) samples were dried at 1508C
under vacuum for 24 h. The obtained MIL-53(Al)-NH2 was washed with
DMF, followed by soaking in methanol at 708C for 24 h. The solid was fi-
nally dried overnight at 1308C under vacuum. The catalysis substrates 5-
cyano-N-methylindole, 4-methoxyl-N-methylindole, 5-methoxyl-N-meth-
ylindole, 6-methoxyl-N-methylindole, 7-methoxyl-N-methylindole, and 1-
methyl-1H-pyrroloACHTUNGTRENNUNG[2,3-b]pyridine were synthesized according to the liter-
atures.[3c] N-(n-Butyl)indole was synthesized by a similar method de-
scribed in the literature[3c] by using indole and butyl bromide in the pres-
ence of NaH at 08C. All other reagents were commercial purchased and
used as received.
Catalyst preparation: Pd/MIL-101(Cr) was prepared through a simple im-
pregnation method. Typically, the activated MIL-101(Cr) powder
(200 mg) was dispersed in deionized water (20 mL) and was subjected to
ultrasonication for 30 min. A fresh aqueous solution of PdACHTNUGTRNEG(UN NO3)2 (10 mg,
10 mL) was slowly added dropwise to this solution under vigorous stir-
ring for about 15 min. The suspension was then stirred at room tempera-
ture for further 24 h. The impregnated MIL-101(Cr) sample was washed
with water till the filtrate became colorless and was dried under vacuum
at 1508C for 24 h. The as synthesized sample was treated in a stream of
H2 at 2008C for 4 h to give Pd/MIL-101(Cr). The Pd loading on the MIL-
101(Cr) was 0.56 wt% based on ICP-AES analysis. Pd/MIL-53(Al)-NH2
was prepared by using an ion exchange method.[19] The Pd loading on the
MIL-53(Al)-NH2 was 0.97 wt% based on ICP-AES analysis.
Typical catalysis experimental procedure: Typically, N-methylindole
(1 mmol), aryl halide (1.2 mmol), CsOAc (2 mmol), and the palladium
catalyst (20 mg, 0.1 mol% Pd) were added to DMF (3 mL). The reaction
mixture was stirred at 1208C for 24 h. After cooling to room tempera-
ture, the solution was centrifuged and washed with ethyl acetate for
three times. The organic phase was subsequently washed with water and
brine and then dried over Na2SO4. The product was purified by silica gel
chromatography (mixture of light petroleum and ethyl acetate as eluent).
[10] a) J. R. Long, O. M. Yaghi, Chem. Soc. Rev. 2009, 38, 1213; b) S. Ki-
tagawa, R. Kitaura, S. Noro, Angew. Chem. 2004, 116, 2388; Angew.
Chem. Int. Ed. 2004, 43, 2334; c) A. Phan, C. J. Doonan, F. J. Uribe-
Romo, C. B. Knobler, M. OꢂKeeffe, O. M. Yaghi, Acc. Chem. Res.
2010, 43, 58; d) J. Li, R. J. Kuppler, H. Zhou, Chem. Soc. Rev. 2009,
38, 1477; e) A. M. Spokoyny, D. Kim, A. Sumrein, C. A. Mirkin,
Chem. Soc. Rev. 2009, 38, 1218; f) T. Dꢃren, Y. Bae, R. Q. Snurr,
1
The identification was conducted by H and 13C NMR measurement.
For the measurement of the Pd leaching during the reaction, a hot-filtra-
tion experiment was run to investigate if the reaction proceeded in a het-
erogeneous or homogeneous fashion. After 6 h, the catalyst was separat-
ed by hot filtration and the filtrate was further treated under the same
conditions for another 24 h. For the recyclability test, the catalyst was re-
covered from each of the reaction of N-methylindole with iodobenzene
at 1208C for 24 h, washed with water and ethanol several times, and then
dried under vacuum at 1508C for the next use.
ˇ
Chem. Soc. Rev. 2009, 38, 1237; g) L. J. Murray, M. Dinca, J. R.
Long, Chem. Soc. Rev. 2009, 38, 1294; h) T. Uemura, N. Yanai, S. Ki-
tagawa, Chem. Soc. Rev. 2009, 38, 1228; i) Z. Wang, S. M. Cohen,
Chem. Soc. Rev. 2009, 38, 1315.
Chem. Eur. J. 2011, 17, 12706 – 12712
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
12711

R. Cao et al.
[11] a) L. Ma, C. Abney, W. Lin, Chem. Soc. Rev. 2009, 38, 1248; b) J.
Lee, O. K. Farha, J. Roberts, K. A. Scheidt, S. T. Nguyen, J. T. Hupp,
Chem. Soc. Rev. 2009, 38, 1450; c) A. Corma, H. Garcꢄa, F. X. L. i.
Xamena, Chem. Rev. 2010, 110, 4606; d) Z. Wang, G. Chen, K.
Ding, Chem. Rev. 2009, 109, 322; e) M. Meilikhov, K. Yusenko, D.
Esken, S. Turner, G. V. Tendeloo, R. A. Fischer, Eur. J. Inorg. Chem.
2010, 3701; f) D. Farrusseng, S. Aguado, C. Pinel, Angew. Chem.
2009, 121, 7638–7649; Angew. Chem. Int. Ed. 2009, 48, 7502–7513;
g) K. Ding, Z. Wang, X. Wang, Y. Liang, X. Wang, Chem. Eur. J.
2006, 12, 5188.
[15] R. J. T. Houk, B. W. Jacobs, F. E. Gabaly, N. N. Chang, A. A. Talin,
D. D. Graham, S. D. House, I. M. Robertson, M. D. Allendorf, Nano
Lett. 2009, 9, 3413–3418.
[16] G. Fꢀrey, C. Mellot-Draznieks, C. Serre, F. Millange, J. Dutour, S.
Surblꢀ, I. Margiolaki, Science 2005, 309, 2040.
[17] a) S. Bernt, V. Guillerm, C. Serre, N. Stock, Chem. Commun. 2011,
47, 2838–2840; b) J. Ehrenmann, S. K. Henninger, C. Janiak, Eur. J.
Inorg. Chem. 2011, 471–474; c) D. Dybtsev, C. Serre, B. Schmitz, B.
Panella, M. Hirscher, M. Latroche, P. L. Llewellyn, S. Cordier, Y.
Molard, M. Haouas, F. Taulelle, G. Fꢀrey, Langmuir 2010, 26,
11283–11290; d) Z. Y. Gu, X. P. Yan, Angew. Chem. 2010, 122,
1519–1522; Angew. Chem. Int. Ed. 2010, 49, 1477–1480; e) N.
Klein, A. Henschel, S. Kaskel, Microporous Mesoporous Mater.
2010, 129, 238–242; f) L. Hamon, C. Serre, T. Devic, T. Loiseau, F.
Millange, G. Fꢀrey, G. De Weireld, J. Am. Chem. Soc. 2009, 131,
8775–8777; g) P. Chowdhury, C. Bikkina, S. Gumma, J. Phys. Chem.
C 2009, 113, 6616–6621; h) P. Kꢃsgens, M. Rose, I. Senkovska, H.
Frçde, A. Henschel, S. Siegle, S. Kaskel, Microporous Mesoporous
Mater. 2009, 120, 325–330; i) S. H. Jhung, J. H. Lee, J. W. Yoon, C.
Serre, G. Fꢀrey, J. S. Chang, Adv. Mater. 2007, 19, 121–124; j) M.
Latroche, S. Surblꢀ, C. Serre, C. Mellot-Draznieks, P. L. Llewellyn, J.
H. Lee, J. S. Chang, S. H. Jhung, G. Fꢀrey, Angew. Chem. 2006, 118,
8407–8411; Angew. Chem. Int. Ed. 2006, 45, 8227–8231.
[18] a) O. V. Zalomaeva, K. A. Kovalenko, Y. A. Chesalov, M. S. Mel’gu-
nov, V. I. Zaikovskii, V. V. Kaichev, A. B. Sorokin, O. A. Kholdeeva,
V. P. Fedin, Dalton Trans. 2011, 40, 1441; b) E. Kockrick, T. Les-
couet, E. V. Kudrik, A. B. Sorokin, D. Farrusseng, Chem. Commun.
2011, 47, 1562–1564; c) N. V. Maksimchuk, K. A. Kovalenko, V. P.
Fedin, O. A. Kholdeeva, Adv. Synth. Catal. 2010, 352, 2943–2948;
d) N. V. Maksimchuk, K. A. Kovalenko, S. S. Arzumanov, Y. A.
Chesalov, M. S. Melgunov, A. G. Stepanov, V. P. Fedin, O. A. Khol-
deeva, Inorg. Chem. 2010, 49, 2920–2930; e) J. Juan-AlcaÇiz, E. V.
Ramos-Fernandez, U. Lafont, J. Gascon, F. Kapteijn, J. Catal. 2010,
269, 229–241; f) J. Kim, S. Bhattacharjee, K. E. Jeong, S. Y. Jeong,
W. S. Ahn, Chem. Commun. 2009, 3904–3906; g) M. Banerjee, S.
Das, M. Yoon, H. J. Choi, M. H. Hyun, S. M. Park, G. Seo, K. Kim,
J. Am. Chem. Soc. 2009, 131, 7524–7525; h) Y. K. Hwang, D. Y.
Hong, J. S. Chang, H. Seo, M. Yoon, J. Kim, S. H. Jhung, C. Serre,
G. Fꢀrey, Appl. Catal. A 2009, 358, 249–253; i) N. V. Maksimchuk,
M. N. Timofeev, M. S. Melgunov, A. N. Shmakov, Y. A. Chesalov,
D. N. Dybtsev, V. P. Fedin, O. A. Kholdeeva, J. Catal. 2008, 257,
315–323.
[12] a) B. Yuan, Y. Pan, Y. Li, B. Yin, H. Jiang, Angew. Chem. 2010, 122,
4148; Angew. Chem. Int. Ed. 2010, 49, 4054; b) Y. Pan, B. Yuan, a Y.
Li, D. He, Chem. Commun. 2010, 46, 2280; c) Y. K. Hwang, D. Y.
Hong, J. S. Chang, S. H. Jhung, Y. K Seo, J. Kim, A. Vimont, M. D,
C. Serre, G. Fꢀrey, Angew. Chem. 2008, 120, 4212; Angew. Chem.
Int. Ed. 2008, 47, 4144; d) D. Y. Hong, Y. K. Hwang, C. Serre, G.
Fꢀrey, J. S. Chang, Adv. Funct. Mater. 2009, 19, 1537; e) M. S. El-
Shall, V. Abdelsayed, A. E. R. S. Khder, H. M. A. Hassan, H. M. El-
Kaderi, T. E. Reich, J. Mater. Chem. 2009, 19, 7625; f) A. Henschel,
K. Gedrich, R. Kraehnert, S. Kaskel, Chem. Commun. 2008, 4192;
g) J. Hermannsdçrfer, R. Kempe, Chem. Eur. J. 2011, 17, 8071; h) S.
Opelt, S. Tꢃrk, E. Dietzsch, A. Henschel, S. Kaskel, E. Klemm,
Catal. Commun. 2008, 9, 1286; i) S. Gao, N. Zhao, M. Shu, S. Che,
Appl. Catal. A 2010, 388, 196; j) S. Hermes, F. Schrçder, S. Amirja-
layer, R. Schmid, R. A. Fischer, J. Mater. Chem. 2006, 16, 2464–
2472; k) M. Mꢃller, O. I. Lebedev, R. A. Fischer, J. Mater. Chem.
2008, 18, 5274; l) D. Esken, X. Zhang, O. I. Lebedev, F. Schrçoder,
R. A. Fischer, J. Mater. Chem. 2009, 19, 1314; m) Y. E. Cheon, M. P.
Suh, Angew. Chem. 2009, 121, 2943–2947; Angew. Chem. Int. Ed.
2009, 48, 2899–2903; n) C. Zlotea, R. Campesi, F. Cuevas, E. Leroy,
P. Dibandjo, C. Volkringer, T. Loiseau, G. Fꢀrey, M. Latroche, J.
Am. Chem. Soc. 2010, 132, 2991; o) Y. Li, R. T. Yang, J. Am. Chem.
Soc. 2006, 128, 726; p) F. X. Llabrꢀs i Xamena, A. Abad, A. Corma,
H. Garcia, J. Catal. 2007, 250, 294; q) M. Sabo, A. Henschel, H.
Frçde, E. Klemmb, S. Kaskel, J. Mater. Chem. 2007, 17, 3827;
r) Y. E. Cheon, M. P. Suh, Chem. Eur. J. 2008, 14, 3961.
[13] a) S. Hermes, M. Schrçter, R. Schmid, L. Khodeir, M. Muhler, A.
Tissler, R. W. Fischer, R. A. Fischer, Angew. Chem. 2005, 117, 6394;
Angew. Chem. Int. Ed. 2005, 44, 6237; b) D. Esken, S. Turner, O. I.
Lebedev, G. V. Tendeloo, R. A. Fischer, Chem. Mater. 2010, 22,
6393–6401; c) S. Hermes, F. Schrçder, R. Chelmowski, C. Wçll,
R. A. Fischer, J. Am. Chem. Soc. 2005, 127, 13744–13745; d) M. P.
Suh, H. R. Moon, E. Y. Lee, S. Y. Jang, J. Am. Chem. Soc. 2006, 128,
4710–4718; e) H. L. Jiang, B. Liu, T. Akita, M. Haruta, H. Sakurai,
Q. Xu, J. Am. Chem. Soc. 2009, 131, 11302–11303; f) H. L. Jiang, T.
Akita, T. Ishida, M. Haruta, Q. Xu, J. Am. Chem. Soc. 2011, 133,
1304–1306; g) X. Zhang, F. X. Llabrꢀs i Xamena, A. Corma, J.
Catal. 2009, 265, 155–160; h) H. Liu, Y. Liu, Y. Li, Z. Tang, H.
Jiang, J. Phys. Chem. C 2010, 114, 13362.
[19] Y. Huang, Z. Zheng, T. Liu, J. Lꢃ, Z. Lin, H. Li, R. Cao, Catal.
Commun. 2011, 14, 27.
[20] C. Evangelisti, N. Panziera, P. Pertici, G. Vitulli, P. Salvadori, C. Bat-
tocchio, G. Polzonetti, J. Catal. 2009, 262, 287.
[21] a) S. Couck, J. F. M. Denayer, G. V. Baron, T. Rꢀmy, J. Gascon, F.
Kapteijn, J. Am. Chem. Soc. 2009, 131, 6326; b) J. Gascon, U. Aktay,
M. D. Hernandez-Alonso, G. P. M. van Klink, F. Kapteijn, J. Catal.
2009, 261, 75.
[14] a) S. Proch, J. Herrmannsdçrfer, R. Kempe, C. Kern, A. Jess, L. Sey-
farth, J. Senker, Chem. Eur. J. 2008, 14, 8204–8212; b) S. M. Luzan,
A. V. Talyzin, Microporous Mesoporous Mater. 2010, 135, 201–205.
Received: June 4, 2011
Published online: September 28, 2011
12712
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Chem. Eur. J. 2011, 17, 12706 – 12712