Aerobic Homocoupling of Arylboronic Acids Catalyzed by Regenerable Pd(II)@MIL-88B-NH2(Cr)

Article abstract of DOI:10.1002/cctc.201900556

A fast and operationally simple method for the aerobic homocoupling of arylboronic acids is described. The process is catalyzed by Pd(II) complexes supported on the metal-organic framework MIL-88B-NH₂(Cr). The benefits of this approach include the use of a benign oxidant/solvent mixture at room temperature with catalytic amounts of base, easy recovery of the catalyst, and easy isolation of the products. Very high conversions and good yields were achieved for a variety of substrates, and the process was also carried out on a larger scale with the same efficiency. The catalyst was found to suffer deactivation due to progressive reduction and agglomeration of palladium into inactive metal clusters/particles. An innovative procedure for the oxidative redispersion and regeneration of the active Pd(II)@MOF species is presented.

Full text of DOI:10.1002/cctc.201900556

Accepted Article
Title: Aerobic Homocoupling of Arylboronic Acids Catalyzed by
Regenerable Pd(II)@MIL-88B-NH2(Cr)
Authors: Alejandro Valiente, Sergio Carrasco, Amparo Sanz-Marco,
Check-Wai Tai, Antonio Bermejo Gómez, and Belén Martín-
Matute
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: ChemCatChem 10.1002/cctc.201900556
Link to VoR: http://dx.doi.org/10.1002/cctc.201900556
A Journal of
www.chemcatchem.org

10.1002/cctc.201900556
ChemCatChem
FULL PAPER
Aerobic Homocoupling of Arylboronic Acids Catalyzed by
Regenerable Pd(II)@MIL-88B-NH2(Cr)
Alejandro Valiente,[a] Sergio Carrasco,[a] Amparo Sanz-Marco,[a] Cheuk-Wai Tai,[c] Antonio Bermejo
Gómez,[a,b] and Belén Martín-Matute*,[a]
Abstract: A fast and operationally simple method for the aerobic homocoupling of arylboronic acids is described. The process is catalyzed by
Pd(II) complexes supported on the metal-organic framework MIL-88B-NH2(Cr). The benefits of this approach include the use of a benign oxidant
/ solvent mixture at room temperature with catalytic amounts of base, easy recovery of the catalyst, and easy isolation of the products. Very
high conversions and good yields were achieved for a variety of substrates, and the process was also carried out on a larger scale with the
same efficiency. The catalyst was found to suffer deactivation due to progressive reduction and agglomeration of palladium into inactive metal
clusters/particles. An innovative procedure for the oxidative redispersion and regeneration of the active Pd(II)@MOF species is presented.
Introduction
heterogeneous palladium catalysts for this reaction. The first one
was reported in 2006 by Yamamoto and coworkers, who reported
the aerobic homocoupling of arylboronic acids in the absence of
a base, mediated by Pd(OAc)2 encapsulated in a polyurea matrix
(Scheme 1a).[ 12 ] In 2016, Li, Wei and coworkers reported a
protocol for the oxidative homocoupling of boronic acids and their
derivatives using Pd(0) supported on Al(OH)3, with Ag2O as the
oxidant and 1 equiv. of base (Scheme 1b).[13] Finally, Kapdi and
coworkers described an aerobic procedure for the same reaction
based on the use of active palladium colloids and 2 equiv. of base
at high temperatures (Scheme 1c).[6]
In recent years, the transition-metal-mediated aerobic oxidation of
organic substrates has become an area of increasing interest for
the chemical community.[ 1 ] The need for efficient oxidation
processes that are compatible with the idea of sustainable
chemistry is hugely important, and this must be addressed
through the development of methods involving benign oxidants,
green solvents, and recyclable catalysts.[2] Heterogeneous Pd-
catalyzed protocols based on the use of molecular oxygen now
represent a highly promising and versatile approach to achieving
this goal. Examples of dehydrogenation reactions[3] or Wacker
processes,[ 4 ] of C-H functionalization[ 5 ] and of C-C bond
Scheme 1. Heterogeneous Pd-catalyzed homocoupling of boronic acids.
6
]
formation[
through heterogeneous Pd-catalyzed aerobic
a)
Pd(II) EnCat 30 (3 − 5 mol%), Air,
oxidation have recently been reported. Representative examples
of the latter type of reaction include the oxidative coupling of
carbon nucleophiles such as arylboronic acids to obtain biaryls,[7]
or the Glaser-Hay reaction to synthesize diynes.[8]
No base, MeOH, 26°C, 24 h
b)
Pd(0)@Al(OH)3 (0.1 mol%), Ag2O (45 mol%)
AcOK (1 equiv.), MeOH, 40°C, 8 - 48 h
HO
OH
B
R
2
R
The oxidative homocoupling of arylboronic acids was first
reported by Davidson and coworkers in 1968 using stoichiometric
amounts of palladium.[9 ] However, it was not until 1996 that
Moreno-Mañas and coworkers reported the first catalytic
oxidative homocoupling of boronic acids, using palladium
complexes with monodentate phosphine ligands.[10] After that,
several protocols for catalytic oxidative homocoupling using
homogeneous palladium complexes were reported.[11] To the best
of our knowledge, there are only three reports of the use of
Pd(0) cat. (0.3 mol%), Air
c)
R
K2CO3 (2 equiv.), CH3CN / H2O (v/v = 1:1), 80°C, 24 h
Pd(II)@MIL-88B-NH2(Cr) (0.1 mol%), O2
Cs2CO3 (25 mol%), EtOH / H2O (v/v = 1:1), rt, 2 - 4 h
This work:
Low catalyst / base loading
Benign oxidant / solvent
Short reaction times
Room temperature
Regenerable catalyst
Metal-organic frameworks (MOFs) are currently some of the
most widely studied materials,[14] and heterogeneous catalysts
based on these materials have become increasingly popular in
the last two decades.[15] MOFs are crystalline polymers made up
of metallic nodes linked by polytopic organic linkers through
strong coordination bonds.[ 16 ] They can act as catalysts as
synthesized,[17] since the presence of Lewis acid / base sites at
metal nodes or linker substituents respectively are reported to
promote a wide variety of reactions.[18,19] They are also widely
used as supports for other catalysts,[ 20 ] such as single-site
transition-metal complexes or metal nanoparticles (NPs).[21]
Our group has developed several procedures using Pd
nanoparticles supported on MIL-101-NH2(Cr) and MIL-88B-
NH2(Cr). The excellent catalytic activity of the resulting materials
has been demonstrated in a wide variety of transformations,
including Suzuki-Miyaura cross-couplings,[ 22 ] C-H activation /
[a]
A. Valiente, Dr. S. Carrasco, Dr. A. Sanz-Marco, Dr. A. Bermejo
Gómez and Prof. Dr. B. Martín-Matute
Department of Organic Chemistry
Stockholm University
The Arrhenius Laboratory 16C, SE-106 91, Stockholm (Sweden)
e-mail: belen.martin.matute@su.se
Dr. A. Bermejo Gómez
Sprint Bioscience
Hälsovägen 7, SE-141 57, Huddinge (Sweden)
Dr. C.-W. Tai
[b]
[c]
Department of Materials and Environmental Chemistry
Stockholm University
The Arrhenius Laboratory 16C, SE-106 91, Stockholm (Sweden)
Supporting information for this article is given via a link at the end of the
document.
This article is protected by copyright. All rights reserved.

10.1002/cctc.201900556
ChemCatChem
FULL PAPER
23
]
24 ]
halogenations,[
selective C=C hydrogenations,[
Heck
couplings,[25] different carbonylation reactions[26] and the aerobic
oxidation of benzylic alcohols.[ 27 ] The catalytic methods we
developed using these heterogeneous Pd catalysts were efficient,
and in some cases they even surpassed their homogeneous
counterparts. Some of the reasons for this high efficiency include
the outstanding performance shown by the catalysts under
continuous-flow conditions,[22b,27] the successful recycling of the
catalyst,[22a,24,27] and the mild reaction conditions used for the
reactions.[22,24,26]
In this paper, we describe an efficient Pd(II)-catalyzed
heterogeneous protocol for the fast aerobic homocoupling of
arylboronic acids. Pd(II)@MIL-88B-NH2(Cr) was chosen as the
catalyst due to its previous good results in terms of activity,
stability, and ease of synthesis.[23,26,27] This method showed a high
substrate tolerance, and gave good product yields at low catalyst
/ base loadings under very mild reaction conditions. Further, we
present an innovative procedure to regenerate the active catalyst
based on the oxidative redispersion of inactive Pd(0) particles at
room temperature.
Table 1. Optimization of the reaction conditions.[a]
Oxidant
Pd(II)@MIL-88B-NH2(Cr)
HO
OH
B
OH
Base, rt
Solvent
+
2
1a
2a
3a
Cat.
(mol
%)
Solvent
(v/v)
Conv
(%)
% Yield
2a[d] / 3a[f]
Entry
Base (equiv.)
1[b]
2
0.4
0.4
0.4
0.4
0.4
0.4
0.4
0.1
0.1
0.1
0.1
0.1
0.1
0.1
EtOH / H2O (1:1)
EtOH / H2O (1:1)
EtOH / H2O (1:1)
EtOH
Cs2CO3 (1)
Cs2CO3 (1)
Cs2CO3 (1)
Cs2CO3 (1)
Cs2CO3 (1)
Cs2CO3 (1)
Cs2CO3 (1)
Cs2CO3 (1)
Cs2CO3 (0.25)
-
67
>99
-
44 / 5
72 / 21
- / -
3[c]
4
91
53 / 10
50 / 13
43 / 13
48 / 22
69 / 24
71 / 22
Traces / -
52 / 18
47 / 21
43 / 20
13 / 11
5
H2O
97
6
EtOH / H2O (3:1)
EtOH / H2O (1:3)
EtOH / H2O (1:1)
EtOH / H2O (1:1)
EtOH / H2O (1:1)
EtOH / H2O (1:1)
EtOH / H2O (1:1)
EtOH / H2O (1:1)
EtOH / H2O (1:1)
>99
>99
>99
>99
-
7
Results and Discussion.
8 [e]
10[e]
11[e]
12[e]
13[e]
14[e]
15[e]
1. Reaction optimization. In 2013, our group reported an
efficient procedure for the Suzuki-Miyaura cross-coupling reaction
catalyzed by palladium NPs supported on MIL-101-NH2(Cr). The
reaction proceeded at room temperature, using 2 equiv. of
Cs2CO3 as the base in a mixed solvent of EtOH / H2O (1:1).[22]
Interestingly, when p-tolylboronic acid (1a) was subjected to
similar reaction conditions in the absence of the aryl halide and
using Pd(II)@MIL-88B-NH2(Cr) (0.4 mol% Pd), a 44% yield of the
homocoupled product (2a) was obtained (Table 1, entry 1)
together with 5% of p-cresol (3a). When the same reaction was
carried out under an oxygen atmosphere, full conversion was
observed within 1 h, and a 72% yield of biaryl 2a was obtained
(entry 2). Other oxidants were screened (see ESI, Table S2), but
oxygen outperformed the other oxidants tested as it was more
efficient and convenient. When the reaction was carried out under
argon, no product formation was observed (entry 3).
K2CO3 (0.25)
KF (0.25)
>99
95
KOAc (0.25)
K3PO4 (0.25)
93
83
[a] Unless otherwise noted: 1a (2 mmol), cat.: Pd(II)@MIL-88B-NH2(Cr),
9.22 wt% Pd, O2 (1 atm), rt, 1 h. [b] Under air. [c] Oxidant-free conditions;
under an argon atmosphere. [d] Isolated yields. [e] 2 h. [f] Yields determined
against an internal standard by 1H NMR spectroscopy; volatile product.
When 25 mol% of other bases were used, no improvement in the
reaction outcome was observed (entries 12 - 15). Thus, Cs2CO3
showed the best performance of all the bases tested (see ESI
Section 3 for further info.).
The crystallinity of the catalyst was analyzed by ex-situ X-Ray
Powder Diffraction (XRPD), which showed that after being
subjected to optimal conditions (entry 10) the structure of the
framework remained unaltered (see ESI, Figure S3).
Concerning the solvent, the effect of the EtOH / H2O ratio was
investigated. When pure ethanol or pure water was used, 53 and
50% yields of 2a were obtained, respectively (entries 4 and 5).
When 3:1 or 1:3 (v/v) mixtures were used, no improvement in the
product yield was observed (43 and 48% respectively; entries 6,
7). Therefore, we continued to use EtOH / H2O 1:1 (v/v) as the
solvent mixture; under these conditions the desired product 2a
was formed in a higher yield after only 1 h. The catalyst loading
was also examined. We found that a catalyst loading of 0.1 mol%
gave a similar yield (69% of 2a; entry 8, TON = 909), increasing
the reaction time to 2 h. Although some base-free homocoupling
protocols are known,[10,11b,12] the need for stoichiometric / excess
base is common in this reaction.[11] Interestingly, under our
reaction conditions, when the amount of Cs2CO3 was lowered
from 100 to 25 mol%, full conversion and a 71% yield of 2a were
obtained after 2 h at room temperature (entry 10). In the absence
of base, though, only traces of product were detected (entry 11).
2. Substrate scope and limitations. A variety of substrates were
screened under the optimized conditions (Table 1, entry 10) to
test the generality of the method (Scheme 2). We first investigated
the homocoupling of para-substituted phenylboronic acids
bearing electron-donating groups (EDG) (2a-2f). Good to
excellent yields (67 - 91%) were obtained within reasonably short
reaction times (2 - 3 h) with the exception of diamine 2e (21%). It
is noteworthy that the method tolerates free benzylic alcohols;
This article is protected by copyright. All rights reserved.

10.1002/cctc.201900556
ChemCatChem
FULL PAPER
product 2d was obtained in good yield without further oxidation.
Additionally, trimethylsilyl substituted arylboronic acid 1f could be
selectively coupled through the C-B28 bond delivering biaryl 2f in
high yield (81%). Unsubstituted biphenyl 2g was synthesized in
78% yield after 2 h. Arylboronic halides were tolerated, and
compounds 2h and 2i were formed in 71 and 65% yields,
respectively. Reaction at the chloride group in 2i was not
observed. We then proceeded with substrates bearing electron-
withdrawing groups at the para position. Aldehyde, nitrile,
trifluoromethyl, and ester functionalities were tolerated, and 2j-2m
were formed in good yields (52 - 66%) after 2 - 4 h. Meta-
substituted substrates bearing EDG delivered biaryls 2n and 2o
in 72 and 64% yields, respectively. Polysubstituted and
polyaromatic arylboronic acids were satisfactorily tolerated, and
compounds 2p-2u were formed in good to excellent yields (57 -
98%). Remarkably, most of the products were isolated by filtration
with no need of additional purification steps; the elemental
analysis of 2a showed that the product isolated in this manner was
of very high purity (See ESI, S5).
conditions. In this experiment, the amount of base was further
lowered to 12 mol% (1.66 g, 5 mmol, ESI, Figure S4). After 2 h at
room temperature, 2.5 g (70%) of biaryl 2a was isolated after a
simple filtration (Scheme 3).
HO
O2 (1 atm)
B
OH Pd(II)@MIL-88B-NH2(Cr) (0.1 mol%)
2
Cs2CO3 (12 mol%)
EtOH / H2O (v/v = 1:1)
rt, 2 h
1a (41 mmol, 5.7 g, 0.2 M)
2a (2.53 g, 70%)
Scheme 3. Large-scale homocoupling of p-tolylboronic acid.
4. Catalyst recycling and regeneration. The recyclability of
Pd(II)@MIL-88B-NH2(Cr) was investigated in the homocoupling
of p-tolylboronic acid over five consecutive runs. The experiments
were carried out at 4 mmol scale. Interestingly, the XRPD pattern
of the recovered material revealed that the framework did not
decompose after five reaction runs (Figure 1a), despite the
previously reported detrimental effect of carbonates on its
mesoporous polymorph MIL-101-NH2.[22c] Slight changes were
observed in the 2Q value and relative intensities of the main
3. Large-scale reactions. To prove that the efficiency of the
method is retained when the reaction is run on gram scale, 41
mmol (5.7 g) of p-tolylboronic acid was subjected to the reaction
R
HO
B
O2 (1 atm)
OH
Pd(II)@MOF (0.1 mol%)
2
H2O / EtOH (v/v = 1:1)
Cs2CO3 (25 mol%)
2 − 4 h, rt
R
R
1a-u
2a-u
------------------------------------------------------------------------------------------------------------------------
Si
N
O
OBn
OH
N
Si
O
HO
BnO
2a (70%, 2 h)
2b (71%, 2 h)
2e (21%, 2 h)
2d (67%, 3 h)
2f (81%, 2 h)
2g (78%, 2 h)
2c (91%, 2 h)
O
F
Cl
CN
O
O
O
CF3
O
F
Cl
NC
O
O
O
F3C
2k (66%, 4 h)
2l (61%, 4 h)
2m (57%, 3 h)
2n (72%, 4 h)
2o (64%, 2 h)
2h (71%, 4 h) 2i (65%, 2 h)
2j (52%, 2 h)
O
O
O
O
O
O
O
O
O
O
O
O
O
O
2t (98%, 2 h)
2p (61%, 4 h)
2r (70%, 2 h)
2u (82%, 2 h)
2s (62%, 2 h)
2q (57%, 4 h)
Scheme 2. Aerobic homocoupling of boronic acids. Reaction conditions: 1a-u (2 mmol), 9.22 wt% Pd(II)@MIL-88B-NH2(Cr)
(0.1 mol%), O2 (1 atm), EtOH / H2O (0.2 M, v/v = 1:1), Cs2CO3 (25 mol%), rt, 2 - 4 h. Isolated yields.
This article is protected by copyright. All rights reserved.

10.1002/cctc.201900556
ChemCatChem
FULL PAPER
by ICP-OES (Inductively Coupled Plasma Optical Emission
Spectrometry) showed that the Pd/Cr ratio decreased from 0.63
(fresh catalyst, run 0) to 0.48 in the recovered material after 2 runs
(Figure 1b, orange bars). However, analysis of the catalyst
recovered after run 5 ruled out catalyst leaching as the reason for
the dramatic decrease in activity, since the Pd/Cr ratio was 0.47,
essentially the same as after run 2.
a)
Fresh Pd(II)MOF
After 1 run
After 5 runs
The in-situ reduction of supported palladium complexes to
form Pd(0) nanoparticles and their agglomeration are a common
cause of catalyst deactivation.[30] Indeed, the analysis by scanning
transmission electron microscopy (STEM) of the recovered
catalyst after 1 run (Figure 2, a) showed the formation of
homogeneously dispersed Pd NPs of 2.6 nm average size (see
ESI, Figure S12) within and on the surface of the MOF matrix.
After the second cycle (Figure 2, b, and Figure S8), bigger NPs
were found (4.9 nm average size). After the 5th run (Figure 2, c),
the particle distribution turned into big surficial agglomerates of
Pd (44 nm average size) with partial crystalline character (See
ESI, Figure S5), coexisting with some remaining smaller particles.
As XRPD data showed (Figure 1a), the STEM images in Figure 2
supported a correct preservation of the MIL-88B-NH2 morphology
at the end of the process.
5
8
10
13
15
18
20
23
2Θ (°)
b)
80
70
60
50
40
30
20
10
0
0,9
0,6
0,3
0
In a control experiment where a Pd(0) surrogate catalyst,
Pd(0)@MIL-101-NH2,[31] of well-defined crystalline NPs[32] (see
ESI, Figures S7, S10) was used under the optimized reaction
conditions, only 15% of 2a (see ESI, Table S3, entry 14) was
isolated after 2 h (compared to 71% using Pd(II)@MIL-88B-NH2;
Table 1, entry 10). We believe that the difference in behaviour
between these two catalysts is not only due to particle size effects,
but to the presence of Pd(II) species. Presumably, when Pd(II) is
reduced in-situ, the initially formed atomic Pd(0) centers or small
Pd(0) clusters react with the reagents before further aggregation
occurs, forming bigger Pd(0) nanoparticles, which have a
diminished activity.[30,33] Similar observations have been reported
by Domingos and coworkers, who reported that only the
palladium(II) oxide species found on the surface of Pd nanocubes
0
1
2
3
4
5
Run
Figure 1. a) XRPD patterns of the fresh material (dark blue) and recovered
material after runs 1 (green) and 5 (orange). b) Recycling experiments on a 4
mmol scale. Isolated yields (left axis, blue bars) and Pd / Cr ratio in the
recovered catalyst after runs 2 and 5 (right axis, orange bars) are represented.
diffraction peaks; this has been reported previously for this MOF,
and ascribed to its flexible nature.[27,29] On the other hand, the
activity of the catalyst was retained only until the second run,
when a yield of 70% of the main product was obtained (Figure 1b,
blue bars). Further runs showed a drastic decrease in the catalytic
activity, from 30% in run 3 to 7% in run 5. The elemental analysis
(a)
(b)
(c)
Figure 2. BF-STEM (bright-field STEM) images of the recovered Pd@MIL-88B-NH2 catalysts after runs 1, 2, and 5 (a, b, and c respectively).
This article is protected by copyright. All rights reserved.

10.1002/cctc.201900556
ChemCatChem
FULL PAPER
act as the active catalytic species, whilst the Pd(0) atoms in the
nanocubes are unable to enter into the catalytic cycle. [34]
preserved. This latter observation was supported by XRPD
analysis, which showed a partial retention of the crystallinity after
run 6’ (See ESI, Figure S13).
For the oxidative coupling reported here, it is therefore
plausible that the reduction and aggregation of Pd(0) atoms /
clusters into large particles is the main deactivation pathway. To
overcome this problem, we envisioned the possibility of restoring
the activity of the catalyst by oxidation of the inactive Pd(0)
particles. The “redispersion” of metal particles by oxidation /
reduction cycles is a known approach for the reactivation of
sintered Pd(0) catalysts.[35] There are examples in the literature
where oxidants such as nitric acid were used to regenerate
sulfide- or carbon-fouled Pd catalysts.[36] However, procedures
where oxidants are used to promote the oxidation and
redispersion of Pd nanoparticles are rather scarce and commonly
performed in very harsh conditions and involving toxic
reagents.[37] Further, no example has been reported with MOFs
as the support of the metal particles. In 2014, Datye and
coworkers described the regeneration of atomically dispersed
Pd(II)@Al(OH)3 by high-temperature calcination (700 °C) in air.[38]
Due to the harsh conditions, this method does not become
suitable for organic-based or hybrid materials (such as MOFs)
and / or those having lower thermal stability. In this case the
calcination temperature needed is higher than the thermal
decomposition of Pd(II)@MIL-88B-NH2(Cr) (Td : 325 °C, see ESI
Section 2).[39] For this reason, we aimed to develop a procedure
whereby Pd particles could be oxidized and redispersed in the
MOF using an oxidant under mild reaction conditions.
a)
b)
[Ox1]
[Ox2]
80
70
60
50
40
30
20
10
0
0,9
0,6
0,3
0
1
2
3
4
5
6
Run
Figure 3. a) Ex-situ oxidative regeneration of the Pd(II)@MOF catalyst.
b) New recycling experiments on a 4 mmol scale (green). Regeneration
of the catalyst was performed after runs 2’ and 5’ (green arrows; yields
obtained using the deactivated catalyst are kept in blue for easier
comparison). Pd / Cr ratio in the catalyst before and after oxidative
regenerations (orange) are represented in the right axis.
Various oxidants were ex-situ screened on Pd(0)@MIL-101-
NH2 composite, and the resulting materials were subsequently
tested for catalytic activity (see ESI, Table S3). We found that
upon treatment with potassium peroxodisulfate (K2S2O8, 5 equiv.
with respect to Pd) in 2 M HCl, the activity of the oxidized
Pd@MIL-101-NH2 emulated that of fresh Pd(II)@MIL-88B-NH2
and, importantly, it did not affect the MOF structure. STEM and
XRPD analysis confirmed a successful dispersion of the initial
NPs into small nanoclusters, keeping intact the morphology of the
support (see ESI, Figures S7, S11).
The Pd content of the framework was analyzed by ICP-OES
after runs 2’, 3’, and 6’. From run 2’ to 3’ (after Ox1), a decrease
of 10% in the Pd / Cr ratio was shown (Figure 3b, orange bars),
although the same ratio (0.43) was retained after run 6’.
The fact that this deactivation-reactivation sequence can be
repeated strengthens the hypothesis that after two reaction runs
with satisfactory performance, the amount of active Pd(II) in the
catalyst matrix decreases critically to form inactive Pd(0) particles.
We then tried to apply the catalyst activation for the
homocoupling reaction (runs 1’- 6’; Figure 3b, green bars) under
the conditions presented in this manuscript. Thus, after two new
runs (1’ and 2’), the deactivated recovered catalyst was subjected
to the oxidative procedure (Figure 3, Ox1), and a 71 % yield of 2a
was obtained in run 3’ (Figure 3b), vs 30% obtained in run 3 (blue
bar, Figure 3b). Interestingly, the reactivated catalyst kept the
same efficiency for an additional run (69% yield in run 4’ vs 12%
in run 4), after which it again showed a decrease in activity (38%
in run 5’). To test whether the method could be repeated, the
deactivated catalyst from run 5’ was again subjected to oxidative
treatment (Figure 3, Ox2). Gratifyingly, the catalyst recovered its
original activity once again, and a yield of 71% of 2a product was
obtained in a sixth run (6’).
Conclusions
A fast and green protocol for the aerobic homocoupling of
arylboronic acids using a heterogeneous Pd(II)@MOF catalyst
has been presented. The process was found to operate efficiently
with catalytic amounts of base in aqueous EtOH (50% v/v) at room
temperature. A wide range of substrates was tolerated, and the
products were formed in good to excellent yields and isolated by
simple filtration. The reaction was scaled up tenfold, and the major
product was obtained in 70% yield after the same reaction time (2
h), even when the base loading was decreased. The catalyst
suffered deactivation after two runs due to progressive formation
of inactive Pd(0) particles. A catalyst regeneration oxidative
procedure was then applied, which efficiently transformed the
Pd(0) clusters into dispersed Pd(II) species, resulting in a restored
catalytic activity. The regenerated catalyst displayed the same
activity than the fresh one for at least two extra runs per treatment.
The STEM analysis of the catalyst obtained after two oxidative
treatments (Ox2) showed that the number of Pd(0) clusters was
dramatically reduced (Figure 4 vs Figure 2; and Figures S8 and
S9), and that the morphology of the MIL-88B-NH2 framework is
This article is protected by copyright. All rights reserved.

10.1002/cctc.201900556
ChemCatChem
FULL PAPER
from the catalyst. This filtrate was then dried with
MgSO4. The solvent was evaporated under
reduced pressure to give the product.
General procedure for the recycling
experiments
The general procedure was followed as
described. When the reaction was complete, the
reaction mixture was transferred to a falcon
tube. Water was added (20 mL) to promote
further product precipitation and dissolution of
inorganic salts. The mixture was centrifuged at
low temperature (10000 rpm, 10 min, 10 °C),
and the liquid phase was decanted. The catalyst
and the precipitated product were recovered as
a pellet. This solid mixture was washed and
centrifuged using EtOH (2 ´ 25 mL) to dissolve
and extract the product. After this procedure, the
remaining clean catalyst was suspended in the
reaction solvent, and the suspension was added
to a new load of reagents (4 mmol scale) under
an oxygen atmosphere for the next run
a
b
General procedure for the oxidative
regeneration of the Pd(II)@MOF catalyst
The catalyst (0.004 mmol) recovered after run 2
was transferred to a polypropylene tube. K2S2O8
(5.4 mg, 0.02 mmol) was added, and the solid
mixture was suspended in HCl (125 µL, 2 M). A
gradual lightening of the color of the starting
dark green catalyst was observed. The mixture
was sonicated for 2 h. After this time, the
activated catalyst was suspended in the reaction
solvent, and the suspension was added to a new
load of reagents (4 mmol scale) under oxygen.
Figure 4. BF- (a, b) and HAADF-STEM (high-angle annular dark-field) images (c, d) of the Pd@MIL-88B-
NH2 catalyst after 5 reaction runs and the second oxidation step (Ox2), prior to run 6’.
c
d
Acknowledgements
This work has been generously supported by the Swedish
Research Council through Vetenskapsrådet and Formas, by the
Göran Gustafsson Foundation, and by the Knut and Alice
Wallenberg Foundation (KAW 2016.0072). The Wenner–Gren
foundation is gratefully acknowledged for a postdoctoral grant to
S.C.
Experimental Section
General procedure for the homocoupling reactions
The boronic acid (2 mmol), cesium carbonate (25 mol%, 163 mg), and the
Pd catalyst (2.6 mg, 9.2 wt% Pd(II)@MIL-88B-NH2) were put into a round-
bottomed flask (50 mL). The atmosphere was purged with oxygen (1 atm),
and the flask was kept under oxygen (1 atm) using a balloon. A mixture of
EtOH / H2O (10 mL, v/v = 1:1) were added. When the reaction was
complete, cold water (20 mL) was added, and the reaction mixture was
filtered using a sintered glass funnel. The collected solid was washed with
cold water (x2) to remove soluble impurities. Dichloromethane was then
added to dissolve the product, and it was collected in the filtrate separated
Keywords: aerobic homocoupling • catalyst deactivation • metal-
organic frameworks
regeneration
•
oxidative redispersion
•
catalyst
[1]
a) R. A. Sheldon, J. K. Kochi in Metal-Catalyzed Oxidations of
Organic Compounds, Academic Press, New York, 1981; b) S.
S. Stahl, Chem. Int. Ed. 2004, 43, 3400 – 3420; c) S. S. Stahl,
Science, 2005, 309, 1824 – 1826; d) J. Piera, J. E. Bäckvall,
Angew. Chem. Int. Ed. 2008, 47, 3506 – 3523; e) I. Funes-
Ardoiz, F. Maseras, ACS Catal. 2018, 8, 1161 – 1172.
[2]
[3]
Y. Liu, G. Zhao, D. Wang, Y. Li, Natl. Sci. Rev. 2015, 2, 150 –
166.
a) Z. Zhang, T. Hashiguchi, T. Ishida, A. Hamasaki, T. Honma,
H. Ohashi, T. Yokoyama, M. Tokunaga, Org. Chem. Front.
2015, 2, 654 – 660; b) S. Akbari, J. Mokhtari, Z. Mirjafari, RSC
Adv. 2017, 7, 40881 – 40886.
This article is protected by copyright. All rights reserved.

10.1002/cctc.201900556
ChemCatChem
FULL PAPER
Prats, K. W. Chapman, C. J. Cramer, L. Gagliardi, J. T. Hupp,
O. K. Farha, ACS Cent. Sci. 2017, 3, 31 – 38; c) C. J. Doonan,
C.J. Sumby, CrystEngComm 2017, 19, 4044 – 4048.
[4]
Z. Zhang, Y. Kumamoto, T. Hashiguchi, T. Mamba, H.
Murayama, E. Yamamoto, T. Ishida, T. Honma, M. Tokunaga,
ChemSusChem 2017, 10, 3482 – 3489.
T. Ishida, Z. Zhang, H. Murayama, M. Tokunaga, J. Synth. Org.
Chem. Jpn. 2017, 75, 1150 – 1161.
V. Sable, K. Maindan, A. R. Kapdi, P. S. Shejwalkar, K. Hara,
ACS Omega 2017, 2, 204 – 217.
A. de Meijere, Handbook of Organopalladium Chemistry for
Organic Synthesis, E. Negishi, Eds., Wiley, New York, 2002.
K. S. Sindhu, G. Anilkumar, RSC Adv. 2014, 4, 27867 - 27887.
J.M. Davidson, C. Triggs, J. Am. Chem. Soc. 1968, 1324 –
1330.
[21] a) Q. Yang, Q. Xu, H. Jiang. Chem. Soc. Rev. 2017, 46, 4774 –
4808; b) A. Dhakshinamoorthya, H. Garcia, Chem. Soc. Rev.,
2012, 41, 5262 – 5284.
[22] a) V. Pascanu, Q. Yao, A. Bermejo Gómez, M. Gustafsson, Y.
Yun, W. Wan, L. Samain, X. Zou, B. Martín-Matute, Chem. Eur.
J. 2013, 19, 17483 – 17493; b) V. Pascanu, P. R. Hansen, A.
Bermejo Gómez, C. Ayats, A. E. Platero-Prats, M. J.
[5]
[6]
[7]
Johansson,
M.
À.
Pericàs,
B.
Martín-Matute,
[8]
[9]
ChemSusChem 2015, 8, 123 – 130; c) F. Carson, V. Pascanu,
A. Bermejo Gómez, Y. Zhang, A. E. Platero-Prats, X. Zou, B.
Martín-Matute, Chem. Eur. J. 2015, 12, 10896 – 10902.
[23] V. Pascanu, F. Carson, M. Vico Solano, J. Su, X. Zou, M. J.
Johansson, B. Martín-Matute, Chem. Eur. J. 2016, 22, 3729 –
3737.
[24] A. Nagendiran, V. Pascanu, A. Bermejo Gómez, G. González
Miera, C.-W. Tai, O. Verho, B. Martín-Matute, Jan-E. Bäckvall,
Chem. Eur. J. 2016, 22, 7184 – 7189.
[25] N. Yuan, V. Pascanu, Z. Huang, A. Valiente, N. Heidenreich, S.
Leubner, A. K. Inge, J. Gaar, N. Stock, I. Persson, B. Martin-
Matute, X. Zou, J. Am. Chem. Soc. 2018, 140, 8206 – 8217.
[26] M. Vico Solano, G. González Miera, V. Pascanu, A. K. Inge, B.
Martín-Matute. ChemCatChem 2018, 10, 1089 – 1095.
[27] V. Pascanu, A. Bermejo Gómez, C. Ayats, A. Platero-Prats, F.
Carson, J. Su, Q. Yao, M. Pericàs, X. Zou, B. Martín-Matute,
ACS Catal. 2015, 5, 472 – 479.
[28] M. Shibata, H. Ito, K. Itami, Chem. Lett. 2017, 46, 1701 – 1704.
[29] M. Ma, A. Bétard, I. Weber, N. S. Al-Hokbany, R. A. Fischer, N.
Metzler-Nolte, Cryst. Growth Des. 2013, 13, 2286 – 2291.
[30] Á. Molnár. Chem. Rev. 2011, 111, 2251 – 2320.
[31] MIL-101-NH2 is the mesoporous polymorph of MIL-88B-NH2.
[32] Two distribution of NPs were observed: 5.2 nm and 38.0 nm
average size particles co-existed.
[10] M. Moreno-Mañas, M. Pérez, R. Pleixats, J. Org. Chem. 1996,
61, 2346 – 2351.
[11] a) A. Lei, X. Zhang, Tetrahedron Lett. 2002, 43, 2525 – 2528;
b) H. Yoshida, Y. Yamaryo, J. Ohshita, A. Kunai, Tetrahedron
Lett. 2003, 44, 1541 – 1544; c) K. Cheng, B. Xin, Y. Zhang, J.
Mol. Catal. A: Chem. 2007, 273, 240 – 243; d) Z. Xu, J. Mao, Y.
Zhang, Catal. Commun. 2008, 9, 97 – 100; e) N. Wu, X. Li, X.
Xu, Y. Wang, Y. Xu, X. Chen. Let. Org. Chem. 2010, 7, 11 – 14;
f) Z. Zhou, Q. Hu, Z. Du, J. Xue, S. Zhang, Y. Xie, Synth. React.
Inorg. Met. Org. Chem. 2012, 42, 940 – 943; g) Z. Zhou, M. Liu,
X. Wu, H. Yu, G. Xu, Y. Xie, Appl. Organometal. Chem. 2013,
27, 562 – 569; h) S. Dwivedi, S. Bardhan, P. Ghosh, S. Das,
RSC Adv. 2014, 4, 41045 – 41050; i) C. A. Contreras-Celedón,
J. A. Rincón-Medina, D. Mendoza-Rayo, L. Chacón-García.
Appl. Organometal. Chem. 2015, 29, 439 – 442; j) J. Xia, M.
Cheng, Q. Chen, M. Cai, Appl. Organometal. Chem. 2015, 29,
113 – 116; k) B. Kar, S. Bardhan, P. Ghosh, B. Ganguly, K.
Kundu, S. Sarkar, B. K.Paul, S. Das, ChemistrySelect 2017, 2,
1079 – 1088.
[12] Y. Yamamoto, R. Suzuki, K. Hattori, H. Nishiyama, Synlett
2006, 7, 1027 – 1030.
[13] X. Li, D. Li, Y. Bai, C. Zhang, H. Chang, W. Gao, W. Wei,
Tetrahedron 2016, 72, 6996 – 7002.
[33] J. Chen, Q. Zhang, Y. Wang, H. Wan, Adv. Synth. Catal. 2008,
350, 453 – 464.
[14] a) Y. Sun, H. Zhou, Sci. Technol. Adv. Mater. 2015, 16, 054202;
b) A. H. Chughtai, N. Ahmad, H. A. Younus, A. Laypkov, F.
Verpoort, Chem. Soc. Rev. 2015, 44, 6804 – 6849; c) S. Yuan,
L. Feng, K. Wang, J. Pang, M. Bosch, C. Lollar, Y. Sun, J.
Qin, X. Yang, P. Zhang, Q. Wang, L. Zou, Y. Zhang, L.
Zhang, Y. Fang, J. Li, H. Zhou, Adv. Mater. 2018, 1704303; d)
J. Gascon, A. Corma, F. Kapteijn, F. X. Llabres i Xamena, ACS
Catal. 2014, 4, 361 – 378; e) D. Farrusseng, S. Aguado, C.
Pinel, Angew. Chem. Int. Ed. 2009, 48, 7502 – 7513.
[15] a) A. Dhakshinamoorthy, A.M. Asiric, H. Garcia, Chem. Soc.
Rev., 2015, 44, 1922 – 1947. For a Perspective, see: V.
Pascanu, G. González Miera, A. K. Inge, B. Martín-Matute, J.
Am. Chem. Soc., accepted for publication.
[16] H. Furukawa, K. E. Cordova, M. O’Keeffe, O. M. Yaghi, Science
2013, 341, 1230444.
[17] a) Z. Hu, D. Zhao. CrystEngComm. 2017, 19, 4066 – 4081; b)
A. Santiago-Portillo, S. Navalin, P. Concepción, M. Álvaro, H.
García, ChemCatChem 2017, 9, 2506 – 2511.
[18] A. Dhakshinamoorthy, A. M. Asirib, H. Garcia, Chem. Commun.
2017, 53, 10851 – 10869.
[19] A. Dhakshinamoorthy, Z. Li, H. Garcia, Chem. Soc. Rev. 2018,
[34] W. C. Elias, A. M. Signori, L. Zaramello, B. L. Albuquerque, D.
C. de Oliveira, J. B. Domingos, ACS Catal. 2017, 7, 1462 –
1469.
[35] K. Morgan, A. Goguet, C. Hardacre, ACS Catal. 2015, 5, 3430
– 3445.
[36] Using hypochlorite: G. V. Lowryand, M. Reinhard, Environ. Sci.
Technol. 2000, 34, 3217 – 3223; Using nitric acid: Q. L. Song,
S. J. Wang, B. X. Shen & J. G. Zhao, Petrol. Sci. Technol. 2010,
28, 1825 – 1833; Using permanganate: D. Angeles-Wedler, K.
Mackenzie, F.-D. Kopinke, Appl. Cat. B. 2009, 90, 613 – 617.
[37] a) O.C. Feeley, W.M.H Sachtler, Appl. Cat. 1991, 75, 93 – 103;
b) S.T. Homeyer, W.M.H. Sachtler, Appl. Cat. 1989, 54, 189 –
202; c) H. Birgersson, M. Boutonnet, F. Klingstedt, D.Y. Murzin,
P. Stefanov, A. Naydenov, A. Appl. Catal., B 2006, 65, 93 – 100;
d) P.S.Lambrou, K. Polychronopoulou, K.C. Petallidou, A.M.
Efstathiou, Catal., B 2012, 111, 349 – 359.
[38] High temperature aerobic oxidation: E. J. Peterson, A. T.
DeLaRiva, S. Lin, R. S. Johnson, H. Guo, J. T. Miller, J. H.
Kwak, C. H. F. Peden, B. Kiefer, L. F. Allard, F. H. Ribeiro, A.K.
Datye, Nat. Commun. 2014, 5, 4885.
[39] For Pd free MIL-88B-NH2 see: H.-L. Wang, H. Yeh, Y.-C. Chen,
Y.-C. Lai, C.-Y. Lin, K.-Y. Lu, R.-M. Ho, B.-H. Li, C.-H. Lin, D.-
47, 8134 - 8172.
[20] a) Z. Li, A. W. Peters, A. E. Platero-Prats, J. Liu, C. Kung, H.
Noh, M. R. DeStefano, N. M. Schweitzer, K. W. Chapman, J. T.
Hupp, O. K. Farha, J. Am. Chem. Soc. 2017, 139, 15251 –
15258; b) Z. Li, A. W. Peters, V. Bernales, M. A. Ortuño, N. M.
Schweitzer, M. R. DeStefano, L. C. Gallington, A. E. Platero-
H. Tsai, ACS Appl. Mater. Interfaces,
2018, 10, 9332 –
9341.
This article is protected by copyright. All rights reserved.

10.1002/cctc.201900556
ChemCatChem
FULL PAPER
Entry for the Table of Contents
FULL PAPER
Runs
Palladium(II) supported on the metal-
organic framework MIL-88B-NH2 is an
excellent catalyst for the aerobic
homocoupling of arylboronic acids. A
detailed study of how the activity of the
catalyst can be restored without
Alejandro Valiente, Sergio Carrasco, Amparo Sanz-M
Cheuk-Wai Tai, Antonio Bermejo Gómez, and Belén
Matute*
R
HO
B
O2
OH
Pd(II)@MOF
2
50% aq. EtOH
Cs2CO3 (25 mol%)
2 − 4 h, rt
R
Active
catalyst
R
O
O
O
Activity
[O]
Page No. – Page No.
O
H2
N
Inactive
catalyst
Pd(II)
compromising
presented.
its
efficiency
is
H2
N
O
O
O
Aerobic Homocoupling of Arylboronic Acids Cata
Regenerable Pd(II)@MIL-88B-NH2(Cr)
O
Oxidative
Redispersion
Pd(0)
This article is protected by copyright. All rights reserved.