Recyclable cellulose-palladium nanoparticles for clean cross-coupling chemistry

Article abstract of DOI:10.1039/c8ob00527c

Cheap, recyclable, and robust cellulose-palladium nanoparticles were developed and fully characterized by FTIR, TEM, XPS, TGA, and NMR. The nanoparticles enabled cross-coupling chemistry in a truly general fashion i.e., Suzuki-Miyaura, Heck, Sonogashira, and C-H activation. Notably, all types of transformations were achieved with a single type of nanocatalyst. Complete recyclability of the catalyst and low traces of palladium in the product demonstrates the greenness of the protocol.

Full text of DOI:10.1039/c8ob00527c

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DOI: 10.1039/C8OB00527C
Organic & Biomolecular Chemistry
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Recyclable Cellulose-Palladium Nanoparticles for Clean Cross-
Coupling Chemistry
Zhichao Lua, Jacek Jasinskib, Sachin Handaa, Gerald B. Hammonda*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Cheap, recyclable, and robust cellulose-palladium nanoparticles were developed and fully characterized by FTIR, TEM, XPS,
TGA, and NMR. The nanoparticles enabled cross-coupling chemistry in a truly general fashion i.e., Suzuki–Miyaura, Heck,
Sonogashira, and C-H activation. Notably, all types of transformations were achieved with a single type of nanocatalyst.
Complete recyclability of the catalyst and low traces of palladium in the product demonstrates the greenness of the
protocol.
www.rsc.org/
can interact with metal nanoparticles to display the desired
catalytic activity. Cellulose possesses an extra handle to fine-
tune its physiochemical behavior, i.e., solubility, dispersity, and
ligation properties. Cellulose and its derivatives have been also
used as efficient, cheap, renewable, and biodegradable
Introduction
supports in catalysis.15-21 Among the numerous methods that
have been used to prepare cellulose-supported catalysts,
deposited Pd particles on cellulose are one of the most widely
studied.22-24 This approach though may cause problems like
catalyst deactivation and metal leaching. Li and other groups
have introduced diphenylphosphinite-anchored cellulose to
coordinate with palladium. But this methodology required a
After peptide bond forming reactions,1-3 palladium-catalyzed
cross-couplings, such as Suzuki–Miyaura, Sonogashira, and
Heck reactions have played
a significant role in the
construction of challenging carbon-carbon bonds,4-6 and in the
recent developments in material chemistry.7,
However,
8
because an economical access to palladium supplies is limited,
this element is regarded as an endangered element.9
Significant efforts have been devoted by the scientific
community to finding better catalysts that can assist in
prolonging the palladium reserve, either by moving away from
tediously long-time for preparation and showed a narrow
range of applications.25,
26
Herein, we report a cellulose-Pd
nanocatalyst with wide catalytic activity. The efficiency and
recyclability of this environmentally friendly cellulose–
palladium catalyst was examined using common palladium-
catalyzed cross coupling reactions (Scheme 1).
10
palladium or by developing alternative technologies.5,
Nonetheless, the high costs associated with ligands, the
difficulty in recycling the catalysts, and, notably, their lack of
generality toward all types of cross-coupling reactions are
major unsolved pitfalls. In addition, catalyst residues inevitably
contaminate the product during these reactions.11 Thus, it is
important to develop a catalyst that exhibits broader activity,
that is designed from environmentally benign materials, that is
easy to recycle without additional effort and without adversely
affecting activity, and that will not cause trace metal
contamination of the product.12
To address the above issues, cellulose, as a sustainable, cost-
effective, environmentally benign, and most abundant natural
14
biopolymer,13, is potentially a suitable scaffold. Its surface
Scheme 1 Cellulose-Pd nanoparticles for general cross-coupling chemistry.
Results and discussion
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Table 1. Catalytic activity of 5 for Suzuki–Miyaura couplings
We began our study using an inexpensive 2-
(diphenylphosphino) benzoic acid that acted as a linker to the
microcrystalline cellulose (Cell) and which was then
coordinated with palladium nanoparticles (NPs). It was
anticipated that the position of the phosphine and ester
linkages was going to be crucial for imparting stability and
efficacy to the resulting catalyst. The steric bulk from the
diphenylphosphine motif was thought to protect the ester
linkage from hydrolysis under basic conditions. At the same
time, the ester group was thought to coordinate with the Pd
center to stabilize the catalyst. The synthetic protocol began
with the nucleophilic substitution of Cell-OTs with 2-
(diphenylphosphino) benzoic acid (Scheme 2). The resulting
microcrystalline cellulose-phosphinite was then doped with
palladium nanoparticles to complete the preparation of 5; this
catalyst was fully characterized by FTIR and NMR. (see
Supporting Information)
Reaction conditions: Aryl halide (0.2 mmol), aryl boronic acid (1.1 equiv), 5 (3 mol
%), K2CO3 (2.0 equiv.), 2 mL EtOH, 1 mL H2O, 80 oC, 3 h.
Table 2. Sonogashira couplings with 5
Scheme 2. Synthetic protocol of Cellulose-Pd NPs.
After obtaining 5, its catalytic activity was surveyed. At first, it
was used in Suzuki-Miyaura (SM) cross-couplings (Table 1).
Aryl bromides and iodides displayed very good reactivity.
MIDA boronate and boronic acid were also tolerated. Fluoro
(
8a), cyclic ether (8a
,
b
,
f
), acetyl (8b
-e,
h), nitrile (8e),
trifluoromethyl (8f), and aldehyde
(
8h
)
functionalities
displayed good-to-excellent reactivity. The activity of this
nanocatalyst was next tested in Sonogashira couplings (Table
2). Aryl iodides and bromides showed good reactivity.
Excellent yields were obtained in all cases. Nitro (11b), acetyl
(
11c), nitrile (11d), ester (11e
sulfonamide (11i), aldehyde (11j), and trifluoromethyl (11k
residues tolerated the reaction conditions without decrease in
reaction yields. Notably, esters 11e did not hydrolyze.
, k), trifluoromethylether (11g),
)
,
k
Reaction conditions: Aryl halide (0.2 mmol), alkyne (1.1 equiv.), 5 (3 mol %), CuI
(5 mol %), Et3N (2.0 equiv.), 1 mL DMF, 80 oC, 15 h. [a] X = Br
The catalytic activity was also examined in Heck cross-
couplings. (Table 3). Both aryl iodide (14a) and bromides (14b
-
g
)
were suitable substrates. Electron-rich and electron-
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14a
ARTICLE
deficient
Different functionalities such as ether (14e), ester (14a, f
ketal (14e), and sulfonamide (14d) were tolerated. Notably,
substrates possessing the difluoromethyl (14b 14e) and
(
,
g
)
residues displayed similar behaviours.
,
g
),
,
pentafluorosulfur (14c) motifs remained intact and no side
reactions were observed. Furthermore, no ester hydrolysis
was observed in cases where coupling partners had ester
residues (14f, g).
Table 3. Catalytic activity for heck couplings
X
+
5 (3 mol%)
Et3N, K2CO3, DMF
0.2 M, 120 oC, 15 h
( X = Br, I)
13
12
14
O
O
Me
HF2C
SF5
14c, 70%
14a, 87%
14b, 80%
F
O
F
Scheme 3. Synthetic value of protocol.
F
O
MeO2C
H2NO2S
14d, 85%
14e, 91%
14f, 81%
Another demonstration of the value of our catalyst was in the
synthesis of organic materials; as shown in Scheme 4,
dibromoperylene diimide (PDIs) 21 underwent simultaneous double
substitution to afford 22 in good yield.30
OMe
MeO2C
14g, 70%
Reaction conditions: Aryl halide (0.2 mmol), alkene (1.1 equiv.), 5 (3 mol %), Et3N
(1.1 equiv.), K2CO3 (1.5 equiv.), 1 mL DMF, 120 oC, 15 h.
The catalyst activity was further tested in a tandem reaction,
namely C—H activation followed by annulation, to prepare a
hydroxylisoindolone derivative.27 As shown in Scheme 3a, the
reaction was completed in one hour, furnishing 17b in
excellent isolated yield. Surprisingly, the bromo functionality
on the aryl residue did not show any reactivity. This
Scheme 4. Synthesis of PDI.
nanocatalyst was then employed on
a
gram scale
intermolecular Heck reaction: within 4 h the product 14h was
obtained in 88% yield, employing only 1 mol% catalyst.
Another application of this protocol was the synthesis of a
ligand precursor. Upon reaction of aryl triflate 19 with a
sterically congested 2,6-dimethylphenylboronic acid, the
product 20 was obtained in 68% isolated yield, along with
catalyst recovery and re-use.28, 29
Our catalyst was recycled by simple filtration, without any
additional manipulation, and without losing its catalytic
activity. A recycling study revealed that the effectiveness of
the catalyst held for up to five cycles. To recycle this catalyst,
the liquid phase was removed after reaction completion by
centrifugation, followed by washing with water to remove the
salt. The catalyst was re-used without adding more palladium
nanoparticles (see SI for details). A control experiment was
also conducted using Pd(OAc)2 and cellulose particles; in it we
observed a 80% reduction in yield in the second recycle event
(Scheme 5a, for details, See SI). In a separate control
experiment, a Heck reaction was conducted with cellulose and
Pd(OAc)2 and none of the desired product was detected,
underscoring the importance of our catalyst grafting process
(Scheme 5b).
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a) Suzuki-Miyaura coupling with grafted catalyst 5 and ungrafted Pd
OH
For the fresh catalyst, a bimodal size distribution is evident
with many nanoparticles having ~1 nm diameter and with the
remaining nanoparticles in a size range of about 3-4 nm (Figure
1b). On the other hand, the recycled catalyst shows almost all
particles in the 3-4 nm range (Figure 1d). XPS analysis of these
two catalysts shows the change in the Pd valence state. As
indicated by the analysis of the Pd3d line, both catalysts show
Pd(II) and Pd(0) states. The relative concentration of these
valence states changed slightly, from 0.44 in the fresh catalyst
(Figure 2a) to 0.39 in the recycled catalyst (Figure 2b), which
helped to explain why the catalyst maintained its catalytic
efficiency. Thermogravimetric analysis was performed to
evaluate the stability of the catalyst at high temperature. As
shown in Figure S2 in the SI, the catalyst system showed high
thermal stability with decomposition occurring around 225 oC.
Br
5
(3 mol%),
K2CO3 (2 equiv.),
B
OH
+
Me
Me
EtOH (4 mL),
H2O (2 mL),
80 oC, 3 h
O
O
0.5 mmol
6
0.55 mmol
7i
8i
b) Heck reaction with ungrafted Pd
O
Pd(OAc)2 (3 mol %),
MCC (6 mol %)
H2N
S
O
no reaction
+
Et3N (1.1 equiv.),
Br
K2CO3 (1.5 equiv.), DMF (1 mL),
120 oC, 15 h
0.2 mmol
0.22 mmol
Figure 2. Deconvoluted high-resolution Pd3d XPS spectra. (a) XPS data of fresh
12
13
catalyst; (b) XPS data of five-times recycled catalyst.
Scheme 5. Catalyst recycling with control experiment.
The residual palladium in the product was also assayed with
inductively coupled plasma mass spectrometry (ICP-MS). Two
products, 8a and 14b, from different types of coupling
reactions were tested and both fell within the normal limits set
by the FDA (8a: 2ppm, 14b: 0.3ppm). The low Pd content
further underscored the usefulness of this cellulose-bound
nanocatalyst.
In order to gain insights into the nature of catalyst
5,
transmission electron microscopic (TEM) images of the fresh as
well as the five-times recycled catalyst were recorded in Figure
1. In both samples, a high concentration of Pd nanoparticles
(appearing as bright spots) was observed on the surface of
carbon support particles (Figure 1 a,c). There is a clear
difference in the Pd nanoparticle size distribution between
these two samples.
Conclusions
In summary, we have developed a new cellulose-palladium
nanocatalyst (Cell-OOCPhPPh2-Pd) using simple starting
materials and a convenient synthesis. This catalyst shows good
activity in C-H activation and three other types of cross-
coupling reactions. The products from those reactions contain
low Pd residues. This catalyst was also easily recycled without
obvious loss in the catalytic activity even after several runs.
Considering the importance of the above features, we believe
that this catalyst could be an excellent choice for the
pharmaceutical industry.
Experimental
General procedure for Suzuki-Miyaura coupling reactions:
An 8-mL vial fitted with a stirring bar was charged with aryl
halide (0.2 mmol), K2CO3 (0.4 mmol), boronic acid (0.22mmol),
Figure 1. (a). Low-magnification STEM data from fresh catalyst, (b) Higher-
magnification STEM images of regions marked in panel (a); (c). Low-magnification STEM
data from five-times recycled catalyst; (d) Higher-magnification STEM images of regions
marked in panels (c).
3% catalyst 5 (4 mg). 3 mL of a mixed solvent (ethanol: water =
2:1) was added and the mixture was flushed with argon for 1
min. The reaction was heated to 80 oC and stirred at 500 r/min
for 2 hours while monitored by GC-MS. After the reaction was
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then washed with 10 mL water, and brine. The organic layer
was dried over Na2SO4. filtered and the filtrate was
concentrated. The resulting crude product was purified with
flash chromatography.
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There are no conflicts to declare
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financial support (CHE-1401700). Z.L. is grateful to the Institute
of Molecular Diversity and Drug Design (IMD3) of the
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