Catalyst shuttling enabled by a thermoresponsive polymeric ligand: Facilitating efficient cross-couplings with continuously recyclable ppm levels of palladium

Article abstract of DOI:10.1039/c9sc02171j

A polymeric monophosphine ligand WePhos has been synthesized and complexed with palladium(ii) acetate [Pd(OAc)₂] to generate a thermoresponsive pre-catalyst that can shuttle between water and organic phases, with the change being regulated by temperature. The structure of the polymeric ligand was confirmed with matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) mass spectrometry and size-exclusion chromatography (SEC) analysis, as well as nuclear magnetic resonance (NMR) measurements. This polymeric metal complex enables highly efficient Pd-catalyzed cross-couplings and tandem reactions using 50 to 500 ppm palladium, and this can facilitate reactions that are tolerant to a broad spectrum of (hetero)aryl substrates and functional groups, as demonstrated with 73 examples with up to 99% isolated yields. Notably, 97% Pd remained in the aqueous phase after 10 runs of catalyst recycling experiments, as determined via inductively coupled plasma-atomic emission spectrometry (ICP-AES) measurements, indicating highly efficient catalyst transfer. Furthermore, a continuous catalyst recycling approach has been successfully developed based on flow chemistry in combination with the catalyst shuttling behavior, allowing Suzuki-Miyaura couplings to be conducted at gram-scales with as little as 10 ppm Pd loading. Given the significance of transition-metal catalyzed cross-coupling and increasing interest in sustainable chemistry, this work is an important step towards the development of a responsive catalyst, in addition to having high activity, by tuning the structures of the ligands using polymer science.

Full text of DOI:10.1039/c9sc02171j

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DOI: 10.1039/C9SC02171J
ARTICLE
Catalyst shuttling enabled by thermoresponsive polymeric ligand:
facilitating efficient cross-couplings with continuously recyclable
ppm levels of palladium
Received 00th January 20xx,
Accepted 00th January 20xx
Erfei Wang and Mao Chen*
DOI: 10.1039/x0xx00000x
A polymeric monophosphine ligand WePhos has been synthesized and complexed with Pd(OAc)2 to generate a
thermoresponsive pre-catalyst that can shuttle between water and organic phases as regulated by temperature. The
structure of polymeric ligand was confirmed with MALDI-TOF mass spectrometry, SEC analysis, as well as NMR
measurements. This polymeric metal complex enables highly efficient Pd-catalyzed cross-couplings and tandem reactions
using 50 to 500 ppm palladium, and facilitates reactions that are tolerant to a broad spectrum of (hetero)aryl substrates and
functional groups as demonstrated with 73 examples in up to 99% isolated yields. Notably, 97% Pd was remained in the
aqueous phase after 10 runs of catalyst recycling experiments as determined by ICP-AES measurement, indicating the highly
efficient catalyst transfer. Furthermore, a continuous-catalyst-recycling approach has been successfully developed based on
flow chemistry in combination with the catalyst shuttling behavior, allowing Suzuki-Miyaura couplings to be conducted at
gram-scales with down to 10 ppm Pd loading. Given the significance of transition-metal-catalyzed cross-coupling and
increasing interests in sustainable chemistry, this work takes an important step towards the development of responsive
catalyst in addition to high activity by tuning the structures of ligands in combination with polymer science.
loaded with Pd are easily recyclable for homo-/heterogeneous
SM couplings,32-42 in comparison to small-molecule catalysts,
polymeric catalysts generally exhibit: a) limited functional group
tolerance, b) decreased reactivity toward deactivated aryl
chlorides, and c) unsatisfactory compatibility with
heterocycles.43 Furthermore, tandem/iterative catalysis based
on chemoselective SM coupling44-46 has been rarely realized
with polymeric catalysts.
Introduction
Transition-metal-catalyzed cross-coupling reactions have
become indispensable tools in organic synthesis. The Pd-
catalyzed Suzuki-Miyaura (SM) coupling is among the most
heavily used name reactions for C-C bond formation,1-3 and has
revolutionized synthetic approaches toward pharmaceuticals,4
agrochemicals,5 polymer materials6 and so on.7 Despite its
extraordinary advances, cost of palladium and its separation, as
well as sustainability of this chemistry are almost always
concerns of SM coupling, especially in process research and
development, so do other precious metal catalyzed reactions.8-
Previous work:
Small molecular ligand
tunable property for highly active catalysis
(i.e., monodentate phosphine)
Polymeric ligand
easy to recycle, limited substrate scope
10
Consequently, methods featured with low Pd loadings,11-16
Cordination site
recyclable catalysts17-18 and aqueous conditions19-21 have
received increasing attentions. For example, the Lipshutz group
disclosed that ppm Pd contained in FeCl3 salt catalyzed aqueous
SM coupling with a dialkylphosphine ligand.11 They also
reported that SM couplings could be facilitated by amphiphilic
molecules in water.12, 22-23 Based on previous achievements of
using electron-rich phosphine ligands to promote SM
homogeneous catalysis
heterogeneous catalysis
·
·
Substituents to regulate
R
P
electronic & steric factors
Polymer backbone
R
R
This work: thermoresponsive polymeric complex
couplings,24-31
the
Carrow
group
revealed
a
Organic phase
tri(adamantyl)phosphine-Pd complex catalyzed process with
low Pd loadings in organic solvent.13 While polymeric materials
R1
X
catalyst
shuttling
heat
R1
R2
+
reaction
R2
B(OH)2
R2P
M
up to 99% yields
scalable with ppm levels of Pd
recycle
a. State Key Laboratory of Molecular Engineering of Polymers, Department of
Macromolecular Science, Fudan University, Shanghai 200433 (China), E-mail:
chenmao@fudan.edu.cn
RT
continuous-flow catalyst recycling
broad substrate scope (73 examples)
Aqueous phase
Homepage: http://chenmaofudan.wixsite.com/polymao
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
Scheme 1 Ligand design in transition-metal-catalyzed cross-coupling.
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Herein we synthesized a novel polymeric pre-catalyst
Journal Name
Scheme 2 Synthetic pathway of WePhos5000 5a and pre-catalyst 6a, Cy = cyclohexyl
View Article Online
group, AcO = acetate group.
DOI: 10.1039/C9SC02171J
composed of methoxy poly(ethylene glycol) (PEG) linked
dicyclohexylphosphine ligand (WePhos) and Pd, which enables
a general, efficient and low Pd loading SM coupling via rapid
catalyst transferring between aqueous and toluene phases
(Scheme 1). This polymeric complex catalyzed reaction is
tolerant of various functional groups as well as
(hetero)aromatic rings, and is realized in tandem coupling with
high chemoselectivity. Moreover, taking advantage of the
thermoresponsive catalyst shuttling, a continuous-catalyst-
recycling approach based on flow chemsitry was developed to
streamline scalable SM couplings using down to 10 ppm
palladium.
The lower critical solution temperature (LCST) behaviour of
PEG is known in polymer science,47-50 allowing PEGylated
materials exhibiting dramatically decreased solubility in water
upon heating above LCST. We reasoned that by introducing a
PEGylated phosphine ligand, the corresponding Pd complex
would display thermoresponsive solubility in a biphasic system,
thereby promoting reaction in organic phase and facilitating
catalyst recycling simply by phase separation.
Subsequently, we synthesized the new ligand WePhos5000 5a
with a synthetic route as illustrated in Scheme 2. Starting from
4-bromophenol 2, a high overall yield of 83% was obtained for
ligand 5a. This compound is air stable, and was characterized
with matrix-assisted laser desorption ionization time of flight
(MALDI-TOF) mass spectrometry. As shown in Fig. 2a, a single
set of peaks is observed in MALDI-TOF mass spectrum, and each
peak is separated by the molar mass of a single repeating unit
in PEG (m/z = 44.05, Fig. 2b). The absolute m/z value is
consistent with the calculated molecular weight of 5a. The y-
intercept of the best-fit trend line of m/z vs number of repeating
units indicates the molecular weight of the chain-end group of
1
5a (Fig. 2c), which is consistent with expectation. The H NMR
(proton nuclear magnetic resonance) analysis51 also confirms
the chemical structure of WePhos5000. Mixing 5a with Pd(OAc)2
in a 2/1 ratio quantitatively generated pre-catalyst 6a. Peak
shift from 1.24 to 45.21 ppm in the 31P NMR spectra reveals the
successful coordination of phosphine to PdII center (Fig. 2d).52-53
a
Results and discussion
At the beginning of our investigation, to confirm and visualize
the shuttling effect, we synthesized a yellow polymeric
compound 1 with PEG5000 (molecular weight, Mn ~ 5000 g/mol)
and carboxyferrocene (Fig. 1). When 1 is dissolved in a mixture
of water and toluene at 25 °C, only water phase shows yellow
color; upon heating to 90 °C, toluene phase turns yellow within
30 s. The whole process is rapid and completely reversible,
clearly exhibiting the thermoresponsive shuttling of a PEG-
supported compound between water and organic phases.
4000
4500
5000
5500
6000
Mass (m/z)
O
PEG5000
O
b
c
n=104
44.05
n=105
n=106
6
5
n=103
44.05
y = 44.05x + 305.18
Fe
90 °C
25 °C
toluene
water
44.05
PEG5000
=
1
stir bar
O
n
Fig. 1 Optical images of the migration behavior of compound 1 between water and
toluene phases in response to temperature.
r2 = 0.9999
4
80
100
120
4840
4960
4880
Mass (m/z)
4920
Repeating unit
d
OH
OH
OTBS
TBSCl, DMAP
DCM, 0 °C
1. nBuLi, THF
TsO-PEG5000
Cs2CO3, DMF
WePhos 5a
2. Cy2PCl, -78 °C
3. nBu4NF, THF, RT
4. HBF4, THF, RT
Cy2P•HBF4
Br
2
Br
3
4
99% yield
91% yield
OPEG5000
Pd(OAc)2
Cy
Cy
P
OAc
pre-catalyst 6a
PEG5000
O
P
Pd
OPEG5000
toluene, RT
Cy
OAc
Cy
PCy2
WePhos5000
pre-catalyst
96% yield
6a
5a
92% yield
(ppm)
2 | J. Name., 2012, 00, 1-3
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a
Fig. 2 a) MALDI-TOF mass spectrum of WePhos5000 5a. b) Magnified MALDI-TOF mass
spectrum of the blue box in Fig. 2a. c) m/z vs number of repeating units for the MALDI-
TOF mass spectrum of 5a. d) 31P NMR spectra of 5a and 6a.
View Article Online
DOI: 10.1039/C9SC02171J
100
Conversion
Yield
Using the same synthetic method, a series of WePhos ligands
were prepared with PEG of different molecular weights (Mn ~
750 g/mol for 5b, Mn ~ 2000 g/mol for 5c, Mn ~ 10000 g/mol for
5d). When these ligands were characterized with size-exclusion
chromatography (SEC) (Fig. 3), the SEC profiles show clear shifts
from high to low retention times with no low-molar-mass tailing
(molecular weight distribution, Mw/Mn = 1.05-1.09), indicating
successful preparation of the polymeric ligands with precise
structure.
75
50
6a
6b
6c
6d
b
100
90
Mw/Mn
5a 1.07
5b 1.05
5c 1.05
5d 1.09
97% Pd is remained in water
phase
Conversion
Yield
80
1
2
3
4
5
6
7
8
9
10
Run
Fig. 4 a) Conversions and yields of SM cross-couplings between bromobenzene and 4-
methoxybenzeneboronic with pre-catalysts 6. b) Conversions and yields of target
product (4-methoxybiphenyl) for the catalyst recycling experiments with 6a. Conversions
and yields were determined by GC analysis.
12
14
16
18
Retention time (min)
Fig. 3 SEC results of WePhos ligands of different molecular weights.
With optimized reaction conditions in hand, the substrate
scope of (hetero)aryl bromides was investigated (Scheme 3). All
substrates underwent complete conversion in 30 min to 5 h,
affording products in good to excellent isolated yields with 50
to 500 ppm of catalyst. The polymeric complex catalyzed SM
reactions could be successfully carried out with para-, meta-,
and ortho-substituted aryl compounds and fused aryl
compounds. Electron-deficient, electron-neutral and electron-
rich aryl halides are all suitable substrates. The reaction
conditions are compatible with a broad scope of functional
groups including ester (9), amide (10), aldehyde (11) acetyl (12-
14) and nitrile (14), as well as unprotected hydroxyl (13-18),
amino (19) and carboxylic acid (20) groups. As we know,
heterocycles are core units of many important pharmaceuticals,
organic materials and natural products.55 However,
heterocycles are likely to coordinate with transition metals,
thus representing a challenging class of starting materials for
metal-catalyzed reactions with low catalyst dosages.56 With this
method, a variety of heterocyclic compounds including pyridine
(24-28), quinoline (29), carbazole (27), dibenzofuran (28), indole
(30), pyrimidine (31-32), pyrazine (33), pyrazole (34),
Next, Pd-complexes of ligands from 5a to 5d were employed
in the SM cross-coupling of bromobenzene and 4-
methoxybenzeneboronic acid with K2CO3 as the base in
water/toluene (v/v = 4/1) at 90 °C. As summarized in Fig. 4a,
when pre-catalyst 6a was used, reaction provided the highest
yield in 20 min reaction time as determined by gas
chromatography (GC yield >99%).54 After cooling down the
reaction mixture with 6a to room temperature, metal-complex
catalyst transferred to the aqueous layer and 4-
methoxybiphenyl product was left in toluene. Through a simple
phase separation, the aqueous layer was collected and reused
in the next SM cross-coupling. The water phase containing
catalyst was recycled for 10 times in this way without the
observation of a clear decrease in GC yields (Fig. 4b). The final
aqueous phase was analysed with inductively coupled plasma–
atomic emission spectrometer (ICP-AES), which indicated that
97% Pd was remaining in the aqueous phase, highlighting the
robust catalyst shuttling facilitated by the thermoresponsive
polymeric ligand.
imidazo[1,2-α]pyrazine
(35),
thiophene
(36-40)
benzothiophene (41) and furan (42) could be utilized to
generate corresponding products, representing the broadest
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substrate scope obtained with a polymeric catalsyt to the best
of our knowledge.
Moreover, the Suzuki-Miyaura cross-coupling using pre-
View Article Online
catalyst 6a was found to be applicable to D(hOeI:te10r.o10)a3r9y/Cl c9hSClo0r2i1d7e1Js
with a wide substrate scope as shonw in Scheme 4. Aryl
chlorides with a substituent group at different positions could
effectively react with aryl boronic acids (45-48) to give biaryl
compounds at 94-98% yields. Functional groups (for example,
acetyl (47), unprotected amino (48) and hydroxyl (49)) and
heterocycles including pyridine (51-52), pyrimidine (53),
thiophene (54-58) and dibenzofuran (58) underwent smooth
reaction with low (50-500 ppm) catalyst loading, and received
complete conversions in 2-5 h.
6a (0.005-0.05 mol%)
R1
R2
R1
R2
B(OH)2
Br +
H2O/toluene (v/v = 4/1)
K2CO3 (1 equiv.), 90 °C
1.02 equiv.
7 - 44
OMe
CF3
CHO
Ac
Ac
F
OH
NHAc
OH
12 92%a
(200 ppm) (500 ppm)
OMe
COOEt
CF3
6a (0.005-0.05 mol%)
7 99%a
8 95%a
(50 ppm)
9 96%a
10 92%a
11 90%a
13 96%a
(50 ppm)
Cl
R1
R2
45 - 58
R1
R2
1.1 equiv.
B(OH)2
+
H2O/toluene (v/v = 4/1)
K2CO3 (2 equiv.), 90 °C
(50 ppm)
(50 ppm) (200 ppm)
OH
OH
Ac
COOH
OH
NH2
OH
tBu
Ph
NH2
Ac
N
CF3
tBu
R3
tBu
CN
14 93%a 15 90%a 16 97%a 17 R3 = tBu 97% (500 ppm) 19 97%a
20 95%a
21 97%a
(50 ppm)
OMe
CN
OMe
46 98%a
(200 ppm)(500 ppm) (50 ppm) 18 R3 = CF3 96% (500 ppm) (500 ppm) (500 ppm)
45 94%a
47 94%a
48 95%a
49 91%a
50 92%a
(200 ppm) (50 ppm)
51 98%a
N
(50 ppm)
(50 ppm) (50 ppm)
(500 ppm)
(200 ppm)
N
CF3
Ac
N
S
N
S
S
S
Ph
N
O
N
OMe
CF3
NPh2
MeO
N
OMe
nBu
S
22 97%a
(50 ppm)
23 90%a
(50 ppm)
24 96%a
(50 ppm)
25 97%a 26 94%a
(50 ppm) (50 ppm) (50 ppm)
27 97%a
N
N
Ac
NPh2
52 97%a 53 96%a 54 96%a 55 91%a
(200 ppm) (500 ppm) (200 ppm) (200 ppm)
56 97%a
(200 ppm)
57 92%a
(200 ppm) (200 ppm)
58 99%a
nBu
H
N
N
N
N
Scheme 4 Cross-coupling of (hetero)aryl chlorides with pre-catalyst 6a. Conditions: R1-X
(0.5 mmol), R2-B(OH)2 (0.55 mmol), 6a (50-500 ppm), K2CO3 (1.0 mmol), water (0.8 mL),
toluene (0.2 mL), 90 °C, 2 h. Catalyst loadings are listed in the parentheses. Isolated yields
based on aryl chlorides. a5 h.
Ph
O
N
N
N
MeO
OMe
28 97%a
(50 ppm)
NH2
29 95%a
(50 ppm)
30 93%a
(50 ppm)
31 97%a
32 95%a
(200 ppm)
(200 ppm)
Bn
N
6a (0.02-0.05 mol%)
N
R1
59 - 65
R2
B(OH)2
1.02 equiv.
Br +
Cl
R1
R2
Cl
N
N
N
N
H2O/toluene (v/v = 4/1)
K2CO3 (2 equiv.), 90 °C
S
S
N
Ph
N
O
Cl
S
Cl
NPh2
37 97%a
(50 ppm)
O
nBu
nBu
OMe
N
H
Cl
33 96%a
34 95%a
35 93%a
36 95%a
(50 ppm)
38 96%a
(50 ppm)
N
Cl
(500 ppm)
(200 ppm)
(500 ppm)
O
S
OPh
S
Cl
62 98%
tBu
59 98%
60 96%
61 97%
O
(200 ppm)
(500 ppm)
(200 ppm)
(500 ppm)
F
O
S
N
O
O
O
F
39 96%a
(50 ppm)
40 97%a
(50 ppm)
41 96%a
42 93%a
(50 ppm) (50 ppm) (50 ppm)
43 97%a 44 97%b
S
F
Cl
O
S
N
H
N
H
Cl
(50 ppm)
HN
Cl
Scheme
3
Cross-coupling of (hetero)aryl bromides using pre-catalyst 6a.
Cl
F
Conditions: R1-Br (0.5 mmol), R2-B(OH)2 (0.51 mmol), 6a (50-500 ppm), K2CO3 (0.5 mmol),
water (0.8 mL), toluene (0.2 mL), 90 °C, (30 min). Catalyst loadings are listed in the
parentheses. Isolated yields based on aryl bromides. a2 h. bR2-BPin (boronic acid pinacol
ester) was used instead of R2-B(OH)2.
63 95%
(500 ppm)
64 92%
(500 ppm)
65 92% Boscalid
(500 ppm)
Scheme 5 Chemoselective cross-coupling of conjunctive dihalide compounds using pre-
catalyst 6a. Conditions: Cl-R1-Br (0.5 mmol), R2-B(OH)2 (0.51 mmol), 6a (50-500
ppm), K2CO3 (1.0 mmol), water (0.8 mL), toluene (0.2 mL), 90 °C, 2 h. Catalyst
4 | J. Name., 2012, 00, 1-3
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loadings are listed in the parentheses. Isolated yields based on conjunctive dihalide
compounds.
obtained for all examples after two-step syntheses in the
presence of heterocycles (for example, thiophene (66),
View Article Online
DOI: 10.1039/C9SC02171J
pyrimidine (67), pyridine (68) and furan (69)) and functional
groups (for example, sulphonamide (69), amide (70) and ester
(71, 72)), demonstrating the high efficiency achieved with this
method.
On the basis of the thermoresponsive catalyst migration, we
anticipated that a continuous-flow synthetic strategy60-67 would
be practical to scale-up SM couplings at ultralow Pd loadings by
continuously recycling of catalyst. To realize this idea, we
assembled a continuous-flow setup (Fig. 5, Scheme 7) to
synthesize 73, a typical unit with aggregation-induced emission
(AIE) behavior, which has been employed in high-tech
applications such as optoelectronic materials and biomedical
sensors.68
Given the different reactivities of C-Br and C-Cl bonds
demonstrated in Pd-catalyzed cross-coupling with many small
molecule catalsyts, we next evaluated the chemical selectivity
of polymeric catalyst 6a as shown in Scheme 5. To our delight,
excellent selectivity was observed in all examined cases. A
variety of functionalized bi(hetero)aryl were produced with
intact aryl chlorides groups (59-65) at above 90% isolated yields,
which could be useful in further metal-catalyzed
transformations. Importantly, the chemoselectivity was not
affected by steric or electronic factors with our polymeric
catalsyt.
B(OH)2
R2
R2
R3
6a (0.05 mol%)
Br
R1
R1
+
H2O/toluene (v/v = 4/1)
K2CO3 (2 equiv.), 90 °C
B(OH)2
continuous recycle
Cl
R3
BPR1
oil bath
pump1
catalyst
OMe
product
RT
BPR3
N
packed-bed reactor
BPR2
MeO
F
pump2
substrates
OMe
F
S
N
toluene phase (product)
water phase (catalyst)
N
66 93%
67 95%
68 91%
reservoir
O
pump
mixer
O
S
O
NH
back-pressure regulator (BPR)
N
H
O
Fig. 5 Setup for Continuous-catalyst-recycling synthesis based on flow chemistry.
tBu
69 93%
70 92%
O
O
Ac
Me
N
S
COOEt
tBu
S
nBu
X = Br
74 95%
71 94%
72 96%
X = Br
73 96%
4.15 g, 10 ppm
X = Cl
75 92%
X = Br
76 94%
Scheme 6 Tandem Suzuki-Miyaura cross-coupling with pre-catalyst 6a. Conditions: R1-X
(0.5 mmol), R2-B(OH)2 (0.51 mmol), R3-B(OH)2 (0.55 mmol), 6a (500 ppm), K2CO3 (1.0
mmol), water (0.8 mL), toluene (0.2 mL), 90 °C. Isolated yields based on conjunctive
dihalide compounds.
2.99 g, 10 ppm
1.78 g, 50 ppm
1.88 g, 20 ppm
S
Ac
HN
OMe
OMe
Tandem SM coupling based on chemoselective reaction
facilitates modular and rapid synthesis of diversified molecules
for applications such as material screening and drug
discovery.44-46, 57-59 We next employed the polymeric catalyst in
tandem SM coupling based on the different reactivities of
electrophiles (Scheme 6). In these reactions, after the first-step
arylation via C-Br bond cleavage, second boronic acids were
subsequently added into reaction mixtures without additional
catalyst and base. To our delight, excellent yields (91-96%) were
X = Br
77 93%
2.80 g, 20 ppm
X = Br
78 94%
2.61 g, 20 ppm
X = Br
79 91%
1.66 g, 20 ppm
Scheme 7 Examples of Suzuki-Miyaura couplings with the continuous-catalyst-recycling
approach based on flow chemistry. Collections were based on 12.5 mmol aryl halides for
all examples. Pd loadings were calculated according to the molar ratio of [Pd]/[aryl
halide]. See the supplementary information for details of flow setup and operations.
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A solution of pre-catalyst and base in water was mixed with a
solution of bromotriphenylethylene and 4-
View Article Online
443.
DOI: 10.1039/C9SC02171J
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methylphenylboronic acid pinacol ester in toluene, and
delivered into a pack-bed reactor (packed with stainless steel
beads)51 submerged in a preheated 110 °C bath using 30 min
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73 was isolated from the collected organic layer using only 1.3
mg pre-catalyst 6a (13.8 μg Pd).
With this flow technique in hand, other bi(hetero)aryl
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successfully synthesized at gram scales with 10-50 ppm of
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In conclusion, we have developed a novel thermoresponsive
polymeric catalyst, which can rapidly shuttle between water
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coupling and tandem reaction with good to excellent isolate
yields at ppm level of catalyst usages. This method allows the
preparation of a broad scope of bi(hetero)aryls, and is well
tolerant to various functional groups. Furthermore, in
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continuous-catalyst-recycling, further promoting the scalability
and efficiency of cross-coupling using ultralow loadings of
palladium. Given the significant influence of transition-metal-
catalyzed cross-coupling and increasing interests in sustainable
chemistry, we believe that based on the presented strategy,
new response modes can be developed by tuning the structure
of ligands with different polymeric species. Also, the
compatibility of this method with other metal-catalyzed
reactions is under exploration, which would promisingly
facilitate diverse applications.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
34 M. Chtchigrovsky, Y. Lin, K. Ouchaou, M. Chaumontet, M.
Robitzer, F. Quignard, F. Taran, Chem. Mater., 2012, 24, 1505-1510.
35 S. Doherty, J. G. Knight, T. Backhouse, E. Abood, H. Alshaikh, A. R.
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J. Warren, I. J. S. Fairlamb, K. R. J. Lovelock, Adv. Synth. Catal., 2018,
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36 R. Shen, W. Zhu, X. Yan, T. Li, Y. Liu, Y. Li, S. Dai, Z.-G. Gu, Chem.
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This research was finally supported by NSFC (no. 21704016), the
start-up funding from Fudan University, and the National
Program for Thousand Young Talents of China.
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[M] migration
DOI: 10.1039/C9SC02171J
R1
X
R2
R1
R2
+
B(OH)2
Organic phase
catalyst
heat
• thermoresponsive catalsyt migration
• broad substrate scope (73 examples)
• up to 99% isolated yields
reaction
recycle
R2P
• continuous-catalyst-recycling synthesis
based on flow chemistry
M
• scalable with ppm Pd
RT
Aqueous phase
A thermoresponsive polymeric Pd-complex was synthesized, enabling highly efficient
cross-couplings and continuous-catalyst-recycling flow reactions with ultralow Pd usages.