Self-supported heterogeneous star-shaped oxime-palladacycle catalysts for the Suzuki coupling reactions

Article abstract of DOI:10.1055/s-2006-941585

A novel strategy to synthesize heterogeneous star-shaped oxime-palladacycle catalysts, which exhibited good catalytic activity and recyclability in the Suzuki coupling of aryl bromides and chlorides, was described. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-941585

LETTER
1503
Self-Supported Heterogeneous Star-Shaped Oxime-Palladacycle Catalysts for
the Suzuki Coupling Reactions
O
xime-Palladacyc
i
le Cata
n
S
uzuki Coup
-
ling Re
a
P
ctions ing Liu,b,c Ying-Chun Chen,*a Yong Wu,a Jin Zhu,b Jin-Gen Deng*a,b
a
b
c
Key Laboratory of Drug-Targeting of Education Ministry and Department of Medicinal Chemistry, West China School of Pharmacy,
Sichuan University, Chengdu 610041, P. R. of China
Fax +86(28)85502609; E-mail: ycchenhuaxi@yahoo.com.cn
Key Laboratory of Asymmetric Synthesis & Chirotechnology of Sichuan Province and Union Laboratory of Asymmetric Synthesis,
Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, P. R. of China
E-mail: jgdeng@cioc.ac.cn
Graduate School of Chinese Academy of Sciences, Beijing, P. R. of China
Received 22 February 2006
R
OH
Abstract: A novel strategy to synthesize heterogeneous star-
shaped oxime-palladacycle catalysts, which exhibited good catalyt-
ic activity and recyclability in the Suzuki coupling of aryl bromides
and chlorides, was described.
NMe2
N
S
P(o-Tol)2
Pd Cl
Pd Cl
Pd Cl
Pd Cl
2
2
2
2
Key words: self-supported, palladacycle, heterogeneous, Suzuki
coupling
Figure 1 Structures of selected palladacycles
For this purpose the star-shaped oxime-based ligands 2
were smoothly prepared in a convergent strategy, using
hexakis(bromomethyl)benzene as the multifunctional
core (Scheme 1).8 We chose the poly(ethylene) glycol as
the tether in order to let the resulting solid catalysts have
better swelling properties in polar solvents. After dissolv-
ing the star-shaped ligand 2 and sodium acetate in metha-
nol, a solution of lithium tetrachloropalladate in methanol
was added. Indeed a brown solid quickly precipitated,
which apparently demonstrated the formation of cross-
linkages amongst star-shaped units. After further stirring
for 72 hours, the solid was collected and thoroughly
washed with water, methanol and acetone.9,10 The result-
ing heterogeneous catalyst was characterized by spectro-
scopic analysis. Its IR spectroscopy exhibited the similar
absorption compared with the monomeric palladacycle
catalyst 4, which indicated the formation of palladacycle
structures in the supported catalyst. Scanning microscopic
(SEM) images showed that the solids were composed of
micrometer particles, the individual scales being about
0.5–5 mm large (Figure 2). From ICP analysis, it was cal-
culated that the Pd-loading for 3a and 3b was 1.98 and
2.03 mmol Pd/g, respectively. Moreover, in combination
with elemental analysis of nitrogen in solid catalyst, we
could calculate that about 48.2% and 55.2% oxime
ligands were coordinated with Pd through chloro-bridges
in 3a and 3b, respectively (molar ratio of Pd/N).
The development of immobilized and recyclable homo-
geneous catalysts triggered ongoing interests because of
the requirement of green chemistry.1 Various supports, in-
cluding inorganic materials, soluble and insoluble organic
polymers, have been widely applied.2,3 However, the re-
duced catalytic activities were usually observed in these
supported catalysts in comparison with the homogeneous
systems. Moreover, the synthetic procedures and charac-
terization of the polymer-immobilized catalysts are gener-
ally proved to be very tedious due to the macromolecular
structures of the polymeric supports. Therefore, the devel-
opment of more efficient protocols to obtain recyclable
supported catalysts becomes essential. Recently the self-
supported heterogeneous catalysts,4 readily promoted by
the linkage of metal’s coordination, have demonstrated to
be very successful in some systems. In this paper, we
would like to present the self-supported star-shaped5
catalysts through the cross-linkage of palladium–chloro
bridges for the first time.
Organopalladium compounds play a very important role
in transition-metal-catalyzed cross-coupling reactions.6
Carbo-metallated Pd(II) complexes, especially palladacy-
cles, have been by far the most developed and studied cat-
alysts owing to their structural versatility, easy synthetic
accessibility, and promising catalytic activity (Figure 1).7
They are structurally stable dimers linked by two Pd–
halide or Pd–acetate bridges. Thus, when multiple star-
shaped ligands and palladium precursor are combined to-
gether, we envision that the self-supported supramolecu-
lar catalysts would be formed owing to the intermolecular
cross-linking of palladium–halide or acetate bridges
amongst individual star-shaped units.
With the desired heterogeneous star-shaped palladacycle
catalysts 3a,b in hand, application in catalysis was tested
in the Suzuki coupling reactions of aryl bromides at ambi-
ent temperature (Table 1).11,12 The solid catalyst was
found to be suspended in the mixture throughout the reac-
tion. It should be noted that all reactions were conducted
at aerobic conditions and all reagents were used as re-
ceived. After examining a number of conditions, we found
that the best results could be obtained in a mixture of
ethanol–water (2:1) using K2CO3 as the base at 1 mol% Pd
SYNLETT 2006, No. 10, pp 1503–1506
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1
.0
6
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0
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Advanced online publication: 12.06.2006
DOI: 10.1055/s-2006-941585; Art ID: W04306ST
© Georg Thieme Verlag Stuttgart · New York

1504
Q.-P. Liu et al.
LETTER
Table 1 Suzuki Coupling of Aryl Bromide with Aryl Boronic
Br
Acida
i, ii
HO(H2CH2CO)n
+
Br
Br
Br
Br
O
1 mol% catalyst
Ar–Ar1
ArBr + Ar1B(OH)2
1
K2CO3, EtOH–H2O (2:1)
O
N
O
Br
OH
N OH
Pd
Entry Ar
Ar1
Catalyst Time Yield
)
Cl
2
(h)
(%)b
OH
O
4
N
N
43
O
1
Ph
Ph
Ph
4
0.3
(98)c
H3COC
OH
O
O
n
n
O
O
O
O
n
iii
32
O
2
3
3a
3b
0.3
0.3
(98)c
H3COC
O
n
O
O
O
n
O
33
O
N
(98)c
H3COC
O2N
O
HO
n
N
O
=
OH
N OH
4
Ph
3b
0.2 97
0.5 98
3a n = 1
3b n = 2
Pd
)
Cl
2
2
OH
N
5
6
7
8
Ph
Ph
Ph
Ph
3b
3b
3b
3b
Scheme 1 Synthesis of self-supported star-shaped oxime-pallada-
cycles. Reagents and conditions: i) NaH, THF; ii) NH2OH·HCl,
NaOAc, EtOH; iii) Li2PdCl4, NaOAc.
OHC
2
3
5
95
96
87
CH3OOC
H3C
H3CO
O2N
H3CO
9
3b
0.2 98
0.25 98
10
11
12
3b
3b
3b
OHC
H3C
H3CO
H3CO
3
5
95
85
H3CO
F
H3CO
O2N
Figure 2 SEM images of self-supported catalyst 3a
13
14
3b
3b
8
79
70
F
F
loading. As shown in Table 1, in the Suzuki coupling of
p-bromoacetophenone and phenylboronic acid, similar
catalytic activity was observed for heterogeneous cata-
lysts 3a,b comparable to the monomeric catalyst 4 (entries
1–3). Under the optimized conditions, various activated
and unactivated aryl bromides could smoothly react with
aryl boronic acid in the presence of 3b (entries 4–12).
However, the electron-withdrawing substitution on aryl
boronic acid tended to greatly decrease the reactivity (en-
tries 13 and 14). In addition, 2-bromopyridines could be
cleanly coupled with aryl boronic acid, while better yields
were obtained at elevated temperature (entries 15–18).
The reactions were quite sluggish when the Pd loading
was lowered to 0.1 mol% at room temperature, but good
results could be obtained at 60 °C (entries 19 and 20).
Moreover, the catalyst 3b showed high catalytic activity
at 0.01 mol% Pd loading at 100 °C for activated aryl bro-
mide (entry 21), and quantitative yield was still obtained
when deactivated p-bromoanisole was applied (entry 22).
H3COC
24
F
15
Ph
3b
3b
3b
18
10
10
37
75
82
N
N
N
N
16d
17d
Ph
H3CO
H3CO
18d
3b
3b
8
1
87
96
COOH
O2N
19d,e
Ph
Synlett 2006, No. 10, 1503–1506 © Thieme Stuttgart · New York

LETTER
Oxime-Palladacycle Catalysts for the Suzuki Coupling Reactions
1505
Table 1 Suzuki Coupling of Aryl Bromide with Aryl Boronic Acida
(continued)
Table 2 Suzuki Coupling of Aryl Chloride with Aryl Boronic Acida
2 mol% cat., K2CO3
ArCl +
Ar–Ar1
1 mol% catalyst
Ar1B(OH)2
Ar–Ar1
ArBr + Ar1B(OH)2
TBAB, DMF, 110 °C
K2CO3, EtOH–H2O (2:1)
Entry Ar
Ar1
Catalyst Time Yield
Entry Ar
Ar1
Catalyst Time Yield
(h)
(%)b
(h)
(%)b
1
2
3
4
Ph
Ph
Ph
4
0.7 95
O2N
20d,e
Ph
Ph
3b
3b
10
67
H3CO
3a
3b
4
2
98
O2N
O2N
21f
1
8
98
98
1.7 98
O2N
22f
Ph
3b
24
68
52
55
70
70
H3CO
H3COC
H3COC
H3CO
H3CO
a Unless otherwise noted, the reaction was conducted at ambient tem-
perature. ArBr–aryl boronic acid–K2CO3 = 1:1.5:2, at 0.2 mmol scale.
b Isolated yield.
5
6
7
8
3a
3b
3b
3b
24
24
23
24
H3COC
OHC
H3CO
c The yield in brackets was obtained after 1 h.
d Reaction was conducted at 60 °C.
Ph
e At 0.1 mol% Pd loading.
f Reaction was conducted at 100 °C at 0.01 mol% Pd loading.
H3CO
OHC
Subsequently, we investigated the catalytic efficacy of the
self-supported heterogeneous catalysts in the Suzuki cou-
pling of aryl chlorides. Unlike aryl bromides, the optimal
conditions were found to be in DMF at 110 °C, using
K2CO3 as the base along with 20 mol% TBAB (tetrabutyl-
ammonium bromide). The reaction rate was dramatically
decreased in the absence of TBAB.9 As summarized in
Table 2, at 2 mol% Pd loading, while slightly lower cata-
lytic activity was observed in comparison with homoge-
neous monomeric catalyst 4 (Table 2, entry 1 vs. entries 2
and 3, entry 4 vs. entries 5 and 6), various activated aryl
chlorides were successfully coupled with aryl boronic
acids catalyzed by heterogeneous 3b (entries 7–11). As
reported above, the electron-deficient aryl boronic acid
also exhibited decreased activity in the coupling with aryl
chloride (entry 12). At 5 mol% Pd loading, chlorobenzene
showed the reactivity but with low yield (entry 13).
CN
9
10
11
Ph
3b
3b
3b
10
24
24
57
78
45
CN
H3CO
H3COC
H3CO
F
O2N
12
3b
3b
8
80
33
F
13c
24
H3CO
a ArCl–aryl boronic acid–K2CO3–TBAB = 1:1.5:2:0.2, at 0.2 mmol
scale.
b Isolated yield.
c At 5 mol% Pd loading.
Furthermore, we studied the stability of the self-supported
star-shaped palladacycle catalyst in the Suzuki coupling
reactions. After the reaction of m-nitrobromobenzene and
phenylboronic acid completed in ethanol–water (2:1) with
1 mol% Pd loading at room temperature, the mixture was
directly filtered. Then other substrates, p-bromoaceto-
phenone, phenylboronic acid and K2CO3, were added to
the aqueous solution. Almost no further coupling reaction
occurred after eight hours at ambient temperature, and
less than 5% of 4-acetylbiphenyl was isolated after heat-
ing at 100 °C for 15 hours. This experiment indicated that
only trace amounts of active species had leached into the
supernatant under above conditions. Moreover, the recy-
cling use of heterogeneous catalyst 3b was investigated in
the coupling of p-nitrochlorobenzene and phenylboronic
acid in DMF at 110 °C (Table 3). After completion, the
catalyst was filtered, washed, dried and directly reused in
the next reaction. High catalytic activity was maintained,
and almost quantitative yield was still obtained in the fifth
use after slight extension of the reaction time (first use,
98% yield after 100 min; fifth use, 95% yield after 130
min). On the other hand, in order to know if some active
species was formed in the supernatant in the presence of
TBAB, p-bromoacetophenone and phenylboronic acid
were added to the filtered DMF solution and allowed to
react at 110 °C. In fact, complete conversion was ob-
served after five hours, which indicated that small amount
of catalysts had leached into the solution in the presence
of TBAB.13 In addition, SEM images showed that the par-
ticles of recovered catalyst enlarged during the reaction,
although quite similar IR absorption was observed in the
recovered catalyst compared with the original one.
In summary, we have presented a novel strategy to synthe-
size the heterogeneous palladacycle catalysts that employ
the cross-linking of individual star-shaped ligands
Synlett 2006, No. 10, 1503–1506 © Thieme Stuttgart · New York

1506
Q.-P. Liu et al.
LETTER
J. Am. Chem. Soc. 2005, 127, 7694. (d) Peng, H. Y.; Lam,
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(i) Takizawa, S.; Somei, H.; Jayaprakash, D.; Sasai, H.
Angew. Chem. Int. Ed. 2003, 42, 5711. (j) For pioneer work
on cross-linked dendritic catalysts, see: Reetz, M. T.; Giebel,
D. Angew. Chem. Int. Ed. 2000, 39, 2498. (k) For self-
supported amphiphilic polymeric Pd-catalyst, see: Yamada,
Y. M. A.; Takeda, K.; Takahashi, H.; Ikegami, S. Org. Lett.
2002, 4, 3371.
Table 3 Recovery Use of Heterogeneous Palladacycle Catalyst 3b
in the Suzuki Reaction of p-Nitrochlorobenzene with Phenylboronic
Acida
2 mol% 3b
+
Cl
O2N
PhB(OH)2
O2N
Ph
K2CO3, TBAB
DMF, 110 °C
Run 1
Yield
Time
Run 2
Yield
Time
Run 3
Yield
Time
Run 4
Yield
Time
Run 5
Yield
Time
98%
98%
98%
98%
95%
100 min
100 min
110 min
120 min
130 min
a ArCl–phenyl boronic acid–K2CO3–TBAB = 1:1.5:2:0.2, at 1.5
mmol scale using 15 mg catalyst 3b.
(5) (a) Rigaut, S.; Delville, M.-H.; Losada, J.; Astruc, D. Inorg.
Chim. Acta 2002, 334, 225. (b) Harada, T.; Nakatsugawa,
M. Synlett 2006, 321.
(6) Metal-Catalyzed Cross-Coupling Reactions, 2nd ed., Vol. 1
and 2; de Meijere, A.; Diederich, F., Eds.; Wiley-VCH:
Weinheim, 2004.
through Pd–chloro bridges for the first time. The self-sup-
ported heterogeneous solids are stable and effective cata-
lysts for the Suzuki coupling of aryl bromides and
chlorides comparable to the homogeneous analogue under
aerobic conditions. Moreover, simple recovery and reuse
of the heterogeneous star-shaped catalysts was demon-
strated while some catalyst leaching was detected in the
presence of TBAB. We believe that this protocol of cross-
linking of appropriate compounds with multiple ligands
by Pd–halide bridges may lead to novel and efficient
heterogeneous catalysts in other palladacycles as well.
Furthermore, application in other transition-metal-halide
linked catalytic systems will be desirable.14
(7) For recent reviews on palladacycles, see: (a) Dupont, J.;
Pfeffer, M.; Spencer, J. Eur. J. Inorg. Chem. 2001, 1917.
(b) Bedford, R. B. Chem. Commun. 2003, 1787. (c) Zapf,
A.; Beller, M. Chem. Commun. 2005, 431. (d) Dupont, J.;
Consorti, C. S.; Spencer, J. Chem. Rev. 2005, 105, 2527.
(8) (a) Závada, J.; Pánková, M.; Holý, P.; Tichý, M. Synthesis
1994, 1132. (b) Weng, L.-L.; Chen, Y.-C.; Zheng, H. Chin.
J. Chem. 1998, 16, 28.
(9) For the synthesis and application of oxime-palladacycles,
see: (a) Alonso, D. A.; Nájera, C.; Pacheco, M. C. Org. Lett.
2000, 2, 1823. (b) Alonso, D. A.; Nájera, C.; Pacheco, M. C.
J. Org. Chem. 2002, 67, 5588. (c) Botella, L.; Nájera, C.
Angew. Chem. Int. Ed. 2002, 41, 179. (d) For recyclable
silica gel supported oxime-palladacycle catalyst, see:
Baleizão, C.; Corma, A.; García, H.; Leyva, A. Chem
Commun. 2003, 606.
Acknowledgment
(10) General Procedure for the Synthesis of Self-Supported
Catalyst 3.
This work was supported by the grant from Sichuan University. We
are grateful for the financial support from the National Natural
Science Foundation of China. We thank Prof. MFH for his help
concerning ICP analysis.
To a solution of Li2PdCl4 (116 mg, 0.44 mmol) and NaOAc
(38.3 mg, 0.46 mmol) in MeOH (4 mL) was added a solution
of the corresponding star-shaped oxime 2 (0.49 mmol) in
MeOH (4 mL). Brown solid precipitated from the solution in
about half an hour. After stirring at r.t. for 1 d, the mixture
was further stirred at 40 °C for 48 h. The mixture was filtered
and washed thoroughly with H2O, MeOH and acetone. The
solid was dried under high vacuum at 50 °C for 10 h. The Pd
loading was determined by ICP analysis.
References and Notes
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(13) TBAB has been documented to stabilize the active
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Synlett 2006, No. 10, 1503–1506 © Thieme Stuttgart · New York