Kaiser oxime resin-derived palladacycle: A recoverable polymeric precatalyst in Suzuki-Miyaura reactions in aqueous media

Article abstract of DOI:10.1016/j.jorganchem.2009.01.016

Representative cross-coupling reactions of aryl bromides with different types of aryl-, alkyl, trivinylboroxine-pyridine complex, and alkenylboronic acids are performed using a polymer-bonded palladacycle derived from Kaiser oxime resin as precatalyst and

Full text of DOI:10.1016/j.jorganchem.2009.01.016

Journal of Organometallic Chemistry 694 (2009) 1658–1665
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Kaiser oxime resin-derived palladacycle: A recoverable polymeric precatalyst
in Suzuki–Miyaura reactions in aqueous media
*
Emilio Alacid, Carmen Nájera
Departamento de Química Orgánica, Facultad de Ciencias, Instituto de Síntesis Orgánica (ISO), Universidad de Alicante, Apdo 99, 03080 Alicante, Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 6 October 2008
Received in revised form 8 January 2009
Accepted 9 January 2009
Available online 20 January 2009
Representative cross-coupling reactions of aryl bromides with different types of aryl-, alkyl, trivinylbo-
roxine–pyridine complex, and alkenylboronic acids are performed using a polymer-bonded palladacycle
derived from Kaiser oxime resin as precatalyst and potassium carbonate as base under water reflux.
These processes afford biphenyls, alkylbenzenes, styrenes, and stilbenes, respectively. The same boronic
acids can be cross-coupled with representative allyl and benzyl chlorides using KOH as base in aqueous
acetone at 50 °C providing allylbenzenes, diarylmethanes, and 1,4-pentadienes. The palladated polymer
can be recovered by filtration and reused during 3–9 cycles with up to 5% of Pd leaching in each run. Very
low Pd leaching levels in the crude product can be determined by ICP–OES analyses. The reaction does not
work when Hg(0) is added. TEM analyses from the solution indicate the formation of Pd nanoparticles.
Ó 2009 Elsevier B.V. All rights reserved.
Keywords:
Oxime-derived palladacycles
Cross-coupling reactions
Polystyrene
Boronic acids
Water
1. Introduction
be possible to recover the unreacted palladacycle and reused it
again, (c) a lower percentage of Pd in the supported palladacycle
Considerable efforts have been devoted to develop supported
Pd–ligand complexes where the ligand is covalently bonded to an
organic polymer or to an inorganic solid in order to facilitate ligand
and specially Pd recovery in cross-coupling reactions [1]. In these
processes and due to the high temperatures that must be used
combined to the high tendency of Pd(II) to be reduced to Pd(0),
the Pd leaching to the solution takes place easily by reactions with
components present in the medium [1b,2]. The formed Pd(0), spe-
cially before aggregation to nanoparticles, is a very active catalyst
able to work through a neutral mechanism [3]. The revival of pal-
ladacycles as catalysts or precatalysts in cross-coupling reactions
occurred in the middle of the nineties when Herrmann et al. used
cyclopalladated tri-o-tolylphosphine as catalyst in Heck reactions
[4]. The stability and, at the same time, high ability of carbapalla-
dacyles to slowly release Pd(0) suppress aggregation and give them
a high efficiency as catalysts in a wide scope of reactions [5]. They
can be easily prepared, show high stability under atmospheric con-
ditions and can be anchored to different solid supports. The use of
solid-supported palladacycles presents advantages compared to
their unsupported counterparts: (a) they can present similar cata-
lytic activity because decompose giving atomic Pd(0), (b) due to
the slow decomposition rates, the supported complex can survive
the cross-coupling process and therefore after filtration it would
decreases the leaching in the final product, which is a very impor-
tant problem in active pharmaceutical ingredients (APIs) [6] and
finally, (d) the product can be easily separated from the polymer.
However, immobilized palladium salts or complexes are usually
active in organic solvents and in some cases bearing small propor-
tions of water. In our previous work, we have reported that dimeric
oxime-derived carbapalladacycles 1 [7] and 2 [8] are excellent pre-
catalysts in cross-coupling reactions under phosphine-free condi-
tions such as, Heck, Stille, Suzuki, Ullmann, Sonogashira, Hiyama,
and Glaser in organic and aqueous media, being even more effi-
cient than Pd salts [9]. Cross-coupling processes such as Suzuki
[8a,b,m] and Hiyama [8h,i,j] reactions could be performed using
water as solvent even with hydrophobic substrates. The great
importance of using water as a reaction solvent, specially in palla-
dium-catalysed cross-coupling reactions has been highlighted in
recent years [10]. However, cross-couplings using polystyrene-
supported palladium complexes in water as solvent have seldom
been studied. Recently, we have described that the palladated Kai-
ser oxime resin 3 is a very active precatalyst in Mizoroki–Heck
reactions in organic and aqueous media [11]. This polymeric com-
plex 3 [12] can be recovered by filtration and reused during several
cycles with rather low leaching of palladium into the solution. In
this paper, we present the catalytic activity and the corresponding
studies about recycling of this polymer-supported palladacycle in
different types of Suzuki–Miyaura cross-coupling reactions [13]
of aryl bromides, allyl and benzyl chlorides with aryl, alkyl, and
alkenylboronic acids in aqueous media.
* Corresponding author. Tel.: +34 96 5903728; fax: +34 96 5903549.
E-mail address: cnajera@ua.es (C. Nájera).
0022-328X/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2009.01.016

E. Alacid, C. Nájera / Journal of Organometallic Chemistry 694 (2009) 1658–1665
1659
6
4
2
obtained, respectively, although in the first case the reaction time
was too long (3 d). Aqueous THF was used for the recycling exper-
iments at rt affording 90%, 81% and 75% crude yield after 3 cycles,
the reaction time being increased from 14 to 70 h (Table 1, entries
13). Room temperature reactions with this Pd loading resulted too
slow and therefore the polymer was degraded during these cross-
couplings. The Pd leaching on the isolated 4-acetylbiphenyl crude
product was between 19 and 27 ppm after filtration of the poly-
meric palladacycle 3 and the polymer contained 56% of Pd loading
after the third run, (determined by ICP–OES, see Section 4).
In order to decrease the reaction time, the temperature was in-
creased to 60 °C for the cross-coupling of 4-bromoacetophenone
with phenylboronic acid in aqueous MeOH (1:3) using K2CO3 as
2. Results and discussion
2.1. Cross-coupling of aryl bromides with boronic acids
The evaluation of palladated Kaiser oxime resin 3, prepared as
previously described [11], as precatalyst in the Suzuki reaction of
4-bromoacetophenone and phenylboronic acid was performed un-
der different reaction conditions using homeopathic loading
(0.01 mol%) of Pd (Table 1). For room temperature conditions,
KOH as base and different aqueous solvents such as, MeOH–H2O
(3:1), N,N-dimethylacetamide (DMAc)–H2O (4:1), n-butanol–H2O
(3:1), acetone–H2O (3:1) and THF–H2O (3:1) were studied. In the
first and last case, high yields (99% and 90%, respectively) were
Table 1
Recycling experiments on the cross-coupling of aryl bromides and chlorides with phenylboronic acid using polymer 3.a
2
Entry
Run
X
Y
Mol% Pd
0.01
Base
KOH
T (°C)
Solvent
Time
Yield (%)b
Pd leachingc
1
2
3
4
5
6
7
8
1
2
3
1
2
3
4
5
6
1
2
3
4
5
1
2
3
4
5
6
7
1
2
3
4
5
6
7
8
1
2
3
4
Br
Ac
25
THF/H2O 3:1
14 h
48 h
70 h
1.5 h
1.8 h
2 h
2.5 h
3.5 h
4 h
90 (75)
81 (69)
75 (62)
99 (93)
95 (89)
92 (83)
94 (84)
96 (88)
90 (79)
96 (90)
91 (83)
92 (86)
89 (83)
90 (82)
99 (92)
99 (95)
99 (91)
96 (90)
95 (88)
96 (91)
94 (90)
94 (82)
92
23.8
26.6
18.9d
1.8
1.2
1.5
Br
Ac
0.01
K2CO3
60
MeOH/H2O 3:1
1.1
1.0
9
1.7e
16.3
10.7
21.1
18.5
16.6f
1.7
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
Br
Br
Ac
Ac
0.01
0.01
K2CO3
K2CO3
60
n-BuOH/H2O 3:1
2 h
3 h
3.5 h
4 h
5.5 h
30 min
1.8 h
2 h
2.5 h
2.5 h
2.5 h
3 h
2.5 h
2.5 h
3 h
100
H2O
1.5
1.5
2.3
1.4
1.4
1.6g
16.5
17.6
20.2
–
Br
MeO
0.1
K2CO3
100
100
H2O
88
89
83
87
89
61
42
75
5 h
6 h
14.4
–
14 h
24 h
24 h
24 h
14 h
14 h
24 h
–
–
h
Cl
Ac
1i
K2CO3
H2O
39.8
42.6
–
39
32
j
–
a
Reaction conditions: aryl halide (10 mmol), phenylboronic acid (1.82 g, 15 mmol), base (20 mmol), 3 (see column) and aqueous solvent (40 mL) or H2O (20 mL).
Isolated yield of the crude product (calculated from 1H NMR, using N,N-dimethylformamide as internal standard). In parenthesis, yield after recrystallization from MeOH–
b
H2O.
c
From ICP–OES analysis (mg Pd/kg product) of the crude product after filtration of the polymer 3.
d
e
f
The polymer 3 was isolated with a 56% Pd loading.
The polymer 3 was isolated with a 72% Pd loading.
The polymer 3 was isolated with a 45% Pd loading.
The polymer 3 was isolated with a 81% Pd loading.
The polymer 3 was isolated with a 76% Pd loading.
In the presence of 0.5 equiv. of TBAB.
g
h
i
j
The polymer 3 was isolated with a 59% Pd loading.

1660
E. Alacid, C. Nájera / Journal of Organometallic Chemistry 694 (2009) 1658–1665
aqueous n-butanol, the reaction time being slightly longer (Table
1, entries 10–14). From ICP–OES analyses can be established that
MeOH is better solvent than n-butanol, affording much lower Pd
leaching in the final product and higher Pd loading in the final
recovered polymer 3.
Recycling experiments were carried out using neat water under
reflux and K2CO3 as base [8b]. The first run of the cross-coupling of
4-bromoacetophenone with phenylboronic acid took place in only
30 min in quantitative yield with only 0.01 mol% Pd loading. The
same process performed in the presence of dimeric palladacycle
2 gave a 88% yield of 4-acetylbiphenyl after 15 min [8b], revealing
that both palladacycles exhibit similar efficiency. High yields were
obtained in the 7 following runs (9994%) increasing the reaction
time until 3 h (Table 1, entries 15–21). It can be deduced that the
polymer showed higher stability using K2CO3 instead of KOH and
that water gave better results than MeOH and n-butanol. The Pd
leaching in the crude product was very low (1.42.3 ppm) and the
polymer was recovered still with 81% Pd contents. When the
cross-coupling (Table 1, entry 15) was performed in the presence
of 300 equiv. of Hg(0) by Pd equiv., the reaction did not take place
after 8 h reaction time. TEM analyses of the solution performed
after this reaction was performed with a 0.1 mol% Pd loading indi-
cated the presence of 3–10 nm sized Pd nanoparticles (Fig. 1). The
same results were observed in the Heck reaction using polymer 3
[11b,c] indicating that the polymer is a precatalyst acting as a
source of Pd(0) [14].
Under the same reaction conditions, K2CO3 as base under water
reflux, the deactivated 4-bromoanisole needed a larger Pd loading
(0.1 mol%) affording good yields (94–89%) during 7 cycles, the
reaction time being in the range of 2.5–24 h (Table 1, entries 22–
29). Pd analyses of the crude 4-methoxybiphenyl indicated a
14.4–20.2 ppm of Pd leaching and the polymer was isolated in
the last run with a 76% of Pd loading.
Aryl bromides are more reactive substrates than chlorides and
they do not need the presence of TBAB as additive [8b]. However,
for the coupling of 4-chloroacetophenone and phenylboronic acid
TBAB, which can act as phase-transfer catalyst and also can stabi-
lize palladium nanoparticles avoiding aggregation, has to be added
Fig. 1. TEM images of the reaction solution after Suzuki reaction of 4-bromoace-
tophenone and phenylboronic acid under water reflux.
base (Table 1, entries 4–9). Under these reaction conditions yields
between 93% and 79% were achieved during 6 cycles, the reaction
time being kept from 1.5 to 4 h. Similar results were obtained in
Table 2
Recycling experiments on the cross-coupling of 4-bromoacetophenone and TMB or n-butylboronic acid using polymer 3.a
n
u
2
3
3
2
3
3
3
2
Entry
Run
Organoboron
TMB
Mol% Pd
1
Time (h)
Yield (%)b
Pd leachingc
1
2
3
4
5
6
7
8
1
2
3
1
2
3
4
5
1
2
3
4
5
7
91 (79)
83
34
95 (82)
84
86
177
14
24
4
144
16d1
1201
917
TMB
5
1
8
14
24
24
2
3.1
4
1133
877
71
42
e
–
9
n-BuB(OH)2
69 (51)f
65f
385
358
269
308
507g
10
11
12
13
62f
8
14
60f
48f
a
Reaction conditions: 4-bromoacetophenone (99 mg, 0.5 mmol), trimethylboroxine or n-butylboronic acid (0.75 mmol), K2CO3 (138 mg, 1 mmol), TBAB (166 mg, 0.5 mmol),
3 (see column) in H2O (2 mL), at 100 °C.
b
Isolated yield of the crude product (calculated from 1H NMR, using N,N-dimethylformamide as internal standard). In parenthesis, yield after flash chromatography
(hexane-EtOAc).
c
From ICP–OES analysis (mg Pd/kg product) of the crude product after filtration of the polymer 3.
The polymer 3 was isolated with a 59% Pd loading.
The polymer 3 was isolated with a 68% Pd loading.
20–30% of 4,40-bis(acetyl)biphenyl was obtained in the crude product.
d
e
f
g
The polymer 3 was isolated with a 81% Pd loading.

E. Alacid, C. Nájera / Journal of Organometallic Chemistry 694 (2009) 1658–1665
1661
[15]. In the first run 1 mol% Pd loading was used giving only 42%
yield of 4-acetylbiphenyl under water reflux after 24 h reaction
time (Table 1, entry 30). Surprisingly, in the second run a higher
75% conversion was obtained after 14 h (Table 1, entry 31),
whereas in the following runs only 39% and 32% yield was ob-
served after 14 and 24 h (Table 1, entries 32 and 33). It seems that
in the second run an unusual higher leaching of Pd(0) to the solu-
tion was produced. From these results it can be concluded that di-
meric 4-hydroxyacetophenone palladacycle 2 [8a,b] shows much
better catalytic efficiency than the palladated polymer 3 for the
cross-coupling with aryl chlorides.
For the formation of aryl–alkyl bonds [16], the cross-coupling of
aryl bromides with trimethylboroxine (TMB) and n-butylboronic
acid was performed under the reaction conditions previously de-
scribed using palladacycle 2 as precatalyst [8b]. The methylation
of 4-bromoacetophenone with TMB was carried out using the poly-
meric palladacycle 3 (1 mol% Pd), K2CO3 as base, and TBAB as addi-
tive under water reflux (Table 2, entries 13). In the first run the
reaction took place in high yield only in 7 h, whereas using the di-
meric complex 2, 10 mol% of Pd loading was used [8b].This appar-
ently contradictory result can be explained by the formation of
larger Pd colloids, which afford the formation of inactive palladium
black [12c]. Unfortunately, in the third cycle only 34% conversion
was obtained after 24 h reaction time. When the Pd loading was in-
creased to 5 mol%, good conversions were observed during 4 cycles
(95–71%) (Table 2, entries 4–8). However, the Pd leaching deter-
mined by ICP–OES analyses of crude products was higher when
using 5 than 1 mol% of Pd loading.
In the case of the cross-coupling of 4-bromoacetophenone with
n-butylboronic acid the alkylation proceeded in moderate yield
due to concomitant homocoupling of 4-bromoacetophenone (Table
2, entries 9–13). However, the formation of 4-butylacetophenone
was similar during 4 cycles (69–60% yield), the reaction time rang-
ing from 2 to 8 h. During the fifth run the conversion decreased to
48% and the reaction time increased to 14 h. Similar results were
observed in the first run using dimeric palladacycle 2 [8b] as pre-
catalyst. The Pd contents in the polymer was analyzed also by
ICP–OES analysis being 81% relative to the starting complex, which
is higher than in the case of the coupling with trimethylboroxine
(Table 2, footnotes d,e,g).
Alkenylboronic derivatives such as, trivinylboroxine–pyridine
complex [16] and styrylboronic acid were chosen as representative
vinylating agents for the synthesis of styrene and stilbene deriva-
tives by means of the Suzuki–Miyaura cross-coupling reaction
Table 3
Recycling experiments on the cross-coupling of aryl bromides with alkenylboronic acids using polymer 3.a
Entry
Run
X
Y
Borane
Mol% Pd
1
TBAB (equiv.)
Time (h)
Yield (%)b
Pd leachingc
1
2
3
4
5
6
7
8
1
2
3
4
5
6
7
1
2
3
4
5
1
2
3
4
5
6
7
1
2
3
4
5
6
Br
Ac
(CH2@CHBO)3 ꢀ Py
1
1
1
1
1
1
1
1
1
1
1
1
–
–
–
–
–
–
–
–
–
–
–
–
–
2.5
3
3.5
5
94 (88)
89
91
93
83
85
76
91 (82)
93
83
238
243
221
222
276
–
9
16
24
6.5
14
14
24
24
5
d
–
Br
Br
MeO
Ac
(CH2@CHBO)3 ꢀ Py
1
279
245
247
363
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
61
48
e
–
(E)-PhCH@CHB(OH)2
0.1
91 (84) [5]f
85 [6]f
81 [18]f
76 [31]f
79 [42]f
76 [35]f
49 [44]f
96 (89) [8]f
89 [21]f
77 [30]f
62 [56]f
55 [50]f
23 [48]f
12.6
11.6
11.5
16.4
13.2
16.8
17.6g
61.8
88.4
87.8
98.9
131.5
93.5h
5
8
14
24
24
24
5
Br
MeO
(E)-PhCH@CHB(OH)2
0.5
6
10
15
24
24
a
Reaction conditions for trivinylboroxine: aryl bromide (0.25 mmol), trivinylboroxine (89 mg, 0.37 mmol), TBAB (83 mg, 0.25 mmol), K2CO3 (60 mg, 0.5 mmol), 3 (80 mg,
1 mmol) and H2O (1.5 mL). Reaction conditions for (E)-styrylboronic acid: aryl bromide (0.5 mmol), (E)-styrylboronic acid (111 mg, 0.75 mmol), K2CO3 (276 mg, 2 mmol), 3
(see column) and H2O (2 mL).
b
Isolated yield of the crude product (calculated from 1H NMR, using N,N-dimethylformamide as internal standard). In parenthesis, yield after flash chromatography
(hexane-EtOAc).
c
From ICP–OES analysis (mg Pd/kg product) of the crude product after filtration of the polymer 3.
The polymer 3 was isolated with a 63% Pd loading.
The polymer 3 was isolated with a 44% Pd loading.
Yield of styrene in the crude product.
The polymer 3 was isolated with a 61% Pd loading.
The polymer 3 was isolated with a 56% Pd loading.
d
e
f
g
h

1662
E. Alacid, C. Nájera / Journal of Organometallic Chemistry 694 (2009) 1658–1665
Table 4
[17–19] with aryl bromides in water (Table 3). The vinylation of 4-
bromoacetophenone and 4-bromoanisole with trivinylboroxine
was carried out using 0.1 mol% Pd loading of dimeric palladacycle
2, K2CO3 as base and in the presence of TBAB under water reflux
affording 4-acetyl and 4-methoxystyrene in 83% and 76% yield
after 5 and 18 h reaction time, respectively. The same reactions
needed a higher 1 mol% Pd loading of palladated polymer 3 to give
the corresponding 4-acetyl and 4-methoxystyrene in 88% and 82%
yield after 2.5 and 6 h reaction time, respectively (Table 3, entries 1
and 8). These are the first cross-coupling reactions of trivinylborox-
ine with aryl bromides in water. Recycling experiments in the first
case took place in 94–76% yield during 7 cycles and during 2.5–
24 h (Table 3, entries 1–7), the polymer being recovered with
63% Pd loading. In the case of the deactivated 4-bromoanisole
moderate yields were obtained in the cycles 4 and 5 (Table 3, en-
tries 8–12) and the polymer 3 was isolated with 44% Pd loading
after 5 runs. In both cases, similar Pd leachings was observed in
the crude product (221–363 ppm Pd).
Styrylboronic acid reacted with representative 4-bromoaceto-
phenone and anisole using 0.1 mol% Pd loading of palladacycle 2
with K2CO3 as base under water reflux and in the absence of TBAB
to afford 4-acetyl and 4-methoxystilbene in 88% and 79% yield and
in 5 and 8 h, respectively. When 0.1 and 0.5 mol% Pd loading of
polymer 3 was used 84% and 89% yield of these stilbenes were ob-
tained after 5 h reaction time, respectively (Table 3, entries 13 and
20). Recycling experiments were carried out during 7 and 6 runs
under these reaction conditions (Table 3, entries 13–25). Thus,
4-acetyl and 4-methoxystilbene were obtained in good yields with
Recycling experiments on the cross-coupling of cinnamyl and benzyl chloride with
phenylboronic acid using polymer 3.a
2
2
2
Entry
Run
Organic chloride
Time (h)
Yield (%)b
Pd leachingc
1
2
3
4
5
6
7
8
1
2
3
4
5
6
7
8
9
1
2
3
4
5
6
Cinnamyl chloride
1
1.3
2
2.5
4
95 (86)
96
92
89
91
83
79
84
73
99 (86)
91
93
96
92
16.0
14.5
17.5
19.1
–
5
8
–
19.8
14.5
14
24
1
1.2
1.6
2
d
9
–
10
11
12
13
14
15
Benzyl chloride
21.0
21.8
20.4
17.4
19.6
21.0e
3.3
4
89
a
Reaction conditions: organic chloride (1 mmol), phenylboronic acid (182 mg,
1.5 mmol), KOH (112 mg, 2 mmol), TBAB (322 mg, 1 mmol), 3 (8 mg, 0.1 mol% Pd)
in 3:2 acetone–H2O (5 mL).
b
Isolated yield of the crude product (1H NMR). In parenthesis yield after flash
chromatography (hexane–EtOAc).
c
From ICP–OES analysis (mg Pd/kg product) of the crude product after filtration
of the polymer 3.
higher than 97:3
a/b regioisomer ratio. However, styrene was
d
The polymer 3 was isolated with a 71% Pd loading.
The polymer 3 was isolated with a 69% Pd loading.
formed under these reaction conditions, these protonolysis being
increased in up to 50% yield during the recycling experiments,
affording lower yield of stilbenes after each consecutive run.
e
2.2. Cross-coupling of allyl and benzyl chlorides with boronic acids
roxine and styrylboronic acid under the same reaction conditions
previously described for phenylboronic acid (Table 5). The vinyla-
tion of cinnamyl chloride took place with trivinylboroxine using
a low 0.1 mol% Pd loading of complex 2, KOH as base, TBAB as addi-
tive in aqueous acetone at 50 °C giving 1-phenylpenta-1,4-diene in
81% yield after 1.5 h. When 0.2 mol% Pd loading of polymer 3 was
used, a similar 80% yield of 1-phenylpenta-1,4-diene was obtained
in 2.5 h (Table 5, entry 1). In the case of styrylboronic acid (1E,4E)-
1,4-diphenylpenta-1,4-diene was obtained in 83% yield using
0.1 mol% Pd loading [22,23] of both complexes 2 and 3 after 1 h
reaction time (Table 5, entry 9). Recycling experiments for both
reactions have been performed during 8 cycles (Table 5, entries
1–16). The efficiency of the polymer 3 as precatalysts started to de-
creased in the cycle 7 and was recovered with a 79% and 61% Pd
loading, respectively. In the case of (E)-styrylboronic acid 5–16%
of styrene was formed due to a deborylation process. A higher
leaching was observed in the case of trivinylboroxine from ICP–
OES analyses of the crude products.
For the formation of allyl–aryl bonds the cross-coupling of allyl
halides with arylboronic acids is the most convenient strategy. The
allylation of arylboronic acids took place easily using palladacycle
2 as precatalyst at rt using KOH as base, TBAB as additive and a 3:2
mixture of acetone-water [8b]. The evaluation of palladated Kaiser
oxime resin 3 as recoverable Pd polymeric complex was performed
with cinnamyl chloride and phenylboronic acid under the above
mentioned reaction conditions at 50 °C (Table 4, entries 1–9). Dur-
ing 9 runs the yield was kept between 95% and 73% and the reac-
tion time increased from 1 to 24 h. The Pd leaching analyzed in the
crude product ranged between 14.5 and 20 ppm and the polymer
was isolated with a 71% Pd content after 9 cycles. When this
cross-coupling reaction (Table 4, entry 1) was performed in the
presence of 200 equiv. of Hg by Pd equiv. during 8 h, the reaction
failed. Again, it can be concluded that the polymer is acting as
source of Pd(0) [14].
The formation of benzyl–aryl bonds was examined using the
cross-coupling of benzyl halides with arylboronic acids. This type
of transformation allows the synthesis of symmetrical and unsym-
metrical diarylmethanes, which are present in supramolecular
structures [20] and biologically active compounds [21]. The reac-
tion between benzyl chloride and phenylboronic acid was per-
formed under the same reaction conditions than cinnamyl
chloride (Table 4, entries 10–15). During 6 cycles the reaction took
place in 1–4 h and 99–89% yield. Similar Pd leaching was observed
in the crude product than in the former cinnamyl chloride. Recov-
ered palladacycle 3 was isolated with 69% Pd loading after 6 runs.
Cross-coupling reactions of allyl chlorides have only been stud-
ied with potassium alkenyltrifluoroborates for the synthesis of 1,4-
pentadienes [22]. We have now studied representative examples of
the cross-coupling reactions of cinnamyl chloride with trivinylbo-
Benzyl chloride was cross-coupled with trivinylboroxine using
0.1 and 0.2 mol% Pd loading of complex 2 and 3, respectively. Thus,
allylbenzene was obtained in 70% and 66% yield, respectively, after
8 h reaction time. Recycling experiments using 3 gave allylbenzene
in 68–82% crude yields during 4 runs (Table 5, entries 17–21). The
reaction of benzyl chloride with styrylboronic acid has been per-
formed, for the first time, using both complexes
2 and 3
(0.1 mol% Pd loading). Thus, (E)-1,3-diphenylprop-1-ene was ob-
tained in 78% and 79% yield and after 3 and 3.5 h reaction time,
respectively (Table 5, entry 22). This Suzuki–Miyaura reaction
can be considered an alternative strategy to the cross-coupling of
allyl chlorides with arylboronic acids for the synthesis of allylbenz-
enes (see Table 4, entries 10–15). However, lower yields and low
recycling results were observed in this type of C(sp3)C(sp2) cou-
plings due to deborylation reactions of alkenylboronic derivatives,

E. Alacid, C. Nájera / Journal of Organometallic Chemistry 694 (2009) 1658–1665
1663
Table 5
Recycling experiments on the cross-coupling of cinnamyl and benzyl chloride with alkenylboronic acids using polymer 3.a
Entry
Run
Organic chloride
Borane
Mol% Pd
0.2
Time (h)
Yield (%)b
Styrene (%)
Pd leachingc
1
2
3
4
5
6
7
8
1
2
3
4
5
6
7
8
1
2
3
4
5
6
7
8
1
2
3
4
5
1
2
3
4
5
6
Cinnamyl chloride
(CH2@CHBO)3 ꢀ Py
2.5
3
3
5
8
14
24
24
1
3
4.5
5
96 (80)
96
92
89
91
83
79
84
96 (83)
94
88
89
92
88
75
61
82 (66)
79
68
71
36
92 (79)
86
76
78
72
37
34.0
29.1
34.8
47.9
–
–
–
–
d
9
Cinnamyl chloride
(E)-PhCH@CHB(OH)2
0.1
–
–
–
–
8.5
11.6
11.6
11.8
10.1
11.2
14.6
17.7e
71.9
62.9
82.5
101.6
109.1f
14.7
16.2
18.6
14.9
21.1
19.2g
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
8
5
14
24
24
8
14
16
24
24
3.5
5
11
12
16
Benzyl chloride
Benzyl chloride
(CH2@CHBO)3 ꢀ Py
0.2
0.1
(E)-PhCH@CHB(OH)2
–
–
5
8
12
21
10
14
24
24
a
Reaction conditions for trivinylboroxine: organic chloride (0.5 mmol), trivinylboroxine (180 mg, 0.75 mmol), TBAB (166 mg, 0.5 mmol), KOH (56 mg, 1 mmol), 3 (10 mg,
0.2 mmol Pd) in 3:2 acetoneH2O (2.5 mL). Reaction conditions for (E)-styrylboronic acid: organic chloride (1 mmol), (E)-styrylboronic acid (222 mg, 1.5 mmol), KOH (112 mg,
2 mmol), TBAB (322 mg, 1 mmol), 3 (8 mg, 0.1 mmol Pd) in 3:2 acetone–H2O (5 mL).
b
Isolated yield of the crude product (1H NMR). In parenthesis yield alter flash chromatography (hexane–EtOAc).
From ICP–OES analysis (mg Pd/kg product) of the crude product after filtration of the polymer 3.
The polymer 3 was isolated with a 79% Pd loading.
The polymer 3 was isolated with a 61% Pd loading.
The polymer 3 was isolated with a 58% Pd loading.
The polymer 3 was isolated with a 78% Pd loading.
c
d
e
f
g
although in less extension (5–21%) than in the cross-coupling with
aryl bromides (Table 3). In the case of trivinylboroxine, the yield
decreased to 36% in the run 5 and for styrylboronic acid in the cycle
6 (Table 5, entries 17–27).
at 50 °C, giving high and fast conversions with high yields during 6
cycles. In general, the immobilized palladacycle was more efficient
than the unsupported counterparts except for the cross-coupling of
aryl chlorides with arylboronic acids. In addition, can be recovered
from the reaction medium and reused for several cycles. With re-
spect to its efficiency, a better performance for fast runs was ob-
served, the activity being lost when the cross-coupling became
slow. In general, ICP–OES analyses showed low Pd contents in
the final crude products and the polymer suffer up to 5% Pd leach-
ing in each recycling run.
3. Conclusions
We can conclude that the Kaiser oxime-based palladacycle is a
very stable and efficient precatalyst for the Suzuki–Miyaura reac-
tion of aryl bromides with aryl boronic acids using homeopathic
Pd loading and K2CO3 as base under water reflux better than in
aqueous alcohols. Under these reaction conditions alkylboronic
acids such as, trimethylboroxine and n-butylboronic acid needed
the presence of TBAB and higher Pd loading. Better recycling re-
sults have been observed for aryl than alkylboronic acids. Under
the same reaction conditions alkenylation reactions of aryl bro-
mides can be performed with trivinylboroxine–pyridine complex
and with styrylboronic acid affording the corresponding styrenes
and stilbenes. Styrylboronic acid suffers deborylation to styrene
during the recycling experiments. In the case of allyl and benzyl
chlorides the cross-coupling reactions either with phenylboronic
acid or with alkenylboronic acids derivatives, needed a low 0.1–
0.2% Pd loading, KOH as base, TBAB as additive in aqueous acetone
4. Experimental
4.1. General
Unless otherwise noted all commercials reagents and dry sol-
vents were used without further purification. Melting points were
determined with a Reichert Thermovar hot plate apparatus and are
uncorrected. IR spectra were recorded on a Nicolet 510 P-FT. 1H
NMR (300 or 400 MHz) and 13C NMR (75 or 100 MHz) spectra were
obtained on a Bruker AC-300 and Bruker AC-400, respectively,
using CDCl3 as solvent and TMS as internal standard, unless other-
wise stated. Low-resolution electron impact (EI) mass spectra were

1664
E. Alacid, C. Nájera / Journal of Organometallic Chemistry 694 (2009) 1658–1665
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obtained at 70 eV on an Agilent 5973 Network. Analytical TLC was
performed on Merck aluminium sheets with silica gel 60 F254. Silica
gel 60, (0.04–0.06 mm) was employed for flash chromatography.
Gas chromatographic analyses were performed on an Agilent
6890N instrument equipped with a WCOT HP-1 fused silica capil-
lary column. The catalyst was weighed up in a electronic micro-
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scale balance Sartorius, XM1000P with precision of 1 lg. ICP–OES
analyses were performed in a Perkin–Elmer Optima 4300 spec-
trometer. The reaction was filtered off and the solution was con-
centrated and treated with 65% aqueous HNO3 (1 mL) overnight.
The sample was diluted with water until 50 mL total volume and
filtered through a HPLC filter. TEM analyses were performed in a
JEOL JEM-2010 coupled to a micro analyzer system Oxford INCA
Energy TEM100.
Kaiser resin is commercially available and can be prepared from
polystyrene cross-linked with 1% divinylbenzene [24]. Palladacy-
cles 2 [8b] and 3 [11b] were prepared as previously described.
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4.2. Typical procedure for the cross-coupling reactions in water
A 2 M solution of K2CO3 (10 mL) was added to a suspension of
aryl halide (10 mmol), boroxine (5 mmol) or boronic acid
(15 mmol), TBAB (see tables), palladacycle 3 (see tables), in water
(20 mL). The mixture was stirred under reflux and the reaction
was monitored by GC until completion. Then the reaction was
cooled down to room temperature and diluted with EtOAc
(40 mL), filtered off (G3) and the polymer was washed with EtOAc
(3 ꢁ 10 mL), EtOAc–MeOH (1:1) (3 ꢁ 10 mL) and MeOH
(3 ꢁ 10 mL), dried under vacuum and reused in a new experiment.
The filtrate was concentrated under vacuum and a small sample
was analyzed by ICP–OES. The rest of the crude product was
poured into EtOAc (20 mL) and washed with water (3 ꢁ 10 mL).
The organic layer was dried over MgSO4 and the solvent removed
under vacuum. The crude product was purified by flash chroma-
tography or by recrystallization.
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4.3. Typical procedure for the cross-coupling reactions in aqueous
acetone
(b) A. Corma, D. Das, H. García, A. Leyva, J. Catal. 228 (2005) 322;
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A 1 M solution of KOH (2 mL) was added to a solution of cin-
namyl or benzyl chloride (1 mmol), TBAB (see Tables), boroxine
(0.5 mmol) or boronic acid (1.5 mmol) and the polymer 3 (see ta-
bles) in acetone (3 mL) and the reaction mixture was heated at
50 °C. The reaction was monitored by GC until completion and
worked-up as above.
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The
compounds
4-acetylbiphenyl,
4-methoxybiphenyl,
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diphenylmethane, 4-butylacetophenone, 4-methylacetophenone,
4-vinylacetophenone, 4-vinylanisole, 1-phenylpenta-1,4-diene,
allylbenzene, (E)-4-acetylstilbene, (E)-4-methoxystilbene are
commercially available. The following compounds (E)-1,3-diphen-
ylpropene [25] and (1E,4E)-1,5-diphenyl-1,4-pentadiene [26] have
been previously described.
(d) C.C. Cassol, A.P. Umpierre, G. Machado, S.I. Wolke, J. Dupont, J. Am. Chem.
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Nielsen, T. Skrydstrup, J. Org. Chem. 73 (2008) 3570.
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(2001) 1977;
Acknowledgments
We thank the financial support from Spanish Ministerio de Edu-
cación y Ciencia (MEC) (projects CTQ 2007-62771/BQU and Consol-
ider Ingenio 2010, CSD2007-00006) and the University of Alicante.
E. Alacid thanks the MEC for a pre-doctoral fellowship.
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