Aminophosphine palladium pincer complexes for Suzuki and Heck reactions

Article abstract of DOI:10.2533/chimia.2009.23

The aminophosphine-based pincer complexes [C₆H ₃-2,6-{NHP(piperidinyl)₂}₂Pd(CI)] (2) and [C₆H₃-2,6-{OP(piperidinyl)₂}₂Pd(CI)] (3) are readily prepared from cheap starting materials by sequential addition of 1,1′,1 "-phosphinetriyltripiperidine and 1,3-diaminobenzene or resorcinol to solutions of [Pd(cod)(CI)₂] (cod = cyclooctadiene) in toluene under N₂ in 'one pot'. Compounds 2 and 3 proved to be not only excellent catalysts for the Suzuki and the Heck cross-coupling reactions, but they are also very convenient to use: The toluene solutions of the 'one-pot' syntheses can be used directly for the catalytic reactions, thereby saving the time-consuming isolation of the catalysts. The Suzuki cross-coupling reaction catalyzed by 2 and 3 can be performed in air at 100 °C in toluene of technical quality: in the presence of only 0.001 mol% of catalyst, several electronically deactivated and sterically hindered aryl bromides are quantitatively coupled with phenylboronic acid within a few minutes of reaction time. Furthermore, complex 2 enables the use of activated and non-activated aryl chlorides as coupling partners in the Suzuki reaction. Compounds 2 and 3 have also been shown to be highly active and reliable Heck catalysts: Very low catalyst loadings and short reaction times are required for the quantitative coupling of several electronically deactivated and sterically hindered aryl bromides with various olefins at 140 °C. At increased temperatures, even electronically deactivated and sterically hindered aryl chlorides can be efficiently coupled with olefins in the presence of only 0.01 mol% of catalyst. Schweizerische Chemische Gesellschaft.

Full text of DOI:10.2533/chimia.2009.23

Yo u n g Ac A d e m ic s in sw it z e r l A n d PA r t i
CHIMIA 2009, 63, No. 1/2 23
doi:10.2533/chimia.2009.23
Chimia 63 (2009) 23–28 © Schweizerische Chemische Gesellschaft
Aminophosphine Palladium Pincer
Complexes for Suzuki and Heck Reactions
Jeanne L. Bolliger and Christian M. Frech*
Abstract: The aminophosphine-based pincer complexes [C6H3-2,6-{NHP(piperidinyl)2}2Pd(Cl)] (2) and [C6H3-
2,6-{OP(piperidinyl)2}2Pd(Cl)] (3) are readily prepared from cheap starting materials by sequential addition of
1,1’,1’’-phosphinetriyltripiperidine and 1,3-diaminobenzene or resorcinol to solutions of [Pd(cod)(Cl)2] (cod = cy-
clooctadiene) in toluene under N2 in ‘one pot’. Compounds 2 and 3 proved to be not only excellent catalysts for
the Suzuki and the Heck cross-coupling reactions, but they are also very convenient to use: The toluene solutions
of the ‘one-pot’ syntheses can be used directly for the catalytic reactions, thereby saving the time-consuming
isolation of the catalysts. The Suzuki cross-coupling reaction catalyzed by 2 and 3 can be performed in air at 100
°C in toluene of technical quality: in the presence of only 0.001mol% of catalyst, several electronically deactivated
and sterically hindered aryl bromides are quantitatively coupled with phenylboronic acid within a few minutes of
reaction time. Furthermore, complex 2 enables the use of activated and non-activated aryl chlorides as coupling
partners in the Suzuki reaction. Compounds 2 and 3 have also been shown to be highly active and reliable Heck
catalysts: Very low catalyst loadings and short reaction times are required for the quantitative coupling of several
electronically deactivated and sterically hindered aryl bromides with various olefins at 140 °C. At increased tem-
peratures, even electronically deactivated and sterically hindered aryl chlorides can be efficiently coupled with
olefins in the presence of only 0.01 mol% of catalyst.
Keywords: Aminophosphines · C–C coupling · Heck reaction · Pincer complexes · Suzuki reaction
Christian Frech re- 1. Introduction
ceived the diploma
relatively high catalyst loadings – all fac-
tors promoting the formation of palladium
in chemistry in 1999 Among the most efficient methods for black and thereby leading to inactivation of
and started his PhD carbon–carbon bond formation are the the active species.
thesis in the same palladium-catalyzed Mizoroki-Heck[1] and
Pincer complexes of palladium are
year at the Institute of Suzuki-Miyaura[2,3] cross-coupling reac- among the most efficient Heck catalysts
Inorganic Chemistry tions, which are nowadays indispensable and continuously attract attention because
at the University of tools in organic synthesis for the catalytic of their unique balance between stability
Zurich with Prof. Dr. formation of symmetric and non-symmet- and reactivity. Seemingly slight electronic
H. Berke, where he ric olefins or biaryls, respectively.
and steric modifications of the pincer core
successfully finished Since both of these palladium-cata- and/or the phosphine substituents have
his studies in 2004. Thereafter he joined lyzed reactions typically use an aryl halide been demonstrated to dramatically influ-
the research group of Prof. D. Milstein at as one of the starting materials and couple ence their catalytic activities.[4a,d,13,14] The
the Weizmann Institute of Science (Israel) it with either an olefin (Heck reaction) or successful application of pincer-type com-
for one year as postdoctoral fellow. Since an arylboronic acid (Suzuki reaction), par- plexes in the Heck reaction considerably
2005 he has been working as habilitant at ticularly catalysts which are able to use de- increased the interest in developing pincer-
the University of Zurich at the Institute of activated and sterically hindered aryl bro- based Suzuki catalysts as well.[15–17] Ever
Inorganic Chemistry at the University of mides or even aryl chlorides as substrates since pincer-type complexes have been
Zurich, working, for example, on the de- are of high general interest.
successfully introduced as highly efficient
velopment of new catalysts for C–C cross-
coupling reactions.
In the last few years, many palladium catalysts in the Heck reaction, it has been
catalysts for either reaction have been discussed whether a PdII/PdIV mechanism
developed, but although some are able to or the formation of palladiumnanoparticles
couple sterically or electronically demand- leads to their high catalytic activity.[4a,d]
ing aryl halides at very low catalyst load- Nowadays, pincer complexes are in most
ings, their syntheses are often not only cases considered as depot forms of palla-
time consuming and difficult, but also dium nanoparticles, but nevertheless, the
require the use of expensive starting ma- involvement of PdIV intermediates in the
terials.[4–12] Most of these palladium cata- catalytic cycle still cannot be excluded
lysts suffer from other drawbacks as well, completely.[18,19]
such as poor thermal stability as well as
Either way, the choice of aminophos-
*Correspondence: Dr. C. M. Frech
Department für Anorganische Chemie
Universität Zürich
Winterthurerstrasse 190
CH-8057 Zurich
Tel.: + 41 44 635 4692
Fax: + 41 44 635 6802
E-mail: chfrech@aci.uzh.ch
poor stability towards oxygen and water, a phine pincer ligands might prove to be an
major problem especially for catalysts em- advantage: Apart from their high σ-donor
ployed in the Heck cross-coupling reaction strength, aminophosphine ligands can do-
because a typical protocol for this reaction nate additional electron density via the
still requires prolonged reaction times at nitrogen lone pairs to the metal center,
high temperatures in combination with thereby making PdIV intermediates more

24 CHIMIA 2009, 63, No. 1/2
Yo u n g Ac A d e m ic s in sw it z e r l A n d PA r t i
easily accessible. On the other hand, if
palladium nanoparticles are the active spe-
cies, pincer complexes should act as clean
sources of palladium nanoparticles. Since
aminophosphines should promote their
formation, enhanced catalytic activity as
well as shorter induction periods should
be observed in comparison with their phos-
phine and phosphite analogues.
In comparison with many other pal-
ladium complexes used to promote the
Mizoroki-Heck reaction or the Suzuki-
Miyaura reaction, the aminophosphine-
based palladium pincer complexes [C6H3-
2,6-{NHP(piperidinyl) } Pd(Cl)] (2) and
[C6H3-2,6-{OP(piperid2in2yl) }2Pd(Cl)] (3)
(Scheme 1) are not only re2adily prepared
from cheap starting materials within a
day, but they are also extremely efficient
catalysts for either reaction: Very low
catalyst loadings and short reaction times
are required for the quantitative coupling
of several electronically deactivated and
sterically hindered aryl bromides with
phenylboronic acid or various olefins. At
increased temperatures, even electronical-
ly deactivated and sterically hindered aryl
chlorides can be efficiently coupled with
olefins in the presence of only 0.01mol%
of catalyst.[14,15]
N
N
H
N P
N 2
H
Pd Cl
H
N P
N
N
NH2
100 °C, 15 min
-piperidine
-piperidinium chloride
2
N
N
2 P(piperidinyl)
N
3
P
Cl Pd Cl
P
toluene, 25 °C, 5 min
[Pd(Cl) (C
O
D)]
2
-cyclooctadiene
OH
N
N
N
OH
1
N
100 °C, 45 min
N
Pd Cl
O P
-piperidine
-piperidinium chloride
O P
N
N
3
Scheme 1. Synthesis of the catalysts 2 and 3.
room temperature with two equivalents of Miyaura and the Mizoroki-Heck cross-
Mechanistic studies performed with P(piperidinyl)3 (which is easily prepared coupling reactions, but they are also very
2 and 3 showed that the Suzuki cross- from phosphorus trichloride and piperi- convenient to use: The toluene solutions
coupling reaction most probably proceeds dine) results immediately in a bright orange of the ‘one-pot’ syntheses can be used di-
via a PdII/PdIV mechanism,[15] while the solution containing compound 1. Addition rectly for the catalytic reactions, thereby
Heck reaction was shown to be catalyzed of an equimolar amount of 1,3-diamin- saving the time-consuming isolation of the
by palladium nanoparticles, for which the obenzene or resorcinol under nitrogen and catalysts. The resulting conversion rates
aminophosphine-based palladium pincer stirring at 100 °C for 15 or 45 min, respec- and yields in the catalytic reactions are es-
complexes 2 and 3 apparently are ideal tively, leads to the exclusive formation of sentially the same as those of freshly pre-
precursors.[14]
compounds 2 and 3. Although removal of pared catalyst solutions from pure 2 and 3,
the volatiles under reduced pressure and respectively.
subsequent extractions with diethyl ether
gives pure 2 and 3 in high yields, the iso- 3.1 Suzuki Reaction
2. One-pot Synthesis of the Pincer
Complexes
lation of the pincer complexes 2 and 3 is
Complex 2 turned out to be an extreme-
unnecessary for their application as cata- ly efficient catalyst for the Suzuki–Miyau-
lysts in C–C cross-coupling reactions. The ra cross-coupling reaction (Scheme 2) and
Instead of synthesizing the pincer li- catalyst solutions of the one-pot syntheses led to very high reaction rates and yields
gand separately in a first step and then can be used for catalytic reactions without in extremely short reaction times and with
reacting it with a suitable palladium pre- purification and remain stable in solution very low catalyst loadings (Table 1). Com-
cursor such as [Pd(Cl) (cod)] (cod = cy- for several months at room temperature.
cloocta-1,5-diene) to th2e desired complex,
Complexes 2 and 3 are thermally very catalytic activities than 2, but still is among
aminophosphine-based pincer complexes stable. No visible decomposition was ob- the best catalysts reported up to date.[15]
of palladium with the general formula served upon heating at 150 °C in NMP or
As a consequence of the extremely
plex 3 generally shows significantly lower
[Pd(Cl)(C H -2,6-XP(piperidinyl)2) ] (X xylene for a week. Toluene solutions of 2 high catalytic activities of 2 and 3, the
= NH, 2, 6X3= O, 3) can be prepa2red by or 3 remain stable at 100 °C in an oxygen cross-coupling of aryl bromides with phe-
facile activation of C–H and P–N bonds. atmosphere for more than a week. On the nylboronic acid can be carried out in tolu-
Their syntheses include the use of the other hand, addition of a few drops of wa- ene of technical quality in flasks open to
readily prepared dichloro(bis(1,1’,1’’- ter to dioxane solutions of 2 or 3 at 100 air. This is possible since biaryl formation
(phosphinetriyl)tripiperidine))palladium °C results in partial palladium deposition is much faster than water-induced catalyst
complex (1) as a template for reactions after 24 h.
with 1,3-diaminobenzene or resorcinol to
build up the aromatic pincer core directly
on the metal center, thus making the inde- 3. Catalytic Activity of the Pincer
pendent synthesis and purification of the Complexes in C–C Cross-Coupling
air- and moisture-sensitive ligand systems Reactions
unnecessary (Scheme 1).
degradation.
Best results were obtained at 100 °C
with toluene as solvent with K PO as base
in presence of 0.001 mol% o3f ca4talyst 2.
Under these conditions, phenylboronic
acid was quantitatively coupled with ac-
tivated, non-activated, and deactivated
Treatment of
a
suspension of
Compounds 2 and 3 proved to be not aryl bromides, such as 4’-bromoacetophe-
[Pd(Cl)2(cod)] in toluene under N2 at only excellent catalysts for the Suzuki- none, bromobenzene, and 4-bromoanisole,

Yo u n g Ac A d e m ic s in sw it z e r l A n d PA r t i
CHIMIA 2009, 63, No. 1/2 25
[Pd], Base
-[HBase]X
[Pd], Base
+
X
+ (HO) B
X = Br, Cl
X
R
2
-[HBase]X
R
R'
R'
R
R
X = Br, Cl
Scheme 2. Suzuki-Miyaura cross-coupling reaction.
Scheme 3. Mizoroki-Heck cross-coupling reaction.
within less than 5 min (Table 1, entries 1, example, complete conversions of chlo- high conversions obtained within a few
4, and 6). Coupling reactions performed robenzene at 100 °C with 0.1 mol% cata- minutes and the facile syntheses of 2 and
with 1,3-dibromobenzene yielded 76% lyst 2 was observed after 90 min (Table 1, 3, these systems belong to the most conve-
1,1’:3’,1’’-terphenyl and 24% 3-bromobi- entry 11). In contrast, coupling reactions nient Suzuki catalysts reported to date.
phenyl after five minutes, while complete with deactivated or sterically hindered aryl
The Suzuki reaction is strongly influ-
conversion into 1,1’:3’,1’’-terphenyl was chlorides were less successful and only led enced by the choice of the solvent and
achieved after ten min (Table 1, entry 5). to approximately 10% conversions after 3 base, as well as the reaction temperature.
The activity of catalyst 2 decreased as h (Table 1, entries 14 and 15).
For example, replacing toluene by NMP
sterically hindered substrates were used
Nevertheless, in most of the examples and/or K PO4 by K CO3 or Cs CO3 led to a
as coupling partners. While coupling re- of the Suzuki–Miyaura cross-coupling substanti3al drop in2the reactio2n rate. Simi-
actions with 2-bromotoluene led to 83% reactions performed (in particular when larly, lowering the reaction temperature to
conversions within 5 min , 62% conversion aryl bromides as well as activated and un- 50 °C led to only 30% conversion after 12
was obtained after 15 min using 2-bromo- activated aryl chlorides were employed), h and 58% conversion after 24 h with 0.01
m-xylene as the substrate (Table 1, entries catalysts 2 (and to a minor extent 3) were mol% of catalyst 2 while almost no activity
8 and 9). Similar conversions but longer re- more efficient than the reference sys- was observed at room temperature.
action times were observed when catalyst tems of [Pd(Cl)(C6H3(NHP(Ph)2)2],[17]
3 was used in place of catalyst 2 for the [Pd2(Cl)2(C6H2(tBu)2O)P(OR)2)2],[11g,h] and 3.2 Heck Reaction
C–C coupling of phenylboronic acid with Pd(OAc)2/PCy Ar.[3h] Comparisons with
The
aminophosphine-based
pal-
bromobenzene, 4-bromoanisole, or 3-bro- the extremely2 active air- and moisture- ladium pincer complexes [C H3-2,6-
mo-m-xylene (Table 1, entries 3 and 7).
stable NHC-bearing [PdII(Cl)(R-allyl)] {NHP(piperidinyl) } Pd(Cl)] (26) and
Reactions carried out with 4’- chlo- (NHC=N-heterocyclic carbene)[20] com- [C6H3-2,6-{OP(pip2er2idinyl)2} Pd(Cl)] (3)
roacetophenone or chlorobenzene also plexes are difficult, since the Suzuki reac- are also extremely efficient 2and reliable
showed high conversion rates in short re- tions were generally performed at room Heck catalysts (Scheme 3).[14]
action times (Table 1, entries 11–13). For temperature.[12k] However, because of the
Very low catalyst loadings and short
reaction times are required for the quan-
titative coupling of several electronically
deactivated and sterically hindered aryl
bromides with various olefins (Table 2). At
increased temperatures, even electronical-
ly deactivated and sterically hindered aryl
chlorides can be efficiently coupled with
olefins in the presence of only 0.01mol%
of catalyst (Table 3).
As in the Suzuki cross-coupling, cata-
lyst 3 is generally less active than 2 in Heck
reactions performed with aryl bromides.
For example, styrene and bromobenzene
underwent complete C–C coupling in the
presence of only 0.002 mol% of 2 and
K2CO within 2.5 h in DMF at 140 °C,
where3as a reaction time of 10 h was neces-
sary with catalyst 3 (Table 2, entries 1 and
2). As demonstrated by the cross-coupling
of styrene with the electronically deac-
tivated 4-bromoanisole or the sterically
hindered 2-bromotoluene, as well as the
reaction of 4-methoxystyrene or 2-meth-
ylstyrene with bromobenzene, catalyst 2
offers two possible pathways to the same
products, which are obtained in high yields
and short reaction times by either way (Ta-
ble 2, entries 5–9). Although a decrease in
activity was observed with 2-bromo-m-
xylene and styrene as substrates, neverthe-
less 95% conversion was obtained after
8 h (Table 2, entry 10). Heck reactions
performed with N,N-dimethyl acrylam-
Table 1. Suzuki cross-coupling reaction of aryl halides with phenylboronic acid catalyzed by
[Pd(Cl)(C6H3-2,6-(YP(piperidinyl)2)2] (Y = NH, 2; Y = O, 3)a
Catalyst
([mol%])
Conv.
[%]b
Entry Aryl halide
t [min]
TOFc
TONd
1
2
3
4
5
6
7
8
9
10
bromobenzene
2 (0.001)
2 (0.0001)
3 (0.001)
100
100
98
5
1’200’000
1’090’909
558’000
1’500’000
600’000
1’140’000
576’000
996’000
248’000
184’000
100’000
1’000’000
294’000
100’000
50’000
95’000
96’000
83’000
62’000
92’000
bromobenzene
bromobenzene
55
10
4
4’-bromoacetophenone 2 (0.001)
100
100
95
1,3-dibromobenzene
4-bromoanisole
2 (0.001)
2 (0.001)
3 (0.001)
2 (0.001)
2 (0.001)
3 (0.001)
10
5
4-bromoanisole
96
10
5
2-bromotoluene
2-bromo-m-xylene
2-bromo-m-xylene
83
62
15
30
92
11
12
13
14
15
chlorobenzene
chlorobenzene
2 (0.1)
3 (0.1)
99
31
92
11
8
90
653
207
6’133
37
980
276
9’200
110
80
90
4’-chloroacetophenone 2 (0.01)
90
2-chloro-m-xylene
2 (0.1)
2 (0.1)
180
180
4-chloroanisole
27
aReaction conditions: 4.0 mmol aryl halide, 6.0 mmol PhB(OH)2, 8.0 mmol K3PO4, 12 ml toluene
(technical quality), catalyst (synthesized in ‘one-pot’ and used without purification) added in
solution, reactions performed in air at 100 °C. bDetermined by GC/MS, based on aryl halide.
cDefined as mol product per mol of catalyst per hour. dDefined as mol product per mol of
catalyst.

26 CHIMIA 2009, 63, No. 1/2
Yo u n g Ac A d e m ic s in sw it z e r l A n d PA r t i
Table 2. Heck cross-coupling reaction of aryl bromides with various olefins catalyzed by [Pd(Cl)(C6H3-2,6-(YP(piperidinyl)2)2] (Y = NH, 2; Y = O, 3)a
Entry
Aryl halide
Olefin
Cat.
Conv. [%]b
t [h]
TOFc
TONd
(ppm)
(cis/trans/gem)
1
bromobenzene
bromobenzene
bromobenzene
1,3-dibromobenzene
4-bromoanisole
bromobenzene
4-bromoanisole
2-bromotoluene
bromobenzene
2-bromo-m-xylene
bromobenzene
bromobenzene
2-bromotoluene
bromobenzene
bromobenzene
4-bromoanisole
bromobenzene
bromobenzene
2-bromo-m-xylene
bromobenzene
2-bromotoluene
bromobenzene
bromobenzene
bromobenzene
styrene
2 (20)
3 (20)
2 (0.2)
2 (20)
2 (20)
2 (20)
3 (20)
2 (20)
2 (20)
2 (20)
2 (20)
3 (20)
2 (20)
2 (50)
3 (50)
2 (50)
2 (50)
3 (50)
2 (50)
2 (200)
2 (200)
2 (200)
2 (50)
2 (50)
>99 (1/90/10)
96 (1/90/10)
>99 (1/90/10)
>99 (1/7/0/0)f
99 (0/10/1)
97 (0/10/1)
97 (0/10/1)
98 (0/20/1)
90 (0/20/1)
95 (2/80/1)
100 (1/20/0)
100 (1/25/0)
100 (1/40/0)
100 (1/100/1)
93 (1/100/0)
99 (1/100/0)
100 (4/3/2)
99 (4/3/2)
2.5
10
36
3.5
2.5
2.5
11
2.5
2.5
8
19’880
4’800
138’333
14’157
19’800
19’400
4’409
19’600
18’000
2’375
25’000
5’000
12’500
4’444
775
49’700
48’000
4’980’000
49’550
49’500
48’500
48’500
49’000
45’000
19’000
50’000
50’000
50’000
20’000
9’300
2
styrene
3e
styrene
4
styrene
5
styrene
6
4-methoxystyrene
styrene
7
8
styrene
9
2-methylstyrene
styrene
10g
11
12
13
14
15
16
17
18
19g
20g
21g
22g
23h
24h
N,N-dimethyl acrylamide
N,N-dimethyl acrylamide
N,N-dimethyl acrylamide
n-butyl acrylate
n-butyl acrylate
n-butyl acrylate
n-butyl vinyl ether
n-butyl vinyl ether
n-butyl vinyl ether
4-vinylpyridine
4-vinylpyridine
2-vinylpyridine
(E)-stilbene
2
10
4
4.5
12
4.5
5
4’400
4’000
1’238
1’800
589
19’800
20’000
19’800
14’400
5’000
16
8
72 (5/3/5)
100 (1/25/0)
100 (1/20/0)
53 (1/10/0)
98
8.5
12
60
20
24
417
5’000
44
2’650
980
19’600
19’800
1,1-diphenylethene
99
825
aReaction conditions: 4.0 mmol aryl halide, 4.4 mmol olefin, 4.4 mmol K2CO3, 5 ml DMF, catalyst (synthesized in ‘one pot’ and used without
purification) added in solution (toluene), reaction performed at 140 °C under N2 atmosphere. bDetermined by GC/MS, based on aryl halide. cDefined
as mol product per mol of catalyst per hour. dDefined as mol product per mol of catalyst. e2.0 mol aryl halide, 2.4 mol olefin, 2.4 mol K2CO3, 1 l
DMF. fProduct distribution refers to (cis–trans/trans–trans/gem–trans/cis-cis). gReactions performed in NMP. hReaction performed at 160 °C.
Table 3. Heck cross-coupling reaction of aryl chlorides with various olefins catalyzed by [Pd(Cl)(C6H3-2,6-(YP(piperidinyl)2)2] (Y = NH, 2; Y = O, 3)a
Entry
Aryl halide
Olefin
Cat.
Conv. [%]b
t [h]
TOFc
TONd
(cis/trans/gem)
1e
2e
3e
4e
5
4’-chloroacetophenone
4’-chloroacetophenone
4’-chloroacetophenone
4’-chloroacetophenone
chlorobenzene
styrene
2
3
2
3
2
3
2
2
2
2
2
3
3
100 (5/100/1)
95 (0/1/0)
2.5
2.5
2.5
2.5
16
16
28
72
12
18
18
18
18
4000
3800
3960
3840
481
569
204
92
10000
9500
9900
9600
7700
9100
5700
6600
8200
8000
9000
10000
9800
styrene
N,N-dimethyl acrylamide
N,N-dimethyl acrylamide
N,N-dimethyl acrylamide
N,N-dimethyl acrylamide
N,N-dimethyl acrylamide
N,N-dimethyl acrylamide
4-methylstyrene
99 (0/1/0)
96 (0/20/1)
77 (3/100/1)
91 (0/60/1)
57 (0/1/0)
6
chlorobenzene
7
2-chloro-m-xylene
4-chloroanisole
8
66 (0/1/0)
9
chlorobenzene
82 (1/80/10)
80 (1/7/0)
683
444
500
556
544
10
11
12
13
4-chlorotoluene
4-methylstyrene
chlorobenzene
4-methoxystyrene
4-methoxystyrene
4-methoxystyrene
90 (1/100/10)
100 (1/100/10)
98 (0/8/1)
chlorobenzene
4-chlorotoluene
aReaction conditions: 4.0 mmol aryl halide, 6.0 mmol olefin, 4.4 mmol K2CO3, 0.6 mmol tetrabutylammonium bromide, 5 ml NMP, 0.01 mol% of
catalyst (synthesized in one pot and used without purification) added in solution (toluene), reaction performed at 200 °C under N2 atmosphere.
bDetermined by GC/MS, based on aryl halide. cDefined as mol product per mol of catalyst per hour. dDefined as mol product per mol of catalyst.
eReaction performed at 160 °C.

Yo u n g Ac A d e m ic s in sw it z e r l A n d PA r t i
CHIMIA 2009, 63, No. 1/2 27
ide exhibit very similar conversion rates dimethyl acrylamide afforded the cou- electronically deactivated and sterically
and yields to those with styrene (Table 2, pling product in 77% yield in the presence hindered aryl bromides with various ole-
entries 11–13). Complete product forma- of catalyst 2 and in 91% yield with cata- fins at 140 °C. At increased temperatures,
tion and excellent selectivities but slightly lyst 3 after 16 h (Table 3, entries 5 and 6). electronically deactivated and sterically
lower conversion rates were observed with Remarkably, even the sterically hindered hindered aryl chlorides can be efficiently
n-butyl acrylate as coupling partner (Table 2-chloro-m-xylene was converted to about coupled with olefins in the presence of only
2, entries 14–16). For instance, using de- 60% of the product after 28 h in the pres- 0.01mol% of catalyst.[14] Further catalytic
activated 4-bromoanisole as substrate led ence of 2 with N,N-dimethyl acrylamide reactions performed with complexes 2 and
to quantitative (97%) product formation as coupling partner (Table 3, entry 7). A 3 are in progress.
within 4.5 h in the presence of only 0.005 prolonged reaction time was required with
Acknowledgement
mol% of 2. Quantitative product formation the electronically deactivated 4-chloro-
but a further decrease in the conversion anisole as substrate (Table 3, entry 8). A
rates accompanied by low selectivity was conversion of 82% was achieved within 12
observed after 5 h with 0.005 mol% of 2 h when chlorobenzene was coupled with
with the electronically deactivated n-butyl 4-methylstyrene (Table 3, entry 9). Even
vinyl ether (Table 2, entries 17–18). Even higher conversions were observed after 18
the sterically hindered 2-bromo-m-xylene h when chlorobenzene or 4-chlorotoluene
was converted to 72% of product after only were allowed to react with 4-methylstyrene
8 h (Table 2, entry 19). When the amount or 4-methoxystyrene as coupling partners
of catalyst was increased to 0.02 mol%, (Table 3, entries 10–13).
This research was supported by the
University of Zurich and the Swiss National
Science Foundation (SNSF).
Received: January 9, 2009
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and the sterically hindered 2-bromotolu- ported up to date, since their catalyst solu-
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‘large-scale’ reaction, in which bromoben- cases comparisons are difficult, since the
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1,1-diphenylethene as coupling partners.
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tribenzene was quantitatively formed with-
in 20 h on addition of 1.1 equivalents of
Insummary,anewconceptfortheshort,
bromobenzene to solutions of (E)-stilbene facile and high yielding synthesis of com-
in DMF (Table 2, entry 23). Notably, the plexes with the general formula [Pd(Cl)
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within 24 h under identical reaction condi- 2; or Y = O, 3) has been developed.[15]
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substrate (Table 2, entry 24), or by adding excellent catalysts for the Suzuki-Miyaura
2.2 equivalents of bromobenzene to solu- and the Mizoroki-Heck cross-coupling re-
tions of styrene in DMF.
actions, but they are also very convenient
In contrast to Heck reactions performed to use: The toluene solutions of the ‘one-
with aryl bromides, catalysts 2 and 3 show pot’ syntheses can be used directly for
the same level of activity with aryl chlo- the catalytic reactions, thereby saving the
rides as substrates. In the presence of 0.01 time-consuming isolation of the catalysts.
mol% of catalyst and about 15% of tetrabu-
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