Palladium catalysts with sulfonate-functionalized-NHC ligands for Suzuki-Miyaura cross-coupling reactions in water

Article abstract of DOI:10.1021/om100960t

Four new Pd(II) complexes containing sulfonate-functionalized N-heterocyclic carbene ligands have been synthesized. All new complexes are palladium bis-NHCs, in which the ligands adopt a monodentate, bis-chelating, and pincer coordination form, so that a good comparison between their catalytic activities can be performed. The complexes have been used in the Suzuki-Miyaura cross-coupling reaction between aryl halides and phenylboronic acid in water and in ⁱPrOH/water. The bis-NHC-palladium complex 1, in which the two NHC ligands are in a relative cis configuration, affords the best catalytic outcomes, with high TON values of 10⁵ for 4-bromoacetophenone and 3.7 - 10⁴ for 4-chloroacetophenone.

Full text of DOI:10.1021/om100960t

6
84 Organometallics 2011, 30, 684–688
DOI: 10.1021/om100960t
Palladium Catalysts with Sulfonate-Functionalized-NHC Ligands for
Suzuki-Miyaura Cross-Coupling Reactions in Water
,
Fernando Godoy,* Candela Segarra, Macarena Poyatos, and Eduardo Peris*
†
‡
‡
,‡
†
Departamento de Quı ´m ica de los Materiales Facultad de Quı´mica y Biologı´a, Universidad de Santiago de
‡
Chile, Santiago, Chile, and Departamento de Quı´mica Inorg aꢀ nica y Org aꢀ nica, Universitat Jaume I, Avenida
Vicente Sos Baynat s/n, Castell oꢀ n. E-12071, Spain
Received October 4, 2010
Four new Pd(II) complexes containing sulfonate-functionalized N-heterocyclic carbene ligands
have been synthesized. All new complexes are palladium bis-NHCs, in which the ligands adopt a
monodentate, bis-chelating, and pincer coordination form, so that a good comparison between their
catalytic activities can be performed. The complexes have been used in the Suzuki-Miyaura cross-
i
coupling reaction between aryl halides and phenylboronic acid in water and in PrOH/water. The bis-
NHC-palladium complex 1, in which the two NHC ligands are in a relative cis configuration, affords
5
4
the best catalytic outcomes, with high TON values of 10 for 4-bromoacetophenone and 3.7 ꢀ 10 for
4
-chloroacetophenone.
Introduction
stability and tolerance to a variety of functional groups, the
number of Pd(NHC) complexes for homogeneous catalysis
5-9
During the last two decades, there has been an increasing
interest in the use of water as solvent for many homoge-
in water is limited to a very few recent examples.
Since the description of the first water-soluble palladium
complex with a NHC ligand functionalized with a noncoor-
1
neously catalyzed reactions. Cost, environmental benefits,
1
0
and safety are among the reasons most often argued to justify
the replacement of organic solvents by water in organic
transformations. The use of water in Pd-catalyzed cross-
coupling reactions goes back to the early development of the
dinating sulfonate, there has been a number of palladium
complexes with similar substituents that have been applied
6
,11
for catalytic purposes.
Among the wide range of palladium-catalyzed C-C cou-
pling reactions, Suzuki-Miyaura coupling between an ar-
ylboronic acid and an aryl halide is one of the most widely
used protocols for the synthesis of biphenyls due to the good
tolerance of various functional groups, and for this reason,
finding a way to perform such a transformation in an envir-
onmentally benign manner is a challenge for the researchers
in homogeneous catalysis. However, only a few examples of
this reaction performed in aqueous media have recently been
2
Suzuki-Miyaura coupling, with the first example being
reported by Calabrese and co-workers in 1990. Since then,
3
a large number of water-soluble Pd catalysts bearing hydro-
philic ligands have been reported, and several reviews have
4
been devoted to this subject. Although the introduction of
N-heterocyclic carbene ligands (NHCs) to the coordination
sphere of metal complexes has a series of advantages, such as
5-7,12
*
To whom correspondence should be addressed. E-mail: fernando.
godoy@usach.cl (F.G.); eperis@qio.uji.es (E.P.).
1) Lamblin, M.; Nassar-Hardy, L.; Hierso, J. C.; Fouquet, E.;
Felpin, F. X. Adv. Synth. Catal. 2010, 352, 33. Lindstrom, U. M. Chem.
Rev. 2002, 102, 2751. Herrmann, W. A.; Kohlpaintner, C. W. Angew.
Chem., Int. Ed. Engl. 1993, 32, 1524. Shaughnessy, K. H. Chem. Rev.
009, 109, 643.
2) Miyaura, N.; Yamada, K.; Suginome, H.; Suzuki, A. J. Am.
Chem. Soc. 1985, 107, 972.
3) Casalnuovo, A. L.; Calabrese, J. C. J. Am. Chem. Soc. 1990, 112,
324.
(4) Carril, M.; SanMartin, R.; Dominguez, E. Chem. Soc. Rev. 2008,
7, 639. Shaughnessy, K. H. Eur. J. Org. Chem. 2006, 1827. Bai, L.;
Wang, J. X. Curr. Org. Chem. 2005, 9, 535. Shaughnessy, K. H.;
DeVasher, R. B. Curr. Org. Chem. 2005, 9, 585. Franzen, R.; Xu, Y. J.
Can. J. Chem.-Rev. Can. Chim. 2005, 83, 266. Genet, J. P.; Savignac, M.
J. Organomet. Chem. 1999, 576, 305.
reported.
Among the complexes bearing chelating NHC ligands,
13
(
pincer NHC-based metal complexes have appeared as an
interesting type of catalysts that can provide improved cata-
1
4
lytic properties. We initially obtained a series of pincer-
NHC-palladium complexes that showed very good activity in
2
(
(
4
(9) Tu, T.; Feng, X. K.; Wang, Z. X.; Liu, X. Y. Dalton Trans. 2010,
39, 10598.
(10) Moore, L. R.; Cooks, S. M.; Anderson, M. S.; Schanz, H. J.;
Griffin, S. T.; Rogers, R. D.; Kirk, M. C.; Shaughnessy, K. H. Organo-
metallics 2006, 25, 5151.
3
(11) Fleckenstein, C.; Roy, S.; Leuthausser, S.; Plenio, H. Chem.
Commun. 2007, 2870.
(
(
(
5) Turkmen, H.; Can, R.; Cetinkaya, B. Dalton Trans. 2009, 7039.
6) Roy, S.; Plenio, H. Adv. Synth. Catal. 2010, 352, 1014.
7) Gu, S. J.; Xu, H.; Zhang, N.; Chen, W. Z. Chem.-Asian J. 2010, 5,
(12) Han, Y.; Lee, L. J.; Huynh, H. V. Organometallics 2009, 28,
2778. Ines, B.; SanMartin, R.; Churruca, F.; Dominguez, E.; Urtiaga,
M. K.; Arriortua, M. I. Organometallics 2008, 27, 2833.
(13) Mata, J. A.; Poyatos, M.; Peris, E. Coord. Chem. Rev. 2007, 251,
841. Poyatos, M.; Mata, J. A.; Peris, E. Chem. Rev. 2009, 109, 3677.
(14) Pugh, D.; Danopoulos, A. A. Coord. Chem. Rev. 2007, 251, 610.
Peris, E.; Crabtree, R. H. C. R. Chim. 2003, 6, 33. Peris, E.; Crabtree,
R. H. Coord. Chem. Rev. 2004, 248, 2239.
1
677.
(
8) Mesnager, J.; Lammel, P.; Jeanneau, E.; Pinel, C. Appl. Catal. A:
Gen. 2009, 368, 22. Ohta, H.; Fujiharaa, T.; Tsuji, Y. Dalton Trans. 2008,
3
2
79. Yang, C.-C.; lin, P.-S.; Liu, F.-C.; Lin, I. J. B. Organometallics 2010,
9, 5959.
pubs.acs.org/Organometallics
Published on Web 02/03/2011
r 2011 American Chemical Society

Article
Organometallics, Vol. 30, No. 4, 2011 685
Scheme 1
Ccarbene is displayed at 163.9 ppm, in the typical region shown
for cis-unbridged ylidenes of the type PdX (NHC)
18,19
2
(trans-
2
18
NHCs appear at lower fields, ∼180 ppm). The NMR spec-
tra of 2 and 3 are consistent with the 2-fold symmetry of the
1
3
complexes. The most representative C NMR signals are
those due to the carbene carbons, which appear at 169.3 (2)
and 166.5 (3) ppm.
Because the introduction of pyridine ligands has demon-
strated to provide highly active catalysts for various Pd-
mediated C-C reactions, by the so-called PEPPSI effect
(
pyridine-enhanced precatalyst preparation, stabilization,
2
0
and initiation), we also prepared the pyridine-substituted
NCN-pincer complex 4, by reaction of 3 with pyridine in the
presence of silver triflate. This complex was characterized by
NMR spectroscopy and ESI-TOF-MS and gave satisfactory
elemental analysis. Regarding the NMR data, its most
1
3
representative C NMR signal is the one due to the meta-
lated carbene carbon at 167.9 ppm.
C-C coupling reactions including Heck, Suzuki-Miyaura,
15
We have tested the Suzuki-Miyaura coupling between
phenylboronic acid and aryl halides in water. We first carried
out a catalyst screening by comparing the activity of 1-4 in
the coupling of 4-bromoacetophenone and 4-chloroaceto-
phenone with phenylboronic acid. The reactions were car-
ried out in neat water at 110 °C with a 1 mol % of catalyst
loading in the presence of K CO . The choice of the base was
and Sonogashira. On the basis of these previous results, we
now present our new studies on the preparation of a series of
palladium complexes with NHC ligands containing sulfonate
functionalities, which have been tested in the Suzuki-Miyaura
coupling of a wide set of substrates in water. This study gives a
good opportunity to compare the catalytic outcomes of mono-
dentate and bis-chelating and pincer-NHC-based palladium
complexes in aqueous solvents.
2
3
done according to previous studies made by Chen and co-
workers, in which a complete analysis on the effect of the
base for the same reaction was performed using their tria-
Results and Discussion
7
zole-based-NHC palladium catalysts. We chose these two
haloacetophenones as substrates for this initial reaction due
to their high solubility in water. The activation of 4-chloro-
acetophenone required the addition of tetrabutylammonium
bromide (TBABr) as phase transfer catalyst. The reac-
tions were monitored by GC analysis after the appropriate
intervals. The results are listed in Table 1.
We initially prepared a series of sulfonate-functionalized-
NHC complexes of Pd(II), in which the ligands behave as
monodentate and bis-chelating and pincer coordinated. We
thought that the choice of this type of coordination modes should
cover a wide set of topologies of palladium NHC complexes that
have proved efficient catalytic properties in nonaqueous solvents.
The preparation of the ligand precursors was based on the use of
As can be seen from the data shown in Table 1, complexes
, 3, and 4 are very active in the arylation of 4-bromoaceto-
1
1,3-propane sultone as alkylating agent, as previously used
for the preparation of other sulfonate-functionalized-NHC
phenone (yields above 90%, entries 2, 6, and 8), while
complex 2 provides only a moderate yield (59%, entry 4).
When the more inert 4-chloroacetophenone is used, only
compound 1 affords a high catalytic outcome (87%, entry 1),
while 3 and 4 provide a moderate yield of the final product
1
0,16
0
such as N,N -(methyl)(propanesulfonate)imida-
ligands,
1
7
zolium, 1a (Scheme 1). As depicted in Scheme 2, the general
preparation of complexes 1-3 implied the reaction between
[
Pd(OAc) ] and the corresponding imidazolium salt during 12 h
2
(
entries 5 and 7). According to the activities shown for the
between 80 and 160 °C in DMSO. All complexes were very
coupling between 4-bromoacetophenone and phenylboronic
acid, catalysts 1 and 3 were the most active ones. This
observation implies that the presence of the pyridine ligand
in 4 does not provide the expected catalytic enhancement
compared to catalyst 3.
To further analyze the catalytic activities of complexes 1
and 3, we studied the coupling reaction of 4-bromoaceto-
phenone and 4-chloroacetophenone with different catalyst
loadings ranging from 0.1 to 10 mol %. The results are
listed in Table 2. As can be seen, both 1 and 3 show excellent
activities in the coupling of 4-bromoacetophenone when
catalyst loadings as low as 10 mol % are used, although 1
provides a higher activity, in terms of both yield and reaction
time (compare entries 6 and 12). These data compare well with
soluble in H O and partially soluble in the lighter alcohols such
2
as MeOH and EtOH. The complexes were very insoluble in
most organic solvents such as CH Cl , CHCl , Et O, THF, and
acetone.
2
2
3
2
All three complexes, 1-3, were characterized by means of
NMR spectroscopy and high-resolution mass spectrometry
(ESI-TOF-MS). Only compound 1 gave satisfactory elemental
analysis because 2 and 3 were highly hygroscopic. Compound 1
-3
1
3
shows CNMR signals that are diagnostic for Pd(NHC)
complexes with mutually cis NHCs. The resonance due to the
-
3
(15) Loch, J. A.; Albrecht, M.; Peris, E.; Mata, J.; Faller, J. W.;
Crabtree, R. H. Organometallics 2002, 21, 700. Peris, E.; Loch, J. A.;
Mata, J.; Crabtree, R. H. Chem. Commun. 2001, 201.
(16) Virboul, M. A. N.; Lutz, M.; Siegler, M. A.; Spek, A. L.; van
Koten, G.; Gebbink, R. Chem.;Eur. J. 2009, 15, 9981.
(
(
17) Azua, A.; Sanz, S.; Peris, E. Organometallics 2010, 29, 3661.
18) Huynh, H. V.; Ho, J. H. H.; Neo, T. C.; Koh, L. L. J. Organomet.
(20) Organ, M. G.; Abdel-Hadi, M.; Avola, S.; Hadei, N.; Nasielski,
J.; O’Brien, C. J.; Valente, C. Chem.;Eur. J. 2007, 13, 150. Organ,
M. G.; Avola, S.; Dubovyk, I.; Hadei, N.; Kantchev, E. A. B.; O’Brien,
C. J.; Valente, C. Chem.;Eur. J. 2006, 12, 4749. O’Brien, C. J.;
Kantchev, E. A. B.; Chass, G. A.; Hadei, N.; Hopkinson, A. C.; Organ,
M. G.; Setiadi, D. H.; Tang, T. H.; Fang, D. C. Tetrahedron 2005, 61,
9723.
Chem. 2005, 690, 3854.
19) Hahn, F. E.; Foth, M. J. Organomet. Chem. 1999, 585, 241.
Herrmann, W. A.; Schwarz, J.; Gardiner, M. G. Organometallics 1999,
8, 4082. Herrmann, W. A.; Elison, M.; Fischer, J.; Kocher, C.; Artus,
G. R. J. Chem.;Eur. J. 1996, 2, 772.
(
1

6
86 Organometallics, Vol. 30, No. 4, 2011
Godoy et al.
Scheme 2
Table 1. Aqueous Suzuki-Miyaura Coupling Reaction of Aryl
Table 2. Aqueous Suzuki-Miyaura Reaction of Aryl Halides and
Phenylboronic Acid Using Catalysts 1 and 3
a
a
Halides and Phenylboronic Acid Using Complexes 1-4
b
entry
catalyst
X
t (h)
yield (%)
catalyst
loading (%)
b
c
entry
catalyst
X
t (h)
yield (%)
TON
1
2
3
4
5
6
7
8
1
Cl
Br
Cl
Br
Cl
Br
Cl
Br
12
4
12
4
12
4
12
4
87
>99
39
59
58
>99
51
90
-
-
-
-
-
-
-
-
1
2
3
1
2
3
1
2
1
2
3
4
5
6
7
8
9
1
10
10
10
10
10
10
10
10
10
10
10
10
Cl
12
85
76
850
7600
2
3
4
37
37 000
1000
10 000
100 000
520
Br
Cl
Br
2
12
3
>99
>99
>99
52
3
31
18
>99
>99
87
3100
18 000
1000
10 000
87 000
a
Reactions conditions: aryl halide (1 mmol), phenylboronic acid (1.2
CO (1.5 mmol), and 1 mol % of catalyst in 5 mL of H O at
10 °C. All reactions with 4-chloroacetophenone were performed with
addition of TBABr (1.5 mmol). Yields determined by GC using anisole
as internal standard.
-3
-1
-2
-3
mmol), K
1
2
3
2
10
11
12
b
a
Reaction conditions: aryl halide (1 mmol), phenylboronic acid (1.2
mmol), K CO (1.5 mmol), and catalyst in 5 mL of H O at 110 °C. All
previously published results for the coupling of 4-bromoace-
2
3
2
7
tophenone. For the reactions carried out with 4-chloroace-
tophenone, 1 affords a good activity when catalyst loadings
reactions with chloro halides were performed with addition of TBABr
b
(1.5 mmol). Yields determined by GC using anisole as internal stan-
c
dard. TON = (mmol of product)/(mmol of catalyst).
-
1
-2
of 10 or even 10 mol % are used (entries 1 and 2), but its
activity dramatically decreases at lower catalyst loadings. For
the same substrate, 3 affords a moderate activity when a cata-
lyst loading of 0.1 mol % is used (entry 7). The activity of 1 in
the coupling of 4-chloroacetophenone compares well with the
results recently published by C- etincaya and co-workers,
i
the reaction in a 1:1 mixture of H O/ PrOH, using catalysts 1
2
and 3. As can be seen from the data shown in Table 3, this
mixture of solvents allows the effective coupling of a variety
of bromoarenes, including nonactivated ones. For the cou-
pling with chloroarenes, both 1 and 3 are very active in the
coupling with 4-chloroacetophenone (entries 1 and 9), but
only 1 is capable of effectively activating other chloroarenes
such as chorobenzene (entry 3). These data are difficult to
compare with the results provided by other authors using the
same substrates and reaction conditions where conversions
5
although in their case a catalyst loading of 1 mol % was used.
One of the most important problems in the use of neat
water in the Suzuki-Miyaura coupling is the poor solubility
of most coupling partners. In order to circumvent this
6
,11,21
problem, mixtures of alcohol and water are often used.
In order to widen the number of aryl halide substrates that
we could use in the coupling reaction, we decided to perform
(generally based on reactants) instead of yields (based on
products) are reported.
6
,11
In order to illustrate this point, we
decided to study the time course of the reactions between
phenylboronic acid and two chloroarenes (Figure 1). As can
be seen from the three plots depicted in Figure 1, the coupling
(
21) Pschierer, J.; Peschek, N.; Plenio, H. Green Chem. 2010, 12, 636.
Fleckenstein, C. A.; Plenio, H. Green Chem. 2007, 9, 1287.

Article
Organometallics, Vol. 30, No. 4, 2011 687
Table 3. Suzuki-Miyaura Reaction of Aryl Halides and
Conclusions
i
Phenylboronic Acid in H O/ PrOH
a,b
2
In this work we have prepared a set of four new palladium
complexes with NHC ligands incorporating sulfonate func-
tionalities. The presence of the sulfonate makes these new
palladium complexes water-soluble, and insoluble in most
organic solvents.
c
entry
catalyst
X
R
t (h)
yield (%)
All four complexes have been tested in the Suzuki-Miyaura
coupling of a series of bromo- and chloroarenes with phenyl-
boronic acid in water, showing that complex 1, containing two
mutually cis NHC-sulfonate ligands, has better catalytic activ-
ity. The activity shown by complex 1is good, but nonetheless its
efficiency is lower than the best systems reported in the
literature for nonaqueous Suzuki-Miyaura coupling reac-
1
2
3
4
5
6
7
8
9
1
Cl
COCH
OCH
H
3
3
3
3
12
>99
35
73
3
CH
COCH
3
34
Br
Cl
Br
4
>99
86
99
94
84
12
31
12
OCH
H
3
2
2
CH
COCH
3
tions, but compares well with the best catalysts used in neat
5,7
3
12
4
water. We believe that our study constitutes a new approach
to the preparation of Pd-based water-soluble efficient catalysts
and may contribute to the implementation of C-C bond
coupling aqueous catalysis.
10
11
12
13
14
15
16
OCH
H
3
CH
COCH
3
>99
81
92
OCH
H
3
Experimental Section
CH
3
73
1
General Procedures. Compound 1a, bis(imidazol-1-yl)-
7
a
23
24
Reaction conditions: aryl halide (1 mmol), phenylboronic acid (1.2
CO (1.5 mmol), and 1 mol % of catalyst. Reactions
performed in a mixture of 2.5 mL of H
methane, and 2,6-bis(imidazol-1-yl)pyridine were pre-
pared according to literature methods. All the other reagents
are commercially available and were used as received. All
reactions were carried out under nitrogen using standard
Schlenk techniques. NMR spectra were recorded on Varian
mmol), K
2
3
i
2
O/2.5 mL of PrOH at 110 °C.
b
All reactions with chloro halides were performed with addition of
TBABr (1.5 mmol). Yields determined by GC using anisole as internal
standard.
c
Innova 300 and 500 MHz spectrometers, using D O as
2
solvent. Electrospray mass spectra (ESI-MS) were recorded
on a Micromass Quatro LC instrument, and nitrogen was
employed as drying and nebulizing gas. High-resolution
mass spectra (HR-MS) were recorded on a Q-TOF Premier
instrument. Elemental analyses were carried out in an EA
1108 CHNS-O Carlo Erba analyzer. The catalytic experi-
ments were carried out using degassed Milli-Q water.
reaction of 4-chloroacetophenone with phenylboronic acid
affords almost quantitative yield of the final biphenyl prod-
uct in just two hours. On the other hand, the maximum yield
achieved for the coupling of 4-chlorotoluene is 35%, after 12 h.
However, the conversion for this latter substrate is above 80%,
as can be seen from the corresponding graphic, a result that is
mainly due to the transformation of substrates in other prod-
ucts than the desired one. For this reaction, we also detected the
0
Synthesis of 1. A solution of N,N -(methyl)(propanesulfona-
te)imidazolium (1a, 182 mg, 0.892 mmol), Pd(OAc)
0.446 mmol), and KI (148 mg, 0.892 mmol) in degassed DMSO
5.0 mL) was heated at 80 °C during 12 h and then at 160 °C for a
2
(100 mg,
0
formation of 1,1 -biphenyl as a consequence of the homocou-
(
pling of phenylboronic acid. We also detected some other
minor unidentified products. These results are interesting
because they suggest that the low catalytic activity of catalyst
further 3 h. During this time the reaction solution turned bright
orange from being initially red. The remaining DMSO was removed
in vacuo at 60 °C to give an orange solid. The crude solid was wash-
1
when deactivated chloroarenes are used is not due to the
ed three times with hot methanol to give the desired product
deactivation of the catalyst along the reaction course, but to the
formation of other kinetically favored products. These results
suggest that probably a careful optimization of the reaction
conditions may afford better outcomes.
1
as a pure orange solid. Yield: 277 mg, 75%. H NMR (D
2
O, 300
MHz): δ 7.18 (s, 2H, CHimid), 7.13 (s, 2H, CHimid), 4.40 (m, 4H,
NCH ), 3.85 (s, 6H, NCH ), 2.96 (m, 4H, CH CH SO ), 2.47 (m,
4H, CH CH SO ). C( H) NMR (D O, 125 MHz): δ 163.9
2
3
2
2
3
13
1
2
2
3
2
It is interesting to see that the activity shown by the complex
containing the mono-NHC ligand, 1, shows a higher catalytic
activity than complex 3. When the first NHC-based-pincer-
2 2 2 3
(NCN), 123.9 (Cimid), 122.4 (Cimid), 49.4 (NCH CH CH SO ),
48.9 (NCH
SO ). Electrospray HR-MS (20 V, m/z): 638.9065 [M - I] ,
66.8188 [M þ H] . Anal. Calcd (%) for C14
844.90): C, 19.90; H, 2.62; N, 6.63. Found: C, 20.12; H, 2.95; N, 7.3.
Synthesis of 2a. The preparation of compound 2a was carried
3 2 2 2 3 2 2 2
), 38.2 (NCH CH CH SO ), 25.4 (NCH CH CH -
-
3
-
15
7
(
2 6 4 2 2
S O N H22PdI K
palladium complexes were reported, one of their main achieve-
ments was precisely their capability to activate C-Cl bonds
compared to other known Pd-NHC compounds, but this only
happened at very high temperatures when high-temperature-
boiling solvents were used such as DMSO or DMF. For
homogenously catalyzed reactions in water we have a strong
temperature limitation, so we believe that we may not be able to
take advantage of the extraordinary high stability of pincer-type
complexes 3and 4, by using them in reactions carried out at high
temperatures. In this regard, and in the course of the processing
of the present article, Tu and co-workers described the catalytic
activity of a hydrophilic pyridine-bridged bis-benzimidazolyli-
dene palladium pincer complex that is extraordinarily active in
the Suzuki-Miyaura coupling of a series of bromoarenes in
aqueous solvents, although its activity has not been tested in the
out by reaction of bis(imidazolyl)methane and 1,3-propane sul-
tone, under different reaction conditions than those reported in the
literature. A suspension of bis(imidazolyl)methane (500 mg,
25
(22) So, C. M.; Yeung, C. C.; Lau, C. P.; Kwong, F. Y. J. Org. Chem.
008, 73, 7803. Navarro, O.; Marion, N.; Mei, J. G.; Nolan, S. P.
2
Chem.;Eur. J. 2006, 12, 5142. Marion, N.; Navarro, O.; Mei, J. G.;
Stevens, E. D.; Scott, N. M.; Nolan, S. P. J. Am. Chem. Soc. 2006, 128,
4
101. Navarro, O.; Marion, N.; Oonishi, Y.; Kelly, R. A.; Nolan, S. P. J.
Org. Chem. 2006, 71, 685.
23) Diezbarra, E.; Delahoz, A.; Sanchezmigallon, A.; Tejeda, J.
Heterocycles 1992, 34, 1365.
24) Caballero, A.; Diez-Barra, E.; Jalon, F. A.; Merino, S.; Tejeda, J.
J. Organomet. Chem. 2001, 617, 395.
25) Papini, G.; Pellei, M.; Lobbia, G. G.; Burini, A.; Santini, C.
Dalton Trans. 2009, 6985.
(
(
(
9
coupling of chloroarenes.

6
88 Organometallics, Vol. 30, No. 4, 2011
Godoy et al.
Figure 1. Time course for the Suzuki-Miyaura reaction of 4-chloroacetophenone and 4-chlorotoluene with phenylboronic acid using
i
catalyst 1 (1 mol %) in H O/ PrOH. Solid lines refer to yields. The dotted line refers to conversion of 4-chlorotoluene.
2
3
(t, J
3
= 8.1 Hz, 1H, CH ), 7.87 (d, J
3
CH
.37 mmol) and 1,3-propane sultone (2.06 g, 16.9 mmol) in
= 2.1 Hz,
H-H
H-H
pyr
3
), 7.55 (d, J
3
CN was heated at 100 °C during 12 h in a Pyrex tube. The
2H, CH
J
imid
= 8.4 HZ, 2H, CHpyr), 7.38 (d,
H-H
3
so-generated solid was collected by filtration and washed sub-
sequently with CH Cl and MeOH. Compound 2a was isolated as
a white, air- and moisture-stable solid. Yield: 1085 mg, 82%.
Synthesis of 2. Compound 2a (129.4 mg, 0.330 mmol),
H-H 2 2 2
= 2.1 Hz, 2H, CHimid), 4.33 (m, 4H, NCH CH CH -
2
2
3 2 2 2 3 2
SO ), 2.89 (m, 4H, NCH CH CH SO ), 2.07 (m, 4H, NCH
CH CH SO ). C( H) NMR (D O, 75 MHz): δ 166.5 (NCN),
2 2 3 2
149.7 (Cortho), 147.2 (Cpara), 124.7 (Cimid), 118.3 (Cimid), 108.9
(Cmeta), 50.9 (NCH CH CH SO ), 47.5 (NCH CH CH -
1
3
1
Pd(OAc)
2
(75 mg, 0.330 mmol), and KI (109.6 mg, 0.660
2
2
2
3
2
2
2
mmol) were placed together in a Schlenk tube and dissolved
in degassed DMSO (5.0 mL). The mixture was heated at
3 2 2 2 3
SO ), 27.1 (NCH CH CH SO ). Electrospray HR-MS (20
V, m/z): 685.8862 [M] .
-
8
0 °C during 2 h and then at 140 °C for a further 12 h. The
Synthesis of 4. Silver triflate (7.0 mg, 0.027 mmol) was
added to a stirred solution of complex 3 (17.7 mg, 0.025 mmol) in
MeOH (5.0 mL). Pyridine (1.0 mL) was then added, and the
resulting solution was heated at reflux overnight. The reaction mix-
ture was filtered through Celite. Removal of the volatiles yielded
solvent was removed in vacuo at 60 °C to give an orange solid.
The crude solid was dissolved in hot methanol (3 ꢀ 10 mL) and
2 2
transferred to a column chromatograph packed with CH Cl /
MeOH (1:1). Elution with CH
2 2
Cl /MeOH (1:9) afforded the
1
separation of a yellow band that contained 2. Yield: 78.6 mg,
= 2.0 Hz,
complex 4 as a pale yellow solid. Yield: 15.6 mg, 98%. H NMR
=3 5.1 Hz, 2H, CHpyr), 8.37 (t,
1
3
3
29%. H NMR (D O, 300 MHz): δ 7.54 (d, J
(D O, 300 MHz): δ 9.14 (d, J
2
H-H
2
H-H
= 8.4 Hz, 1H, CHpyr), 8.25 (t, J
3
3
2
J
H, CHimid), 7.24 (d, JH-H = 2.0 Hz, 2H, CHimid), 6.61 (d,
J
= 8.1 Hz, 1H, CHpyr),
H-H
7.94 (d, J
H-H
= 2.1 Hz, 2H, CH ), 7.85 (t, J
2
2
3
3
H-H = 13.5 Hz, 1H, CHbridge), 6.27 (d, JH-H = 13.5 Hz, 1H,
H-H
=7.5 Hz,
H-H
= 8.1
H-H 2 2
= 7.5 Hz, 4H, NCH CH -
H-H
CHpyr), 7.67 (d, J
imid
3
=8.1 Hz, 2H, CH ), 7.36 (d, J
3
CHbridge), 3.92 (m, 2H, NCH ), 3.56 (m, 2H, NCH ), 2.61 (m, 4H,
2
2
H-H
pyr
13
1
3
CH
5 MHz): δ 169.3 (NCN), 123.2 (Cimid), 122.3 (Cimid), 64.1
NCH N), 49.3 (NCH CH CH SO ), 47.9 (NCH CH CH SO ),
6.6 (NCH CH CH SO ). Electrospray HR-MS (20 V, m/z):
2
CH
2
SO
3
), 2.01 (m, 4H, CH
2
CH
2
SO
3
). C( H) NMR (D
2
O,
Hz, 2H, CHimid),3 3.41 (t,
J
7
(
2
CH SO ), 2.42 (t, J =7.5 Hz, 4H, NCH CH CH SO ), 1.86
3
(m, 4H, NCH CH CH SO ). C( H) NMR (D O, 75 MHz):
2 2 2 3 2
2
3
H-H
2
2
2
13
1
2
2
2
2
3
2
2
2
3
2
2
2
3
δ 172.8 (Cpyr), 167.9 (NCN), 152.7 (Cpyr), 151.5 (Cpyr), 128.5 (Cpyr),
123.7 (Cimid), 118.4 (Cimid), 109.2 (Cpyr), 82.1 (Cpyr), 49.1 (NCH2-
CH CH SO ), 47.7 (NCH CH CH SO ), 26.5 (NCH CH CH -
-
6
22.8752 [M - I] . The compound was very hygroscopic, and
satisfactory analysis could not be obtained.
Synthesis of 3a. A suspension of 2,6-bis(imidazol-1-yl)pyridine
2
2
3
2
2
2
3
2
2
2
SO ). Electrospray HR-MS (20 V, m/z): 581.9175 [M - pyr þ
3
þ
(530 mg, 2.51 mmol) and 1,3-propane sultone (1.53 g, 12.6 mmol)
in CH
Na] . Anal. Calcd (%) for C S O N H Pd (639.01): C, 41.55;
6
22
2
6
24
3
CN was heated at 100 °C during 12 h in a Pyrex tube. The
H, 3.79; N, 13.15. Found: C, 41.23, H, 3.61, N, 14.6.
so-generated solid was collected by filtration and washed subse-
quently with CH Cl and MeOH. Compound 3a was isolated as a
General Procedure for the Suzuki-Miyaura Cross-Coupling
Reaction. In a typical run, a Pyrex tube was charged with aryl
halide (1 mmol), phenylboronic acid (1.2 mmol), K CO (1.5
2
2
1
white, air- and moisture-stable solid. Yield: 972 mg, 85%. H NMR
2
3
3
-1
-2
-3
(
D
2
O, 300 MHz): δ 9.94 (s, 2H, NCHN), 8.50 (t, JH-H = 8.1 Hz,
mmol), and catalyst (1, 10 , 10 , 10 mol %). The activa-
tion of aryl chlorides required the addition of 1.5 mmol of
TBABr as phase transfer catalyst. The solids were dissolved in
5 mL of degassed Milli-Q water or in a degassed 1:1 mixture of
3
1H, CHpyr), 8.42 (s, 2H, CHimid), 8.07 (d, JH-H = 8.1 Hz, 2H,
3
CHpyr),37.90 (s, 2H, CH ), 4.62 (t, J
= 7.2 Hz, 4H, NCH ),
2
), 2.51 (t, JH-H=7.2 Hz,
O, 75 MHz): δ 145.84
imid
H-H
3
3.08 (t, JH-H=7.2 Hz, 4H, CH
2
CH SO
2
3
13
1
). C( H) NMR (D
i
4H, CH
CH SO
2 2
3
2
Milli-Q water/ PrOH. The reaction mixture was then vigor-
(
(
NCHN), 145.04 (Cortho), 135.33 (Cpara), 123.86 (Cimid), 120.10
Cimid), 115.09 (Cmeta), 49.00 (NCH CH CH SO ), 47.48 (NCH -
ously stirred at 110 °C. After the desired reaction time, the
solution was allowed to cool. The reaction mixture was
extracted with dichloromethane (3 ꢀ 5 mL), and the organic
phase dried over Na SO . The solvent was removed by eva-
poration to give a crude product. The reaction mixture was
analyzed by gas chromatography using anisole as internal
standard.
2
2
2
3
2
CH
m/z): 334.2 [M - C
455.51): C, 44.83; H, 4.65; N, 15.37. Found: C, 44.64; H, 4.32;
N, 14.21.
Synthesis of 3. Compound 3a (304 mg, 0.67 mmol), Pd-
OAc) (150 mg, 0.67 mmol), and KI (111.2 mg, 0.67 mmol)
2
CH
2
SO
3
), 25.17 (NCH
2
CH
2
CH
2 3
SO ). Electrospray MS (20 V,
þ
3
H
6
3
SO ] . Anal. Calcd (%) for C17
21 5 2 6
H N S O
2
4
(
(
2
were placed together in a Schlenk tube and dissolved in
degassed DMSO (5.0 mL). The mixture was subsequently
heated at 80 °C for 2 h and at 140 °C for 12 h. The solvent
was removed in vacuo at 60 °C to give an orange solid. The
crude solid was dissolved in the minimum amount of water
and transferred to a column chromatograph packed with
Acknowledgment. We gratefully acknowledge financial
support from the Ministerio de Ciencia e Innovaci oꢀ n of
Spain (CTQ2008-04460) and Bancaixa (P1.1B2007-04). We
also thank the Ramon y Cajal Program (M.P.). C.S. thanks
the Ministerio de Ciencia e Innovaci oꢀ n for a fellowship. The
authors are grateful to the Serveis Centrals d’Instrumentacioꢀ
2 2
CH Cl /MeOH (1:1). Elution with MeOH afforded the se-
paration of an orange band that contained compound 3.
´
Cientıfica (SCIC) of the Universitat Jaume I for providing us
with spectroscopic facilities.
1
Yield: 87.2 mg, 18%. H NMR (D O, 300 MHz): δ 8.29
2