Microwave-promoted Heck coupling using ultralow metal catalyst concentrations

Article abstract of DOI:10.1021/jo048052k

(Chemical Equation Presented) We show that Heck couplings can be performed in water using microwave heating and Pd catalyst concentrations as low as 500 ppb. The methodology is simple; all that is required as the catalyst is a stock solution of palladium.

Full text of DOI:10.1021/jo048052k

Microwave-Promoted Heck Coupling Using Ultralow Metal
Catalyst Concentrations
Riina K. Arvela and Nicholas. E. Leadbeater*
Department of Chemistry, University of Connecticut,
Unit 3060, 55 North Eagleville Road, Storrs, Connecticut 06269-3060
nicholas.leadbeater@uconn.edu
Received November 2, 2004
We show that Heck couplings can be performed in water using microwave heating and Pd catalyst
concentrations as low as 500 ppb. The methodology is simple; all that is required as the catalyst is
a stock solution of palladium.
Introduction
reaction proceeds via the formation of palladium colloids
and that there is an equilibrium between these and a
lower-order species such a monomeric or dimeric moiety
that is the actual catalytically active species.6 They, and
others, have suggested that many of the palladacyclic
complexes reported as catalysts for the Heck reaction are,
in essence, sources of palladium nanoparticles or clusters
which are the real catalyst precursors, these again being
in equilibrium with lower-order palladium species.7
Choudary8 and co-workers have obtained high turnover
numbers in Heck couplings with aryl chlorides when
using layered double hydroxide supported nanopalladium
catalysts. They suggest that the reaction occurs at the
surface of the nanoparticles. Ko¨hler and co-workers have
recently studied the Heck reaction using a range of solid
catalysts.9 Their results point toward the fact that there
is in-situ generation of highly active dissolved palladium
species and thus that the catalysis is in effect homoge-
neous with palladium dissolution, reprecipitation being
a crucial and inherent part of the catalytic cycle. Similar
observations have been reported for Suzuki coupling
reactions.8,10,11 One drawback with using these ultralow
Palladium-catalyzed Heck reactions between aryl ha-
lides and alkenes continue to attract attention within the
chemistry community because of the versatility of the
reaction and the use of the products formed.1 Of all the
work undertaken, the area that has perhaps received
most research effort is the development of new catalysts
and ligands for Heck coupling reactions and then chem-
ists using these catalyst systems in, for example, natural
product synthesis. Recently, there has been increasing
interest in the use of “ligand-free” palladium catalysis
of the Heck reaction, either using simple palladium salts,
metallic palladium, or palladium nanoclusters immobi-
lized on inorganic supports. In addition, there have been
several reports that have recently appeared in the
literature that suggest that Heck coupling reactions can
be catalyzed by trace quantities of ligand-free palladium
sources. This is an area of considerable current interest
and discussion in the literature and here we want to
present findings from our laboratory.
Reetz and co-workers and also De Vries and co-workers
have shown that the reaction between aryl iodides or
bromides and alkenes can be run with the addition of
what they term “homeopathic” quantities of palladium
acetate using NMP as a solvent.2-5 They suggest that the
(5) de Vries, A. H. M.; Parlevliet, F. J.; Schmieder-van de Vonder-
voort, L.; Mommers, J. H. M.; Henderickx, H. J. W.; Walet, M. A. M.;
de Vries, J. G. Adv. Synth. Catal. 2002, 344, 996-1002.
(6) For a recent review of C-C bond formation using transition-
metal nanoparticles as catalysts see: Moreno-Manas, M.; Pleixats, R.
Acc. Chem. Res. 2003, 36, 638-643.
(1) For selected recent reviews of the Heck reaction see: (a) Brase,
S.; de Meijere, A. In Metal-catalyzed Cross-Coupling Reactions; Dieder-
ich, F., Stang, P. J., Eds.; Wiley-VCH: Weinheim, Germany, 1998;
Chapter 3. (b) Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000,
100, 3009-3066. (c) Whitcombe, N. J.; Hii, K. K.; Gibson, S. E.
Tetrahedron 2001, 57, 7449-7476.
(7) For discussion of whether heterogeneous catalysts could be
precursors to homogeneous catalysts for the Heck reaction see: (a)
Widegren, J. A.; Finke, R. G. J. Mol. Catal., A. 2003, 198, 317-341.
(b) Biffis, A.; Zecca, M.; Basato, M. Eur. J. Inorg. Chem. 2001, 1131-
1133. (c) Davies, I. W.; Matty, L.; Hughes, D. L.; Reider, P. J. J. Am.
Chem. Soc. 2001, 123, 10139-10140.
(8) Choudary, B. M.; Madhi, S.; Chowdari, N. S.; Kantam, M. L.;
Sreedhar, B. J. Am. Chem. Soc. 2002, 124, 14127-14136.
(9) Prockl, S. S.; Kleist, W.; Gruber, M. A.; Kohler, K. Angew. Chem.,
Int. Ed. 2004, 43, 1881-1182.
(10) Smith, M. D.; Stepan, A. F.; Ramarao, C.; Brennan, P. E.; Ley,
S. V. Chem. Commun. 2003, 2652-2653.
(2) For a recent review of the area see: Reetz, M. T.; de Vries, J. G.
Chem. Commun. 2004, 1559-1563.
(3) Reetz, M. T.; Westermann, E.; Lohmer, R.; Lohmer, G. Tetra-
hedron Lett. 1998, 39, 8449-8452.
(4) de Vries, A. H. M.; Mulders, J. M. C. A.; Mommers, J. H. M.;
Henderickx, H. J. W.; de Vries, J. G. Org. Lett. 2003, 5, 3285-3288.
10.1021/jo048052k CCC: $30.25 © 2005 American Chemical Society
Published on Web 01/29/2005
1786
J. Org. Chem. 2005, 70, 1786-1790

Microwave-Promoted Heck Coupling
catalyst loadings can be the rate of reaction when using
conventional heating. For example, De-Vries and co-
workers in their work showed that palladium acetate
catalyzed Heck reactions of aryl bromides work well if
the palladium concentration is kept between 0.01 and
0.1 mol %. At lower palladium concentrations, the reac-
tion is too slow to be practical.4
lammonium bromide (TBAB) as a phase-transfer agent.
Our interest in studying the Heck reaction sprang from
a knowledge that the Suzuki reaction can be greatly
accelerated by running the reaction using water as
solvent and, in some cases, by using microwave heating
as opposed to conventional heating. The total reaction
time is between 5 and 10 min and low palladium loadings
are used. The reactions can be performed on small
(1 mmol) scales using sealed tubes or larger scales
(20-50 mmol) using open reaction vessels.22,23 We sub-
sequently reported that it is possible to perform the
coupling without the need for addition of a transition-
metal catalyst.24,25 We now believe that, although the
reaction can be run without the need for addition of a
metal catalyst, palladium contaminants down to a level
of 50 ppb found in commercially available sodium car-
bonate are responsible for the generation of the biaryl
rather than, as previously suggested, an alternative
nonpalladium-mediated pathway.26 We wanted to see if
it was possible to accelerate the Heck reaction using
similar reaction conditions to our palladium-mediated
Suzuki couplings, with particular focus on the use of
ultralow catalyst concentrations.
In our group, we have an interest in using water as a
solvent in conjunction with microwave heating. The
concept of efficient and selective synthesis in water has
been exemplified as the rates, yields, and selectivity
observed for many reactions in water have begun to
match, or in many cases, surpass those in organic
solvents.12 Water also offers practical advantages over
organic solvents. It is cheap, readily available, nontoxic,
and nonflammable. There have been several reports of
Heck couplings using water or water/organic solvent
mixtures as solvent.13,14 Simple palladium salts have been
used as catalysts for the reaction.15 Beletskaya and co-
workers have shown that the coupling of acrylic acid and
acrylonitrile with aryl halides can be effected in neat
water or in DMF-water or HMPA-water mixtures at
70-100 °C with good yields.16 The reaction can be
performed under milder conditions using potassium
acetate. Jeffery and co-workers have shown that reac-
tions involving water-insoluble substrates can be ef-
ficiently performed in water, in the presence of a com-
bination of an alkali metal carbonate and a quaternary
ammonium salt.17
Microwave-promoted synthesis is an area of increasing
research interest as evidenced by the number of papers
and recent reviews appearing in the literature.18,19 As
well as being energy efficient, microwaves can also
enhance the rate of reactions and in many cases improve
product yields. Microwave heating has been used for the
Heck reaction before, a range of solvents and catalysts
being utilized.20 The use of water in conjunction with
microwave heating for Heck couplings has been re-
ported.21 The phosphine-ligated palladium complex PdCl2-
(PPh3)2 (5 mol %) is used as the catalyst and tetrabuty-
Results and Discussion
In our initial experiments, we chose to study the
coupling of 4-bromoanisole with styrene. Our data are
summarized in Table 1. Since we wanted to work with
very low catalyst loadings, we needed a reliable source
of palladium, the concentration of which could be guar-
anteed. When working in water, a major problem can be
precipitation of palladium from a stock solution, particu-
larly when working with a salt such as palladium acetate.
This is, however, avoided by using an acid-stabilized
stock solution. We therefore used a commercially avail-
able 1000 ppm palladium solution stabilized with 20%
HCl as our catalyst source. This was diluted accordingly
to give solutions of the desired concentrations. For low
concentrations, a couple of drops of HCl were added to
avoid precipitation of the palladium from solution. In
addition, the solutions were prepared freshly each day
from the 1000 ppm stock. Working on a 1 mmol scale of
4-bromoanisole, 2 mmol of styrene, and using a palladium
loading of 0.38 mol %, 6.0 mmol K2CO3 as base, 2 mL
water, and 1 mmol of TBAB as a phase-transfer agent,
(11) Conlon, D. A.; Pipik, B.; Ferdinand, S.; LeBlond, C. R.; Sowa,
J. R.; Izzo, B.; Collins, P.; Ho, G. J.; Williams, J. M.; Shi, Y. J.; Sun, Y.
K. Adv. Synth. Catal. 2003, 345, 931-935.
(12) For a general introduction to organic synthesis in water see:
(a) Grieco, P. A., Ed. Metal Catalysis in Water; Blackie Academic and
Professional: London, 1998. (b) Li, C.-J.; Chen, T.-H. Recent Develop-
ments of Palladium (0) Catalyzed Reactions in Aqueous Medium;
Klewer Academic Publishers: Dordrecht, The Netherlands, 1997.
(13) For reviews see: (a) Sinou, D. Top. Curr. Chem. 1999, 206, 41-
59. (b) Genet, J. P.; Savignac, M. J. Organomet. Chem. 1999, 576, 305-
317.
(14) For recent reports of Heck couplings in water see: (a) Botella,
L.; Najera, C. Tetrahedron Lett. 2004, 45, 1833-1836. (b) Mukho-
padhyay, S.; Rothenberg, G.; Joshi, A.; Baidossi, M.; Sasson, Y. Adv.
Synth. Catal. 2002, 344, 348-354. (c) Uozumi, Y.; Kimura, T. Synlett.
2002, 2045-2048.
(20) For selected reports see: (a) Bergbreiter, D. E.; Furyk, S. Green
Chem. 2004, 6, 280-285. (b) Xie, X. G.; Lu, J. P.; Chen, B.; Han, J. J.;
She, X. G.; Pan, X. F. Tetrahedron Lett. 2004, 45, 809-811. (c) Stadler,
A.; Yousefi, B. H.; Dallinger, D.; Walla, P.; Van der Eycken, E.; Kaval,
N.; Kappe, C. O. Org. Proc. Res. Dev. 2003, 7, 707-716. (d) Vallin, K.
S. A.; Emilsson, P.; Larhed, M.; Hallberg, A. J. Org. Chem. 2002, 67,
6243-6246. (e) Villemin, D.; Caillot, F. Tetrahedron Lett. 2001, 42,
639-642. (f) Diaz Ortiz, A.; Prieto, P.; Vazquez, E. Synlett. 1997, 269-
270. (g) Larhed, M.; Hallberg, A. J. Org. Chem. 1996, 61, 9582-9584.
(21) Wang, J.-X.; Liu, Z.; Hu, Y.; Wei, B.; Bai, L. J. Chem. Res. (S)
2000, 484-485.
(15) For a recent discussion of ligand-free Heck couplings, albeit not
in water, see: Yao, Q.; Kinney, E. P.; Yang, Z. J. Org. Chem. 2003,
68, 7528-7531.
(16) Bumagin, N. A.; More, P. G.; Beleteskaya, I. P. J. Organomet.
Chem. 1999, 371, 397-401.
(17) Jeffery, T. Tetrahedron Lett. 1994, 35, 3051-3054.
(18) For reviews on the area see: (a) Kappe, C. O. Angew. Chem.,
Int. Ed. 2004, 43, 6250-6284. (b) Larhed, M.; Moberg, C.; Hallberg,
A. Acc. Chem. Res. 2002, 35, 717-727. (c) Lew, A.; Krutzik, P. O.; Hart,
M. E.; Chamberlain, A. R. J. Comb. Chem. 2002, 4, 95-105.
(d) Lidstro¨m, P.; Tierney, J.; Wathey, B.; Westman, J. Tetrahedron
2001, 57, 9225-9283.
(22) Leadbeater, N. E.; Marco, M. Org. Lett. 2002, 4, 2973-2976.
(23) Leadbeater, N. E.; Marco, M. J. Org. Chem. 2003, 68, 888-
892.
(24) Leadbeater, N. E.; Marco, M. Angew. Chem., Int. Ed. 2003, 42,
1407-1409.
(25) Leadbeater, N. E.; Marco, M. J. Org. Chem. 2003, 68, 5660-
5667.
(19) For a review on the concepts see: Gabriel, C.; Gabriel, S.; Grant,
E. H.; Halstead, B. S.; Mingos, D. M. P. Chem. Soc. Rev. 1998, 27,
213-223.
(26) Arvela, R. K.; Leadbeater, N. E.; Sangi, M. S.; Williams, V. A.;
Granados, P.; Singer, R. D. J. Org. Chem. 2005, 70, 161-168.
J. Org. Chem, Vol. 70, No. 5, 2005 1787

Arvela and Leadbeater
TABLE 1. Effects of Palladium Concentration on
Product Yield in the Heck Coupling of 4-Bromoanisole
and Styrene in Water Using Microwave Heatinga
bond-forming reactions, the problem of slow reaction rate
encountered using conventional heating being overcome.
For dilution of our 1000 ppm Pd stock solution, we
needed to use water. Both this and the reagents we use
in the reaction could be sources of additional palladium,
thereby making our results inaccurate. To address this,
we used ultrapure water, purified to a specific resistance
of >16 mΩ‚cm in all of our dilutions. We analyzed this
for palladium and found levels in the region of 0.24 ppb
which we believe does not affect our results. The organic
reagents used in the reactions we believe to be palladium
free. The only reagent we believe could have contained
traces of palladium is the potassium carbonate. However,
analysis of a solution of our potassium carbonate in
ultrapure water showed levels of palladium correspond-
ing to <1 ppb in the concentrations used in our experi-
ments.
In all the reactions, yields are significantly higher
when the reaction mixture is NOT stirred. We attribute
this to problems associated with competitive decomposi-
tion of the starting aryl halide and styrene during the
reaction. In the absence of stirring, the reaction mixture
forms two distinct phases: a lower aqueous layer con-
taining the base and an upper organic layer containing
the organic substrates. We believe that one of the key
roles of the water is simply to dissolve the base and that
the coupling reaction takes place either at the aqueous/
organic interface or else the palladium migrates to the
organic phase where it could feasibly be stabilized as a
cluster or lower-order species by the TBAB. When the
reaction mixture is stirred, the aryl halide is more
exposed to the basic aqueous medium and this could
accelerate the competitive decomposition process. The
reason we do not observe similar decomposition in our
palladium-mediated Suzuki coupling protocol is, we
believe, because the Suzuki coupling is significantly
faster than the Heck coupling, and thus the aryl halide
is consumed at a greater rate and hence any competitive
decomposition pathway is not so much of a problem.
To probe more fully the role of water in the reaction,
we ran the coupling of 4-bromoanisole and styrene in the
absence of water. Since it is not possible to prepare
accurately ultralow concentrations of Pd without the use
of a stock solution of metal in a suitable solvent, we had
to run the solvent-free reaction at the higher catalyst
loading of 0.4 mol % Pd(OAc)2 to obtain reliable data. We
obtained a 53% yield of the desired product. This there-
fore suggests that water is not essential to the success
of the reaction, although higher yields are obtained if
water is used.27 We believe that one of the key roles of
the water is simply to dissolve the base and that the
reaction takes place at the aqueous/organic interface.
Using water does offer a convenient way to use very low
catalyst loadings and also makes workup very easy.
Running the reaction in organic solvents such as DMF,
NMP, and DMSO did not meet with success at low
catalyst loadings (<0.05 mol %). We obtained significant
decomposition in all of these solvents.
palladium
concentration (ppm)
catalyst
loading (mol %)
entry
yield/%
1b
200
200
10
2.5
1
0.5
0.5
0.3773
0.3773
0.0188
0.0047
0.0019
0.0009
0.0009
90
92
90
83
59
55
80
2c
3c
4c
5c
6c
7c,d
a Initial microwave irradiation of 70-100 W was used, the
temperature being ramped from r.t. to 170 °C where it was then
held for 10 min. Reactions were run using 1 mmol 4-bromoanisole
and 2 mmol styrene. A total water volume of 2 mL was used.
b Using 6.0 equiv K2CO3. c Using 3.7 equiv K2CO3. d The temper-
ature was ramped from r.t. to 170 °C where it was then held for
20 min.
it was possible to obtain a yield of 4-methoxystilbene of
90% after 10-min microwave irradiation (Table 1, entry
1). Using an inital microwave power of 70-100 W, we
ramped the temperature from room temperature (r.t.) to
170 °C, this taking 80-100 s, and then held the reaction
mixture at this temperature for 10 min. [CAUTION: The
water is heated well above its boiling point so all
necessary precautions should be taken when performing
such experiments. Vessels designed to withhold elevated
pressures must be used. The microwave apparatus used
here incorporates a protective metal cage around the
microwave vessel in case of explosion. After completion
of an experiment, the vessel must be allowed to cool to a
temperature below the boiling point of the solvent before
removal from the microwave cavity and opening to the
atmosphere.] Our motivation for using such a large
quantity of base was that we thought it would be
necessary to neutralize the acid from the stock solution
and have enough base left for the reaction. However, if
we decrease the base to 3.7 equivalents, we obtain a
comparable yield of the desired product (Table 1, entry
2). Smaller quantities of base are deleterous to product
yield. A quick screen of other mineral bases (sodium
carbonate, sodium hydroxide, and potassium acetate)
showed us that potassium carbonate was the best. We
also investigated the effect of decreasing the reaction time
but found that this has a deleterious effect on the product
yield. Our primary objective was to see how low we could
take the catalyst concentration without a significant drop
in product yield. Our data are summarized in Table 1.
Dropping the catalyst loading from 0.38 mol % to 0.0188
mol % has no effect on product yield (Table 1 entry 3).
Below this limit, product yield does begin to drop.
Catalyst loadings of 0.0047 mol %, 0.0019 mol %, and
0.0009 mol % lead to product yields of 83%, 59%, and
55%, respectively (Table 1, entries 4-6). Running the
reaction with a catalyst loading of 0.0009 mol % for
20 min as opposed to 10 min does lead to an increase of
yield from 55% to a very respectable 80% (Table 1 entry
7). This corresponds to a catalyst concentration of
500 ppb Pd and shows that, using microwave heating,
ultralow palladium concentrations can be used for C-C
We next wanted to probe the substrate scope of the
reaction (Table 2). We find that the coupling using 0.0019
(27) This agrees with other reports of Heck reaction run using
solvent-free conditions but in the presence of tetra-alkylammonium
salts. See: Bouquillon, S.; Ganchegui, B.; Estrine, B.; Henin, F.;
Muzart, J. J. Organomet. Chem. 2001, 634, 153-156.
1788 J. Org. Chem., Vol. 70, No. 5, 2005

Microwave-Promoted Heck Coupling
TABLE 2. Heck Coupling in Water Using Microwave Heatinga
J. Org. Chem, Vol. 70, No. 5, 2005 1789

Arvela and Leadbeater
Table 2. (Continued)
a Initial microwave irradiation of 70-100 W was used, the temperature being ramped from r.t. to 170 °C where it was then held for 10
min. Reactions were run using 1 mmol aryl halide and 2 mmol alkene. A total water volume of 2 mL was used. b Ramped from r.t. to 170
°C where it was then held for 20 min. c Loss of material noted.
microwave cavity. Initial microwave irradiation of 70 W was
used, the temperature being ramped from r.t. to the desired
temperature of 170 °C. Once this was reached, the reaction
mixture was held at this temperature for 10 min. After
allowing the mixture to cool to room temperature, the reaction
vessel was opened and the contents poured into a separating
funnel. Water (30 mL) and ethyl acetate (30 mL) were added
and the organic material was extracted and removed. After
further extraction of the aqueous layer with ethyl acetate,
combining the organic washings and drying them over MgSO4,
the ethyl acetate was removed in vacuuo leaving the crude
product. Product was characterized by comparison of NMR
data with that in the literature.28 1H NMR (CDCl3) δ 7.46-
7.53 (m, 4H), 7.37 (t, J ) 7.6 Hz, 2H), 7.26 (t, J ) 7.3 Hz, 1H),
7.10 (d, J ) 16.3 Hz, 1H), 7.00 (d, J ) 16.3 Hz, 1H), 6.93 (dd,
J ) 8.8 Hz, J ) 1.9 Hz, 2H), 3.85 (s, 3H); 13C NMR (CDCl3)
δ 159.4, 137.7, 130.2, 128.7, 128.3, 127.8, 127.2, 126.7, 126.3,
114.2, 55.3.
mol % and 0.0009 mol % Pd is unfortunately currently
limited to aryl halide substrates bearing certain func-
tional groups. Bromotoluene (both 2- and 4-), 4-bromo-
acetophenone, and bromobenzene all couple with styrene
in respectable yields (Table 2, entries 2-8). To put our
results in context, however, a review of the literature
shows that the majority of reports of Heck couplings at
high temperatures in aqueous media and ionic liquids
tend to focus on simple substrates. The same is also true
of some studies in organic solvents at elevated temper-
ature. We believe that the main problem, certainly in our
case, is again competitive decomposition of the starting
aryl/heteroaromatic halide. In an additional series of
experiments, we screened the coupling of 4-bromoaceto-
phenone, 4-bromotoluene, and 4-bromoanisole with acrylic
acid. We find that yields are not as high as those obtained
in analogous experiments using styrene, the desired
cinnamic acids being obtained between 25 and 67% yields
(Table 2, entries 18-22). Representative aryl iodides
were also screened in the coupling reaction using our
methodology (Table 2, entries 11-16) but product yields
were lower than their bromo- counterparts, as was
observed previously in both Heck and Suzuki couplings
using water as a solvent. Aryl chlorides could be coupled
only in very low yields using the current methodology
(Table 2, entry 17).
Representative Example of a Heck Coupling Using
Acrylic Acid as the Alkene Coupling Partner. Reaction
between 4-Bromoanisole and Acrylic Acid. The reaction
mixture was prepared and run as with the reaction using
styrene as a coupling partner but replacing the styrene with
acrylic acid (144 mg, 0.137 mL, 2 mmol) and using an increased
quantity of K2CO3 (600 mg, 4.7 mmol). After allowing the
mixture to cool to room temperature, the reaction vessel was
opened and the contents were poured into a separating funnel.
Water (30 mL) and ethyl acetate (30 mL) were added and the
aqueous layer was acidified using HCl. The organic material
was then extracted and removed. After further extraction of
the aqueous layer with ethyl acetate, combining the organic
washings and drying them over MgSO4, the ethyl acetate was
removed in vacuuo leaving the crude product. Product was
characterized by comparison of NMR data with that in the
Conclusions
In summary, we have presented here our observations
that Heck couplings can be performed in water using
microwave heating and Pd catalyst concentrations as low
as 500 ppb. The methodology is simple; all that is
required is a stock solution of palladium, but admittedly
the substrate scope is currently somewhat limited. We
are continuing our studies in the area and our results
will be reported in due course.
1
literature. H NMR (CDCl3) δ 7.75 (d, J ) 15.9 Hz, 1H), 7.51
(d, J ) 8.7 Hz, 2H), 6.92 (d, J ) 8.8 Hz, 2H), 6.32
(d, J ) 15.9 Hz, 1H), 3.85 (s, 3H); 13C NMR (CDCl3) δ 172.3,
161.8, 146.7, 130.1, 126.8, 114.6, 114.4, 55.4.
Acknowledgment. The University of Connecticut
Research Foundation is thanked for funding. Victoria
A. Williams is thanked for additional experiments.
Experimental Section
Representative Example of a Heck Coupling Using
Styrene as the Alkene Coupling Partner. Reaction
between 4-Bromoanisole and Styrene. In a 10-mL glass
tube was placed 4-bromoanisole (187 mg, 0.125 mL, 1.0 mmol),
styrene (208 mg, 0.230 mL, 2.0 mmol), K2CO3 (511 mg,
3.7 mmol), tetrabutylammonium bromide (322 mg, 1.0 mmol),
palladium stock solution (0.4 mL of a 1000 ppm solution in
water), and water (1.6 mL) to give a total volume of water of
2 mL and a total palladium concentration of 200 ppm. The
vessel was sealed with a septum, shaken, and placed into the
Supporting Information Available: General experimen-
tal and spectral data for the coupling products. This material
is available free of charge via the Internet at http://pubs.acs.org.
JO048052K
(28) Aggarwal, V. K.; Fulton, J. R.; Sheldon, C. G.; de Vicente, J. J.
Am. Chem. Soc. 2003, 125, 6034-6035.
1790 J. Org. Chem., Vol. 70, No. 5, 2005