Carbon-Carbon Bond Formation via Palladium-Catalyzed Reductive Coupling of Aryl Halides in Air and Water

Article abstract of DOI:10.1002/1615-4169(200206)344:3/4<399::AID-ADSC399>3.0.CO;2-X

Palladium-catalyzed reactions in general are carried out under an inert atmosphere because the palladium intermediates involved in the catalytic cycles are often known to be sensitive to oxygen. In this paper, we report that various palladium-catalyzed reductive couplings proceed smoothly under an air atmosphere and in aqueous medium. Under the air atmosphere reaction conditions, palladium-triphenylphosphine complex was found to be inactive. By using zinc as the reducing reagent, aryl halides were homo-coupled to give symmetrical biaryls either in aqueous acetone or in water in the presence of a catalytic amount of 18-crown-6 at room temperature. Both aryl iodides and aryl bromides reacted efficiently under the current reaction conditions. The reaction of arylhalosilanes with aryl halides under refluxing conditions in air and water catalyzed by palladium generated unsymmetrical biaryls efficiently in the presence of either KOH or NaF. Such air-stable couplings are also suitable for a Suzuki-type coupling and a Stille-type coupling.

Full text of DOI:10.1002/1615-4169(200206)344:3/4<399::AID-ADSC399>3.0.CO;2-X

FULL PAPERS
Carbon-Carbon Bond Formation via Palladium-Catalyzed
Reductive Coupling of Aryl Halides in Air and Water
Sripathy Venkatraman, Taisheng Huang, Chao-Jun Li*
Department of Chemistry, Tulane University, NewOrleans, Louisiana 70118, USA
Fax: ( ‡ 1)-504-8655596, e-mail: cjli@tulane.edu
Received: November 1, 2001; Accepted: February 24, 2002
Abstract: Palladium-catalyzed reactions in general amount of 18-crown-6 at room temperature. Both aryl
are carried out under an inert atmosphere because iodides and aryl bromides reacted efficiently under
the palladium intermediates involved in the catalytic the current reaction conditions. The reaction of
cycles are often known to be sensitive to oxygen. In arylhalosilanes with aryl halides under refluxing
this paper, we report that various palladium-catalyzed conditions in air and water catalyzed by palladium
reductive couplings proceed smoothly under an air generated unsymmetrical biaryls efficiently in the
atmosphere and in aqueous medium. Under the air presence of either KOH or NaF. Such air-stable
atmosphere reaction conditions, palladium-triphenyl- couplings are also suitable for a Suzuki-type coupling
phosphine complex was found to be inactive. By using and a Stille-type coupling.
zinc as the reducing reagent, aryl halides were homo-
coupled to give symmetrical biaryls either in aqueous Keywords: aryl halides; biaryls; CÀC coupling; cross-
acetone or in water in the presence of a catalytic coupling; crown compounds; palladium
Introduction
Results and Discussion
Palladium-catalyzed reductive couplings are among the Ullmann-Type Coupling to Generate Symmetrical
most important carbon-carbon bond forming reactions Biaryls
[
1]
in modern synthetic organic chemistry. Such reactions
[
2]
include the p-ally1 chemistry (also asymmetric), the Conventionally, symmetrical biaryls have been synthe-
[
3]
[4]
[10]
Stille coupling, the Heck reaction, the Suzuki sized via the Ullmann reaction of reductive aryl halide
[5]
[6]
[11]
reaction, the Sonogashira coupling, and many others. coupling,
where copper is used in stoichiometric
[
12]
While these reactions have also been successful in quantities. Generally, the Ullmann coupling is also
aqueous media,[ they are generally very sensitive carried out at a high temperature, typically above
towards air and, often, particular care needs to be taken 200 8C. Recently, it has been shown that, in the presence
to exclude air from the reaction system. In addition to of copper(I) thiophene-2-carboxylate, these reactions
the requirement of an inert gas atmosphere, these can be carried out under mild conditions. Palladium
reactions are often carried out in the presence of a has also been shown to catalyze aryl halide homo-
phosphine compound (which served as the coordinating couplings under elevated reaction temperatures in the
7]
[
13]
[
14]
ligand to stabilize the reactive palladium intermediate). presence of a reducing reagent. Ni/C has also been
In the course of our quest for novel methodologies in found by Lipshutz to be an effective catalyst for coupling
[8]
[15]
aqueous media, we came across this unusual condition of aryl halides. As an effort in developing transition
wherein the palladium catalyst seemed to be stable in metal-catalyzed carbon-carbon bond formation reac-
the air.[ Subsequently, we found that contrary to tions in water, we examined the potential of carrying out
generalbeliefs, palladium-catalyzed reductivecouplings such couplings by using palladium-catalyzed couplings
in air and water are quite general. Herein, we report the in water, Equation (1).
9]
detailed study of using such catalytic reactions to
synthesize symmetrical biaryls via Ullmann-type
homo-coupling of aryl halides and unsymmetrical
biaryls via cross-coupling of arylhalosilanes with aryl
halides.
Pd cat.
ArX
Ar-Ar
(1)
M/solvent
air atmosphere
Adv. Synth. Catal. 2002, 344, No. 3+4
¹ VCH Verlagsgesellschaft mbH, 69451 Weinheim, Germany, 2002 1615-4150/02/3443+4-399 ± 405 $ 17.50+.50/0
399

FULL PAPERS
Sripathy Venkatraman et al.
To begin our study, p-iodoanisole was stirred with zinc in presence of catalytic amounts of Pd/C and 18-crown-6.
a mixture of water/acetone (1:1) in the presence of a In the absence of the crown ether, the yield of the
catalytic amount of palladium acetate (8 mol %) for desired product diminished considerably (compare
1
2 h (and, accidentally, under an air atmosphere), GC/ entries 1 and 2, 7 and 8). An increase in steric hindrance
MS analysis of the reaction mixture revealed the resulted in a decrease of the yield of the coupled product
complete disappearance of the starting material and (compare entries 6, 7, 13 and entries 4, 5, 15). Bromo-
the corresponding homo-coupled product was gener- benzene was similarly coupled in generating the carbon-
ated in ca. 48% yield together with the dehalogenated carbon bond formation product (compare entries 1 and
anisole. No reaction was observed with other metals 3). Chloro and fluoro groups were inert under the
(
such as Ni powder or PtO ) as the catalyst. Subse- reaction conditions, which imparts chemoselectivity
2
quently, extensive investigations were made to evaluate (entries 9 and 10). On the other hand, only dehaloge-
the extent of such an air- and water-tolerant reaction. To nation was observed with an electron-deficient aryl
evaluate conditions for the desired coupling, conver- halide (entry 14). Subsequent to our initial report,
sions of starting materials were measured by GC/MS Sasson and co-workers found that under a refluxing
and the results are summarized in Table 1. It appears temperature, aryl chloride also reacted similarly.[
that the use of a mixture of water/acetone is important.
19]
The use of acetone alone resulted in a very low
conversion of the starting material, whereas in water Coupling of Aryl Halides with Phenylboronic Acid,
alone no reaction was observed. Interestingly, the Phenyl(ethynyl)tributyltin, and Aryhalosilanes to
presence of triphenylphosphine inhibited rather than Generate Unsymmetrical Biaryls and
facilitated the reaction. DMSO, DMFor THF could also Diphenylacetylene
serve as the co-solvent but they were much less effective
(
entries 10, 11, 12). When the catalyst was changed from In order to explore the scope of the air-stable palladium
[
16]
Pd(OAc) to Pd/C, the efficiency of the coupling was catalytic system, both Suzuki and Stille couplings of
2
increased and the dehalogenated product decreased iodobenzene were briefly examined with phenylboronic
(
compare entries 1 and 2). The use of other metals (such acid (3) and phenyl(ethynyl)tributyltin (5), Equa-
as tin and indium) as the reducing agent resulted in a low tions (3) and (4), in water. Both reactions generated
[
17]
reactivity (entries 5 and 6). The ratio of the homo- the desired coupling products 4 and 6 when Pd(OAc)2
coupled product can be optimized when the reaction was used as the catalyst in aqueous acetone and under an
temperature was controlled at 0 ± 10 8C. This might air atmosphere. However, low conversions of the
suggest that the coupling reaction is kinetically favored. starting materials were observed at room temperature
To validate the air-stable nature of this palladium in both cases. Interestingly, no reaction was observed
catalytic system, the reductive coupling was examined when Pd/C was used as the catalyst in these cases. Upon
and found to be successful even under an oxygen refluxing overnight, the reaction of PhI with PhB(OH)2
atmosphere. Comparative experiments were carried out and Bu SnCCPh in the presence of Pd(OAc)2
3
(
with iodoanisole, zinc, and Pd/C in aqueous acetone) (10 mol %) and Cs CO (1 equivalent) provided the
2 3
under nitrogen, oxygen, and air atmospheres, virtually desired product 4 (yield: 91%) and 6 (yield: 71%)
identical results were obtained in all cases. However, a smoothly. Although both the Suzuki and Stille couplings
relatively lowisolated yield of the desired product was
reactions are successful under the same reaction con-
obtained for coupling of iodobenzene under the con- ditions, a drawback of the Stille coupling is the involve-
ditions of acetone/water mixture. Subsequently it was ment and generation of relatively toxic tin reagents and
found that, in the presence of a catalytic amount of 18- by-products. In the boronic acid case, the limitations
[
18]
crown-6 (10 mol %), the zinc ( < 10 microns, the use with regard to synthesis and stability of boron reagents
[
20]
of larger particles sizes reduced the efficiency of the have also been noted. These limitations led us to
reaction) mediated reductive coupling of aryl halides 1 investigate other alternative reactions.
catalyzed by Pd/C provided improved isolated yields of
Recently, the use of hypervalent silicon reagents for
the Ullmann-type products 2 at ambient temperature, in palladium-catalyzed cross couplings has been studied by
[
21]
[22]
water alone, and under an atmosphere of air, Equa- Hiyama, DeShong and others. On the other hand,
tion (2). Denmark and co-workers have developed highly acti-
As shown in Table 2, various aromatic iodides and vated silicon reagents for palladium-catalyzed couplings
[
23]
bromides were coupled by zinc in water with the with aryl halides. A common requirement for these
studies has also been performance under anhydrous
conditions and in an inert gas atmosphere. Our recent
Pd/C cat.
discovery that rhodium-catalyzed conjugated additions
of arylhalosilanes proceeded effectively in air and
ArX
Ar-Ar
(2)
Zn, H2O/18-crown-6
air atmosphere
[
24]
water, led us to study the coupling of arylhalosilanes
with various aryl halides catalyzed by palladium in air
2
1
400
Adv. Synth. Catal. 2002, 344, 399 ± 405

Carbon-Carbon Bond Formation via Palladium-Catalyzed Reductive Coupling of Aryl Halides
FULL PAPERS
Table 1. Optimization of air-atmosphere reductive coupling of aryl halides under a variety of conditions.[a]
coupling/dehalogenation[b]
entry
1
substrate
metal
Zn
catalyst
solvent
Pd(OAc)2
acetone/H2O (1:1)
48/50
80/20
H3CO
I
I
2
Zn
Pd/C
acetone/H2O (1:1)
H3CO
3
4
Zn
Zn
Pd(OAc)2
Pd(OAc)2
acetone
7/trace
30/30
H3CO
H3CO
I
I
acetone/H2O (9:1)
5
6
Sn
In
Pd(OAc)2
Pd(OAc)2
acetone/H2O (1:1)
acetone/H2O (1:1)
5/trace
H3CO
I
I
26/trace
H3CO
7
8
9
Zn
Zn
Zn
Zn
Zn
Pd(OAc)2
acetonitrile
8/trace
I
OCH3
I
Ni
acetone/H2O (1:1)
acetone/H2O (1:1)
DMSO/H2O (1:1)
DMF/H2O (1:1)
no reaction
H3CO
H3CO
PtO2
I
no reaction
19/80
1
0
I
OCH3
I
Pd(OAc)2
Pd(OAc)2
11
20/40
OCH3
12
I
Zn
Pd(OAc)2
THF/H2O (1:1)
17/20
OCH3
[
[
a]
b]
All reactions were carried out at room temperature under an air atmosphere on 100 mg scale of aryl halides with aryl halide/M (1:3)
and 8 mmol % of the catalyst.
Conversion ratios were based on GC/MS analysis of ether extract of the reaction mixtures, the data are only for optimization purpose
and may not reflect the actual ratios of the amount of products.
and water. For the reaction of 4-iodoanisole with various
Subsequently, the reaction was evaluated by the
organosilanes 7, a preliminary test indicated the for- overall conversion of starting material, the isolated
mation of three coupled products 8a, 8b, and 8c under yield of the desired product 8b, and the ratio of product/
such reaction conditions, Equation (5).
by-products (Table 3). The reaction of phenyltrichloro-
Pd(OAc)2 cat.
(3)
B(OH)2
+
I
H2O/Cs2CO3/100 °C
overnight
3
91%
4
Pd(OAc)2 cat.
I
H2O/Cs2CO3/100 °C
overnight
SnBu3
+
(4)
5
6
71%
Adv. Synth. Catal. 2002, 344, 399 ± 405
401

FULL PAPERS
Sripathy Venkatraman et al.
Pd cat.
CH3O
I
+
PhRSiCl2
+
OCH3
+
H3CO
OCH3
(5
H2O/additives
air atmosphere
7
8a
8b
8c
silane with 4-iodoanisole under refluxing conditions
overnight [with Pd(OAc) being used as the catalyst]
2
Table 2. Zinc-mediated reductive coupling of aryl halides
generated the desired product in 20% isolated yield
together with a large amount of unreacted 4-iodoani-
sole. The use of diphenyldichlorosilane in combination
with sodium fluoride slightly improved the yield. The
yield was further improved by using phenylmethyldi-
chlorosilane as the silicon reagent. The use of KOH
instead of NaF provided higher yields for both diphe-
nyldichlorosilane and phenylmethyldichlorosilane re-
actions. Very similar but slightly better results were
observed with Pd/C as the catalyst. In this case, no
reaction was observed in the absence of KOH. The
relative ratios of the desired product and homo-coupled
by-products were quite constant in all cases.
Subsequently, the reaction of methylphenyldichloro-
silane (9) with a variety of aryl halides was examined
under the Pd/C-catalyzed conditions to generate the
unsymmetrical biaryls 10, Equation (6) (Table 4, see
page 404). Nearly the same results were obtained with
either iodo or bromo derivatives. Iodo- and bromo-
naphthalenes (entries 1, 2, and 8) reacted similarly. A
slightly better yield was obtained with an electron-
deficient aryl iodide (entries 3, 9, 10, and 11) than with
electron-rich aryl halides. It is worthy of mentioning that
catalyzed by Pd/C under air atmosphere.[a]
entry
substrate (1)
product (2)
yield [%]
54
I
1
2
21[d]
I
3
Br
44
61
H3C
H3C
4
I
CH3
CH3
5
6
H3C
I
H3C
H3CO
68
57
I
H3CO
H3CO
OCH3
OCH3
7
8
I
H3CO
51
12[d]
H3CO
Cl
I
H3CO
Cl
OCH3
Cl
9
I
60
60
10
F
I
F
F
4-bromophenol (bearing a free hydroxy group) reacted
smoothly to generate the desired product (entry 6). The
use of simple iodobenzene provided the corresponding
product quantitatively (part of the product may be due
to homo-coupling of the silicon reagent).
11
~
40[b]
I
Br
O
O
12
70[c]
Pd/C
Br
Ar-Ph (6)
ArX + PhRSiCl2
KOH (or NaF)/H O
2
air atmosphere
H3CO
9
10
13
I
40
OCH3
OCH3
Mechanistic Discussions
A tentative mechanism (similar to the one proposed by
O
1
4
5
dehalogenation
only
Br
[
25]
Jutand ) for the Ullmann-type coupling is proposed
involving the oxidative addition of the palladium
catalyst to the aryl halides to generate a palladium
intermediate (Scheme 1). The intermediate then under-
goes reduction by zinc to give an arylpalladium anion.
The arylpalladium anion then reacts with another aryl
halide to give the diarylpalladium intermediate, which
then undergoes reductive elimination to give the homo-
CH3
H3C
CH3
I
1
37
[
[
a] Yields were isolated ones after a short chromatography on silica gel.
b] The product was isolated as a mixture of coupling and dehalogenation,
with the ratio being estimated by GC/MS.
c] No coupling product was isolated.
d] No crown ether was added.
[
[
402
Adv. Synth. Catal. 2002, 344, 399 ± 405

Carbon-Carbon Bond Formation via Palladium-Catalyzed Reductive Coupling of Aryl Halides
FULL PAPERS
Table 3. Coupling of 4-iodoanisole with arylhalosilanes (7) under various conditions.
entry
silicon
reagent 7
additive[a]
8a:8b:8c[b]
yield [%][c]
of 8b
conversion
catalyst
[b]
[
%]
PhSiCl3
Ph2SiCl2
Pd(OAc)2
Pd(OAc)2
no
30
15:65:20
20
1
2
3
NaF
NaF
KOH
KOH
54
70
15:75:10
11:79:10
40
47
PhMeSiCl2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
4
5
6
7
Ph2SiCl2
PhMeSiCl2
PhSiCl3
91
90
50
87
97
0
12:79:8
11:81:8
5:74:21
2:88:10
3:91:6
0
70
71
36
74
80
0
Pd/C
Pd/C
Pd/C
Pd/C
KOH
KOH
KOH
no
Ph2SiCl2
8
9
PhMeSiCl2
PhMeSiCl2
[
[
[
a]
b]
c]
6
- 8 equivalents of additives were used.
Ratios and conversions were estimated (may not reflect the actual ratios) by GC/MS.
Isolated yields.
coupled product. For the synthesis of unsymmetrical In the presence of either KOH or NaF, arylhalosilanes
biaryls, the usual mechanism involving the oxidative were coupled with aryl halides under refluxing con-
addition of the palladium catalyst to the aryl halides ditions in air and water catalyzed by Pd(OAc) and Pd/C
2
[
26]
generates a palladium intermediate. The intermedi- to generate unsymmetrical biaryls efficiently. This air-
ate then reacts with phenylboronic acid, phenyl(eth- and water-tolerant palladium catalytic system provides
ynyl)tributyltin, or the silicate (generated from the an operational convenience for synthesis.
arylhalosilane derivative and KOH or NaF) to afford
the diarylpalladium species, which undergoes reductive
elimination to give the cross-coupling product and to
regenerate the active palladium catalyst.
Experimental Section
General Remarks
Conclusion
Unless otherwise noted, all reagents and solvents were
obtained from commercial sources and were used without
further purification. Chromatography was carried out using
Various palladium-catalyzed reductive couplings were
found to proceed smoothly under an air atmosphere and Merck 60 230 ± 400-mesh silica gel. IR spectra of liquid were
in aqueous media. By using zinc as the reducing reagent, recorded as thin films on NaCl plates and IR spectra of solids
were recorded as KBr pellets. Chemical shift in NMR spectra is
expressed in ppm. All NMR spectra were obtained at room
aryl halides were homo-coupled to give symmetrical
biaryls catalyzed by Pd/C in air and water in the
presence of either acetone or 18-crown-6 at room
temperature. Such air-stable couplings were also found
to be suitable for Suzuki-type and Stille-type couplings.
temperature in CDCl with TMS as an internal standard. All
3
products for the current studies are known compounds and
their characterizations have been compared with authentic
samples or literature data.
Ar-X
Ar-Ar
Pd(0)
Typical Experimental Procedure for Ullmann-Type
Coupling
To a suspension of 4-iodotoluene (300 mg, 1.3 mmol) in 10 mL
of de-ionized water in a 50 mL test-tube were added Pd/C
Ar-Pd-X
Ar-Pd-Ar
(
10%, 291 mg, 0.27 mmol), 18-crown-6 (73 mg, 0.27 mmol) and
zinc powder (273 mg, 4.12 mmol). The test tube was capped
and the mixture stirred overnight, diluted with 4 mL of 1 N
aqueous HCl, filtered through celite and washed with ether.
The filtrate was extracted with ether and concentrated. The
resulting crude material was passed through a short column of
silica gel eluting with hexane to give 4,4'-dimethylbiphenyl;
yield: 85 mg (68%).
Zn
X–
[
Ar-Pd]–
Ar-X
ZnX+
Scheme 1. Proposed mechanism for the zinc-mediated Ull-
mann-type coupling catalyzed by palladium in air and water.
Adv. Synth. Catal. 2002, 344, 399 ± 405
403

FULL PAPERS
Sripathy Venkatraman et al.
Table 4. Coupling of various aryl halides with methylphenylhalosilane 9.[a]
Coupling of Phenyl(ethynyl)tributyltin with
Iodobenzene
product 10
yield [%][b]
entry
aryl halide
I
A
1
0
suspension of phenyl(ethynyl)tributyltin (469 mg,
.2 mmol) PhI (204 mg, 1.0 mmol), Pd(OAc)2 (22 mg,
.1 mmol), Cs CO (326 mg, 1 mmol) in water (5 mL) was
1
2
3
72
stirred at reflux temperature overnight. After the reaction was
completed, 15 mL of ethyl acetate was added. The organic
phase was separated and the aqueous phase was extracted with
ethyl acetate (3 Â 10 mL). The combined organic layer was
Br
6
5 (66%)[c]
2
washed with brine (15 mL, dried over MgSO , filtered, and
4
concentrated in vacuo. The crude product was purified by a
flash chromatography on silica gel to give 126 mg (yield 71%)
of diphenylacetylene.
H3COC
H3C
H3COC
H3C
I
8
1
3
4
I
61
80
59
Typical Procedure for Arylhalosilanes Coupling with
Aryl Halides
H3CO
HO
H3CO
HO
I
5
A mixture of 4-iodoanisole (234 mg, 1 mmol), dichlorome-
thylphenylsilane (382 mg, 2 mmol), KOH (448 mg, 8 mmol),
and Pd/C (5 mol %) in 10 mL of water was stirred at 100 8C (oil
bath temperature) for 12 h under an air atmosphere. The
reaction mixture was cooled and extracted with ethyl acetate
Br
100
I
7
8
(
3 Â ). After the combined organic phase was dried and
Br
concentrated under vacuum, the residue was separated by
silica gel chromatography eluting with hexane to give the
desired biaryl product; yield: 140 mg (80%).
51
O2N
9
O2N
I
I
1
00
O2N
O2N
Acknowledgements
10
100
NO2
We are grateful to the NSF Career Award program and the NSF-
EPA joint program for support of our research.
NO2
I
11
100
F3C
F
1
2
F3C
F
I
I
7
1
References and Notes
13
65
[1] For representative reviews, see: B. M. Trost, Tetrahedron,
1
977, 33, 2615; J. Tsuji, TopicsCurr. Chem. 1980, 91, 29;
[
[
[
a]
All reactions were cartried out with Pd/C, KOH/H2O, under refluxing conditions for 12 - 36 h.
Isolated yields.
Ph2SiCl2 was used.
M. Kumada, Pure Appl. Chem. 1980, 52, 669; E. I.
Negishi, Acc. Chem. Res. 1982, 15, 340; J. Tsuji, Organic
Synthesis with Palladium Compounds, Springer-Verlag,
Berlin, 1980; J. E. B‰ckvall, Pure Appl. Chem. 1983, 55,
b]
c]
1
669; R. H. Heck, Palladium Reagentsfor Organic
Coupling of Phenylboronic Acid with Iodobenzene
Synthesis, Academic Press, NewYork, 1985; W. Oppolz-
er, Angew. Chem. Int. Ed. Engl. 1989, 28, 38; B. M. Trost,
Acc. Chem. Res. 1990, 23, 34; R. C. Larock, Adv. Met.-
Org. Chem. 1994, 3, 97; J. Tsuji, Transition Metal
Reagentsand Cataly si s. Innovationsin Organic Synthe si s
Wiley-VCH, NewYork, 2000; G. Poli, G. Giambastiani,
A. Heumann, Tetrahedon 2000, 56, 5959.
A suspension of PhB(OH) (146 mg, 1.2 mmol) PhI (204 mg,
2
1
.0 mmol), Pd(OAc)2 (22 mg, 0.1 mmol), Cs CO (326 mg,
2 3
1
mmol) in water (5 mL) was stirred at reflux temperature
overnight. After the reaction was completed, 15 mL of ethyl
acetate were added. The organic phase was separated and the
aqueous phase was extracted with ethyl acetate (3 Â 10 mL).
The combined organic layer was washed with brine (15 mL),
,
[
[
2] For a representative review, see: B. M. Trost, D. L. Van
Vranken, Chem. Rev. 1996, 96, 395.
dried over MgSO , filtered, and concentrated in vacuo. The
4
crude product was purified by a flash chromatography on silica
gel to give 140.1 mg (yield 91%) of biphenyl.
3] For representative reviews, see: J. K. Stille, Angew.
Chem. Int. Ed. Engl. 1986, 25, 508; V. Farina, V.
Krishnamurthy, W. J. Scott, Org. React. 1997, 50, 1.
4] For representative reviews, see: R. H. Heck, Acc. Chem.
Res. 1979, 12, 146; L. E. Overman, Pure Appl. Chem.
[
1
994, 66, 1423; I. P. Beletskaya, A. V. Cheprakov, Chem.
404
Adv. Synth. Catal. 2002, 344, 399 ± 405

Carbon-Carbon Bond Formation via Palladium-Catalyzed Reductive Coupling of Aryl Halides
FULL PAPERS
Rev. 2000, 100, 3009; G. T. Crisp, Chem. Soc. Rev. 1998,
7, 427.
5] For a representative review, see: N. Miyaura, A. Suzuki,
Chem. Rev. 1995, 95, 2457.
[13] Recently, Liebeskind reported an ambient temperature
Ullmann-type coupling, see: S. Zhang, D. Zhang, L. S.
Liebeskind, J. Org. Chem. 1997, 62, 2312, and references
cited therein.
2
[
[
6] For a representative review, see: K. Sonogashira, Metal-
Catalyzed Cross-Coupling Reactions (Eds.: F. Diedrich,
P. J. Stang), Wiley-VCH, NewYork, 1998, Chapter 5.
7] For representative reviews on transition metal-catalyzed
reactions in aqueous media, see: F. Joo, Z. Toth, J. Mol.
Catal. 1980, 8, 369; D. Sinou, Bull. Soc. Chim. Fr. 1987,
[14] P. Bamfield, P. M. Quan, Synthesis 1978, 537; J. Hassan,
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405