Homocoupling of aryl iodides and bromides promoted by sulfur-containing palladacycles

Article abstract of DOI:10.1016/S0040-4039(02)00276-9

Sulfur-containing palladacycles, in particular those derived from the orthometalation of benzylthioethers, effectively promote the homocoupling of aryl iodides and bromides, under relatively mild reaction conditions to furnish symmetrical biphenyls in good yields.

Full text of DOI:10.1016/S0040-4039(02)00276-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 2327–2329
Homocoupling of aryl iodides and bromides promoted by
sulfur-containing palladacycles
Priscila B. Silveira, Vanusa R. Lando, Jairton Dupont* and Adriano L. Monteiro*
Laboratory of Molecular Catalysis, IQ, UFRGS. Av. Bento Gon c¸ alves, 9500 Porto Alegre, 91501-970 RS Brazil
Received 3 December 2001; revised 7 February 2002; accepted 8 February 2002
Abstract—Sulfur-containing palladacycles, in particular those derived from the orthometalation of benzylthioethers, effectively
promote the homocoupling of aryl iodides and bromides, under relatively mild reaction conditions to furnish symmetrical
biphenyls in good yields. © 2002 Elsevier Science Ltd. All rights reserved.
Biaryls possess a large variety of physical and chemical
properties and they have a broad range of applications,
encompassing various areas such as intermediates for
natural product synthesis, monomers for conducting1
polymers and ligands for organometallic catalysis.
These compounds are traditionally prepared by the
Ulmann homocoupling reaction, which involves the
condensation of two aryl halide molecules in the pres-
homocoupling reaction is accompanied by the forma-
tion of significant amounts of reduced aryl halide
product. Therefore, the development of an effective
catalytic protocol for this reaction, in particular involv-
ing less reactive bromo arenes, remains a challenge is
this area.
We have recently shown that sulfur-containing
2
8
ence of stoichiometric amounts of copper salts. More
palladacycles (Fig. 1) are effective catalyst precursors
recently, symmetrical biphenyls have been prepared
from arylboronic acids, arylstannanes and arylzinc
for the Heck, Suzuki and hydro-arylation coupling
reactions, under mild reactions. In the case of the
3
4
5
9
reagents. These methods are quite effective for the
generation of biphenyls although the necessity for the
preparation of these organometallic reagents and their
use in stoichiometric amounts are the major drawbacks.
Heck reaction of aryl iodides with tetrahydropyrans, a
significant amount of arene homocoupling product was
observed depending on the reaction conditions, suggest-
ing that palladacycle 1 is a potential catalyst precursor
for arene homocoupling reactions. We wish to dis-
close herein our preliminary results on the use of the
palladacycle 1, derived from the orthometallation of
t-butylmethylbenzyl sulfide, on the homocoupling of
aryl iodides and bromides (Eq. (1)).
9c
The transition-metal catalyzed homocoupling of aryl
halides is a catalytic alternative for the generation of
biphenyls starting from commercially available starting
6
7
materials. Indeed, various nickel and palladium cata-
lyst precursors have been reported to promote the
coupling of aryl halides, under relatively mild reaction
conditions. Amongst these, palladium acetate associ-
ated with phosphines, arsines, tetrabutylammonium
bromide and phosphapalladacycles have been success-
fully used in the aryl halide homocoupling reaction.
However, in most of the cases reported, the method is
only effective for aryl iodides and activated aryl bro-
mides in the presence of large quantities of the palla-
dium catalyst precursor (2–5%). Moreover, the
Figure 1. Sulfur-containing palladacycles used as catalyst pre-
cursors for C–C coupling reactions.
(1)
*
0
Corresponding author. Tel.: +55 51 33166321; fax: +55 51 33167304; e-mail: dupont@iq.ufrgs.br
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00276-9

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328
P. B. Sil6eira et al. / Tetrahedron Letters 43 (2002) 2327–2329
Initially, we tested the homocoupling of iodobenzene
catalyzed by this palladacycle at 130°C for 24 h using
different solvents and bases (Table 1).
eration of biphenyls from aryl iodides, reported to
date.
Once the protocol was established we turned our
attention to the homocoupling of the less reactive
aryl bromides. However, attempts to perform the
homocoupling of aryl bromides, under the same reac-
tion conditions employed for aryl iodides, have failed
and the starting materials were recovered almost
quantitatively after catalysis. We have thus reinvesti-
gated the reaction conditions by studying the homo-
coupling of 4-bromoanisole as a model reaction. The
use of K PO as a base in DMF at 100°C gave the
It is evident from the data in Table 1 (entries 1–8),
that for the homocoupling of iodobenzene, the reac-
tion performed in DMF using triethylamine as base
gave complete conversion and excellent isolated yields
of the biphenyl product (entry 8, Table 1). Moreover,
under these reaction conditions the biphenyl was the
sole product detected by GC–MS without traces of
by-products, such as benzene—the product resulting
from the reduction of the iodobenzene—usually
observed in most of the palladium-catalyzed homo-
coupling reactions reported to date.
3
4
best results in terms of selectivity and yields of the
biphenyl products (Table 2).
This experimental protocol has been successfully
extended to other para, meta and ortho substituted
iodo arenes (entries 9–14, Table 1), giving almost
complete conversion and excellent isolated yields of
biphenyl products with the exception of the ortho
substituted aryl iodides. In these cases (entries 13
and 14, Table 1), a substantial amount of the methyl-
benzoate and naphthalene by-products were formed,
indicating that this reaction is sensitive to steric fac-
tors. Nonetheless, palladacycle 1 is one of the most
effective and selective catalyst precursors for the gen-
However, in all cases significant amounts of reduced
bromoarene products were formed. The proportion of
these by-products increases with the introduction of
ortho substituents in the bromo-arene moiety (see entries
5–7, Table 2). In the case of 2-trifluoromethylbromoben-
zene (entry 5, Table 2), besides the high amount of the
reduction product, a mixture of biphenyl isomers was
obtained (Eq. (2)). The formation of these isomers is
probably related to a side reaction involving benzyne
intermediates, analogous to those already reported in
10
1
1
other related palladium-catalyzed coupling reactions.
a
Table 1. Palladacycle 1-catalyzed homocoupling of aryl iodides
Entry
ArI
Base
Solvent
Conv. (%)
ArH yield (%)b
Ar–Ar yield (%)b
1
2
3
4
5
6
7
8
9
PhI
PhI
PhI
PhI
PhI
PhI
PhI
PhI
Cs CO
DMA
DMA
DMA
DMA
Dioxane
Toluene
MeCN
DMF
DMF
DMF
DMF
DMF
DMF
DMF
18
27
93
96
39
55
87
100
99
93
2
9
68
79
10
3
34
100 (96)
98 (94)
94 (84)
96 (82)
97 (83)
54
2
3
K PO
3
4
NaOAc
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
NEt3
–
–
–
–
–
46
37
4-MeC H I
4-MeOC H I
4-AcC H I
3-FC H I
2-MeO CC H I
1-C10H7I
6
4
10
11
12
13
14
6
4
99
6
4
100
100
100
6
4
2
6
4
63
a
Reaction conditions: 0.5 mol% palladacycle 1, 1 mmol of iodo arene, 1.4 mmol of base, 5 mL of solvent, 130°C, 24 h.
GC yields using undecane as internal standard. Isolated yields in parentheses.
b
a
Table 2. Palladacycle 1-catalyzed homocoupling of aryl bromides
Entry
Ar–Br
Time (h)
Conv. (%)
Ar–H (%)
Ar–Ar (%)b
1
2
3
4
5
6
7
4-MeOC H Br
87
95
90
90
90
100
99
85
79
65
30
13
29
34
50
74
72
70 (61)
56 (56)
46 (40)
35 (35)
15
12
28
6
4
4-AcC H Br
6
4
4-F CC H Br
3
6
4
3-F CC H Br
3
6
4
c
2-F CC H Br
3
6
4
2,5-Me C H Br
115
143
95
100
2
6
3
1-C10H Br
7
a
Reaction conditions: 1.0 mol% palladacycle 1, 1 mmol of bromo arene, 1.4 mmol of base (K PO ), 5 mL of solvent (DMF), 100°C.
GC yields using undecane as internal standard. Isolated yields in parentheses.
Mixture of six isomers.
3
4
b
c

P. B. Sil6eira et al. / Tetrahedron Letters 43 (2002) 2327–2329
2329
(2)
It is interesting to note that all of these reactions
employ DMF as solvent and catalytic activity and
selectivity were strongly dependent on the DMF
Tillement, O. Tetrahedron 2001, 57, 531; (b) Lin, G.-Q.;
Hong, R. J. Org. Chem. 2001, 66, 2877; (c) Howarth, J.;
James, P.; Dai, J. Tetrahedron Lett. 2000, 41, 10319; (d)
Massicot, F.; Schneider, R.; Fort, Y. J. Chem. Res. 1999,
664.
1
2
source . It is well known that, depending on its source,
DMF contains different impurities such as dimethyl-
amine and formate or that such impurities may be
7. (a) Hassan, J.; Penalva, V.; Lavenot, L.; Gozzi, C.;
Lemaire, M. Tetrahedron 1998, 54, 13793; (b) Luo, F.-T.;
Jeevanandam, A.; Basu, M. K. Tetrahedron Lett. 1998,
39, 7939; (c) Venkatraman, S.; Li, C.-J. Org. Lett. 1999,
1, 1133; (d) Hennings, D. D.; Iwama, T.; Rawal, V. H.
Org. Lett. 1999, 1, 1205; (e) Boger, D. L.; Goldberg, J.;
Andersson, C.-M. J. Org. Chem. 1999, 64, 2422; (f)
Hassan, J.; Hathroubi, C.; Gozzi, C.; Lemaire, M. Tetra-
hedron 2001, 57, 7845.
1
3,14
generated in situ.
Moreover, it was proposed earlier
that these impurities could react with Pd(II) species to
generate Pd–H intermediates, which are reduced to
13
Pd(0) by the action of the base. In our case, the
generation of Pd–H intermediates can explain the for-
mation of the Ar–H by-products through a reductive
elimination step. We can note that the hydrogen source
in the reduction process is not water that may be
present in the medium, since reactions performed with
8. Dupont, J.; Pfeffer, M.; Spencer, J. Eur. J. Inorg. Chem.
4
-bromoanisole in the presence of D O indicated no
2001, 4, 1917.
2
D-incorporation (by GC–MS) in the anisole formed.
9. (a) Gruber, A. S.; Zim, D.; Monteiro, A. L.; Dupont, J.
Org. Lett. 2000, 2, 1287; (b) Zim, D.; Gruber, A. S.;
Dupont, J.; Monteiro, A. L. Org. Lett. 2000, 2, 2881; (c)
Dupont, J.; Gruber, A. S.; Fonseca, G. S.; Monteiro, A.
L.; Ebeling, G.; Burrow, R. A. Organometallics 2001, 20,
171.
10. Typical procedure: An oven-dried resealable Schlenk
flask was charged with palladacycle 1 (0.005–0.01 mmol).
The flask was evacuated and backfilled with argon and
then were added aryl halide (1.0 mmol), base (1.5 mmol)
and 5 mL of solvent. The reaction mixture was stirred at
the desired temperature. The solution was then allowed
to cool to room temperature, taken up in ether (20 mL)
and washed with aqueous NaOH (1 M, 2×10 mL) and
In summary, sulfur-containing palladacycles such as 1
are excellent catalyst precursors for the homocoupling
of aryl iodides. They are also effective for the homo-
coupling of aryl bromides. Further work is in progress
in our laboratory in order to understand the role of
DMF impurities in these reactions.
Acknowledgements
This work was supported by grants from the CNPq and
FAPERGS (Brazil).V.L. thanks CAPES for a Ph.D.
grant and P.B.S thanks FAPERGS for a scholarship.
brine (2×10 mL) and then dried over MgSO . After
4
filtration, the product was isolated by chromatography.
All biphenyl products reported in this work are known
and have spectroscopic data in accord with those
1
13
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