Multifold and sequential cross-coupling reactions with indium organometallics

Article abstract of DOI:10.1039/b206346h

Multifold and sequential palladium-catalyzed cross-coupling reactions can be performed between triorganoindium compounds and oligohaloarenes using only a small excess of the organometallic reagent, low catalyst charge loading and short reaction times.

Full text of DOI:10.1039/b206346h

Multifold and sequential cross-coupling reactions with indium
organometallics†
Miguel A. Pena, Ignacio Pérez, José Pérez Sestelo* and Luis A. Sarandeses*
Departamento de Química Fundamental, Universidade da Coruña, E-15071 A Coruña, Spain.
E-mail: qfsarand@udc.es; Fax: +34 981 167 065; Tel: +34 981 167 000
Received (in Cambridge, UK) 2nd July 2002, Accepted 27th August 2002
First published as an Advance Article on the web 10th September 2002
Multifold and sequential palladium-catalyzed cross-cou-
pling reactions can be performed between triorganoindium
compounds and oligohaloarenes using only a small excess of
the organometallic reagent, low catalyst charge loading and
short reaction times.
quantitative yield. 1,3,5-Triphenylbenzene (4a) and its acet-
ylenic derivative 4b (Fig. 1) have interesting physical properties
as liquid crystals10 or non-linear optical materials. Other
triphenyl- and triethynylbenzene derivatives can be prepared
using the same experimental procedure (Table 1, entries 3 and
11
4
). Remarkable features in this process are the small excess of
In used, the short reaction times and the high yields
obtained.
Encouraged by these results, we explored the reactivity of
other types of aromatic ring. Aryl-substituted pyridines have
The chemistry of compounds containing highly unsaturated,
conjugated p-systems has received a great deal of attention in
recent years due the potential uses of these compounds in
materials science.1 Among the wide variety of conjugated
architectures, polyphenylene and polyphenylacetylene struc-
tures, as well as derivatives bearing a heterocyclic unit in their
structure, are of particular interest. Their utility as liquid
R
3
,2
1
2
received significant attention as fluorescent chemosensors
1
3
and as chelating agents in coordination chemistry, but the
preparation of these compounds by cross-coupling reactions
have involved certain synthetic difficulties. The reaction of
3
4
14
crystals, core structures for dendrimers, building blocks for
5
two-dimensional carbon networks, electronic and optoelec-
2,6-dibromopyridine (2) with triphenylindium (80 mol%) or
tri(phenylethynyl)indium (100 mol%) in the presence of a
catalytic amount of Pd(dppf)Cl (4 mol%) afforded the twofold
2
tronic devices,6 and molecular wires,2 has been studied
extensively.
Although several synthetic approaches to these highly
unsaturated and conjugated p-systems have been developed,
palladium-catalyzed cross-coupling reactions remain the most
cross-coupling products 5a and 5b, respectively, in excellent
yields (Table 1, entries 5 and 6). Other organic residues such as
the vinyl group or acetylenic derivatives could also be
efficiently coupled, although in these cases larger amounts of
1,7
useful and straightforward strategies. Usually, the cross-
coupling reactions are performed between oligohaloarenes and
the appropriate acetylenic or organometallic partners to afford
the desired multifold cross-coupling products in one step.
Unfortunately, the reactions usually require a large excess of the
organometallic reagent, harsh reaction conditions (high tem-
peratures and pressure, long reaction times) and the yields
obtained are sometimes low.8
We recently developed an atom-efficient palladium-cata-
lyzed cross-coupling reaction between triorganoindium com-
pounds (R
3
In) and electrophiles, where the indium organome-
tallics transfer all three organic groups to the electrophile (eqn.
9
(
1)). The high efficiency of this procedure, which is carried out
Fig. 1 Multifold cross-coupling products.
with only a small excess of organometallic reagent and a low
catalyst loading, has stimulated our interest in its application to
multifold cross-coupling reactions. The first successful exam-
ples of the use of triorganoindium compounds in multiple and
sequential palladium-catalyzed cross-coupling reactions are
described herein.
Table 1 Results of the multifold cross-coupling reaction of triorganoindium
compounds (R In) with oligohaloarenes (1–3)
3
(1)
3
R In
(mol%)
As the starting oligohaloarenes we chose a benzene deriva-
tive, 1,3,5-tribromobenzene (1), an electron-deficient hetero-
aromatic compound, 2,6-dibromopyridine (2), and an electron-
rich heteroaromatic compound, 2,5-dibromothiophene (3). As
c
Product Yield (%)b
Entry
Ar–X a
n
R
1
2
3
4
5
6
7
8
9
1
2
3
Ph
130
130
150
130
80
100
200
150
200
150
150
4a
4b
4c
4d
5a
5b
5c
5e
6a
6b
6c
97
99
80
70
91
99
88
70
84
91
77
PhC·C
R
3
In we were mainly interested in the introduction of acetylenic
and aromatic units.‡ In our first attempt the cross-coupling of
,3,5-tribromobenzene (1) and Ph In (130 mol%) in the
presence of Pd(dppf)Cl (4 mol%) afforded, after 6 h under
Me SiC·C
3
mMeOC H
6
4
1
3
Ph
PhC·C
Me
CH
Ph
PhC·C
Me SiC·C
2
3
SiC·C
reflux in THF, 1,3,5-triphenylbenzene (4a) in 97% yield, a
result that demonstrates the efficient transfer of all three organic
groups attached to the indium(III). Following the same experi-
mental procedure, the reaction of 1 with tri(phenylethynyl)-
indium afforded the threefold cross-coupling product 4b in
2
NCH
1
1
a
0
1
3
1
: 1,3,5-Tribromobenzene; 2: 2,6-dibromopyridine; 3: 2,5-dibromothio-
phene. Isolated yield. Reactions were carried out in THF at reflux in 1–7
h using 4 mol% of Pd(dppf)Cl as catalyst.
b
c
1
†
Electronic supplementary information (ESI) available: H and 13C NMR
2
data for compounds. See http://www.rsc.org/suppdata/cc/b2/b206346h/
2
246
CHEM. COMMUN., 2002, 2246–2247 This journal is © The Royal Society of Chemistry 2002

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indium organometallic reagent were necessary (Table 1, entries
7
and 8).
The multiple cross-coupling with an electron-rich aromatic
ring, i.e. thiophene 3, was also tested. The phenyl or ethynyl
groups were efficiently incorporated, although up to 200 mol%
of the indium organometallic was necessary to optimize the
yield (Table 1, entries 9–11). The twofold cross-coupling
products obtained (6a–c, Fig. 1) have been proposed as
molecular wires.2
Scheme 2 Sequential cross-coupling reactions with triorganoindium
compounds (R In).
3
3
At this stage we envisioned the use of R In in the synthesis of
dendritic-type molecules by successive multifold cross-cou-
pling reactions.15 The reaction of 1,3,5-tribromobenzene (1)
with tris(p-methoxyphenyl)indium, in the presence of
In conclusion, we have demonstrated that indium organome-
tallics can be efficiently employed in multifold palladium-
catalyzed cross-coupling reactions using polyhalogenated aro-
matic compounds. Comparing with other organometallics, the
reactions are performed under relatively milder conditions and
short reaction times. In addition, a novel sequential cross-
coupling reaction using indium organometallics is reported. The
study of further applications of this methodology is now
underway.
This work was supported by the Ministerio de Ciencia y
Tecnología (DGI, Spain, BQU2000-0249). M.A.P. thanks the
Ministerio de Educación, Cultura y Deporte (Spain) for a
predoctoral fellowship (FPU).
Pd(dppf)Cl
in 90% yield (Scheme 1). In order to obtain the next
generation dendrimer, trimethoxyphenylene 7 was converted
into the tristriflate 8 by treatment with BBr and subsequent
reaction with triflic anhydride (78% yield, two steps). The
cross-coupling reaction of 8 with Ph In afforded the poly-
2
as catalyst, afforded the threefold coupling product
7
3
3
phenylene dendritic-type compound 9 in 75% yield. The
synthesis of 9 demonstrates the scope of indium organome-
tallics in multifold cross-coupling reactions towards poly-
phenylene dendrimers.
Notes and references
‡
Triorganoindium compounds were prepared by treatment of the corre-
sponding organolithium or Grignard reagents (3 equiv.) with InCl (1.1
3
equiv.) in dry THF at 278 °C and warming up to room temperature. For
further experimental details, see ref. 9.
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2
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Scheme 1 Synthesis of polyphenylene 9.
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reactions. The successive addition of different indium organo-
metallics to an oligohaloarene such 1-bromo-4-iodobenzene
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10) could provide information about the chemoselectivity of
1
these reagents. On the other hand, the construction of a variety
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3 4
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good yields (81 and 82% respectively, Scheme 2). These results
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symmetrically substituted aromatic compounds.
2
477–2486.
1
1
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CHEM. COMMUN., 2002, 2246–2247
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