Iron-catalyzed Suzuki-Miyaura cross-coupling reaction

Article abstract of DOI:10.1002/adsc.200900281

An efficient, mild, and simple protocol for iron-catalyzed Suzuki-Miyaura type cross-coupling reaction between iodo- or bromoaryl derivatives and arylboronic acids was developed. In the presence of iron(III) chloride (10 mol%) and a stoichiometric amount of potassium fluoride, aryl iodides and bromides reacted with arylboronic acids in ethanol at 100 °C under air to give the corresponding bis-aryl compounds with good to excellent yields.

Full text of DOI:10.1002/adsc.200900281

RETRACTION
Retraction: Iron-Catalyzed Suzuki–Miyaura Cross-Coupling
Reaction
David Bꢀziera and Christophe Darcela,*
a
UMR 6226 CNRS-Universitꢀ de Rennes 1 “Sciences Chimiques de Rennes”, Equipe “Catalyse et Organomꢀtalliques”,
Campus de Beaulieu, Bat 10C, Avenue du Gꢀnꢀral Leclerc, 35042 Rennes Cedex, France
Fax : (+33)-2-2323-6939; e-mail: christophe.darcel@univ-rennes1.fr
Received: February 16, 2010; Published online: April 15, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900281.
Keywords: bis-aryl compounds; boronic acid; cross-coupling; homogeneous catalysis; iron; Suzuki–Miyaura
reaction
The following article from Advanced Synthesis & Cat-
alysis, “Iron-Catalyzed Suzuki-Miyaura Cross-Cou-
pling Reaction” by David Bꢀzier and Christophe
Darcel, published online on July 27, 2009, in Wiley In-
terScience (www.interscience.wiley.com), and in print
in Volume 351, Issue 11+12, 2009, pages 1732–1736,
has been retracted by agreement between the authors,
the journal Editor, Joe P. Richmond, and Wiley-VCH
Verlag GmbH & Co. KGaA. The retraction has been
agreed due to the following.
Initially, the use of potassium fluoride 99% from
Acros lead to complete conversion with aryl iodides
and activated aryl bromides. With several batches of
iron(III) chloride 99.99% the authors succeeded to re-
produce those results and the blank tests without
iron(III) chloride 99.99% did not lead to any conver-
sion. Those tests were made several times with differ-
ent substrates. However, attempts to repeat this work
in two independent laboratories have been unsuccess-
ful.
Entry Origin of KF
Blank reaction[a] with- With FeCl3
out FeCl3 99.99%
99.99%[a]
1
2
Acros 99%
(original batch)
Alfa Aesar
99% anhy-
drous
No conversion
Full conver-
sion[b]
No conversion
No conver-
sion
3
4
Aldrich
99.99%
Acros 99%
(new batch)
No conversion
No conversion
No conver-
sion
No conver-
sion
[a]
Reaction performed with iodobenzene, bromoacetophe-
none and bromoanisole.
[b] full conversion for iodobenzene, bromoacetophenone,
20% conversion for bromoanisole.
It clearly seems that this reaction is sensitive to the
quality of KF and as the authors cannot reproduce
Therefore, the authors decided to re-examine the such reactions even with KF of the same quality from
reaction, and more particularly to use different types the same supplier, this communication has to be re-
of KF from different suppliers. The results are report- tracted.
ed in the following table.

COMMUNICATIONS
DOI: 10.1002/adsc.200900281
Iron-Catalyzed Suzuki–Miyaura Cross-Coupling Reaction
David Bꢀziera and Christophe Darcela,*
a
UMR 6226 CNRS-Universitꢀ de Rennes 1 “Sciences Chimiques de Rennes”, Equipe “Catalyse et Organomꢀtalliques”,
Campus de Beaulieu, Bat 10C, Avenue du Gꢀnꢀral Leclerc, 35042 Rennes Cedex, France
Fax : (+33)-2-2323-6939; e-mail: christophe.darcel@univ-rennes1.fr
Received: April 21, 2009; Published online: July 27, 2009
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200900281.
Abstract: An efficient, mild, and simple protocol
for iron-catalyzed Suzuki–Miyaura type cross-cou-
pling reaction between iodo- or bromoaryl deriva-
tives and arylboronic acids was developed. In the
series is certainly that the complexes are usually air-
sensitive.
In the environmental context of today, one of the
challenging issues for chemists is to develop cost-ef-
presence of ironA C H T U N G T R E N N U N G (III) chloridefe(c1t0ivme,ogl%re)ena,nmd ialds,toain-d efficient catalytic routes that
chiometric amount of potassium fluoride, aryl io-
dides and bromides reacted with arylboronic acids
in ethanol at 1008C under air to give the corre-
sponding bis-aryl compounds with good to excellent
yields.
minimize hazardous waste. On the other hand, many
catalysts are derived from heavy or rare metals and
their toxicity and prohibitive prices can constitute
severe drawbacks for large-scale applications. In con-
trast, iron is one of the most abundant metals on the
earth, and one of the most inexpensive and environ-
mentally friendly ones. Despite the fact that the coor-
dination chemistry of iron was widely developed in
the past decades, it is really surprising that, until
lately, iron was under-represented in the field of ho-
mogeneous catalysis relative to the other transition
metals. However, the last few years have seen a rise
in the use of iron as a catalyst,[6] and very efficient
Keywords: bis-aryl compounds; boronic acid; cross-
coupling; homogeneous catalysis; iron; Suzuki–
Miyaura reaction
For the construction of carbon-carbon bonds, some of processes that are now able to compete with other
the most common and powerful methods involve the metal-catalyzed ones have emerged in the hydrosilyla-
use of transition metal-mediated reactions. Among tion,[7] oxidation,[8] epoxidation[9] and even hydrogena-
these methods, the Suzuki–Miyaura cross-coupling re- tion areas.[10] In the field of carbon-carbon bond for-
action[1] has become one of the most useful and mation via cross-coupling reactions of Grignard deriv-
À
worthy synthetic methods for selective biaryl C C atives, an intensive work was accomplished since the
bond formation,[2] which are often included as partial pioneering reports of Kochi[11] and the iron-catalyzed
structures in natural products,[3] pharmaceuticals,[4] cross-coupling methodology is able to compete with
functional materials,[5] etc. This reaction is actually the palladium-catalyzed one.[12] Iron-catalyzed cross-
one of the most frequently used transition metal-cata- coupling reactions were also realized with organome-
lyzed ones either in academic or in industrial areas. tallics reagents such as zinc,[13] copper,[14] or manga-
However, the most interesting features of organobor- nese[15] derivatives. During the course of this work, a
on reagents and their by-products are their low toxici- pioneering communication related to the cross-cou-
ty, making these compounds environmentally practi- pling reaction of phenylboronic acid with a limitated
cal compared to other organometallic reagents, partic- number of bromoaryl derivatives catalyzed by
[16]
ularly organostannanes. Countless improvements on pyridyl
the original Suzuki–Miyaura protocol for the cross-
A C H T U N G T R E N N U N G iron complexes was published.
In continuing our work on the use of iron as cata-
couplings of aryl halides with arylboronic acids have lyst to promote environmentally benign synthetic
been recorded. Important contributions include great methodologies,[17–19] we describe herein an cross-cou-
improvements in substrate scope, catalyst/ligand sys- pling reaction of halogenoaryl compounds (X=I, Br)
tems and solvents, as well as enhanced experimental with arylboronic acid in ethanol in the presence of a
conditions. One important drawback in the palladium catalytic amount of FeCl3 in combination with a stoi-
chiometric amount of KF (Scheme 1).
1732
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Adv. Synth. Catal. 2009, 351, 1732 – 1736

Iron-Catalyzed Suzuki–Miyaura Cross-Coupling Reaction
COMMUNICATIONS
when a hydrated precursor FeCl3·6H2O was used,
only 22% of the biphenyl derivative was obtained
(Table 1, entry 12). A control experiment in the ab-
sence of an iron salt confirmed the crucial role which
the iron catalyst plays in the described cross-coupling
reaction as the reaction did not occur.
Scheme 1. Iron-catalyzed Miyaura–Suzuki cross-coupling re-
action.
It must be also underlined that when the reaction
In the initial attempts to improve this iron-cata- was performed under argon, at 1008C for 16 h in a
lyzed Suzuki–Miyaura type cross-coupling reaction, sealed tube using FeCl3 as catalyst in ethanol in the
iodobenzene was chosen as a test substrate to opti- presence of KF, no conversion was observed. This
mize the reaction conditions (Scheme 1). An ethanol result shows the crucial role of air in the iron-catalytic
solution of iodobenzene was allowed to react with process.
phenylboronic acid (2 equivalents) at 1008C in the
To get more information on the optimal catalyst
presence of a catalytic amount of iron salt (10 mol%) conditions, we carried out also intensive investigations
and 3.5 equivalents of KF. After warming in a sealed to define the best solvent for this transformation. 6
Schlenk tube at 1008C for 16 h, the reaction afforded different solvents were tested at reflux for 16 h using
the cross-coupling product with complete conversion 10 mol% of FeCl3 as catalyst. Table 2 lists representa-
of the iodobenzene. We then carried out extensive in- tive data collected for the synthesis of biphenyl 3a as
vestigations to define the best reaction conditions, a model reaction.
and Table 1 lists representative data obtained for the
Among the different solvents screened, ethanol has
cross-coupling reaction of iodobenzene with phenyl- been found to be a far better solvent: biphenyl 3a was
boronic acid with various commercially available obtained with excellent GC yield (100%) (Table 2,
iron(II) and iron
First of all, on using acetate iron salts such as ether, THF or methanol, surprisingly, no reaction
Fe T 2 or T 3 as atal(yasctasc, )o ly o(dacearac)te GC took place (Table 2, entries 1–4). When the reaction
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(III) salts.
entry 7). In some classical solvents such as toluene,
A
C
H
U N FG eTA RC EH N NU UN cNG GT R E N N nU N mG
yields were obtained (28 and 40%, respectively) was conducted in refluxing isopropyl alcohol or etha-
(Table 1, entries 2 and 3). Interestingly, the use of nol, only low conversions were observed, 10 and 25%,
FeA C H T 2U oN rG FT eRSOE 4N·7N HU 2ON G g(aOveAcs)atisfactory results respectively (Table 2, entries 5 and 6). We also might
(65% GC yield) (Table 1, entries 6 and 7). Iron halide point out the crucial role of the pressure on the cross-
salts seem to be then best catalyst precursors coupling process. When the reaction was performed
(Table 1, entries 8–11), and dry FeCl3 was the best in an open flask under reflux for 16 h, only 25% con-
iron salt for the formation of the biphenyl compound version was observed. On the contrary, when it was
(100% GC yield). (Table 1, entry 11) Interestingly, conducted in a sealed tube at 1008C, 100% conver-
sion was observed. It should be noted that the reac-
tion was clean and only the cross-coupling product
was detected on GC. Interestingly, reduction of the
Table 1. Iron salt screening for the Miyaura–Suzuki cross-
coupling reaction of phenyl iodide with phenylboronic acid.
Table 2. Investigation of solvents and additives on the model
reaction.
Entry Additive[a] Solvent Conditions
GC Yield [%][b]
Entry
Iron salt (10 mol%)[a]
–
GC yield [%][b]
1
2
3
4
KF
KF
KF
KF
THF
Toluene Reflux, 16 h
Ether Reflux, 16 h
MeOH Reflux, 16 h
Reflux, 16 h
0
0
0
0
1
2
3
4
5
6
7
8
0
Fe
Fe
A
A
C
C
H
H
T 2
T 3
U
U
N
N
G
G
T
T
R
R
E
E
N
N
N
N
U
U
N
N
G
G
(2a8cac)
(4a0cac)
30
16
65
(6O5Ac)
75
75
95
100
22
Fe2O3
FeF2
5
KF
i-PrOH Reflux, 16 h 10
6
7
8
9
10
11
12
KF
KF
KO-t-Bu
Cs2CO3
K3PO4
KOAc
CsF
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
Reflux, 16 h 25
1008C, 16h[c] 100
1008C, 16 h[c] 22
FeSO4·7H2O
Fe 2U
A
C
H
T
N
G
T
R
E
N
N
U
N
G
FeBr2
FeCl2
FeF3
FeCl3
FeCl3·6H2O
1008C, 16 h[c]
1008C, 16 h
1008C, 16 h[c]
5
0
0
9
10
11
12
1008C, 16 h[c] 80
[a]
Experimental conditions: bromobenzene (0.5 mmol), phe-
nylboronic acid (1 mmol), additive (1.75 mmol,
3.5 equiv.), FeCl3 (10 mol%) in 3 mL of solvent for 16 h.
GC yield.
[a]
Experimental conditions: bromobenzene (0.5 mmol), phe-
nylboronic acid (1 mmol), KF (1.75 mmol), iron salt
(10 mol%) in 3 mL of ethanol for 16 h in a sealed tube.
GC yield.
[b]
[c]
[b]
Reaction performed on a sealed tube.
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1733

David Bꢀzier and Christophe Darcel
COMMUNICATIONS
aryl halides was not observed and only trace amounts was used, the biphenyl derivative 3a was obtained
of biphenyl derivatives (<1%) resulting from the ho- with 80% GC yield (Table 2, entry 12),
mocoupling of arylboronic acids were detected by
GC-MS analysis.
We next examined the scope and limitations of this
iron-catalyzed cross-coupling reaction with various
In those conditions, a small pressure in the sealed types of iodo- and bromoaryl derivatives and arylbor-
reactor favoured the reaction. One very recent com- onic acids (Table 3). All reactions were carried out
munication supported this opinion: Young and co- with 10 mol% of FeCl3 in HPLC grade ethanol at 90–
workers reported that the metal-catalyzed Suzuki– 1008C in the presence of a stoichiometric amount of
Miyaura cross-coupling reaction between bromoben- KF in a sealed tube. In general, all reactions were
zene and phenylboronic acid can be promoted at high clean, and bis-aryl derivatives 3 were obtained in
pressure (15 kbar). In particular, using FeCl3/2-(diphe- good yields.
nylphosphino)pyridine as catalyst (5 mol%), 97%
The cross-coupling reaction of iodoaryl derivative
conversion was observed after 48 h at 1008C.[20] They was amenable to both electron-rich and electron-poor
suggested that the main influence of pressure on the aromatic iodoaryl derivatives such as iodobenzene or
iron-catalyzed reaction should be the acceleration of para-substituted (Me, OMe, CF3) iodobenzenes, and
the reduction of the metal to a catalytically active oxi- the reaction gave the corresponding bis-aryl com-
dation state. Usually, in iron-catalyzed cross-coupling pounds 3 in good to excellent yields (75–98%;
reaction, a reducing agent such as a Grignard reagent Table 3, entries 1–4). No great influence of the para-
is required to reduce the iron salt to its low valent substituted group on the arylboronic acid partner was
state as the catalytically active species.[12d,e]
observed for the reaction with iodobenzene; both
The nature of the additive has also a crucial role on arylboronic acids which possess an electron-donating
the reaction. When Cs2CO3, K3PO4, or KOAc were or electron-withdrawing group on the aryl ring gave
used as additives (3.5 equivalents) instead of KF, the the corresponding bis-aryl products 3 in good to ex-
formation of only trace amount of the desired product cellent isolated yield (77–98%) (Table 3, entries 5–8).
3a was detected on GC. (Table 2, entries 9–11) With It must be pointed out, with p-fluoro and p-acetylphe-
KO-t-Bu as additive, a better conversion was ob- nylboronic acids, to avoid a degradation procedure of
served (22%) (Table 2, entry 8), Finally, when CsF the starting compounds, that the reaction was con-
ducted at 908C (Table 3, entries 6 and 8).
Table 3. Scope of the reaction.
Entry
Ar-X
Ar’-B(OH)2
Conditions[a]
Compound
Yield [%][b]
1
2
3
4
5
6
7
8
Ph-I
Ph-B(OH)2
Ph-B(OH)2
Ph-B(OH)2
Ph-B(OH)2
p-CF3-C6H4B(OH)2
p-F-C6H4B(OH)2
p-OEt-C6H4B(OH)2
p-MeCO-C6H4B(OH)2
Ph-B(OH)2
Ph-B(OH)2
Ph-B(OH)2
Ph-B(OH)2
p-MeCO-C6H4B(OH)2
p-CF3-C6H4B(OH)2
p-F-C6H4B(OH)2
p-Me-C6H4B(OH)2
p-OEt-C6H4B(OH)2
1-NaphthylB(OH)2
16 h/1008C
16 h/1008C
16 h/1008C
16 h/1008C
16 h/1008C
30 h/908C
16 h/1008C
30 h/908C
16 h/1008Cc
16 h/1008C
16 h/1008C
16 h/1008C
16 h/908C
16 h/1008C
30 h/908C
36 h/1008C
16 h/1008C
16 h/1008C
Ph-Ph
p-Me-C6H4-Ph
p-OMe-C6H4-Ph
p-CF3-C6H4-Ph
Ph-C6H4-p-CF3
Ph-C6H4-p-F
Ph-C6H4-p-OEt
Ph-C6H4-p-COMe
p-NO2-C6H4-Ph
p-CF3-C6H4-Ph
p-MeCO-C6H4-Ph
p-MeO-C6H4-Ph
p-MeCO-C6H4-C6H4-p-COMe
p-MeCO-C6H4-C6H4-p-CF3
p-MeCO-C6H4-C6H4-p-F
p-MeCO-C6H4-C6H4-p-Me
p-MeCO-C6H4-C6H4- p-OEt
p-MeCO-C6H4-1-Naphthyl
3a
3b
3c
3d
3d
3e
3f
3g
3h
3d
3g
3c
3i
96
75
80
98
98
77
96
85
98
99
98
35
99
97
97
97
83
32
p-Me-C6H4-I
p-OMe-C6H4-I
p-CF3-C6H4-I
Ph-I
Ph-I
Ph-I
Ph-I
9
p-NO2-C6H4-Br
p-CF3-C6H4-Br
p-MeCO-C6H4-Br
p-MeO-C6H4-Br
p-MeCO-C6H4-Br
p-MeCO-C6H4-Br
p-MeCO-C6H4-Br
p-MeCO-C6H4-Br
p-MeCO-C6H4-Br
p-MeCO-C6H4-Br
10
11
12
13
14
15
16
17
18
3j
3k
3l
3m
3n
[a]
Experimental conditions: aryl halide (0.5 mmol), arylboronic acid (1 mmol), KF (1.75 mmol, 3.5 equiv.), FeCl3 (10 mol%)
in 3 mL of ethanol in a sealed tube.
Isolated yield.
CsF instead KF.
[b]
[c]
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Iron-Catalyzed Suzuki–Miyaura Cross-Coupling Reaction
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The reaction progress was monitored by GC. The mixture
was cooled to room temperature, extracted with EtOAc
(20 mL) and washed with distilled water (2ꢂ15 mL) and
then dried over MgSO4. Then, the solvent was removed
under vacuum, and the residue was purified by flash column
(petroleum ether/ethyl acetate, 95:5), Bis-aryl derivatives
Interestingly, the cross-coupling reaction can be
also successful with bromobenzene derivatives. para-
Electron-withdrawing group substituted (NO2, MeCO,
CF3) bromobenzenes, coupled with phenylboronic
acid in excellent yields (98–99%) (Table 3, entries 9–
11). Worthy of note is that an electron-rich bromo-
benzene, such as p-methoxybromobenzene, led to the
1
were obtained as solids. H and 13C NMR data for the prod-
ucts were in accordance with literature values.
bis-aryl product with
a moderate yield (35%)
(Table 3, entry 12). Even after a prolonged reaction
time (60 h at 1008C), no better result was obtained.
Next, the reaction of various boronic acids with an
electron-poor bromobenzene was also examined using
the present catalytic system. The reaction of bromo-
benzene with various p-electron-withdrawing groups
(MeCO, F, CF3) and p-electron-donating (Me, OMe)
substituted phenylboronic acids led to the correspond-
ing cross-coupling compounds 3 with good to excel-
lent isolated yields (83–99%) (Table 3, entries 13–17).
Furthermore, it must also be underlined that, in our
experimental conditions, hindrance hampers the reac-
tion. Indeed, with a sterically hindered ortho-subtitut-
ed bromobenzene such as o-trifloromethyl-, o-nitro-,
or o-acetylbromobenzene, no reaction occurred after
16 h at 1008C. In the case of a more sterically hin-
dered arylboronic acid such as 1-naphthylboronic
acid, only 32% yield for the coupling product with
the p-acetylbromobenzene was isolated (Table 3,
entry 18).
Acknowledgements
We are grateful to CNRS and Ministꢀre de l’Enseignement
Supꢁrieur et de la Recherche for support, and the latter for a
Ph.D grant to D.B.
References
[1] For reviews of the palladium-catalyzed Suzuki–Miyaura
coupling reactions, see: a) N. Miyaura, A. Suzuki,
Chem. Rev. 1995, 95, 2457–2483; b) A. Suzuki, J. Orga-
nomet. Chem. 1999, 576, 147–168; c) N. Miyaura, Top.
Curr. Chem. 2002, 219, 11–59; d) S. Kotha, K. Lahiri,
D. Kashinath, Tetrahedron 2002, 58, 9633–9695; e) F.
Bellina, A. Carpita, R. Rossi, Synthesis 2004, 15, 2419–
2440; f) R. Martin, S. L. Buchwald, Acc. Chem. Res.
2008, 41, 1461–1473; g) H. Doucet, Eur. J. Org. Chem.
2008, 2013–2030.
[2] J. Hassan, M. Sevignon, C. Gozzi, E. Schulz, M. Lem-
In summary, we have developed an interesting and
useful iron-catalyzed protocol for Suzuki–Miyaura
coupling reactions. It proceeds at 1008C under small
pressure in ethanol in a sealed tube in the presence of
aire, Chem. Rev. 2002, 102, 1359–1470.
[3] S. R. Chemler, D. Trauner, S. J. Danishefsky, Angew.
Chem. 2001, 113, 4676–4701; Angew. Chem. Int. Ed.
2001, 40, 4544–4568.
a
stoichiometric amount of potassium fluoride
[4] N. Yasuda, J. Organomet. Chem. 2002, 253, 279-/287.
[5] a) L. Liao, A. Cirpan, Q. Chu, F. E. Karasz, Y. Pang, J.
Polym. Sci. Part A: Polym. Chem. 2007, 45, 2048–2058.
[6] For complete reviews of the state of the art, see: a) C.
Bolm, J. Legros, J. Le Paih, L. Zani, Chem. Rev. 2004,
104, 6217–6254; b) S. Enthaler, K. Junge, M. Beller,
Angew. Chem. 2008, 120, 3363–3367; Angew. Chem.
Int. Ed. 2008, 47, 3317–3321; c) A. Correa, O. Garcia
Mancheno, C. Bolm, Chem. Soc. Rev., 2008, 37, 1108–
1117.
[7] a) A. M. Tondreau, E. Lobkovsky, P. J. Chirik, Org.
Lett. 2008, 10, 2789–2792; b) N. S. Shaikh, S. Enthaler,
K. Junge, M. Beller, Angew. Chem. 2008, 120, 2531–
2535; Angew. Chem. Int. Ed. 2008, 47, 2497–2501;
c) F. G. Gelalcha, B. Bitterlich, G. Anilkumar, M. K.
Tse, M. Beller, Angew. Chem. 2007, 119, 7431–7435;
Angew. Chem. Int. Ed. 2007, 46, 7293–7296; d) N. S.
Shaikh, K. Junge, M. Beller, Org. Lett. 2007, 9, 5429–
5432; e) H. Nishiyama, A. Furuta, Chem. Commun.
2007, 760–762; f) A. Furuta, H. Nishiyama, Tetrahe-
dron Lett. 2007, 48, 110–113.
(3.5 equivalents) and 10 mol% of FeCl3. Although the
literature enumerates a number of procedures for
Suzuki cross-coupling reactions, the simplicity, envi-
ronmental acceptability, and inexpensiveness of our
procedure makes it a practical alternative. As a result
of its ease of manipulation, low-cost, and benign char-
acter, the new iron catalyst described appears promis-
ing for large-scale applications. Studies to improve
the catalyst performance and to expand the substrate
scope of the method are currently in progress in our
laboratory.
Experimental Section
General Procedure for Iron-Catalyzed Suzuki–
Miyaura Reaction[21]
FeCl3 (8.2 mg, 0.05 mmol, 10 mol%; 98% from Aldrich) was
dissolved in in HPLC grade ethanol (3 mL). The aryl halide
(0.5 mmol, 1 equiv.) and phenylboronic acid (122 mg,
1 mmol, 2 equiv.) were then added to the mixture which was
stirred 10 min at room temperature. Finally, KF (102 mg,
1.75 mmol, 3.5 equiv.) was introduced and the reaction mix-
ture was then warmed at 1008C for 16 h in a sealed tube.
[8] a) F. Shi, M. K. Tse, Z. Li, M. Beller, Chem. Eur. J.
2008, 14, 8793–8797; b) M. Nakanishi, C. Bolm, Adv.
Synth. Catal. 2007, 349, 861–864; c) C. Pavan, J.
Legros, C. Bolm, Adv. Synth. Catal. 2005, 347, 703–
705; d) J. Legros, C. Bolm, Chem. Eur. J. 2005, 11,
1086–1092; e) J. Legros, C. Bolm, Angew. Chem. 2004,
Adv. Synth. Catal. 2009, 351, 1732 – 1736
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David Bꢀzier and Christophe Darcel
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116, 4321–4324; Angew. Chem. Int. Ed. 2004, 43, 4225–
4228; f) J. Legros, C. Bolm, Angew. Chem. 2003, 115,
5645–5647; Angew. Chem. Int. Ed. 2003, 42, 5487–
5489; g) Z. Li, L. Cao, C.-J. Li, Angew. Chem. 2007,
119, 6625–6627; Angew. Chem. Int. Ed. 2007, 46, 6505–
6507; h) Z. Li, R. Yu, H. Li, Angew. Chem. 2008, 120,
7607–7610; Angew. Chem. Int. Ed. 2008, 47, 7497–
7500.
mura, J. Am. Chem. Soc. 2004, 126, 3686–3687; o) T.
Nagano, T. Hayashi, Org. Lett. 2004, 6, 1297–1299;
p) R. B. Bedford, D. W. Bruce, R. M. Frost, J. W.
Goodby, M. Hird, Chem. Commun. 2004, 2822–2823;
q) G. Cahiez, C. Chaboche, F. Mahuteau-Betzer, M.
Ahr, Org. Lett. 2005, 7, 1943–1946; r) R. B. Bedford,
D. W. Bruce, R. M. Frost, M. Hird, Chem. Commun.
2005, 4161–4163; s) R. B. Bedford, M. Betham, D. W.
Bruce, A. A. Danopoulos, R. M. Frost, M. Hird, J. Org.
Chem. 2006, 71, 1104–1110; t) G. Cahiez, V. Habiak, C.
Duplais, A. Moyeux, Angew. Chem. 2007, 119, 4442–
4444; Angew. Chem. Int. Ed. 2007, 46, 4364–4366;
u) G. Cahiez, O. Gager, V. Habiak, Synthesis 2008,
2636–2644; v) G. Cahiez, V. Habiak, O. Gager, Org.
Lett. 2008, 10, 2389–2392; w) B. D. Sherry, A. Fꢃrstner,
Acc. Chem. Res. 2008, 41, 1500–1511.
[9] a) B. Bitterlich, K. Schroeder, M. K. Tse, M. Beller,
Eur. J. Org. Chem. 2008, 29, 4867–4870; b) F. G. Gelal-
cha, G. Anilkumar, M. K. Tse, A. Bruckner, M. Beller,
Chem. Eur. J. 2008, 14, 7687–7698; c) F. G. Gelalcha,
B. Bitterlich, G. Anilkumar, M. K. Tse, M. Beller,
Angew. Chem. 2007, 119, 7431–7435; Angew. Chem.
Int. Ed. 2007, 46, 7293–7296; d) K. Schroeder, X. Tong,
B. Bitterlich, M. K. Tse, F. G. Gelalcha, A. Brueckner,
M. Beller, Tetrahedron Lett. 2007, 48, 6339–6342; e) B.
Bitterlich, G. Anilkumar, F. G. Gelalcha, B. Spilker, A.
Grotevendt, R. Jackstell, M. K. Tse, M. Beller, Chem.
Asian J. 2007, 2, 521–529; f) G. Anilkumar, B. Bitter-
lich, F. G. Gelalcha, M. K. Tse, M. Beller, Chem.
Commun. 2007, 289–291.
[13] For an example of iron-catalyzed cross-coupling using
organozinc reagents, see: a) R. B. Bedford, M. Huwe,
M. C. Wilkinson, Chem. Commun. 2009, 600–602;
b) G. Cahiez, L. Foulgoc, A. Moyeux, Angew. Chem.
2009, 121, 3013 –3016; Angew. Chem. Int. Ed. 2009, 48,
2969–2972.
[10] a) S. Gaillard, J.-L. Renaud, ChemSusChem 2008, 1,
505–509; b) S. Enthaler, B. Hagemann, G. Erre, K.
Junge, M. Beller, Chem. Asian J. 2006, 1, 598–604;
c) S. C. Bart, E. Lobkovsky, P. J. Chirik, J. Am. Chem.
Soc. 2004, 126, 13794–13807.
[11] For pioneering examples of iron-catalyzed cross-cou-
pling using Grignard reagents, see: a) M. Tamura, J. K.
Kochi, J. Am. Chem. Soc. 1971, 93, 1487–1489; b) M.
Tamura, J. K. Kochi, Synthesis 1971, 303–305; c) M.
Tamura, J. K. Kochi, J. Organomet. Chem. 1971, 31,
289–309; d) M. Tamura, J. K. Kochi, Bull. Chem. Soc.
Jpn. 1971, 44, 3063–3073; e) J. K. Kochi, Acc. Chem.
Res. 1974, 7, 351–360; f) S. M. Neumann, J. K. Kochi, J.
Org. Chem. 1975, 40, 599–606; g) R. S. Smith, J. K.
Kochi, J. Org. Chem. 1976, 41, 502–509;.
[14] For examples of iron-catalyzed cross-coupling using or-
ganocopper reagents, see: a) C. C. Kofink, B. Blank, S.
Pagano, N. Gçtz, P. Knochel, Chem. Commun.
2007,1954–1956; b) I. Sapountzis, W. Lin, C. Kofink, C.
Despotopoulou, P. Knochel, Angew. Chem. 2005, 117,
1682–1685; Angew. Chem. Int. Ed. 2005, 44, 1654–
1657; c) P. Knochel, I. Sapountzis, T. Korn, W. Lin, C.
Kofink, Ger. Offen. DE102004049508, 2006.
[15] For examples of iron-catalyzed cross-coupling using or-
ganomanganese reagents, see: a) G. Cahiez, S. Mar-
quais, Tetrahedron Lett. 1996, 37, 1773–1776; b) G.
Cahiez, S. Marquais, Pure Appl. Chem. 1996, 68, 53–
60.
[16] T. Kylmꢄlꢄ, A. Valkonen, K. Rissanen, Y. Xu, R. Fran-
zꢀn, Tetrahedron Lett. 2008, 49, 6679–6681.
[12] For recent examples of iron-catalyzed cross-coupling
using Grignard reagents, see : a) G. Molander, B.
Rahn, D. C. Shubert, S. E. Bonde, Tetrahedron Lett.
1983, 24, 5449–5452; b) G. Cahiez, H. Avedissian, Syn-
thesis 1998, 1199–1205; c) W. Dohle, F. Kopp, G.
Cahiez, P. Knochel, Synlett 2001, 1901–1904; d) A.
Fꢃrstner, A. Leitner, M. Mendez, H. Krause, J. Am.
Chem. Soc. 2002, 124, 13856–13863; e) A. Fꢃrstner, A.
Leitner, Angew. Chem. 2002, 114, 632–635; Angew.
Chem. Int. Ed. 2002, 41, 609–612; f) A. Fꢃrstner, M.
Mendez Angew. Chem. 2003, 115, 5513–5515; Angew.
Chem. Int. Ed. 2003, 42, 5355–5357; g) A. Fꢃrstner, A.
Leitner Angew. Chem. 2003, 115, 320–323; Angew.
Chem. Int. Ed. 2003, 42, 308–311; h) M. Hocek, H.
Dvorakova J. Org. Chem. 2003, 68, 5773–5776; i) A.
Fꢃrstner, D. de Souza, L. Parra-Rapado, J. T. Jensen,
Angew. Chem. 2003, 115, 5516–5518; Angew. Chem.
Int. Ed. 2003, 42, 5358–5360; j) K. Shinokubo, K.
Oshima. Eur. J. Org. Chem. 2004, 2081–2091; k) B.
Scheiper, M. Bonnekessel, H. Krause, A. Fꢃrstner. J.
Org. Chem. 2004, 69, 3943–3949; l) G. Seidel, D. Laur-
ich, A. Fꢃrstner, J. Org. Chem. 2004, 69, 3950–3952;
m) R. Martin, A. Fꢃrstner. Angew. Chem. 2004, 116,
4045–4047; Angew. Chem. Int. Ed. 2004, 43, 3955–
3957; n) M. Nakamura, K. Matsuo, S. Ito, E. Naka-
[17] X.-F. Wu, C. Darcel, Eur. J. Org. Chem. 2009, 1144–
1147.
[18] X.-F. Wu, D. Bezier, C. Darcel, Adv. Synth. Catal 2009,
351, 367–370.
[19] X.-F. Wu, C. Vovard-Le Bray, L. Bechki, C. Darcel,
Tetrahedron 2009, doi: 10.1016/j.tet.2009.07.29>.
[20] Y. Guo, D. J. Young, T. S. A. Hor, Tetrahedron Lett.
2008, 49, 5620–5621.
[21] Following the recent correspondence from Bolm and
Buchwald (Angew Chem. Int. Ed., 2009, DOI: 10.1002/
anie.200902237) about the crucial role of copper (in
commercial FeCl3) which can be responsible for a
number of reactions alleged to be “iron-catalyzed”, we
did, as an example, the reaction of 4-bromoacetophe-
none with phenylboronic acid in the presence of
10 mol% of FeCl3 (99.99% from Aldrich) in our stan-
dard conditions which led to a complete conversion
and only to the product resulting from the cross-cou-
pling reaction. Furthermore, when 1 mol% of Cu2O
was added to FeCl3 99.99%, even if the conversion was
also complete, a mixture of products resulting of the
cross-coupling (87%) and from the homocoupling of
boronic acid (13%) was obtained. These reactions show
clearly that iron is the catalyst for this Suzuki cross-
coupling reaction.
1736
asc.wiley-vch.de
ꢁ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2009, 351, 1732 – 1736