Iron-mediated direct arylation of unactivated arenes in air

Article abstract of DOI:10.1002/ejoc.201301620

Biaryls are a common motif in both natural and synthetic chemicals. Several methods have recently been reported for the preparation of these compounds using direct arylation catalyzed by iron, other base metals, or transition-metal-free systems. To date, these methods have all required inert and/or forcing conditions, which limited their application in routine organic synthesis. In this article we report a protocol for direct arylation using a convenient FeCl₃/1,10-phenanthroline system as precatalyst. The reaction proceeds under mild conditions (100 °C), under air, and with non-distilled solvent. A simple, environmentally benign catalytic system based on iron trichloride and phenanthroline has been developed for the direct arylation of unactivated arenes with aryl halides under air. Copyright

Full text of DOI:10.1002/ejoc.201301620

Job/Unit: O31620
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Date: 12-05-14 11:32:47
Pages: 7
FULL PAPER
DOI: 10.1002/ejoc.201301620
Iron-Mediated Direct Arylation of Unactivated Arenes in Air
[a]
[a]
[a]
Yuxing Huang, Marc-Etienne Moret, and Robertus J. M. Klein Gebbink*
Keywords: Synthetic methods / Cross-coupling / Arenes / Biaryls / Iron / Aryl halides
Biaryls are a common motif in both natural and synthetic
chemicals. Several methods have recently been reported for
the preparation of these compounds using direct arylation
catalyzed by iron, other base metals, or transition-metal-free
systems. To date, these methods have all required inert and/
or forcing conditions, which limited their application in rou-
tine organic synthesis. In this article we report a protocol for
direct arylation using a convenient FeCl /1,10-phenanthrol-
3
ine system as precatalyst. The reaction proceeds under mild
conditions (100 °C), under air, and with non-distilled solvent.
Introduction
and efficient protocols. We report a catalytic system based
on FeCl , 1,10-phenanthroline, and KOtBu, that mediates
3
Efficient routes for the synthesis of biaryl compounds are
targets of prime importance for organic chemists due to the
ubiquity of these moieties in both natural and synthetic
the direct arylation of benzene with a range of aryl halides.
The reaction proceeds under mild conditions under air and
uses nondistilled solvents as the reaction medium, whereas
the previously reported systems generally require strictly in-
[
1]
chemicals. The last decades have witnessed the develop-
ment of a plethora of strategies for biaryl synthesis relying
for the most part on the cross-coupling of aryl halides with
[
10]
ert and/or forcing conditions.
Importantly, air tolerance
is lost in the absence of iron, demonstrating a practical ad-
vantage of iron catalysis.
various aromatic nucleophiles catalyzed by transition met-
als.[2] Following an effort to minimize environmental impact
in terms of waste generation and toxic metal consumption,
catalytic direct arylation of unactivated arenes has emerged
as an environmentally benign alternative toward the synthe-
sis of biaryls. So far, most of the successful applications of
these reactions still rely on the use of precious metals.
Very recently, promising alternative systems combining a for the direct arylation of iodoarenes, we reasoned that a
Results and Discussion
Inspired by the report by Charette that Fe(OAc)
bathophenanthroline constitute an efficient catalytic system
and
2
[
3–6]
[
7]
chelating N-donor ligand, a strong base, and a source of more practical system could be achieved by using a non-
iron, have been reported.[
7–9]
Although the mechanisms for air-sensitive iron(III) source such as FeCl combined with
3
these reactions are not yet fully understood, most of the simple 1,10-phenanthroline as a ligand. The direct arylation
experimental evidence points to a radical pathway involving of 4-iodoanisole with benzene was chosen as a model reac-
attack of an aryl radical on benzene (or other nonfunction- tion in this study (Table 1). In a first set of experiments
alized arene) as the key step. The utility of iron and other (entries 1–4), we investigated the activity of catalytic sys-
transition metals for this class of reactions is currently un- tems generated in situ from FeCl , 1,10-phenanthroline, and
3
der scrutiny, and related systems that do not use a transition KOtBu. The reactions were performed under ambient at-
metal have been found to effectively mediate the direct aryl- mosphere in a closed vessel and with nondistilled benzene
[
10]
ation of arenes. Shi and Hayashi both reported arylation as both substrate and solvent. Encouragingly, some activity
of benzene with aryl halides in the presence of alkali metal was observed for the FeCl /1,10-phenanthroline systems.
tert-butoxide (KOtBu or NaOtBu) and catalytic amounts of Elevating the temperature and the ligand/metal ratio was
,10-phenanthroline and its derivatives, and Lei reported found to lead to higher product yields, with a maximal yield
performing the arylation reaction with N,NЈ-dimethyleth- of 32% for a 3:1 ligand/metal ratio at 100 °C.
3
1
ane-1,2-diamine and KOtBu.[
In the present study, we reinvestigated the iron-catalyzed these in situ runs might be attributed to the low solubility
procedures with the aim of developing operationally simple of FeCl in benzene hampering complex formation. There-
11–13]
We hypothesized that the rather low activity found in
3
fore, we opted to perform the complexation reaction in a
different solvent prior to catalysis. Mixing ethanolic solu-
[
a] Organic Chemistry & Catalysis, Debye Institute for
Nanomaterials Science, Faculty of Science, Utrecht University,
Universiteitsweg 99, 3584 CG Utrecht, The Netherlands
E-mail: r.j.m.kleingebbink@uu.nl
tions of FeCl with 1,10-phenanthroline (2 equiv.) yielded
3
an orange precipitate that was isolated by centrifugation
and dried in vacuo. Elemental analysis (C, 50.85; H, 4.11;
N, 8.73) and inductively coupled plasma optical emission
www.uu.nl/science/occ
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301620.
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Y. Huang, M.-E. Moret, R. J. M. Klein Gebbink
FULL PAPER
Table 1. Screening of several iron-based catalysts in the direct aryl- as well as for aryl iodides bearing electron-rich substituents
ation of benzene with 4-iodoanisole.[
a]
were good (entries 1–3, 8, and 10) to moderate (entries 4, 5,
7
2
, and 12). The lower yields observed for 2-iodotoluene and
-iodo-1,3-dimethylbenzene are tentatively attributed to the
effects of steric hindrance (entries 4 and 6), but the reason
for the moderate yields of the reactions reported in entries
Entry [Fe] [mol-%]
Ligand [mol-%] Yield [%][b]
5
and 7 is not fully understood. Interestingly, although re-
[
c]
1
2
3
4
5
6
7
8
FeCl
FeCl
FeCl
FeCl
[Fe(bipy)
Fe/phen (10)
Fe(tpa)Cl (10)
Fe(OAc) (5)
3
3
3
3
(10)
(10)
(10)
(10)
phen (20)
phen (30)
phen (20)
phen (30)
16
27
25
32
Ͻ1
garded as sterically hindered, 2-iodoanisole afforded 77%
isolated yield, compared with 30% for 2-iodotoluene (en-
tries 10 vs. 4). This can be rationalized by the fact that a
methoxy group is less bulky and more electron-donating
[
c]
2
Cl
2
]Cl (10)
–
–
–
[
d,e]
96 (95) (64)[g] than a methyl group. For 3-iodoanisole, both cross-coupling
[f]
3
84
and etherification products (1-methoxy-3-phenyl-, 1-tert-
butoxy-3-methoxy- and 1-tert-butoxy-4-methoxy-benzene)
bathophen (10) Ͻ1 (91)[
h]
2
[
a] Reaction conditions: 4-iodoanisole (0.5 mmol), KOtBu were obtained in irreproducible ratios, in contrast to Cha-
(
1.5 mmol), benzene (50 mmol), catalyst, 100 °C, 24 h. [b] Yields
rette’s observation of a clean cross-coupling reaction for
were determined by GC analysis using pentadecane as internal
standard. [c] Reactions were carried out at 80 °C. [d] Fe/phen desig-
nates the precipitate isolated after mixing ethanolic solutions of
[7]
this substrate (entry 9). The etherification products likely
[
16,17]
result from a competing benzyne pathway.
Despite the
FeCl
based on Fe. [f] Reaction carried out by heating to reflux for 30 h.
g] Reaction carried out in water-saturated benzene (water content
90 ppm). [h] Reaction was carried out in distilled benzene under
for 20 h.
3
and 1,10-phenanthroline in a 1:2 ratio. [e] Catalyst loading fact that the amino group is a strongly electron-donating
group, the use of 4-iodoaniline in the reaction afforded an
isolated yield of only 7% (entry 13); N,N-dimethyl-4-
iodoanisole gave 25% isolated yield (entry 14). Possible ex-
planations for this observation include coordination of the
amino moiety to iron to generate low-activity species and/or
[
7
N
2
spectrometry (ICP-OES) analysis (Fe, 11.03) of this solid the existence of competitive pathways involving N-centered
could not be reduced to a simple stoichiometry, but the N/ radicals.
Fe molar ratio of 3.2 indicated an approximate phen-
anthroline/Fe ratio of 1.6. This material will be designated strates, but still afforded moderate yields for 4-iodobenzo-
by “Fe/phen” hereon. nitrile, 4Ј-iodoacetophenone, ethyl 4-iodobenzoate, and 1-
The reaction was less efficient for electron-deficient sub-
Gratifyingly, we found out that Fe/phen is an excellent chloro-4-iodobenzene (Table 2, entries 15, 16, 17, 20). For
precatalyst for the direct arylation of 4-iodoanisole with the two latter substrates, byproducts were detected: 4Ј-
benzene, affording a GC product yield of 96%, outper- iodoacetophenone gave small amounts of 1-(4-phen-
forming the well-defined complexes Fe(tpa)Cl [tpa = tris- ylphenyl)-2-(4-acetylphenyl)ethanone (3pЈ), which were de-
3
(
2
picolyl)amine] (84% yield) and [Fe(bipy) Cl ]Cl (bipy = tected by GC–MS and identified by comparison with a
2 2
,2Ј-bipyridine) (Ͻ1% yield).[
14,15]
The Fe/phen system dis- sample isolated from the reaction of 4Ј-bromoacetophenone
plays good tolerance towards air and moisture, but requires with benzene (see below), and 1-chloro-4-iodobenzene gave
neither oxygen nor water: performing the reaction under 14% 1,4-diphenylbenzene (3tЈ). The mechanistic implica-
inert conditions afforded an identical yield of 96%. To ver- tions of these byproducts are discussed below. 1-(Trifluoro-
ify that the apparent air tolerance does not originate from methyl)-4-iodobenzene afforded 12% 4-(trifluoromethyl)bi-
initial consumption of the finite amount of oxygen con- phenyl (entry 19). 1-Iodo-4-nitrobenzene was fully con-
tained in a closed vessel, the reaction was also performed sumed during the reaction but provided an intractable mix-
in an open vessel under reflux conditions. The reaction time ture of products (entry 18), which can be attributed to the
was longer, as expected from the lower temperature, but a susceptibility of the nitro group to attack by radical inter-
[
18]
yield of 95% was obtained after 30 h. For practical reasons mediates.
we carried out further reactions in closed pressure tubes product (entry 11), whereas 2-iodonaphthalene afforded an
unless stated otherwise). In water-saturated benzene (ca. isolated yield of the desired product in 59% (entry 12). Fi-
90 ppm H O), the yield was somewhat decreased (64%), nally, 2-iodopyridine and 3-iodopyridine afforded 59 and
1-Iodonaphthalene gave 48% of the arylated
(
7
2
and the remaining organic fraction contained only starting 60% isolated yields of the respective product (entries 21 and
material (39% by GC), suggesting that the low yield is due 22).
to catalyst deactivation rather than side reactions involving
To explore further the scope of our catalytic system, we
water. For comparison, we reproduced the results of Cha- investigated the reactivity of other aryl halides and arenes
rette by using the Fe(OAc) /bathophenanthroline system (Table 3). Next to benzene, three substituted arenes were
2
under inert conditions (91% GC yield) but found no ac- tested as coupling partners for aryl iodides. The reaction of
tivity with this system in nondistilled benzene under air.
toluene and anisole with 4-iodoanisole and 4-iodotoluene,
With the optimized conditions in hand, we explored the respectively, gave a mixture of regioisomers with a slight
scope of our method by using a range of aryl iodides as preference for ortho-substitution, as is commonly observed
[
7,13]
substrates for the direct arylation of benzene. The results in related radical reactions (entries 1 and 2).
The ame-
are summarized in Table 2, yields obtained for iodobenzene nability of chloroarenes to coupling was tested in the reac-
2
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Iron-Mediated Direct Arylation of Unactivated Arenes in Air
Table 2. Substrate scope with aryl iodides.[a]
[
a] Reaction conditions: 1 (0.5 mmol), KOtBu (1.5 mmol), benzene (50 mmol), Fe/phen (10 mol-% Fe), 100 °C, 24 h. Isolated yields are
given. [b] Product yields were not reproducible (see text).
tion of 4-iodoanisole with 4-chlorotoluene, which afforded for which we observed the cross-coupling and etherification
a moderate yield (32%) of a ca. 1:1 mixture of regioisomers products (1-methoxy-3-phenyl-, 1-tert-butoxy-3-methoxy-
(entry 3).
and 1-tert-butoxy-4-methoxy-benzene) in irreproducible ra-
The coupling of aryl bromides with benzene proceeded tios, as in the case of 3-iodoanisole. A lower yield (26%)
at a higher temperature (120 °C) and required longer reac- was also obtained in the coupling of 4-bromoacetophenone
tion time (48 h) than that of aryl iodides, while no activity with benzene (entry 7), for which a byproduct was isolated
was found for aryl chlorides (Table 3, entry 8), as expected in 11% yield and identified as 1-(4-phenylphenyl)-2-(4-acet-
from the corresponding Ar–X bond dissociation ener- ylphenyl)ethanone (3pЈ, Scheme 2; see below) by NMR and
[
19]
gies. The isolated yield of coupling product was good for IR spectroscopic analysis, and mass spectrometry.
4-bromotoluene (89%) and slightly lower for bromobenz- A series of control experiments were performed to pro-
ene (76%) (entries 4 and 5); for the latter, small amounts of vide a first insight into the mechanism of the reaction
phenyl tert-butyl ether were observed by GC–MS, suggest- (Table 4). Importantly, no reaction was observed in the ab-
ing that the reduced yield is due to a competing benzyne sence of FeCl , 1,10-phenanthroline, or both (entries 1–3),
3
pathway becoming accessible at 120 °C. This pathway is ruling out a metal-free pathway under our conditions.[12,20]
even more prevalent in the case of 4-bromoanisole (entry 6), In addition, KOtBu was found to be critical for the reac-
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Y. Huang, M.-E. Moret, R. J. M. Klein Gebbink
FULL PAPER
Table 3. Substrate scope with aryl halides and arenes.[a]
proved to be ineffective in our system (entries 7–9).[8,13] This
strongly indicates that the combination of iron, base, and
ligand is essential for the arylation under our reaction con-
ditions.
Recently, Bolm and Buchwald reported that catalytic re-
actions involving FeCl might be affected by trace amounts
3
[
21]
of other metals such as Pd or Cu.
ICP-OES analysis of
Fe/phen prepared in our laboratory revealed the presence
of ca. 12 ppm Cu, whereas no Pd was detected. To exclude
the possibility that our reaction might be catalyzed by trace
amounts of copper, we performed control experiments with
Cu salts (Table 5). Copper salts alone were ineffective to
catalyze the arylation (entries 1 and 2), and the combina-
tion of Fe and Cu proved to be detrimental, with 1 and 7%
yields for CuCl and CuCl, respectively (entries 3 and 4).
2
We also performed the reaction of 4-idoanisole and benzene
with sublimed KOtBu (see the Supporting Information for
ICP-MS trace analysis) and found that the obtained yield
of 87% was only slightly lower than that obtained with the
technical grade KOtBu (96%), showing that catalytic ac-
tivity does not arise from trace impurities in the base.
Table 5. Control experiments with Cu salts.[a]
Entry
Salt
Yield [%][b]
[
a] Reaction conditions: 1 (0.5 mmol), KOtBu (1.5 mmol), 2
1
2
3
4
CuCl
CuCl
2
9
2
1
7
(
50 mmol), Fe/phen (10 mol-% Fe), 100 °C, 24 h for aryl iodides;
or 120 °C, 48 h for aryl bromides and aryl chloride. Isolated yields
are given. [b] NMR yield with 1,4-dioxane as internal standard.
FeCl
FeCl
3
+ CuCl
+ CuCl
2
3
[
c] Product yields for this reaction were not reproducible (see text).
[a] Reaction conditions: 4-iodoanisole (0.5 mmol), KOtBu
(
1.5 mmol), benzene (50 mmol), salt(s) (0.05 mmol), 1,10-phen-
anthroline (0.1 mmol), 100 °C, 24 h. [b] Yield determined by GC
analysis using pentadecane as internal standard.
tion, and weaker inorganic bases such as K PO , K CO ,
3
4
2
3
and KOH were found to be ineffective (entries 4–6). Other
bases that are employed in other catalytic systems to cata-
lyze direct arylation, such as NaOtBu, LiHMDS, also
The inclusion of radical scavengers such as Galvinoxyl
or 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) was
found to completely shut down the arylation of 4-iodo-
anisole with benzene. In addition, a competition experiment
with C H and C D afforded only a small kinetic isotope
Table 4. Control experiments.[a]
6
6
6
6
effect of 1.12. Monitoring the direct arylation between 4-
iodoanisole and benzene revealed a long induction period
(ca. 7 h), after which the reaction was rapid (see the Sup-
porting Information). The irreproducible branching ratio
between the arylation and benzyne pathways in the reaction
of 3-iodoanisole and 4-bromoanisole, in addition to the
long induction period, suggests complex kinetics that are
typical for radical chain reactions.
These observations are consistent with the radical chain
mechanism depicted in Scheme 1. The fact that the reaction
Entry [Fe]
Ligand
Base
Yield [%][b]
1
2
3
4
5
6
7
8
9
–
phen
–
–
phen
phen
phen
–
–
–
KOtBu
KOtBu
KOtBu
Ͻ1
Ͻ1
Ͻ1
Ͻ1
Ͻ1
Ͻ1
0
FeCl
–
FeCl
FeCl
FeCl
Fe/phen
Fe/phen
Fe/phen
3
[22–24]
3
3
3
K
3
PO
KOH
CO
4
K
2
3
NaOtBu
LiHMDS
KHMDS
requires both FeCl and the phenanthroline ligand suggests
3
7
0
that the whole reaction is initiated by an inner-sphere elec-
tron transfer between an iron complex and the aryl halide,
in which the iron catalyst abstracts a halogen atom from
the substrate to give an aryl radical. The C–C bond-forming
step then consists of attack of the aryl radical on the arene
to form an intermediate cyclohexadienyl radical, as earlier
[
a] Reaction conditions: 4-iodoanisole (0.5 mmol), base (1.5 mmol),
benzene (50 mmol), FeCl (0.05 mmol), 1,10-phenanthroline
0.1 mmol) if used; or Fe/phen (0.05 mmol), 100 °C, 24 h. [b] Yield
3
(
determined by GC analysis using pentadecane as internal standard.
HMDS = hexamethyldisilazane.
4
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Iron-Mediated Direct Arylation of Unactivated Arenes in Air
proposed by Charette, Lei, and Shi.[7–9] Two additional This observation provides evidence for the involvement of
propagation steps follow: proton transfer to KOtBu to form a radical anion intermediate in the propagation steps
[
25]
a biphenyl radical anion, followed by electron-transfer to (Scheme 3).
Previously reported iron-based and transi-
the aryl halide to yield the arylated product and generate a tion-metal-free catalytic systems have also been shown to
[
8,11–13]
short-lived radical anion, which fragments into a new aryl afford 3tЈ in varying amounts,
suggesting that the bi-
radical and a halide anion.[
26]
aryl radical anion is a common intermediate to this family
[
26]
of reactions,
and that the rate of its oxidation can be
tuned by modifying the system. These interesting observa-
tions have prompted us to investigate further the mecha-
nism of the present catalytic system and the nature of the
precatalyst. Such activities are ongoing in our laboratory.
Scheme 3. Competition of intermolecular electron transfer and hal-
ide extrusion.
Scheme 1. Possible radical chain mechanism for Fe/phen-catalyzed
direct arylations.
The proposed mechanism is also consistent with the by-
products that have been observed in some of the reactions.
The formation of 3pЈ from the reaction of 4-haloaceto-
phenones with benzene likely arises from a competing reac-
tion of the 4-acetylphenyl radical intermediate with enolate
A derived from substrates 1p or 1z to generate a transient
ketyl radical B, as has been postulated as the key propaga-
tion step in SRN1 substitution of aryl halides with enolates
Conclusions
We have demonstrated that a preformed Fe/phen com-
plex catalyzes the direct C–H arylation of arenes with aryl
halides. This precatalyst can be conveniently prepared on a
large scale from an inexpensive and readily available iron
source (FeCl ) and ligand (1,10-phenanthroline) and can be
3
[
16]
(Scheme 2).
Intermediate B subsequently loses a halide
stored on the bench without particular precautions; no de-
crease in activity was observed after 6 months. Its use allevi-
ates the requirement for anhydrous solvents and inert atmo-
sphere of the previously reported iron-based and metal-free
systems, resulting in a broadly applicable, environmentally
benign protocol for benzene C–H arylation.
ion to form aryl radical C en route to 3pЈ.
Furthermore, the reaction of 1-chloro-4-iodobenzene
with benzene yields 14% 1,4-diphenylbenzene (3tЈ) in ad-
dition to the major product 4-chlorobiphenyl (3t, 67%).
Experimental Section
General: All reagents were purchased from commercial suppliers
1
and used without further purification. H NMR (400 MHz) chemi-
cal shifts were measured relative to CDCl
3
as the internal reference
: δ = 7.24 ppm). C NMR (100 MHz) chemical shifts were
given using CDCl as the internal standard (CDCl : δ = 77.0 ppm).
1
3
(CDCl
3
3
3
The following abbreviations were used to designate the multiplicit-
ies: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet.
GC analyses were performed using pentadecane as internal stan-
dard.
Preparation of Fe/phen: A solution of FeCl
in ethanol (30 mL) was added dropwise to a stirred solution of
,10-phenanthroline (0.913 g, 5.00 mmol) in the same solvent
60 mL). During the addition, the solution became an orange-yel-
3
(0.418 g, 2.50 mmol)
1
(
low suspension that was subsequently stirred for 1 h. The resulting
solid was collected through centrifugation, and dried under vac-
uum for 20 min, to give a yellowish powder. Anal. found C 50.85,
Scheme 2. Proposed mechanism for the formation of 1-(4-phen-
ylphenyl)-2-(4-acetylphenyl)ethanone.
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Y. Huang, M.-E. Moret, R. J. M. Klein Gebbink
FULL PAPER
H 4.11, N 8.73. ICP-OES: Fe 11.03%; Cu 12.39 ppm; Pd
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[
Ͻ0.0162 ppm. FTIR (ATR): ν˜ = 3048, 1586, 1516, 1425, 1341,
–1
3138; Angew. Chem. 2007, 119, 3196.
1
223, 1146, 1105, 1050, 852, 782, 723, 647 cm .
[
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General Procedure for the Synthesis of Biaryl Products: In a glove
box under a nitrogen atmosphere, KOtBu (1.5 mmol, 3 equiv.) was
added to a 15 mL Ace pressure tube equipped with a stir bar. The
tube was transferred out of the glove box and the cap was un-
screwed. To the open tube, aryl iodide (0.5 mmol, 1 equiv.) and Fe/
phen (10 mol-% based on Fe) were added. Reagent grade benzene
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(50 mmol, 100 equiv.) was added to the tube, the screw cap of the
tube was closed, and the reaction mixture was stirred vigorously at
room temperature for 5 min to form a dark-grey suspension. The
reaction was then heated at 100 °C for 24 h while stirring. Different
workup procedures were used for aryl iodides and aryl bromides
as follows. For aryl iodides, following cooling, the solution was
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2 2
filtered through a silica pad. The pad was then rinsed with CH Cl /
hexanes (1:1 v/v, 100 mL). The combined solution was concen-
trated and the crude mixture was purified by column chromatog-
raphy to afford the biaryl products. For aryl bromides, following
cooling, the reaction was quenched with water and extracted with
CH Cl (3ϫ15 mL). The combined solution was concentrated and
2 2
the crude mixture was purified by column chromatography to af-
ford the biaryl products.
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Received: October 29, 2013
9
Acknowledgments
[
2
Y. H. is grateful to the China Scholarship Council (CSC) for a doc-
toral scholarship. M.-E. M. and R. J. M. K. G. acknowledge the
National Research School Combination Catalysis (NRSC-C) for
financial support. The authors are thankful to Ton Zalm and Helen
de Waard of the Petrology group, Faculty of Geosciences, Utrecht
University for ICP-OES analysis.
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Published Online: ᭿
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www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O31620
/KAP1
Date: 12-05-14 11:32:47
Pages: 7
Iron-Mediated Direct Arylation of Unactivated Arenes in Air
Cross-Coupling with Iron
Y. Huang, M.-E. Moret,
R. J. M. Klein Gebbink* ................... 1–7
Iron-Mediated Direct Arylation of Unacti-
vated Arenes in Air
A simple, environmentally benign catalytic
system based on iron trichloride and phen-
anthroline has been developed for the
direct arylation of unactivated arenes with
aryl halides under air.
Keywords: Synthetic methods / Cross-cou-
pling / Arenes / Biaryls / Iron / Aryl halides
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7