Iron-catalyzed quick homocoupling reaction of aryl or alkynyl Grignard reagents using a phosphonium ionic liquid solvent system

Article abstract of DOI:10.1002/hc.20696

The iron-catalyzed homocoupling reaction of aryl Grignard reagent was completed very quickly when the reaction was carried out in a phosphonium salt ionic liquid solvent system at 0°C for 5 min. Using a similar reaction system, the first example of the iron-catalyzed homocoupling reaction of alkynyl Grignard reagents has also been accomplished using the ionic liquid technology.

Full text of DOI:10.1002/hc.20696

Heteroatom Chemistry
Volume 22, Number 3/4, 2011
Iron-Catalyzed Quick Homocoupling Reaction
of Aryl or Alkynyl Grignard Reagents Using a
Phosphonium Ionic Liquid Solvent System
Keisuke Kude, Shuichi Hayase, Motoi Kawatsura,
and Toshiyuki Itoh
Department of Chemistry and Biotechnology, Graduate School of Engineering,
Tottori University, Tottori 680-8552, Japan
Received 26 August 2010; revised 3 November 2010
thiophenes [8] or pyrroles [9], and the enantioselec-
ABSTRACT: The iron-catalyzed homocoupling re-
tive Michael addition of thiols to α, β-unsaturated
action of aryl Grignard reagent was completed very
carbonyl compounds [10].
Excellent examples have also been reported
recently by two groups on the iron-catalyzed
biaryl-coupling reaction, including Hayashi [11]
and Cahiez [12] independently. The iron-catalyzed
homo- or heterocoupling reaction of aryl Grignard
reagents has been recognized as an easy and effi-
cient access to the production of symmetrical di- or
polyaromatic compounds [13].
quickly when the reaction was carried out in a phos-
phonium salt ionic liquid solvent system at 0◦C for
5 min. Using a similar reaction system, the first ex-
ample of the iron-catalyzed homocoupling reaction
of alkynyl Grignard reagents has also been accom-
ꢀ
C
plished using the ionic liquid technology.
2011 Wi-
ley Periodicals, Inc. Heteroatom Chem 22:397–404, 2011;
View this article online at wileyonlinelibrary.com. DOI
10.1002/hc.20696
Ionic liquids (ILs) are now widely recognized
as suitable for use in organic reactions and provide
possibilities for improvement in the control of
product distribution, enhanced reactivity, ease of
product recovery, catalyst immobilization, and
recycling. However, ILs have been considered
inappropriate for strong base-mediated reactions.
Recently, several examples have been reported,
which show the possibility of using these liquids as
reaction media for strong base-mediated reactions
such as the Grignard reaction [14–16]. We also
succeeded in designing an IL that is appropri-
ate for this reaction; introduction of alkyl ether
moiety on the side arm of phosphonium salt was
quite effective in improving the capability of the
phosphonium salt ILs as solvent for the Grignard
INTRODUCTION
Iron is recognized as an economical and pollution-
free metal source, and various types of iron metal-
catalyzed organic transformations have been re-
ported during the past decades [1]. We were also
fascinated by the possibility of iron-catalyzed re-
actions and developed several of them, that is the
intramolecular cyclization of cyclopropanedithioac-
etals [2], the [2 + 2]-cycloaddition of trans-anethol
[3], the [2 + 3]-type cycloaddition of styrene deriva-
tives with 1,4-benzoquinone [4], the 1,4-addition of
β-ketoesters to vinylketones [5], the alkylation of in-
doles and pyrrole [6,7], the Nazaov cyclization of
reaction;
methoxyethyl(tri-n-butyl)phosphonium
bis(trifluoromethanesulfonyl)imide ([P444ME][NTf2])
was thus synthesized [17].
Clyburne and his colleagues reported that
an alkyl Grignard reagent was reacted with
Dedicated to Professor Kin-ya Akiba on the occasion of his 75th
birthday.
Correspondence to: T. Itoh; e-mail: titoh@chem.tottori-u.ac.jp.
c
ꢀ
2011 Wiley Periodicals, Inc.
397

398 Kude et al.
ate in ILs solvent, but the form was unstable in ILs
due to their noncoordinating property; and the reac-
tion was thus significantly accelerated [19]. In fact,
we found that a charge-separated transition path-
way was involved in our the iron(III) salt-mediated
[2 + 3]-type cycloaddition reaction by observing pos-
itive solvatochromism during the course of the re-
action [4c]. Hence, we hypothesized that acceler-
ation of iron(III) chloride-mediated homocoupling
of the aryl Grignard reagent might be expected if
the reactions were conducted in ILs because both
electron transfer and transmetallation might take
place easily in the solvent. On the basis of this work-
ing hypothesis, we tested the iron-catalyzed homo-
coupling reaction of the aryl Grignard reagent de-
veloped by Hayashi [11b] in our phosphonium IL
([P444ME][NTf2]) [17] as a solvent and found that a
desired homocoupling reaction did, in fact, proceed
very quickly.
Conventional organic synthesis generally appre-
ciates high productivity and selectivity. However, re-
cently, the development of quick reactions has also
become very important in many stages of organic
synthesis. For example, the criteria for synthetic ef-
ficiency in an in vivo PET (positron emission tomog-
raphy) study using 11C or 18F as a positron nuclide are
different. The investigation requires a rapid chemi-
cal reaction for the incorporation of these atoms into
bioactive organic compounds, because of the time
limitation of the short-lived positron emitter (half-
life of 11C is 20.3 min and that of 18F is 110 min)
[20].
In this article, we report the results of iron-
catalyzed types of the quick homocoupling reac-
tion of aryl Grignard reagents or alkylnyl Grignard
reagents in the IL solvent system [21].
FIGURE 1 Working hypothesis of iron-catalyzed quick ho-
mocoupling of aryl Grignard reagent in the IL solvent system.
RESULTS AND DISCUSSION
benzoquinone to provide not the simple addition
product, but the corresponding coupling product
with hydroquinone through a single electron trans-
fer and transmetallation process [18].
Homocoupling Reaction of Aryl
Grignard Reagents
We tested the reaction of phenyl magnesium bro-
mide (PhMgBr) in the presence of 1 mol% of iron(III)
chloride using 1,2-dichloroethane as an oxidant (Eq.
(1)): The desired coupling reaction of PhMgBr (1a)
was completed in less than 5 min at 0◦C, and
biaryl 2a was obtained in excellent yield in a pure
[P444ME][NTf2] solvent. Since PhMgBr was prepared
in a tetrahydrofurane (THF) solvent, we initially pre-
pared an IL solution of PhMgBr by removing this
solvent under reduced pressure at 0◦C and then mix-
ing it with FeCl3 and the oxidant. However, we soon
found that we could bypass such a nuisance process
because no significant reduction in the reaction rate
Hayashi and Nagano proposed the reaction
mechanism for the iron(III) chloride-mediated ho-
mocoupling reaction of the aryl Grignard reaction:
The key step might be a reduction step of iron(III)
cation by an aryl Grignard reagent or a transmetal-
lation step on the iron as illustrated in Fig. 1 [11b].
We previously reported that iron(III)-catalyzed
[2 + 3]-type cycloaddition of trans-anethol with ben-
zoquinone was drastically accelerated when the re-
action was changed by acetonitrile to an IL [4].
Fuchigami and co-workers reported that formation
of a charge-separated transition state did acceler-
Heteroatom Chemistry DOI 10.1002/hc

Iron-Catalyzed Quick Homocoupling Reaction of Aryl or Alkynyl Grignard Reagents 399
TABLE 1 Iron-Catalyzed Homocoupling of Aryl Grignard Reagents 1
Entry
Substrate 1
Solventa
Temperature (◦C)
Time (min)
Product 2
Yield (%)b
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1b
1c
1d
1e
1f
[P444ME][NTf2]
[P4441][NTf2]
[bdmim][NTf2]
THF
0
0
0
40
0
0
5
5
5
60
55
5
5
5
30
5
5
2a
2a
2a
2a
2a
2a
2b
2c
2d
2e
2f
100
99
90
90
2
100
99
86
18d
97
94
99
91
51
HMPA
[P444ME][NTf2]c
[P444ME][NTf2]
[P444ME][NTf2]
[P444ME][NTf2]
[P444ME][NTf2]
[P444ME][NTf2]
[P444ME][NTf2]
[P444ME][NTf2]
[P444ME][NTf2]
0
25
25
0
0
0
9
10
11
12
13
14
1g
1h
1i
5
10
10
2g
2h
2i
25
25
aThe reaction was carried out in a mixed solvent (IL and THF = 5:1). See details in the Experimental section.
bIsolated yield.
cResult using recycled IL (five times).
d1,3,5-Trimethylbenzene was detected by GC-MS analysis as a major by-product.
1a: R H, 1b: R 4-Me, 1c: R 2-Me, 1d: R 2,4,6-Me, 1e: R 4-MeO, 1f: R 2-MeO, 1g: R 4-F, 1h: 2-ThienylMgBr, 1i: BenzylMgBr
was recorded even when the reaction was conducted
in a mixed solvent of [P444ME][NTf2] and THF (5:1)
(entry 1). But, it should be emphasized that the pres-
ence of the IL [P444ME][NTf2] as a major component
of the mixed solvent was essential for accelerating
the reaction; it required at least 60 min to complete
the reaction, even when the reaction was conducted
in a pure THF solvent system at 40◦C. Optimization
of the ratio of ionic liquid showed that the presence
of this liquid at more than ca. 70–80% (v/v) versus
THF caused no drop in the reaction rate. Therefore,
we conducted further experiments using a mixed sol-
vent of IL and THF (5:1) and the results are summa-
rized in Table 1.
[bdmim][NTf2], although a slightly reduced yield of
2a (90%) was recorded (entry 3). On the contrary, it
took at least 1 h under reflux conditions when the
reaction was carried out in pure THF, although the
chemical yield of 2a was excellent (90%; entry 4).
Only 2% of 2a was obtained when hexamethylphos-
phoramide (HMPA) was used as the solvent (entry
5). A very rapid homocoupling reaction of the aryl
Grignard reagent has thus been accomplished us-
ing the IL solvent system. One of the benefits of
using IL as a solvent for organic reactions is that
purification of ILs is easily accomplished by a sim-
ple method, and it can be used repeatedly. In fact,
we obtained the desired product 2a in quantitative
yield even when the reaction was conducted in the
recycled [P444ME][NTf2] (five times; entry 6). Further-
more, the present oxidative homocoupling could be
readily scaled up to the reaction of 15.0 mmol of
the Grignard reagent 1a using 1 mol% of the FeCl3
catalyst, which gave 99% yield (1.14 g) of biaryl 2a
without any by-products.
The electric property of the substituent on the
benzene ring had no influence on the chemical
yield of the products. The desired coupling prod-
ucts 2b or 2e were obtained in almost quantita-
tive yields for substrate 1b (entry 7) or 1e (entry
10), which have the electron-donating methyl or
methoxy group, respectively. Substrate 1g that has
electron-withdrawing fluorine on the phenyl group
also provided the coupling product 2g in 99% yield
(entry 12).
Although 2a was also obtained in excellent yield
in the mixed solvent of [P4441][NTf2] and THF (5:1)
(entry 2), isolation of the product was troublesome
because [P4441][NTf2] was very soluble in many or-
ganic solvents, such as hexane and ether. On the
other hand, easy extraction was accomplished us-
ing [P444ME][NTf2] or [bdmim][NTf2] as a solvent.
The coupling reaction proceeded very rapidly in
On the other hand, steric bulkiness of the sub-
stituent affected the reaction greatly. It was found
Heteroatom Chemistry DOI 10.1002/hc

400 Kude et al.
that 25◦C was required to complete the reaction
when o-tolyl MgBr (1c) was used as the substrate,
and the desired biaryl compound 2c was obtained
in 86% yield (entry 8), although the acceleration
obtained still compared to that in the ether sol-
vent because 12 h under reflux conditions was re-
quired to complete the same reaction when the re-
action was carried out with ether as the solvent
[11b]. Introduction of an electron-donating group
is effective to improve the reaction rate, and a very
rapid coupling was again accomplished when o-
methoxyphenyl MgBr (1f) was employed for the re-
action (entry 11).
1c, because it is expected that both reduction and
transmetallation take place more easily using the
electron-rich Grignard reagent. Since the reaction
mixture turned black after addition of the Grignard
reagent, iron nanoparticles may be produced under
the reaction conditions and this may contribute to
completing the coupling reaction. To the best of our
knowledge, there is no report of the production of
iron (0) nanoparticles in ILs. However, the forma-
tion of several transition metal nanoparticles in ILs
has been reported in [22]. We have not yet, how-
ever, succeeded in obtaining any evidence for this
possibility.
The reaction of the 2,4,6-trimethylphenyl Grig-
nard reagent (1d) proceeded very slowly, and no re-
action took place at 0◦C; homocoupling product 2d
was obtained in 18% yield when the reaction was
performed at 25◦C for 30 min (entry 9). It was con-
firmed that 1,3,5-trimethylbenezene was formed by
GC-MS analysis as a major by-product of this reac-
tion. Unfortunately, no improvement in the chemical
yield of 2d was achieved when the reaction was car-
ried out at more than 40◦C; the reaction resulted only
in production of 1,3,5-trimethylbenzene because IL
[P444ME][NTf2] has an acidic proton. Furthermore, it
was found that the Grignard reagent gradually lost
its activity when the reaction was prolonged more
than 30 min at room temperature (rt). Therefore, the
highest temperature of the present reaction might be
below 40◦C and the reaction should be completed in
30 min.
It was applicable to use the reaction for a thionyl
Grignard reagent 1h and benzyl Grignard reagent
1i, and the desired coupling product 2h and 2i was
obtained in 91% and 51%, respectively (entries 13
and 14). Although there are several limitations, a
simple and quick homocoupling reaction of the aryl
Grignard reaction using FeCl3 a catalyst has thus
been accomplished in the phosphonium IL solvent
system.
Homocoupling Reaction of Alkynyl
Grignard Reagents
It is well known that the homocoupling reaction
of alkynyl Grignard reagents is catalyzed by pal-
ladium [23], copper [24], or manganese [12b,25],
whereas we recognize that there is no example of
iron-catalyzed homocoupling of this reagent. We
tested the reaction using 2-phenylethynyl magne-
sium bromide (3a) as a model substrate in the pres-
ence of 1 mol% of FeCl3 as the catalyst using 1,2-
dichloroethane (DCE) or 1,2-diiodoethane (DIE) as
an oxidant in THF or ether. However, as anticipated,
no desired product was obtained when the reaction
was conducted in these solvents (entry 1, Table 2).
To our delight, we discovered that the desired cou-
pling product was obtained in 30% yield when the
reaction was carried out in a mixed solvent of IL and
THF using DCE as an oxidant (entry 2). Like the re-
action of aryl Grignard reagents, IL was essential to
realize the reaction because no desired product 4a
was obtained when the reaction was carried out in
a pure THF or Et2O solvent system (entry 1). After
attempting the optimization of the ratio of IL and
THF, we succeeded in obtaining 4a in a mixed sol-
vent of IL and THF that included at least ca. 60% (v/v)
of [P444ME][NTf2]. Furthermore, a choice of the oxi-
dant was also important; chemical yield of 4a was in-
creased to 55% (entry 3) when DIE was used instead
of DCE (entry 2) as an oxidant. Among several ox-
idants such as iodomethane, 1,2-dichloroisobutane,
1,2-dibromoethane, and dry air, DIE gave the best
result. Furthermore, a reduced chemical yield (40%)
was recorded when the reaction was carried out
in [bdmim][NTf2] and THF (2:1) (entry 4). For the
catalyst, FeCl3 gave the best result (55%) (entry 3),
and Fe(BF4)2·6H2O afforded the second best (51%)
(entry 5) whereas reduced chemical yield of the
product was recorded when Fe(ClO4)3 · nH2O (20%),
Fe(acac)3 (40%), FeCl2 (39%), FeBr2 (44%), FeI2
(44%), or Fe(acac)2 (33%) was used as the catalyst.
As mentioned before, Hayashi proposed that the
key step might be the reduction step of iron(III)
cation by the aryl Grignard reagent or a transmet-
allation step on the iron as illustrated in Fig. 1
[11b]. We assume that Hayashi’s idea might be sup-
ported by the fact that the coupling reaction of more
electron-rich 1f proceeded more rapidly than that of
Heteroatom Chemistry DOI 10.1002/hc

Iron-Catalyzed Quick Homocoupling Reaction of Aryl or Alkynyl Grignard Reagents 401
TABLE 2 Iron Salt-Catalyzed Homo Coupling of Alkynyl Grignard Reagents 3
Entry
Substrate 3
Fe Salt (1 mol%)
Oxidant
Solvent a
Product 4
Yield (%)b
1
2
3
4
5
6
7
8
9
3a
3a
3a
3a
3a
3b
3c
3d
3e
3f
FeCl3
FeCl3
FeCl3
DCE
DCE
DIE
DIE
DIE
DIE
DIE
DIE
DIE
DIE
THF or Et2O
[P444ME][NTf2]
[P444ME][NTf2]
[bdmim][NTf2]
[P444ME][NTf2]
[P444ME][NTf2]
[P444ME][NTf2]
[P444ME][NTf2]
[P444ME][NTf2]
[P444ME][NTf2]
4a
4a
4a
4a
4a
4b
4c
4d
4e
4f
0
30
55
40
51
52
80
46
37
35
FeCl3
Fe(BF4)2·6H2O
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
10
aThe reaction was carried out in a mixed solvent of IL and THF (2:1). See details in the experimental section.
bIsolated yield.
Increased addition of the amount of FeCl3 caused
a significant reduction in the yield due to forma-
tion of a large amount of polymerized compound;
4a was obtained in only 8% when the reaction was
performed in the presence of 20% of FeCl3
0◦C using only 1 mol% of economical FeCl3 as the
catalyst. We further established an iron-catalyzed
homocoupling reaction of the alkynyl Grignard re-
action using this liquid solvent system. It should
also be noted that IL was essential for realizing the
coupling reaction because no reaction took place in
a pure THF or ether solvent system. To the best
of our knowledge, this is the first example of the
iron-catalyzed homocoupling reaction of the alkynyl
Grignard reagent.
Recently, development of quick reactions has be-
come a very important task in many stages of organic
synthesis, as mentioned in the Introduction. Further
investigation of the scope and limitations of this re-
action will make it even more valuable.
On the basis of these results, we conducted the
homocoupling reaction of various types of alkynyl
Grignard reagents using DIE as an oxidant in a
mixed solvent, [P444ME][NTf2] and THF (2:1), in the
presence of 1 mol% of FeCl3 (see entries 6–10 in
Table 2). Comparing the reaction of 3b, which has
the electron-donating methoxy group on the benzene
ring (entry 6) and that of 3c, which has an electron-
withdrawing trifluoromethyl group (entry 7). Com-
pound 3c gave a better result, and diyne 4c was ob-
tained in 80% yield. This was assumed to be due
to the stable nature of 4c against the acid-catalyzed
polymerization because 4b was easily polymerized
when it was stored under atmospheric conditions.
It should be noted that the coupling product 4d or
4f was also obtained using the present reaction sys-
tem, although the chemical yields were insufficient
(entries 9 and 10).
EXPERIMENTAL
General Procedures
Reagents and solvents were purchased from com-
mon commercial sources and were used as re-
ceived or purified by distillation from appropriate
drying agents. Reactions requiring anhydrous con-
ditions were run under an atmosphere of dry ar-
gon. Wako gel C-300 and Wako gel B5F were used
for flash column chromatography and thin-layer
We have established a very rapid iron-catalyzed
homocoupling reaction of aryl and alkynyl Grignard
reagents using a phosphonium IL solvent system.
The reaction was completed in less than 5 min at
Heteroatom Chemistry DOI 10.1002/hc

402 Kude et al.
chromatography (TLC), respectively. NMR spectra
were recorded on JEOL MH-500 (500 MHz for H
Purification Method of [P444ME][NTf2]
for Recyling Use
1
and 125 MHz for 13C) spectrometers, and chem-
ical shifts are expressed in ppm downfield from
tetramethylsilane (TMS) in CDCl3 as an internal ref-
erence. IR spectra were obtained on a Shimadzu
FTIR-8000 spectrometer. GC-MS analysis was ob-
tained on a Shimadzu GCMS-QP2010 spectrome-
ter. [P444ME][NTf2] is now commercially available
from Tokyo Chemical Industry (T2564). Water con-
tent of the ionic liquids employed was determined
by a Karl Fischer moisture titrator. The values
are listed as follows: [bdmim][NTf2]: 110 ppm;
[P4441][NTf2] (Nippon Chemical Co., Ltd.): 145 ppm;
[P444ME][NTf2](TCI T2564): 120 ppm; HMPA (Wako):
150 ppm.
The IL was washed with water (five times) and a
mixed solvent of hexane and ethyl acetate (5:1), then
treated with active charcoal as an acetone solution.
After removing the charcoal by filtration, the filtrate
was evaporated and dried under vacuum at 60◦C
for 5 h.
Synthesis of Biphenyl (2a)
FeCl3(0.9 mg) was placed in a flask under dry nitro-
gen, and DCE (65.3 mg) and [P444ME][NTf2] (1.0 mL)
were then added. To the resulting mixture, a THF
solution of 0.35 mL of PhMgBr (1.57 M, 0.54 mmol)
was added at 0◦C under argon and this was stirred for
5 min at the same temperature. The reaction mixture
was diluted with 3 mL of a mixed solvent (hexane
and diethyl ether = 2:1) to give the biphasic layer.
Organic layers were collected by decantation, then
evaporation and silica gel thin layer chromatogra-
phy (TLC) to give 2a (0.27 mmol, 42.0 mg) in quan-
titative yield. Using the same method, biaryls 2b–2i
were obtained in the yields listed in Table 1.
Preparation and Purification Method
of [P444ME][NTf2]
To an ethanol (20 mL) solution of 1-bromo-2-
methoxyethane (4.68 g, 40 mmol), tributylphos-
phine (7.5 g, 37 mmol) was added and the resulting
mixture was stirred for 22 h at 80◦C. After being
cooled to rt, hexane was added to form the precip-
itate, which was removed by filtration. The result-
ing filtrate was evaporated under vacuum to give
the bromine salt (12.31 g, 36 mmol) in 97% yield.
The salt was dissolved in ethanol (18 mL), and
lithium bis(trifluoromethanesulfonyl)imide (11.37 g,
40 mmol) powder was added. Then the mixture was
stirred at rt for 17 h to form lithium bromide as the
precipitate. The precipitate was removed by filtra-
tion, the filtrate was washed with hexane three times,
and the solvent was removed using lyophilization.
The resulting oil was dissolved in acetone and was
treated with active charcoal, and the charcoal was
then removed by filtration. The filtrate was passed
through active alumina (type II) and dried under vac-
uum at 50◦C for 5 h to give [P444ME][NTf2] (19.15 g,
35 mmol) as colorless oil in 95% yield. This IL
is now commercially available from Tokyo Chem-
Biphenyl (2a): mp = 66–68◦C. Rf = 0.49 (hexane);
1H NMR (400 MHz, CDCl3) δ 7.34 (2 H, t, J = 7.3 Hz),
7.43 (4H, dd, J1 = 7.3 Hz, J2 = 7.3 Hz), 7.59 (4 H,
d, J = 7.3 Hz); 13C NMR (125 MHz, CDCl3) δ 127.1,
127.2, 128.7, 141.2; IR (KBr) 3030, 1944, 1880, 1575,
1480, 1338, 1171, 1083, 902, 745, 704 cm−1.
1-(4-Methylphenyl)-4-methylbenzene (2b): mp =
120–122◦C; Rf = 0.48 (hexane); 1H NMR (400 MHz,
CDCl3) δ 2.38 (6H, s), 7.22 (4H, d, J = 8.0 Hz), 7.47
(4H, d, J = 8.0 Hz); 13C NMR (125 MHz, CDCl3) δ
21.1, 126.8, 129.4, 136.7, 138.2; IR (KBr) 3027, 2917,
1502, 1114, 1006, 836, 804, 725, 549, 509 cm−1.
1-(2-Methylphenyl)-2-methybenzene (2c), CAS
Registry Number: 605-39-0: mp = 18◦C; Rf = 0.52
(hexane); 1H NMR (400 MHz, CDCl3) δ 2.05 (6H, s),
7.10 (2H, d, J = 7.0 Hz), 7.20–7.27 (6H, m); 13C NMR
(125 MHz, CDCl3) δ 19.9, 125.6, 127.2, 129.4, 129.9,
135.9, 141.7; IR (neat) 3059, 3019, 2922, 1478, 1458,
1379, 1125, 1009, 754, 729, 625, 457 cm−1.
1
ical Industry (T2564): H NMR (500 MHz, CDCl3)
δ 0.979 (9H, t, J = 6.85 Hz), 1.45–1.55 (12H, m),
2.10–2.20 (6H, m), 2.53 (2H, q, J = 5.95 Hz),
3.36 (3H, s), 3.75 (2H, dt, J = 14.2 Hz, J =
5.95 Hz); 13C NMR (125 MHz, CDCl3) δ 13.00, 19.16
(d, JC−P = 46.7 Hz), 19.98 (d, JC−P = 46.7 Hz), 23.24
(d, JC−P = 4.78 Hz), 23.60 (d, JC−P = 16.2 Hz),
1-(2,4,6-Trimethylphenyl)-2,4,6-trimethylbenzene
(2d), CAS Registry Number: 50431-97-5: mp = 100–
101◦C; Rf = 0.78 (hexane); 1H NMR (400 MHz,
CDCl3) δ 1.86 (12H, s), 2.33 (6H, s), 6.93 (4H, s); 13
C
NMR (125 MHz, CDCl3) δ 19.8, 21.1, 128.2, 135.5,
136.0, 137.0; IR (KBr) 2916, 2853, 1611, 1474, 1437,
1375, 1005, 853, 596, 530 cm−1.
58.82, 65.08 (d, JC−P = 7.64 Hz), 119.80 (q, JC−F
=
315.5 Hz); 31P NMR (202.46 MHz, CDCl3) δ 39.08
(d, JP−C = 26.1 Hz); 19F NMR (170.6 MHz, CDCl3,
C6F6) δ 92.91; IR (neat) 2937, 2878, 1400, 1194, 1057,
738 cm−1.
1-(4-Methoxyphenyl)-4-methoxybenzene
(2e),
CAS Registry Number: 2132-80-1: mp = 173–
1
175◦C; Rf = 0.56 (hexane/EtOAc = 10/1); H NMR
(400 MHz, CDCl3) δ 3.84 (6H, s), 6.96 (4H, d, J =
Heteroatom Chemistry DOI 10.1002/hc

Iron-Catalyzed Quick Homocoupling Reaction of Aryl or Alkynyl Grignard Reagents 403
9.0 Hz), 7.47 (4H, d, J = 9.0 Hz);13C NMR (125 MHz,
132.5; IR (KBr) 3050, 2924, 1551, 1067, 1024, 914,
756, 687, 527, 463 cm−1.
CDCl3) δ 55.3, 114.1, 127.7, 133.5, 158.7; IR (KBr)
1614, 1506, 1276, 1250, 1178, 1040, 1015, 825,
805 cm−1.
1,4-Bis(4-methoxyphenyl)buta-1,3-diyne
(4b),
CAS Registry Number: 22779-05-1: mp = 142–
144◦C; Rf = 0.41 (hexane/CH2Cl2 = 6/1);1H NMR
(400 MHz, CDCl3) δ 3.83 (6H, s), 6.85 (2H, d, J =
8.8 Hz), 7.46 (2H, d, J = 8.8 Hz);13C NMR (125 MHz,
CDCl3) δ 55.3, 72.9, 81.2, 114.0, 114.1, 134.0, 160.2;
IR (KBr) 2974, 2841, 1503, 1439, 1292, 1246, 1169,
1022, 831, 691, 538 cm−1.
1-(2-Methoxyphenyl)-2-methoxybenzene
(2f),
CAS Registry Number: 4877-93-4: mp = 153–155◦C;
Rf = 0.39 (hexane/CH2Cl2 = 2/1); 1H NMR (400 MHz,
CDCl3) δ 3.77 (6H, s), 6.98 (2H, d, J = 8.0 Hz),
7.01 (2H, t, J = 7.0 Hz), 7.25 (4H, dd, J1 = 8.0 Hz,
J2 = 2.0 Hz), 7.33 (4H, dt,J1 = 2.0 Hz, J2 = 7.0 Hz);13C
NMR (125 MHz, CDCl3) δ 55.7, 111.1, 120.3, 127.8,
128.6, 131.4, 157.0; IR (KBr) 1588, 1506, 1429, 1310,
1281, 1255, 1240, 1220, 1168, 1112, 1061, 1025, 999,
933, 764 cm−1.
1,4-Bis(4-(trifluoromethyl)phenyl)buta-1,3-diyne
(4c), CAS Registry Number: 151362-06-0: mp =
166–168◦C; Rf = 0.57 (hexane);1H NMR (400 MHz,
CDCl3) δ 7.62 (2H, d, J = 8.5 Hz), 7.65 (2H, d,
J = 8.5 Hz);13C NMR (125 MHz, CDCl3) δ 75.6, 81.0,
1-(4-Fluorophenyl)4-fluorobenzene (2g), CAS
Registry Number: 398-23-2: mp = 88–89◦C; Rf =
123.7 (q, JCF = 272.5 Hz), 124.8, 125.4 (q, JC−CCF
=
3.9 Hz), 131.4 (q, JC−CF = 32.7 Hz), 132.8;19F NMR
(470 MHz, CDCl3) δ 98.68; IR (KBr) 2963, 1560,
1508, 1408, 1316, 1177, 1132, 1065, 839, 733, 594,
521 cm−1.
1
0.63 (hexane); H NMR (400 MHz, CDCl3) δ 7.12
(4H, t, J = 9 Hz), 7.49 (4H, dd, J = 9 Hz,
5 Hz); 13C NMR (125 MHz, CDCl3) δ 115.66 (d,
JC−CF = 21.0 Hz), 128.54 (d, JC−CCF = 8.6 Hz),
1,4-Dio-tolylbuta-1,3-diyne (4d), CAS Registry
Number: 136053-56-0: mp = 80–82◦C; Rf = 0.52
(hexane);1H NMR (400 MHz, CDCl3) δ 2.50 (6H, s),
7.14–7.50 (6H, m), 7.51 (2H, d, J = 1.5 Hz); 13C NMR
(125 MHz, CDCl3) δ 20.7, 77.5, 81.1, 121.7, 125.6,
129.1, 129.6, 132.9, 141.6; IR (KBr) 3055, 2947, 1477,
1456, 1107, 941, 750, 714, 453 cm−1.
1,4-Dicyclohexenylbuta-1,3-diyne (4e), CAS Reg-
istry Number: 2979-05-7: mp = 60–61˚C; Rf = 0.50
(hexane);1H NMR (400 MHz, CDCl3) δ 1.55–1.63
(8H, m), 2.10–2.12 (8H, m), 6.24 (2H, t, J =
1.8 Hz);13C NMR (125 MHz, CDCl3) δ 21.3, 22.1, 25.8,
28.7, 71.5, 82.7, 120.0, 138.1; IR (KBr) 2931, 2860,
2128, 1433, 1334, 1138, 916, 841, 797, 515 cm−1.
1,4-Bis(trimethylsilyl)buta-1,3-diyne (4f), CAS
Registry Number: 4526-07-2: Rf = 0.68 (hexane); 1H
NMR (400 MHz, CDCl3) δ 0.19 (18H, s); 13C NMR
(125 MHz, CDCl3) δ −0.5, 85.9, 88.0; IR (neat) 2971,
2912, 2064, 1408, 1255, 1064, 849, 766, 701 cm−1.
136.38 (d, JC−CCCF = 2.8 Hz), 162.41 (d, JCF
=
245.8 Hz); 19F NMR (470 MHz, CDCl3) δ 45.95; IR
(KBr) 3073, 1890, 1603, 1501, 1322, 1235, 1112,
825 cm−1.
2,2’-Bithiophene (2h), CAS Registry Number:
492-97-7: mp = 31–33◦C; Rf = 0.42 (hexane); 1H
NMR (400 MHz, CDCl3) δ 6.94 (2 H, dd, J1 = 5.0 Hz,
J2 = 3.6 Hz), 7.10 (2H, dd, J1 = 3.6 Hz, J2 = 1.3 Hz),
7.14 (2H, dd, J1 = 5.0 Hz, J2 = 1.3 Hz); 13C NMR
(125 MHz, CDCl3) δ 123.7, 124.3, 127.7, 137.4; IR
(KBr) 3091, 3065, 1527, 1417, 1323, 1209, 1050, 828,
817, 700 cm−1.
Synthesis of 1,4-Diphenylbuta-1,3-diyne (4a)
To a THF (0.4 mL) solution of 3-phenylethyne
(51.1 mg, 0.50 mmol) was added 0.37 mL of
ether solution of ethylmagnesium bromide (1.48 M,
0.55 mmol) at 0◦C under dry nitrogen and the mix-
ture was stirred for 1 h at the same temperature.
The resulting solution was added to the mixture of
1.5 mL of [P444ME][NTf2], FeCl3(0.9 mg), and DIE
(169.1 mg, 0.60 mmol) using a cannula and the re-
sulting mixture was stirred at 0◦C for 20 min under
dry nitrogen. The reaction was quenched by addition
of 3.0 mL of a mixed solvent (hexane and ether 2:1)
to give the biphasic layer. Organic layers were col-
lected by decantation five times, then by evaporation
and silica gel TLC to give 4a (28 mg, 0.14 mmol) in
55% yield.
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Heteroatom Chemistry DOI 10.1002/hc