Fe(II)-catalysed homocoupling of arenediazonium tetrafluoroborates

Article abstract of DOI:10.3184/174751912X13496236042652

An efficient procedure for the synthesis of biaryls was catalysed by Fe(acac)2 and zinc powder in carbon tetrachloride solution at 60 °C using arenediazonium salts is reported. Symmetrical bi-aryl molecules with various substituents on the phenyl ring (methyl, trifluoromethyl, halogen, nitro, methoxyl) were synthesised in good yields in a short time under air. Zinc powder was used as reductant in the reaction to facilitate the regeneration of the iron(II) catalyst.

Full text of DOI:10.3184/174751912X13496236042652

672 RESEARCH PAPER
NOVEMBER, 672–674
JOURNAL OF CHEMICAL RESEARCH 2012
Fe(II)-catalysed homocoupling of arenediazonium tetrafluoroborates
Jiatian Zhou, Shuangshuang Yu, Kai Cheng* and Chenze Qi
Institute of Applied Chemistry and Department of Chemistry, University of Shaoxing, Shaoxing, Zhejiang Province 312000, P. R. China
An efficient procedure for the synthesis of biaryls was catalysed by Fe(acac)2 and zinc powder in carbon tetrachloride
solution at 60 °C using arenediazonium salts is reported. Symmetrical bi-aryl molecules with various substituents on
the phenyl ring (methyl, trifluoromethyl, halogen, nitro, methoxyl) were synthesised in good yields in a short time
under air. Zinc powder was used as reductant in the reaction to facilitate the regeneration of the iron(II) catalyst.
Keywords: homocoupling, iron catalysis, zinc powder, arenediazonium salts, diphenyls, biaryls
Biaryls represent key intermediates in a wide range of prepara-
tive organic processes and are an important class of organic
compounds since numerous compounds of natural origin,
pharmaceutical activity and with optoelectronic properties
contain this structural motif.1,2 Developing straightforward and
environment-friendly methods for aryl–aryl coupling are a
matter of wide interest. The reductive coupling of aryl halides
is one of the important protocols for the synthesis of symmetri-
cal biaryls. Historically, the Ullmann reaction was the first effi-
cient process enabling the synthesis of symmetrical biaryls.3–5
However, the reaction typically required harsh conditions such
as high temperatures, extended reaction time, and in some
cases, stoichiometric amounts of copper. This has spawned the
development of a number of milder palladium,6–9 rhodium10,11
and gold12,13 mediated protocols for the synthesis of these com-
pounds from both aryl halides and aryl sulfonates. More recent
developments involve the use of new catalysts based on cheap
metals such as nickel,14 copper15–17 and iron.18–22 The involve-
ment of iron in cross-coupling reactions23–28 has recently
attracted attention for the formation of C–C linkages.
The development of new catalysts and electrophilic partners
for these reactions has extended to cross-coupling chemistry.
Arenediazonium salts are both attractive and useful partners
which represent alternatives to aryl halides or triflates because
of their easily availability, superior reactivity and environmen-
tally friendly use.29–35 Recently, palladium-catalysed cross-
coupling reactions have been developed in which diazonium
salts have been used as electrophilic partners instead of the
more usual halides or oxygen-based electrophilic components.
These include Mizoroki–Heck,36,37 Suzuki–Miyaura,38 Stille39
and Hiyama40 reactions. Therefore, it is of particular interest to
explore the synthetic utility of the homocoupling reactions of
arenediazonium salts which may provide a simple and general
alternative to the Ullmann reaction. However, limited attention
has been paid to the development of a practical method for the
coupling of arenediazonium salts to symmetrical biaryls and
only a few studies have been reported in this area. Hanna Jr41
reported the first palladium-catalysed homocoupling of arene-
diazonium salts in refluxing methanol. Cepanec42 reported that
copper(I) triflate acts as an efficient stoichiometric reagent for
the homocoupling of arenediazonium salts to yield symmetri-
cal biaryls. Recently, we have discovered the homocoupling
reactions of arenediazonium salts with stoichiometric amounts
of ferrous salts in carbon tetrachloride solution under mild
reaction conditions.43 Moreover, this novel homocoupling
has been shown to proceed via an electron transfer reaction
mechanism and iron(III) salts was formed by the oxidation
of iron(II). Consequently, we considered whether we could
find a suitable reductant to reduce Fe(III) in order to regenerate
the Fe(II), which could make the transformation catalytic in
Fe(II).
Results and discussion
We started our investigation on the reaction of a benzenediazo-
nium salt with 10 mol% of FeCl2 in CCl4 under 60 °C. Only a
5% yield of the homocoupling biphenyl product was observed.
We screened many reductants for their ability to regenerate
Fe(II) (Table 1, entries 1–5). Metal salts with reducing anion
such as S2−, I− and SO32− did not show any obvious influence on
the reaction (Table 1, entries 1–3). To our delight, a sharp
increase in yield was observed with the addition of a reductive
metal powder. Fe powder and Cu powder afforded biphenyl
with a yield of 61% and 66%. Zn powder performed the best
(Table 1, entries 4–6). In contrast, the corresponding massive
metals were inefficienct in homocoupling reactions. We then
began to test the activities of many iron(II) salts (Table 1,
entries 7–12). FeI2 and FeBr2 gave biphenyl with a yield
of 64% and 63% respectively. However, the yield with
Fe(NO3)2·6H2O and Fe(C2O4)2·2H2O decreased to below 30%.
Other Fe(II) containing complexes with a higher solubility in
CCl4 showed higher activities, and Fe(acac)2 was the best.
We found that the solvent exerts an obvious effect on the
reaction. We evaluated the influence of different solvents
on the reactions. CH2Cl2, CHCl3 and acetone were totally
ineffective to this transformation (Table 2, entries 1–3). When
methanol was used as solvent, a 26% yield was obtained in the
presence of 10 mol% FeCl2 (Table 2, entry 4). To our delight,
a 78% yield of biphenyl was obtained in CCl4 over 3h (Table 2,
entry 5). Comparable yields were obtained when THF, 1,4-
dioxan or MTBE (2-methoxy-2-methylpropane) were used
(Table 2, entries 6–8). The homocoupling reaction cannot be
performed in aromatic solvents such as toluene or xylene
(Table 2, entries 9–10). Detailed studies of the reaction condi-
tions were also made. In studies of temperature dependence,
the formation of biaryl product was not observed below room
Table 1 The screening of reductant and catalyst for coupling
reaction in the presence of catalytic iron(II) chloride
Entry Reductant Yield /%a,c Entry Catalyst/mol % Yield/%b,c
1
2
3
4
5
6
Na2S
KI
11
13
16
61
66
71
7
8
FeI2
64
63
28
26
77
78
FeBr2
Na2SO3
9
Fe(NO3)2·6H2O
Fe(C2O4)2·2H2O
Fe(OTs)2
Fe powder
Cu powder
Zn powder
10
11
12
Fe(acac)2
Reaction conditions: a phenyldiazonium tetrafluoroborate salt
(1 mmol), FeCl2 (10 mol%), reductant (1.5 mmol), CCl4 (1 mL),
60 °C, 3h; b phenyldiazonium tetrafluoroborate salt (1 mmol),
catalyst (10 mol%), Zn powder (1.5 mmol), CCl4 (1 mL), 60 °C,
3 h.
* Correspondent. E-mail: chengkai@usx.edu.cn
c Isolated yields.

JOURNAL OF CHEMICAL RESEARCH 2012 673
Table 2 Solvent effect of coupling reaction in the presence of
homocoupled biaryls were obtained in moderate yield
(Table 3, entry 13).
Fe(acac)2a
In our preliminary investigation of the mechanism, this
homocoupling was terminated in the presence of radical
scavengers (hydroquinone or 2,6-di-tert-butylphenol). This
showed that a free radical was formed in the reaction system.
Therefore, this iron-mediated homocoupling reaction might
proceed via a possible single-electron transfer radical pathway
as shown in Scheme 1. Through the homolysis of the C–N
bond in the presence of Fe2+, both phenyl cation radical and
Fe3+ were formed with the release of nitrogen. Zn powder acted
as a reductant to reduce Fe(III) in order to regeneration Fe(II),
which could complete the catalytic cycle. The desired homo-
coupling products were obtained after the C–C bond formation
through chain termination.
Entry Solvent/mol % Yield/%b Entry
Solvent
Yield/% b
1
2
3
4
5
Acetone
CHCl3
CH2Cl2
CCl4
Methanol
Trace
Trace
Trace
78
6
7
THF
1,4-Dioxane
MTBE
Toluene
Xylene
40
46
41
8
9
10
Complex
Complex
26
a Reaction conditions: phenyl diazonium tetrafluoroborate salt
(1 mmol), Fe(acac)2 (10 mol%), Zn powder (1.5 mmol), solvent
(1 mL), 60 °C, 3 h.
b Isolated yields.
Conclusion
We have reported an efficient simple method to prepare
symmetrical biaryls which is catalysed by Fe(acac)2 under
mild conditions and with moderate to good yields. In contrast
to the traditional protocols, diazonium salts have been used
as electrophilic partners instead of the more usual halides or
oxygen-based electrophilic components. During our experi-
ments biaryls were obtained by running the reaction directly
under air and without using additional additives. This provides
a simple alternative to the traditional Ullmann reaction and
provides an addition to iron catalysis chemistry.
temperature. Only a 33% yield of the desired product was
obtained when the temperature was raised to 40 °C. The yield
was increased to 70% at 50 °C, and 78% at 60 °C. Higher tem-
peratures did not further enhance the activity. In studies on the
dependence on reaction time, we carried out the experiment
for 1h, 2h, 3h, 4h, and obtained biaryls in the yield of 52%,
66%, 78% and 76%, respectively.
We next examined the scope of the homocoupling reaction
with respect to the substituents on the arenediazonium salts
(Table 3). In general, 4-substituted arenediazonium salts with
substituents such as methyl, fluoro, chloro, bromo, trifluoro-
methyl or nitro groups afforded the corresponding biaryl
products in moderate to good yields, which ranged from 70 to
81% (Table 3, entries 1–7). Electron-withdrawing or electron-
donating groups in the aryl diazonium salts did not show
significant effects. It was noted that the 3-methoxy substituted
arenediazonium salt group could also be coupled although
with lower yields than fluoro substituted compound (Table 3,
entries 8 and 9). Sterically demanding aryl diazonium salts
also reacted in good yield (Table 3, entries 10–12). Further-
more, the homocoupling of 4-bromophenyl diazonium tetra-
fluoroborate gave exclusively the 4,4′-dibromobiphenyl in
79% yield, showing good chemoselectivity. This compound is
difficult to synthesise by the traditional Ullmann coupling
of an aryl bromide. (Table 3, entry 5). Other aryl compounds
such as naphthalenes have also been tested and the desired
Experimental
Starting materials were purchased from common commercial sources
and solvents were all purified and dried according to standard
methods prior to use. Column chromatography was carried out on
SiO2 (300–400 mesh). 1H NMR spectra were recorded with a Bruker
400 MHz spectrometer using TMS as internal standard. 13C NMR
spectra were recorded at 100 MHz using TMS as internal standard.
The multiplicities are reported as follows: singlet (s), doublet (d),
doublet of doublets (dd), multiplet (m). Mass spectroscopic data were
collected with a Finnigan Mat Mass Spectrometer.
Homocoupling reactions; general procedure
A mixture of the arenediazonium tetrafluoroborate salt (1 mmol),
Fe(acac)2 (0.1 mmol) and zinc powder (1.5 mmol) was stirred in CCl4
(1 mL) at 60 °C for 3h. Afterwards, the reaction solution was cooled
to r.t. and filtered through a filter paper. The organic phase was evapo-
rated under reduced pressure. The residue was purified on a SiO2
column to afford the desired product.
4,4′-Dimethylbiphenyl (T3-1): M.p. 123–124 °C (lit.44 122–123 °C).
1H NMR (400 MHz, CDCl3, TMS): δ 7.66 (d, 4 H, J = 8.0 Hz), 7.41
(d, 4 H, J = 8.0 Hz), 2.56 (s, 6 H) ppm. MS (EI) m/z (%): 182 (100),
167 (55), 152 (12), 89 (11), 76 (3).
Table 3 The screening of various arenediazonium saltsa
Biphenyl (T3-2): M.p. 70–71 °C (lit.44 70–71 °C). 1H NMR
(400 MHz, CDCl3, TMS): δ 7.60 (d, 4 H, J = 7.4 Hz), 7.44 (d, 4 H,
J = 7.8 Hz), 7.35 (d, 2 H, J = 7.3 Hz) ppm. MS (EI) m/z (%): 154
(100), 76 (7).
Entry
R
Yield/%b
4,4′-Difluorobiphenyl (T3-3): M.p. 89–90 °C (lit.44 87–88 °C).
1H NMR (400 MHz, CDCl3, TMS): δ 7.48 (m, 4 H), 7.09 (t, 4 H,
J = 8.6 Hz) ppm. MS (EI) m/z (%): 190 (100), 170 (20).
4,4′-Dichlorobiphenyl (T3-4): M.p. 147–148 °C (lit.44 146–147 °C).
1H NMR (400 MHz, CDCl3, TMS): δ 7.45 (d, 4 H, J = 10.8 Hz), 7.40
1
2
4-CH3
H
70
78
79
81
79
76
74
71
75
73
72
76
69
3
4-F
4
4-Cl
4-Br
5
6
4-CF3
4-NO2
3-OCH3
3-F
2-CH3
2-Cl
7
8
9
10
11
12
13
2-NO2
2-Naphth
a Reaction conditions: arenediazonium tetrafluoroborate salt
(1 mmol), Fe(acac)2 (10 mol%), Zn powder (1.5 mmol), CCl4
(1 mL), 60 °C, 3 h.
b Isolated yields.
Scheme 1

674 JOURNAL OF CHEMICAL RESEARCH 2012
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1
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Paper 1201427 doi: 10.3184/174751912X13496236042652
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