One-pot, nickel triflate-catalysed homocoupling of aryl chlorides in the presence of metallic magnesium

Article abstract of DOI:10.3184/030823409X460759

The homocoupling reaction of aryl chlorides was successfully performed in one-pot without preparation of a Grignard reagent in advance. Various aryl chlorides underwent homocoupling reactions affording the corresponding symmetrical biaryls in moderate to good yields. The nickel triflate catalyst was recovered easily and reused smoothly with only a little loss of its activity.

Full text of DOI:10.3184/030823409X460759

JOURNAL OF CHEMICAL RESEARCH 2009
JUNE, 397–399
RESEARCH PAPER 397
One-pot, nickel triflate-catalysed homocoupling of aryl chlorides in the
presence of metallic magnesium
Dan Lv, Yan-Yan Zhang and Jing-Hua Li*
College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, 310032, P. R. China
The homocoupling reaction of aryl chlorides was successfully performed in one-pot without preparation of a
Grignard reagent in advance. Various aryl chlorides underwent homocoupling reactions affording the corresponding
symmetrical biaryls in moderate to good yields. The nickel triflate catalyst was recovered easily and reused smoothly
with only a little loss of its activity.
Keywords: homocoupling, aromatic chlorides, nickel triflate
Carbon–carbon coupling reactions using transition metal
complexes as catalysts are one of the most important and
5% mol Cat./Auxiliary
Cl
1.2 equiv Mg , BrCH2CH2Br
basic reactions in organic synthesis and are widely used in
pharmaceutical chemistry. In 1972, Kumada1 and Corriu2 first
discovered the aryl-aryl coupling reaction using palladium
and nickel complexes as catalysts. This was further developed
mainly because its wide scope and excellent compatibility
with many functional groups.3,4 Since then there have been
a large number of publications concerning nickel-catalysed
coupling reactions.5-10 However, many catalysts generally
involve toxic and ecologically unsatisfactory ligands such
as phosphines11,12 in order to catalyse the coupling reaction
effectively. Therefore, a more efficient synthetic methodology
for carbon–carbon bond formation is still required.
Metal triflates are excellent catalysts with ecological
advantages. They are soluble in water and can be recovered
and reused with only a little loss of activity after several
cycles.13-17 Aryl chlorides are cheaper than aryl bromides, and
are better suited for large-scale application. We report here
a convenient one-pot method for the homocoupling of aryl
chlorides catalysed by nickel salts in the presence of metallic
lithium and magnesium.
The coupling reaction of chlorobenzene, catalysed by
5% mol NiCl2, when performed in refluxing THF, gave the
corresponding coupled product in moderate yield (69%,
Scheme 1). The catalytic effect of Ni, Yb, Fe etc. on the
homocoupling reaction of chlorobenzene was investigated
in the presence of 1.2 equiv. magnesium strips and 2% mol
BrCH2CH2Br (Table 1).
It was found that better yields were obtained with the
addition of PPh3, dppe or Li in the presence of the catalyst
NiCl2. Lithium gave the most satisfactory result with an 80%
isolated yield (entries 2, 3 and 4 in Table 1). When a catalytic
amount of Ni(acac)2 or PhNiCl(PPh3)2 was added with 5%
mol Li, the desired biaryl was obtained in moderate yield
(entries 5 and 6 in Table 1). A better result was obtained with
metal triflates as the catalysts (entry 7 in Table 1).
Scheme 1
Table 1 Optimisation of the catalytic homocoupling reaction
of chlorbenzenea
Entry
Catalyst
Auxiliary
Solvent
Yield/b%
1
2
NiCl2
0
PPh3
dppe
Li
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
Ether
69
75
68
80
81
78
89
77
68
62
65
84
72
68
62
64
80
75
77
NiCl2
3
NiCl2
NiCl2
4
5
Ni(acac)2
PhNiCl(PPh3)2
Ni(OTf)2
Ni(OTf)2
Yb(OTf)3
VO(OTf)2
Mn(OTf)2
Fe(OTf)3
Zn(OTf)2
Gd(OTf)3
Cu(OTf)2
Sc(OTf)3
Ni(OTf)2
Ni(OTf)2
Ni(OTf)2
Li
6
Li
7
Li
8
0
9
Li
10
11
12
13
14
15
16
17
18
19
Li
Li
Li
Li
Li
Li
Li
Li
Li Benzene
Li
Toluene
aReaction condition: 1 mmol PhCl, 1.2 mmol Mg, 0.02 mmol
BrCH2CH2Br, 0.05 mmol Cat., 0.05 mmol auxilary reagents,
reflux temperature, time: 6 h, solvent: 5 mL.
bIsolated yield.
(entries 2, 3, 5 and 6 in Table 2). Note that the present
reaction system is tolerant of strong electron-withdrawing
group such as trifluoromethyl and carbonyl, but the desired
products were obtained in low yields (entries 7, 8 and 9 in
Table 2). Heteroaryl chlorides such as 2-chlorothiophene and
a-chloronaphthalene reacted poorly in this system (entries 10
and 11 in Table 2). These require further study in the catalytic
homocoupling reaction.
An advantage of the catalyst is that it could be recovered
from the aqueous layer during the work-up of the reaction and
reused in subsequent reactions (see Table 3). It was found that
the activity was maintained at a satisfactory level.
In summary, an efficient homocoupling reaction of chloro
compounds is reported employing a combination of the
catalytic Ni(OTf)2/Li/Mg system. The reaction can be carried
out in one-pot and the catalyst was recovered easily and reused
smoothly with only a little loss of its activity.
Compared with Yb(OTf)3 and Fe(OTf)3, Ni(OTf)2 gave
the best yield (entries 7–16 in Table 1). Meanwhile, several
solvents such as ether, benzene and toluene were examined for
the Ni(OTf)2-catalysed coupling reaction, but no improvement
was observed (entries 17, 18 and 19 in Table 1).
To explore the scope of this catalytic coupling system, other
chloro compounds were used as substrates (Scheme 2 and
Table 2). A variety of aryl chlorides underwent homocoupling
reactions with the catalytic Ni(OTf)2/Li/Mg system in
refluxing THF to give the corresponding symmetrical
hydrocarbons in moderate to good yields (Table 2).
Aromatic chlorides substituted with electron-donating
groups (methyl, methoxy etc.) at the m- or p- position can
be efficiently converted into the corresponding biaryls
Experimental
All reactions were carried out under an atmosphere of nitrogen in
oven dried glassware with magnetic stirring, THF was distilled
from a benzophenone-sodium adduct and stored over sodium wire.
* Correspondent. E-mail: lijh@zjut.edu.cn

398 JOURNAL OF CHEMICAL RESEARCH 2009
5% mol Ni(OTf)2/Li
Cl
R
1.2 equiv Mg ,
THF
BrCH2CH2Br,
R
R
1
2
Scheme 2
(about 40 mg) of 10% 1,2-dibromoethane/THF. The resulting mixture
was stirred at room temperature and a piece of Li (about 4 mg for 10
pieces of Li) was added and ArCl 1 mmol in THF 2 mL was then
slowly added. The reaction mixture was stirred under reflux for 6 h,
and then quenched with saturated NH4Cl. The solvent was evaporated
and the residue treated with Et2O (10 mL) and water (15 mL). The
organic layer was separated and the aqueous layer was extracted
with Et2O (3 ¥ 10 mL). Concentration of the combined organic layer,
dried over MgSO4 in advance, afforded the crude product which was
further purified by column chromatography on silica gel to give the
pure homocoupling product.
Table 2 Ni(OTf)2 catalysed homocoupling reaction of
substituted aryl chloridesa
Entry
1
Reagent 1
Product 2
Yield/b%
89
2a
Cl
Me
Me
Cl
2
3
2b
2c
81
79
The aqueous layer containing Ni(OTf)2 in the above work-up
procedure was evaporated under reduced pressure and the residue
was extracted with ethyl acetate (3 ¥ 10 mL). The organic phases
were combined, evaporated under reduced pressure and dried at 70°C
for 2 h to give pure Ni(OTf)2 in 92% recovery. The recovered catalyst
was reused in the same way for the next run.
Cl
Cl
Me
Me
4
5
2d
2e
70
86
Biphenyl (2a): M.p. 68–70°C (lit.18 68–71°C). 1H NMR (400 MHz,
CDCl3): d 7.35–7.47 (m, 6H), 7.58–7.62 (m, 4H). MS (EI): m/z (%):
154 (M+, 100), 153 (35), 152(20), 115 (3), 76 (13), 51(4).
MeO
Cl
4,4'-Dimethylbiphenyl (2b): M.p. 119–120°C (lit.18 119–120°C).
1H NMR (400 MHz, CDCl3): d 2.56 (s, 6H), 7.41 (d, 4H, J = 7.6 Hz),
7.66 (d, 4H, J = 7.6 Hz). MS (EI): m/z (%): 182 (M+, 100), 167 (55),
152 (12), 89 (11), 76 (3).
t-BuO
Cl
6
7
2f
88
45
F3C
O
Cl
2g
3,3'-Dimethylbiphenyl (2c): Oil.18 1H NMR (400 MHz, CDCl3):
d 2.42 (s, 6H), 7.16 (d, 2H, J = 6.0 Hz), 7.32–7.40 (m, 6H). MS (EI):
m/z (%): 182 (M+, 100), 167 (33), 152 (12), 89 (8), 76 (4).
2,3,2',3'-Tetramethylbiphenyl (2d): M.p. 114–115°C (lit.19114–
Cl
8
9
2h
2i
56
40
H3C
1
115°C). H NMR (400 MHz, CDCl3): d 1.95 (s, 6H), 2.33 (s, 6H),
F3C
6.96 (d, 2H, J = 6.8 Hz), 7.16–7.10 (m, 4H). MS (EI): m/z (%):
210 (M+, 93), 195 (100), 180 (25), 165 (19), 89 (11), 76 (3).
4,4'-Dimethoxydiphenyl (2e): M.p. 177–179°C (lit.18 177–179°C).
1H NMR (400 MHz, CDCl3): d 3.84 (s, 6H), 6.95 (d, 4H, J = 8.8 Hz),
7.47 (d, 4H, J = 8.8 Hz). MS (EI): m/z (%): 182 (M+, 100), 167 (55),
152 (12), 89 (11), 76 (3).
Cl
F3C
Cl
10
11
2j
52
48
S
4,4'-Diisobutyloxydiphenyl (2f)20: M.p. 149–150°C. 1H NMR (400
MHz, CDCl3): d 1.39 (s, 18H), 7.05 (d, 4H), 7.48 (d, 4H). MS (EI):
m/z (%): 298 (2), 186 (100), 157 (9), 57 (31).
Cl
4,4'-Bis(trifluoromethyl)biphenyl (2g): M.p. 89–91°C (lit.2183–
84°C). 1H NMR (400 MHz, CDCl3): d 7.38 (d, 4H, J = 8.0 Hz), 7.48
(d, 4H, J = 8.0 Hz). MS (EI): m/z (%): 290 (M+, 100), 271 (25), 240
(10), 219 (6), 201 (20), 152 (14), 145 (5).
2k
aReaction condition: 1 mmol ArCl, 1.2 mmol Mg, 0.05 mmol
Ni(OTf)2/Li, 0.02 mmol BrCH2CH2Br, reflux temperature, time:
6 h, solvent: 5 mL THF.
4,4'-Diacetylbiphenyl (2h): M.p. 191–192°C (lit.22 190–192°C).
1H NMR (400 MHz, CDCl3): d 2.63 (s, 6H), 7.67 (d, 4H), 8.02 (d, 4H).
13C NMR (100 HZ, CDCl3): d 197.5, 144.3, 136.6, 129.0, 127.4, 26.7.
3,5,3',5'-Tetrakis(trifluoromethyl)biphenyl (2i): M.p. 68–70°C
(lit.18 68–71°C). 1H NMR (400 MHz, CDCl3): d 7.96 (s, 2H), 8.04 (s,
4H). MS (EI): m/z (%): 426 (M+, 100), 407 (42), 357 (15), 337 (15),
287 (10), 213 (8).
bIsolated yield.
Table 3 Catalyst recyclinga
Use
Recovery of catalyst/%
Yield/b%
1st
2nd
3rd
92
91
92
80
76
78
1
3,3'-Bithienyl (2j): M.p. 130–131°C (lit.23 132–133°C). H NMR
(400 MHz, CDCl3): d 7.33–7.35 (m, 4H), 7.37–7.38 (m, 2H). MS
(EI): m/z (%): 166 (M+, 100), 83 (21).
aReaction condition: 1 mmol PhCl, 1.2 mmol Mg, 0.05 mmol
Ni(OTf)2/Li, 0.02 mmol BrCH2CH2Br, reflux temperature, time: 6
h, solvent: 5 mL THF.
1,1'-Binaphthyl (2k): M.p. 154–156°C (lit.19 154–156°C).
1H NMR (400 MHz, CDCl3): d 7.95 (d, 2H, J = 48.2 Hz), 7.94 (d,
2H, J = 8.0 Hz),7.59 (t, 2H, J = 8.0 Hz,), 7.50–7.47 (m, 4H), 7.38 (d,
2H, J = 8.3 Hz), 7.28 (t, 2H, J = 7.8 Hz); 13C NMR (100 HZ, CDCl3):
d 138.8, 133.5, 132.8, 128.1, 127.9, 127.8, 126.6, 126.0, 125.8, 125.3.
bIsolated yield.
1H NMR spectra were performed on a Varian Plus-400(400 MHZ)
apparatus(CDCl3 solution), MS spectra were performed on an AEI
MS-902 apparatus, melting points were performed on X-4/micro
melting point apparatus.
Received 16 February 2009; accepted 14 April 2009
Paper 09/0449 doi: 10.3184/030823409X460759
Published online: 2 July 2009
Homocoupling reaction catalysed by Ni(OTf)2 and the recovery of
Ni(OTf)2
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