Catalytic activities of a bis(carbene)-derived nickel(II)-pincer complex in Kumada-Tamao-Corriu and Suzuki-Miyaura coupling reactions for the synthesis of biaryl compounds

Article abstract of DOI:10.1055/s-2007-983845

The catalytic activities of a pincer type bis(imidazolin-2-ylidene) nickel(II) complex were evaluated. The complex was found to be an effective catalyst in the Kumada-Tamao-Corriu and Suzu-M-Miyaura coupling reactions of a broad range of aryl-X (X = Br, Cl and F) compounds, providing a variety of biaryl compounds, generally in good yield. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-983845

PAPER
2853
Catalytic Activities of a Bis(carbene)-Derived Nickel(II)-Pincer Complex in
Kumada–Tamao–Corriu and Suzuki–Miyaura Coupling Reactions for the
Synthesis of Biaryl Compounds
N
K
HC-DerivedNi(I
i
I)-Pinc
y
er
C
omplex
o
for
B
iaryl Sy
f
nthesis umi Inamoto,* Jun-ichi Kuroda, Takao Sakamoto, Kou Hiroya
Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3, Aoba, Aramaki, Aoba-ku, Sendai, 980-8578, Japan
Fax +81(22)7956864; E-mail: inamoto@mail.pharm.tohoku.ac.jp
Received 23 April 2007
This paper is dedicated to Professor Yoshihiko Ito for his great contribution to organic chemistry.
pling reactions and in this report, iodobenzene and
Abstract: The catalytic activities of a pincer type bis(imidazolin-2-
bromobenzene were the only substrates employed.1
7c
ylidene)nickel(II) complex were evaluated. The complex was found
to be an effective catalyst in the Kumada–Tamao–Corriu and Suzu- In this article, we describe the catalytic activities of nick-
ki–Miyaura coupling reactions of a broad range of aryl-X (X = Br,
Cl and F) compounds, providing a variety of biaryl compounds,
generally in good yield.
el(II)-pincer complex 1 in Grignard coupling reactions
and show that a range of substituted aryl bromides and
chlorides react with certain Grignard reagents smoothly in
the presence of 1, to give a wide array of unsymmetrical
Key words: nickel, N-heterocyclic carbenes, pincer ligands, Ku-
mada–Tamao–Corriu coupling, Suzuki–Miyaura coupling
biaryls, generally in good yields. Even more significantly,
activation of the C–F bond – a more challenging process –
was realized under mild conditions, employing a catalytic
amount of nickelacycle 1. We also present herein, full de-
The development of methods for the efficient synthesis of
biaryl compounds remains an attractive target as these
1
tails of the results obtained from complex 1 catalyzed Su-
2
compounds are frequently found in natural products,
18
zuki–Miyaura coupling reactions.
3
4
drugs and materials. Members of this class of com-
pounds have historically been prepared through the palla-
dium- or nickel-catalyzed coupling reactions of aryl
halides or pseudohalides with Grignard (Kumada–
Tamao–Corriu), organoboron (Suzuki–Miyaura), organo-
Br
N
N
N
N
N
N
Ni
2Br
5
N
N
N
N
tin (Stille) or organozinc (Negishi) reagents. It is gener-
Me
Me
Me
Me
Br
ally accepted that aryl iodides and bromides are more
reactive in these reactions. Recent efforts, however, have
enabled the activation of certain, less reactive, bonds such
1
2
Figure 1 NHC-derived Ni(II)-pincer complex 1 and its precursor 2
6
7,8,9
10
11
as C–Cl, C–F,
C–OR and C–OCONR2. Although
monodentate or bidentate phosphines are largely em-
ployed as ancillary ligands in these reactions, N-heterocy-
clic carbenes (NHCs) have been found to be attractive
alternatives to phosphine ligands, due to their unique
properties. To date, many catalytically active systems
based on the combination of palladium and NHCs, have
been developed. In contrast, there are only a few reports
The catalytic activity of nickelacycle 1 in Grignard cou-
pling reactions was first evaluated for the reaction of
4
-bromotoluene
with
phenylmagnesium
halide
1
9
1
2
(Table 1). To our satisfaction, we found that the desired
biaryl compound was obtained in high yield in the pres-
ence of 1–5 mol% of 1 in tetrahydrofuran at room temper-
ature (entries 1, 2 and 4). In contrast, use of a combination
on the utilization of NHCs as ligands in nickel-catalyzed
cross-coupling processes.13 However, replacing palladi-
of Ni(acac) and a second pincer-type imidazolium salt 2,
2
gave a significantly lower yield (entry 3). Interestingly,
using phenylmagnesium chloride rather than the corre-
sponding bromide, gave better results, both in terms of re-
activity and product distribution (entry 1 vs. 2).
um with nickel catalysts in cross-coupling reactions is
highly desirable from a cost effectiveness viewpoint and
some nickel catalysts have even been shown to be more
effective than the palladium catalysts. Very recently, we
demonstrated that the novel NHC-derived nickel(II)-pin-
cer complex 1 (Figure 1) can serve as an efficient catalyst
in the Heck reaction.15,16,17 To the best of our knowledge,
there is only one other report in the literature on the cata-
lytic activity of a pincer-type nickel catalyst in cross-cou-
1
4
Cross-coupling reactions that illustrate the scope of this
system are shown in Table 2. Suitable substrates include
both electron-rich and neutral aryl halides, and a variety of
biaryls were obtained, generally in good to high yields
(
entries 1–11 and 20–26); electron-poor aryl halides, how-
ever, were relatively less reactive (entries 12 and 27). This
method was also tolerant of silyl ether moieties (entries 13
and 28) and heteroaryl halides (entries 14–16, 29 and 30).
Furthermore, in the reaction of vinyl bromide, the corre-
SYNTHESIS 2007, No. 18, pp 2853–2861
x
x.
x
x
.
2
0
0
7
Advanced online publication: 08.08.2007
DOI: 10.1055/s-2007-983845; Art ID: F07107SS
Georg Thieme Verlag Stuttgart · New York
©

2
854
K. Inamoto et al.
PAPER
Table 1 Optimization of Reaction Conditions in Grignard Cou-
plings Catalyzed by Nickelacycle 1
sponding coupling product was obtained in moderate
yield with no evidence of the formation of the regioisomer
a
(
entry 19). On the other hand, substrates such as aniline
PhMgX
and phenol gave essentially no coupling products, al-
though nearly all of the starting materials were consumed
1
Me
Br
Me
Ph + Ph Ph
THF
r.t., 9–48 h
(entries 31 and 32). With respect to the reactivity (yield
3
4
and reaction rate) of the Grignard reagents employed,
phenylmagnesium chloride was superior to both phenyl-
magnesium bromide and para-methoxyphenylmagne-
sium bromide in most cases, with the exception of the
reactions of 3-halopyridine.
Entry
1
(
X
Time
(h)
Yield of 3 3:4
b
mol%)
(%)
1
2
3
4
5
5
Br
Cl
Cl
Cl
Cl
Cl
9
9
70
1: 0.33
5
87
1: 0.10
1: 1.11
1: 0.43
1: 0.55
Furthermore, this system is not limited to aryl bromides
2
–c
and chlorides; the catalytic cleavage of C(sp )-fluorine
9
27
bonds, normally extremely challenging because of the in-
herent strength of this bond, was achieved using the reac-
tion conditions established above with no modifications
1
16
48
24
79
0.1
None
59
(
Table 3). Several aryl fluorides were reacted with aryl
6
No reaction
Grignard reagents in the presence of catalyst 1, giving the
desired biaryls in moderate to good yields, albeit with
longer reaction times.2
a
Reagents: 4-Bromotoluene (1.0 mmol), PhMgX (1.5 mmol) and 1 in
0a,b
THF (5 mL).
b
1
Yield and product ratio were determined by H NMR as the average
of two runs, using mesitylene as an internal standard.
c
A combination of Ni(acac) and imidazolium salt 2 was used as the
2
catalyst in place of 1.
Table 2 Catalytic Activity of Nickelacycle 1 in Grignard Couplingsa
1
Ar
halide
+
Ar'MgX
Ar
Ar'
THF
r.t.
b
Yield (%)c
89
Entry
1
Ar halide
Ar¢MgX
Product
Time (d)
2
C
5
Br
2
3
A
C
3
6
0.4
2
87d
92
Me
Me
Br
4
5
A
C
7
8
0.4
2
75d
87
Br
6
Me
C
9
4
68
Br
7
8
A
A
5
1
1
67
70
MeO
MeO
Br
10
Br
9
0
A
C
11
12
0.7
2
83d
71
tBu
Br
1
1
1
A
13
2
72
Br
O
O
1
2
C
14
2
49
F3C
Br
Synthesis 2007, No. 18, 2853–2861 © Thieme Stuttgart · New York

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NHC-Derived Ni(II)-Pincer Complex for Biaryl Synthesis
2855
a
Table 2 Catalytic Activity of Nickelacycle 1 in Grignard Couplings (continued)
1
Ar
halide
+
Ar'MgX
Ar
Ar'
THF
r.t.
Entry
Ar halide
Ar¢MgXb
Product
Time (d)
1
Yield (%)c
83
1
3
A
15
Br
TBSO
N
1
1
1
4
5
6
A
B
C
16
16
17
1
2
2
20
56
77
Br
Br
1
1
7
8
A
C
18
19
0.7
2
75d
81
1
2
9
0
Br
C
C
20
5
2
2
68
Ph
(
E/Z = 5:1)
(
E/Z = 10:1)
81
Cl
2
2
1
2
A
C
3
6
1
2
69d
65
Me
Cl
2
2
3
4
Me
A
C
7
8
1
2
81d
79
Cl
2
5
Me
C
9
4
46
Cl
2
2
2
6
7
8
A
C
A
5
14
15
0.7
2
64
43
76
MeO
F3C
Cl
Cl
1
Cl
TBSO
2
3
9
0
B
C
16
17
2
2
81
81
Cl
N
3
3
1
2
A
A
22
23
1
1
0
0
H2N
Cl
Cl
HO
a
b
c
d
Reagents: Aryl halide (1.0 mmol), Grignard reagent (1.5 mmol) and 1 (0.05 mmol) in THF (5 mL).
Ar¢MgX = PhMgCl (A), PhMgBr (B), 4-MeOC H MgBr (C).
6
4
Isolated yield, average of two runs.
1
Yield was determined by H NMR using mesitylene as an internal standard.
We then examined the catalytic activity of 1 in Suzuki– to afford the desired biaryl in 83% yield (entry 3). The use
Miyaura coupling reactions. The reaction of 4-bromoben- of other bases led to decreased yields (entries 5–7). We
zonitrile with phenylboronic acid was chosen first in order also found that catalyst loading could be reduced to 0.1
to optimize the reaction conditions (Table 4). Among the mol% without significant decrease in yield (entries 8 and
solvents employed, dioxane proved to be superior to both 9). The combination of Ni(acac) and pincer-type imida-
2
toluene and N,N-dimethylformamide (entries 1–3). Thus, zolium salt 2 did not exhibit any catalytic activity, as was
4
-bromobenzonitrile was successfully reacted with phe- the case in the Grignard coupling reactions (entry 10). The
nylboronic acid in dioxane, in the presence of 5 mol% use of Ni(acac) alone gave essentially no coupling prod-
2
complex 1 together with potassium phosphate at 120 °C, uct (entry 11).
Synthesis 2007, No. 18, 2853–2861 © Thieme Stuttgart · New York

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856
K. Inamoto et al.
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Table 3 Nickelacycle 1 Catalyzed Grignard Couplings of Aryl Fluoridesa
1
Ar
F
+
Ar'MgX
Ar
Ar'
THF
r.t.
b
Yield (%)c
Entry
1
Ar halide
Ar¢MgX
Product
Time (d)
4
C
5
71
62
52
F
2
3
C
C
6
8
6
4
Me
Me
F
F
4
5
A
A
5
6
6
44
70
MeO
F
15
F
TBSO
N
6
7
B
C
16
17
6
4
61
72
F
a
Reagents: Aryl fluoride (1.0 mmol), Grignard reagent (1.5 mmol) and 1 (0.05 mmol) in THF (5 mL).
Ar¢MgX = PhMgCl (A), PhMgBr (B), 4-MeOC H MgBr (C).
b
c
6
4
Isolated yield, average of two runs.
Table 4 Optimization of Reaction Conditions in Suzuki–Miyaura Couplings Catalyzed by Nickelacycle 1a
PhB(OH)2
Ni catalyst
base
NC
Br
NC
Ph
1
h
24
Entry
Ni catalyst (mol%)
Base
Solvent
DMF
Temp (°C)
120
Time (h)
Yield (%)b
24 (39)c
67 (19)c
83
1
2
3
4
5
6
7
8
9
1 (5)
K PO
1
1
3
4
4
4
4
K PO
Toluene
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
120
3
K PO
120
0.5
16
1
3
K PO
100
73
3
Cs CO
120
64
2
3
Na CO
120
1
28 (51)c
46 (35)c
83
2
3
K CO
120
1
2
3
1 (1)
K PO
120
1
3
4
1 (0.1)
K PO
120
6
80
3
4
4
4
1
1
0
1
Ni(acac) /2 (5/5)
K PO
120
1
trace (88)c
trace (88)c
2
3
Ni(acac) (5)
K PO
120
1
2
3
a
b
c
Reagents: 4-Bromobenzonitrile (1.0 mmol), PhB(OH) (3.0 mmol), base (2.0 mmol) and solvent (5 mL).
Isolated yield.
Recovered yield of starting material in parentheses.
2
Synthesis 2007, No. 18, 2853–2861 © Thieme Stuttgart · New York

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NHC-Derived Ni(II)-Pincer Complex for Biaryl Synthesis
2857
Table 5 aCatalytic Activity of Nickelacycle 1 in Suzuki–Miyaura
In the former reaction, the range of suitable substrates was
quite broad; in addition to various aryl bromides and chlo-
rides, less reactive aryl fluorides were also successfully
reacted under mild conditions, in the presence of 1. Cata-
lyst 1 also proved highly active in the Suzuki–Miyaura
couplings; in the presence of catalyst 1 (1 mol%), reac-
tions involving a wide variety of aryl halides proceeded
smoothly and with good functional group tolerance. As a
result, variously substituted biaryl compounds could be
obtained, generally in good to high yields, from these two
reactions. It is worth noting that catalyst 1, which is easily
prepared from inexpensive, commercially available mate-
rials, is highly stable to both air and moisture, obviating
the need for a strictly inert atmosphere in carrying out
these reactions. Although the precise reaction mecha-
Couplings
PhB(OH)2
complex 1
K3PO4
Ar
X
Ar
Ph
dioxane
20 °C
1
X = Br, Cl
Entry
X
Ar
Time Product Yield
(
b
h)
1
2
1
2
2
1
8
2
8
2
2
2
1
2
4
4
(%)
83
87
85
71
85
81
73
71
58
86
86
79
94
66
69
76
84
77
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
Br
4-CNC H
24
25
26
5
6
4
4
4
3-CNC H
6
2-CNC H
6
4-MeOC H
20
6
4
4
nisms remain to be elucidated, the results in this report
clearly indicate that nickel-pincer complexes, which have
so far been insufficiently studied, possess the potential for
catalytic activity in a wide range of coupling reactions.
The preparation of other nickel-pincer complexes and
their evaluation as candidates for the catalysis of cross-
coupling reactions is underway in our laboratory.
3-MeOC H
10
27
28
22
29
13
15
18
16
24
30
31
28
16
6
4-EtO CC H
4
2
6
2-MeCOC H
6
4
4-NH C H
2
6
4
4
2-NH C H
2
6
All reactions were carried out under an Ar atmosphere unless other-
wise noted. THF and 1,4-dioxane were distilled from benzophenone
ketyl under an Ar atmosphere. DMF and toluene were distilled from
sodium under an Ar atmosphere. Sealed tubes (18 × 180 mm, 27
mL) were used for Suzuki–Miyaura coupling reactions. Melting
points were measured with a Yazawa micro melting-point apparatus
and are uncorrected. IR spectra were recorded on a SHIMADZU
1
1
1
1
1
1
1
1
(3,4-OCH O-)C H
2 6 3
4-TBSOCH C H
4
2
6
1-Naphthyl
3-Pyridyl
1
FTIR-8400. H NMR spectra were recorded on a JEOL JNM-AL-
Cl
4-CNC H
6 4
400 (400 MHz) using TMS as an internal standard. Chemical shifts
(
d) are given relative to TMS (d = 0 ppm) and coupling constants
4-MeO CC H
4
2
6
are expressed in Hertz (Hz). The following abbreviations are used:
s = singlet, d = doublet, t = triplet, q = quartet, dd = double doublet,
dt = double triplet, td = triple doublet, m = multiplet and br
4-MeCOC H
6
4
4
1
3
2-MeCOC H
12
2
s = broad singlet. C NMR spectra were recorded on a JEOL
6
JNM-AL400 (100 MHz) and chemical shifts (d) are given relative
1
3-Pyridyl
to CDCl (77.0 ppm). Mass spectra (EI, 70 eV) and high-resolution
3
mass spectra were measured on JEOL JMS-DX303 and MS-AX500
instruments, respectively.
a
Reagents: Aryl halide (1.0 mmol), PhB(OH) (3.0 mmol), K PO
4
2.0 mmol), 1 (1 mol%) and dioxane (5 mL).
Isolated yield, average of two runs.
2
3
(
b
Nickelacycle 1 Catalyzed Grignard Coupling Reactions (Tables
1
, 2 and 3); General Procedure
To a suspension of an aryl halide (1.0 mmol) and nickelacycle 1
0.001–0.05 mmol) in THF (3.5 mL), was slowly added Grignard
(
For a number of aryl bromides and chlorides, nickelacycle
catalyzed Suzuki–Miyaura coupling reactions proceed-
ed in generally high yields (Table 5). Both activated and
deactivated aryl halides with various substituents (includ-
ing sterically demanding ortho-substituted substrates) combined organic extracts were washed with sat. aq NaCl (10 mL)
were successfully cross-coupled in the presence of 1 and dried over MgSO . The solvent was removed under reduced
mol% 1, to furnish unsymmetrical biaryls. Functional
groups such as cyano (entries 1–3 and 14), carbonyl (en-
tries 7, 16 and 17) and alkoxycarbonyl (entries 6 and 15),
were tolerated during the course of this reaction. In addi-
tion, heteroaromatic (entries 13 and 18) and condensed ar-
reagent (1.5 mL, 1.5 mmol, 1.0 M in THF solution) over 3 h via a
syringe pump and the mixture was stirred at r.t. The reaction mix-
1
ture was treated with sat. aq NH Cl (10 mL) and then filtered
4
®
through Celite , followed by extraction with Et O (3 × 15 mL). The
2
4
pressure and the crude material was purified by silica gel column
chromatography to give the corresponding biaryl.
Nickelacycle 1 Catalyzed Suzuki-Miyaura Coupling Reactions
(
Tables 4 and 5); General Procedure
A mixture of aryl halide (1.0 mmol), phenylboronic acid (0.37 g, 3.0
omatic compounds (entry 12) also served as useful mmol), nickelacycle 1 (0.001–0.05 mmol) and K PO (0.45 g, 2.0
3
4
coupling agents.
mmol) in dioxane (5 mL), was allowed to react in a sealed tube. The
reaction mixture was treated with H O (15 mL) then extracted into
2
In summary, the catalytic activities of NHC-derived nick-
el(II)-pincer complex 1 were investigated in the Kumada–
Tamao–Corriu and Suzuki–Miyaura coupling reactions.
Et O (3 × 15 mL). The combined organic extracts were washed with
2
sat. aq NaCl (10 mL) and dried over MgSO . The solvent was re-
4
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K. Inamoto et al.
PAPER
1
3
moved under reduced pressure and the crude material was purified
by silica gel column chromatography to give the corresponding bi-
aryl.
C NMR (100 MHz, CDCl ): d = 20.6, 55.2, 113.4, 125.6, 126.9,
3
129.8, 130.1, 130.2, 134.3, 135.3, 141.4, 158.4.
+
MS (EI): m/z (%) = 198 (100) [M] , 183 (26).
HRMS: m/z calcd for C H O: 198.1045; found: 198.1027.
4
-Methylbiphenyl (3)
14 14
1
H NMR (400 MHz, CDCl ): d = 2.39 (s, 3 H), 7.24–7.36 (m, 3 H),
7
3
3
-Methoxybiphenyl (10)
.40–7.50 (m, 4 H), 7.58 (t, J = 7.4 Hz, 2 H).
–
1
IR (neat): 1599, 1038 cm .
1
3
C NMR (100 MHz, CDCl ): d = 21.1, 126.9, 127.07, 127.15,
28.6, 129.4, 136.9, 138.3, 141.0.
3
1
H NMR (400 MHz, CDCl ): d = 3.83 (s, 3 H), 6.88 (dd, J = 7.8, 1.6
1
3
Hz, 1 H), 7.12 (t, J = 1.6 Hz, 1 H), 7.16 (dd, J = 7.8, 1.6 Hz, 1 H),
MS (EI): m/z (%) = 168 (100) [M]+.
7
.31–7.35 (m, 2 H), 7.41 (t, J = 7.8 Hz, 2 H), 7.57 (d, J = 7.8 Hz,
HRMS: m/z calcd for C H : 168.0939; found: 168.0926.
2 H).
1
3
12
1
3
C NMR (100 MHz, CDCl ): d = 55.3, 112.6, 112.8, 119.6, 127.1,
3
4
-Methoxybiphenyl (5)
1
27.3, 128.6, 129.6, 141.0, 142.6, 159.8.
2
1
Colorless prisms; mp 86–87 °C (Lit. 85–87 °C).
MS (EI): m/z (%) = 184 (100) [M]+.
–
1
IR (film): 1609, 1036 cm .
HRMS: m/z calcd for C H O: 184.0888; found: C H O:
1
13 12
13 12
H NMR (400 MHz, CDCl ): d = 3.83 (s, 3 H), 6.96 (d, J = 8.8 Hz,
H), 7.29 (t, J = 7.5 Hz, 1 H), 7.40 (t, J = 7.5 Hz, 2 H), 7.51–7.55
3
1
84.0867.
2
(
1
m, 4 H).
4
-tert-Butylbiphenyl (11)
3
1
C NMR (100 MHz, CDCl ): d = 55.3, 114.1, 126.56, 126.64,
H NMR (400 MHz, CDCl ): d = 1.36 (s, 9 H), 7.34 (t, J = 7.8 Hz,
2 H), 7.40–7.45 (m, 5 H), 7.53 (d, J = 7.8 Hz, 2 H).
3
3
1
28.0, 128.6, 133.7, 140.7, 159.0.
+
13
MS (EI): m/z (%) = 184 (100) [M] , 169 (43), 141 (26).
HRMS: m/z calcd for C H O: 184.0888; found: 184.0886.
C NMR (100 MHz, CDCl ): d = 31.4, 34.6, 125.6, 126.7, 126.9,
3
1
27.1, 128.7, 138.2, 141.1, 150.1.
1
3
12
+
MS (EI): m/z (%) = 210 (45) [M] , 195 (100).
4
-Methoxy-4¢-methylbiphenyl (6)
HRMS: m/z calcd for C H : 210.1409; found: 210.1394.
2
1
16 18
Colorless scales; mp 107–108 °C (hexane; Lit. 106–107 °C).
–
1
IR (film): 1609, 1038 cm .
4-tert-Butyl-4¢-methoxybiphenyl (12)
1
Colorless scales; mp 137–139 °C (hexane).
H NMR (400 MHz, CDCl ): d = 2.37 (s, 3 H), 3.82 (s, 3 H), 6.95
d, J = 8.8 Hz, 2 H), 7.21 (d, J = 8.0 Hz, 2 H), 7.43 (d, J = 8.0 Hz,
3
–
1
(
IR (film): 1605, 1038 cm .
2
H), 7.49 (d, J = 8.8 Hz, 2 H).
1
H NMR (400 MHz, CDCl ): d = 1.36 (s, 9 H), 3.84 (s, 3 H), 6.96
3
1
3
C NMR (100 MHz, CDCl ): d = 21.1, 55.3, 114.1, 126.5, 127.8,
(d, J = 8.8 Hz, 2 H), 7.42–7.52 (m, 6 H).
13
3
1
29.3, 133.6, 136.2, 137.9, 158.8.
C NMR (100 MHz, CDCl ): d = 31.4, 34.5, 55.3, 114.1, 125.6,
3
+
MS (EI): m/z (%) = 198 (100) [M] , 183 (50).
126.3, 127.9, 133.6, 137.8, 149.5, 158.8.
+
HRMS: m/z calcd for C H O: 198.1045; found: 198.1037.
MS (EI): m/z (%) = 240 (60) [M] , 225 (100).
1
4
14
HRMS: m/z calcd for C H O: 240.1514; found: 240.1498.
1
7
20
3
-Methylbiphenyl (7)
1
H NMR (400 MHz, CDCl ): d = 2.41 (s, 3 H), 7.15 (d, J = 7.2 Hz,
1
3
3
,4-Methylenedioxybiphenyl (13)
H), 7.30–7.45 (m, 6 H), 7.56–7.59 (m, 2 H).
–1
IR (neat): 1601, 1038 cm .
1
3
C NMR (100 MHz, CDCl ): d = 21.6, 124.2, 127.1, 127.2, 127.9,
28.6, 128.7, 129.4, 138.2, 141.1, 141.3.
1
3
H NMR (400 MHz, CDCl ): d = 5.97 (s, 2 H), 6.86 (d, J = 8.0 Hz,
3
1
1
H), 7.03–7.06 (m, 2 H), 7.29 (t, J = 7.2 Hz, 1 H), 7.38 (dd, J = 8.2,
MS (EI): m/z (%) = 168 (100) [M]+.
7.2 Hz, 2 H), 7.50 (dd, J = 8.2, 1.2 Hz, 2 H).
1
3
HRMS: m/z calcd for C H : 168.0939; found: 168.0923.
C NMR (100 MHz, CDCl ): d = 101.0, 107.6, 108.5, 120.5,
1
3
12
3
1
26.77, 126.80, 128.6, 135.5, 140.8, 146.9, 148.0.
4
¢-Methoxy-3-methylbiphenyl (8)
MS (EI): m/z (%) = 198 (100) [M]+.
2
2
Colorless prisms; mp 51–52 °C (hexane; Lit. 54 °C).
HRMS: m/z calcd for C H O : 198.0681; found: 198.0705.
–
1
13 10
2
IR (film): 1609, 1034 cm .
1
H NMR (400 MHz, CDCl ): d = 2.39 (s, 3 H), 3.18 (s, 3 H), 6.94
4-Methoxy-4¢-trifluoromethylbiphenyl (14)
23
3
(
d, J = 8.2 Hz, 2 H), 7.10 (d, J = 6.8 Hz, 1 H), 7.26–7.35 (m, 3 H),
Colorless plates; mp 125–126 °C (hexane; Lit. 124–125 °C).
7
.50 (d, J = 8.2 Hz, 2 H).
IR (film): 1605, 1038, 822 cm–1.
1
3
C NMR (100 MHz, CDCl ): d = 21.6, 55.3, 114.1, 123.8, 127.3,
27.4, 128.0, 128.5, 133.8, 138.1, 140.7, 158.9.
1
3
H NMR (400 MHz, CDCl ): d = 3.86 (s, 3 H), 6.99 (dt, J = 9.7, 2.7
3
1
Hz, 2 H), 7.53 (dt, J = 9.7, 2.7 Hz, 2 H), 7.62–7.67 (m, 4 H).
+
MS (EI): m/z (%) = 198 (100) [M] , 183 (47).
13
C NMR (100 MHz, CDCl ): d = 55.4, 114.4, 124.3 (q, J = 263.2
3
HRMS: m/z calcd for C H O: 198.1045; found: 198.1032.
Hz), 125.6 (q, J = 3.5 Hz), 126.8, 128.3, 128.5 (q, J = 50.3 Hz),
1
4
14
1
32.1, 144.2, 159.7.
MS (EI): m/z (%) = 252 (100) [M] , 237 (30).
HRMS: m/z calcd for C H F O: 252.0762; found: 252.0745.
4
¢-Methoxy-2-methylbiphenyl (9)
+
–
1
IR (neat): 1612, 1038 cm .
1
14 11 3
H NMR (400 MHz, CDCl ): d = 2.27 (s, 3 H), 3.85 (s, 3 H), 6.94
3
(
dt, J = 8.8, 2.0 Hz, 2 H), 7.20–7.26 (m, 6 H).
4
-tert-Butyldimethylsilyloxymethylbiphenyl (15)
Colorless prisms; mp 61–62 °C (hexane).
Synthesis 2007, No. 18, 2853–2861 © Thieme Stuttgart · New York

PAPER
NHC-Derived Ni(II)-Pincer Complex for Biaryl Synthesis
2859
–
1
13
IR (film): 1092 cm .
1
C NMR (100 MHz, CDCl ): d = 55.3, 114.1, 126.2, 126.6, 127.2,
3
127.7, 128.2, 128.6, 130.2, 137.7, 159.3.
H NMR (400 MHz, CDCl ): d = 0.12 (s, 6 H), 0.96 (s, 9 H), 4.78
s, 2 H), 7.32 (t, J = 7.2 Hz, 1 H), 7.38–7.44 (m, 4 H), 7.55–7.59 (m,
3
+
(
MS (EI): m/z (%) = 210 (100) [M] , 195 (19), 179 (54).
4
H).
HRMS: m/z calcd for C H O: 210.1045; found: 210.1033.
1
5
14
1
3
C NMR (100 MHz, CDCl ): d = –5.2, 18.4, 26.0, 64.7, 126.5,
27.0, 127.06, 127.10, 128.7, 139.9, 140.5, 141.1.
3
1
4-Aminobiphenyl (22)
Light-brown scales; mp 52–53 °C (hexane–EtOAc; Lit. 51 °C).
2
7
+
MS (EI): m/z (%) = 298 (4) [M] , 283 (1), 241 (74), 211 (7), 167
–
1
(
100).
IR (film): 3423, 3393, 3298, 3202, 1620 cm .
1
HRMS: m/z calcd for C H OSi: 298.1753; found: 298.1758.
H NMR (400 MHz, CDCl ): d = 3.65 (br s, 2 H), 6.70 (d, J = 8.4
1
9
26
3
Hz, 2 H), 7.24 (t, J = 7.3 Hz, 1 H), 7.35–7.40 (m, 4 H), 7.51 (d,
3
-Phenylpyridine (16)
J = 7.3 Hz, 2 H).
–1
IR (neat): 3396 cm .
13
C NMR (100 MHz, CDCl ): d = 115.3, 126.2, 126.3, 127.9, 128.6,
3
1
H NMR (400 MHz, CDCl ): d = 7.35–7.43 (m, 2 H), 7.48 (t,
131.4, 141.1, 145.8.
3
J = 7.4 Hz, 2 H), 7.58 (d, J = 7.4 Hz, 2 H), 7.87 (dt, J = 7.8, 1.9 Hz,
MS (EI): m/z (%) = 169 (100) [M]+.
1
H), 8.59 (d, J = 4.0 Hz, 1 H), 8.85 (s, 1 H).
HRMS: m/z calcd for C H N: 169.0892; found: 169.0896.
1
3
12 11
C NMR (100 MHz, CDCl ): d = 123.4, 127.1, 128.0, 129.0, 134.2,
36.5, 137.7, 148.2, 148.3.
3
1
4
-Cyanobiphenyl (24)
MS (EI): m/z (%) = 155 (100) [M]+.
Colorless prisms; mp 85–86 °C (hexane; Lit. 84–86 °C).
21
–
1
HRMS: m/z calcd for C H N: 155.0735; found: 155.0738.
IR (film): 2228 cm .
1
1
9
1
H NMR (400 MHz, CDCl ): d = 7.40–7.50 (m, 3 H), 7.58 (dd,
3
3
-(4-Methoxyphenyl)pyridine (17)
J = 7.2, 1.2 Hz, 2 H), 7.66–7.73 (m, 4 H).
2
4
Colorless prisms; mp 60–61 °C (hexane–EtOAc; Lit. 60–61 °C).
1
3
C NMR (100 MHz, CDCl ): d = 110.8, 118.9, 127.1, 127.6, 128.6,
–
1
3
IR (film): 3373, 1611, 1032 cm .
1
29.0, 132.5, 139.0, 145.5.
1
H NMR (400 MHz, CDCl ): d = 3.86 (s, 3 H), 7.01 (d, J = 8.2 Hz,
H), 7.33 (dd, J = 7.7, 4.7 Hz, 1 H), 7.52 (d, J = 8.2 Hz, 2 H), 7.83
d, J = 7.7 Hz, 1 H), 8.54 (d, J = 4.7 Hz, 1 H), 8.81 (s, 1 H).
MS (EI): m/z (%) = 179 (100) [M]+.
3
2
(
HRMS: m/z calcd for C H N: 179.0735; found: 179.0739.
13
9
1
3
C NMR (100 MHz, CDCl ): d = 55.4, 114.5, 123.4, 128.1, 130.2,
3
3
-Cyanobiphenyl (25)
1
33.7, 136.1, 147.8, 147.9, 159.6.
–1
IR (neat): 2230 cm .
+
MS (EI): m/z (%) = 185 (100) [M] , 170 (43).
1
H NMR (400 MHz, CDCl ): d = 7.40 (t, J = 7.3 Hz, 1 H), 7.47 (t,
3
HRMS: m/z calcd for C H NO: 185.0841; found: 185.0851.
J = 7.3 Hz, 2 H), 7.51–7.56 (m, 3 H), 7.61–7.63 (m, 1 H), 7.80 (d,
1
2
11
J = 7.6 Hz, 1 H), 7.85 (s, 1 H).
1
-Phenylnaphthalene (18)
13
C NMR (100 MHz, CDCl ): d = 112.8, 118.8, 127.0, 128.3, 128.8,
1
3
H NMR (400 MHz, CDCl ): d = 7.39–7.53 (m, 9 H), 7.84–7.90 (m,
3
3
1
29.0, 129.4, 130.6, 131.4, 138.7, 142.3.
H).
MS (EI): m/z (%) = 179 (100) [M]+.
1
3
C NMR (100 MHz, CDCl ): d = 125.3, 125.7, 125.92, 125.94,
3
HRMS: m/z calcd for C H N: 179.0735; found: 179.0719.
1
1
26.8, 127.1, 127.5, 128.2 (2 × C), 130.0, 131.5, 133.7, 140.2,
13
9
40.7.
2
-Cyanobiphenyl (26)
MS (EI): m/z (%) = 204 (100) [M]+.
–1
IR (neat): 2224 cm .
HRMS: m/z calcd for C H : 204.0939; found: 204.0921.
1
1
6
12
H NMR (400 MHz, CDCl ): d = 7.39–7.50 (m, 5 H), 7.54–7.56 (m,
3
2
1
H), 7.62 (td, J = 7.8, 1.3 Hz, 1 H), 7.74 (dd, J = 7.8, 1.3 Hz, 1 H).
1
-(4-Methoxyphenyl)naphthalene (19)
3
2
5
C NMR (100 MHz, CDCl ): d = 111.1, 118.6, 127.4, 128.59,
Colorless prisms; mp 113–115 °C (hexane; Lit. 111–112 °C).
3
1
28.61, 128.64, 130.0, 132.7, 133.6, 138.0, 145.4.
–
1
IR (film): 1609, 1034 cm .
MS (EI): m/z (%) = 179 (100) [M]+.
1
H NMR (400 MHz, CDCl ): d = 3.88 (s, 3 H), 7.02 (d, J = 8.2 Hz,
3
HRMS: m/z calcd for C H N: 179.0735; found: 179.0725.
2
2
H), 7.39–7.52 (m, 6 H), 7.82 (d, J = 8.2 Hz, 1 H), 7.88–7.93 (m,
13
9
H).
4
-Ethoxycarbonylbiphenyl (27)
1
3
C NMR (100 MHz, CDCl ): d = 55.4, 113.7, 125.3, 125.6, 125.8,
28
3
Colorless prisms; mp 49–51 °C (hexane; Lit. 48–49 °C).
1
26.0, 126.8, 127.2, 128.2, 131.0, 131.7, 133.0, 133.7, 139.8, 158.8.
–
1
IR (film): 1711, 1277 cm .
1
+
MS (EI): m/z (%) = 234 (100) [M] , 219 (31).
H NMR (400 MHz, CDCl ): d = 1.40 (t, J = 7.2 Hz, 3 H), 4.38 (q,
3
HRMS: m/z calcd for C H O: 234.1045; found: 234.1028.
1
7
14
J = 7.2 Hz, 2 H), 7.36 (t, J = 7.5 Hz, 1 H), 7.44 (t, J = 7.5 Hz, 2 H),
7
.59–7.64 (m, 4 H), 8.10 (d, J = 8.4 Hz, 2 H).
(
E)-4-Methoxystilbene (20)
Colorless plates; mp 122–124 °C (hexane–EtOAc; Lit. 136–
38 °C).
1
3
2
6
C NMR (100 MHz, CDCl ): d = 14.4, 60.9, 126.8, 127.1, 128.0,
3
1
28.8, 129.1, 129.9, 139.9, 145.3, 166.3.
1
+
–
1
MS (EI): m/z (%) = 226 (71) [M] , 198 (26), 181 (100), 152 (40),
1
IR (film): 1603, 1030 cm .
05 (50), 77 (21).
1
H NMR (400 MHz, CDCl ): d = 3.83 (s, 3 H), 6.90 (d, J = 7.9 Hz,
3
HRMS: m/z calcd for C H O : 226.0994; found: 226.0968.
2
7
H), 6.97 (d, J = 16.4 Hz, 1 H), 7.07 (d, J = 16.4 Hz, 1 H), 7.21–
.50 (m, 1 H), 7.34 (t, J = 7.9 Hz, 2 H), 7.44–7.50 (m, 4 H).
15 14
2
Synthesis 2007, No. 18, 2853–2861 © Thieme Stuttgart · New York

2
860
K. Inamoto et al.
PAPER
see: (a) Kiso, Y.; Tamao, K.; Kumada, M. J. Organomet.
Chem. 1973, 50, C12. (b) Bohm, V. P. W.; Gstottmayr, C.
W. K.; Weskamp, T.; Herrmann, W. A. Angew. Chem. Int.
Ed. 2001, 40, 3387. (c) Mongin, F.; Mojovic, L.; Guillamet,
B.; Trecourt, F.; Queguiner, G. J. Org. Chem. 2002, 67,
8991. (d) Saeki, T.; Takashima, Y.; Tamao, K. Synlett 2005,
2
-Acetylbiphenyl (28)
–1
IR (neat): 1688 cm .
1
H NMR (400 MHz, CDCl ): d = 2.00 (s, 3 H), 7.32–7.44 (m, 7 H),
3
7
.50 (td, J = 7.5, 1.5 Hz, 1 H), 7.56 (dd, J = 7.5, 0.8 Hz, 1 H).
1
3
C NMR (100 MHz, CDCl ): d = 30.5, 127.3, 127.76, 127.78,
3
1
28.6, 128.7, 130.1, 130.6, 140.4, 140.6, 140.8, 204.7.
1771. (e) Yoshikai, N.; Mashima, H.; Nakamura, E. J. Am.
+
Chem. Soc. 2005, 127, 17978. (f) Ackermann, L.; Born, R.;
Spatz, J. H.; Meyer, D. Angew. Chem. Int. Ed. 2005, 44,
MS (EI): m/z (%) = 196 (74) [M] , 181 (100).
HRMS: m/z calcd for C H O: 196.0888; found: 196.0860.
1
4
12
7216. (g) Dankwardt, J. W. J. Organomet. Chem. 2005, 690,
9
32. (h) Ackermann, L.; Born, R.; Spatz, J. H.; Althammer,
2
-Aminobiphenyl (29)
A.; Gschrei, C. J. Pure Appl. Chem. 2006, 78, 209.
9) For C–F bond activation by palladium (selected references),
see: (a) Kim, Y. M.; Yu, S. J. Am. Chem. Soc. 2003, 125,
1696. (b) Widdowson, D. A.; Wilhelm, R. Chem. Commun.
2003, 578.
–
1
IR (neat): 3466, 3373, 1614 cm .
(
1
H NMR (400 MHz, CDCl ): d = 3.74 (br s, 2 H), 6.76 (dd, J = 7.7,
3
0
7
.9 Hz, 1 H), 6.82 (td, J = 7.7, 0.9 Hz, 1 H), 7.11–7.17 (m, 2 H),
.30–7.46 (m, 5 H).
1
3
(10) Dankwardt, J. W. Angew. Chem. Int. Ed. 2004, 43, 2428.
C NMR (100 MHz, CDCl ): d = 115.5, 118.6, 127.1, 128.4, 128.7,
3
(11) Sengupta, S.; Leite, M.; Raslan, D. S.; Quesnelle, C.;
1
29.0, 130.3, 132.5, 139.4, 143.4.
Snieckus, V. J. Org. Chem. 1992, 57, 4066.
MS (EI): m/z (%) = 169 (100) [M]+.
(
12) For recent reviews, see: (a) Crudden, C. M.; Allen, D. P.
Coord. Chem. Rev. 2004, 248, 2247. (b) Kantchev, E. A. B.;
O’Brien, C. J.; Organ, M. G. Angew. Chem. Int. Ed. 2007,
46, 2768. (c) Kuhl, O. Chem. Soc. Rev. 2007, 36, 592.
HRMS: m/z calcd for C H N: 169.0892; found: 169.0885.
1
2
11
4
-Methoxycarbonylbiphenyl (30)
2
1
Colorless prisms; mp 116–117 °C (hexane; Lit. 114–115 °C).
(13) Compared to the Pd/NHC system, there are only a few
reports on Ni/NHC system catalyzed coupling reactions, for
example: (a) For Grignard coupling, see: Matsubara, K.;
Ueno, K.; Shibata, Y. Organometallics 2006, 25, 3422.
(b) For Suzuki–Miyaura coupling, see: Lee, C.-C.; Ke,
W.-C.; Chan, K.-T.; Lai, C.-L.; Hu, C.-H.; Lee, H.-M. Chem.
Eur. J. 2007, 13, 582. (c) For amination, see: Desmarets, C.;
Schneider, R.; Fort, Y. J. Org. Chem. 2002, 67, 3029.
–
1
IR (film): 1709, 1269 cm .
1
H NMR (400 MHz, CDCl ): d = 3.94 (s, 3 H), 7.39 (t, J = 7.5 Hz,
3
1
H), 7.46 (t, J = 7.5 Hz, 2 H), 7.62 (d, J = 7.5 Hz, 2 H), 7.66 (d,
J = 8.0 Hz, 2 H), 8.10 (d, J = 8.0 Hz, 2 H).
1
3
C NMR (100 MHz, CDCl ): d = 52.2, 127.0, 127.2, 128.1, 128.8,
3
1
28.9, 130.1, 139.9, 145.6, 166.9.
(
14) (a) Blakey, S. B.; MacMillan, D. W. C. J. Am. Chem. Soc.
+
MS (EI): m/z (%) = 212 (81) [M] , 181 (100).
2003, 125, 6046. (b) Powell, D. A.; Maki, T.; Fu, G. C. J.
HRMS: m/z calcd for C H O : 212.0837; found: 212.0829.
Am. Chem. Soc. 2005, 127, 510.
15) Inamoto, K.; Kuroda, J.-I.; Hiroya, K.; Noda, Y.; Watanabe,
1
4
12
2
(
4
-Acetylbiphenyl (31)
M.; Sakamoto, T. Organometallics 2006, 25, 3095.
2
1
Colorless needles; mp 121–122 °C (hexane; Lit. 117–119 °C).
(16) For reviews on NHC-derived metal-pincer complexes, see:
a) Peris, E.; Crabtree, R. H. Coord. Chem. Rev. 2004, 248,
239. (b) Pugh, D.; Danopoulos, A. Coord. Chem. Rev.
(
2
–1
IR (film): 1680 cm .
1
H NMR (400 MHz, CDCl ): d = 2.64 (s, 3 H), 7.40 (t, J = 7.8 Hz,
3
2007, 251, 610.
1
H), 7.40 (t, J = 7.8 Hz, 2 H), 7.47 (t, J = 7.8 Hz, 2 H), 7.47 (d,
(17) Compared to Pd-pincer complexes, reports on the synthesis
and catalytic activities of Ni-pincer complexes are much
rarer, for example: (a) For NCN-type, see: Gossage, R. A.;
van de Kuil, L. A.; van Koten, G. Acc. Chem. Res. 1998, 31,
J = 8.4 Hz, 2 H), 8.03 (d, J = 8.4 Hz, 2 H).
1
3
C NMR (100 MHz, CDCl ): d = 26.9, 127.26, 127.31, 128.3,
28.96, 129.00, 135.9, 139.9, 145.8, 197.7.
3
1
423; and references therein. (b) For NNN-type, see:
+
MS (EI): m/z (%) = 196 (64) [M] , 181 (100).
Baldovino-Pantaleon, O.; Hernandez-Ortega, S.; Morales-
Morales, D. Inorg. Chem. Commun. 2005, 8, 955. (c) For
PNP-type, see: Liang, L.-C.; Chien, P.-S.; Lin, J.-M.;
Huang, M.-H.; Huang, Y.-L.; Liao, J.-H. Organometallics
HRMS: m/z calcd for C H O: 196.0888; found: 196.0884.
1
4
12
References
2006, 25, 1399.
(
18) Preliminary results on nickelacycle 1 catalyzed Suzuki–
Miyaura coupling has been reported previously, see
reference 15.
(1) For a recent review, see: Alberico, D.; Scott, M. E.; Lautens,
M. Chem. Rev. 2007, 107, 174.
(
(
2) Bringmann, G.; Menche, D. Acc. Chem. Res. 2001, 34, 615.
3) Hajduk, P. J.; Bures, M.; Praestgaard, J.; Fesik, S. W. J. Med.
Chem. 2000, 43, 3443.
(
(
19) For preparation of nickelacycle 1, see reference 15.
20) (a) Compared to Herrmann’s Ni-NHC monodentate
8
b
system, the rate of this reaction with nickelacycle 1 is
considerably slower. (b) Herrmann proposed a polar
reaction mechanism with his system in the Grignard
(
(
4) Yamamoto, T. Synlett 2003, 425.
5) There are a number of books for Pd- and Ni-catalyzed cross-
coupling reactions, see: de Meijere, A.; Diederich, F. Metal-
Catalyzed Cross-Coupling Reactions, 2nd ed.; Wiley-VCH:
Weinheim, 2004.
8
b
couplings of aryl fluorides. (c) Involvement of a SET
single electron transfer) mechanism in the Grignard
(
couplings of aryl chlorides in the presence of amido pincer
complexes of nickel was suggested recently, see: Wang,
Z.-X.; Wang, L. Chem. Commun. 2007, 2423.
(
6) For recent reviews, see: (a) Littke, A. F.; Fu, G. C. Angew.
Chem. Int. Ed. 2002, 41, 4176. (b) Bedford, R. B.; Cazin, C.
S. J.; Holder, D. Coord. Chem. Rev. 2004, 248, 2283.
7) For a review, see: Kiplinger, J. L.; Richmond, T. G.;
Osterberg, C. E. Chem. Rev. 1994, 94, 373.
(
21) Percec, V.; Golding, G. M.; Smidrkal, J.; Weichold, O. J.
Org. Chem. 2004, 69, 3447.
22) Suresh, C. R. M.; Krishna, R. G. S. Synthesis 1987, 23.
(
(
(
8) For C–F bond activation by nickel (selected references),
Synthesis 2007, No. 18, 2853–2861 © Thieme Stuttgart · New York

PAPER
NHC-Derived Ni(II)-Pincer Complex for Biaryl Synthesis
2861
(
(
23) Denmark, S. E.; Ober, M. H. Org. Lett. 2003, 5, 1357.
24) Parmeintier, M.; Gros, P.; Fort, Y. Tetrahedron 2005, 61,
(26) Zhou, L.; Wang, L. Synthesis 2006, 2653.
(27) Najera, C.; Gil-Molto, J.; Karlström, S.; Falvello, L. R. Org.
Lett. 2003, 5, 1451.
3261.
(
25) Kobayashi, Y.; William, A. D.; Mizojiri, R. J. Organomet.
Chem. 2002, 653, 91.
(28) Ueura, K.; Satoh, T.; Miura, M. Org. Lett. 2005, 7, 2229.
Synthesis 2007, No. 18, 2853–2861 © Thieme Stuttgart · New York