Suzuki-Miyaura coupling reaction of aryl chlorides using di(2,6-dimethylmorpholino)phenylphosphine as ligand

Article abstract of DOI:10.1016/j.tet.2006.12.001

Suzuki-Miyaura coupling was achieved on a variety of aryl chlorides by using di(2,6-dimethylmorpholino)phenylphosphine (L1) as a bulky electron-rich monoaryl phosphine ligand. We report the couplings of various chlorobenzenes and heteroaryl chlorides.

Full text of DOI:10.1016/j.tet.2006.12.001

Tetrahedron 63 (2007) 1345–1352
Suzuki–Miyaura coupling reaction of aryl chlorides using
di(2,6-dimethylmorpholino)phenylphosphine as ligand
Su-Dong Cho,a Ho-Kyun Kim,b Heung-seop Yim,b Mi-Ra Kim,c Jin-Kook Lee,a,
*
Jeum-Jong Kimd and Yong-Jin Yoond,
*
aDepartment of Polymer Science and Engineering, Pusan National University, Busan 609-735, Republic of Korea
bDepartment of Chemistry and Graduate School for Molecular Materials and Nanochemistry,
Gyeongsang National University, Jinju 660-701, Republic of Korea
cCenter for Plastic Information System, Pusan National University, Busan 609-735, Republic of Korea
dDepartment of Chemistry and Environmental Biotechnology National Core Research Center, Graduate School for Molecular
Materials and Nanochemistry, Gyeongsang National University, Jinju 660-701, Republic of Korea
Received 9 June 2006; revised 30 November 2006; accepted 4 December 2006
Abstract—Suzuki–Miyaura coupling was achieved on a variety of aryl chlorides by using di(2,6-dimethylmorpholino)phenylphosphine (L1)
as a bulky electron-rich monoaryl phosphine ligand. We report the couplings of various chlorobenzenes and heteroaryl chlorides.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
ferrocenyldialkylphosphine,17 aryldialkylphosphine,36–38
phosphinous acid,39 palladacycle,15,40 or heterocyclic carb-
ene41–43 classes have been investigated for these reactions.
While several ligands exhibiting improved abilities in assist-
ing the palladium-catalyzed coupling are now available,
a general solution has not yet been completely found for
the metal-catalyzed aryl coupling of all substrates. Thus,
as a part of our ongoing efforts to develop efficient methods
for the coupling of aryl chloride, we investigated the synthe-
sis and coupling reaction of novel air stable phenyl back-
bone-derived PN2 ligands that are easy to prepare. The
reaction setup is experimentally simple and does not require
the use of a glovebox for these reactions.
Pd-catalyzed cross-coupling reactions have become an ex-
tremely versatile tool in organic synthesis for connecting
two fragments via formation of a carbon–carbon bond or
carbon–heteroatom bond.1–4 The Pd-catalyzed Suzuki–
Miyaura coupling reaction is one of the most attractive
method for preparing biaryl compounds thanks to the advan-
tages of wide functional group tolerance and use of stable
and nontoxic organoborane reagents.5–13 Since the general
procedures were discovered, efforts have been made toward
in increasing the substrate scope and efficiency. Although
the use of alternative bases or solvents can be beneficial,
electronic and steric tuning of the supporting ligand has
the most impact on increasing efficacy and reactivity in these
processes.14–29 A major impetus to this field was provided by
the ability to activate the notoriously unreactive but rela-
tively cheap aryl chlorides.30 Not surprisingly, a plethora
of Pd-catalyst systems featuring a Pd-bound ligand are
now accessible for achieving the aforementioned transfor-
mation involving aryl chlorides. It has been well recognized
that ligands employed in these processes have a significant
impact on the outcome of the reactions.31,32 Therefore, de-
signing ligands with appropriate features and great diversity
is crucial in dealing with the challenging substrates in this
area. Typically, the electronically rich and sterically hin-
dered ligands belonging to the trialkylphosphine,33–35
We used ligands 1–4 for the Suzuki–Miyaura coupling of aryl
chlorides as monophenyl backbone-derived PN2 ligands
(Scheme 1). Ligand 4 is commercially available, and ligands
2 and 3 were prepared by the literature method.44 The
ligand 1 was synthesized from dichlorophenylphosphine (5)
(Scheme 2). Here, we report the results of coupling aryl chlo-
ride with phenylboronic acid by using novel PN2 ligands.
O
O
N
N
N
N
N
N
N
N
P
P
P
P
O
O
Keywords: Suzuki–Miyaura coupling; Pd-catalyzed coupling of aryl chlo-
rides; PN2 ligand; C–C coupling reaction.
3
4
2
1
Scheme 1. Bulky electron-rich ligands used in the coupling of aryl
chlorides.
* Corresponding authors. Tel.: +82 55 751 6019; fax: +82 55 761 0244;
e-mail: yjyoon@gnu.ac.kr
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.12.001

1346
S.-D. Cho et al. / Tetrahedron 63 (2007) 1345–1352
Table 2. Screening of Pd-catalystsa
NRR'
NRR'
Cl
Cl
TEA, CH2Cl2
0 °C to reflux
P
+
HNRR'
P
Pd-catalyst, ligand 1,
Cl
B(OH)2
Cs2CO3
NC
5
+
N
N
1,4-Dioxane, reflux
N
-NRR' =
NC
O
2
O
1
3
Entry
Palladium catalyst
Time (min)
Productb (%)
Scheme 2. Syntheses of ligands 1, 2, and 3.
1
Pd2(dba)3
PdCl2
90
90
125
80
95
91
84
92
92
83
32
—
2c
3c
4c
5c
6c
7c
8d
Pd(OAc)2
Pd(PPh3)4
PdCl2(PPh3)2
PdCl2(dppf)2
Pd/C
2. Results and discussion
2.1. Synthesis of ligand 1
80
100
16 h
3 h
Pd2(dba)3
Reaction of dichlorophenylphosphine (5) with 2,6-dimethyl-
morpholin (6) in the presence of triethylamine in refluxing
dichloromethane or toluene gave the corresponding ligand
1 (68%). This ligand in coupling reaction was used without
further purification. The structure of ligand 1 was estab-
lished by IR, NMR, and elemental analysis.
a
Reaction conditions: chlorocyanobenzene (1.0 equiv), phenylboronic
acid (1.25 equiv), ligand 1 (10 mol %), Pd-catalyst (1 mol %), Cs2CO3
(2 equiv), and 1,4-dioxane (20 mL) at reflux temperature.
Isolated yield after silica gel chromatography.
Self-coupling product from boronic acid was isolated in small amounts.
Coupling reaction was carried out in the absence of ligand 1.
b
c
d
Table 3. Screening of basesa
Cl B(OH)2
2.2. Ligand, Pd-catalyst, solvent, and base screening
Pd2(dba)3, ligand 1,
To test the feasibility of the ideas described above, we
initially conducted the reaction of p-cyanochlorobenzene
with phenylboronic acid in refluxing 1,4-dioxane as shown
in Table 1. We used 1.0 mol % of Pd(OAc)2 in combination
with 5 mol % of ligand 1. This reaction proceeded to
successfully afford the desired product in 91% isolated yield
after 1.5 h (Entry 1 in Table 1). With this encouraging result,
we evaluated the efficiency of the three ligands 2–4 in the
same screening. When ligand 2 was used, the product gave
a 74% yield. This reaction, however, did not occur when
ligands 3 and 4 were used.
Base
NC
+
1,4-Dioxane, reflux
NC
Entry
Base
Time (h)
Isolated yield (%)
1
2
3
4
5
6
7
t-BuOK
Cs2CO3
K3PO4
K2CO3
Rb2CO3
KF
3.5
1
1.5
51
1
88
96
87
63
90
36
25
36
36
DMAP
a
Reaction conditions: chlorocyanobenzene (1.0 equiv), phenylboronic
acid (1.25 equiv), ligand 1 (10 mol %), Pd2(dba)3 (1 mol %), base
(4.2 mmol, 2.1 equiv), and 1,4-dioxane (20 mL) at reflux temperature.
Next, we investigated the effect of a variety of palladium
compounds for this reaction. Among the palladium com-
pounds explored, Pd2(dba)3 showed the best result (Entry 1
in Table 2). The coupling reaction, however, did not occur
in the absence of ligand 1 under same condition (Entry 8
in Table 2).
yield (Entries 2 and 5 in Table 3). According to the litera-
tures,45–47 cesium carbonate is a very effective base for
most Pd-catalyzed coupling procedures using phosphine
ligand. We investigated some solvents for coupling reaction
catalyzed by the Pd2(dba)3/1/Cs2CO3 system (Table 4).
Toluene and 1,4-dioxane were found to be an efficacious
solvent (Entries 1 and 4 in Table 4). In general, nonpolar
hydrocarbon (toluene) and ethereal solvent (1,4-dioxane)
are useful solvents in Pd-catalyzed coupling reactions.48
We also investigated a variety of bases for the aforemen-
tioned coupling reaction catalyzed by the Pd2(dba)3/1
system (Table 3). The coupling reaction of chlorocyanobenz-
ene by using Pd2(dba)3/1 system in the presence of Cs2CO3
or Rb2CO3 gave biphenyl-4-carbonitrile in 96% or 90%
Table 1. Screening of ligandsa
Table 4. Screening of solventsa
Pd2(dba)3, ligand 1,
Pd(OAc)2, ligand,
Cl
B(OH)2
t-BuOK
Cl
B(OH)2
Cs2CO3
NC
NC
+
+
Solvent, reflux
1,4-Dioxane, reflux
NC
NC
Entry
Ligand
Time (h)
Productb (%)
Entry
Solvent
Toluene
Acetonitrile
Ethanol
1,4-Dioxane
Tetrahydrofuran
Water
Time (h)
Isolated yield (%)
1
2
3
4
1
2
3
4
1.5
18
24
24
91
74
1
2
3
4
5
6
1
2
4
1
2
24
95
94
85
96
83
14
No reaction
No reaction
a
Reaction conditions: chlorocyanobenzene (2.0 mmol, 1.0 equiv), phenyl-
boronic acid (2.5 mmol, 1.25 equiv), ligand (5 mol %), Pd(OAc)2
(1 mol %), t-BuOK (4.2 mmol, 2.1 equiv), and 1,4-dioxane (20 mL) at
reflux temperature.
a
Reaction conditions: chlorocyanobenzene (1.0 equiv), phenylboronic
acid (1.25 equiv), ligand 1 (10 mol %), Pd2(dba)3 (1 mol %), Cs2CO3
(2 equiv), and solvent (20 mL) at reflux temperature.
b
Isolated yield after silica gel chromatography.

S.-D. Cho et al. / Tetrahedron 63 (2007) 1345–1352
1347
Table 5. Optimization for the coupling of chlorocyanobenzene with phenyl-
boronic acid using 1a
Table 6. Pd-catalyzed coupling of aryl chloridesa
Pd2(dba)3, 1
Pd2(dba)3, ligand 1,
Cs2CO3
Cl
+
B(OH)2
Cs2CO3
B(OH)2
NC
Ar
1,4-Dioxane, reflux
+
Ar-Cl
1,4-Dioxane, reflux
NC
Entry
1 (mol %)
Pd2(dba)3 (mol %)
Time (h)
Yieldb (%)
Entry
1
Aryl chloride
MeO
Time (h)
14
Product yieldb (%)
1
2
3
4
5
1
2
5
10
10
0.5
1
1
1
2
62
43
13
1
82
89
92
96
95
(77)
Cl
MeO
OMe
Cl
OMe
1
2
10
7
(75)
a
Reaction conditions: chlorocyanobenzene (1.0 equiv), phenylboronic
acid (1.25 equiv), ligand 1 (1–10 mol %), Pd2(dba)3 (1 mol %), Cs2CO3
(2 equiv), and 1,4-dioxane (20 mL) at reflux temperature.
Isolated yield after silica gel chromatography.
MeO
MeO
b
3
(70)
Cl
We optimized the coupling of chlorocyanobenzene with
phenylboronic acid by using the Cs2CO3/Pd2(dba)3/1 system
in 1,4-dioxane (Table 5). The ArCl (1 equiv)/ArB(OH)2
4
22
26
1.5
14
16
15
12
10
18
14
(81)
Cl
(1.25 equiv)/Cs2CO3
(2 equiv)/Pd2(dba)3 (1 mol %)/1
(10 mol %) system in 1,4-dioxane showed the best result
(Entry 4 in Table 5).
5
(78)
MeHN
H2N
Cl
MeHN
H2N
Applying the conditions optimized in this research, we eval-
uated the scope of the coupling of various aryl and heteroaryl
chlorides with phenylboronic acid. The coupling of chloro-
benzene containing various substituents with phenylboronic
acid by using Cs2CO3 (2 equiv)/Pd2(dba)3 (1 mol %)/1
(10 mol %) system in 1,4-dioxane gave the corresponding
biphenyls in good to excellent yields (Table 6). The coupling
of chlorobenzenes did not show the general tendency that
depended on the kind of substituents in phenyl ring.
6
(78)
(72)
(96)
(93)
(97)
(87)
(90)
(94)
Cl
O2N
Me
O2N
Me
7
Cl
Cl
8
O
O
On the other hand, the coupling of chloroheteoarenes such as
2-chloropyridine, 2-chlorothiophene, 2-chloropyrimidine,
4-chloropyridazin-3(2H)-one, 4-chlorotetrazole, 2-chloroqui-
noline, and 2-chlorothioxanthen-9-one with phenylboronic
acid under our system gave the corresponding phenyl-
substituted products in good to excellent yields (Table 7).
9
NC
Cl
NC
10
11
12
13
PhO2S
OHC
Cl
PhO2S
OHC
We also investigated the coupling of chlorocyanobenzene
with some arylboronic acids by using the system we devel-
oped (Table 8). The homo-coupling of phenylboronic acids
was predominant when phenylboronic acids containing the
electron-withdrawing groups such as chloro, formyl, and
nitro substituents were used (Entries 1, 4, and 5 in Table 8).
However, the cross-coupling of chlorocyanobenzene was
predominant when 4-methoxy and 4-(N,N-dimethylamino)-
phenylboronic acids were used (Entries 2 and 3 in Table 8).
Cl
MeO2C
O2N
Cl
MeO2C
O2N
Cl
The self-coupling products from the corresponding boronic
acids on TLC were not detected by the coupling of chloro-
cyanobenzene with 2-furanboronic acid and 4-pyridine-
boronic acid.
Cl
14
7
(98)
3. Conclusion
In conclusion, we developed ligand 1 as a new PN2 ligand for
Pd-catalyzed Suzuki–Miyaura coupling of aryl chlorides
with phenylboronic acids. This ligand 1 also has the follow-
ing advantages: as an efficient ligand for Pd-catalyzed cross-
coupling of aryl chlorides, it is stable in air and in organic
a
Reaction conditions: ArCl (1.0 equiv), phenylboronic acid (1.25 equiv),
ligand 1 (10 mol %), Pd2(dba)3 (1 mol %), Cs2CO3 (2 equiv), and 1,4-
dioxane (20 mL) at reflux temperature.
b
Isolated yield after silica gel chromatography.

1348
S.-D. Cho et al. / Tetrahedron 63 (2007) 1345–1352
Table 7. Pd-catalyzed coupling of heteroaryl chloridesa
Pd2(dba)3,1
Cs2CO3
B(OH)2
Ar-Cl
+
Ar
1,4-Dioxane, reflux
Entry
1
Aryl chloride
Time (h)
Product yieldb (%)
OEt
OEt
(96)
N
3
15
7
Cl
N
S
S
Cl
2
3
4
5
6
7
(38)
N
Cl
N
(70)
N
N
OEt
OEt
N
Cl
1.5
N
(95)
N
N
Et
O
Et
O
N
N
6
7
(93)
MeO
N
N
N
MeO
N
Cl
Cl
N
N
N
(72)
N
N
N
N
N
Cl
2
8
(96)
O
O
Cl
8
(95)
S
S
a
Reaction conditions: ArCl (1.0 equiv), phenylboronic acid (1.25 equiv), ligand 1 (10 mol %), Pd2(dba)3 (1 mol %), Cs2CO3 (2 equiv), and 1,4-dioxane
(20 mL) at reflux temperature.
Isolated yield after silica gel chromatography.
b
solvents at high temperature, and easily prepared from cheap
and commercially available dichlorophenylphosphine.
4.2. Typical preparation of PN2 ligands
A mixture of 2,6-dimethylmorpholine (2 equiv), triethyl-
amine (2.2 equiv), and dichloromethane (50 mL) was stirred
for 10 min at room temperature. A dichloromethane solution
of dichlorophenylphosphine 5 (20 mmol of 5 in 200 mL
dichloromethane) was slowly dropped to the above amine
solution, and the mixture was refluxed for 24 h until phos-
phine 5 disappeared. After evaporating the solvent under
reduced pressure, the resulting residue was triturated in
n-hexane, filtered, and washed with n-hexane. The filtrates
containing the product were combined and evaporated under
reduced pressure. The resulting residue was applied to
the top of an open-bed silica gel column (3.0ꢀ7 cm). The
column was eluted with dichloromethane/diethyl ether
(10/1, v/v). Fractions containing the product were com-
bined and evaporated under reduced pressure to give
4. Experimental
4.1. General
Melting points were determined with a capillary apparatus
and are uncorrected. 1H and 13C NMR spectra were recorded
on a 300 MHz spectrometer with the chemical shift values
reported in d units (ppm) relative to an internal standard
(TMS). The IR spectra were obtained on an IR spectropho-
tometer. Elemental analyses were performed with a Perkin–
Elmer 240C. The open-bed chromatography was carried out
on silica gel (70w230 mesh, Merck) using gravity flow. The
column was packed with slurries made from the elution
solvent.

S.-D. Cho et al. / Tetrahedron 63 (2007) 1345–1352
1349
Table 8. Pd-catalyzed coupling of aryl chlorides with some phenylboronic
was purified by chromatography on silica gel using dichloro-
methane/n-hexane (1:2, v/v) to afford the coupled product.
acidsa
Pd2(dba)3,1
Cs2CO3
Cl
Ar
CN
4.3.1. Biphenyl. Mp 68–71 ꢂC (lit.49 mp 68–70 ꢂC); IR (po-
tassium bromide) n 3008, 2986, 1602, 1424 cmꢁ1; 1H NMR
(CDCl3) d 7.18–7.65 (m, 10H) ppm; 13C NMR (CDCl3)
d 127.23, 127.31, 128.81, 141.32 ppm. Elemental analysis
calcd for C12H10: C, 93.46; H, 6.54. Found: C, 93.51; H 6.60.
+
Ar-B(OH)2
1,4-Dioxane, reflux
NC
Entry
Boronic acid
Time
(h)
Product yieldb (%)
1c
2d
3d
4e
5f
36
6
(—)
CN
4.3.2. Biphenyl-4-carbonitrile. Mp 85–87 ꢂC, IR (potas-
Cl
B(OH)2
Cl
1
sium bromide) n 3012, 2984, 2224, 1432 cmꢁ1; H NMR
(CDCl3) d 7.24–7.66 (m, 9H) ppm; 13C NMR (CDCl3)
d 110.80, 118.95, 127.22, 127.70, 128.72, 129.16, 132.59,
139, 145.56 ppm. Elemental analysis calcd for C13H9N: C,
87.12; H, 5.06; N, 7.82. Found: C, 87.17; H, 5.11; N, 7.88.
Elemental analysis calcd for C13H9N: C, 87.12; H, 5.06;
N, 7.82. Found: C, 87.20; H, 5.12; N, 7.91.
(92)
CN
MeO
(Me)2N
OHC
B(OH)2
MeO
(Me)2N
OHC
6
(90)
CN
B(OH)2
B(OH)2
6
(52)
CN
4.3.3. 4-Nitrobiphenyl. Mp 113–115 ꢂC; IR (potassium
1
bromide) n 3062, 3028, 1602, 1550, 1518, 1340 cmꢁ1; H
B(OH)2
CN
NMR (CDCl3) d 8.31–8.26 (m, 2H), 7.75–7.70 (m, 2H),
7.63–7.60 (m, 2H), 7.52–7.41 (m, 3H) ppm; 13C NMR
(CDCl3) d 147.63, 147.15, 138.79, 129.15, 128.91, 127.79,
127.38, 124.09 ppm. Elemental analysis calcd for
C12H9NO2: C, 72.35; H, 4.55; N, 7.03. Found: C, 72.40;
H, 4.58; N, 7.09.
24
40
3
(19)
O2N
O2N
O
O
6g
(6)
B(OH)2
CN
CN
7
(76)
N
B(OH)2
N
4.3.4. Biphenyl-4-carboxylic acid methyl ester. Mp 115–
117 ꢂC. IR (potassium bromide) n 3042, 2988, 1738, 1622,
a
Reaction conditions: chlorocyanobenzene (1.0 equiv), boronic acid
(1.25 equiv), ligand (10 mol %), Pd2(dba)3 (1 mol %), Cs2CO3
1460, 1422, 1308, 1130, 764 cmꢁ1 1H NMR (CDCl3)
;
1
d 8.10 (d, J¼8.4 Hz, 2H), 7.65–7.58 (m, 4H), 7.47–7.36
(m, 3H), 3.92 (s, 3H) ppm; 13C NMR (CDCl3) d 166.97,
145.64, 140.02, 130.11, 128.96, 128.93, 127.27, 127.04,
52.07 ppm. Elemental analysis calcd for C14H12O2: C,
79.22; H, 5.70. Found: C, 80.2; H, 5.81.
(2 equiv), and 1,4-dioxane (20 mL) at reflux temperature.
Isolated yield after silica gel chromatography.
Only self-coupling product from boronic acid was isolated in poor yield.
Self-coupling product from boronic acid was detected on TLC.
Self-coupling product from boronic acid was isolated in poor yield.
b
c
d
e
f
Self-coupling product from boronic acid was isolated as the main product.
Reaction was not proceeded completely.
g
4.3.5. 2-Methoxybiphenyl. Colorless oil (lit.50 mp 30–
33 ꢂC); IR (potassium bromide) n 3060, 2926, 1599, 1499,
di(2,6-dimethylmorpholino)phenylphosphine (1). Ligand in
coupling reaction was used without further purification.
1482, 1258, 1025 cmꢁ1 1H NMR (CDCl3) d 7.81–7.78
;
(m, 2H), 7.66–7.50 (m, 5H), 7.29–7.17 (m, 2H), 3.98 (s,
3H) ppm; 13C NMR (CDCl3) d 156.75, 138.86, 131.11,
131.02, 129.80, 128.84, 128.20, 127.12, 121.10, 111.57,
55.70 ppm. Elemental analysis calcd for C13H12O: C,
84.75; H, 6.57. Found: C, 84.79; H, 6.59.
4.2.1. Ligand 1. Yield: 68%. Colorless oil, IR (potassium
1
bromide) n 3012, 2904, 1436, 1366, 1120, 1048 cmꢁ1; H
NMR (CDCl3) d 7.81–7.30 (m, 5H), 3.87–3.78 (m, 4H),
3.51–3.44 (m, 2H), 2.99 (d, J¼12.16 Hz, 4H), 2.44–2.40
(m, 2H), 1.10 (s, CH3), 1.08 (s, CH3) ppm; 13C NMR
(CDCl3) d 11.69, 47.92, 69.71, 128.15, 128.32, 126.60,
129.74 ppm. Elemental analysis calcd for C18H29N2O2P:
C, 64.26; H, 8.69; N, 8.33. Found: C, 64.31; H, 8.71; N 8.40.
4.3.6. 3-Methoxybiphenyl. Colorless oil; IR (potassium
1
bromide) n 3054, 2959, 1599, 1479, 1266, 1220 cmꢁ1; H
NMR (CDCl3) d 7.57–7.53 (m, 2H), 7.41–7.35 (m, 2H),
7.32–7.26 (m, 2H), 7.16–7.09 (m, 2H), 6.87–6.83 (m, 1H),
3.78 (s, 3H) ppm; 13C NMR (CDCl3) d 160.14, 142.92,
141.25, 129.90, 128.87, 127.55, 127.32, 119.83, 113.09,
112.85, 55.36 ppm. Elemental analysis calcd for C13H12O:
C, 84.75; H, 6.57. Found: C, 84.78; H 6.61.
4.3. Typical C–C coupling of aryl chlorides
A dried resealable Schlenk tube was charged with Pd2(dba)3
(0.03 mmol, 1 mol % of Pd), aryl chloride (2.0 mmol),
phenylboronic acid (2.5 mmol, 1.25 equiv), and ligand 1
(10 mol %) in 1,4-dioxane (20 mL). The mixture was stirred
for 5 min at room temperature under nitrogen atmosphere.
Cesium carbonate (4.2 mmol, 2.1 equiv) was added to the re-
action mixture. After the septum was replaced with a Teflon
screwcap, the mixture was refluxed until aryl chloride had
been completely consumed as judged by TLC. The reaction
mixture was then cooled to room temperature and filtered.
The filtrate was concentrated in vacuo. The crude material
4.3.7. 4-Methoxybiphenyl. Mp 89–90 ꢂC (lit.50 mp 86–
90 ꢂC); IR (potassium bromide) n 3050, 2958, 1606, 1516,
1485, 1272, 1037 cmꢁ1 1H NMR (CDCl3) d 7.56–7.49
;
(m, 4H), 7.43–7.38 (m, 2H), 7.31–7.26 (m, 1H), 6.99–6.94
(m, 2H), 3.84 (s, 3H) ppm; 13C NMR (CDCl3) d 159.20,
140.87, 133.83, 128.72, 128.16, 126.75, 126.66, 114.24,
55.35 ppm. Elemental analysis calcd for C13H12O: C,
84.75; H, 6.57. Found: C, 84.77; H, 6.60.

1350
S.-D. Cho et al. / Tetrahedron 63 (2007) 1345–1352
4.3.8. 1-Biphenyl-4-ylpropan-1-one. Mp 96–98 ꢂC; IR
(potassium bromide) n 3048, 2982, 1680, 1600, 1218,
128.21, 127.93, 127.66, 127.34 ppm. Elemental analysis
calcd for C18H14O2S: C, 73.44; H, 4.79. Found: C, 73.50;
H, 4.82.
1
750 cmꢁ1; H NMR (CDCl3) d 8.04–8.02 (m, 2H), 7.68–
7.59 (m, 4H), 7.49–7.36 (m, 3H), 3.04 (q, J¼7.26 Hz, 2H),
1.25 (t, J¼7.24 Hz, 3H) ppm; 13C NMR (CDCl3) d 200.40,
145.55, 139.97, 135.68, 128.93, 128.57, 128.16, 127.25,
127.20, 31.83, 8.32 ppm. Elemental analysis calcd for
C15H14O: C, 85.68; H, 6.71. Found: C, 85.73; H, 6.79.
4.3.15. 9-Phenylanthracene. Mp 153–154 ꢂC (lit.52 mp
153–155 ꢂC); IR (potassium bromide) n 3046, 1436, 1008,
1
870, 726, 696 cmꢁ1; H NMR (CDCl3) d 8.62 (br s, 1H),
8.11–8.16 (m, 2H), 7.36–7.65 (m, 11H) ppm; 13C NMR
(CDCl3) d 126.10, 126.42, 127.21, 127.54, 128.29, 129.43,
131.02, 131.94, 132.44, 137.71, 139.62 ppm. Elemental
analysis calcd for C20H14: C, 94.45; H, 5.55. Found: C,
94.51; H, 5.58.
4.3.9. 40-Methoxybiphenyl-4-carbonitrile. Mp 103–
104 ꢂC; IR (potassium bromide) n 3038, 2988, 2220, 1602,
1
1242, 1174, 1132, 822 cmꢁ1; H NMR (CDCl3) d 7.69–
7.60 (m, 4H), 7.55–7.50 (m, 2H), 7.02–6.97 (m, 2H),
3.85 (s, 3H) ppm; 13C NMR (CDCl3) d 160.27, 145.22,
132.55, 131.51, 128.35, 127.10, 119.06, 114.59, 110.16,
55.40 ppm. Elemental analysis calcd for C14H11NO: C,
80.36; H, 5.30; N, 6.69. Found: C, 80.41; H, 5.37; N, 6.71.
4.3.16. Biphenyl-4-carbaldehyde. Mp 56–58 ꢂC (lit.49 mp
57–59 ꢂC); IR (potassium bromide) n 3006, 2832, 1690,
1
1592, 1200, 720 cmꢁ1; H NMR (CDCl3) d 10.05 (s, 1H),
7.96–7.92 (m, 2H), 7.76–7.73 (m, 2H), 7.65–7.61 (m, 2H),
7.50–7.38 (m, 3H), 5.25 (d, J¼10.88 Hz, 1H), 2.83 (s,
3H) ppm; 13C NMR (CDCl3) d 191.83, 147.21, 139.75,
135.26, 130.25, 129.01, 128.47, 127.69, 127.37 ppm. Ele-
mental analysis calcd for C13H10O: C, 85.69; H, 5.53.
Found: C, 85.72; H, 5.55.
4.3.10. 1,5-Diphenyl-1H-tetrazole. Mp 144–145 ꢂC; IR
(potassium bromide) n 3070, 1590, 1495, 1470, 1110, 760,
1
696 cmꢁ1; H NMR (CDCl3) d 7.82–7.78 (m, 2H), 7.61–
7.39 (m, 7H), 7.33–7.25 (m, 1H) ppm; 13C NMR (CDCl3)
d 159.41, 153.53, 133.17, 130.04, 129.75, 129.46, 126.53,
122.22, 119.37 ppm. Elemental analysis calcd for
C13H10N4: C, 70.26; H, 4.54; N, 25.21. Found: C, 70.30;
H, 4.60; N, 25.27.
4.3.17. 3-Ethoxy-2-phenylpyridine. Colorless oil; IR
(potassium bromide) n 3053, 2974, 1628, 1444, 1400,
1
1340, 1274, 1256, 1160, 950, 782, 698 cmꢁ1; H NMR
(CDCl3) d 8.25 (dd, J¼1.54, 4.41 Hz, 1H), 7.80–7.96 (m,
2H), 7.42–7.28 (m, 3H), 7.12–7.02 (m, 2H), 3.89 (q,
J¼7.2 Hz, 2H), 1.29 (t, J¼7.2 Hz, 3H) ppm; 13C NMR
(CDCl3) d 152.98, 147.92, 141.20, 137.96, 129.46, 128.17,
127.84, 122.90, 119.71, 64.10, 14.62 ppm. Elemental analy-
sis calcd for C13H13NO: C, 78.36; H, 6.58; N, 7.03. Found:
C, 78.40; H, 6.61; N, 7.09.
4.3.11. 5-Ethoxy-2-ethyl-4-phenyl-2H-pyridazin-3(2H)-
one. Mp 88–89 ꢂC; IR (potassium bromide) n 3042, 2966,
1
1632, 1444, 1400, 1340, 1258, 1160, 950 cmꢁ1; H NMR
(CDCl3) d 7.88 (s, 1H), 7.49–7.42 (m, 5H), 4.26 (q,
J¼7.18 Hz, 2H), 3.86 (q, J¼7.11 Hz, 2H), 1.39 (t,
J¼7.17 Hz, 3H), 1.28 (t, J¼7.13 Hz, 3H) ppm; 13C NMR
(CDCl3) d 160.71, 154.72, 130.42, 130.38, 128.25, 127.78,
127.63, 121.38, 57.15, 47.36, 13.59, 13.54 ppm. Elemental
analysis calcd for C14H16N2O2: C, 68.83; H, 6.60; N,
11.47. Found: C, 68.88; H, 6.67; N, 11.51.
4.3.18. 4-Methyl-3-nitrobiphenyl. Mp 61–62 ꢂC, IR
(potassium bromide) n 3052, 2960, 1522, 1496, 1434, 880,
1
742, 686 cmꢁ1; H NMR (CDCl3) d 8.12 (d, J¼1.93 Hz,
1H), 7.64 (dd, J¼1.95, 7.95 Hz, 1H), 7.54–7.50 (m, 2H),
7.44–7.31 (m, 4H), 2.57 (s, 3H) ppm; 13C NMR (CDCl3)
d 149.63, 140.27, 138.46, 133.24, 132.20, 131.25, 129.11,
128.27, 126.88, 122.87, 20.07 ppm. Elemental analysis
calcd for C13H11NO2: C, 73.23; H, 5.20; N, 6.57. Found:
C, 73.26; H, 5.24; N, 6.61.
4.3.12. Biphenyl-4-yl-methylamine. Mp 67–69 ꢂC; IR (po-
tassium bromide) n 3402, 3042, 2874, 2800, 1600, 1490,
1
822, 756 cmꢁ1; H NMR (CDCl3) d 7.55–7.51 (m, 2H),
7.46–7.42 (m, 2H), 7.39–7.34 (m, 2H), 7.26–7.20 (m, 1H),
6.67–6.62 (m, 2H), 3.67 (br s, NH), 2.83 (s, 3H) ppm; 13C
NMR (CDCl3) d 148.81, 141.39, 130.23, 128.69, 127.94,
126.34, 126.07, 112.75, 30.80 ppm. Elemental analysis
calcd for C13H13N: C, 85.21; H, 7.15; N, 7.64. Found: C,
85.24; H, 7.19; N, 7.70.
4.3.19. 2-Phenylthioxanthen-9-one. Mp 128–129 ꢂC; IR
(potassium bromide) n 3036, 1642, 1594, 1442, 1324,
1
1136, 750 cmꢁ1; H NMR (CDCl3) d 8.84 (d, J¼2.11 Hz,
1H), 8.62 (dd, J¼1.30, 8.10 Hz, 1H), 7.82 (dd, J¼2.14,
8.37 Hz, 1H), 7.70–7.67 (m, 2H), 7.60–7.55 (m, 3H), 7.49–
7.43 (m, 3H), 7.40–7.35 (m, 1H) ppm; 13C NMR (CDCl3)
d 179.89, 139.48, 139.29, 137.16, 136.06, 132.24, 130.95,
129.94, 129.47, 129.23, 128.99, 127.87, 127.80, 127.06,
126.52, 126.31, 126.04 ppm. Elemental analysis calcd for
C19H12OS: C, 79.14; H, 4.19. Found: C, 79.18; H, 4.23.
4.3.13. 4-Vinylbiphenyl. Mp 118–120 ꢂC (lit.51 mp 119–
121 ꢂC); IR (potassium bromide) n 3006, 2996, 1464,
1
1382, 994, 842 cmꢁ1; H NMR (CDCl3) d 7.60–7.54 (m,
4H), 7.49–7.39 (m, 4H), 7.34–7.29 (m, 1H), 6.75 (dd,
J¼10.88, 17.59 Hz, 1H), 5.75 (s, J¼17.59 Hz, 1H), 5.25
(d, J¼10.88 Hz, 1H) ppm; 13C NMR (CDCl3) d 140.79,
140.64, 136.67, 136.47, 128.80, 127.33, 127.25, 126.99,
126.68, 113.89 ppm. Elemental analysis calcd for C14H12:
C, 93.29; H, 6.71. Found: C, 93.32; H, 6.74.
4.3.20. 2-Phenylpyrazine. Mp 74–75 ꢂC; IR (potassium
bromide) n 3050, 1474, 1447, 1409, 1082, 1010, 772, 744,
1
692 cmꢁ1; H NMR (CDCl3) d 9.00 (d, J¼1.54 Hz, 1H),
4.3.14. 4-Benzenesulfonylbiphenyl. Mp 148–149 ꢂC; IR
8.60 (dd, J¼1.61, 2.49 Hz, 1H), 8.47 (d, J¼2.51 Hz, 1H),
8.02–7.98 (m, 2H), 7.52–7.44 (m, 3H) ppm; 13C NMR
(CDCl3) d 152.84, 144.15, 142.81, 142.14, 136.28, 129.90,
129.01, 126.92 ppm. Elemental analysis calcd for C10H8N2:
C,76.90;H, 5.16;N,17.94.Found:C,76.98;H,5.21;N,18.01.
1
(potassium bromide) n 3072, 1320, 1160, 1116 cmꢁ1; H
NMR (CDCl3) d 8.01–7.96 (m, 4H), 7.69–7.66 (m, 2H),
7.58–7.35 (m, 8H) ppm; 13C NMR (CDCl3) d 146.18,
141.81, 140.20, 139.16, 133.19, 129.33, 129.06, 128.60,

S.-D. Cho et al. / Tetrahedron 63 (2007) 1345–1352
1351
4.3.21. 3-(4-Methoxyphenoxy)-6-phenylpyridazine. Mp
171–172 ꢂC; IR (potassium bromide) n 3082, 2992, 1520,
1442, 1306, 1254, 1214, 1042, 850 cmꢁ1 1H NMR
(CDCl3) d 8.03–7.98 (m, 2H), 7.85 (d, J¼9.21 Hz, 1H),
7.51–7.44 (m, 3H), 7.20–7.08 (m, 3H), 6.97–6.92 (m, 2H),
3.82 (s, 3H); 13C NMR (CDCl3) d 165.38, 157.04, 155.98,
146.97, 135.98, 129.58, 128.93, 127.45, 126.62, 122.22,
117.35, 114.90, 55.68 ppm. Elemental analysis calcd for
C18H16N2O: C, 78.24; H, 5.84; N, 10.14. Found: C, 78.28;
H, 5.90; N, 10.18.
References and notes
;
1. Handbook of Organopalladium Chemistry for Organic
Synthesis; Negishi, E.-I., Ed.; Wiley Interscience: New York,
NY, 2002.
2. Heck, R. F. Palladium Reagents in Organic Synthesis;
Academic: New York, NY, 1985.
3. Principles and Applications of Organotransition Metal
Chemistry; Collman, J. P., Hegedus, L. S., Norton, J. R.,
Finke, R. G., Eds.; University Science: Mill Valley, CA, 1987.
4. Metal-Catalyzed Cross-Coupling Reactions; Diederich, F.,
Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998.
5. Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
6. Suzuki, A. Metal-Catalyzed Cross-Coupling Reagents;
Diederichc, F., Stang, P. J., Eds.; Wiley-VCH: Weinheim,
Germany, 1998, Chapter 2.
7. Suzuki, A. J. Organomet. Chem. 1999, 576, 147.
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Int. Ed. 2001, 40, 4544.
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12. Suzuki, A. Morden Arene Chemistry; Astruc, D., Ed.; Wiley-
VCH: Weinheim, 2002; pp 53–106.
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14. Zapf, A.; Ehrentraut, A.; Beller, M. Angew. Chem., Int. Ed.
2000, 39, 4153.
4.3.22. 2-Phenylquinoline. Mp 83–84 ꢂC (lit.53 mp 84–
85 ꢂC); IR (potassium bromide) n 3062, 3032, 1604,
1
1550 cmꢁ1; H NMR (CDCl3) d 8.20–8.14 (m, 4H), 7.86–
7.78 (m, 2H), 7.73–7.68 (m, 1H), 7.54–7.42 (m, 4H) ppm;
13C NMR (CDCl3) d 157.41, 148.33, 139.72, 136.78,
129.75, 129.67, 129.33, 128.85, 127.61, 127.47, 127.22,
126.29, 119.03 ppm. Elemental analysis calcd for
C15H11N: C, 87.77; H, 5.40; N, 6.82. Found: C, 87.80; H,
5.44; N, 6.86.
4.3.23. 2-Phenylthiophene. Mp 34–36 ꢂC (lit.54 mp 34–
36 ꢂC); IR (potassium bromide) n 3065, 3014, 1596, 1523,
1
1486 cmꢁ1; H NMR (CDCl3) d 7.63–7.57 (m, 3H), 7.46–
7.26 (m, 5H) ppm; 13C NMR (CDCl3) d 141.27, 128.86,
128.73, 127.44, 127.23, 127.16, 125.97, 124.77 ppm. Ele-
mental analysis calcd for C10H8S: C, 74.96; H, 5.03. Found:
C, 74.99; H, 5.09.
15. Schnyder, A.; Indolese, A. F.; Studer, M.; Blaser, H.-U. Angew.
Chem., Int. Ed. 2002, 41, 3668.
16. Stambuli, J. P.; Kuwano, R.; Hartwig, J. F. Angew. Chem., Int.
Ed. 2002, 41, 4746.
17. Kataoka, N.; Shelby, Q.; Stambuli, J. P.; Hartwig, J. F. J. Org.
Chem. 2002, 67, 5553.
18. Li, G. Y. J. Org. Chem. 2002, 67, 3643.
19. Hu, Q.; Lu, Y.; Tang, Z.; Yu, H. J. Am. Chem. Soc. 2003, 125,
2856.
4.3.24. 4-(Pyridine-4-yl)benzonitrile. Mp 77–78 ꢂC (lit.55
mp 75–76 ꢂC); IR (potassium bromide) n 3036, 2226,
1598, 1398 cmꢁ1; 1H NMR (CDCl3) d 8.73 (d, J¼4.85 Hz,
2H), 7.73–7.81 (m, 4H), 7.51 (d, J¼5.93 Hz, 2H) ppm; 13C
NMR (CDCl3) d 150.60, 146.36, 142.62, 132.91, 127.77,
121.62, 118.38, 112.83 ppm. Elemental analysis calcd for
C12H8N2: C, 79.98; H, 4.47; N, 15.55. Found: C, 80.01; H,
4.50; N, 15.61.
20. Altenhoff, G.; Goddard, R.; Lehmann, C. W.; Glorius, F.
Angew. Chem., Int. Ed. 2003, 42, 3690.
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26. Colacot, T. L.; Shea, H. A. Org. Lett. 2004, 6, 3731.
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4.3.25. 40-(Dimethylamino)biphenyl-4-carbonitrile. Mp
218–220 ꢂC (lit.56 mp 222–223 ꢂC); IR (potassium bromide)
n 3048, 2910, 2226, 1593, 1529, 1492, 1446, 1360,
812 cmꢁ1 1H NMR (CDCl3) d 7.63 (m, 4H), 7.51 (d,
;
J¼8.83 Hz, 2H), 6.79 (d, J¼8.85 Hz, 2H), 3.02 (s,
6H) ppm; 13C NMR (CDCl3) d 150.77, 145.59, 132.51,
127.88, 126.37, 126.32, 119.43, 112.54, 108.99,
40.33 ppm. Elemental analysis calcd for C15H14N2: C,
81.05; H, 6.35; N, 12.60. Found: C, 81.01; H, 6.32; N, 12.59.
4.3.26. 40-Formylbiphenyl-4-carbonitrile.17 Mp 151–
152 ꢂC (lit.57 mp 150–150.5 ꢂC); IR (potassium bromide) n
3043, 2226, 1702, 1598, 1394, 1261, 1095, 1022,
1
812 cmꢁ1; H NMR (CDCl3) d 10.09 (s, 1H), 7.71–8.02
(m, 8H) ppm; 13C NMR (CDCl3) d 191.60, 144.92,
144.16, 136.15, 132.80, 130.43, 128.05, 127.93,
112.18 ppm. Elemental analysis calcd for C14H9NO:
C, 81.14; H, 4.38; N, 6.76. Found: C, 81.13; H, 4.40; N, 6.79.
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Acknowledgements
This study was financially supported by Pusan National
University in Program Post-Doc 2006.

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