Versatile palladium(II)-catalyzed Suzuki-Miyaura coupling in ethanol with a novel, stabilizing ligand

Article abstract of DOI:10.1016/j.tet.2015.04.052

Suzuki-Miyaura coupling reactions of arylboronic acids with aryl bromides were mediated by PdCl₂ and bdppmapy (N,N-bis-(diphenylphosphanylmethyl)-2-aminopyridine) that both stabilizes and solubilizes the catalyst in predominantly ethanol as a solvent. Excellent yields for a wide variety of substrates were obtained under relatively mild conditions in this 'green' solvent.

Full text of DOI:10.1016/j.tet.2015.04.052

Tetrahedron 71 (2015) 4000e4006
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Versatile palladium(II)-catalyzed SuzukieMiyaura coupling
in ethanol with a novel, stabilizing ligand
Jin-Jiao Ning , Jian-Feng Wang , Zhi-Gang Ren *, David James Young c,
a
a
a,b,
a,b,
*
Jian-Ping Lang
a
College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, PR China
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 210032, PR China
School of Science, Monash University Malaysia, Jalan Lagoon Selatan, 47500 Bandar Sunway, Selangor Darul Ehsan, Malaysia
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
SuzukieMiyaura coupling reactions of arylboronic acids with aryl bromides were mediated by PdCl2 and
bdppmapy (N,N-bis-(diphenylphosphanylmethyl)-2-aminopyridine) that both stabilizes and solubilizes
the catalyst in predominantly ethanol as a solvent. Excellent yields for a wide variety of substrates were
obtained under relatively mild conditions in this ‘green’ solvent.
Received 6 February 2015
Received in revised form 15 April 2015
Accepted 18 April 2015
Available online 23 April 2015
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
SuzukieMiyaura coupling
Palladium(II)
P-Donor ligand
Aryl halide
Arylboronic acid
0
0
1
. Introduction
instance, a tetraphosphine ligand, N,N,N ,N -tetra(diphenylphos-
phinomethyl)-1,2-ethylenediamine (dppeda), was used in the
coupling of aryl and heteroaryl bromides, which led to the yield of
Numerous modifications have been made to the reaction con-
ditions of the SuzukieMiyaura cross-coupling reaction and the
13e
98% with the PdCl
2
loading of 0.001 mol %.
However, such
carbonylative SuzukieMiyaura reaction since their discoveries in
1
a catalyst system sometimes involves ligands that are complicated
and difficult to synthesize.
979 and 1993,2 respectively. Diaryl compounds are widespread
1
14
structural motifs in natural products and pharmacologically active
The most frequently used solvents for these coupling reactions
are acetone, toluene, THF, acetonitrile, and DMF, which can be
3
15
compounds. The SuzukieMiyaura reactions have provided highly
4
efficient routes to otherwise challenging Csp2eCsp2 bond formation.
somewhat expensive, toxic, and difficult to recycle. Water-phase
SuzukieMiyaura reactions are an area of intensive investigation,
but plagued with the low solubility of most substrates and
Recent advances in this chemistry include ligand-free and/or ‘green’
5
,6
reaction conditions with water or alcohol solubilizing ligands.
7
10b,16e19
These include bulky or electron rich phosphines, nitrogen-do-
nors, N-heterocyclic carbenes, and other ligands capable of in-
catalysts.
8
9
10
Ethanol is an alternative renewable solvent, which is relatively
cheap and nontoxic. Importantly, the range of organic substrates
soluble in this solvent is much greater than those that are soluble in
water. However, ethanol soluble palladium catalyst systems are not
well studied.
creasing the electron density at palladium and thereby accelerating
11
the oxidative addition step in the catalytic cycle. Among these li-
gands, phosphines are the best known and still widely used because
12
of their superior stabilization of the catalytically active Pd(0).
One disadvantage of palladium catalysts is their cost and the
potential for toxic contamination of pharmaceutical products.
Many groups have therefore investigated Pd composites that can be
easily separated and/or ultra-low loadings of catalyst.13 For
P- and N-donor ligands bearing large groups are of interest
because of their ability to stabilize transition metal catalysts.
Additional N-donors in the ligand also accelerate certain re-
6
c
actions, even when there is no observable metalenitrogen in-
2
0
teraction in the pre-catalyst.
For example, a N-containing
bis(phosphine) ligand displayed much higher activity in rhodium-
21
catalyzed hydroformylation than did its all carbon analogue. An
amino-substituted P,S-phosphinite was also found to be more
*
Corresponding authors. Tel.: þ86 512 6588 2865; fax: þ86 512 6588 0328;
e-mail address: jplang@suda.edu.cn (J.-P. Lang).
http://dx.doi.org/10.1016/j.tet.2015.04.052
0
040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

J.-J. Ning et al. / Tetrahedron 71 (2015) 4000e4006
4001
efficient in the palladium-catalyzed Heck reaction22 and in a rho-
We initially evaluated the importance of different ligands (Table
1). Without ligand, the yield after 1.5 h was low relatively (13%,
Table 1, entry 1). The utilization of bidentate ligands led to higher
yields (Table 1, entries 4e6) than with monodentate triphenyl-
phosphine and the backbone structure of the phosphines influ-
enced the reaction rate (Table 1, entry 3). The highest yield was
obtained with bdppmapy (Table 1, entry 2). Because the role of the
pyridyl group in bdppmapy is unknown, a controlled experiment
using its phenyl analogue, N,N-bis((diphenylphosphanyl)methyl)
dium-catalyzed hydroformylation compared to the corresponding
2
3
ligand without an amino group.
A new complex [(bdppmapy)PdCl
2
2
], constructed from PdCl and
a hybrid diphosphine-pyridine ligand bdppmapy (N,N-bis-(diphe-
nylphosphanylmethyl)-2-aminopyridine) exhibits good catalytic
performance in the decarboxylative CeC coupling of 4-piconic acid
2
4
and aromatic bromides. We herein report the extension of this
investigation to the SuzukieMiyaura cross-coupling reaction of
arylboronic acids with aryl halides in predominantly ethanol as
a solvent.
2
5
aniline (bdppma), was performed. The yield (Table 1, entry 7) was
the same as that using bdppmapy, implying that the pyridyl group
in bdppmapy worked in the same manner as the phenyl group in
bdppma, and could not coordinate to the Pd(II) center during the
catalysis. Both groups only exhibited the steric hindrance effect,
2
6
which is beneficial to the catalysis of the coupling reactions.
We then investigated the lower limit of the catalyst loading
0
(
Table 2). The electron-poor substrate 4 -bromoacetophenone was
almost completely converted into the desired product using
ꢀ
0
2
0
.01 mol % PdCl
2
and 0.01 mol % bdppmapy for 0.5 h at 78 C (Table
,
entry 1). When the catalyst loading was decreased to
.005 mol %, 4 -bromoacetophenone could not be detected after 1 h
2
. Results and discussion
0
(
0
Table 2, entry 2). A yield of 99% was still achieved in the presence of
.002 mol % catalyst after 1.5 h (Table 2, entry 3), but only 82% yield
0
The coupling of 4 -bromoacetophenone (1 mmol) and 4-
methoxyphenylboronic acid (1.5 mmol) was chosen as a model
reaction. Because the amount of the catalyst loading was quite low
was observed after 1 h (Table 2, entry 4). Finally, a high yield was
obtained with a catalyst loading as low as 0.001 mol % if the re-
action time was prolonged to 4 h (Table 2, entry 5). These results
indicated that the catalyst system has good longevity, which is at-
tributed to the effective stabilization of the active palladium species
by this bidentate phosphine. This lower catalyst loading was the
same as the literature value using a tetraphosphine ligand (dppe-
da).
performed in dioxane in a longer time (20 h) and at a higher
temperature (90 C).
(
ranging 0.001e0.01 mol %) in this work, which related to the
weighing of less than 0.067 mg, [(bdppmapy)PdCl ] was used as
a 0.01 M DMF solution to prevent large deviation (the solubility of
(bdppmapy)PdCl ] is lower in ethanol and its 0.01 M ethanol so-
lution could not be prepared). As we reported previously, the
solution of [(bdppmapy)PdCl ] in DMF was the same as that made
in situ from mixing PdCl with equimolar bdppmapy in DMF. All
reactions were performed by using 1e10 L of such a PdCl
bdppmapy DMF solution and 4 mL of ethanol. The positive-ion ESI
mass spectrum of this palladium/bdppmapy complex in DMF (2 L)
2
[
2
2
4
2
13e
However, the latter reaction reached 98% yield but was
2
m
2
/
ꢀ
m
in ethanol (4 mL) was examined and provided an insight into its
solution behavior (Fig. 1). A significant signal at m/z¼716.08 could
Table 1
þ
The effect of different phosphine ligands on the SuzukieMiyaura cross-coupling
reaction
be assigned to the [(bdppmapy)Pd$DMF$CH
3
CH
2
O] cation (Fig. 1).
2
þ
The detection of this cation implied that the ligand and Pd were
coordinated and stable in solution. Similar cations were observed in
the corresponding ESI investigation of the more commonly used
triphenylphosphine or diphosphines N,N-bis((diphenylphos-
Entry
Ligand
Yield (%)
2
5
0
phanyl)methyl)aniline (bdppma),
1,1 -bis(diphenylphosphino)
1
2
3
4
5
6
7
No ligand
bdppmapy
PPh3
dppm
dppe
13
99
79
85
80
82
99
methane (dppm), 1,2-bis(diphenylphosphino)ethane (dppe) or 1,3-
bis(diphenylphosphino)propane (dppp) (Fig. S1eS5, Suppl
ementary data).
dppp
bdppma
0
Reaction conditions: 4 -bromoacetophenone 1 mmol, 4-methoxyphenylbor-onic
acid 1.5 mmol, K
3
PO
4
3 mmol, ethanol 4 mL, L/PdCl
2
¼1:1 (entries 2e7), catalyst
ꢀ
0.002 mol % Pd, 1.5 h, 78 C, analyzed by GC, average of two runs.
Table 2
2
The effect of time and PdCl loadings on the SuzukieMiyaura cross-coupling
reaction
Entry
Pd loading (mol %)
Time (h)
Yield (%)
1
2
3
4
5
0.01
0.5
1
1.5
1
99
99
99
82
99
0.005
0.002
0.002
0.001
4
0
Reaction conditions: 4 -bromoacetophenone 1 mmol, 4-methoxyphenylbor-onic
ꢀ
Fig. 1. The positive-ion ESI mass spectrum (top) and the calculated isotope pattern
acid 1.5 mmol, K
average of two runs.
3
PO
4
3 mmol, ethanol 4 mL, L/PdCl
2
¼1:1, 78 C, analyzed by GC,
þ
(
below) of the [(bdppmapy)Pd$DMF$CH
3
CH
2
O] in the catalyst system.

4002
J.-J. Ning et al. / Tetrahedron 71 (2015) 4000e4006
Next, we investigated the influence of solvents, bases, and
could be coupled with good to excellent yields, even over extended
periods, under-scoring the stabilizing ability of this ligand.
temperatures on this coupling reaction (Table 3). The reactions
were performed in some common solvents (4 mL) in the presence
of the palladiumebisphosphine bdppmapy catalyst (0.01 mol %),
combined in a small quantity of DMF, and with a base (3 mmol) at
4. Experimental
4.1. General
2
different temperatures for 2 h under a N atmosphere. Only 15% of
0
0
product 1-(4 -methoxy-[1,1 -biphenyl]-4-yl)ethan-1-one was ob-
ꢀ
tained with water as solvent and K
entry 1). Ethanol and K PO
and an environmentally friendly combination (Table 3, entry 5).
This catalytic reaction could adopt EtOH/H O as a mixed solvent
system. The yield could reach 99% when the ratio of EtOH/H O was
:2 (entries 9e12). However, it fell to 37% when the ratio of EtOH/
3
PO
4
as base at 100 C (Table 3,
All reactions were carried out under nitrogen atmosphere using
standard Schlenk-techniques. Solvents were dried by conventional
methods. The two ligands (bdppma and bdppmapy) were prepared
3
4
, however, proved to be both efficient
2
5,27
2
according to the literature procedures.
All other reagents were
1
13
2
used as received from commercial suppliers. H NMR and C NMR
spectra were recorded at ambient temperature on a Varian
UNITYplus-300, 400 and 600 spectrometers. H NMR and C NMR
chemical shifts were referenced to the solvent signal in CDCl or
DMSO-d . Electrospray ion mass spectra (ESI-MS) were performed
1
H
1
13
2
O was 1:4 (entry 13). The reaction did depend on the tempera-
ture as the yield decreased to 94% and 3% as the reaction was car-
3
ꢀ
ꢀ
ried out at 60 C and 40 C, respectively (entries 14 and 15). Thus,
we decided to choose ethanol as the optimized solvent taking into
account the solubility of different substrates and the refluxing
temperature.
6
on an Agilent 1200/6200 mass spectrometer. GC measurements
were recorded on an Agilent 7820A Gas Chromatograph with an
Agilent HP-5 chromatographic column and N as mobile phase. The
2
With optimal reaction conditions in hand, we turned our at-
tention to the range of potential substrates. Unsurprisingly, aryl
bromides were better substrates than an aryl fluoride or chloride
LCeMS were recorded in a Rapid Resolution HT-3 chromatographic
column on an Agilent 1260 Infinity Liquid Chromatograph with
6120 Quadrupole Mass Spectrometer and MeCN as mobile phase.
(
Table 4, entries 12 and 25, respectively) and an activating group at
the para-position of the aryl bromide was the highest yielding
Table 4, entry 1). In contrast, reaction with the same group at the
more hindered ortho-position leads to a significantly lower yield
Table 4, entry 5). These coupling conditions were tolerant of a wide
4.2. General procedure for the SuzukieMiyaura reaction
(
2
The ligand bdppmapy (4.9 mg, 0.01 mmol) and PdCl (1.8 mg,
(
0.01 mmol) were added to a Schlenk tube containing a magnetic
stirrer bar, and then degassed DMF (1 mL) was added. The mixture
range of functionality in the aryl halide (Table 4, entries 6e13) and
arylboronic acid (Table 4, entries 14e24).
0
was stirred 3 h at room temperature. 4 -Bromoacetophenone
While the heteroaryl 2-bromopyridine was a reasonable sub-
strate under these conditions (Table 4, entry 13), heteroaryl boronic
acids were variable (Table 4, entries 20e23), with thiophen-2-
ylboronic acid reacting very slowly (Table 4, entry 21). One-pot
double arylation of o-, or m-, or p-dibromobenzene (Table 4, en-
tries 26e28) with 4-methoxyphenylboronic acid proceeded in
reasonable to good yields.
(199 mg,1 mmol), 4-methoxyphenylboronic acid (228 mg,1.5 mmol),
and K
with a magnetic stirrer bar. The dissolved mixture of bdppmapy/
PdCl (2 L, 0.00002 mmol) was transferred to the Schlenk tube of
3 4
PO (637 mg, 3 mmol) were added to another Schlenk tube
2
m
reactants by syringe. Then, ethanol (4 mL) was added. The reaction
mixture was heated at reflux for 1.5 h. At the end of the reaction, the
solution was cooled to room temperature and water (5 mL) was
added. The mixture solution was extracted with ethyl acetate
(3ꢁ5 mL) and the organic layer was dried over magnesium sulfate.
The dried solution was filtered and reduced to approx.1e2 mL under
vacuum, then purified with silica gel chromatography to give the
corresponding product with an isolated yield. See Supplementary
data for general experimental details, ESI-MS data of the catalysts,
and characterization data for the catalytic products.
3
. Conclusions
2
In summary, we have developed an efficient PdCl /bdppmapy
catalytic system for the SuzukieMiyaura coupling reaction of
arylboronic acid with aryl bromides in predominantly ethanol as
a solvent under moderate conditions. A wide range of substrates
.2.1. 1-(4 -Methoxy-[1,1 -biphenyl]-4-yl)ethanone. 1H
400 MHz, CDCl , ppm):
8.00 (d, J¼8.0 Hz, 2H), 7.64 (d, J¼8.0 Hz,
2H), 7.58 (d, J¼8.0 Hz, 2H), 7.00 (d, J¼8.0 Hz, 2H), 3.86 (s, 3H), 2.62
0
0
28
NMR
4
(
Table 3
3
d
The effect of solvents, bases, and temperature on the SuzukieMiyaura cross-
coupling reaction
13
(
3
s, 3H). C NMR (100 MHz, CDCl , ppm): d 197.7, 159.9, 145.4, 135.3,
132.3, 129.0, 128.4, 126.6, 114.4, 55.4, 26.7.
ꢀ
Entry
Solvent
Base
T ( C)
Yield (%)
.2.2. 1-(2 -Methoxy-[1,1 -biphenyl]-4-yl)ethanone. 1H
, ppm):
8.00 (d, J¼8.0 Hz, 2H), 7.63 (d, J¼8.0 Hz,
H), 7.38e7.32 (q, 2H), 7.07e6.99 (m, 2H), 3.82 (s, 3H), 2.63 (s, 3H).
29
0
0
4
(
NMR
1
2
3
4
5
6
7
8
9
H
2
O
3
K PO
3
K PO
3
K PO
3
K PO
3
K PO
4
4
4
4
4
100
100
100
100
78
78
78
78
78
78
78
78
78
60
40
15
65
59
99
99
72
85
67
99
99
99
99
37
94
3
400 MHz, CDCl
3
d
DMF
2
Dioxane
Toluene
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol/H
Ethanol/H
Ethanol/H
Ethanol/H
Ethanol/H
Ethanol
Ethanol
1
3
C NMR (100 MHz, CDCl
129.8, 129.5, 128.1, 121.0, 114.4, 55.6, 26.7.
3
, ppm): d 197.9, 156.5, 143.6, 135.5, 130.7,
KOH
CO
NaOH
K
2
3
.2.3. 1-(3 -Methoxy-[1,1 -biphenyl]-4-yl)ethanone.. 1H
400 MHz, CDCl , ppm):
8.03 (d, J¼8.0 Hz, 2H), 7.68 (d, J¼8.0 Hz,
2H), 7.39 (t, J¼8.0 Hz, 1H), 7.21 (d, J¼8.0 Hz, 1H), 7.15 (s, 1H), 6.95 (d,
30
0
0
4
(
NMR
3
d
2
O¼4:1
2
O¼2:1
2
O¼1:1
2
O¼1:2
2
O¼1:4
3
K PO
3
K PO
3
K PO
3
K PO
3
K PO
3
K PO
3
K PO
4
4
4
4
4
4
4
1
1
1
1
1
1
0
1
2
3
4
5
13
J¼8.0 Hz, 1H), 3.88 (s, 3H), 2.64 (s, 3H). C NMR (100 MHz, CDCl
ppm): 197.8, 160.0, 145.6, 141.4, 136.0, 130.0, 128.9, 127.3, 119.8,
13.5, 113.1, 55.4, 26.7.
3
,
d
1
4.2.4. 1-(4 -Methoxy-[1,1 -biphenyl]-3-yl)ethanone. 1H
400 MHz, CDCl , ppm):
8.14 (t, J¼2.0 Hz, 1H), 7.88 (d, J¼8.0 Hz,
1H), 7.75 (d, J¼8.0 Hz, 1H), 7.56 (d, J¼8.0 Hz, 2H), 7.51 (t, J¼8.0 Hz,
0
0
29
NMR
0
Reaction conditions: 4 -bromoacetophenone 1 mmol, 4-methoxyphenylboro-nic
(
3
d
acid 1.5 mmol, base 3 mmol, solvent 4 mL, L/PdCl
analyzed by GC, average of two runs.
2
¼1:1, catalyst 0.01 mol % Pd, 2 h,

J.-J. Ning et al. / Tetrahedron 71 (2015) 4000e4006
4003
Table 4
SuzukieMiyaura coupling of aryl halide with arylboronic acid
0
Entry
1
ArX
Ar B(OH)
2
Product
Yield (%)
99
95
2
3
4
92
82
5
6
70
91
7
8
9
94
95
93
93
1
0
1
1
82
1
1
2
3
65
75
1
1
4
5
96
95
1
1
1
6
7
8
92
91
80
1
2
9
78
0a
90
(
continued on next page)

4004
J.-J. Ning et al. / Tetrahedron 71 (2015) 4000e4006
Table 4 (continued )
0
Entry
ArX
Ar B(OH)
2
Product
Yield (%)
2
2
2
2
1a
2a
3a
4a
Trace
93
92
nr
2
5a
32
2
2
6a,b
7a,b
90
73
2
8a,b
65
Reaction conditions: aryl halides 1 mmol, arylboronic acids 1.5 mmol, K
3
PO
4
3 mmol, ethanol 4 mL, L/PdCl
2
¼1:1, catalyst 0.01 mol % PdCl
2
, reflux, 1.5 h, isolated yield, average
of two runs.
a
2
Catalyst 0.1 mol % PdCl .
Aryl halides 1 mmol, arylboronic acids 3 mmol, K PO 6 mmol, ethanol 8 mL.
3 4
b
1
H), 7.00 (d, J¼8.0 Hz, 2H), 3.86 (s, 3H), 2.65 (s, 3H). 13C NMR
(d, J¼8.0 Hz, 2H), 3.86 (s, 3H). 13C NMR (100 MHz, CDCl
3
, ppm):
(
100 MHz, CDCl
3
, ppm):
d
198.2, 159.5, 141.3, 137.6, 131.3, 129.0,
d
160.2, 145.2, 132.6, 131.5, 128.4, 127.1, 119.1, 114.5, 110.1, 55.4.
1
28.2, 126.6, 126.4, 114.3, 55.4, 26.8.
.2.11. 4 -Methoxy-3,5-bis(trifluoromethyl)-1,1 -biphenyl. 1H NMR
, ppm):
7.96 (s, 2H), 7.80 (s, 1H), 7.55 (d, J¼8.0 Hz,
2H), 7.04e7.01 (d, J¼12.0 Hz, 2H), 3.87 (s, 3H). C NMR (100 MHz,
CDCl , ppm): 160.3, 142.9, 131.9, 130.6, 128.4, 127.5, 126.7, 124.8,
122.1, 120.2, 119.4, 114.7, 55.4.
0
0
32
4
.2.5. 1-(4 -Methoxy-[1,1 -biphenyl]-2-yl)ethanone. 1H
0
0
29
NMR
(400 MHz, CDCl
d
4
3
13
(
400 MHz, CDCl
3
, ppm):
d
7.53e7.47 (q, 2H), 7.38 (t, J¼8.0 Hz, 2H),
7
3
.27 (d, J¼8.0 Hz, 2H), 6.96 (d, J¼8.0 Hz, 2H), 3.85 (s, 3H), 2.01 (s,
3
d
13
3
H). C NMR (100 MHz, CDCl , ppm): d 205.3, 159.5, 140.9, 133.0,
1
30.6, 130.1, 130.0, 127.8, 127.0, 114.1, 55.3, 30.4.
0
0
29
4
.2.12. 4-Fluoro-4 -methoxy-1,1 -biphenyl. 1H NMR (400 MHz,
CDCl , ppm): 7.50e7.45 (q, 4H), 7.11e7.07 (t, 2H), 6.98e6.95 (d,
J¼12.0 Hz, 2H), 3.84 (s, 3H). C NMR (100 MHz, CDCl
160.9, 159.1, 137.0, 132.8, 128.3, 128.2, 128.0, 115.6, 115.4, 114.2, 55.3.
.2.6. 4-Methoxy-4 -methyl-1,1 -biphenyl. 1H NMR (400 MHz,
, ppm):
7.57 (d, J¼8.0 Hz, 2H), 7.50 (d, J¼8.0 Hz, 2H), 7.23
d, J¼8.0 Hz, 2H), 7.00 (d, J¼8.0 Hz, 2H), 3.79 (s, 3H), 2.32 (s, 3H).
NMR (100 MHz, DMSO-d , ppm): 158.6, 136.9, 135.8, 132.4, 129.4,
0
0
28
d
4
3
13
DMSO-d
6
d
3
, ppm): d 163.3,
1
3
(
C
6
d
127.4, 125.9, 114.2, 55.1, 20.6.
4.2.13. 2-(4-Methoxyphenyl)pyridine.28 1H NMR (400 MHz, CDCl
ppm):
8.66 (d, J¼4.0 Hz, 1H), 7.96 (d, J¼12.0 Hz, 2H), 7.74 (t,
3
,
d
0
0
28
1
4.2.7. 4,4 -Dimethoxy-1,1 -biphenyl.
H NMR (400 MHz, CDCl
3
,
C
J¼8.0 Hz, 1H), 7.68 (d, J¼8.0 Hz, 1H), 7.21e7.17 (m, 1H), 7.00 (d,
13
13
ppm):
NMR (100 MHz, CDCl
d
7.47 (d, J¼8.0 Hz, 4H), 6.95 (d, J¼8.0 Hz, 4H), 3.83 (s, 6H).
J¼12.0 Hz, 2H), 3.86 (s, 3H). C NMR (100 MHz, CDCl
3
, ppm):
3
, ppm):
d
158.7, 133.5, 127.7, 114.2, 55.4.
d
160.6, 156.9, 149.2, 137.0, 131.6, 128.2, 121.5, 120.0, 114.2, 55.4.
.2.8. 4-Methoxy-4 -nitro-1,1 -biphenyl. 1H NMR (400 MHz,
CDCl , ppm):
8.26 (d, J¼8.0 Hz, 2H), 7.68 (d, J¼8.0 Hz, 2H), 7.58 (d,
J¼8.0 Hz, 2H), 7.03e7.00 (d, J¼12.0 Hz, 2H), 3.87 (s, 3H). C NMR
100 MHz, CDCl , ppm): 160.5, 147.2, 146.6, 131.1, 128.6, 127.1,
24.2, 114.6, 55.5.
0
0
28
4.2.14. 1-(4 -Methyl-[1,1 -biphenyl]-4-yl)ethan-1-one. 1H
(400 MHz, CDCl , ppm):
2H), 7.53 (d, J¼8.0 Hz, 2H), 7.28 (d, J¼8.0 Hz, 2H), 2.63 (s, 3H), 2.41
0
0
33
NMR
4
3
d
3
d
8.01 (d, J¼8.0 Hz, 2H), 7.67 (d, J¼8.0 Hz,
13
13
(
1
3
d
(s, 3H). C NMR (100 MHz, CDCl , ppm): 197.8, 145.7, 138.2, 136.9,
3
d
135.5, 129.7, 128.9, 127.1, 126.9, 26.7, 21.2.
.2.9. 4 -Methoxy-[1,1 -biphenyl]-4-carbaldehyde.31 1H
400 MHz, CDCl , ppm):
10.03 (s, 1H), 7.92 (d, J¼8.0 Hz, 2H), 7.71
d, J¼8.0 Hz, 2H), 7.59 (d, J¼8.0 Hz, 2H), 7.01 (d, J¼8.0 Hz, 2H), 3.87
0
0
NMR
4.2.15. 1-([1,1 -Biphenyl]-4-yl)ethan-1-one. 1H NMR (400 MHz,
0
29
4
(
(
(
3
d
CDCl , ppm):
3
d
8.03 (d, J¼8.0 Hz, 2H), 7.68 (d, J¼8.0 Hz, 2H),
7.63e7.62 (d, J¼4.0 Hz, 2H), 7.47 (d, J¼8.0 Hz, 2H), 7.40 (t, J¼8.0 Hz,
1
3
13
s, 3H). C NMR (100 MHz, CDCl
3
, ppm):
d
191.9, 160.1, 146.8, 134.7,
1H), 2.63 (s, 3H). C NMR (100 MHz, CDCl
139.8, 135.8, 128.9, 128.2, 127.2, 26.6.
3
, ppm): d 197.7, 145.7,
1
32.0, 130.3, 128.5, 127.0, 114.5, 55.4.
.2.10. 4-Cyano-4 -methoxy-1,1 -biphenyl. 1H NMR (400 MHz,
0
0
28
4.2.16. 1-(4 -Fluoro-[1,1 -biphenyl]-4-yl)ethan-1-one. 1H
0
0
33
NMR
4
CDCl
3
, ppm):
d
7.70e7.62 (q, 4H), 7.55e7.52 (d, J¼12.0 Hz, 2H), 7.00
(400 MHz, CDCl , ppm):
3
d
8.04e8.01 (d, J¼12.0 Hz, 2H), 7.63 (d,

J.-J. Ning et al. / Tetrahedron 71 (2015) 4000e4006
4005
J¼8.0 Hz, 2H), 7.61e7.57 (q, 2H), 7.16 (t, J¼8.0 Hz, 2H), 2.64 (s, 3H).
Higher Education Institutions, and the ‘SooChow Scholar’ Program
of Soochow University. The authors are grateful to the comments of
the reviewers and the editor.
13
3
C NMR (100 MHz, CDCl , ppm): d 197.6, 164.2, 161.8, 144.7, 136.0,
135.9, 135.8, 129.0, 128.9, 127.1, 116.0, 115.8, 26.7.
0 0
.2.17. 1-(4 -(Trifluoromethyl)-[1,1 -biphenyl]-4-yl)ethan-1-
4
Supplementary data
10b 1
one.
.73 (s, 4H), 7.69 (d, J¼8.0 Hz, 2H), 2.65 (s, 3H). C NMR (100 MHz,
CDCl , ppm): 197.6, 144.2, 143.4, 136.6, 130.4, 130.1, 129.1, 127.6,
H NMR (400 MHz, CDCl
3
, ppm):
d
8.06 (d, J¼8.0 Hz, 2H),
13
7
1H and 13C NMR spectra for the isolated products. Supplemen-
tary data associated with this article can be found in the online
version, at http://dx.doi.org/10.1016/j.tet.2015.04.052.
3
d
1
27.5, 126.0, 125.9, 125.8, 122.8, 26.7.
.2.18. 1-(4 -Nitro-[1,1 -biphenyl]-4-yl)ethan-1-one. 1H
, ppm):
8.35e8.32 (d, J¼12.0 Hz, 2H), 8.10 (d,
J¼8.0 Hz, 2H), 8.04 (d, J¼8.0 Hz, 2H), 7.93 (d, J¼8.0 Hz, 2H), 2.65 (s,
0
0
34
NMR
4
(
References and notes
400 MHz, DMSO-d
6
d
1
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13
3
6
H). C NMR (75 MHz, DMSO-d , ppm): d 198.0, 147.6, 145.7, 142.4,
2
137.2, 129.5, 128.0, 124.6, 27.3.
2
4
5
. Wolfe, J. P.; Buchwald, S. L. Angew. Chem., Int. Ed. 1999, 38, 2413.
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4
.2.19. 1-(4-(Naphthalen-1-yl)phenyl)ethan-1-one.35 1H
, ppm):
8.09 (d, J¼8.0 Hz, 2H), 7.92 (t, J¼8.0 Hz,
H), 7.84 (d, J¼8.0 Hz, 1H), 7.61 (d, J¼8.0 Hz, 2H), 7.56e7.50 (m, 2H),
NMR
(
400 MHz, CDCl
3
d
6. (a) Liu, C.; Ni, Q. J.; Bao, F. Y.; Qiu, J. S. Green Chem. 2011, 13, 1260; (b) Wu, Q. X.;
2
13
Wu, L. L.; Zhang, L.; Fu, H. Y.; Zheng, X. L.; Chen, H.; Li, R. X. Tetrahedron 2014,
7
7.47e7.42 (m, 2H), 2.69 (s, 3H). C NMR (100 MHz, CDCl
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, ppm):
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. (a) Mori, K.; Yamaguchi, K.; Hara, T.; Mizugaki, T.; Ebitani, K.; Kaneda, K. J. Am.
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197.9, 145.8, 139.0, 136.0, 133.8, 131.2, 130.3, 128.4, 128.3, 126.9,
7
126.4, 126.0, 125.6, 125.3, 26.7.
2
4
.2.20. 1-(4-(Thiophen-3-yl)phenyl)ethan-1-one.36 1H
, ppm):
8.10e8.08 (q, 1H), 8.00 (d, J¼8.0 Hz,
H), 7.89 (d, J¼8.0 Hz, 2H), 7.71e7.69 (q, 1H), 7.68e7.66 (q, 1H), 2.60
, ppm): 197.7, 140.7, 139.8,
NMR
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6
d
8
9
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2
(
s, 3H). 13C NMR (75 MHz, DMSO-d
d
6
135.7, 129.4, 128.0, 126.7, 126.5, 123.6, 27.2.
2
4
.2.21. 1-(4-(Benzofuran-2-yl)phenyl)ethan-1-one.37 1H
, ppm):
8.04e7.92 (q, 4H), 7.61 (d, J¼8.0 Hz, 1H),
.54 (d, J¼8.0 Hz, 1H), 7.35e7.31 (t, J¼8.0 Hz, 1H), 7.25e7.24 (d,
NMR
6
(
400 MHz, CDCl
3
d
1
7
13
J¼4.0 Hz, 1H), 7.15 (s, 1H), 2.63 (s, 3H). C NMR (100 MHz, CDCl
3
,
11. Mondal, M.; Bora, U. Tetrahedron Lett. 2014, 55, 3038.
ppm): 197.3, 155.2, 154.5, 136.5, 134.6, 128.9, 125.2, 124.8, 123.3,
d
12. Surry, D. S.; Buchwald, S. L. Angew. Chem., Int. Ed. 2008, 47, 6338.
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nomet. Chem. 2012, 26, 342.
4
.2.22. 1-(4-(Benzo[b]thiophen-2-yl)phenyl)ethan-1-one.38 1H NMR
, ppm):
8.01 (d, J¼8.0 Hz, 2H), 7.86e7.78 (m, 4H),
(
400 MHz, CDCl
3
d
13
7.66 (s, 1H), 7.38e7.35 (m, 2H), 2.63 (s, 3H). C NMR (100 MHz,
1
4. (a) Shi, J. C.; Zhou, Z. G.; Zheng, S.; Qing, Z.; Li, J.; Lin, J. H. Tetrahedron Lett. 2014,
CDCl
3
, ppm):
d
197.3, 142.6, 140.5, 139.9, 138.7, 136.4, 129.1, 126.4,
55, 2904; (b) Monnereau, L.; Moll, H. E.; S eꢀ meril, D.; Matt, D.; Toupet, L. Eur. J.
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125.0, 124.8, 122.4, 121.2, 26.6.
1
5. Liu, L. F.; Wang, W. D.; Xiao, C. Y. J. Organomet. Chem. 2014, 749, 83.
0
0
0
0
00
39
4
CDCl
.2.23. 4,4 -Dimethoxy-1,1 :4 ,1 -terphenyl. 1H NMR (400 MHz,
1
6. (a) Greico, P. A. Organic Synthesis in Water; Blackie Academic & Professional:
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3
, ppm):
d
7.61 (s, 4H), 7.57 (d, J¼8.0 Hz, 4H), 7.01e6.98 (d,
1
3
J¼12.0 Hz, 4H), 3.86 (s, 6H). C NMR (100 MHz, CDCl
3
, ppm):
d
159.1, 139.1, 133.3, 128.0, 127.0, 114.2, 55.3.
1
7. (a) Sakurai, H.; Tsukuda, T.; Hirao, T. J. Org. Chem. 2002, 67, 2721; (b) Bumagin,
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0
0
0
0
00
39
4
18. (a) Bedford, R. B.; Blake, M. E.; Butts, C. P.; Holder, D. Chem. Commun. 2003, 466;
CDCl
3
, ppm):
d
7.72 (s, 1H), 7.58 (d, J¼8.0 Hz, 4H), 7.50e7.46 (m, 3H),
(b) Badone, D.; Baroni, M.; Cardamone, R.; Ielmini, A.; Guzzi, U. J. Org. Chem.
13
7.69 (d, J¼8.0 Hz, 4H), 3.86 (s, 6H). C NMR (100 MHz, CDCl
3
, ppm):
1997, 62, 7170; (c) Arvela, R. K.; Leadbeater, N. E. Org. Lett. 2005, 7, 2101; (d)
Arcadi, A.; Cerichelli, G.; Chiarini, M.; Correa, M.; Zorzan, D. Eur. J. Org. Chem.
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159.2, 141.3, 133.8, 129.1, 128.2, 125.3, 125.1, 114.2, 55.4.
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3
083; (f) Xin, B. W.; Zhang, Y. H.; Cheng, K. Synthesis 2007, 13, 1970; (g) Lead-
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, ppm):
7.39e7.34 (m, 4H), 7.06 (d, J¼8.0 Hz, 4H), 6.76 (d,
J¼8.0 Hz, 4H), 3.77 (s, 6H). C NMR (100 MHz, CDCl
40.0, 134.1, 130.9, 130.5, 127.1, 113.3, 55.1.
0
0
0
0
00
40
4
CDCl
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3
d
1
3
3
, ppm): d 158.2,
1
2
2
3. Kostas, I. D.; Steele, B. R.; Andreadaki, F. J.; Potapov, V. A. Inorg. Chim. Acta 2004,
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The authors thank the financial supports from the National
Natural Science Foundation of China (21171124, 21271134 and
1371126) and State Key Laboratory of Organometallic Chemistry,
2
Shanghai Institute of Organic Chemistry, Chinese Academy of Sci-
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