Acyclic aminocarbene-like palladium complex-catalyzed Suzuki-Miyaura reaction at low catalyst loadings

Article abstract of DOI:10.1016/j.tet.2015.10.033

A series of air-stable aminocarbene-like palladium(II) complexes were easily prepared by the reaction of bis-aromaticisocyanide-dichloropalladium(II) with N-arylbenzamidines. 0.1 mol % of the optimal palladium complex 3a showed excellent catalytic activity for Suzuki-Miyaura cross-coupling reaction at room temperature and the desired products were isolated in up to 98% yields. Moreover, a large-scale reaction showed that 0.01 mol % 3a was enough to catalyze the coupling reaction efficiently at room temperature to give the desired product in 93% yield.

Full text of DOI:10.1016/j.tet.2015.10.033

Tetrahedron 71 (2015) 9679e9683
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Acyclic aminocarbene-like palladium complex-catalyzed
SuzukieMiyaura reaction at low catalyst loadings
*
*
Yi Fang, Shun-Yi Wang , Shun-Jun Ji
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science & Collaborative Innovation
Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 18 June 2015
Received in revised form 11 October 2015
Accepted 14 October 2015
Available online 2 November 2015
A series of air-stable aminocarbene-like palladium(II) complexes were easily prepared by the reaction of
bis-aromaticisocyanide-dichloropalladium(II) with N-arylbenzamidines. 0.1 mol % of the optimal palla-
dium complex 3a showed excellent catalytic activity for SuzukieMiyaura cross-coupling reaction at room
temperature and the desired products were isolated in up to 98% yields. Moreover, a large-scale reaction
showed that 0.01 mol % 3a was enough to catalyze the coupling reaction efficiently at room temperature
to give the desired product in 93% yield.
Keywords:
Isocyanide
Ó 2015 Elsevier Ltd. All rights reserved.
Acyclic aminocarbene
SuzukieMiyaura cross-coupling
Palladium catalyst
1. Introduction
reactions.7 Pd-PEPPSIÔ (Fig. 1), a commercial palladium catalyst
based on cyclic imidazole carbene ligands, showed great catalytic
Since 1950s, the development and application of cross-coupling
reactions including Kumada coupling,1 Heck coupling,2 Suzu-
kieMiyaura coupling3 and Negishi coupling4 have made great
contribution to the rapid development of organic synthetic chem-
istry, pharmaceutical chemistry and chemistry of materials.5 It is an
attractive field that scientists are focusing on pioneering highly
efficient catalysts to achieve the above coupling reactions. Phos-
phine ligands, a series of efficient ligands for cross-coupling re-
actions, have been applied in various palladium-catalyzed coupling
reaction for a long time.6 However, most of the phosphine ligands
are toxic and sensitive to air and water. It is of great importance to
develop the phosphine-free ligand for the Pd-catalyzed coupling
activity in the CeC8 and CeN9 coupling reactions. However, there
are less researches focused on the synthesis of complex based on
the acyclic aminocarbene ligands and their catalytic activity,10
comparatively. Recently, it has drawn attentions to design and
synthesize new metal catalysts based on the acyclic aminocarbene
ligands,11 due to its diverse configurations and regulatable struc-
tures. Acyclic aminocarbene complex has been reported to catalyze
the SuzukieMiyaura coupling reactions.12 However, the catalyst is
difficult to be prepared and air-sensitive. What’s more, the reaction
required high catalyst loading under heating conditions. It is still
a challenge to develop efficient acyclic aminocarbene complexes for
such coupling reactions.
It is well known that metaleisocyanide complex could react
with nucleophile to give the corresponding acyclic aminocarbene
complex. As a continuation on the study of isocyanide chemistry,13
herein, we demonstrate the synthesis of air-stable acyclic
aminocarbene-like palladium complexes by the reaction of bis-
aromaticisocyanide-dichloropalladium(II) with N-arylbenzami-
dines (Scheme 1) and study their catalytic activities on classic
SuzukieMiyaura cross-coupling.
2. Results and discussion
Fig. 1. Selected carbenes-contained palladium complexes.
Our investigation was initiated by the reaction of bis(2,6-
dimethylphenylisocyanide)dichloropalladium 1a with N-phenyl
benzylamidine 2a in toluene at room temperature. The reaction
* Corresponding authors. Fax: þ86 512 65880307; e-mail addresses: shunyi@
suda.edu.cn (S.-Y. Wang), shunjun@suda.edu.cn (S.-J. Ji).
http://dx.doi.org/10.1016/j.tet.2015.10.033
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

9680
Y. Fang et al. / Tetrahedron 71 (2015) 9679e9683
Table 1
Optimization of the reaction conditions for the SuzukieMiyaura reaction catalyzed
by 3aa
Entry
Base
Solvent
Yield (%)b
1
2
3
4
5
6
7
8
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
K2CO3
THF
MeCN
DMF
Acetone
DME
EtOH
t-AmylOH
n-PrOH
i-PrOH
t-BuOH
MeOH
EtOH
Trace
N.D.
N.D.
Trace
38
>99
Trace
91
95
13
83
74
9
10
11
12
13
14
15c
16c,d
Na2CO3
NaOAc
t-BuOK
K2CO3
EtOH
EtOH
EtOH
EtOHeH2O
39
Trace
>99
>99
a
4a (0.5 mmol), 5a (0.75 mmol), 3a (0.5 mol %), base (1.0 mmol), solvent (2 mL),
rt, 12 h.
b
c
Yields were determined by GC analysis using tridecane as an internal standard.
3a (0.1 mol %) was used.
4a (0.5 mmol), 5a (0.75 mmol), K2CO3 (1 mmol), EtOHeH2O (2:1, 2 mL), rt, 12 h.
Scheme 1. Synthesis of acyclic aminocarbene-like palladium(II) complexes.
d
proceeded smoothly to afford the acyclic aminocarbene-like com-
plex 3a in 62% yield. The structure of 3a was confirmed by NMR, IR,
HRMS and further confirmed by X-ray single crystal diffraction. To
our delight, 3a is stable under air atmosphere and even stable in
toluene under the reflux conditions, which indicates that it is
a promising potential palladium catalyst. Inspired by these results,
a series of the acyclic aminocarbene-like complexes 3bee were
prepared in 62%e75% yields under the identical conditions.
Then, we tried the SuzukieMiyaura reaction of 0.5 mmol 3-
methyliodobenzene 4a with 0.75 mmol 4-methoxylphenylboronic
acid 5a as model reaction catalyzed by 0.5 mol % 1a to optimize
the reaction conditions. The coupling reaction did not go smoothly
in THF, MeCN, DMF or acetone using KOtBu as the base (Table 1,
entries 1e4). When the reaction was carried out in DME in the
presence of KOtBu, the corresponding product 6a was formed in
38% GC-yield. Further screening of solvents showed that the re-
action could react well in different alcohols (Table 1, entries 6e11).
6a could be observed in >99% GC-yield when using ethanol as the
solvent catalyzed by 0.5 mol % 3a (Table 1, entry 6). We also studied
the effects of the base additives (Table 1, entry 12e14). KOtBu was
the most suitable base for the reaction in EtOH (method A), which
led to 6a in almost quantitative GC yield even utilizing 0.1 mol % 3a
as the catalyst (Table 1, entry 15). It should be noted that the re-
action in EtOHeH2O (2:1) in the presence of inexpensive K2CO3
(method B) could also give 6a in almost quantitative GC yield cat-
alyzed by 0.1 mol % 3a (Table 1, entry 16).
Next, we investigated the catalytic activities of the above acyclic
aminocarbene-like palladium(II) complexes 3bee under the opti-
mal reaction conditions (method A). We were pleased to find that
all of the complexes 3bee (0.1 mol %) were able to catalyze the
SuzukieMiyaura reaction to give 6a in 73%e83% GC-yields, re-
spectively (Table 2, entries 2e5).
With the optimal conditions in hand, we investigated the sub-
strate scope. The results are summarized in Table 3. Different
substituted phenylboronic acid was able to react with the iodo-
benzene, 4-methoxyiodobenzene and 3-methyliodobenzene
smoothly to give the desired products in good to excellent yields,
respectively. When electron-rich (3,4-dimethoxyphenyl)boronic
Table 2
The reactions of 4a with 5a catalyzed by palladium complexes 3a
Entry
Catalyst
Time
yield(%)b
1
2
3
4
5
3a
3b
3c
3d
3e
12 h
12 h
12 h
12 h
12 h
>99
73
83
73
80
a
4a (0.5 mmol), 5a (0.75 mmol), t-BuOK (1.0 mmol), EtOH (2 mL), rt, 12 h.
Yields were determined by GC analysis using tridecane as an internal standard.
b
acid was employed in the reaction with 4a and iodobenzene, 6d
and 6g were observed in 96% and 97% yields, respectively. The re-
action of (4-acetylphenyl)boronic acid with iodobenzene resulted
in 6h in 91% yield. The reaction of 2-aminoiodobenzene with 5a
could also afford the desired product 6k in 70% yield. The reaction
of electron-defect 1-iodo-4-nitrobenzene also gave the product 6l
in 90% yield. Notably, we could obtain the product 6j in 74% yield,
which showed the CeCl bond was stable under the optimal con-
ditions. Next, we investigated the coupling reactions of bromo-
benzene derivatives using water as the co-solvent and K2CO3 as the
base (Method B). All the reactions also reacted smoothly to afford
the desired products. When bromobenzene was subjected to the
reaction with (4-methylphenyl)boronic acid and (4-methoxy)bo-
ronic acid, 6e and 6f were be obtained in 82% and 96% yields, re-
spectively (Method B). The reaction of (3,4-dimethoxyphenyl)
boronic and with bromobenzene resulted in 6g in 97% and 52%
yields under method A and method B, respectively. When electron-
defect arylboronic acids were employed in the reaction, we could
isolate the desired product in moderate yields (Table 3, 6n, 6o, 6h).
It is worthy of note that the reactions of strong base sensitive
substituents 3-bromobenzaldehyde and 5-bromoindole with 5a in
the presence of K2CO3 (Method B) led to 6q and 6r in 94% and 95%

Y. Fang et al. / Tetrahedron 71 (2015) 9679e9683
9681
Table 3
Table 4
Substrate scope of the SuzukieMiyaura reaction catalyzed by 3aa,b
Investigation of the SuzukieMiyaura reaction of PhOTf catalyzed by 3aa,b,c
Scheme 2. The reaction of 4a and 5a catalyzed by 0.01 mol % 3a.
3. Conclusion
In summary, we have synthesized a series of air-stable amino-
carbene-like palladium catalysts under mild conditions. The cata-
lytic activity in the SuzukieMiyaura coupling reaction is also
investigated in the paper. It shows that 0.01 mol % catalyst is
enough for the cross-coupling reaction. Further studies on the ap-
plication of the acyclic aminocarbene-like palladium catalyst are
ongoing in our laboratory.
4. Experimental section
4.1. General remarks
All reactions were carried out in oven-dried glassware under air.
Progresses of reactions were monitored by TLC. IR spectra were
recorded on a Varian FT-1000 spectrometer using KBr optics. NMR
spectra were recorded at room temperature in CDCl3 at 400 Hz for
1H NMR and 100 Hz for 13C NMR. High resolution mass spectra
(HRMS) were obtained on a TOF-MS instrument with ESI source.
yields, respectively. When these two reactions were carried out
utilizing KOtBu in EtOH, 6q and 6r were observed in 82% and 50%
yields, respectively (Method A). This result indicates that 3a could
catalyze SuzukieMiyaura cross-coupling reaction efficiently under
the alternative conditions (Method A or Method B) based on the
substituents activities.
4.2. General procedure for the synthesis of palladium(II)
complex 3ae3e
Next, we carried out the reaction of PhOTf (phenyl tri-
fluoromethanesulfonate) with different substituted phenyl-
boronic acid using 3a as the catalyst. The results are summarized
in Table 4. We could isolate the products in moderate to good
yields. However, the employment of electron-defect (4-
cyanophenyl)boronic acid 5n in the reaction led to a sharp
drop in yield. In addition, no product was detected when PhOTs
(phenyl 4-methylbenzenesulfonate) was employed under the
catalytic conditions.
In order to further investigate the catalytic activity of 3a, we
carried out a large-scale reaction of 3-methyliodobenzene and 4-
methoxylphenylboronic acid by using 0.01 mol % 3a as the cata-
lyst. To our delight, the reaction of 4a with 5a at room temperature
for 8 h afforded the desired product 6a in 93% yield, of which the
TON is 9300 and the TOF is 1162 hꢀ1 (Scheme 2).
In a 10 mL round-bottom flask, cis-[PdCl2(CNR)2] (0.11 mmol,
1.1 equiv) and HN]C(Ph)NHPh (0.1 mmol, 1 equiv) were mixed in
toluene (2 mL). The reaction mixture was stirred for at room tem-
perature. After 12 h, the reaction mixture was dissolved in ethyl
acetate and evaporated to dryness. The solid residue was purified
by silica gel column chromatography to obtain the product (3ae3e)
as solid in light yellow to yellow colors. Yields were 62e75%.
3a: Yield: 62%. Yellow solid. mp: 180.9e182.0 ꢁC. IR: nmax
(cmꢀ1)¼3230, 2187, 1655, 1587. 1H NMR (400 MHz, Chloroform-d)
d
7.39e7.08 (m, 13H), 6.97 (d, J¼7.6 Hz, 2H), 6.67 (d, J¼7.5 Hz, 2H),
6.12 (t, J¼7.5 Hz, 1H), 2.25 (s, 6H), 2.13 (s, 6H). 13C NMR (100 MHz,
Chloroform-d)
d 171.16, 163.84, 150.65, 139.34, 134.37, 131.17,
130.90,129.79,129.03,128.83,128.62, 128.00,127.50,127.44,127.32,
123.36, 19.40, 18.64. HRMS (ESIþ, MeCN): found, 564.1429 [MꢀCl]þ,
calcd for C31H29N4Pd, 564.1427.

9682
Y. Fang et al. / Tetrahedron 71 (2015) 9679e9683
Crystallographic data for the structures of 3a reported in this
Na2SO4, filtered and concentrated. The residue was purified by
silica gel column chromatography (petroleum ether as the eluent)
to obtain the desired product.
paper have been deposited at the Cambridge Crystallographic Data
Centre as supplementary publication with No. CCDC 1009376. Copies
of this information may be obtained free of charge from The Director,
CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK (E-mail: lin-
stead@ccdc.cam.ac.uk or deposit@ccdc.cam.ac.uk; fax: þ44 01223
336033). Structural parameters for product 3a: data collection:
Rigaku Mercury CCD area detector; crystal size: 0.5ꢂ0.3ꢂ0.2 mm3;
4.3.3. 40-Methoxy-3-methyl-1,10-biphenyl (6a). 1H NMR (400 MHz,
CDCl3)
7.03e6.96 (m, 2H), 3.87 (s, 3H), 2.44 (s, 3H). 13C NMR (101 MHz,
CDCl3) 159.20, 140.94, 138.39, 134.02, 128.76, 128.28, 127.68,
d 7.60e7.50 (m, 2H), 7.42e7.30 (m, 3H), 7.19e7.11 (m, 1H),
d
C
31H29ClN4Pd, Mr¼599.43, triclinic, space group P-1, a¼9.2173(3),
127.54, 123.97, 114.26, 55.46, 21.69.
ꢀ
b¼11.9396(3), c¼13.8881(4) A,
a¼80.036(2),
b
¼83.490(2),
3
ꢀ
g
¼69.718(3), V¼1409.65(8) A , Z¼2, Dcalcd¼1.412
g
cmꢀ3
, R
4.3.4. 40-Fluoro-3-methyl-1,10-biphenyl (6b). 1H NMR (400 MHz,
[I>2
s
(I)]¼0.0259, wR[I>2
s
(I)]¼0.0971.
CDCl3)
d
7.64e7.59 (m, 2H), 7.46e7.38 (m, 3H), 7.27e7.17 (m, 3H),
163.74, 140.34, 138.53,
3b: Yield: 62%. Yellow solid. mp: 184.9e185.9 ꢁC. IR: nmax
(cmꢀ1)¼3372, 2188, 1636, 1586. 1H NMR (400 MHz, Chloroform-d)
2.50 (s, 3H). 13C NMR (101 MHz, CDCl3)
d
128.84, 128.82, 128.74, 128.12, 127.94, 124.24, 115.75, 115.54, 21.63.
d
7.37e7.27 (m, 5H), 7.25e7.10 (m, 6H), 6.82 (s, 2H), 6.47 (s, 2H), 2.23
(d, J¼15.2 Hz, 11H), 2.07 (s, 7H). 13C NMR (100 MHz, Chloroform-d)
4.3.5. 3,40-Dimethyl-1,10-biphenyl (6c). 1H NMR (400 MHz, CDCl3)
d
171.08,164.36,148.73,139.43,138.99,133.97,133.39,131.12,131.01,
d
7.68e7.64 (m, 2H), 7.64e7.52 (m, 2H), 7.48 (t, J¼7.5 Hz, 1H), 7.40 (d,
129.80, 128.80, 128.61, 128.27, 128.07, 128.03, 127.93, 127.21, 21.27,
19.98, 19.35, 18.51. HRMS (ESIþ, MeCN): found, 591.1741 [MꢀCl]þ,
calcd for C33H33N4Pd, 591.1740.
J¼8.0 Hz, 2H), 7.31 (d, J¼7.5 Hz, 1H), 2.58 (s, 3H), 2.56 (s, 3H). 13C NMR
(101 MHz, CDCl3) 13C NMR (101 MHz, Chloroform-d)
d 141.25, 138.56,
138.34,136.96,129.53,128.74,127.87,127.83,127.10,124.19, 21.66, 21.20.
4.3.6. 3,4-Dimethoxy-30-methyl-1,10-biphenyl (6d). 1H
3c: Yield: 73%. Pale yellow solid. mp: 172.6e173.6 ꢁC. IR: nmax
(cmꢀ1)¼3355, 2178, 1636, 1588. 1H NMR (400 MHz, Chloroform-d)
NMR
d
7.35e7.14 (m, 12H), 7.06 (d, J¼7.8 Hz, 2H), 6.84 (d, J¼7.6 Hz, 2H),
(400 MHz, CDCl3) d 7.45e7.31 (m, 3H), 7.21e7.13 (m, 3H), 6.96 (d,
6.51 (t, J¼7.7 Hz, 1H), 3.15e2.96 (m, 4H), 1.36 (s, 4H), 1.23 (d,
J¼8.2 Hz, 1H), 3.98 (s, 3H), 3.94 (s, 3H), 2.46 (s, 3H). 13C NMR
J¼6.8 Hz, 13H), 0.93 (d, J¼6.9 Hz, 6H). 13C NMR (100 MHz, Chlo-
(101 MHz, CDCl3)
d 149.05, 148.48, 141.00, 138.25, 134.31, 128.63,
roform-d)
d
170.84, 163.28, 149.14, 144.67, 139.50, 137.05, 131.19,
127.60, 127.58, 123.95, 119.35, 111.38, 110.40, 55.89, 55.87, 21.53.
130.88, 129.77, 129.71, 128.71, 128.63, 128.11, 127.98, 123.49, 123.03,
122.42, 29.33, 28.57, 22.96, 22.64, 22.29. HRMS (ESIþ, MeCN):
found, 675.2698 [MꢀCl]þ, calcd for C39H45N4Pd, 675.2700.
3d: Yield: 65%. Off-white solid. mp: 200.2e201.4 ꢁC. IR: nmax
(cmꢀ1)¼3398, 2188, 1636, 1589. 1H NMR (400 MHz, Chloroform-d)
4.3.7. 4-Methyl-1,10-biphenyl (6e). 1H NMR (400 MHz, CDCl3)
d
7.85e7.58 (m, 2H), 7.58e7.39 (m, 4H), 7.38e7.24 (m, 3H), 2.43 (s,
3H). 13C NMR (101 MHz, CDCl3)
141.28, 138.48, 137.15, 129.61,
128.84, 127.12, 127.10, 126.94, 21.24.
d
d
7.39e7.22 (m, 7H), 7.14e6.93 (m, 6H), 6.70 (dd, J¼31.4, 7.5 Hz, 2H),
6.12 (t, J¼7.5 Hz, 1H), 2.36e2.20 (m, 14H), 2.14 (s, 4H). 13C NMR
4.3.8. 4-Methoxy-1,10-biphenyl (6f). 1H NMR (400 MHz, CDCl3)
7.69e7.38 (m, 6H), 7.37e7.27 (m, 1H), 7.06e6.95 (m, 2H), 3.87 (s,
3H). 13C NMR (101 MHz, CDCl3,)
159.24, 140.93, 133.88, 128.85,
(100 MHz, Chloroform-d)
d
171.15, 164.15, 136.36, 134.37, 131.59,
d
129.04, 128.77, 128.72, 128.55, 128.36, 127.99, 127.92, 127.78, 127.65,
127.53, 127.42, 127.26, 123.56, 19.84, 18.88, 18.68. HRMS (ESIþ,
MeCN): found, 591.1741 [MꢀCl]þ, calcd for C33H33N4Pd, 591.1740.
3e: Yield: 75%. Yellow solid. mp: 205.4e206.7 ꢁC. IR: nmax
(cmꢀ1)¼3397, 2193, 1630, 1585. 1H NMR (400 MHz, Chloroform-d)
d
128.27, 126.85, 126.78, 114.31, 77.48, 77.16, 76.84, 55.46.
4.3.9. 1-([1,10-Biphenyl]-4-yl)ethan-1-one (6g). 1H NMR (400 MHz,
CDCl3)
1H), 7.23e7.12 (m, 2H), 6.98 (d, J¼8.2 Hz,1H), 3.98 (s, 3H), 3.96 (s, 3H).
13C NMR (101 MHz, CDCl3)
149.21, 148.68, 141.15, 134.34, 128.84,
d
7.64e7.55 (m, 2H), 7.46 (dd, J¼8.2,6.9Hz,2H),7.35(t, J¼7.3 Hz,
d
7.39e7.22 (m, 7H), 7.14e6.93 (m, 6H), 6.70 (dd, J¼31.4, 7.5 Hz, 2H),
6.12 (t, J¼7.5 Hz, 1H), 2.36e2.20 (m, 14H), 2.14 (s, 4H). 13C NMR
d
(100 MHz, Chloroform-d)
d
171.05, 164.65, 149.10, 138.98, 138.43,
126.97, 126.95, 119.49, 111.54, 110.52, 77.48, 77.16, 76.84, 56.08, 56.03.
136.36, 133.94, 133.55, 131.51, 130.57, 128.65, 128.51, 128.32, 128.28,
128.24, 127.29, 127.25, 21.26, 19.92, 19.76, 18.86, 18.51. HRMS (ESIþ,
MeCN): found, 619.2047 [MꢀCl]þ, calcd for C35H37N4Pd, 619.2048.
4.3.10. 3,4-Dimethoxy-1,10-biphenyl (6h). 1H NMR (400 MHz, CDCl3)
d
8.12e8.01 (m, 2H), 7.75e7.63 (m, 4H), 7.54e7.47 (m, 2H), 7.47e7.34
(m,1H), 2.67 (s, 3H).13C NMR (101 MHz, CDCl3)
d
197.92,145.90,139.98,
4.3. General procedure for the SuzukieMiyaura reactions
135.94,129.08,129.04,128.36,127.39,127.35, 77.48, 77.16, 76.84, 26.82.
4.3.1. Method A. In
a
reaction tube, 1-iodo-3-methylbenzene
4.3.11. 4,40-Dimethoxy-1,10-biphenyl (6i). 1H NMR (400 MHz,
(0.5 mmol, 1 equiv), (4-methoxyl phenyl)boronic acid (0.75 mmol,
1.5 equiv) and KOtBu (1 mmol, 2 equiv) were dissolved in 3 mL
anhydrous EtOH. The reaction mixture was stirred at ambient
temperature and monitored by TLC. After completion, 10 mL water
was added to the resulting mixture, then it was extracted with ethyl
acetate (3ꢂ10 mL). The combined organic layer was dried over
Na2SO4, filtered and concentrated. The residue was purified by silica
gel column chromatography (petroleum ether as the eluent) to
obtain the desired product.
CDCl3) d
7.52e7.45 (m, 4H), 7.00e6.93 (m, 4H), 3.85 (s, 6H). 13C
NMR (101 MHz, CDCl3) d 158.70, 133.49, 127.74, 114.17, 77.36, 77.04,
76.72, 55.36.
4.3.12. 4-Chloro-40-methyl-1,10-biphenyl (6j). 1H NMR (400 MHz,
CDCl3)
7.56e7.48 (m, 4H), 7.47e7.40 (m, 2H), 7.29 (d, J¼7.9 Hz,
2H), 2.45 (s, 3H). 13C NMR (101 MHz, CDCl3)
139.68, 137.52, 137.18,
d
d
133.13, 129.71, 128.95, 128.27, 126.91, 77.48, 77.16, 76.84, 21.22.
4.3.13. 40-Methoxy-[1,10-biphenyl]-2-amine (6k). 1H NMR (400 MHz,
4.3.2. Method B. In a reaction tube, bromobenzene (0.5 mmol,
1 equiv), (4-methoxyl phenyl)boronic acid (0.75 mmol, 1.5 equiv)
and K2CO3 (1 mmol, 2 equiv) were dissolved in 3 mL mixed solvent
(EtOH:H2O, 2:1). The reaction mixture was stirred at ambient
temperature and monitored by TLC. After completion, 10 mL water
was added to the resulting mixture, then it was extracted with ethyl
acetate (3ꢂ10 mL). The combined organic layer was dried over
CDCl3)
(td, J¼7.5, 1.2 Hz, 1H), 6.78 (dd, J¼7.9, 1.2 Hz, 1H), 3.87 (s, 3H), 3.68 (s,
2H). 13C NMR (101 MHz, CDCl3)
158.80, 143.67, 131.81, 130.53,
d 7.47e7.37 (m, 2H), 7.25e7.11 (m, 2H), 7.08e6.97 (m, 2H), 6.85
d
130.24,128.24,127.43,118.69,115.61,114.26, 77.48, 77.16, 76.84, 55.36.
4.3.14. 4-Methyl-40-nitro-1,10-biphenyl (6l). 1H NMR (400 MHz,
CDCl3)
d
10.09 (s, 1H), 8.08 (t, J¼1.9 Hz, 1H), 7.88e7.79 (m, 2H),

Y. Fang et al. / Tetrahedron 71 (2015) 9679e9683
9683
7.59 (dd, J¼8.4, 6.7 Hz, 3H), 7.06e6.99 (m, 2H), 3.88 (s, 3H). 13C
Programs Foundation of Ministry of Education of China
(2013201130004), the Young Natural Science Foundation of Jiangsu
Province (BK2012174), PAPD, and Soochow University for financial
support.
NMR (101 MHz, CDCl3)
d 192.54, 159.76, 141.79, 136.96, 132.67,
132.18, 129.52, 128.27, 128.17, 127.70, 114.51, 77.48, 77.16, 76.84,
55.46.
4.3.15. 2,5-Dimethoxy-1,10-biphenyl (6m). 1H NMR (400 MHz,
Supplementary data
CDCl3)
7.44e7.38 (m, 1H), 7.02e6.90 (m, 3H), 3.87 (s, 3H), 3.81 (s, 3H).
13C NMR (101 MHz, CDCl3)
153.83, 150.83, 138.48, 131.76,
d
7.66e7.59 (m, 2H), 7.49 (dd, J¼8.5, 6.8 Hz, 2H),
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2015.10.033.
d
129.52, 128.09, 127.13, 116.80, 113.15, 112.76, 77.48, 77.16, 76.84,
56.35, 55.79.
References and notes
4.3.16. [1,10-Biphenyl]-4-carbonitrile (6n). 1H NMR (400 MHz,
CDCl3)
3H). 13C NMR (101 MHz, CDCl3)
128.19, 127.25, 126.75, 118.47, 110.42, 76.92, 76.60, 76.29.
d
7.70 (q, J¼8.5 Hz, 4H), 7.63e7.55 (m, 2H), 7.55e7.38 (m,
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145.18, 138.68, 132.12, 128.64,
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4.3.17. Methyl
[1,10-biphenyl]-4-carboxylate
8.16e8.08 (m, 1H), 7.70e7.59 (m, 2H), 7.52e7.36
167.12, 145.74,
(6o). 1H
NMR
(400 MHz, CDCl3)
d
(m, 2H), 3.95 (s, 1H). 13C NMR (101 MHz, CDCl3)
d
140.10, 130.21, 129.03, 128.25, 128.22, 127.39, 127.16, 77.48, 77.16,
76.84, 52.24.
4.3.18. 4-Methoxy-40-(trifluoromethoxy)-1,10-biphenyl (6p). 1H NMR
(400 MHz, CDCl3)
d
7.42e7.32 (m, 4H), 7.12 (d, J¼8.3 Hz, 2H),
6.87e6.79 (m, 2H), 3.70 (s, 3H). 13C NMR (101 MHz, CDCl3)
d
159.58,
148.33, 148.31, 139.73, 132.42, 128.24, 128.04,124.55, 122.00, 121.34,
119.45, 116.90, 114.44, 77.48, 77.16, 76.84, 55.36.
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4.3.19. 40-Methoxy-[1,10-biphenyl]-3-carbaldehyde (6q). 1H NMR
(400 MHz, CDCl3)
d
10.09 (s, 1H), 8.08 (t, J¼1.9 Hz, 1H), 7.88e7.79 (m,
2H), 7.59 (dd, J¼8.4, 6.7 Hz, 3H), 7.06e6.99 (m, 2H), 3.88 (s, 3H). 13C
NMR (101 MHz, CDCl3)
d 192.54, 159.76, 141.79, 136.96, 132.67,
132.18,129.52,128.27, 128.17,127.70,114.51, 77.48, 77.16, 76.84, 55.46.
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4.3.20. 5-(4-Methoxyphenyl)-1H-indole (6r). 1H NMR (400 MHz,
CDCl3)
(t, J¼2.8 Hz, 1H), 7.04e6.98 (m, 2H), 6.64e6.58 (m, 1H), 3.87 (s, 3H).
13C NMR (101 MHz, CDCl3)
158.56, 135.32, 135.10, 133.18, 128.50,
d 8.15 (s, 1H), 7.83 (s,1H), 7.63e7.57 (m, 2H), 7.43 (s, 2H), 7.23
d
€
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128.45, 124.91, 121.81, 118.85, 114.22, 111.30, 103.01, 77.48, 77.16,
76.84, 55.49.
Acknowledgements
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We gratefully acknowledge the Natural Science Foundation of
China (No. 21172162, 21372174, 21542015, 21202111), the Ph.D.