Base-assisted, copper-catalyzed N-arylation of (benz)imidazoles and amines with diarylborinic acids

Article abstract of DOI:10.1016/j.tet.2017.10.043

N-Arylation of (benz)imidazoles and amines with diarylborinic acids as cost-effective aryl source has been efficiently effected via Cu(OAc)₂-catalyzed Chan-Lam coupling in assistance of tetramethylethylenediamine (TMEDA) in methanol and pyridine (Py) in dichloromethane, respectively, in air at room temperature. The diarylborinic acids could be well accommodated by the Chan-Lam coupling oxidative conditions containing a proper combination of bases and solvents. The steric hindrance appeared to affect the copper-catalyzed N-arylation using the high-order arylboron reagent more significantly than the electronic factors, especially for low reactive anilines and aliphatic amines.

Full text of DOI:10.1016/j.tet.2017.10.043

Accepted Manuscript
Base-assisted, copper-catalyzed N-arylation of (benz)imidazoles and amines with
diarylborinic acids
Changwei Guan, Yuanyuan Feng, Gang Zou, Jie Tang
PII:
S0040-4020(17)31071-2
10.1016/j.tet.2017.10.043
TET 29046
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 29 August 2017
Revised Date: 15 October 2017
Accepted Date: 17 October 2017
Please cite this article as: Guan C, Feng Y, Zou G, Tang J, Base-assisted, copper-catalyzed N-
arylation of (benz)imidazoles and amines with diarylborinic acids, Tetrahedron (2017), doi: 10.1016/
j.tet.2017.10.043.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
Graphical Abstract
Base-assisted, copper-catalyzed N-arylation
of (benz)imidazoles and amines with
diarylborinic acids
Changwei Guana, Yuanyuan Fenga, Gang Zoua,* and Jie Tangb,*
Leave this area blank for abstract info.
a) School of Chemistry & Molecular Engineering, East China University of Science & Technology, 130
Meilong Rd, Shanghai, China.
b) Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, Shanghai
Key Laboratory of Green Chemistry and Chemical Processes, SCME, East China Normal University,3663
North Zhongshan Rd. Shanghai, China.

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Base-assisted, copper-catalyzed N-arylation of (benz)imidazoles and amines with
diarylborinic acids
Changwei Guana , Yuanyuan Fenga, Gang Zoua,*and Jie Tangb,*
a School of Chemistry & Molecular Engineering, East China University of Science & Technology, 130 Meilong Rd, Shanghai, China. Email:
zougang@ecust.edu.cn.
b Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, Shanghai Key Laboratory of Green Chemistry and Chemical
Processes, SCME, East China Normal University,3663 North Zhongshan Rd. Shanghai, China. Email: jtang@chem.ecnu.edu.cn.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
N-Arylation of (benz)imidazoles and amines with diarylborinic acids as cost-effective aryl
source has been efficiently effected via Cu(OAc)2-catalyzed Chan-Lam coupling in assistance of
tetramethylethylenediamine (TMEDA) in methanol and pyridine (Py) in dichloromethane,
respectively, in air at room temperature. The diarylborinic acids could be well accommodated by
the Chan-Lam coupling oxidative conditions containing a proper combination of bases and
solvents. The steric hindrance appeared to affect the copper-catalyzed N-arylation using the
high-order arylboron reagent more significantly than the electronic factors, especially for low
reactive anilines and aliphatic amines.
Available online
Keywords:
N-Arylation
Diarylborinic acids
Chan-Lam coupling
Copper
2017 Elsevier Ltd. All rights reserved
.
1. Introduction
of the higher reducing ability of high-order arylborons than the
corresponding boronic acids,11 it seems to be challengeable to use
both aryl groups of diarylborinic acids under the oxidative
conditions of Chan-Lam coupling because of their fast
degradation to arylboronic acids. In fact, only one phenyl group
appeared to be useful in a microwave-assisted, copper-mediated
N-arylation of sodium tetraphenylborate with primary amines.12
In continuation of our efforts to develop practical arylation
protocols by efficiently using high-order arylborons, we report
Copper-mediated arylation of N-nucleophiles with arylboronic
acids, Chan-Lam CAr-N coupling,1 has made the N-arylation
reaction, which otherwise requires harsh conditions and / or
complicated catalyst systems, one of the operationally simplest
organic synthesis techniques under the mildest conditions: at
room temperature in open vessels. However, under the
operational simplicity and mild conditions, the original Chan-
Lam N-arylation procedure required excess amount of
arylboronic acids, high-loading of copper salts and / or long
reaction time. Therefore, a great of efforts have been devoted to
improve the original procedure with respect to copper / ligand
systems, solvents, bases and oxidative additives.2 Important
progresses have been achieved such as development of catalytic
systems,3 recognition of the key role of solvents,4 conquest of
some difficult substrates5 and shedding a light on its complicated
mechanism.6 In contrast, arylboronic acids have still
overwhelmingly dominated the aryl source in Chan-Lam CAr-N
coupling. In fact, even arylboronic acid pinacol esters have been
problematic in coupling with aryl amines until recently.7
herein
a base-assisted, Cu(OAc)2-catalyzed Chan-Lam N-
arylation of (benz)imidazoles, anilines and aliphatic amines with
diarylborinic acids, from which both aryl groups could be
utilized.
2. Results and Discussion
2.1 N-Arylation of (benz)imidazoles
Imidazoles and benzimidazoles have proven to be highly
reactive substrates in Chan-Lam coupling of arylboronic acids.
Therefore, we began with (benz)imidazoles to explore the
reactivity of diarylborinic acids in Chan-Lam CAr-N arylation.
The cross-coupling of benzimidazole (1a) with dehydration-
resisting bis(p-tolyl)borinic acid (2a) was chosen as the model
reaction for convenience (Table 1). Although the reaction
proceeded sluggishly under a base-free condition the desired
product, 1-(p-tolyl)benzimidazole (3aa), was obtained in good
yields with 0.75 equiv. 2a (1.5 equiv. with respect to aryl) in the
presence of 1.0 equiv. tertiary amine, e.g. NEt3 or 1,4-
diazabicyclo[2.2.2]octane (DABCO), in methanol by using 10
Compared with arylboronic acids, Ar2B(OH) could be more
economically prepared from aryl halides, magnesium and
boronates8 or amine-boranes9 under noncryogenic conditions if
no hampered by sensitive functional groups. We have shown that
high-order arylborons could be used as cost-effective alternatives
to arylboronic acids in nickel or palladium-catalyzed carbon-
carbon bond forming arylation procedures.10 However, because

2
Tetrahedron
mol% Cu(OAc)2 as catalyst at room temperature (Table 1,
coupling (Table 1, entries 18-20). Taking all factors into account,
ACCEPTED MANUSCRIPT
entries 1-3).
the optimal conditions for the copper-catalyzed Chan-Lam
coupling of benzimidazoles with diarylborinic acids were set as
0.65 equiv. diarylborinic acids (1.3 equiv. with respect to aryl)
with 5 mol% Cu(OAc)2·H2O catalyst in the presence of 1 equiv.
TMEDA as base in methanol at room temperature.
Table 1. Establishment of conditions for arylation of
benzimidazoles with diarylborinic acidsa
Structural effects of diarylborinic acids on the copper-
catalyzed Chan-Lam coupling with (benz)imidazoles were
explored under the optimal conditions (Table 2). Both the steric
and electronic factors showed negligible influence on the
reactivity of diarylborinic acids. For example, an electron-neutral
(H, 2b in form of anhydride), -withdrawing (4-F, 2c), or -
donating group (4-MeO, 2d; 2-Me, 2e; 2-MeO, 2f; or 2-Et, 2g)
on the aromatic ring of diarylborinic acids provided the
corresponding 1-arylbenzimidazole (3ab-3ag) in excellent yields
Entry 2a/1ab Copper(mol%) Basec
Sol.
Time(h) Yield%
1
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.65
0.65
0.55
0.55
0.65
0.65
0.65
0.65
Cu(OAc)2 (10)
Cu(OAc)2(10)
/
MeOH
MeOH
12
12
12
12
9
2
Et3N
76
84
23
16
11
38
95
17
25
99
99
99
99
81
92
75
80
62
55
50
3
Cu(OAc)2 (10) DABCO MeOH
Cu(OAc)2 (10) DABCO EtOH
4
(94-99%).
The
sterically
demanding
bis(2-
5
Cu(OAc)2 (10) DABCO CH2Cl2 12
Cu(OAc)2 (10) DABCO THF 12
Cu(OAc)2 (10) DABCO CH3CN 12
isopropoxyphenyl)borinic acid (2h) also reacted smoothly to give
1-(2-isoproponoxyphenyl)benzimidazole (3ah) in 85% yield.
However, a large steric effect from a substituent on the 2-position
of benzimidazole was observed. For example, 2-
methylbenzimidazole (1b) reacted with bis(p-tolyl)borinic acid
(2a) to give 3ba in significantly lower yield (71%) than that of
the parent benzimidazole (1a). A phenyl group at 2-position of
benzimidazole almost completely blocked the reaction, producing
2-phenyl-1-(p-tolyl)benzimidazole (3ca) in just 10% yield after
12 hours. Imidazoles (1d and 1e) reacted similarly to the
corresponding benzimidazoles.
6
7
8
Cu(OAc)2 (10) Pyridine
Cu(OAc)2 (10) DMAP
Cu(OAc)2 (10) NMI
MeOH
MeOH
MeOH
12
12
12
4
9
10
11
12
13
14
15
16
17
18
19
20
21
Cu(OAc)2 (10) TMEDA MeOH
Cu(OAc)2 (5)
Cu(OAc)2 (1)
Cu(OAc)2 (5)
Cu(OAc)2(1)
Cu(OAc)2 (5)
Cu(OAc)2(1)
Cu(NO3)2(1)
CuBr2 (1)
TMEDA MeOH
TMEDA MeOH
TMEDA MeOH
TMEDA MeOH
TMEDA MeOH
TMEDA MeOH
TMEDA MeOH
TMEDA MeOH
TMEDA MeOH
TMEDA MeOH
4
8
Table 2. Scope of TMEDA-assisted, Cu(OAc)2-catalyzed N-
arylation of (benz)imidazoles with diarylborinic acidsa
4
8
4
8
8
8
CuSO4(1)
8
CuCl2(1)
8
aIsolated yield
bMolar ratio
c1.0equiv. used
Attempts to increase the yield by changing solvent met with
failure since the common solvents, e.g. EtOH, CH2Cl2, THF and
CH3CN, performed much less efficiently than MeOH (Table 1,
entries 4-7). However, base screening was fruitful. An excellent
yield (95%) could be obtained by using pyridine as the base
while 4-dimethylaminopyridine (DMAP) and N-methylimidazole
(NMI) performed poorly (Table 1, entries 8-10). Further, when
tetramethylethylenediamine (TMEDA) was used as the base the
model reaction completed in 4-8 hours with 1-5 mol%
Cu(OAc)2·H2O loading to provide 3aa in almost quantitative
yield (99%) (Table 1, entries 11-13). The loading of diarylborinic
acid could be reduced to 0.65 equiv. by using 5 mol%
Cu(OAc)2·H2O while a slight decrease in yield (92%) was
observed when 0.55 equiv. 2a was used (Table 1, entries 14-17).
Given the high reducing ability of diarylborinic acids, it is
surprising that more oxidative Cu(NO3)2·3H2O performed
similarly to Cu(OAc)2·H2O at 1 mol% loading, better than the
other copper salts, e.g. CuSO4·5H2O, CuCl2 and CuBr2, in the
model reaction, indicating diarylborinic acids could be well
accommodated by the oxidative conditions of Chan-Lam
a Isolated yield.
b0.3 equiv. anhydride (Ph2B)2O used.
2.2 Arylation of amines
Encouraged by the results obtained for (benz)imidazoles, we
further explored the reaction of diarylborinic acids with aryl and

3
alkyl amines which are generally less reactive than
(benz)imidazoles in Chan-Lam coupling (Table 3).
conditions (Table 3, entries 7 and 8).3f A proper combination of
ACCEPTED MANUSCRIPT
solvents and bases also proved to be crucial in the coupling of
amines. The yields of 5aa could be increased to 87-93% from
73% by changing solvents from MeOH to CH2Cl2 by using 100
mol% Cu(OAc)2·H2O in the assistance with 1-2 equiv. pyridine
while TMEDA, NEt3 and DABCO gave lower yields (34-61%)
(Table 3, entries 9-14). In fact, the reaction also proceeded
smoothly with catalytic amount of Cu(OAc)2 (20 mol%) and 0.75
equiv. borinic acid (2a) to give 5aa in 90% yield in the presence
of 2 equiv. pyridine although the yields decreased significantly
when further lowering the loadings of Cu(OAc)2 (10 mol%, 85%)
or pyridine (1 equiv., 68%) or borinic acid (2a, 0.65 equiv., 81%)
(Table 3, entries 15, 17 and 19). Therefore, the optimal
conditions for the copper-catalyzed N-arylation of amines with
diarylborinic acids were set as 0.75 equiv. borinic acids loading,
Table 3. Optimization of Chan-Lam CAr-N coupling of amines
with diarylborinic acidsa
Entry 2a/4ab Cat.(mol%)
Base
Sol.
Yield %c
1
0.65
1
Cu(OAc)2(10)
Cu(OAc)2(10)
TMEDA(1) MeOH
TMEDA(1) MeOH
TMEDA(1) MeOH
15
17
2
3
35
12
27
1
1
Cu(OAc)2(100)
Cu(NO3)2 (10)
Cu(NO3)2 (100)
Cu(OAc)2 (100)
4
TMEDA(1)
MeOH
.
20 mol% Cu(OAc)2 H2O as catalyst in the presence of 2 equiv.
5
1
TMEDA(1)
MeOH
pyridine as base in CH2Cl2 at room temperature in air for 24 h.
6
1
Py (1)
MeOH
MeOH
MeOH
MeOH
60
47
Generality of the base-assisted, copper-catalyzed N-arylation
of amines with diarylborinic acids was explored (Table 4). Both
electronic and steric effects from aromatic amines were
obviously observed. Reactions of bis(p-tolyl)borinic acid (2a)
with electron-deficient anilines, e.g. 4-bromoaniline (4d), 4-
nitroaniline (4e), 4-aminobenzoate (4f), 4-acetylaniline (4g) and
pyridin-2-amine (4j), gave the diarylamines 5da-5ja in lower
yields (31-80%) than those of electron-neutral and -rich ones, e.g.
aniline (4a, 92%), p-toluidine (4b, 94%) and 4-methoxyaniline
(4c,85%). The highest yield (80%) obtained from 3-acetylaniline
(4i) among the ortho-, meta-, and para-isomers also reflected both
the electronic and steric effects from aromatic amines. Electron-
rich but sterically demanding anilines, mesidine (4k), and 2,6-
diisopropylaniline (4l), could couple with 2a to give diarylamines
5ka and 5la albeit in low yields of 58% and 20%, respectively.
The electronic influence from diarylborinic acids appeared to be
small while a large steric effect was observed. For example,
diarylborinic acids bearing an electron-neutral (H, 2b in form of
anhydride), -withdrawing (F, 2c) or -donating (MeO, 2d) group
on the phenyl rings, reacted with p-toluidine (4b) to give the
corresponding diarylamines (5aa, 5bc, 5ca) in excellent yields
(84-94%). However, the reactions of diarylborinic acids with an
ortho-substituent on the phenyl rings, e.g. 2-methyl (2e), 2-
methoxy (2f) and 2-ethyl (2g) with p-toluidine (4b) gave the N-
arylation products (5be-5bg) in much lower yields (25-55%) than
those of their para-isomers.
7
0.65
0.65
1
Cu(DMAP)4I2 (10) Py (1)
8
Cu(DMAP)4I2 (10)
/
51
73
9
Py (2)
Py (2)
Py (1)
Cu(OAc)2 (100)
Cu(OAc)2 (100)
Cu(OAc)2 (100)
Cu(OAc)2 (100)
Cu(OAc)2 (100)
10
11
12
13
14
15
16
17
18
19
20
21
1
CH2Cl2 93
CH2Cl2 87
1
1
TMEDA(1) CH2Cl2
DABCO(2) CH2Cl2
61
46
34
1
1
NEt3 (2)
Py(2)
CH2Cl2
Cu(OAc)2 (100)
Cu(OAc)2(10)
1
CH2Cl2 85
CH2Cl2
1
Py (2)
Py(1)
92
Cu(OAc)2 (20)
Cu(OAc)2 (20)
1
CH2Cl2 68
0.75
0.65
0.75
0.75
Cu(OAc)2 (20)
Cu(OAc)2 (20)
Py(2)
CH2Cl2 90
Py(2)
CH2Cl2 81
Cu(DMAP)4I2 (10) Py(2)
Cu(DMAP)4I2 (10)
CH2Cl2 Traced
CH2Cl2 Traced
/
a Reaction was run in 1mmol scale with respect to 4a for 24h.
b mol/mol.
c Isolated yield.
dThe homocoupling of 2a, instead of its Chan-Lam coupling with 4a,
occurred overwhelmingly to give 4,4’-dimethylbiphyl in 90% yield
Aliphatic amines could also be N-arylated with diarylborinic
acids under the above optimal conditions for anilines to give N-
alkyl anilines in modest to good yields. Steric hindrance from
both amines and borinic acids affected the coupling remarkably.
The yields of N-alkyl p-toluidines (5ma-5pa) decreased along
the increase of steric hindrance in primary alkyl amines, benzyl
(4m, 83%), butyl (4p, 82%), cyclohexyl (4n, 75%) and tert-butyl
(4o, trace) in the reaction with bis(p-tolyl)borinic acid (2a).
Similarly, diarylborinic acids bearing a substituent like methyl
(2e), methoxy (2f) or ethyl (2g) at ortho-position of aryl groups
reacted with benzyl amine (4m) to give N-benzylanilines in
lower yields (28-56%) than those of their analogs without an
ortho-substituent (76-87%). Further, piperidine, a sterically
undemanding secondary amine, could react with diarylborinic
acids with a group at para-position of aryl groups to offer N-aryl
piperidines in modest yields while almost no reaction occurred
for bis(o-tolyl)borinic acid (2e) under the otherwise identical
conditions.
The reaction of bis(p-tolyl)borinic acid (2a) with aniline (4a)
gave the desired diarylamine, 4-methyl-N-phenylaniline (5aa), in
just 15% yield under the optimal conditions established for
(benz)imidazoles in 24 hours (Table 3, entry 1). Using high
loadings of copper catalyst (Cu(OAc)2·H2O, 100 mol%) or / and
bis(p-tolyl)borinic acid (2a) (2 equiv. with respect to aryl group)
just slightly increased the yields of 5aa (17-35%). Copper nitrate
(Cu(NO3)2·3H2O), which catalyzed the arylation of
(benz)imidazoles as efficiently as Cu(OAc)2·H2O, also performed
poorly. However, when pyridine was used as base in placement
of TMEDA, 5aa could be isolated in 60% yield, implying a
crucial role of bases in the Chan-Lam CAr-N arylation of
diarylborinic acids (Table 3, entry 6). Only modest yields (47-
51%) for 5aa were obtained with 10 mol% Cu(DMAP)4I2 as the
catalyst that was reported to catalyze Chan-Lam coupling of
amines with a variety of boronic acids in minutes under base-free

4
Tetrahedron
ACCEPTED MANUSCRIPT
Table 4. Scope of Py-assisted, Cu(OAc)2-catalyzed N-arylation of amines with diarylborinic acidsa
a Isolated yield.
b 0.35 equiv. anhydride (Ph2B)2O used.
metalation between L2CuIIX2 and ArnB(OH)3-n or Arn-1B(OH)3-n
X
determines the turnover rate, which could be facilitated by base
as well as protic solvents, particularly methanol. However, for
the less reactive substrates, e.g. amines, the rate-determining step
switches to involve transmetalation between L2CuIII(Ar)X2 and
HNR2, requiring a different copper catalytic system, e.g. solvent
(CH2Cl2), ligand (Py), and base (Py), from that for
(benz)imidazole (TMEDA/MeOH). The better performance of Py
than TMEDA in the amine arylation could be attributed to the
higher electrophilicity of Py-ligated aryl copper intermediates
(Py)2CuIII(Ar)X2 than the more stable TMEDA-chelated one, thus
facilitating the rate-determining transmetalation with HNR2.
However, the low stability of the former, thus high tendency to
decompose, led to the requirement of high loadings of catalyst
(20mol%) and borinic acids (0.75equiv.) for the pyridine-assisted
2.3 Mechanistic discussion
Although the mechanism of Chan-Lam coupling is still rather
controversial,2 the results obtained in present work appear to be
consistent with the catalytic cycle proposed by Stahl et al.,6 in
which the rate-determining steps involve transmetalations
between copper and boron species (i) and / or N-centered
nucleophiles (iii) depending on reaction conditions (Scheme 1).
The additives, TMEDA or Py, play dual roles: promote the
transmetalations as base and stabilize copper species as
supporting ligand. Both aryl groups of diarylborinic acids could
take part in the arylation since transfer of the first one generates
arylboronic derivatives, the aryl source in original Chan-Lam
coupling. For highly reactive imidazole substrates, trans-

5
copper-catalyzed arylation of amines. The observed large steric
effects from both diarylborinic acids and amines are also
consistent with the rate-determining role of transmetaltion
between (Py)2CuIII(Ar)X2 and amines in the catalytic cycle.
mol%), and MeOH (10 mL). The mixture was stirred at room
ACCEPTED MANUSCRIPT
temperature in air monitored by TLC until the starting materials
were completely consumed. The solvent was removed by
rotavapor to give a residue, from which the product was isolated
by column chromatography on silica gel with MeOH/CH2Cl2 or
EtOAc/petroleum ether as eluents.
4.3. 1-(4-Methylphenyl)benzimidazole (3aa).2a
B.HX
Pale yellow liquid (0.206 g, 99%); 1H NMR (400 MHz, CDCl3)
δ: 8.20 (s, 1H), 7.94-7.91 (m, 1H), 7.51-7.49 (m, 1H), 7.39-7.31
(m, 6H), 2.45 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 143.9,
142.4, 138.1, 133.9, 133.8, 130.6, 124.0, 123.6, 122.7, 120.5,
110.5, 21.2.
B + H2O
n = 2
ArnB(OH)3-n
n = 1,2
Arn-1B(OH)3-n
X
L2CuIIX2
H2O
O2 + HX
4.4.1-Phenylbenzimidazole (3ab).5
i
iv
Pale yellow liquid (0.190 g, 98%); 1H NMR (400 MHz,
CDCl3) δ: 8.12 (s, 1H), 7.90-7.88 (m, 1H), 7.60-7.45 (m, 6H),
7.36-7.31 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 144.0, 142.3,
136.4, 133.7, 130.1, 128.1, 124.1, 123.7, 122.8, 120.6, 110.5.
L2CuII(Ar)X
L2CuIX
CuIIX2
CuIX
Ar-NR2
ii
L2CuIII(Ar)X2
iv
4.5 1-(4-Flurophenyl)benzimidazole (3ac).14
o
1
L2CuIII(Ar)(NR2)X
iii
White solid (0.208 g, 98%); m.p. 114-115 C; H NMR (400
MHz, CDCl3) δ: 8.07 (s, 1H), 7.89-7.87 (m, 1H), 7.50-7.45 (m,
3H), 7.35-7.25 (m, 4H); 13C NMR (100 MHz, CDCl3) δ: 162.0 (d,
J = 246.9 Hz), 143.9, 142.3, 133.9, 132.4 (d, J = 3.1 Hz), 126.1
(d, J = 8.6 Hz), 123.8, 122.9, 120.7, 117.1 (d, J = 22.8 Hz), 110.2.
B.HX HNR2 + B
Scheme 1. A plausible mechanism stemming from Stahl’s
postulation
4.6. 1-(4-Methoxyphenyl)benzimidazole (3ad).5
o
1
3. Conclusions
Pale yellow solid (0.222 g, 99%); m.p. 94-95 C; H NMR (400
MHz, CDCl3) δ: 8.05 (s, 1H), 7.88-7.86 (m, 1H), 7.47-7.44 (m,
1H), 7.42-7.39 (m, 2H), 7.34-7.29 (m, 2H), 7.09-7.05 (m, 2H),
3.89 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 159.3, 143.8, 142.6,
134.2, 129.2, 125.7, 123.5, 122.6, 120.5, 115.1, 110.4, 55.7.
In summary, N-arylation of (benz)imidazoles and amines with
diarylborinic acids as cost-effective aryl source has been
efficiently effected via base-assisted, Cu(OAc)2-catalyzed Chan-
Lam CAr-N cross-coupling by using proper combinations of bases
and solvents. (Benz)imidazoles, except for those bearing a
substituent at 2-position, showed high reactivities, coupling with
slight excess (0.65 equiv., 1.3 equiv. with respect to aryl) of
electronically and sterically various diarylborinic acids to give 1-
aryl (benz)imidazoles in excellent yields by using 5 mol% copper
acetate in the presence of 1 equiv. TMEDA in methanol at room
temperature in air. The reaction of less reactive substrates,
anilines and aliphatic amines, required higher loadings of
Cu(OAc)2 (20 mol%) and borinic acids (0.75 equiv.) with the
assistance of 2 equiv. pyridine in CH2Cl2 to proceed smoothly
and was significantly affected by steric factors from amines and /
or diarylborinic acids while the electronic influences appeared to
be small or negligible. These results indicated that the relatively
less oxygen-tolerant diarylborinic acids could be also efficiently
used as aryl sources even under oxidative conditions, provided
that a proper catalyst system could be developed.
4.7. 1-(2-Methylphenyl)benzimidazole (3ae).5
Pale yellow liquid (0.202 g, 97%); 1H NMR (400 MHz,
CDCl3) δ: 7.97 (s, 1H), 7.89 (d, J = 7.6 Hz, 1H), 7.44-7.41 (m,
2H), 7.39-7.28 (m, 4H), 7.14 (d, J = 7.6 Hz, 1H), 2.10 (s, 3H);
13C NMR (100 MHz, CDCl3) δ: 143.3, 143.0, 135.4, 134.8, 134.7,
131.5, 129.4, 127.7, 127.2, 123.5, 122.5, 120.4, 110.5, 17.6.
4.8. 1-(2-Methoxyphenyl)benzimidazole (3af).5
Pale yellow liquid (0.211 g, 94%); 1H NMR (400 MHz,
CDCl3) δ: 8.11 (s, 1H), 7.91-7.89 (m, 1H), 7.50-7.44 (m, 2H),
7.36-7.31 (m, 3H), 7.16-7.13 (m, 2H), 3.82 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ: 154.0, 143.9, 143.3, 134.5, 129.8, 127.3,
124.8, 123.3, 122.4, 121.0, 120.2, 112.5, 110.8, 55.8.
4.9. 1-(2-Ethylphenyl)benzimidazole (3ag).
Pale yellow liquid (0.211 g, 95%); 1H NMR (400 MHz,
CDCl3) δ: 7.99 (s, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.52-7.48 (m,
2H), 7.41-7.28 (m, 4H), 7.16 (d, J = 7.6 Hz, 1H), 2.43 (q, J = 7.6
Hz, 2H), 1.07 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ:
143.2, 141.6, 135.3, 134.1, 129.8, 129.7, 128.1, 127.1, 123.5,
122.5, 120.4, 110.5, 24.1, 15.0. HRMS (ESI) m/z [M+1]+ calcd
for C15H15N2 223.1235, found 223.1234.
4. Experimental Section
4.1. Materials and instruments
All reactions were carried out in air unless otherwise stated.
Commercially available chemicals were used as received.
Diarylborinic acids13 and [Cu(DMAP)4I]I3f were prepared
according to previously reported procedures.1H and 13C NMR
spectra were recorded in CDCl3 or DMSO-d6 at ambient
temperature. Chemical shifts in NMR are reported in ppm (δ),
relative to the internal standard of tetramethylsilane (TMS).
4.10. 1-(2-Isopropoxyphenyl)benzimidazole (3ah).
Pale yellow liquid (0.214 g, 85%); 1H NMR (400 MHz,
CDCl3) δ: 8.13 (s, 1H), 7.90-7.88 (m, 1H), 7.46-7.30 (m, 5H),
7.16-7.10 (m, 2H), 4.55-4.49 (m, 1H), 1.21 (d, J = 6.0 Hz, 6H);
13C NMR (100 MHz, CDCl3) δ: 152.2, 144.0, 143.3, 129.4, 127.2,
126.0, 123.1, 122.2, 121.0, 120.1, 115.5, 110.9, 71.4, 21.8.
HRMS (ESI) m/z [M+1]+ calcd for C16H17N2O 253.1341, found
253.1337.
4.2. General procedure for arylation of (benz)imidazoles
To a 25 mL flask were added (benz)imidazoles (1.0 mmol),
diarylborinic acid (0.65 mmol, 1.3 equiv. with respect to aryl
group), TMEDA (1.0 mmol), Cu(OAc)2·H2O (0.05 mmol, 5

6
Tetrahedron
ACCEPTED MANUSCRIPT
o
1
4.11. 2-Methyl-1-p-tolylbenzimidazole (3ba).15
Pale solid (0.218 g, 80%); m.p. 99-101 C; H NMR (400
MHz, CDCl3) δ: 7.22 (d, J = 8.8 Hz, 2H), 7.01 (d, J = 8.0 Hz,
2H), 6.89 (d, J = 8.4 Hz, 2H), 6.78 (d, J = 8.8 Hz, 2H), 5.49 (br s,
1H), 2.23 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 142.2, 138.5,
131.0, 130.6, 128.9, 118.4, 117.0, 110.7, 19.7.
o
1
Pale yellow solid (0.158 g, 71%); m.p. 94-96 C; H NMR
(400 MHz, DMSO-d6) δ: 7.63 (d, J = 7.2 Hz, 1H), 7.40 (dd, J1 =
14.4, J2 = 8.4 Hz, 4H), 7.22-7.14 (m, 2H), 7.09 (d, J = 8.0 Hz,
1H), 2.51 (s, 3H), 2.41 (s, 3 Hz); 13C NMR (100 MHz, DMSO-d6)
δ: 151.5, 142.3, 138.3, 136.1, 133.0, 130.4, 126.6, 122.2, 121.8,
118.4, 109.7, 20.7, 14.0.
4.20. 4-Methyl-N-(4-nitrophenyl)aniline (5ea).19
Pink solid (0.103 g, 39%); m.p. 139-140oC; H NMR (400
1
4.12. 2-Phenyl-1-p-tolylbenzimidazole (3ca).16
MHz, CDCl3) δ: 8.08 (d, J = 9.2 Hz, 2H), 7.19 (d, J = 8.4 Hz,
2H), 7.11 (d, J = 8.4 Hz, 2H), 6.86 (d, J = 9.2 Hz, 2H), 6.36 (br
s,1H), 2.36 (s, 3H); 13CNMR (100 MHz, CDCl3) δ: 150.9, 139.4,
136.8, 134.8, 130.3, 126.3, 122.7, 113.2, 20.9.
Pale yellow liquid (0.028 g, 10%); 1H NMR (400 MHz,
DMSO-d6) δ: 7.79 (d, J = 7.6 Hz, 1H), 7.56-7.53 (m, 2H), 7.43-
7.26 (m, 9H), 7.18 (d, J = 7.2 Hz, 1H), 2.41 (s, 3H); 13C NMR
(100 MHz, DMSO-d6) δ: 152.3, 142.9, 138.9, 137.7, 134.3, 131.0,
130.3, 130.0, 129.5, 128.8, 127.7, 123.8, 123.1, 119.8, 110.9,
21.2.
4.21. Ethyl 4-(p-tolylamino)benzoate (5fa).3d
White solid (0.174 g, 72%); m.p. 104-106oC; H NMR (400
1
MHz, CDCl3) δ: 7.89 (d, J = 8.8 Hz, 2H), 7.14 (d, J = 8.4 Hz,
2H), 7.07 (d, J = 8.0 Hz, 2H), 6.91 (d, J = 8.8 Hz, 2H), 6.01 (br s,
1H), 4.32 (q, J = 7.2 Hz, 3H), 2.33 (s, 3H), 1.36 (t, J = 7.2 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ: 166.6, 148.7, 138.2, 133.1,
131.4, 130.0, 121.3, 120.9, 114.0, 60.4, 20.8, 14.4.
4.13. 1-(p-Tolyl)imidazole (3da).2a
Pale yellow oil (0.157 g, 99%); 1H NMR (400 MHz, CDCl3) δ
(ppm): 7.82 (s, 1H), 7.27 (s, 4H), 7.25 (s, 1H), 7.19 (s, 1H), 2.40
(s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm): 137.5, 135.6,
135.0, 130.4, 130.2, 121.5, 118.4, 21.0.
4.22. 1-(4-(p-Tolylamino)phenyl)ethanone (5ga).3d
1
4.14. 2-Methyl-1-(p-tolyl)imidazole (3ea).3a
Pale solid (0.144 g, 66%); m.p. 117-118oC; H NMR (400
MHz, CDCl3) δ: 7.87 (d, J = 8.8 Hz, 2H), 7.19 (d, J = 8.0 Hz,
2H), 7.12 (d, J = 8.0 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 6.18 (br s,
1H), 2.55 (s, 3H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3) δ:
196.5, 149.1, 137.8, 133.4, 130.7, 130.1, 128.5, 121.6, 113.8,
26.2, 20.9.
Pale yellow oil (0.146 g, 85%); 1H NMR (400 MHz, CDCl3) δ:
7.27 (d, J = 8.0 Hz, 2H), 7.17 (d, J = 8.4 Hz, 2H), 7.01 (s, 1H),
7.00 (s, 1H), 2.42 (s, 3H), 2.34 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ: 144.8, 138.2, 135.5, 130.0, 127.5, 125.3, 120.7, 21.1,
13.7.
4.23. 1-(2-(p-Tolylamino)phenyl)ethanone (5ha).20
4.15. General Procedure for Arylation of Amines.
Pale yellow liquid (0.103 g, 46%); 1H NMR (400 MHz,
CDCl3) δ: 10.46 (br s, 1H), 7.78 (dd, J1 = 8.4, J2 = 1.6 Hz, 1H),
7.28-7.24 (m, 1H), 7.16-7.12 (m, 5H), 6.70-6.66 (m, 1H), 2.62 (s,
3H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 201.1, 148.6,
137.6, 134.6, 133.9, 132.6, 130.0, 123.8, 118.6, 116.1, 114.0,
28.1, 21.0.
To a 25 mL flask were added aniline or alkylamine (1.0
mmol), diarylborinic acid (0.75 mmol, 1.5 equiv. with respect to
aryl group), Cu(OAc)·H2O (48.40 mg, 0.2 mmol) and pyridine
(162 ul, 2 mmol) and CH2Cl2 (10 ml). The mixture was stirred at
room temperature in air for 24 h. The reaction mixture was
diluted with CH2Cl2 (20 mL), followed by washing with H2O (2
× 10 mL). The organic layer was dried over Na2SO4, filtered, and
evaporated under reduced pressure to give crude product, which
was purified by column chromatography on silica gel with
MeOH/CH2Cl2 or EtOAc/petroleum ether as eluents.
4.24. 1-(3-(p-Tolylamino)phenyl)ethanone (5ia).
Pale solid (0.180 g, 80%); m.p. 95-97oC; 1H NMR (400 MHz,
CDCl3) δ: 7.55 (t, J = 2.0 Hz, 1H), 7.41 (d, J = 7.6 Hz, 1H), 7.29
(t, J = 7.6 Hz, 1H), 7.19-7.17 (m, 1H), 7.10 (d, J = 8.4 Hz, 2H),
7.01 (d, J = 8.4 Hz, 2H), 5.83 (br s, 1H), 2.55 (s, 3H), 2.31 (s,
3H); 13C NMR (100 MHz, CDCl3) δ: 198.4, 144.7, 139.5, 138.3,
131.8, 130.1, 129.5, 120.7, 120.1, 119.6, 115.6, 26.8, 20.8.
HRMS (ESI) m/z [M+1]+ calcd for C15H16NO 226.1232, found
226.1229.
4.16. N-Phenyl-4-methylaniline (5aa).17
1
Pale yellow solid (0.170 g, 93%); m.p. 90-91oC; H NMR
(400 MHz, CDCl3) δ: 7.15 (t, J = 7.8 Hz, 2H), 7.00 (d, J = 8.0 Hz,
2H), 6.93-6.90 (m, 4H), 6.79 (t, J = 7.4 Hz, 1H), 5.50 (br s,1H),
2.22 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 142.9, 139.2, 129.9,
128.8, 128.3, 119.2, 117.8, 115.8, 19.6.
4.25. N-(p-Tolyl)pyridin-2-amine (5ja).21
1
4.17. Di-p-Tolylamine (5ba).17
White solid (0.057 g, 31%); m.p. 101-103oC; H NMR (400
MHz, CDCl3) δ: 8.20 (d, J = 2.8 Hz, 1H), 7.49 (m, 1H), 7.22 (d, J
= 8.4 Hz, 2H), 7.16 (d, J = 8.0 Hz, 2H), 6.85 (d, J = 8.4 Hz, 1H),
6.74-6.71 (m, 2H), 2.36 (s, 3H); 13C NMR (100 MHz, CDCl3) δ:
156.6, 148.3, 137.7, 137.7, 132.9, 129.9, 121.3, 114.6, 107.7,
20.9.
Pale solid (0.185 g, 94%); m.p. 77-80 oC; 1H NMR (400 MHz,
CDCl3) δ: 7.15 (d, J = 8.4 Hz, 4H), 7.03 (d, J = 8.4 Hz, 4H), 5.57
(br s, 1H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 141.2,
130.2, 130.0, 118.0, 20.7.
4.18. 4-Methoxy-N-(p-tolyl)aniline (5ca).2a
4.26. 2,4,6-Trimethyl-N-(p-tolyl)aniline (5ka).3d
1
Pale solid (0.181 g, 85%);m.p. 82-84oC; H NMR (400 MHz,
Pink liquid (0.140 g, 58%); 1H NMR (400 MHz, CDCl3)
δ:6.87 (d, J = 8.0 Hz, 2H), 6.85 (s, 2H), 6.33 (d, J = 8.4 Hz, 2H),
4.92 (br s, 1H), 2.22 (s, 3H), 2.15 (s, 3H), 2.08 (s, 6H); 13C NMR
(100 MHz, CDCl3) δ: 143.3, 134.9, 134.6, 134.0, 128.7, 128.2,
126.1, 112.4, 19.8, 19.4, 17.2.
CDCl3) δ: 7.04-7.00 (m, 4H), 6.85-6.82 (m, 4H), 5.38 (br s,1H),
3.78 (s, 3H), 2.27 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 154.8,
142.4, 136.7, 129.8, 129.3, 121.1, 116.5, 114.7, 55.6, 20.6.
4.19. 4-Bromo-N-(p-tolyl)aniline (5da).18
4.27. 2,6-Diisopropyl-N-(p-tolyl)aniline (5la).22

7
Pale yellow liquid (0.054 g, 20%); 1H NMR (400 MHz,
CDCl3) δ: 7.29-7.19 (m, 3H), 6.93 (d, J = 8.4 Hz, 2H), 6.40 (d, J
= 8.4 Hz, 2H), 5.02 (br s, 1H), 3.23-3.16 (m, 2H), 2.22 (s, 3H),
1.13 (d, J = 6.8 Hz, 12H); 13C NMR (100 MHz, CDCl3) δ: 147.4,
145.9, 135.7, 129.8, 127.0, 126.9, 123.8, 113.1, 28.3, 23.9, 20.5.
6.68 (d, J = 9.2 Hz, 2H), 4.36 (s, 2H), 3.82 (s, 3H); 13C NMR
ACCEPTED MANUSCRIPT
(100 MHz, CDCl3) δ: 152.2, 142.6, 139.8, 128.7, 127.6, 127.3,
115.0, 114.2, 55.9, 49.3.
4.37. N-Benzylaniline (5mb).7b
Pale yellow solid (0.160 g, 87%); m.p. 34-35 oC; H NMR
1
4.28. 4-Fluoro-N-(p-tolyl)aniline (5bc).23
(400 MHz, CDCl3) δ: 7.48-7.43 (m, 4H), 7.40-7.36 (m, 1H), 7.28
(t, J = 8.0 Hz, 2H), 6.83 (t, J = 7.6 Hz, 1H), 6.73 (d, J = 8.0 Hz,
2H), 4.42 (s, 2H), 4.11 (br s, 1H); 13C NMR (100 MHz, CDCl3) δ:
148.3, 139.6, 129.4, 128.8, 127.6, 127.3, 117.7, 113.0, 48.4.
Pink solid (0.190 g, 94%); m.p. 49-50oC; 1H NMR (400 MHz,
CDCl3) δ: 7.14 (d, J = 8.0 Hz, 2H), 7.03-6.97 (m, 6H), 5.54 (br s,
1H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 157.7 (d, J =
237.7 Hz), 141.1, 139.8, 130.6, 130.0, 119.4 (d, J = 7.7 Hz),
117.9, 115.9 (d, J = 22.3 Hz), 20.7.
4.38. N-Benzyl-2-methylaniline (5me).26
Pale solid (0.110 g, 56%); m.p. 56-57 oC; 1H NMR (400 MHz,
CDCl3) δ: 7.53-7.47 (m, 4H), 7.44-7.40 (m, 1H), 7.26-7.21 (m,
2H), 6.82 (t, J = 7.4 Hz, 1H), 6.75 (d, J = 7.6 Hz, 1H), 4.50 (s,
2H), 3.99 (br s, 1H), 2.30 (s, 3H); 13C NMR (100 MHz, CDCl3) δ:
146.1, 139.6, 130.2, 128.8, 127.6, 127.3, 127.3, 122.0, 117.3,
110.0, 48.4, 17.7.
4.29. 2-Methyl-N-(p-tolyl)aniline (5be).23
1
Pink liquid (0.109 g, 55%); H NMR (400 MHz, CDCl3) δ:
7.24-7.12 (m, 5H), 6.98-6.91 (m, 3H), 5.35 (br s, 1H), 2.36 (s,
3H), 2.30 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 142.1, 141.1,
130.9, 129.9, 127.0, 126.8, 121.1, 118.7, 117.2, 20.7, 17.9.
4.30. 2-Methoxy-N-(p-tolyl)aniline (5bf).3d
4.39. N-Benzyl-2-methoxyaniline (5mf).26
1
Pink liquid (0.053 g, 25%); H NMR (400 MHz, CDCl3) δ:
Pale yellow liquid (0.059 g, 28%); 1H NMR (400 MHz,
CDCl3) δ: 7.38-7.31 (m, 4H), 7.27-7.24 (m, 1H), 6.85-6.77 (m,
2H), 6.69-6.65 (m, 1H), 6.58 (dd, J1 = 7.6 Hz, J2 = 1.2 Hz, 1H),
4.62 (br s, 1H), 4.34 (s, 2H), 3.83 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ: 146.8, 139.6, 138.2, 128.6, 127.6, 127.2, 121.3, 116.7,
110.1, 109.4, 55.4, 48.1.
7.29-7.27 (m, 1H), 7.18-7.12 (m, 4H), 6.94-6.85 (m, 3H), 6.14
(br s, 1H), 3.94 (s, 3H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ:147.9, 140.0, 133.9, 131.1, 129.9, 120.9, 119.7, 119.2, 113.7,
110.4, 55.6, 20.8.
4.31. 2-Ethyl-N-(p-tolyl)aniline (5bg).24
4.40. N-Benzyl-2-ethylaniline (5mg).27
Pink liquid (0.106 g, 50%); 1H NMR (400 MHz, CDCl3)
δ:7.29-7.24 (m, 2H), 7.20-7.12 (m, 3H), 7.02-6.94 (m, 3H), 5.39
(br s, 1H), 2.67 (q, J = 7.6 Hz, 2H), 2.36 (s, 3H), 1.32 (t, J = 7.6
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 141.6, 141.4, 133.4,
130.2, 129.9, 128.9, 126.7, 121.7, 118.5, 118.3, 24.3, 20.7, 13.8.
Pale yellow liquid (0.106 g, 50%); 1H NMR (400 MHz,
CDCl3) δ: 7.55-7.49 (m, 4H), 7.45-7.42 (m, 1H), 7.28-7.25 (m,
2H), 6.89 (t, J = 7.4 Hz, 1H), 6.79 (d, J = 8.8 Hz, 1H), 4.52 (s,
2H), 4.11 (br s, 1H), 2.67 (q, J = 7.6 Hz, 2H), 1.43 (t, J = 7.6 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ: 145.6, 139.8, 128.9, 128.0,
127.7, 127.4, 127.2, 117.6, 48.5, 24.1, 13.1.
4.32. N-Benzyl-4-methylaniline (5ma).25
Pale yellow liquid (0.164 g, 83%); 1H NMR (400 MHz,
CDCl3) δ: 7.45-7.28 (m, 5H), 7.06 (d, J = 8.4 Hz, 2H), 6.63 (d, J
= 8.4 Hz, 2H), 4.37 (s, 2H), 3.96 (br s, 1H), 2.32 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ: 146.0, 139.7, 129.8, 128.7, 127.6,
127.2, 126.8, 113.1, 48.7, 20.5.
4.41. 1-(p-Tolyl)piperidine (5qa).3d
1
Colorless liquid (0.091 g, 52%); H NMR (400 MHz, CDCl3)
δ: 7.11 (d, J = 8.4 Hz, 2H), 6.91 (d, J = 8.8 Hz, 2H), 3.14 (t, J =
5.6 Hz, 4H), 2.31 (s, 3H), 1.79-1.73 (m, 4H), 1.63-1.57 (m, 2H);
13C NMR (100 MHz, CDCl3) δ: 150.3, 129.6, 128.8, 117.0, 51.4,
26.0, 24.3, 20.5.
4.33. N-Cyclohexyl-4-methylaniline (5na).3d
Pale yellow liquid (0.143 g, 75%); 1H NMR (400 MHz,
CDCl3) δ: 7.05 (d, J = 8.4 Hz, 2H), 6.60 (d, J = 8.4 Hz, 2H),
3.33-3.26 (m, 1H), 2.31 (s, 3H), 2.15-2.11 (m, 2H), 1.86-1.80 (m,
2H), 1.75-1.70 (m, 1H), 1.49-1.39 (m, 2H), 1.35-1.15 (m, 3H);
13C NMR (100 MHz, CDCl3) δ: 145.2, 129.8, 126.1, 113.5, 52.1,
33.6, 26.1, 25.1, 20.5.
4.42. 1-(4-Fluorophenyl)piperidine (5qc).28
Pale yellow liquid (0.088 g, 49%); 1H NMR (400 MHz,
CDCl3) δ: 7.00-6.90 (m, 4H), 3.09 (t, J = 5.4 Hz, 4H), 1.78-1.72
(m, 4H), 1.62-1.56 (m, 2H); 13C NMR (100 MHz, CDCl3) δ:
157.0 (d, J = 236.9 Hz), 149.1, 118.4 (d, J = 7.5 Hz), 115.4 (d, J
= 21.8 Hz), 51.9, 26.0, 24.1.
4.34. N-Butyl-4-methylaniline (5pa).24
4.43. 1-(4-Methoxyphenyl)piperidine (5qd).3f
1
Pale liquid (0.135 g, 82%); H NMR (400 MHz, CDCl3) δ:
7.03 (d, J = 8.0 Hz, 2H), 6.59 (d, J = 8.4 Hz, 2H), 3.13 (t, J = 7.2
Hz, 2H), 2.29 (s, 3H), 1.68-1.60 (m, 2H), 1.52-1.43 (m, 2H), 1.00
(t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 146.3, 129.7,
126.3, 112.9, 44.1, 31.8, 20.4, 20.4, 14.0.
Pale yellow liquid (0.105 g, 55%); 1H NMR (400 MHz, CDCl3) δ:
6.98-6.94 (m, 2H), 6.89-6.85 (m, 2H), 3.80 (s, 3H), 3.06 (t, J =
5.4 Hz, 4H), 1.79-1.73 (m, 4H), 1.61-1.55 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ: 153.7, 146.7, 118.9, 114.3, 55.5, 52.5, 26.1,
24.2.
4.35. N-Benzyl-4-fluoroaniline (5mc).26
Acknowledgments
Pale yellow liquid (0.157 g, 78%); 1H NMR (400 MHz,
CDCl3) δ: 7.42-7.29 (m, 5H), 6.94 (t, J = 8.8 Hz, 2H), 6.63-6.60
(m, 2H), 4.34 (s, 2H), 3.98 (br s, 1H); 13C NMR (100 MHz,
CDCl3) δ: 155.9 (d, J = 233.6 Hz), 144.5, 139.3, 128.7, 127.5,
127.4, 115.7 (d, J = 22.3 Hz), 113.7 (d, J = 7.4 Hz), 48.9.
We are grateful for financial support provided by the National
Natural Science Foundation of China (21472041) and National
Key Technology R&D Program, the Ministry of Science and
Technology of China (2015BAK44B00).
4.36. N-Benzyl-4-methoxyaniline (5md).25
References and notes
1
Pale yellow solid (0.162 g, 76%); m.p. 48-49 oC; H NMR
1. (a) Chan, D. M. T.; Monaco, K. L.; Wang, R.-P.; Winters, M. P.
Tetrahedron Lett. 1998, 39, 2933-2936. (b) Lam, P. Y. S.; Clark,
(400 MHz, CDCl3) δ: 7.47-7.34 (m, 5H), 6.87 (d, J = 9.2 Hz, 2H),

8
Tetrahedron
ACCEPTED MANUSCRIPT
C. G.; Saubern, S.; Adams, J.; Winters, M. P.; Chan, D. M. T.;
Combs, A. Tetrahedron Lett. 1998, 39, 2941-2944.
2. (a) Rao, K. S.; Wu, T.-S. Tetrahedron 2012, 68, 7735-7754. (b)
Qiao, J. X.; Lam, P. Y. S. Synthesis 2011, 6, 829-856. (c) Bariwal,
J.; Eycken, E. V. Chem. Soc. Rev. 2013, 43, 9283-9303.
3. For catalytic copper, see: (a) Collman, J. P.; Zhong, M.; Zhang,
C.; Costanzo, S. Org. Lett. 2000, 2, 1233-1236. (b) Collman, J. P.;
Zhong, M.; Zhang, C.; Costanzo, S. J. Org. Chem. 2001, 66, 7892-
7897. (c) Lam, P. Y. S.; Vincent, G.; Clark, C. G.; Deudon, S.;
Jadhav, J. K. Tetrahedron Lett. 2001, 42, 3415-3418. (d) Kwong,
F. Y.; Klapars, A.; Buchwald, S. L. Org. Lett. 2002, 4, 581-584.
(e) Quach, T. D.; Batey, R. A. Org. Lett. 2003, 5, 4397-4400. (f)
Roy, S.; Sarma, M. J.; Kashyap, B.; Phukan, P. Chem. Commun.
2016, 52, 1170-1173.
4. Lan, J.-B.; Chen, L.; Yu, X.-Q.; You, J.-S.; Xie, R.-G. Chem.
Commun. 2004, 40, 188-189.
5. Wentzel, M. T.; Hewgley, J. B.; Kamble, R. M.; Wall, P. D.;
Kozlowski, M. C. Adv. Synth. Catal. 2009, 351, 931-937.
6. King, A. E.; Brunold, T. C.; Stahl, S. S. J. Am. Chem. Soc. 2009,
131, 5044-5045.
7. (a) Tzschucke, C.; Murphy, J.; Hartwig, J. F. Org. Lett. 2007, 9,
761-764. (b) Sueki, S.; Kuninobu, Y. Org. Lett. 2013, 15, 1544-
1547. (c) McGarry, K. A.; Duenas, A. A.; Clark, T. B. J. Org.
Chem. 2015, 80, 7193-7204. (d) Vantourout, J. C.; Law, R. P.;
Albert, I.-L.; Atkinson, S. J.; Watson, A. J. B. J. Org. Chem. 2016,
81, 3942-3950.
8. (a) Cole, T. E.; Haly, B. D. Organometallics 1992, 11, 652-657.
(b) Brown, H. C.; Racherla, U. S. J. Org. Chem. 1986, 51, 427-
432.
9. (a) Marciasini, L.; Cacciuttolo, B.; Vaultier, M.; Pucheault, M.
Org. Lett. 2015, 17, 3532-3535. (b) Richard, J.; Birepinte, M.;
Charbonnier, J. B.; Liautard, V.; Pinet, S.; Pucheault, M.
Synthesis, 2017, 49, 736-744.
10. (a) Chen, X.; Ke, H.; Chen, Y.; Guan, C.; Zou, G. J. Org. Chem.
2012, 77, 7572-7578. (b) Chen, X.; Ke, H.; Zou, G. ACS Catal.
2014, 4, 379-385. (c) Ke, H.; Chen, X.; Zou, G. J. Org. Chem.
2014, 79, 7132-7140. (d) Li, X.; Zou, G. J. Organomet. Chem.
2015, 794, 136-145. (e) Si S.; Wang C.; Zhang N.; Zou G. J. Org.
Chem. 2016, 81, 4364−4370. (f) Wang, C.; Zhang, J.; Tang, J.;
Zou G. Adv. Synth. Catal. 2017, 359, 2514-2519. (g) Zhang N.;
Wang C.; Zou G.; Tang J. J. Organomet. Chem. 2017, 842, 54-58.
11. (a) Turner, W. R.; Elving, P. J. Anal. Chem. 1965, 37, 207−211.
(b) Geske, D. H. J. Chem. Phys. 1959, 63, 1062-1070.
12. Das, P.; Basu, B. Synth. Commun. 2004, 34, 2177-2184.
13. Li, X.; Feng, Y.; Lin, L.; Zou, G. J. Org. Chem. 2012, 77, 10991-
10995.
14. Diness, F.; Fairlie, D. Angew. Chem. Int. Ed. 2012, 51, 8012-8016.
15. Yang, D.; Fu, H.; Hu, L.; Jiang, Y.; Zhao, Y. J. Org. Chem. 2008,
73, 7841-7844.
16. Zhao, D.; Hu, J.; Wu, N.; Huang, X.; Qin, X.; Lan, J.; You, J. Org.
Lett. 2011, 13, 6516-6519.
17. Li, G. Y.; Zheng, G.; Noonan, A. F. J. Org. Chem. 2001, 66,
8677-8681.
18. Yu, J.; Wang, Y.; Zhang, P.; Wu, J. Synlett 2013, 24, 1448-1454.
19. Liu, X.; Zhang, S. Synlett 2011, 8, 1137-1142.
20. Wray, B. C.; Stambuli, J. P, Org. Lett. 2010, 12, 4576-4579.
21. Wang, H.; Wang, Y.; Peng, C.; Zhang, J.; Zhu, Q. J. Am. Chem.
Soc. 2010, 132, 13217-13219.
22. Reddy, C. V.; Kingston, J. V.; Verkade, J. G. J. Org. Chem. 2008,
73, 3047-3062.
23. Hajra, A.; Wei, Y.; Yoshikai, N. Org. Lett. 2012, 14, 5488-5491.
24. Samblanet, D. C.; Schmidt, J. A. R. J. Organomet. Chem. 2012,
720, 7-18.
25. Zhang, H.; Cai, Q.; Ma, D. J. Org. Chem. 2005, 70, 5164-5173.
26. Zhou, W.; Fan, M.; Yin, J.; Jiang, Y.; Ma, D. J. Am. Chem. Soc.
2015, 137, 11942-11945.
27. Corre, Y.; Iali, W.; Hamdaoui, M.; Trivelli, X.; Djukic, J.-P.;
Agbossou-Niedercorn, F.; Michon, C. Catal. Sci. Technol., 2015,
5, 1452-1458.
28. Lerma, I. C.; Cawley, M. J.; Cloke, F. G. N.; Arentsen, K.; Scott,
J. S.; Pearson, S. E.; Hayler, J.; Caddick, S. J. Organomet. Chem.
2005, 690, 5841-5848.