Chemoselective amination of bromoiodobenzenes with diarylamines by palladium/Xantphos or ligand-free copper catalysts

Article abstract of DOI:10.1016/j.tet.2015.01.028

We report the chemoselective amination of bromoiodobenzenes with diarylamines by palladium/Xantphos or a ligand-free copper catalyst. The reactions by these two types of catalysts proceeded with a high chemoselectivity and afforded monobrominated triarylamines in good yields. These products are useful intermediates for the synthesis of unsymmetrical bistriarylamines.

Full text of DOI:10.1016/j.tet.2015.01.028

Accepted Manuscript
Chemoselective Amination of Bromoiodobenzenes with Diarylamines by Palladium/
Xantphos or Ligand-free Copper Catalysts
Yoshinori Kanazawa, Tomo Yokota, Hiroshi Ogasa, Hirotaka Watanabe, Taisyun
Hanakawa, Shinichi Soga, Motoi Kawatsura
PII:
S0040-4020(15)00071-X
10.1016/j.tet.2015.01.028
TET 26351
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 21 December 2014
Revised Date: 12 January 2015
Accepted Date: 13 January 2015
Please cite this article as: Kanazawa Y, Yokota T, Ogasa H, Watanabe H, Hanakawa T, Soga S,
Kawatsura M, Chemoselective Amination of Bromoiodobenzenes with Diarylamines by Palladium/
Xantphos or Ligand-free Copper Catalysts, Tetrahedron (2015), doi: 10.1016/j.tet.2015.01.028.
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
Chemoselective Amination of Bromoiodobenzenes with Diarylamines
by Palladium/Xantphos or Ligand-free Copper Catalysts
Yoshinori Kanazawa,† Tomo Yokota,† Hiroshi Ogasa,† Hirotaka Watanabe,‡ Taisyun
Hanakawa,‡ Shinichi Soga,§ Motoi Kawatsura*,‡
†Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori
University, Koyama, Tottori 680-8552, Japan
‡Department of Chemistry, College of Humanities & Sciences, Nihon University, Sakurajosui,
Setagaya-ku, Tokyo 156-8550, Japan
§Tosoh Organic Chemical Co., Ltd., 4988 Kaisei-cho, Shunan, Yamaguchi 746-0006, Japan
E-mail: kawatsur@chs.nihon-u.ac.jp

ACCEPTED MANUSCRIPT
Chemoselective Amination of Bromoiodobenzenes with Diarylamines
by Palladium/Xantphos or Ligand-free Copper Catalysts
Yoshinori Kanazawa,† Tomo Yokota,† Hiroshi Ogasa,† Hirotaka Watanabe,‡Taisyun Hanakawa,‡
Shinichi Soga,§ Motoi Kawatsura*,‡
†Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori
University, Koyama, Tottori 680-8552, Japan
‡Department of Chemistry, College of Humanities & Sciences, Nihon University, Sakurajosui,
Setagaya-ku, Tokyo 156-8550, Japan
§Tosoh Organic Chemical Co., Ltd., 4988 Kaisei-cho, Shunan, Yamaguchi 746-0006, Japan
E-mail: kawatsur@chs.nihon-u.ac.jp
Abstract: We report the chemoselective amination of bromoiodobenzenes with diarylamines
by palladium/Xantphos or a ligand-free copper catalyst. The reactions by these two types of
catalysts proceeded with a high chemoselectivity and afforded monobrominated triarylamines in
good yields. These products are useful intermediates for the synthesis of unsymmetrical
bistriarylamines.
Keywords:
Palladium
Copper
Amination
Chemoselectivity
Triarylamine
1. Introduction
The transition-metal-catalyzed amination of arylhalides is one of the most powerful
carbon-nitrogen bond forming reactions,1 and this reaction is widely used for preparing
arylamines in the field of material and pharmaceutical research. For example, triarylamine is
an important unit of organic electroactive materials2 and the preparation of such compounds was

ACCEPTED MANUSCRIPT
attained by the Buchwald-Hartwig amination reaction (palladium catalysts)3 or the Ullmann
type C-N coupling reaction (copper catalysts)4-6 of arylhalides with diarylamines, and
bistriarylamines were also prepared by the reaction of dihalogenated arenes with diarylamines.
As shown in scheme 1, symmetrical bistriarylamines were easily obtained by the reaction of
dihalogenated arenes with diarylamines, and this reaction is useful for preparing the
symmetrical bistriarylamines (Scheme 1, i-a).
The synthesis of unsymmetrical
bistriarylamines requires the chemoselective monoamination reaction of dihalogenated arenes
with diarylamines at first step and subsequent second amination reaction (Scheme 1, i-b).
Therefore, to obtain the unsymmetrical bistriarylamine, the chemoselective monoamination
reaction is essential, but the selective formation of the monoaminated triarylamine from
dihalogenated arenes, which possess the same two halogen atoms on the aromatic group, is a
difficult process because the reaction of dibromo- or diiodoarenes usually provides a mixture of
monoaminated and bisaminated products with a low selectivity (Scheme 1, ii).7 On the other
hand, the bromoiodoarene or bromochloroarene, which have two different halogen atoms on the
aromatic rings, can potentially provide the monoaminated product by undergoing the
chemoselective reactions. Actually, the realization of the chemoselective amination of
bromochloroarenes is an easy process because there is a significant difference in the reactivity
between the boromoarenes and chloroarenes (Scheme 1, iii).8 However, the reaction using
chlorinated arenes is not suitable for industrial purposes because these reactions potentially
produce PCBs (polychlorinated biphenyls) and related compounds, which are highly toxic and
prohibited to produce any amount as a byproduct. Based on these reasons, for the industrial
purpose, bromoiodoarene is the only usable commercially available dihalogenatedarens to
realize the formation of a monoaminated product by a chemoselective process, but the
reactivities of the bromoarene and iodoarene are not so different compare to the reactivities of
bromoarene and chloroarene, and difficult to obtain the monoaminated product with a high
chemoselectivity (Scheme 1, iv).9 To the best of our knowledge, there are some examples of
the chemoselective Buchwald-Hartwig reactions of bromoiodoarenes, but those reports are
limited to the reaction with aliphatic amines,10 while there are no reports about the reaction of
bromoiodoarene with diarylamines. On the other hand, there are also some reports about the
chemoselective amination of bromoiodoarenes with diarylamines using a copper catalyst, but
these reactions required a relatively high temperature (>100 ˚C) and appropriate ligand.5a,11
Based on this background, we now report the selective formation of monobrominated
triarylamines by the palladium-catalyzed chemoselective amination of bromoiodobenzene with

ACCEPTED MANUSCRIPT
diarylamines, and the ligand-free copper catalyzed reaction under mild reaction conditions.

ACCEPTED MANUSCRIPT
2. Results an discussion
2.1. Palladium Catalysts
To realize the chemoselective amination of dihalogenated arenes with diarylamines
by a palladium catalyst, we first examined the reaction of 1-bromo-4-iodobenzene (1a) with
diphenylamine (2a) using several palladium catalysts. As shown in Table 1, the reactions by
Pd(OAc)2 with monophosphine ligands, such as PPh3 or PtBu3, exhibited a low chemoselectivity
and gave a mixture of mono- and bisaminated products (3aa and 4aa) (Table 1, entries 1 and 2).
On the other hand, we observed that the bisphosphine ligands, such as DPPE or DPPF,
selectively provided the monoaminated product 3aa, but the yields of these reactions were not
satisfactory (entries 3 and 4). Based on these observations, we confirmed that bisphosphine
ligands play an important role to realize the chemoselective amination reaction. Therefore, we
further screened other bisphosphine ligands, such as BINAP or Xantphos, and succeeded in
obtaining 3aa in an acceptable yield with a high chemoselectivity using Xantphos as the ligand
(Table 1, entries 6 and 7). We also demonstrated the reaction in dioxane, and confirmed that
the reaction by 1 mol% of catalyst provided better results (89% yield, >99% chemoselectivity)
than the reaction by 5 mol% (71% yield, 96% chemoselectivity) (Table 1, entries 8 and 9). We
further examined the reaction of 1a with 2a using other palladium precatalysts, but lower yields
were observed in all cases (Table 1, entries 10-13). Based on these results, we concluded that
the optimized reaction conditions, which realize the intended chemoselective amination reaction
of 1a, is using the Pd(OAc)2/Xanthphos catalyst in dioxane at 100 ˚C.11
With the optimized reaction conditions in hand, we investigated the chemoselective
monoamination of bromoiodobenzenes 1a-c with some commercially available diarylamines
2a-h. As shown in Table 2, all reactions proceeded with a high chemoselectivity and afforded
the monoaminated products in good yields.
For example, the reactions of
1-bromo-4-iodobenzene (1a) with diarylamines 2b, 2c and 2g provided the desired
monobrominated triarylamines 3ab, 3ac, and 3ag in 87%, 95%, and 93% isolated yields,
respectively (Table 2, entries 1-3). The Pd(OAc)2/Xantphos catalyzed chemoselective
reactions of 1-bromo-3-iodobenzene (1b) with diarylamines also smoothly proceeded and gave
the intended aminated products in the range of 71-97% yields (entries 4-11). Although the
reaction of 1-bromo-2-iodobenzene (1c) with 2a resulted in a slightly lower yield (58%), an
acceptable yield (75%) was obtained by increasing the catalyst amount from 1 mol% to 5 mol%
(entries 12 and 13).

ACCEPTED MANUSCRIPT
Table 1. Palladium Catalysts for the Chemoselective Amination of 1-Bromo-4-iodobenzene
(1a) with Diphenylamine (2a)a
entry [Pd] (mol%)
L (mol%)
PPh3 (20)
PtBu3 (5)
DPPE (5)
DPPF (5)
BNAP (5)
yieldb,c
51%
79%
33%
74%
74%
3aa : 4aad
71 : 29
59 : 41
>99 : 1
>99 : 1
84 : 16
97 : 3
1
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (1)
Pd(OAc)2 (5)
Pd(OAc)2 (1)
Pd2(dba)3 (2.5)
[PdCl(C3H5)]2 (2.5)
2
3
4
5
6
Xantphos (5) 86%
Xantphos (1) 86%
Xantphos (5) 71%
Xantphos (1) 89%
Xantphos (5) 60%
Xantphos (5) 66%
7
92 : 8
8e
9e
10e
11e
12e
13e
96 : 4
>99 : 1
93 : 7
94 : 6
[Pd(C3H5)(cod)]BF4 (5) Xantphos (5) 62%
92 : 8
PdCl2(PhCN)2 (5) Xantphos (5) 60%
93 : 7
a Reaction conditions: 1a (0.36 mmol), 2a (0.43 mmol), NaOtBu (0.53 mmol), palladium, and
ligand in toluene (0.5 mL) for 12 h at 100 ˚C under nitrogen. b The yields were determined by
HPLC analysis of the crude materials. c Yields of 3aa and 4aa. d The ratios were determined
by HPLC analysis of the crude materials. eDioxane was used as the solvent.

ACCEPTED MANUSCRIPT
Table 2. Palladium-catalyzed Chemoselective Amination of 1a-c with 2a-ha
entry
1
yieldb
3 : 4c
1
2
>99 : 1
1a
2b
87% (3ab)
95% (3ac)
2
3
4
>99 : 1
>99 : 1
>99 : 1
1a
1a
1b
2c
2g
2a
93% (3ag)
93% (3ba)

ACCEPTED MANUSCRIPT
5
6
>99 : 1
>99 : 1
>99 : 1
>99 : 1
>99 : 1
>99 : 1
1b
1b
1b
1b
1b
1b
2b
95% (3bb)
2c
82% (3bc)
7
2d
71% (3bd)
8
2e
85% (3be)
9
2f
79% (3bf)
10
2g
97% (3bg)

ACCEPTED MANUSCRIPT
11
>99 : 1
1b
2h
85% (3bh)
12
>99 : 1
>99 : 1
1c
1c
2a
58% (3ca)
13d
75% (3ca)
2a
a Reaction conditions: 1 (0.36 mmol), 2 (0.43 mmol), NaOtBu (0.53 mmol), Pd(OAc)2 (0.0036
b
mmol), and Xantphos (0.0036 mmol) in toluene (0.5 mL) for 12 h at 100 ˚C under nitrogen.
d
Isolated yields. c The ratios were determined by HPLC analysis of the crude materials.
Conditions: 5 mol% Pd(OAc)2 and Xantphos were used.
2.2. Copper Catalysts
To develop an alternative chemoselective amination of bromoiodobenzenes with
diarylamines, we further investigated the copper-catalyzed reaction. There are some reports
about the chemoselective amination of bromoiodobenzenes with diarylamines by a copper
catalyst,5a,12 but those reactions generally required a relatively high reaction temperature (>100
˚C) and an appropriate ligand. Based on such information, we initiated a study to realize the
intended chemoselective amination reaction by a copper catalyst system under milder
conditions.
For our objective of discovering an effective copper catalyst, we again selected the
reaction of 1-bromo-4-iodobenzene (1a) with diphenylamine (2a) as the standard reaction
system. As we expected, the reaction by 2 mol% of CuCl/1,10-phen in the presence of KOH
(powder) at 125 ˚C, which is a reported reaction condition,12a,b provided the intended
monoaminated product 3aa in 87% yield with a high chemoselectivity (Table 3, entry 1). We
further confirmed that CuBr and CuI also exhibited the same reactivity and chemoselectivity
under the same reaction conditions (entries 2 and 3). Based on these initial results, we further
tried to find the milder conditions by copper catalyst. When the reaction was conducted under

ACCEPTED MANUSCRIPT
lower temperature (80 ˚C), the copper catalysts did not exhibit any catalytic activities, resulting
in no reaction (entries 4 and 5). To our delight, changing the base from KOH to NaOtBu12c,13
was an effective way to allow the amination reaction, and the CuI/1,10-phen catalyst gave an
acceptable result (75% yield, 97% chemoselectivity) at 80 ˚C (entry 7). To attain the perfect
chemoselectivity under milder reaction conditions, we further examined the reaction at 60 ˚C.
On the other hand, the reactions catalyzed by CuI with several ligands, such as 1,10-phen,
pybox or TMHD, resulted in a low yield (entries 8-10). To our delight, we revealed that the
reaction catalyzed by CuI14 without a ligand exhibited higher yields (entry 11), and the
increased amount of catalyst from 2 mol% to 10 mol% realized a high yield with a high
chemoselectivity (entries 12 and 13). The best yield was obtained by the less use of base (2.5
equiv.) (entry 14).

ACCEPTED MANUSCRIPT
Table 3. Copper Catalysts for the Chemoselective Amination of 1a with 2aa
entry [Cu]
(mol%)
L (mol%)
base (equiv.)
temp yieldb
(˚C)
3 : 4c
1d
2d
3d
4d
5d
6
CuCl (2)
CuBr (2)
CuI (2)
CuCl (2)
CuI (2)
CuCl (2)
CuI (2)
CuI (2)
CuI (2)
CuI (2)
CuI (2)
CuI (4)
CuI (10)
CuI (10)
1,10-phen
1,10-phen
1,10-phen
1,10-phen
1,10-phen
1,10-phen
1,10-phen
1,10-phen
pybox
KOH (5)
125
125
125
80
87%
81%
87%
<2%
<2%
28%
75%
25%
26%
49%
56%
75%
94%
98%
>99 : 1
>99 : 1
>99 : 1
nd
KOH (5)
KOH (5)
KOH (5)
KOH (5)
80
nd
NaOtBu (5)
NaOtBu (5)
NaOtBu (5)
NaOtBu (5)
NaOtBu (5)
NaOtBu (5)
NaOtBu (5)
NaOtBu (5)
NaOtBu (2.5)
80
90 : 10
97 : 3
96 : 4
>99 : 1
96 : 4
>99 : 1
>99 : 1
>99 : 1
>99 : 1
7
80
8
60
9
60
10
11
12
13
14
TMHD
–––
60
60
–––
60
–––
60
–––
60
a Reaction conditions: 1a (0.36 mmol), 2a (0.43 mmol), base, copper, and ligand in THF (0.5
mL) for 12 h under nitrogen. b The yields were determined by HPLC analysis of the crude
materials. c The ratios were determined by HPLC analysis of the crude materials. d Dioxane
was used as the solvent.

ACCEPTED MANUSCRIPT
Table 4. Copper-catalyzed Chemoselective Amination of 1a with 2a
entry
yieldb,c
84%
92%
46%
92%
95%
3 : 4d
2
1
97 : 3
>99 : 1
97 : 3
94 : 6
94 : 6
2b
2c
2g
2g
2h
2
3
4e
5
a Reaction conditions: 1a (0.36 mmol), 2 (0.43 mmol), NaOtBu (0.90 mmol), CuI (0.036 mmol),
and THF (0.5 mL) for 12 h at 60 ˚C under nitrogen. b The yields were determined by HPLC
c
analysis of the crude materials.
Yields of 3 and 4. d The ratios were determined by HPLC
analysis of the crude materials. e The reaction was conducted at 100 ˚C.
The optimized copper catalyst condition also effectively worked for the reaction of
1a with other diarylamines. For example, the reactions with 2b or 2c provided the intended
products 4ab and 4ac in good yields with high chemoselctivities (Table 4, entries 1 and 2).
The reaction of 1a with 2g resulted in a low yield (46%), but elevated reaction temperature
realized a high yield (92%) with a good chemoselectivity (94%) (entries 3 and 4). The
reaction of 1a with 2h also smoothly proceeded at 60 ˚C and provided the desired product 4ah
in 95% yield with a 94% chemoselectivity (entry 5).
We further demonstrated the synthesis of the unsymmetrical bistriarylamine through
the monobrominated triarylamines, which was obtained by the chemoselective amination
reaction (eq 1). As listed in Table 3, the monobrominated triarylamine 3aa, which was
prepared by the reaction of ligand-free copper catalyzed chemoselective amination of 1a with

ACCEPTED MANUSCRIPT
2a, and 3aa, was easily converted to the unsymmetrical bistriarylamine 5 under the standard
conditions of the Buchwald-Hartwig reaction.
3. Conclusions
In conclusion, we developed the chemoselective amination of bromoiodobenzenes
with diarylamines using the palladium/Xantphos or ligand-free copper catalyst. The reaction
proceeded with a high chemoselectivity and afforded the monobrominated triarylamines in good
yields. We further demonstrated the transformation of the monobrominated triarylamines to
unsymmetrical bistriarylamines by the Buchwald-Hartwig reaction.
4. Experimental section
4.1. General
All manipulations were carried out under a nitrogen atmosphere. NMR spectra were recorded
1
13
on a JEOL EX-270 spectrometer (270 MHz for H with C6D6, and 67 MHz for C with C6D6),
1
JEOL JNM LA-400 spectrometer (400 MHz for H with CDCl3, C6D6 or acetone-d6, and 100
MHz for 13C with CDCl3, C6D6 or acetone-d6), or JEOL JNM ECP-500 spectrometer (500 MHz
1
for H with C6D6 or acetone-d6, and 125 MHz for 13C with C6D6 or acetone-d6). Chemical
shifts are reported in δ ppm referenced to an internal SiMe4 standard, residual acetone (δ 2.09)
or residual benzene (δ 7.15) for 1H NMR, and residual chloroform (δ 77.4), residual acetone (δ
13
13
30.6) or residual benzene (δ 128.6) were used as internal reference for C NMR. 1H and C
1
NMR spectra were recorded at 25 ˚C. The chemoselectivity was determined by H NMR
spectra and/or HPLC analysis using Inertsil ODS-3V (CH3CN, flow: 1.0 mL/min, 254 nm).
All chemical including palladium salts, copper salts, phosphine ligands, dihalogenated arenes
and amines were purchased from commercial sources and used without further purification.

ACCEPTED MANUSCRIPT
4.2. General procedure for the palladium-catalyzed reaction
A solution of Pd(OAc)2 (0.8 mg, 0.0036 mmol), Xantphos (2.1 mg, 0.0036 mmol), NaOtBu (51
mg, 0.53 mmol), 1-bromo-4-iodobenzene (1a) (100 mg, 0.35 mmol), and N,N-diphenylamine
(2a) (72 mg, 0.43 mmol) in toluene (0.5 mL) was stirred at 100 ˚C for 12 h. The reaction was
quenched with H2O, and extracted with CH2Cl2 (3 x 3 mL). The chemoselectivity (3aa/4aa =
92/8) was measured by HPLC analysis using Inertsil ODS-3V. The pure monoaminated
product 3aa (99 mg, 86%) was obtained by flash chromatography (hexane/CH2Cl2 = 97/3) as a
white solid.
4.3. General procedure for the copper-catalyzed reaction
A solution of CuI (6.7 mg, 0.035 mmol), NaOtBu (85 mg, 0.88 mmol), 1-bromo-4-iodobenzene
(1a) (100 mg, 0.35 mmol), and N,N-diphenylamine (2a) (90 mg, 0.53 mmol) in THF (0.5 mL)
was stirred at 60 ˚C for 12 h. The reaction was quenched with H2O, and extracted with CH2Cl2
(3 x 4 mL). The chemoselectivity (3aa/4aa = >98/2) was measured by HPLC analysis using
Inertsil ODS-3V. The pure monoaminated product 3aa (113 mg, 98%) was obtained by flash
chromatography (hexane/CH2Cl2 = 97/3) as a white solid. The minor product (bisaminated
product) 4aa was also obtained by following flash chromatography (hexane/CH2Cl2/Et3N =
90/5/5) as a white solid with containing unknown impurities and triethylamine.
4.4. Characterization data of products
4.4.1. 4-Bromo-N,N-diphenylaniline (3aa).7a,15 White solid (99 mg, 86%). Mp 106–111 ˚C.
1H NMR (500 MHz, acetone-d6) δ 6.92–6.94 (m, 2H), 7.02–7.07 (m, 6H), 7.28–7.32 (m, 4H),
7.38–7.41 (m, 2H). 13C NMR (125 MHz, acetone-d6) δ 114.08, 123.48, 124.48, 124.80,
129.29, 129.50, 132.12, 147.33. HPLC analysis: tR = 5.78 min.
4.4.2. 4-Bromo-N,N-di-p-tolylaniline (3ab).7b White solid (108 mg, 87%). Mp 100–104 ˚C.
1H NMR (400 MHz, acetone-d6) δ 2.30 (s, 6H), 6.87 (d, J = 8.0 Hz, 2H), 6.97 (d, J = 8.0 Hz,
4H), 7.14 (d, J = 8.0 Hz, 4H), 7.36 (d, J = 8.0 Hz, 2H). 13C NMR (125 MHz, acetone-d6) δ
20.21, 113.14, 123.70, 125.01, 130.29, 132.11, 133.29, 145.10, 147.92. HPLC analysis: tR =
7.48 min.
4.4.3. N-(4-Bromophenyl)-3-methyl-N-(m-tolyl)aniline (3ac). White solid (118 mg, 95%).

ACCEPTED MANUSCRIPT
Mp 93–95 ˚C. 1H NMR (400 MHz, acetone-d6) δ 2.25 (s, 6H), 6.85 (d, J = 9.3 Hz, 2H),
6.88–6.93 (m, 6H), 7.19 (t, J = 8.28 Hz, 2H), 7.37-7.40 (m, 2H). 13C NMR (125 MHz,
acetone-d6) δ 23.10, 116.27, 124.40, 126.92, 127.15, 127.80, 131.90, 134.61, 141.82, 149.99,
150.13. IR (KBr) 593, 765, 829, 1185, 1474, 2934 cm–1. HRMS (ESI): m/z: calcd for
C20H19BrN+ (M+H+) 352.0701, found 352.0715. HPLC analysis: tR = 7.15 min.
4.4.4. N-(4-Bromophenyl)-N-phenylnaphthalen-1-amine (3ag).7a White solid (123 mg, 93%).
Mp 95–97 ˚C. 1H NMR (500 MHz, C6D6) δ 6.35 (d, J = 8.6 Hz, 2H), 6.48 (t, J = 6.8 Hz, 1H),
6.62–6.67 (m, 4H), 6.69–6.88 (m, 6H), 7.21 (t, J = 7.8 Hz, 1H), 7.33 (d, J = 8.2 Hz, 1H), 7.70 (d,
J = 8.3 Hz, 1H). 13C NMR (125 MHz, C6D6) δ 114.18, 122.62, 123.45, 124.48, 125.83, 126.52,
126.60, 126.82, 127.32, 128.30, 128.77, 129.55, 131.43, 132.37, 135.78, 143.64, 147.93, 148.40.
HPLC analysis: tR = 6.15 min.
4.4.5. 3-Bromo-N,N-diphenylaniline (3ba).7c White solid (107 mg, 93%). Mp 91–96 ˚C.
1H NMR (400 MHz, CDCl3) δ 6.95–7.09 (m, 8H), 7.19–7.29 (m, 6H). 13C NMR (100 MHz,
CDCl3) δ 121.5, 122.7, 123.5, 124.7, 124.9, 125.7, 129.4, 130.3, 147.1, 149.3. IR (KBr) 2956
cm–1. HPLC analysis: tR = 5.48 min.
4.4.6. 3-Bromo-N,N-di-p-tolylaniline (3bb). White solid (118 mg, 95%). Mp 97–101 ˚C.
1H NMR (400 MHz, acetone-d6) δ 3.04 (s, 6H), 7.62–7.64 (m, 1H), 7.72–7.78 (m, 6H),
7.86–7.90 (m, 5H). 13C NMR (100 MHz, acetone-d6) δ 20.8, 120.4, 122.9, 124.0, 124.1, 125.9,
130.8, 131.2, 134.2, 145.2, 150.7. IR (KBr) 988, 1068, 1324, 1475, 2956 cm–1. HRMS
(ESI): m/z: calcd for C20H19BrN+ (M+H+) 352.0701, found 352.0691. HPLC analysis: tR =
6.88 min.
4.4.7. 3-Bromo-N,N-di-m-tolylaniline (3bc). Pale yellow solid (102 mg, 82%). Mp 95–99
˚C. 1H NMR (400 MHz, acetone-d6) δ 3.03 (s, 6H), 7.60–7.67 (m, 7H), 7.80–7.96 (m, 5H).
13C NMR (100 MHz, acetone-d6) δ 21.2, 79.0, 121.6, 124.9, 125.2, 125.4, 126.1, 126.3, 130.0,
131.4, 140.0, 147.8, 150.6. IR (KBr) 775, 1318, 1472, 1581, 2920 cm–1. HRMS (ESI): m/z:
calcd for C20H19BrN+ (M+H+) 352.0701, found 352.0692. HPLC analysis: tR = 6.57 mi.
4.4.8. 3-Bromo-N,N-bis(4-methoxyphenyl)aniline (3bd).6e Brown solid (97 mg, 71%). Mp
82–86 ˚C. 1H NMR (400 MHz, acetone-d6) δ 3.78 (s, 6H), 6.89–6.93 (m, 6H), 7.03–7.09 (m,

ACCEPTED MANUSCRIPT
6H). 13C NMR (100 MHz, acetone-d6) δ 55.7, 115.5, 116.0, 118.2, 121.8, 122.9, 128.2, 131.3,
140.6, 151.5, 157.7. IR (KBr) 1474, 2840, 2933 cm–1. HRMS (ESI): m/z: calcd for
C20H19BrNO2 (M+H+) 384.0599, found 384.0591. HPLC analysis: tR = 4.77 min.
4.4.9. 3-Bromo-N-phenyl-N-(p-tolyl)aniline (3be). Semi-solid (102 mg, 85%). 1H NMR
(500 MHz, acetone-d6) δ 3.68 (s, 3H), 8.30–8.67 (m, 13H). 13C NMR (125 MHz, acetone-d6) δ
20.6, 121.1, 122.9, 124.2, 124.7, 124.8, 125.2, 126.2, 130.1, 130.9, 131.3, 134.5, 145.1, 147.8,
150.5. IR (KBr) 695, 1068, 1278, 1474, 1583, 2955 cm–1. HRMS (ESI): m/z: calcd for
C19H17BrN+ (M+H+) 338.0544, found 338.0538. HPLC analysis: tR = 6.14 min.
4.4.10. 3-Bromo-N-phenyl-N-(m-tolyl)aniline (3bf). Black oil (94 mg, 79%). 1H NMR
(500 MHz, acetone-d6) δ 2.22–2.26 (m 3H), 6.73–6.74 (m, 1H), 6.74–6.91 (m, 1H), 7.10–7.15
(m, 5H), 7.21–7.30 (m, 6H). 13C NMR (125 MHz, acetone-d6) δ 21.6, 116.1, 118.6, 118.7,
118.8, 119.2, 119.3, 119.4, 122.8, 123.8, 129.8, 129.9, 139.4, 139.5, 144.3, 144.4, 144.5. IR
(KBr) 690, 1299, 1493, 1584, 2915 cm–1. HRMS (ESI): m/z: calcd for C19H17BrN+ (M+H+)
338.0544, found 338.0534. HPLC analysis: tR = 5.99 min.
4.4.11. N-(3-Bromophenyl)-N-phenylnaphthalen-1-amine (3bg).16 Reddish brown oil (128
mg, 97%). 1H NMR (400 MHz, acetone-d6) δ 6.87–6.89 (m, 1H), 7.01–7.17 (m, 6H),
7.28–7.32 (m, 2H), 7.40–7.52 (m, 2H), 7.92–8.03 (m, 3H), 7.53–7.61 (m, 2H). 13C NMR (125
MHz, acetone-d6) δ 122.0, 122.5, 123.2, 124.8, 125.1, 125.2, 125.8, 126.0, 126.1, 126.4, 127.3,
127.8, 128.4, 130.1, 130.4, 131.4, 131.7, 145.5, 147.9, 150.4. IR (KBr) 1473, 3060 cm–1.
HRMS (ESI): m/z: calcd for C22H17BrN+ (M+H+) 374.0544, found 374.0535. HPLC analysis:
tR = 6.34 min.
4.4.12. N-(3-Bromophenyl)-N-phenylnaphthalen-2-amine (3bh). Reddish brown oil (112 mg,
85%). 1H NMR (400 MHz, acetone-d6) δ 6.70–7.32 (m, 12H), 7.52–7.51 (m, 1H), 7.66–7.69
(m, 2H), 7.84 (s, 1H). 13C NMR (125 MHz, acetone-d6) δ 119.8, 123.2, 123.4, 123.8, 124.0,
124.4, 127.2, 127.3, 127.5, 128.0, 128.3, 129.4, 130.1, 130.5, 131.5, 131.9, 136.2, 143.4, 148.2,
151.0. IR (KBr) 774, 1392, 1473, 1583, 3060 cm–1. HRMS (ESI): m/z: calcd for C22H17BrN+
(M+H+) 374.0544, found 374.0537. HPLC analysis: tR = 5.72 min.
4.4.13. 2-Bromo-N,N-diphenylaniline (3ca). Yellow oil (86 mg, 75%). 1H NMR (400 MHz,

ACCEPTED MANUSCRIPT
C6D6) δ 6.59–6.62 (m, 1H), 6.80–6.84 (m, 4H), 6.97–7.06 (m, 4H), 7.19–7.27 (m, 1H),
7.29–7.30 (m, 1H), 7.39–7.41 (m, 2H), 8.07–8.09 (m, 1H). 13C NMR (100 MHz, C6D6) δ
123.2, 128.0, 128.2, 129.4, 130.3, 130.4, 132.7, 135.6, 147.0, 148.4. IR (KBr) 697, 1277,
1472, 1580, 3451 cm–1. HRMS (ESI): m/z: calcd for C18H15BrN+ (M+H+) 324.0388, found
324.0407. HPLC analysis: tR = 4.68 min.
4.4.14. N1,N1,N4,N4-Tetraphenylbenzene-1,4-diamine (4aa).17 White solid. Mp 200–204 ˚C.
The product contains inseparable impurities and triethylamine after silicagel column
chromatography and/or recrystallization. 1H NMR (400 MHz, C6D6) δ 6.42 (t, J = 7.2 Hz, 4H),
6.63 (t, J = 7.2 Hz, 8H), 6.70–6.75 (m, 12H). 13C NMR (125 MHz, C6D6) δ 121.21, 122.68,
124.29, 128.00, 141.86, 146.85. HPLC analysis: tR = 7.48 min.
4.4.15. N1,N4-Di(naphthalen-2-yl)-N1,N4-diphenylbenzene-1,4-diamine (4ab).18 White solid.
Mp 196–200 ˚C. The product contains inseparable impurities and triethylamine after silicagel
column chromatography and/or recrystallization. 1H NMR (270 MHz, C6D6) δ 6.89 (t, J = 6.8
Hz, 5H), 7.04-7.20 (m, 11H), 7. 33(dd, J = 8.9, 1.6 Hz, 4H), 7.48-7.57 (m, 8H). 13C NMR
(125 MHz, C6D6): δ 120,7 123.1, 124.5, 124.7, 124.8, 126.5, 127.3, 129.4, 129.7, 130.6 135.1
143.5 145.9, 148.4. HPLC analysis: tR = 11.50 min.
4.4.16. N1,N1,N4,N4-Tetra-p-tolylbenzene-1,4-diamine (4ah).19 White solid. Mp 209–214 ˚C.
The product contains inseparable impurities and triethylamine after silicagel column
chromatography and/or recrystallization. 1H NMR (270 MHz, C6D6) δ 2.09 (s, 12H), 6.88 (d,
J = 8.4 Hz, 8H), 7.08 (d, J = 8.4 Hz, 8H), 7.13 (s, 4H). 13C NMR (67 MHz, C6D6): δ 20.8,
123.5, 124.9, 130.2, 132.3, 146.1, 148.9. HPLC analysis: tR = 7.88 min.
4.4.17. N1,N4-Di(naphthalen-1-yl)-N1,N4-diphenylbenzene-1,4-diamine (4ag).18 Pale yellow
solid. Mp 197–205 ˚C. The product contains inseparable impurities and triethylamine after
silicagel column chromatography and/or recrystallization. 1H NMR (500 MHz, C6D6) δ 6.29
(d, J = 8.70 Hz 4H), 6.35 (t, J = 7.35 Hz 2H), 6.49–6.57 (m, 2H), 6.62 (t, J = 7.80 Hz, 4H),
6.68–6.74 (m, 8H), 6.80 (t, J = 6.90 Hz 2H), 6.95 (d, J = 6.85 Hz, 2H), 7.20 (d, J = 8.25 Hz,
2H), 7.32 (d, J = 8.25 Hz, 2H). 13C NMR (125 MHz, C6D6) δ 116.62, 117.65, 120.60, 121.19,

ACCEPTED MANUSCRIPT
122.61, 123.35, 125.63, 125.70, 128.19, 128.29, 128.50, 128.73, 129.52, 135.26, 139.38, 145.37.
HPLC analysis: tR = 9.10 min.
4.4.18. N1-(naphthalen-2-yl)-N1,N4,N4-triphenylbenzene-1,4-diamine (5).19 Semi-solid (117
mg, 73%). 1H NMR (400 MHz CDCl3) δ 6.78 (t, J = 7.6 Hz, 4H), 6.89–6.90 (m, 4H),
7.02–7.15 (m, 4H), 7.26 (t, J = 8.0 Hz, 2H), 7.35 (t, J = 8.0 Hz, 4H), 7.65 (d, J = 8.0 Hz, 2H),
7.77 (d, J = 8.0 Hz, 2H), 7.87 (d, J = 8.0 Hz, 2H). 13C NMR (125 MHz, CDCl3) δ 120.88,
121.01, 122.20, 123.41, 123.51, 124.30, 125.63, 126.09, 126.29, 126.33, 126.36, 127.09, 128.38,
129.00, 129.10, 129.32, 131.25, 135.28, 141.98, 143.52, 143.75, 147.90, 148.61.
Supplementary data
Supplementary data related to this article can be found at http:// dx.doi.org/10.1016/
References
1. (a) Yang, B. H.; Buchwald, S. L. J. Organomet. Chem. 1999, 576, 125–146. (b) Hartwig,
J. F. Synlett 2006, 1283–1294. (c) Hartwig, J. F. Acc. Chem. Res. 2008, 41, 1534–1544.
(d) Surry, D. S.; Buchwald, S. L. Angew. Chem. Int. Ed. 2008, 47, 6338–6361.
2. (a) Shirota, Y.; Kageyama, H. Chem. Rev. 2007, 107, 953–1010. (b) Ning, Z.; Chen, Z.;
Zhang, Q.; Yan, Y.; Qian, S.; Cao, Y.; Tian, H. Adv. Funct. Mater. 2007, 17, 3799–3807.
(c) Ning, Z.; Tian, H. Chem. Commun. 2009, 5483–5495.
3
(a) Hartwig, J. F.; Kawatsura, M.; Hauck, S. I.; Shaughenessy, K. H.; Alcazar-Roman, L. M.
J. Org. Chem. 1999, 64, 5575–5580. (b) Chae, H. K.; Eddaoudi, M.; Kim, J.; Hauck, S. I.;
Hartwig, J. F.; O’Keeffe, M.; Yaghi, O. M. J. Am. Chem. Soc. 2001, 123, 11482–11483.
(c) Kataoka, N.; Shelby, Q.; Stambuli, J. P.; Hartwig, J. F. J. Org. Chem. 2002, 67,
5553–5566. (d) Kuwano, R.; Utsunomiya, M.; Hartwig, J. F. J. Org. Chem. 2002, 67,
6479–6486. (e) Urgaonkar, S.; Xu, J.-H.; Verkade, J. G. J. Org. Chem. 2003, 68,
8416–8423. (f) Urgaokar, S.; Verkade, J. G. J. Org. Chem. 2004, 69, 9135–9142. (g)
Reddy, C. V.; Kingston, J. V.; Verkade, J. G. J. Org. Chem. 2008, 73, 3047–3062. (h)
Kuwano, R.; Matsumoto, Y.; Shige, T.; Tanaka, T.; Soga, S.; Hanasaki, Y. Synlett 2010,
1819–1824. (i) Hirai, Y.; Uozumi, Y. Chem. Commun. 2010, 46, 1103–1105. (j) Dogan,
Ö.; Demir, S.; Özdemir, I.; Cetinkaya, B. Appl. Organometal. Chem. 2011, 25, 163–167.
(k) Kamino, B. A.; Mills, B.; Reali, C.; Gretton, M. J.; Brook, M. A.; Bender, T. P. J. Org.
Chem. 2012, 77, 1663–1674. (l) Guo, S.; Wang, Y.; Sun, C.; Li, J.; Zou, D.; Wu, Y.; Wu, Y.

ACCEPTED MANUSCRIPT
Tetrahedron Lett. 2013, 54, 3233–3237. (m) Riedmüller, S.; Kaufhold, O.; Spreitzer, H.;
Nachtsheim, B. J. Eur. J. Org. Chem. 2014, 1391–1394.
4
5
(a) Hassan, J.; Sévignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem. Rev. 2002, 102,
1359–1469. (b) Ma, D.; Cai, Q. Acc. Chem. Res. 2008, 41, 1450–1460. (c) Lefèvre, G.;
Franc, G.; Tlili, A.; Adamo, C.; Taillefer, M.; Ciofini, I.; Jutand, A. Organometallics 2012,
31, 7694–7707.
(a) Gujadhur, R.; Venkataraman, D.; Kintigh, J. T. Tetrahedron Lett. 2001, 42, 4791–4793.
(b) Gajare, A. S.; Toyota, K.; Yoshifuji, M.; Ozawa, F. Chem. Commun. 2004, 1994–1995.
(c) Rao, H.; Fu, H.; Jiang, Y.; Zhao, Y. J. Org. Chem. 2005, 70, 8107–8109. (d) Zhu, D.;
Wang, R.; Mao, J.; Xu, L.; Wu, F.; Wan, B. J. Mol. Catal. A: Chemical 2006, 256, 256–260.
(e) Lam, M. S.; Lee, H. W.; Chan, A. S. C.; Kwong, F. Y. Tetrahedron Lett. 2008, 49,
6192–6194. (f) Liu, Z.-J.; Vors, J.-P.; Gesing, E. R. F.; Bolm, C. Adv. Synth. Catal. 2010,
352, 3158–3162. (g) Bahlaouan, Z.; Thibonnet, J.; Duchêne, A.; Parrain, J.-L.; Elhilali,
M.; Abarbri, M. Synlett 2011, 2509–2512.
6
(a) Gujadhur, R. K.; Bates, C. G.; Venkataraman, D. Org. Lett. 2001, 3, 4315–4317. (b)
Kelkar, A. A.; Patil, N. M.; Chaudhari, R. V. Tetrahedron Lett. 2002, 43, 7143–7146. (c)
Patil, N. M.; Kelkar, A. A.; Chaudhari, R. V. J. Mol. Catal. A: Chemical 2004, 223, 45–50.
(d) Tlili, A.; Monnier, F.; Taillefer, M. Chem. Commun. 2012, 48, 6408–6410. (e) Polit,
W.; Mücke, P.; Wuttke, E.; Exner, T.; Winter, R. F. Organometallics 2013, 32, 5461–5472.
(f) Safaei-Ghomi, J.; Akbarzadeh, Z.; Ziarati, A. RSC Adv. 2014, 4, 16385–16390.
(a) Chang, Y. J.; Chow, T. J. Tetrahedron 2009, 65, 4726–4734. (b) Chang, Y. J.; Chow, T.
J. Tetrahedron 2009, 65, 9626–9632. (c) Lin, Y.-D.; Chien, C.-T.; Lin, S.-Y.; Chang,
H.-H.; Liu, C.-Y.; Chow, T. J. J. Photochem. Photobiol. A: Chem. 2011, 222, 192–202.
Yan, X. Z.; Pawlas, J.; Goodson, T., III; Hartwig, J. F. J. Am. Chem. Soc. 2005, 127,
9105–9116.
7
8
9
(a) McIlroy, S. P.; Cló, E.; Nikolajsen, L.; Frederiksen, P. K.; Nielsen, C. B.; Mikkelsen, K.
V.; Gothelf, K. V.; Ogilby, P. R. J. Org. Chem. 2005, 70, 1134–1146. (b) Seok, J. H.; Park,
S. H.; El-Khouly, M. E.; Araki, Y.; Ito, O.; Kay, K.-Y. J. Organomet. Chem. 2009, 694,
1818–1825. (c) Mom, S.; Platon, M.; Cattey, H.; Spencer, H. J.; Low, P.; Hierso, J.-C.
Catal. Commun. 2014, 51, 10–14.
10 (a) Ji, J.; Li, T.; Bunnelle, W. H. Org. Lett. 2003, 5, 4611–4614. (b) Stroup, B. W.;
Szklennik, P. V.; Forster, C. J.; Serrano-Wu, M. H. Org. Lett. 2007, 9, 2039–2042. (c)
Monguchi, Y.; Kitamoto, K.; Ikawa, T.; Maegawa, T.; Sajiki, H. Adv. Synth. Catal. 2008,

ACCEPTED MANUSCRIPT
350, 2767–2777. (d) Larsen, S. B.; Bang-Andersen, B.; Johansen, T. N.; Jørgensen, M.
Tetrahedron 2008, 64, 2938–2950. (e) Smith, J. A.; Jones, R. K.; Booker, G. W.; Pyke, S.
M. J. Org. Chem. 2008, 73, 8880–8892.
11 Reaction with excess of Ph2NH (2.5 equiv.) gave the decreased chemoselectivity (94%)
without losing the yield (87%).
12 (a) Goodbrand, H. B.; Hu, N.-X. J. Org. Chem. 1999, 64, 670–674. (b) Anémian, R.;
Cupertino, D. C.; Mackie, P. R.; Yeates, S. G. Tetrahedron Lett. 2005, 46, 6717–6721. (c)
Li, Z. H.; Wong, M. S. Org. Lett. 2006, 8, 1499–1502. (d) Wang, Z.; Fu, H.; Jiang, Y.;
Zhao, Y. Synlett 2008, 2540–2546. (e) Yong, F.-F.; Teo, Y.-C. Synlett 2010, 3068–3072.
13 We also examined the reaction with other bases, such as NaOH, KOtBu, NaOEt, Cs2CO3, or
K3PO4, at 60 ˚C, but all reactions resulted in no reaction or low yield (<10%).
14 We used 99.999% purity of CuI purchased from Aldrich, and also confirmed that the other
CuI (98% purity) provided same results.
15 Xiao, H.; Shen, H.; Lin, Y.; Su, J.; Tian, H. Dye Pigments 2007, 73, 224–229.
16 Chen, H.-Y.; Chen, C.-T.; Chen, C.-T. Macromolecules 2010, 43, 3613–3623.
17 Chen, C.; Yang, L.-M. Org. Lett. 2005, 7, 2209–2211.
18 Koene, B. E.; Loy, D. E.; Thompson, M. E. Chem. Mater. 1998, 10, 2235–2250.
19 Plater, M. J.; Jackson, T. J. Chem. Soc., Perkin Trans. 1 2001, 2548–2552.

ACCEPTED MANUSCRIPT
SUPPORTING INFORMATION
Chemoselective Amination of Bromoiodobenzenes with
Diarylamines by Palladium/Xantphos or Ligand-free Copper
Catalysts
Yoshinori Kanazawa,† Tomo Yokota,† Hiroshi Ogasa,† Hirotaka Watanabe,‡ Taisyun
Hanakawa,‡ Shinichi Soga,§ Motoi Kawatsura*,‡
†Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori
University, Koyama, Tottori 680-8552, Japan
‡Department of Chemistry, College of Humanities & Sciences, Nihon University, Sakurajosui,
Setagaya-ku, Tokyo 156-8550, Japan
§Tosoh Organic Chemical Co., Ltd., 4988 Kaisei-cho, Shunan, Yamaguchi 746-0006, Japan
E-mail: kawatsur@chs.nihon-u.ac.jp
• 1H and 13C NMR spectra of all compounds
• IR chart for new compounds

ACCEPTED MANUSCRIPT
3aa (1H NMR)
3aa (13C NMR)

ACCEPTED MANUSCRIPT
3ab (1H NMR)
3ab (13C NMR)

ACCEPTED MANUSCRIPT
3ac (1H NMR)
3ac (13C NMR)

ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
3ag (1H NMR)
3ag (13C NMR)

ACCEPTED MANUSCRIPT
3ba (1H NMR)
3ba (13C NMR)

ACCEPTED MANUSCRIPT
3bb (1H NMR)
3bb (13C NMR)

ACCEPTED MANUSCRIPT
3bc (1H NMR)