N-heterocyclic carbene-Pd(II)-2-methyl-4,5-dihydrooxazole complex-catalyzed highly chemoselective mono-amination of dichlorobenzenes

Article abstract of DOI:10.1016/j.tet.2020.130944

The palladium-catalyzed chemoselective mono-amination of dichlorobenzenes was reported in this paper. Under the suitable conditions, all reactions involving the three isomers of dichlorobenzenes with various secondary and primary amines in the presence of

Full text of DOI:10.1016/j.tet.2020.130944

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N-heterocyclic carbene-Pd(II)-2-methyl-4,5-dihydrooxazole complex-catalyzed highly
chemoselective mono-amination of dichlorobenzenes
Kai-Xin Sun, Jin-Hui Zhou, Qian-Wei He, Li-Xiong Shao, Jian-Mei Lu
PII:
S0040-4020(20)30034-X
https://doi.org/10.1016/j.tet.2020.130944
TET 130944
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 7 December 2019
Revised Date: 3 January 2020
Accepted Date: 7 January 2020
Please cite this article as: Sun K-X, Zhou J-H, He Q-W, Shao L-X, Lu J-M, N-heterocyclic carbene-
Pd(II)-2-methyl-4,5-dihydrooxazole complex-catalyzed highly chemoselective mono-amination of
dichlorobenzenes, Tetrahedron (2020), doi: https://doi.org/10.1016/j.tet.2020.130944.
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Graphic Abstract
N-Heterocyclic carbene-Pd(II)-2-methyl-4,5-dihydrooxazole
complex-catalyzed highly chemoselective mono-amination of
dichlorobenzenes
Kai-Xin Sun, Jin-Hui Zhou, Qian-Wei He, Li-Xiong Shao and Jian-Mei Lu*

Graphical Abstract
N-Heterocyclic carbene-Pd(II)-2-methyl-4,5-
dihydrooxazole complex-catalyzed highly
chemoselective mono-amination of
dichlorobenzenes
Leave this area blank for abstract info.
Kai-Xin Sun, Jin-Hui Zhou, Qian-Wei He, Li-Xiong Shao and Jian-Mei Lu
College of Chemistry and Materials Engineering, Wenzhou University, Chashan University Town, Wenzhou,
Zhejiang Province 325035, People’s Republic of China.
*

1
Tetrahedron
journal homepage: www.elsevier.com
N-Heterocyclic carbene-Pd(II)-2-methyl-4,5-dihydrooxazole complex-catalyzed
highly chemoselective mono-amination of dichlorobenzenes
Kai-Xin Sun, Jin-Hui Zhou, Qian-Wei He, Li-Xiong Shao and Jian-Mei Lu
College of Chemistry and Materials Engineering, Wenzhou University, Chashan University Town, Wenzhou, Zhejiang Province 325035, People’s Republic of
China.
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
The palladium-catalyzed chemoselective mono-amination of dichlorobenzenes was reported in
this paper. Under the suitable conditions, all reactions involving the three isomers of
dichlorobenzenes with various secondary and primary amines in the presence of a well-defined
N-heterocyclic carbene-palladium(II)-2-methyl-4,5-dihydrooxazole complex, gave the desired
mono-aminated products in moderate to high yields as the major or sole one.
Available online
2009 Elsevier Ltd. All rights reserved
.
keywords:
N-heterocyclic carbene-palladium complex
amines
dichlorobenzenes
chemoselective C-N coupling
synthetic method
1. Introduction
During the past decades, as air-, moisture and thermal-stable
ligands, N-heterocyclic carbenes (NHCs) and their palladium
complexes have been used as efficient catalysts in the cross-
coupling reactions, especially for the challenging substrates such
as aryl chlorides.1 However, almost no attention was paid on the
NHC-Pd(II) complexes-catalyzed chemoselective mono-coupling
of polychlorinated arenes, though the corresponding products are
very useful intermediates in organic synthesis.2,3 Recently, we
have developed a novel N-heterocyclic carbene-palladium(II)-2-
methyl-4,5-dihydrooxazole complex 1, which showed efficient
catalytic activity in the highly chemoselective mono-Suzuki-
Miyaura coupling of dichlorobenzenes under mild conditions
(Scheme 1).4 In addition, although various NHC-Pd(II)
complexes have been developed for the C-N coupling of aryl
chlorides, very few examples on their use on the chemoselective
mono-C-N coupling of dichlorobenzenes was reported to date.5
Therefore, encouraged by the successful results of NHC-Pd(II)
complex 1-catalyzed mono-Suzuki-Miyaura coupling of
dichlorobenzenes under mild reaction conditions, we then turned
our interest to the mono-C-N coupling of dichlorobenezenes in
the presence of such NHC-Pd(II) complex to expand its
application in organic synthesis. Herein, we report these results
in detail.
2. Results and discussion
At the outset of this investigation, selecting KOtBu (1.3 equiv)
as the base, the reaction of 1,3-dichlorobenzene 2a (0.7 mmol)
with morpholine 3a (0.7 mmol) (2a:3a = 1:1) was carried out in
the presence of NHC-Pd(II) complex 1 (1.0 mol%) in toluene
o
(1.0 mL) at 70 C for 12 h. It was found that the desired mono-
aminated product 4a can be obtained in 71% yield, along with the
di-aminated product 5a in 28% yield (Table 1, entry 1). The ratio
of substrates 2a to 3a had some effect on the reactions. For
instance, when the amount of 3a increased to 1.4 mmol (2a:3a =
1:2), the yield of 4a almost kept untouched, while that of 5a
———
Corresponding author. Tel.: +86-577-86689300; fax: +86-577-86689300; e-mail: ljm@wzu.edu.cn

2
Tetrahedron
decreased from 28 to 23% (Table 1, entries 1 vs 2). When the
amount of 3a was adjusted to 2.1 mmol (2a:3a = 1:3), the mono-
selectivity was further improved (Table 1, entry 3). When 2a (1.4
mmol) and 3a (0.7 mmol) (2a:3a = 2:1) was tested, similar yields
were obtained (Table 1, entries 3 vs 4). Once the ratio of 2a to 3a
was changed to be 3:1, the best mono-selectivity was achieved,
giving product 4a in 84% yield and 5a in 12% yield, respectively
(Table 1, entry 5).
12
13
14
15
16
toluene
DMF
dioxane
THF
CH3COOK
KOtBu
No Reaction
47
17
20
22
9
KOtBu
73
76
32
KOtBu
DMAc
KOtBu
a
All reactions were carried out using 2a (2.1 mmol), 3a (0.7
mmol), base (1.3 equiv), 1 (1.0 mol%) in solvent (1.0 mL) at 70
oC for 12 h. b Isolated yields.
Once the optimal condition in hand (Table 2, entry 1), the
reactions between three isomers of dichlorobenzenes 2 and kinds
of secondary amines 3 were then investigated to show the scope
and limitation of such transformation. The results are illustrated
in Table 3. All reactions performed well to give the desired
mono-aminated products 4 in moderate to high yields as the
major one. In addition, to our pleasure, in most cases, products 4
were achieved as the sole one, implying the high
chemoselectivity of such transformation under the optimal
conditions. For example, the reactions of 1,3-dichlorobenzene 2a
with N-methylaniline 3b, piperidine 3c, N,2-dimethylaniline 3g,
N,3-dimethylaniline 3h, N,4-dimethylaniline 3i, and the reactions
of 1,4-dichlorobenzene 2c with morpholine 3a and N-
methylaniline 3b, gave the mono-aminated products 4 as the
major one, along with the corresponding di-aminated products 5
in minor yields (Table 3, entries 1, 2, 6-8, 13 and 14). For all
other reactions examined, the mono-aminated products 4 were
observed as the sole one. Steric-hindrance affected the reactions
to some extent. For example, somewhat lower yields for both
products were found for the reaction of 1,3-dichlorobenzene 2a
with N,2-dimethylaniline 3g (Table 3, entry 6). Relatively lower
yields were observed for the reactions involving 1,2-
dichlorobenzene 2b (Table 3, entries 10-12).
Entrya
2a (mmol) 3a (mmol)
Yield (%)b
5a
4a
71
72
78
77
84
1
2
3
4
5
0.7
0.7
0.7
1.4
2.1
0.7
1.4
2.1
0.7
0.7
28
23
20
19
12
a All reactions were carried out using KOtBu (1.3 equiv) and 1
(1.0 mol%) in toluene (1.0 mL) at 70 oC for 12 h. b Isolated
yields.
Based on the above results, a variety of bases were then tested
under identical reaction conditions (Table 2, entries 1-12).
Compared to KOtBu, for other bases screened, all of them gave
inferior results. For example, in the presence of NaOtBu, the
desired product 4a was observed in 25% yield (Table 2, entry 2),
while in the presence of other bases such as LiOtBu, KOH,
NaOH, K2CO3, Na2CO3, KHCO3, Cs2CO3, NaHCO3, K3PO4 and
CH3COOK, nearly no reaction took place (Table 2, entries 3-12).
Finally, using KOtBu as the base, some common solvents were
examined (Table 2, entries 13-16). For example, when dioxane
and THF were used, good total yields were obtained in both cases
(Table 2, entries 14 and 15), with product 4a in moderate yields,
respectively. However, both are still inferior than that obtained in
toluene. In other solvents such as DMF and DMAc, very low
yields were given (Table 2, entries 13 and 16).
Table 3
1
2
NHC-Pd(II) complex -catalyzed C-N coupling of dichlorobenzenes
3
.
with secondary amines
CI
1
NHC-Pd(II)
R1
H
(1.0 mol%)
KOtBu, toluene
12 h
R1
N
+
+
R2
N
N
R2
R1
Cl
N
R1
R2
3
5
R2
4
CI
2a
2b
2c
(3-Cl)
(2-Cl)
(4-Cl)
Entrya
2
3
Temp
(oC)
Yield (%)b
4
5
1
2a
70
4b, 80
5b, 15
3b
2
3
2a
2a
110
90
4c, 63
4d, 72
5c, 17
Entrya
Solvent
Base
Yield (%)b
4a
5a
3c
1
2
3
4
5
6
7
8
9
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
KOtBu
NaOtBu
LiOtBu
KOH
84
12
---
25
trace
trace
trace
trace
trace
trace
trace
3d
NaOH
4
5
2a
2a
110
70
4e, 68
4f, 83
---
---
K2CO3
Na2CO3
KHCO3
Cs2CO3
NaHCO3
K3PO4
No Reaction
3e
No Reaction
No Reaction
No Reaction
No Reaction
No Reaction
3f
10
11

3
6
2a
70
4g, 51
<5
3g
7
8
2a
2a
70
70
4h, 65
4i, 78
5d, 12
5e, 10
3h
3i
3j
Entrya
1
2
3
4
5
6
7
2
6 (R)
6a (2-Me)
6b (3-Me)
6c (4-Me)
6d (2,4-Me2)
6e (2,6-Me2)
6f (2-OMe)
6g (2,4,6-Me3)
6h (3-F)
Temp (oC)
130
130
130
130
130
110
130
110
110
110
130
130
130
130
110
130
110
110
110
Yield (%)b
7a, 86
7b, 60
7c, 76
7d, 63
7e, 75
7f, 61
7g, 85
7h, 64
7i, 71
7j, 82
7k, 73
7l, 73
7m, 79
7n, 89
7o, 70
7p, 80
7q, 71
7r, 74
7s, 60
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
9
2a
2b
70
70
4j, 88
4k, 49
---
---
10
3a
8
9
6i (2-F)
6j (4-F)
11
12
13
14
15
16
17
18
19
20
21
22
2b
2b
2c
2c
2c
2c
2c
2c
2c
2c
2c
2c
3b
3j
110
70
4l, 69
4m, 66
4n, 92
4o, 85
4p, 77
4q, 82
4r, 69
4s, 94
4t, 77
4u, 70
4v, 73
4w, 90
---
---
<5
<5
---
---
---
---
---
---
---
---
10
11
12
13
14
15
16
17
18
19
2b 6a
2b 6c
2b 6d
2b 6e
2b 6f
2b 6g
2b 6j
3a
3b
3c
3d
3e
3f
70
70
110
90
2c
2c
6a
6b
110
70
a All reactions were carried out using 2 (0.7 mmol), 6 (2.1 mmol),
KOtBu (1.5 equiv), 1 (1.0 mol%) in toluene (1.0 mL) for 12 h.
b Isolated yields.
3g
3h
3i
70
70
70
3. Conclusion
3j
70
In conclusion, the palladium-catalyzed chemoselective
amination between dichlorobenzenes and various secondary and
primary amines was achieved in this paper. Using a well-defined
NHC-Pd(II)-2-methyl-4,5-dihydrooxazole complex as the
catalyst, all reactions took place well to give the desired highly
chemoselective mono-aminated products as the major or sole one.
a All reactions were carried out using 2 (2.1 mmol), 3 (0.7 mmol),
1 (1.0 mol%), KOtBu (1.3 equiv) in toluene (1.0 mL) for 12 h.
b Isolated yields.
Subsequently, the chemoselective mono-amination between
dichlorobenzenes 2 and various primary amines 6 was also
investigated under the optimal conditions. The results are shown
in Table 4. Compared to the reactions of dichlorobenzenes 2 with
4. Experimental section
o
secondary amines 3, which can be performed at 70 C in most
4.1 General remarks
cases, higher reaction temperature is necessary to give good
yields for the corresponding reactions of primary amines. In
addition, excessive primary amines 6 are good for these reactions.
At the ratio of dichlorobenzenes 2 to primary amines 6 to be 1:3
at the elevated temperatures, all reactions took place smoothly to
give the desired mono-aminated products 7 in moderate to high
yields. Substituents on the anilines 6 have some effect on the
reactions. For instance, for anilines 6 bearing sterically hindered
NMR spectra were recorded at 500 MHz (for 1H NMR) or 125
MHz (for 13C NMR), respectively. H and 13C NMR spectra
1
recorded in CDCl3 solutions were referenced to TMS (0.00 ppm)
and the residual solvent peak (77.0 ppm), respectively. J-values
are given in Hz. All solvents were dried by standard methods.
The mass analyzer type for the high resolution mass spectra
(HRMS) is quadrupole or DART. All amines were distilled prior
to using. Other commercially obtained reagents were used
without further purification. Flash column chromatography was
performed on silica gel (300-400 mesh).
o
substituents, higher temperature (130 C) is necessary to achieve
satisfactory yields in some cases (Table 2, entries 1, 4, 5, 7, 11,
13, 14 and 16). In some cases, steric-hindered substituents on the
anilines 6 are beneficial to better yields for the mono-amination
(Table 4, entries 1, 5, 7, 14 and 16). It should be noted here that
for some reactions tested in this Table, some other minor
products can be detected by TLC, which cannot be isolated
effectively by flash column chromatography. In addition, the by-
products were further determined by GC-MS, implying that the
diaminated products, the further arylation of products 7, and
others were included.
4.2 Experimental procedure
4.2.1 General procedure for the NHC-Pd(II) complex 1-
catalyzed amination of dichlorobenzenes with secondary
amines. Under N2 atmosphere, NHC-Pd(II) complex 1 (1.0
mol%), KOtBu (1.3 equiv), toluene (1.0 mL), secondary amines 3
(0.7 mmol) and dichlorobenzenes
successively added into a Schlenk reaction tube. The mixture was
2
(2.1 mmol) were

4
Tetrahedron
HRMS (ESI): calcd. for C14H15ClN [M+H]+: 232.0888; found:
232.0896.
4.2.1.10. Compound 4j: colorless liquid. H NMR (CDCl3, 500
stirred at the specified temperature for 12 h. Then the solvent was
removed under reduced pressure and the residue was purified by
flash column chromatography (SiO2) to give the corresponding
products.
1
MHz, TMS) δ 7.18 (d, J = 9.0 Hz, 2H), 7.04 (t, J = 8.5 Hz, 1H),
6.90 (d, J = 9.0 Hz, 2H), 6.68 (d, J = 7.0 Hz, 2H), 6.56 (d, J = 8.0
Hz, 1H), 3.79 (s, 3H), 3.21 (s, 3H). 13C NMR (CDCl3, 125 MHz)
δ 157.1, 150.8, 141.1, 134.7, 129.7, 127.3, 117.4, 115.0, 114.2,
112.6, 55.4, 40.4. IR (neat) ν 3069, 3039, 2998, 2952, 2907,
2835, 2812, 1608, 1564, 1440, 1350, 1237, 1180, 1135, 1107,
1081, 1032, 986, 955, 933, 904, 837, 806, 765, 737 cm-1. MS (EI)
(m/z, %): 247 (M+, 79), 232 (100). HRMS (DART): calcd. for
C14H15ONCl [M+H]+: 248.0837; found: 248.0835.
1
4.2.1.1. Compound 4a6: colorless liquid. H NMR (CDCl3, 500
MHz, TMS) δ 7.17 (t, J = 8.0 Hz, 1H), 6.87-6.82 (m, 2H), 6.77
(dd, J = 8.0, 2.0 Hz, 1H), 3.84 (t, J = 5.0 Hz, 4H), 3.14 (t, J = 5.0
Hz, 4H). 13C NMR (CDCl3, 125 MHz) δ 152.3, 135.0, 130.0,
119.6, 115.4, 113.5, 66.7, 48.8.
1
4.2.1.2. Compound 4b7: colorless liquid. H NMR (CDCl3, 500
MHz, TMS) δ 7.31 (t, J = 7.5 Hz, 2H), 7.11-7.05 (m, 4H), 6.87
(s, 1H), 6.80 (d, J = 7.5 Hz, 1H), 6.75 (d, J = 8.0 Hz, 1H), 3.27
(s, 3H). 13C NMR (CDCl3, 125 MHz) δ 150.2, 148.2, 134.7,
129.9, 129.5, 123.4, 123.3, 119.5, 117.4, 115.7, 40.2.
1
4.2.1.11. Compound 4k12: yellow liquid. H NMR (CDCl3, 500
MHz, TMS) δ 7.37 (d, J = 7.5 Hz, 1H), 7.26-7.22 (m, 1H), 7.04
(d, J = 8.0 Hz, 1H), 6.99 (t, J = 7.5 Hz, 1H), 3.88 (t, J = 4.5 Hz,
4H), 3.06 (t, J = 4.5 Hz, 4H). 13C NMR (CDCl3, 125 MHz) δ
149.0, 130.7, 128.8, 127.6, 123.9, 120.2, 67.1, 51.7.
1
4.2.1.3. Compound 4c8: yellow liquid. H NMR (CDCl3, 500
MHz, TMS) δ 7.13 (d, J = 8.0 Hz, 1H), 6.87 (d, J = 2.0 Hz, 1H),
6.79-6.74 (m, 2H), 3.16 (t, J = 5.5 Hz, 4H), 1.71-1.66 (m, 4H),
1.60-1.56 (m, 2H). 13C NMR (CDCl3, 125 MHz) δ 153.1, 134.8,
129.9, 118.6, 116.0, 114.2, 50.1, 25.6, 24.2.
1
4.2.1.12. Compound 4l13: colorless liquid. H NMR (CDCl3, 500
MHz, TMS) δ 7.48 (d, J = 8.0 Hz, 1H), 7.28-7.26 (m, 2H), 7.21-
7.17 (m, 3H), 6.76 (t, J = 7.5 Hz, 1H), 6.60 (d, J = 8.5 Hz, 2H),
3.24 (s, 3H). 13C NMR (CDCl3, 125 MHz) δ 148.7, 145.4, 133.7,
131.0, 130.2, 129.0, 128.2, 127.4, 117.9, 113.6, 39.0.
1
4.2.1.4. Compound 4d9: yellow liquid. H NMR (CDCl3, 500
MHz, TMS) δ 7.17-7.13 (m, 2H), 6.47 (d, J = 8.5 Hz, 2H), 3.25
(t, J = 6.5 Hz, 4H), 2.02-1.99 (m, 4H). 13C NMR (CDCl3, 125
MHz) δ 148.9, 134.9, 129.9, 115.1, 111.4, 109.8, 47.6, 25.4.
1
4.2.1.13. Compound 4m: yellow liquid. H NMR (CDCl3, 500
MHz, TMS) δ 7.42 (d, J = 8.0 Hz, 1H), 7.23-7.20 (m, 2H), 7.13-
7.10 (m, 1H), 6.77 (d, J = 9.0 Hz, 2H), 6.61 (d, J = 9.0 Hz, 2H),
3.73 (s, 3H), 3.20 (s, 3H). 13C NMR (CDCl3, 125 MHz) δ 152.6,
146.3, 143.2, 132.6, 130.8, 128.8, 127.9, 126.3, 116.0, 114.4,
55.6, 39.7. IR (neat) ν 3024, 2920, 2814, 1595, 1564, 1482,
1380, 1343, 1256, 1191, 1167, 1129, 1107, 1090, 1039, 987, 934,
841, 766, 734, 726, 707 cm-1. MS (EI) (m/z, %): 232 (13) [M-
15]+, 231 (65), 201 (51), 181 (100). HRMS (DART): calcd. for
C14H15ONCl [M+H]+: 248.0837; found: 248.0835.
1
4.2.1.5. Compound 4e10: yellow liquid. H NMR (CDCl3, 500
MHz, TMS) δ 7.15 (t, J = 8.0 Hz, 1H), 6.87 (s, 1H), 6.79 (t, J =
9.0 Hz, 2H), 3.20 (t, J = 5.0 Hz, 4H), 2.55 (t, J = 5.0 Hz, 4H),
2.34 (s, 3H). 13C NMR (CDCl3, 125 MHz) δ 152.2, 134.8, 129.9,
119.1, 115.6, 113.8, 54.7, 48.4, 45.9.
1
4.2.1.6. Compound 4f11: colorless liquid. H NMR (CDCl3, 500
MHz, TMS) δ 7.30 (t, J = 7.5 Hz, 2H), 7.23 (t, J = 7.5 Hz, 1H),
7.18 (d, J = 7.5 Hz, 2H), 7.07 (t, J = 8.0 Hz, 1H), 6.70 (t, J = 2.0
Hz, 1H), 6.65 (dd, J = 8.0, 1.0 Hz, 1H), 6.57 (dd, J = 8.5, 2.0 Hz,
1H), 4.49 (s, 2H), 2.98 (s, 3H). 13C NMR (CDCl3, 125 MHz) δ
150.7, 138.2, 135.1, 130.0, 128.6, 127.0, 126.6, 116.3, 112.0,
110.4, 56.3, 38.5.
1
4.2.1.14. Compound 4n12: yellow solid. H NMR (CDCl3, 500
MHz, TMS) δ 7.20 (d, J = 9.0 Hz, 2H), 6.81 (d, J = 9.0 Hz, 2H),
3.83 (t, J = 4.5 Hz, 4H), 3.09 (t, J = 4.5 Hz, 4H). 13C NMR
(CDCl3, 125 MHz) δ 149.8, 128.9, 124.7, 116.8, 66.7, 49.2.
1
4.2.1.7. Compound 4g: yellow liquid. H NMR (CDCl3, 500
1
4.2.1.15. Compound 4o14: yellow liquid. H NMR (CDCl3, 500
MHz, TMS) δ 7.29 (d, J = 7.0 Hz, 1H), 7.24-7.19 (m, 2H), 7.10
(d, J = 7.5 Hz, 1H), 7.04 (t, J = 8.0 Hz, 1H), 6.65 (d, J = 8.0 Hz,
1H), 6.50 (s, 1H), 6.34 (d, J = 8.5 Hz, 1H), 3.19 (s, 3H), 2.12 (s,
3H). 13C NMR (CDCl3, 125 MHz) δ 150.2, 145.9, 136.7, 134.9,
131.5, 129.8, 128.3, 127.7, 126.9, 116.5, 112.3, 110.9, 39.0, 17.7.
IR (neat) ν 2372, 1593, 1560, 1540, 1487, 1348, 1245, 1113,
1036, 983, 949, 915, 894, 867, 833, 806, 768, 735, 720 cm-1. MS
(ESI): 232 [M+H]+. HRMS (ESI): calcd. for C14H15ClN [M+H]+:
232.0888; found: 232.0895.
MHz, TMS) δ 7.28 (td, J = 7.5, 2.0 Hz, 2H), 7.20-7.16 (m, 2H),
7.02 (dd, J = 8.5, 0.5 Hz, 2H), 6.99 (t, J = 7.5 Hz, 1H), 6.90-6.87
(m, 2H), 3.27 (s, 3H). 13C NMR (CDCl3, 125 MHz) δ 148.7,
147.7, 129.3, 129.0, 125.6, 122.2, 121.4, 120.6, 40.3.
1
4.2.1.16. Compound 4p8: yellow solid. H NMR (CDCl3, 500
MHz, TMS) δ 7.16 (d, J = 8.5 Hz, 2H), 6.82 (d, J = 8.5 Hz, 2H),
3.09 (t, J = 5.5 Hz, 4H), 1.70-1.66 (m, 4H), 1.58-1.53 (m, 2H).
13C NMR (CDCl3, 125 MHz) δ 150.8, 128.8, 123.8, 117.6, 50.6,
25.7, 24.1.
1
4.2.1.8. Compound 4h: colorless liquid. H NMR (CDCl3, 500
1
4.2.1.17. Compound 4q9: yellow solid. H NMR (CDCl3, 500
MHz, TMS) δ 7.21 (t, J = 7.5 Hz, 1H), 7.10 (t, J = 8.0 Hz, 1H),
6.92 (d, J = 3.5 Hz, 2H), 6.90 (s, 1H), 6.85 (s, 1H), 6.79 (d, J =
7.5 Hz, 1H), 6.74 (dd, J = 8.0, 1.5 Hz, 1H), 3.26 (s, 3H), 2.32 (s,
3H). 13C NMR (CDCl3, 125 MHz) δ 150.4, 148.3, 139.5, 134.8,
129.9, 129.4, 124.6, 124.3, 120.8, 119.2, 117.2, 115.5, 40.3, 21.5.
IR (neat) ν 2862, 2815, 1590, 1580, 1564, 1487, 1341, 1259,
1126, 1086, 985, 932, 839, 766, 707 cm-1. MS (ESI): 232
[M+H]+. HRMS (ESI): calcd. for C14H15NCl [M+H]+: 232.0888;
found: 232.0892.
MHz, TMS) δ 7.14 (d, J = 8.5 Hz, 2H), 6.46 (d, J = 8.5 Hz, 2H),
3.23 (t, J = 6.5 Hz, 4H), 2.00 (t, J = 6.5 Hz, 4H). 13C NMR
(CDCl3, 125 MHz) δ 146.5, 128.8, 120.1, 112.6, 47.7, 25.4.
1
4.2.1.18. Compound 4r15: yellow solid. H NMR (CDCl3, 500
MHz, TMS) δ 7.20 (d, J = 8.5 Hz, 2H), 6.84 (d, J = 8.5 Hz, 2H),
3.17 (t, J = 5.0 Hz, 4H), 2.56 (t, J = 5.0 Hz, 4H), 2.34 (s, 3H). 13
C
NMR (CDCl3, 125 MHz) δ 149.8, 128.8, 124.4, 117.1, 54.9,
49.0, 46.0.
1
4.2.1.19. Compound 4s16: colorless liquid. H NMR (CDCl3, 500
1
4.2.1.9. Compound 4i: colorless liquid. H NMR (CDCl3, 500
MHz, TMS) δ 7.30 (t, J = 7.5 Hz, 2H), 7.23 (t, J = 7.0 Hz, 1H),
7.17 (d, J = 7.5 Hz, 2H), 7.12 (d, J = 9.0 Hz, 2H), 6.62 (d, J = 9.0
Hz, 2H), 4.48 (s, 2H), 2.98 (s, 3H). 13C NMR (CDCl3, 125 MHz)
δ 148.3, 138.4, 128.9, 128.6, 127.0, 126.6, 121.3, 113.5, 56.6,
38.7.
MHz, TMS) δ 7.15 (d, J = 8.0 Hz, 2H), 7.07 (t, J = 8.0 Hz, 1H),
7.03 (d, J = 8.0 Hz, 2H), 6.79 (s, 1H), 6.74 (d, J = 8.0 Hz, 1H),
6.67 (d, J = 8.5 Hz, 1H), 3.25 (s, 3H), 2.34 (s, 3H). 13C NMR
(CDCl3, 125 MHz) δ 150.5, 145.7, 134.7, 134.0, 130.2, 129.8,
124.6, 118.4, 115.8, 114.1, 40.3, 20.8. IR (neat) ν 2921, 2875,
2809, 1593, 1557, 1511, 1481, 1341, 1249, 1172, 1136, 1083,
1017, 985, 904, 841, 821, 761, 722 cm-1. MS (ESI): 232 [M+H]+.
1
4.2.1.20. Compound 4t: yellow liquid. H NMR (CDCl3, 500
MHz, TMS) δ 7.18-7.15 (m, 3H), 6.86-6.81 (m, 5H), 3.24 (s,

5
3H), 2.29 (s, 3H). 13C NMR (CDCl3, 125 MHz) δ 148.6, 147.7,
139.2, 129.2, 128.9, 125.2, 123.3, 122.4, 120.2, 118.9, 40.3, 21.4.
IR (neat) ν 2359, 1593, 1560, 1540, 1484, 1338, 1245, 1123,
1113, 987, 950, 906, 836, 819, 773, 760, 728, 713 cm-1. MS
(ESI): 232 [M+H]+. HRMS (ESI): calcd. for C14H15ClN [M+H]+:
232.0888; found: 232.0893.
mol%), KOtBu (1.5 equiv), toluene (1.0 mL), primary amines 6
(2.1 mmol) and dichlorobenzenes (0.7 mmol) were
2
successively added into a Schlenk reaction tube. The mixture was
stirred at the specified temperature for 12 h. Then the solvent was
removed under reduced pressure and the residue was purified by
flash column chromatography (SiO2) to give the corresponding
products.
1
4.2.1.21. Compound 4u: colorless liquid. H NMR (CDCl3, 500
4.2.2.1. Compound 7a18: yellow liquid. H NMR (CDCl3, 500
1
MHz, TMS) δ 7.27 (d, J = 7.0 Hz, 1H), 7.13 (t, J = 7.0 Hz, 1H),
7.18 (t, J = 7.0 Hz, 1H), 7.09 (t, J = 8.5 Hz, 3H), 6.42 (d, J = 9.0
Hz, 2H), 3.18 (s, 3H), 2.11 (s, 3H). 13C NMR (CDCl3, 125 MHz)
δ 147.7, 146.3, 136.6, 131.5, 128.7, 128.2, 127.6, 126.7, 121.6,
113.8, 39.1, 17.7. IR (neat) ν 2911, 2809, 1605, 1580, 1487,
1334, 1262, 1186, 1123, 1096, 1000, 983, 919, 878, 818, 798,
783, 771, 710 cm-1. MS (ESI): 232 [M+H]+. HRMS (ESI): calcd.
for C14H15ClN [M+H]+: 232.0888; found: 232.0897.
MHz, TMS) δ 7.20 (d, J = 7.5 Hz, 2H), 7.15 (t, J = 7.5 Hz, 1H),
7.10 (t, J = 8.0 Hz, 1H), 6.99 (t, J = 7.5 Hz, 1H), 6.83 (s, 1H),
6.80 (d, J = 8.0 Hz, 1H), 6.72 (d, J = 8.0 Hz, 1H), 5.36 (s, 1H),
2.21 (s, 3H). 13C NMR (CDCl3, 125 MHz) δ 146.0, 140.0, 135.0,
131.1, 130.2, 130.1, 126.9, 123.5, 121.1, 119.8, 116.1, 114.5,
17.8.
4.2.2.2. Compound 7b19: yellow liquid. H NMR (CDCl3, 500
1
1
4.2.1.22. Compound 4v17: colorless liquid. H NMR (CDCl3, 500
MHz, TMS) δ 7.14 (t, J = 8.0 Hz, 1H), 7.09 (t, J = 8.0 Hz, 1H),
6.95 (s, 1H), 6.86-6.78 (m, 5H), 5.57 (s, 1H), 2.28 (s, 3H). 13C
NMR (CDCl3, 125 MHz) δ 144.9, 141.8, 139.3, 134.9, 130.2,
129.2, 122.9, 120.2, 119.7, 116.6, 116.1, 115.0, 21.4.
MHz, TMS) δ 7.12 (d, J = 9.0 Hz, 2H), 7.11 (d, J = 9.0 Hz, 2H),
6.97 (d, J = 8.0 Hz, 2H), 6.77 (d, J = 8.5 Hz, 2H), 3.22 (s, 3H),
2.31 (s, 3H). 13C NMR (CDCl3, 125 MHz) δ 148.0, 146.1, 132.9,
130.0, 128.8, 124.1, 123.2, 118.5, 40.3, 20.7.
4.2.2.3. Compound 7c20: yellow liquid. H NMR (CDCl3, 500
1
4.2.1.23. Compound 4w: white solid. 1H NMR (CDCl3, 500
MHz, TMS) δ 7.10 (d, J = 9.0 Hz, 2H), 7.06 (d, J = 9.0 Hz, 2H),
6.88 (d, J = 9.0 Hz, 2H), 6.66 (d, J = 9.0 Hz, 2H), 3.79 (s, 3H),
3.20 (s, 3H). 13C NMR (CDCl3, 125 MHz) δ 156.6, 148.3, 141.7,
128.6, 126.5, 122.8, 116.4, 114.9, 55.4, 40.5. IR (neat) ν 2998,
2926, 2833, 1591, 1567, 1509, 1488, 1459, 1442, 1347, 1303,
1289, 1275, 1267, 1244, 1182, 1118, 1103, 1095, 1070, 1032,
1006, 871, 834, 814, 795, 718, 705 cm-1. MS (EI) (m/z, %): 247
(M+, 52), 232 (85), 207 (100). HRMS (DART): calcd. for
C14H15ONCl [M+H]+: 248.0837; found: 248.0835.
MHz, TMS) δ 7.13-7.10 (m, 3H), 7.00 (d, J = 8.0 Hz, 2H), 6.95
(s, 1H), 6.82-6.80 (m, 2H), 5.61 (s, 1H), 2.31 (s, 3H). 13C NMR
(CDCl3, 125 MHz) δ 145.7, 139.1, 135.0, 132.2, 130.3, 130.0,
120.1, 119.8, 115.8, 114.3, 20.7.
4.2.2.4. Compound 7d: yellow liquid. 1H NMR (CDCl3, 500 MHz,
TMS) δ 7.10-7.03 (m, 3H), 6.97 (d, J = 7.5 Hz, 1H), 6.75-6.73
(m, 2H), 6.63 (d, J = 9.0 Hz, 1H), 5.28 (s, 1H), 2.30 (s, 3H), 2.17
(s, 3H). 13C NMR (CDCl3, 125 MHz) δ 146.8, 137.0, 134.9,
133.7, 131.8, 131.3, 130.2, 127.4, 122.7, 118.9, 115.0, 113.5,
20.7, 17.7. IR (neat) ν 3403, 3018, 2921, 2855, 1594, 1506, 1479,
1384, 1312, 1277, 1218, 1162, 1093, 1074, 1035, 991, 937, 903,
852, 813, 766, 727 cm-1. MS (EI) (m/z, %): 231 (M+, 100).
HRMS (DART): calcd. for C14H15NCl [M+H]+: 232.0888; found:
232.0886.
1
4.2.1.24. Compound 5a6: yellow liquid. H NMR (CDCl3, 500
MHz, TMS) δ 7.19 (t, J = 8.0 Hz, 1H), 6.49 (s, 1H), 6.47 (s, 2H),
3.86 (t, J = 5.0 Hz, 8H), 3.15 (t, J = 5.0 Hz, 8H). 13C NMR
(CDCl3, 125 MHz, TMS) δ 152.4, 129.7, 108.2, 103.9, 66.9,
49.7.
4.2.2.5. Compound 7e: yellow liquid. 1H NMR (CDCl3, 500 MHz,
TMS) δ 7.11-7.10 (m, 3H), 7.04 (t, J = 8.0 Hz, 1H), 6.69 (d, J =
8.0 Hz, 1H), 6.44 (s, 1H), 6.37 (d, J = 8.0 Hz, 1H), 5.19 (s, 1H),
2.19 (s, 6H). 13C NMR (CDCl3, 125 MHz) δ 147.7, 137.3, 136.2,
135.1, 130.2, 128.7, 126.3, 118.0, 113.1, 111.6, 18.2. IR (neat) ν
3406, 1652, 1597, 1585, 1492, 1478, 1419, 1379, 1315, 1277,
1163, 1143, 1093, 1050, 987, 961, 939, 914, 891, 859, 846, 824,
806, 796, 770, 763, 721 cm-1. MS (EI) (m/z, %): 231 (M+, 100).
HRMS (DART): calcd. for C14H15NCl [M+H]+: 232.0888; found:
232.0886.
1
4.2.1.25. Compound 5b10: yellow liquid. H NMR (CDCl3, 500
MHz, TMS) δ 7.26 (t, J = 7.5 Hz, 4H), 7.16 (t, J = 8.5 Hz, 1H),
7.03 (d, J = 8.0 Hz, 4H), 6.93 (t, J = 7.0 Hz, 2H), 6.70 (s, 1H),
6.62 (dd, J = 8.0, 1.5 Hz, 2H), 3.28 (s, 6H). 13C NMR (CDCl3,
125 MHz) δ 149.9, 149.0, 129.7, 129.1, 121.1, 120.4, 113.7,
112.8, 40.2.
1
4.2.1.26. Compound 5c10: yellow liquid. H NMR (CDCl3, 500
MHz, TMS) δ 7.12 (t, J = 8.0 Hz, 1H), 6.54 (s, 1H), 6.46 (d, J =
8.0 Hz, 2H), 3.12 (t, J = 5.5 Hz, 8H), 1.72-1.68 (m, 8H), 1.58-
1.55 (m, 4H). 13C NMR (CDCl3, 125 MHz) δ 153.3, 129.3, 108.5,
106.0, 51.1, 26.0, 24.4.
4.2.2.6. Compound 7f: brown solid. 1H NMR (CDCl3, 500 MHz,
TMS) δ 7.30-7.28 (m, 1H), 7.14 (t, J = 8.0 Hz, 1H), 7.10 (s, 1H),
6.95 (d, J = 8.0 Hz, 1H), 6.90-6.84 (m, 4H), 6.13 (s, 1H), 3.84 (s,
3H). 13C NMR (CDCl3, 125 MHz) δ 148.8, 144.4, 134.9, 131.7,
130.2, 121.1, 120.8, 120.5, 117.3, 116.1, 115.7, 110.7, 55.5. IR
(neat) ν 3408, 3052, 3023, 2975, 2923, 2855, 1594, 1487, 1457,
1393, 1380, 1308, 1248, 1229, 1174, 1159, 1112, 1092, 1048,
1007, 986, 936, 880, 819, 773, 749, 721, 702 cm-1. MS (EI)
(m/z, %): 233 (M+, 50), 183 (100). HRMS (DART): calcd. for
C13H13ONCl [M+H]+: 234.0680; found: 234.0678.
1
4.2.1.27. Compound 5d: yellow liquid. H NMR (CDCl3, 500
MHz, TMS) δ 7.16-7.13 (m, 3H), 6.85-6.83 (m, 4H), 6.75 (d, J =
7.5 Hz, 2H), 6.68 (s, 1H), 6.60 (d, J = 8.0 Hz, 2H), 3.26 (s, 6H),
2.29 (s, 6H). 13C NMR (CDCl3, 125 MHz) δ 149.9, 148.9, 138.9,
129.6, 128.9, 122.1, 121.1, 117.6, 113.3, 112.5, 40.2, 21.6. IR
(neat) ν 2921, 2862, 1590, 1580, 1491, 1398, 1335, 1172, 1126,
1116, 1007, 992, 957, 922, 891, 856, 819, 795, 770, 743, 700 cm-
1. MS (ESI): 317 [M+H]+. HRMS (ESI): calcd. for C22H25N2
[M+H]+: 317.2012; found: 317.2024.
1
4.2.2.7. Compound 7g: white solid. H NMR (CDCl3, 500 MHz,
1
TMS) δ 7.05 (t, J = 8.0 Hz, 1H), 6.94 (s, 2H), 6.67 (d, J = 8.0 Hz,
1H), 6.42 (s, 1H), 6.36 (d, J = 8.0 Hz, 1H), 5.13 (s, 1H), 2.30 (s,
3H), 2.16 (s, 6H). 13C NMR (CDCl3, 125 MHz) δ 148.0, 136.1,
136.0, 135.1, 134.6, 130.2, 129.3, 117.7, 112.8, 111.4, 20.9, 18.1.
IR (neat) ν 3395, 3016, 2918, 2857, 2732, 1613, 1476, 1397,
1377, 1320, 1298, 1269, 1252, 1239, 1220, 1161, 1093, 1073,
1034, 1011, 990, 959, 936, 905, 853, 798, 765, 746 cm-1. MS (EI)
(m/z, %): 245 (M+, 100). HRMS (DART): calcd. for C15H17NCl
[M+H]+: 246.1044; found: 246.1043.
4.2.1.28. Compound 5e: yellow liquid. H NMR (CDCl3, 500
MHz, TMS) δ 7.08-7.06 (m, 5H), 6.97 (d, J = 8.0 Hz, 4H), 6.54
(s, 1H), 6.46 (d, J = 8.0 Hz, 2H), 3.23 (s, 6H), 2.30 (s, 6H). 13C
NMR (CDCl3, 125 MHz) δ 150.2, 146.7, 131.5, 129.7, 129.4,
122.0, 111.0, 109.4, 40.3, 20.7. IR (neat) ν 2915, 2855, 2796,
1593, 1511, 1491, 1394, 1328, 1189, 1133, 1109, 947, 937, 894,
821, 813, 798, 718, 697 cm-1. MS (ESI): 317 [M+H]+. HRMS
(ESI): calcd. for C22H25N2 [M+H]+: 317.2012; found: 317.2025.
4.2.2 General procedure for the NHC-Pd(II) complex 1-
catalyzed amination of dichlorobenzenes with primary
amines. Under N2 atmosphere, NHC-Pd(II) complex 1 (1.0
1
4.2.2.8. Compound 7h: yellow liquid. H NMR (CDCl3, 500
MHz, TMS) δ 7.24-7.18 (m, 2H), 7.07 (s, 1H), 6.94 (t, J = 5.5 Hz,

6
Tetrahedron
2H), 6.81-6.77 (m, 2H), 6.65 (t, J = 8.0 Hz, 1H), 5.77 (s, 1H). 13
NMR (CDCl3, 125 MHz) δ 163.7 (d, JC-F = 243.375 Hz), 144.2 (d,
JC-F = 10.25 Hz), 143.7, 135.1, 130.6 (d, JC-F = 9.875 Hz), 130.4,
C
J = 7.5 Hz, 1H), 6.16 (d, J = 8.0 Hz, 1H), 5.61 (s, 1H), 2.31 (s,
3H), 2.15 (s, 6H). 13C NMR (CDCl3, 125 MHz) δ 142.7, 136.4,
136.1, 134.7, 129.24, 129.18, 127.6, 118.9, 117.8, 112.3, 20.9,
18.0.
121.6, 118.0, 116.3, 113.6 (d, JC-F = 2.5 Hz), 108.2 (d, JC-F
=
1
4.2.2.17. Compound 7q3a: colorless liquid. H NMR (CDCl3, 500
21.375 Hz), 104.8 (d, J = 24.75 Hz). IR (neat) ν 3412, 3193,
3068, 2925, 2854, 1669, 1621, 1516, 1480, 1455, 1391, 1337,
1281, 1254, 1228, 1167, 1144, 1096, 1074, 1002, 994, 971, 914,
845, 768, 712 cm-1. MS (EI) (m/z, %): 221 (M+, 100), 185 (94).
HRMS (DART): calcd. for C12H10NFCl [M+H]+: 222.0480;
found: 222.0479.
MHz, TMS) δ 7.33 (d, J = 7.5 Hz, 1H), 7.12-7.00 (m, 6H), 6.77 (t,
J = 7.5 Hz, 1H), 5.99 (s, 1H). 13C NMR (CDCl3, 125 MHz) δ
159.0 (d, JC-F = 240.875 Hz), 141.1, 137.3 (d, JC-F = 2.625 Hz),
129.7, 127.5, 123.2 (d, JC-F = 70.875 Hz), 120.8, 120.0, 116.1 (d,
J
C-F = 22.375 Hz), 114.6.
1
4.2.2.18. Compound 7r14: yellow liquid. H NMR (CDCl3, 500
MHz, TMS) δ 7.20-7.11 (m, 5H), 6.95 (t, J = 7.0 Hz, 1H), 6.82
(d, J = 9.0 Hz, 2H), 5.32 (s, 1H), 2.22 (s, 3H). 13C NMR (CDCl3,
125 MHz) δ 142.8, 140.6, 131.0, 129.1, 128.9, 127.6, 126.8,
124.8, 122.6, 119.5, 118.2, 17.8.
4.2.2.9. Compound 7i: yellow liquid. 1H NMR (CDCl3, 500 MHz,
TMS) 7.32 (t, J = 8.0 Hz, 1H), 7.19 (t, J = 8.0 Hz, 1H), 7.12-7.05
(m, 3H), 6.95-6.91 (m, 3H), 5.79 (s, 1H). 13C NMR (CDCl3, 125
MHz) δ 153.6 (d, JC-F = 240.375 Hz), 143.8, 135.1, 130.5 (d, JC-F
= 11.25 Hz), 130.4, 124.4 (d, JC-F = 3.75 Hz), 121.9 (d, JC-F
=
1
7.25 Hz), 121.4, 118.7, 117.6, 115.9, 115.7 (d, JC-F = 19.125 Hz).
IR (neat) ν 3420, 3066, 2954, 2925, 2853, 1620, 1598, 1515,
1482, 1460, 1411, 1378, 1329, 1176, 1245, 1226, 1186, 1164,
1100, 1076, 1033, 994, 921, 851, 800, 769, 746 cm-1. MS (EI)
(m/z, %): 221 (M+, 100), 185 (69). HRMS (DART): calcd. for
C12H110NFCl [M+H]+: 222.0480; found: 222.0478.
4.2.2.19. Compound 7s14: yellow liquid. H NMR (CDCl3, 500
MHz, TMS) δ 7.18 (d, J = 9.0 Hz, 2H), 7.15 (t, J = 8.0 Hz, 1H),
6.95 (d, J = 8.5 Hz, 2H), 6.84-6.83 (m, 2H), 6.77 (d, J = 7.5 Hz,
1H), 5.60 (s, 1H), 2.30 (s, 3H). 13C NMR (CDCl3, 125 MHz) δ
142.6, 142.0, 139.3, 129.22, 129.20, 125.3, 122.4, 118.8, 115.2,
21.5.
1
4.2.2.10. Compound 7j21: yellow liquid. H NMR (CDCl3, 500
Acknowledgments
MHz, TMS) δ 7.13 (t, J = 8.0 Hz, 1H), 7.05 (dd, J = 9.0, 5.0 Hz,
2H), 7.00 (t, J = 8.5 Hz, 2H), 6.91 (s, 1H), 6.82 (d, J = 8.0 Hz,
1H), 6.78 (dd, J = 8.0, 1.5 Hz, 1H), 5.59 (s, 1H). 13C NMR
(CDCl3, 125 MHz) δ 158.7 (d, JC-F = 240.375 Hz), 145.7, 137.8
(d, JC-F = 2.375 Hz), 135.1, 130.4, 122.0 (d, JC-F = 7.875 Hz),
120.1, 116.1 (d, JC-F = 22.5 Hz), 115.7, 114.2.
Financial support from the National Natural Science
Foundation of China (No. 21471115) is greatly appreciated.
References and notes
1
4.2.2.11. Compound 7k22: yellow liquid. H NMR (CDCl3, 500
MHz, TMS) δ 7.32 (d, J = 8.0 Hz, 1H), 7.16-7.12 (m, 3H), 7.10-
7.05 (m, 3H), 6.74 (t, J = 7.5 Hz, 1H), 6.01 (s, 1H), 2.32 (s, 3H).
13C NMR (CDCl3, 125 MHz) δ 141.2, 139.6, 131.2, 131.1, 129.5,
127.4, 126.8, 123.9, 122.2, 120.8, 119.6, 115.0, 17.8.
1. For some selected reviews, please see: (a) Shi, S.; Nolan, S. P.;
Szostak, M. Acc. Chem. Res. 2018, 51, 2589-2599. (b) Froese, R.
D. J.; Lombardi, C.; Pompeo, M.; Rucker, R. P.; Organ, M. G. Acc.
Chem. Res. 2017, 50, 2244-2253. (c) Çalimsiz, S.; Hoi, K. H.;
Mallik, D.; Sayah, M.; Organ, M. G. Angew. Chem. Int. Ed. 2012,
51, 3314-3332. (d) Fortman, G. C.; Nolan, S. P. Chem. Soc. Rev.
2011, 40, 5151-5169. (e) Marion, N.; Nolan, S. P. Acc. Chem. Res.
2008, 41, 1440-1449. (f) Würtz, S.; Glorius, F. Acc. Chem. Res.
2008, 41, 1523-1533.
2. For some selected examples on the metal-catalyzed selective C-C
coupling of polyhalogenated arenes, please see: (a) Laulhé, S.;
Miles Blackburn, J.; Roizen, J. L. Org. Lett. 2016, 18, 4440-4443.
(b) Ullah, E.; McNulty, J.; Robertson, A. Eur. J. Org. Chem. 2012,
2127-2131. (c) Toguem, S.-M. T.; Fatunsin, O.; Villinger, A.;
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M.; Khera, R. A.; Hung, N. T.; Langer, P. Org. Biomol. Chem.
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1
4.2.2.12. Compound 7l3a: colorless liquid. H NMR (CDCl3, 500
MHz, TMS) δ 7.32 (d, J = 8.0 Hz, 1H), 7.16-7.06 (m, 6H), 6.74 (t,
J = 7.5 Hz, 1H), 6.02 (s, 1H), 2.33 (s, 3H). 13C NMR (CDCl3, 125
MHz) δ 141.0, 138.7, 132.7, 130.0, 129.6, 127.4, 121.3, 120.8,
119.7, 114.7, 20.8.
1
4.2.2.13. Compound 7m: yellow liquid. H NMR (CDCl3, 500
MHz, TMS) δ 7.30 (d, J = 8.0 Hz, 1H), 7.12 (d, J = 8.0 Hz, 1H),
7.06 (s, 1H), 7.02 (t, J = 8.0 Hz, 1H), 6.99 (d, J = 8.0 Hz, 1H),
6.74 (d, J = 8.0 Hz, 1H), 6.69 (t, J = 8.0 Hz, 1H), 5.79 (s, 1H),
2.31 (s, 3H), 2.20 (s, 3H). 13C NMR (CDCl3, 125 MHz) δ 141.9,
136.7, 134.2, 132.3, 131.8, 129.4, 127.42, 127.40, 123.8, 120.1,
118.9, 114.1, 20.8, 17.7. IR (neat) ν 3405, 3019, 2920, 2856,
2733, 1596, 1516, 1455, 1417, 1383, 1314, 1291, 1217, 1157,
1123, 1048, 1034, 928, 877, 798, 743, 718 cm-1. MS (EI)
(m/z, %): 217 (M+, 31), 207 (45), 167 (45), 44 (100). HRMS
(DART): calcd. for C13H13NCl [M+H]+: 218.0731; found:
218.0729.
1
4.2.2.14. Compound 7n23: colorless liquid. H NMR (CDCl3, 500
3. For some selected examples on the metal-catalyzed selective C-N
coupling of polyhalogenated arenes, please see: (a) Platon, M.;
Roger, J.; Royer, S.; Hierso, J.-C. Catal. Sci. Technol. 2014, 4,
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Lett. 2001, 42, 247-250.
MHz, TMS) δ 7.31 (d, J = 8.0 Hz, 1H), 7.21 (s, 3H), 6.97 (t, J =
7.5 Hz, 1H), 6.65 (t, J = 7.5 Hz, 1H), 6.16 (d, J = 8.0 Hz, 1H),
5.67 (s, 1H), 2.19 (s, 6H). 13C NMR (CDCl3, 125 MHz) δ 142.3,
137.4, 136.6, 129.2, 128.6, 127.6, 126.5, 119.0, 118.1, 112.4,
18.1.
4. Sun, K.-X.; He, Q.-W.; Xu, B.-B.; Wu, X.-T.; Lu, J.-M. Asian J.
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1
4.2.2.15. Compound 7o19: yellow solid. H NMR (CDCl3, 500
5. For some selected papers on the NHC-Pd(II) complexes catalyzed
C-N coupling of aryl chlorides, please see: (a) Zhang, F.-Y.; Lan,
X.-B.; Xu, C.; Yao, H.-G.; Li, T.; Liu, F.-S. Org. Front. Chem.
2019, 6, 3292-3299. (b) Zinser, C. M.; Warren, K. G.; Nahra, F.;
Al-Majid, A.; Barakat, A.; Islam, M. S.; Nolan, S. P.; Cazin, C. S.
J. Organometallics 2019, 38, 2812-2817. (c) Liu, F.; Hu, Y.-Y.;
Li, D.; Zhou, Q.; Lu, J.-M. Tetrahedron 2018, 74, 5683-5690. (d)
Huang, F.-D.; Xu, C.; Lu, D.-D.; Shen, D.-S.; Li, T.; Liu, F.-S. J.
MHz, TMS) δ 7.31 (d, J = 8.0 Hz, 1H), 7.12 (d, J = 8.5 Hz, 2H),
7.05 (t, J = 8.0 Hz, 1H), 6.96 (d, J = 8.5 Hz, 1H), 6.89 (d, J = 8.5
Hz, 2H), 6.71 (t, J = 8.0 Hz, 1H), 5.95 (s, 1H), 3.80 (s, 3H). 13C
NMR (CDCl3, 125 MHz) δ 156.4, 142.1, 134.0, 129.5, 127.4,
124.5, 120.0, 119.0, 114.7, 113.8, 55.5.
1
4.2.2.16. Compound 7p23: white solid. H NMR (CDCl3, 500
MHz, TMS) δ 7.30 (d, J = 8.0 Hz, 1H), 6.98-6.95 (m, 3H), 6.64 (t,

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Highlights
1) The palladium-catalyzed chemoselective amination between dichlorobenzenes and
various secondary and primary amines was achieved in this paper.
2) Using a well-defined NHC-Pd(II)-2-methyl-4,5-dihydrooxazole complex as the
catalyst, all reactions took place well to give the desired highly chemoselective mono-
aminated products as the major or sole one.

Declaration of interests
☒ The authors declare that they have no known competing financial interests or personal relationships
that could have appeared to influence the work reported in this paper.
☐The authors declare the following financial interests/personal relationships which may be considered
as potential competing interests: