Ligand-controlled chemoselectivity in potassium tert-amylate-promoted direct C-H arylation of unactivated benzene with aryl halides

Article abstract of DOI:10.1016/j.tet.2015.05.082

Direct C-H arylation of unactivated benzene with aryl halides under various simple ligands (EDA, DMEDA, ethylene glycol, etc.) in the presence of potassium tert-amylate (t-AmOK) base at mild temperature (80 °C) have been developed. This transition-metal-free radical cross-coupling offers an efficient way to synthesize various biaryls in good yields through base-promoted homolytic aromatic substitution. And mechanistic investigations have provided insight into the chemoselectivity of couplings between haloiodobenzenes and benzene and showed that phenanthroline and its derivatives not only initiate these radical reactions like most of other ligands (EDA, DMEDA, ethylene glycol, etc.), but also participate in the electron transfer process of biaryl radical anion intermediates.

Full text of DOI:10.1016/j.tet.2015.05.082

Accepted Manuscript
Ligand-controlled chemoselectivity in potassium tert-amylate-promoted direct C-H
arylation of unactivated benzene with aryl halides
Wei Liu, Lige Xu
PII:
S0040-4020(15)00789-9
10.1016/j.tet.2015.05.082
TET 26800
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 15 April 2015
Revised Date: 20 May 2015
Accepted Date: 22 May 2015
Please cite this article as: Liu W, Xu L, Ligand-controlled chemoselectivity in potassium tert-amylate-
promoted direct C-H arylation of unactivated benzene with aryl halides, Tetrahedron (2015), doi:
10.1016/j.tet.2015.05.082.
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
Ligand-controlled chemoselectivity in potassium tert-amylate-promoted
direct C-H arylation of unactivated benzene with aryl halides
Wei Liu,* Lige Xu
College of Food Science and Technology, Henan University of Technology, Lianhua
Street, Zhengzhou 450001, Henan, P. R. China.
* Corresponding author. E-mail: liuwei307@hotmail.com;
Tel: +86-371-67758022; Fax: +86-371-67758022
Abstract
Direct C-H arylation of unactivated benzene with aryl halides under various simple
ligands (EDA, DMEDA, ethylene glycol, etc.) in the presence of potassium
o
tert-amylate (t-AmOK) base at mild temperature (80 C) have been developed. This
transition-metal-free radical cross-coupling offers an efficient way to synthesize
various biaryls in good yields through base-promoted homolytic aromatic substitution.
And mechanistic investigations have provided insight into the chemoselectivity of
couplings between haloiodobenzenes and benzene and showed that phenanthroline
and its derivatives not only initiate these radical reactions like most of other ligands
(EDA, DMEDA, ethylene glycol, etc.), but also participate in the electron transfer
process of biaryl radical anion intermediates.
Keywords
C-H arylation; unactivated arenes; transition-metal-free; chemoselective coupling;
radical
1. Introduction
Direct C-H arylation of unactivated arenes is one of the most challenging and
1

ACCEPTED MANUSCRIPT
powerful transformations to construct biphenyl derivatives.1 Although various
transition metal-catalysis have been successfully developed in this area,2
transition-metal-free version of direct C-H arylation reactions are becoming an
attractive strategy.3
Recently, t-butoxides (eg. t-BuOK) mediated transition-metal-free direct C-H
arylation of unactivated arenes with aryl halides involving base-promoted homolytic
aromatic substitution (BHAS) has aroused great interest in organic syntheses.4-6 In
these processes, the combination of t-BuOM (M = K or Na) and a catalytic amount of
diamine ligands (N,N’-dimethylethylenediamine, 1,10-phenanthroline and its
derivatives, etc.)4 could efficiently promote the radical cross-coupling between
unactivated arenes (eg. benzene) and aryl halides (eg. iodides). And
photoirradiation-stimulated biaryl synthesis via base-promoted HAS reaction was also
established recently.7 A number of authors suggested that the products arose from
reactions where aryl radicals were featured as intermediates (Scheme 1).4-6 And after
addition of the aryl radical (5) to benzene, deprotonation of the resulting
cyclohexadienyl radical (6) was achieved by strong base t-BuOK. The product would
be the radical anion of a biaryl (7), which could then transfer an electron to another
molecule of aryl halide (1) to form the biaryl product 3 and a new radical anion of an
aryl halide (4) in a chain reaction.
2

ACCEPTED MANUSCRIPT
Previous works:
t-BuOK/Ligand
Ar
X
H
+
Ar
80-155 oC
t-BuOK/Ligand
Ar
I
Ar
I
Ar
SET
5
1
4
I
chain transfer
Ar
3
H
t-BuOK
deprotonation
Ar
Ar
7
6
Scheme 1. t-BuOK-mediated radical cross-coupling between benzene and aryl halides.
However, to the best of our knowledge, most reported examples of ligand-promoted
direct C-H arylation of unactivated arenes focused on using t-BuOK as base.8
Potassium tert-Amylate (t-AmOK), as an efficient strong base like t-BuOK, has been
used in many organic synthesis.9 Building on our continuing studies in this area,5g,q
we began to consider whether such radical cross-coupling is also efficient by using
other tertiary alkoxy base (eg. t-AmOK) and different ligands showed the same
activity in the presence of t-AmOK base (Scheme 2). Herein, we report our results
that t-AmOK can efficiently promote direct C-H arylation of benzene with various
aryl halides in the presence of a catalytic amount of simple ligands at mild
temperature (80 oC).
This wor k:
t-AmOK/Ligand
Ar X + H
Ar
80 oC
Scheme 2. t-AmOK-mediated radical cross-coupling reactions.
2. Results and Discussion
3

ACCEPTED MANUSCRIPT
The coupling reaction between 4-iodoanisole (1a) and benzene (2a) was chosen as
a model reaction to survey the reaction conditions (Table 1). In the presence of
t-AmOK base (3.0 equiv), no coupling reaction occurred at 80 oC after 24 h (Table 1,
entry 1). Then a set of simple diamine ligands were examined as “catalyst” for this
reaction in the presence of t-AmOK. TMEDA (N,N,N’,N’-tetramethylethanediamine)
showed no efficiency under standard conditions (Table 1, entry 2). To our delight,
when
other
1,2-diamines
(20
mol%),
such
as
DMEDA
(N,N’-dimethylethane-1,2-diamine) and EDA were examined, 90% and 84% yields of
corresponding direct C-H arylation product 4-methoxybiphenyl (3a) were detected,
respectively (Table 1, entries 3-4). In the coupling reaction promoted by DMEDA or
by EDA, successful coupling reactions were accompanied by formation of colored
reaction mixtures, indicative of the formation of conjugated substances. Interestingly,
propane-1,3-diamine (20 mol%) and CH3(CH2)3NH2 (20 mol%) were not efficient
under the same reaction conditions (Table 1, entries 5-6), which suggested that the
structure of 1,2-diamines is efficient to generate electron donors.10 And other ligands,
such as HOCH2CH2OH and n-BuOH, were used and moderate to good outcomes
were obtained (Table 1, entries 8-9). However, changing HOCH2CH2OH to
MeOCH2CH2OMe led to no coupling reaction (Table 1, entry 10). Moreover, Bipy
and Phen (1,10-phenanthroline) were tested and no coupling reaction occurred (Table
1, entries 11-12). When other phenanthroline derivatives (Neo and Bathophen) were
used, 77% and 79% yields of desired direct C-H arylation product 3a were obtained
(Table 1, entries 13-14).11 Further, decreasing the amount of t-AmOK base (2.0 equiv)
4

ACCEPTED MANUSCRIPT
used in the model reaction led to a reduced yield in the presence of 20 mol% of
DMEDA (Table 1, entry 15).
Table 1. Ligand effect on t-AmOK-mediated direct C-H arylation of benzenea.
Ligand
t-AmOK
80 oC, 24 h
MeO
I
+ H
MeO
1a
2a
3a
H2N
NH2
H2N
NH2
EDA
Me NH HN Me
DMEDA
Propane-1,3-diamine
Ph
Ph
N
N
Me
N
N
N
N
Me
Bathophen
Conv.b (%)
Phen
Entry Ligand (mol%)
Neo
Base (equiv)
t-AmOK (3)
t-AmOK (3)
t-AmOK (3)
t-AmOK (3)
t-AmOK (3)
t-AmOK (3)
t-AmOK (3)
t-AmOK (3)
t-AmOK (3)
t-AmOK (3)
t-AmOK (3)
t-AmOK (3)
t-AmOK (3)
t-AmOK (3)
t-AmOK (2)
Yieldb (%)
1
none
<5
0
0
2
TMEDA (20)
DMEDA (20)
EDA (20)
0
3
100
100
8
90
84(80)c
4
5
NH2(CH2)3NH2 (20)
CH3(CH2)3NH2(20)
L-proline (20)
HO(CH2)2OH (20)
n-BuOH (40)
<5
6
<5
86
90
68
<5
<5
9
0
7
72
8
77
9
50
10
11
12
13
14
15
MeO(CH2)2OMe (20)
Bipy (20)
0
0
Phen (20)
6
Neo (20)
100
100
100
77
79(74)c
Bathophen (20)
DMEDA (20)
80
aStandard reactions conditions: 1a (0.5 mmol), t-AmOK (3.0 equiv), benzene (4.0 mL), 80 oC, 24
h, N2.
bCalibrated GC yields were reported using hexadecane as the internal standard.
cYields in brackets were isolated yields.
With optimal conditions available, the substrate scope of direct C-H arylation of
benzene was investigated (Scheme 3). In general, the yields of direct arylation of
5

ACCEPTED MANUSCRIPT
benzene with electron-rich or electron-deficient aryl iodides were good to excellent
under DMEDA catalysis. 4-iodoanisole (1a), iodobenzene (1b) and 4-iodotoluene (1c)
produced corresponding arylated products (3a, 3b and 3c) in 84%, 75% and 76%
yields, respectively. Ortho-substituted aryl iodides, such as 2-iodotoluene (1e),
o
2-iodoanisole (1f) and 1-iodo-2,4-dimethoxybenzene (3l) were also efficient at 80 C
and afforded the corresponding aromatic C-H arylated products (3e, 3f and 3l) in
moderate yields (54%, 60% and 63%), respectively. Notably, 4-FC6H4-I (1g),
3-FC6H4-I (1h) and 2-FC6H4-I (1i) all reacted with benzene smoothly and generated
the desired arylated products (3g, 3h and 3i) in 77%, 64% and 70% yields,
respectively. 4-iodobiphenyl (1j) could transformed into 1,4-diphenylbenzene (3j) in
76% yield. And 1-iodonaphthalene (1k) was also suitable with a yield of 64% targeted
arylation product 3k. No coupling reaction occurred when 4-bromoanisole or
o
4-chloroanisole were examined at 80 C after 24 h. In the presence of cheap
1,2-diamine ligand EDA (20 mol%), 4-iodoanisole (1a), iodobenzene (1b),
4-iodotoluene (1c), 3-iodotoluene (1d), 2-iodotoluene (1e) and 2-iodoanisole (1f)
could also produced corresponding arylated products (3a-3f) in 52-80% yields,
respectively. When cheap ethane-1,2-diol (HOCH2CH2OH) was used as ligand, aryl
iodides (1a-1f) could afford similar outcomes (3a-3f, 50-75%) with diamines
(DEMDA or EDA). Moreover, changing to Bathophen ligand (20 mol%), the
reactions of selected aryl iodides (1a-1f) with benzene (2a) provided the similar yields
(3a-3f, 52-74%) with DEMDA, EDA or ethane-1,2-diol ligands. In addition, other
unactivated arenes were also examined using bathophen as ligand. Toluene (2b)
6

ACCEPTED MANUSCRIPT
o
reacted with 4-iodobenzene (1a) smoothly at 110 C and produced the direct C-H
arylation product (3ab) in 42% yield. When p-xylene (2c) was tested, 43% yield of
direct C-H arylation product 3ac was isolated.
Method A, B, C or D
X
H
+
80 oC, 24 h, N2
R
R
1
2a
3
a Method A
: DMEDA (20 mol%)/t-AmOK (3 equiv)
b Method B: EDA (20 mol%)/t-AmOK (3 equiv)
c Method C: HO(CH2)2OH (20 mol%)/t-AmOK (3 equiv)
d Method D
: Bathophen (20 mol%)/t-AmOK (3 equiv)
MeO
Me
a
a
a
3a
, X = I, 84%
3b
3c
, X = I, 76%
, X = I, 75%
80%b
75%c
74%d
74%b
71%c
70%d
74%b
70%c
71%d
Me
3d
Me
OMe
a
a
a
3e
3f
, X = I, 72%
, X = I, 54%
52%b
, X = I, 60%
58%b
71%b
70%c
68%d
50%c
50%d
55%c
52%d
F
F
F
3g, X = I, 77%a
3h, X = I, 64%a
3i, X = I, 70%a
Ph
MeO
OMe
3j, X = I, 76%a
3k, X = I, 64%a
Me
3l, X = I, 63%a
Me
MeO
Me
MeO
3ab, X = I,
42% (o/ m/ p = 3.2/1.3/1.0)d
d
3ac,
X = I, 43%
Scheme 3. t-AmOK-mediated radical cross-coupling in the presence of different ligands.
Realizing that the above ligands (DMEDA, EDA, HOCH2CH2OH and Bathophen)
7

ACCEPTED MANUSCRIPT
showed highly efficiency to promote the cross-coupling between unactivated benzene
o
and aryl iodides at such mild reaction temperature (80 C), we began to consider
whether different type of ligands could effect the chemoselectivity in the reactions of
haloiodobenzenes, which could take place mono-substitution or disubstitution.4e, 12 We
next examined the chemoselectivity in cross-coupling of 4-chloroiodobenzene (1m)
and benzene (2a) in the presence of t-AmOK (Table 2). In the presence of t-AmOK
(3.0 equiv) base, introducing EDA (20 mol%) or DMEDA (20 mol%) to the reactions,
complete conversions were observed and bis-arylation product 1,4-diphenylbenzene
(3j) were obtained as the main products (Table 2, entries 2-3, 61% and 62%), which
indicated that unactive C-Cl bond could become "activated" at such conditions.4c
Changing the ligand from diamines to ethylene glycol (20 mol%), bis-arylation
product 3j was produced as the main product (59%) as well (Table 2, entry 4). And
the use of L-proline (20 mol%) also led to bis-arylation product 3j as the main
product, albeit in a low yield (26%) (Table 2, entry 5). On the contrary, the use of
Phen (20 mol%) achieved chemoselective cross-coupling of 1m with benzene and
afforded 51% yield of 4-chlorobiphenyl (3m) as the main product under the same
reaction conditions (Table 2, entry 6). The use of other phenanthroline derivatives
(Neo or Bathophen) could also achieve chemoselective cross-coupling with 100%
conversions and afforded 3m as the main products (44% and 47%, respectively)
(Table 2, entries 8-9). And increasing the amount of Phen to 40 mol%, the
cross-coupling reaction afforded 62% yield of mono-arylation product 3m and only
9% yield of bis-arylation product 3j (Table 2, entry 7). Moreover, when the amount of
8

ACCEPTED MANUSCRIPT
DMEDA was decreased to 10 mol%, bis-arylation product 3j could also be formed in
65% yield as the main product (Table 2, entry 10). And reduced amount of Phen (10
mol%) could not promote such cross-coupling reaction (Table 2, entry 11). The above
observations suggested that the amount of ligand employed did not effect the
chemoselectivity (mono-arylation or bis-arylation) (Table 2, entries 3, 10 vs entries
6-7) once the arylations take place smoothly.
Table 2. Direct C-H arylation of benzene with 4-chloro-iodobenzenea
Ph
Ph
Ph
I
Ligand
t-AmOK (3 equiv)
+
+
80 oC, 24 h
Ph-H
Cl
Ph
3j
Cl
1m
3b
3m
Yield b(%)
Entry Ligand (mol%)
Conv.b (%)
3b
3m
0
3j
1
none
13
<5
15
11
24
8
0
2
EDA (20)
DMEDA (20)
100
100
0
61
62
59
26
23
9
3
2
4
HO(CH2)2OH (20)
L-proline (20)
Phen (20)
100
61
7
5
8
6
100
100
100
100
100
30
10
8
51
62
44
47
0
7
Phen (40)
8
Neo (20)
7
32
25
65
0
9
Bathophen (20)
DMEDA (10)
Phen (10)
9
10
11
9
14
0
aStandard reactions conditions: 1m (0.5 mmol), t-AmOK (1.5 mmol), benzene (4.0 mL), 80 oC,
24 h, N2.
bCalibrated GC yields were reported using hexadecane as the internal standard.
Based on the above results, we focused on the reactivity and chemoselectivity of
aryl iodides bearing halo substituent (Cl, Br and I) with phen or DMEDA as ligand
(Table 3). Using Phen (40 mol%) as ligand, 4-chloroiodobenzene (1m),
9

ACCEPTED MANUSCRIPT
3-chloroiodobenzene (1n) and 2-chloroiodobenzene (1o) could efficiently react with
benzene and afforded the corresponding mono-arylated products 4-chlorobiphenyl
(3m), 3-chlorobiphenyl (3n) and 2-chlorobiphenyl (3o) in 56%, 52% and 40% yields,
respectively (Table 3, entries 1, 3, 5). When DMEDA ligand was introduced,
4-chloroiodobenzene (1m) produced bis-arylated product 3j in 60% yield (Table 3,
entry 2). Due to steric hindrance, 2-chloroiodobenzene (1o) only afforded the
corresponding bis-arylated product o-terphenyl (4o) in 28% yield (Table 3, entry 6).
Moving to other dihalide substrates, 4-bromoiodobenzene (1p) and
3-bromoiodobenzene (1q) readily afforded the desired aryl-iodine bond arylated
products 4-bromobiphenyl (3p) and 3-bromobiphenyl (3q) in 40% and 65% yields,
respectively (Table 3, entries 7, 9). The above results indicated that Phen was effective
to distinguish C-I bond and C-Br (or C-Cl) bond, which resulted halogenated biaryl
products could be further functionalized on the aromatic ring. And the use of DMEDA
ligand led to disubstitution of 1p and 1q and produced bis-arylation products 3j and
4n in 39% and 44% yields, respectively (Table 3, entries 8, 10). Moreover, direct C-H
arylation of benzene with 1,4-diiodobenzene (1r) in the presence of Phen or DMEDA
ligand both provided the bis-arylated product 1,4-diphenylbenzene (3j) in 48% and
53% yields, respectively (Table 3, entries 11-12).
We proposed that such direct arylation of unactivated benzene go through radical
pathway, which was similar to previous t-BuOK/ligand systems4-5. To confirm our
hypothesis, radical inhibitor TEMPO (2,2,6,6-tetramethyl-1-piperidinoxyl) was
subjected to t-AmOK/DMEDA or t-AmOK/Bathophen reaction systems, both of the
10

ACCEPTED MANUSCRIPT
coupling reactions were completely blocked by 1.0 equiv of TEMPO (Scheme 4).
These results demonstrated that this biaryl coupling involves radical reaction
mechanism.
Table 3. Direct C-H arylation of benzene with haloiodobenzenea.
Ph
4
I
Ph
Ligand
t-AmOK
+ Ph
X
X
o
Ph-H
80 C,
1
3
Entry Haloiodobenzene (1) Ligand
Product
Yieldb (%)
1
4-ClC6H4-I (1m)
4-ClC6H4-I (1m)
3-ClC6H4-I (1n)
3-ClC6H4-I (1n)
2-ClC6H4-I (1o)
2-ClC6H4-I (1o)
4-BrC6H4-I (1p)
4-BrC6H4-I (1p)
3-BrC6H4-I (1q)
3-BrC6H4-I (1q)
4-IC6H4-I (1r)
Phen
4-ClC6H4-Ph (3m)
4-PhC6H4-Ph (3j)
3-ClC6H4-Ph (3n)
3-PhC6H4-Ph (4n)
2-ClC6H4-Ph (3o)
2-PhC6H4-Ph (4o)
4-BrC6H4-Ph (3p)
4-PhC6H4-Ph (3j)
3-BrC6H4-Ph (3q)
3-PhC6H4-Ph (4n)
4-PhC6H4-Ph (3j)
4-PhC6H4-Ph (3j)
56
60
52
35c
40
28d
40
39
65
44
48
53
2
DMEDA
Phen
3
4
DMEDA
Phen
5
6
DMEDA
Phen
7
8
DMEDA
Phen
9
10
11
12
DMEDA
Phen
4-IC6H4-I (1r)
DMEDA
aStandard reactions conditions: 1 (0.5 mmol), t-AmOK (3.0 equiv), Phen (40 mol%) or
DMEDA (20 mol%), benzene (4.0 mL), 80 oC, 24 h, N2.
bIsolated yields.
c3n was isolated in 28% yield.
dBiphenyl was isolated in 22% yield.
Ligand (20 mol%)
t-AmOK (3 equiv)
80 oC, 24 h, N2
MeO
I + H
MeO
1a
2a
3a
DMEDA
Bathophen
DMEDA/
90%
79%
0%
TEMPO
(1.0 equiv)
Bathophen/TEMPO (1.0 equiv) 0%
11

ACCEPTED MANUSCRIPT
Scheme 4. Radical-trapping experiments.
Considering unactivated C-Cl bond in 4-chloroiodobenzene (1m) became
o
"activated" at mild temperature (80 C) in the presence of simple ligands (DMEDA,
EDA, HO(CH2)2OH, etc.) and took place direct arylation with benzene to produce
bis-arylated products (Table 2), we selected 4-Cl-biphenyl (3m) as the substrate to
test the reactivity of C-Cl bond under the same reaction conditions (Scheme 5).
However, 3m could not efficiently react with benzene under a catalytic amount of
DMEDA or EDA at 80oC. Moreover, introducing a catalytic amount of iodobenzene
(Ph-I, 20 mol%) to initiate the radical chain reaction, 4-Cl-biphenyl (3m) still did not
take place direct arylation with benzene. The above observations suggested that the
reaction process involves biaryl radical anion intermediates.13
Ph-H
Ph-H
Cl
I
Cl
Ph
Ph
Ph
Step 1
Step 2
1m
1q
3j
mono-arylation
bis-arylation
Ligand (20 mol%)
t-AmOK (3.0 equiv)
80 oC, 24 h, N2
Cl
Ph-H
1q
3j
DMEDA,
EDA,
<5%
<5%
(20 mol%), <5%
Ph-I
DMEDA/
Scheme 5. Control experiments.
Thus, we propose that this aromatic C-H arylation also go through base-promoted
homolytic aromatic substitution (BHAS) (Scheme 6).4d An aryl iodides radical anion
A is generated from Ar-I 1 though single electron transfer (SET) process in the
presence of t-AmOK/ligand14 and converted into an aryl radical B upon
12

ACCEPTED MANUSCRIPT
dehalogenation. B add to benzene, giving cyclohexadienyl radical C. After a
deprotonation with the assistance of strong base t-AmOK, biaryl radical anion D is
generated. Then a radical chain transfer occurs between D and Ar-I 1, resulting in the
formation of direct C-H arylation product 3 and the regeneration of radical anion A.
Ar
H
Base/Ligand
Ar I
Ar-I
-
Ar
B
SET
- I
1
A
C
Ar
Ar
3
Ar
H
Ar-I
Base
Ar-I
+
ET
C
A
biaryl radical
anion (D)
X
X
Ph
ETinter
Ar I
ETintra
X
-
-
Ph
D
Ph
3
Ph
Ph
4
E
Scheme 6. Possible mechanism of t-AmOK-mediated radical coupling.
When dihalides substrates (1m-q) were introduced, first-formed biaryl radical
anion D can occur intramolecular or intermolecular electron transfer (ET) (Scheme 6).
When phen or its derivatives (Neo and Bathophen) was used as ligand, it is
remarkable to note that biaryl radical anion D can occur intermolecular ET faster than
intramolecular ET, which results the chemoselective mono-arylation products as the
main products.4d When other type of ligands (DMEDA, EDA, ethylene glycol, etc.)
were used, the intramolecular ET of biaryl radical anion D was faster, then the
precursor haloiodobenzene (1) was railroaded directly to the bis-arylation products.4
13

ACCEPTED MANUSCRIPT
Although the mechanisms of initiation of such radical coupling in the presence of
phen and t-BuOK have been suggested by several authors,14 the origin of
chemoselectivity in the reactions of haloiodobenzenes and benzene remained
unknown. Base on above results, we speculated that phen or its derivatives not only
initiate this radical coupling but also have effect on electron transfer process of biaryl
radical anion D. To test our hypothesis, several control experiments were conducted
(Scheme 7). The use of DMEDA ligand (20 mol%) led to bis-arylation (62%) when
1m was used. And 10 mol% of Phen ligand could not initiate such radical coupling.
To our surprise, introducing 10 mol% of Phen into DMEDA-catalysis system could
afford mono-arylation product 3m as the main product (50%). These important results
can unambiguously support our hypothesis that Phen-type ligands affect the electron
transfer process of biaryl radical anion D.
Ligand
t-AmOK (3.0 equiv)
80 oC, 24 h, N2
Cl
I
Ph Ph
Ph
Cl
+
Ph-H
1m
3m
3j
DMEDA (20 mol%)
Phen (10 mol%)
2%
0%
62%
0%
DMEDA (20 mol%)
/Phen (10 mol%)
50%
11%
Scheme 7. Control experiments.
3. Conclusion
In conclusion, we have disclosed a novel transition-metal-free direct C-H arylation
of unactivated arenes with aryl iodides to prepare biaryl compounds in good to
o
excellent yields in the presence of t-AmOK base at 80 C. And ligands play crucial
14

ACCEPTED MANUSCRIPT
role to catalyse such homolytic aromatic substitution reactions and control the
chemoselectivity in direct C-H arylation of benzene with haloiodobenzenes. And phen
and its derivatives not only initiate this radical coupling but also have effect on
electron transfer process of biaryl radical anion intermediates, which can result
chemoselective cross-coupling of haloiodobenzenes with benzene and generate the
mono-arylation products.
4. Experimental Section
4.1. General information
Aryl halides were purchased from commercial sources and used without prior
treatments. Potassium tert-pentyloxide (t-AmOK), 25% w/w in toluene, purchased
from Alfa Aesar, used after removing the toluene under reduced pressure. Benzene
was dried and distilled from sodium/benzophenone immediately prior to use under a
nitrogen atmosphere. All other reagents and solvents were used as it from commercial
sources. Unless noted below, all other compounds have been reported in the literatures
or are commercially available. Thin layer chromatography (TLC) employed glass 0.25
mm silica gel plates. Flash chromatography columns were packed with 200-300 mesh
1
13
silica gel in hexane. H and C NMR data were recorded in CDCl3 solutions with
NMR spectrometers (300 MHz) using tetramethylsilane (TMS) as the internal
standard. Gas chromatography (GC) was performed using a Gas Chromatography
fitted with a flame ionization detector (FID).
4.2. General procedure for direct C-H arylation of benzene with 4-iodoanisole:
A Schlenk tube was charged with t-AmOK (1.5 mmol) under an atmosphere of
15

ACCEPTED MANUSCRIPT
nitrogen, and the solvent (toluene) was removed under reduced pressure. Then
4-iodoanisole (117 mg, 0.5 mmol), ligand and benzene (4.0 mL) was added. The
resulting mixture was stirred at 80 oC for 24 h. After cooling to room temperature, the
reaction mixture was quenched with water and extracted with ethyl acetate (10 mL×3).
The organic layers were combined, dried over Na2SO4 and concentrated under
reduced pressure, and then purified by silica gel chromatograph (petroleum ether) to
yield the desired product as a white solid.
1
4.2.1. 4-methoxybiphenyl (3a)5d: H NMR (300 MHz, CDCl3): δ 7.58-7.53 (m, 4H),
7.43 (t, J = 7.5 Hz, 2H), 7.31 (t, J = 8.7 Hz, 1H), 6.99 (d, J = 6.6 Hz, 2H), 3.87 (s, 3H);
13C NMR (75 MHz, CDCl3): δ 159.2, 140.9, 133.8, 128.7, 128.2, 126.8, 126.7, 114.2,
55.4.
4.2.2. biphenyl (3b)5d: 1H NMR (300 MHz, CDCl3): δ 7.63 (d, J = 7.2Hz, 4H), 7.48 (t,
J = 7.4 Hz, 4H), 7.33 (t, J = 7.4 Hz, 2H); 13C NMR (75 MHz, CDCl3): δ 141.2, 128.8,
127.3, 127.2.
1
4.2.3. 4-methylbiphenyl (3c)5d: H NMR (300 MHz, CDCl3): δ 7.66 (d, J = 7.2 Hz,
2H), 7.48 (d, J = 6.3 Hz, 2H), 7.49 (t, J = 7.4 Hz, 2H), 7.38 (t, J = 7.4 Hz, 1H), 7.32
(d, J = 7.8 Hz, 2H), 2.46 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 141.2, 138.4, 137.1,
129.5, 128.8, 127.1, 127.0, 127.0, 21.2.
1
4.2.4. 3-methylbiphenyl (3d)5d: H NMR (300 MHz, CDCl3): δ 7.65 (d, J = 8.1 Hz,
13
2H), 7.52-7.45 (m, 6H), 7.25 (d, J = 8.7 Hz, 1H), 2.49 (s, 3H); C NMR (75 MHz,
CDCl3): δ 141.4, 141.3, 138.4, 128.7, 128.7, 128.0, 128.0, 127.2, 127.2, 124.3, 21.6.
1
4.2.5. 2-methylbiphenyl (3e)5d: H NMR (300 MHz, CDCl3): δ 7.47-7.27 (m, 9H),
16

ACCEPTED MANUSCRIPT
2.31 (s, 3H); 13C NMR (75 MHz, CDCl3): δ 142.1, 135.4, 130.4, 129.9, 129.3, 128.8,
128.1, 127.3, 126.8, 125.9, 20.5.
1
4.2.6. 2-methoxybiphenyl (3f)5d: H NMR (300 MHz, CDCl3): δ 7.58 (d, J = 8.7 Hz,
2H), 7.45 (t, J = 8.0 Hz, 2H), 7.39-7.33 (m, 3H), 7.10-7.00 (m, 2H), 3.84 (s, 3H); 13C
NMR (75 MHz, CDCl3): δ 155.4, 137.5, 129.8, 129.6, 128.5, 127.6, 126.9, 125.9,
119.8, 110.1, 54.5.
4.2.7. 4-fluorobiphenyl (3g)5d: 1H NMR (300 MHz, CDCl3): δ 7.63-7.56 (m, 4H), 7.51
13
(t, J = 8.4 Hz, 2H), 7.38 (t, J = 8.6 Hz, 1H), 7.16 (t, J = 7.8 Hz, 2H); C NMR
(75MHz, CDCl3): δ 162.4 (d, J = 244.5 Hz), 140.2, 137.2, 128.8, 128.7 (d, J = 7.7 Hz),
127.3, 127.0, 115.6 (d, J = 21.0 Hz).
1
4.2.8. 3-fluorobiphenyl (3h)5d: H NMR (300 MHz, CDCl3): δ 7.61 (d, J = 6.6 Hz,
13
2H), 7.59-7.38 (m, 5H), 7.32 (d, J = 7.5 Hz, 1H), 7.07 (t, J = 7.5 Hz, 1H); C NMR
(75MHz, CDCl3): δ 163.2 (d, J = 183.0 Hz), 143.5 (d, J = 6.0 Hz), 139.9, 130.2 (d, J
= 6.0 Hz), 128.9, 127.9, 127.1, 122.8 (d, J = 2.3 Hz), 114.1 (d, J = 15.0 Hz), 113.9.
1
4.2.9. 2-fluorobiphenyl (3i)5d: H NMR (300 MHz, CDCl3): δ 7.63-7.61 (m, 2H),
13
7.53-7.50 (m, 3H), 7.49-7.19 (m, 4H); C NMR (75 MHz, CDCl3): δ 159.8 (d, J =
184.5 Hz), 135.9, 130.8 (d, J = 2.3 Hz), 129.1 (d, J = 5.3 Hz), 129.1, 129.0, 129.0,
128.5, 127.7, 124.4 (d, J = 3.0 Hz), 116.1 (d, J = 17.3 Hz).
4.2.10. 1,4-diphenylbenzene (3j)7b: 1H NMR (300 MHz, CDCl3): δ 7.71-7.66 (m, 8H),
13
7.51-7.48 (m, 4H), 7.40 (t, J = 6.0 Hz, 2H); C NMR (75 MHz, CDCl3): δ 140.7,
140.1, 128.8, 127.5, 127.4, 127.1.
1
4.2.11. 1-phenylnaphthalene (3k)2c: H NMR (300 MHz, CDCl3): δ 7.96 (d, J = 6.3
17

ACCEPTED MANUSCRIPT
13
Hz, 2H), 7.92 (d, J = 6.3 Hz, 1H), 7.60-7.46 (m, 9H); C NMR (75 MHz, CDCl3): δ
140.8, 140.3, 133.8, 131.7, 130.1, 128.3, 127.7, 127.3, 127.0, 126.1, 125.8, 125.4.
1
4.2.12. 2,4-dimethoxybiphenyl (3l)5g: H NMR (300 MHz, CDCl3) δ 7.41 (d, J = 8.4
Hz, 2H), 7.30 (t, J = 7.5 Hz, 2H), 7.22-7.12 (m, 2H), 6.50-6.43 (m, 2H), 3.75 (s, 3H),
13
3.70 (s, 3H); C NMR (75 MHz, CDCl3) δ 160.3, 157.5, 138.4, 131.3, 129.5, 128.0,
126.5, 123.6, 104.6, 99.0, 55.6, 55.4.
1
1
4.2.13. 3ab4b: The regioisomers were determined by H NMR. H NMR (400 MHz,
CDCl3): δ 7.56-7.50 (m, 3.5H), 7.36-7.21 (m, 12.2H), 6.97-6.94 (m, 4.1H), 3.84 (s,
3.0H), 3.84 (s, 1.2H), 3.84 (s, 1.0H), 2.40 (s, 1.3H), 2.38 (s, 0.8H), 2.28 (s, 3.0H).
1
4.2.14. 4’-methoxy-2,5-dimethylbiphenyl (3ad)4b: H NMR (400 MHz, CDCl3): δ
7.30-7.28 (m, 3H), 7.19 (d, J = 8.0 Hz, 1H), 7.00-6.98 (m, 2H), 3.90 (s, 3H), 2.39 (s,
13
3H), 2.28 (s, 3H); C NMR (100 MHz, CDCl3): δ 158.7, 141.6, 135.4, 134.7, 132.6,
130.9, 130.5, 129.3, 127.9, 113.7, 55.5, 21.2, 20.3.
1
4.2.15. 4-chlorobiphenyl (3m)15: H NMR (300 MHz, CDCl3): δ 7.60-7.53 (m, 4H),
13
7.50-7.37 (m, 5H); C NMR (75 MHz, CDCl3): δ 140.0, 139.7, 133.4, 128.9, 128.9,
128.4, 127.6, 127.0.
1
4.2.16. 3-chlorobiphenyl (3n)15: H NMR (300 MHz, CDCl3): δ 7.61-7.58 (m, 3H),
13
7.51-7.46 (m, 3H), 7.42-7.33 (m, 3H); C NMR (75 MHz, CDCl3): δ 143.1, 139.8,
134.7, 130.0, 129.0, 127.9, 127.3, 127.3, 127.2, 125.3.
1
4.2.17. 2-chlorobiphenyl (3o)15: H NMR (300 MHz, CDCl3): δ 7.50 (d, J = 6.6 Hz,
13
1H), 7.47-7.28 (m, 8H); C NMR (75 MHz, CDCl3): δ 140.5, 139.4, 132.5, 131.4,
130.0, 129.5, 128.8, 128.6, 128.1, 127.2.
18

ACCEPTED MANUSCRIPT
1
4.2.18. 4-bromobiphenyl (3p)16: H NMR (300 MHz, CDCl3): δ 7.62-7.57 (m, 4H),
13
7.51-7.46 (m, 4H), 7.40 (t, J = 7.5 Hz, 1H); C NMR (75 MHz, CDCl3): δ 140.1,
140.0, 131.9, 128.9, 128.8, 127.7, 127.0, 121.6.
1
4.2.19. 3-bromobiphenyl (3q)17: H NMR (300 MHz, CDCl3): δ 7.82 (s, 1H),
13
7.63-7.49 (m, 6H), 7.44 (t, J = 5.4 Hz, 1H), 7.36 (t, J = 5.8 Hz, 1H); C NMR (75
MHz, CDCl3): δ 143.4, 139.8, 130.4, 130.3, 130.3, 129.0, 128.0, 127.2, 125.8, 123.0.
1
4.2.20. 1,3-diphenylbenzene (4n)7b: H NMR (300 MHz, CDCl3): δ 7.94 (s, 1H),
13
7.78-7.56 (m, 11H), 7.48 (t, J = 5.6 Hz, 2H); C NMR (75 MHz, CDCl3): δ 141.9,
141.3, 129.3, 128.9, 127.5, 127.4, 126.3, 126.2.
4.2.21. 1,2-diphenylbenzene (4o)7b: 1H NMR (300 MHz, CDCl3): δ 7.50-7.45 (m, 4H),
13
7.28-7.23 (m, 6H), 7.20-7.18 (m, 4H); C NMR (75 MHz, CDCl3): δ 141.5, 140.6,
130.6, 129.9, 127.9, 127.5, 126.5.
Acknowledgements
This work was supported by the National Natural Science Foundation of China (No.
21102036), Science and Technology Research Project of Department of Education in
Henan Province (No. 14B550006) and Project of Henan University of Technology
Excellent Young Teachers.
Supporting Information
Copies of 1H and 13C NMR spectra of products can be found in supplementary data.
References
1. (a) Alberico, D.; Scott, M. E.; Lautens, M. Chem. Rev. 2007, 107, 174. (b) Daugulis,
O.; Do, H. Q.; Shabashov, D. Acc. Chem. Res. 2009, 42, 1074. (c) McGlacken, G. P.;
Bateman, L. M. Chem. Soc. Rev. 2009, 38, 2447. (d) Lei, A.; Liu, W.; Liu, C.; Chen,
19

ACCEPTED MANUSCRIPT
M. Dalton Trans. 2010, 39, 10352. (e) Arockiam, P. B.; Bruneau, C.; Dixneuf, P. H.
Chem. Rev. 2012, 112, 5879.
2. For selected examples on transition-metal catalyzed biaryl formation in the
presence of t-BuOK base, see: (a) Fujita, K.; Nonogawa, M.; Yamaguchi, R. Chem.
Commun. 2004, 1926. (b) Kobayashi, O.; Uraguchi, D.; Yamakawa, T. Org. Lett. 2009,
11, 2679. (c) Vallee, F.; Mousseau, J. J.; Charette, A. B. J. Am. Chem. Soc. 2010, 132,
1514. (d) Liu, W.; Cao, H.; Lei, A. Angew. Chem., Int. Ed. 2010, 49, 2004. (e) Li, H.;
Sun, C.-L.; Yu, M.; Yu, D.-G.; Li, B.-J.; Shi, Z.-J. Chem.–Eur. J. 2011, 17, 3593. (f)
Xie, G; Li, T.; Qu, X.; Mao, J. J. Mol. Catal. A: Chem. 2011, 340, 48.
3. Sun, C.-L.; Shi, Z.-J. Chem. Rev. 2014, 114, 9219.
4. (a) Yanagisawa, S.; Ueda, K.; Taniguchi, T.; Itami, K. Org. Lett. 2008, 10, 4673. (b)
Sun, C.-L.; Li, H.; Yu, D.-G.; Yu, M.; Zhou, X.; Lu, X.-Y.; Huang, K.; Zheng, S.-F.; Li,
B.-J.; Shi, Z.-J. Nat. Chem. 2010, 2, 1044. (c) Liu, W.; Cao, H.; Zhang, H.; Zhang, H.;
Chung, K. H.; He, C.; Wang, H. B.; Kwong, F. Y.; Lei, A. J. Am. Chem. Soc. 2010,
132, 16737. (d) Shirakawa, E.; Itoh, K.; Higashino, T.; Hayashi, T. J. Am. Chem. Soc.
2010, 132, 15537. (e) Studer, A.; Curran, D. P. Angew. Chem., Int. Ed. 2011, 50, 5018.
5. Literatures for other ligands or initiators on this base-promoted direct C-H arylation
of unactivated arenes: (a) Qiu, Y. T.; Liu, Y. H.; Yang, K.; Hong, W. K.; Li, Z.; Wang,
Z. Y.; Yao, Z. Y.; Jiang, S. Org. Lett. 2011, 13, 3556. (b) Yong, G.-P.; She, W.-L.;
Zhang, Y.-M.; Li, Y.-Z. Chem. Commun. 2011, 47, 11766. (c) Chen, W.-C.; Hsu, Y.-C.;
Shih, W.-C.; Lee, C.-Y.; Chuang, W.-H.; Tsai, Y.-F.; Chen, P. P.-Y.; Ong, T.-G. Chem.
Commun. 2012, 48, 6702. (d) Tanimoro, K.; Ueno, M.; Takeda, K.; Kirihata, M.;
Tanimori, S. J. Org. Chem. 2012, 77, 7844. (e) Liu, H.; Yin, B.; Gao, Z.; Li, Y.; Jiang,
H. Chem. Commun. 2012, 48, 2033. (f) Zhao, H.; Shen, J.; Guo, J.; Ye, R.; Zeng, H.
Chem. Commun. 2013, 49, 2323. (g) Liu, W.; Tian, F.; Wang, X.; Yu, H.; Bi, Y. Chem.
20

ACCEPTED MANUSCRIPT
Commun. 2013, 49, 2983. (h) Dewanji, A.; Murarka, S.; Curran, D. P.; Studer, A. Org.
Lett. 2013, 15, 6102. (i) Li, B.; Qin, X.; You, J.; Cong, X.; Lan, J. Org. Biomol. Chem.
2013, 11, 1290. (j) Sharma, S.; Kumar, M.; Kumar, V.; Kumar, N. Tetrahedron Lett.
2013, 54, 4868. (k) A, S.; Liu, X.; Li, H.; He, C.; Mu, Y. Asian J. Org. Chem. 2013, 2,
857. (l) Zhou, S.; Anderson, G. M.; Mondal, B.; Doni, E.; Ironmonger, V.; Kranz, M.;
Tuttle, T.; Murphy, J. A. Chem. Sci. 2014, 5, 476. (m) Ghosh, D.; Lee, J.-Y.; Liu, C.-Y.;
Chiang, Y.-H.; Lee, H. M. Adv. Syn. Cat. 2014, 356, 406. (n) Zhu, Y.-W.; Yi, W.-B.;
Qian, J.-L.; Cai, C. ChemCatChem 2014, 6, 733. (o) Bhakuni, B. S.; Yadav, A.;
Kumar, S.; Kumar, S. New J. Chem. 2014, 38, 827. (p) Wu, Y.; Choy, P. Y.; Kwong, F.
Y. Org. Biomol. Chem. 2014, 12, 6820. (q) Liu, W.; Xu, L.; Bi, Y. RSC Adv. 2014, 4,
44943. (r) Song, Q.; Zhang, D.; Zhu, Q.; Xu, Y. Org. Lett. 2014, 16, 5272.
6. For selected examples on t-BuOK promoted other type of radical coupling
reactions, see: (a) Roman, D. S.; Takahashi, Y.; Charette, A. B. Org. Lett. 2011, 13,
3242. (b) Sun, C.-L.; Gu, Y.-F.; Huang, W.-P.; Shi, Z. J. Chem. Commun. 2011, 47,
9813. (c) Rueping, M.; Leiendecker, M.; Das, A.; Poisson, T.; Bui, L. Chem. Commun,
2011, 47, 10629. (d) Bhakuni, B. S.; Kumar, A.; Balkrishna, S. J.; Sheikh, J. A.; Konar,
S.; Kumar, S. Org. Lett. 2012, 14, 2838. (e) De, S.; Ghosh, S.; Bhunia, S.; Sheikh, J.
A.; Bisai, A. Org. Lett. 2012, 14, 4466. (f) Wu, Y.; Wong, S. M.; Mao, F.; Chan, T. L.;
Kwong, F. Y. Org. Lett. 2012, 14, 5306. (g) Masters, K.-S.; Bräse, S. Angew. Chem.,
Int. Ed. 2013, 52, 866. (h) De, S.; Mishra, S.; Kakde, B. N.; Dey, D.; Bisai, A. J. Org.
Chem. 2013, 78, 7823. (i) Shirakawa, E.; Zhang, X.; Hayashi, T. Angew. Chem., Int.
Ed. 2011, 50, 4671. (j) Sun, C.-L.; Gu, Y.-F.; Wang, B.; Shi, Z.-J. Chem.–Eur. J. 2011,
17, 10844.
21

ACCEPTED MANUSCRIPT
7. (a) Buden, M. E.; Guastavino, J. F.; Rossi, R. A. Org. Lett., 2013, 15, 1174. (b)
Cheng, Y.; Gu, X.; Li, P. Org. Lett. 2013, 15, 2664.
8. For selected reviews, see: (a) Yanagisawa, S.; Itami, K. ChemCatChem 2011, 3, 827.
(b) Chan, T. L.; Wu, Y.; Choy, P. Y.; Kwong, F. Y. Chem.-Eur. J. 2013, 19, 15802. (c)
Mehta, V. P.; Punji, B. RSC Adv. 2013, 3, 11957.
9. For examples on organic synthesis using t-AmOK as base, see: (a) Viciu, M. S.;
Kissling, R. M.; Stevens, E. D.; Nolan, S. P. Org. Lett. 2002, 4, 2229. (b) Pelegrí, A.
S.; Elsegood, M. R. J.; McKee, V.; Weaver, G. W. Org. Lett. 2006, 8, 3049. (c)
Chartoire, A.; Boreux, A.; Martin, A. R.; Nolan, S. P. RSC Adv. 2013, 3, 3840.
10. Zhou, S.; Doni, E.; Anderson, G. M.; Kane, R. G.; MacDougall, S. W.; Ironmonger,
V. M.; Tuttle, T.; Murphy, J. A. J. Am. Chem. Soc. 2014, 136, 17818.
11. Bathophen showed no efficiency in the coupling of aryl iodides with benzene in
the presence of t-BuOK at 80oC was reported by Charette (see ref 2d, Table 4 in their
manuscript).
12. For selected examples on chemoselective radical reactions involving
haloiodoarenes as substrates, see: (a) Kawamoto, T.; Okada, T.; Curran, D. P.; Ryu, I.
Org. Lett. 2013, 15, 2144. (b) Kawamoto, T.; Sato, A.; Ryu, I. Org. Lett. 2014, 16,
2111.
13. Bunnett, J. F.; Creary, X. J. Org. Chem. 1974, 39, 3611.
14. For mechanism study on t-BuOK promoted radical biaryl coupling, see: (a) Zhou,
S.; Anderson, G. M.; Mondal, B.; Doni, E.; Ironmonger, V.; Kranz, M.; Tuttle, T.;
Murphy, J. A. Chem. Sci. 2014, 5, 476. (b) Cuthbertson, J.; Gray, V. J.; Wilden, J. D.
22

ACCEPTED MANUSCRIPT
Chem. Commun. 2014, 50, 2575. (c) Yi, H.; Jutand, A.; Lei, A. Chem. Commun. 2015,
51, 545.
15. Liu, W.; Cao, H.; Xin, J.; Jin, L.; Lei, A. Chem. Eur. J. 2011, 17, 3588.
16. Cella, R.; Cunha, R. L. O. R.; Reis, A. E. S.; Pimenta, D. C.; Klitzke, C. F.;
Stefani, H. A. J. Org. Chem. 2006, 71, 244.
17. Demir, A. S.; Reis, O.; Emrullahoglu, M. J. Org. Chem. 2003, 68, 578.
23

ACCEPTED MANUSCRIPT
Graphaical Abstract:
Ligand-controlled chemoselectivity in potassium tert-amylate-promoted
direct C-H arylation of unactivated benzene with aryl halides
Wei Liu,* Lige Xu
E-mail: liuwei307@hotmail.com
Ligand A:
Ligand B:
EDA, DMEDA,
HOCH2CH2OH,
L-proline, etc.
Phen, Neo,
Bathophen,
etc.
Ph
X
Ph
I
t-AmOK (3.0 equiv)
80 oC, Ph-H
t-AmOK (3.0 equiv)
o
Ph-H
80 C,
X
Ph
X
= Cl, Br
Direct C-H arylation of unactivated benzene with aryl halides under various simple
ligands (EDA, DMEDA, ethylene glycol, etc.) in the presence of potassium
tert-amylate base at mild temperature (80 oC) have been developed. This
transition-metal-free radical cross-coupling offers an efficient way to synthesize
various biaryls in good yields through base-promoted homolytic aromatic substitution.
And mechanistic investigations have provided insight into the chemoselectivity of
couplings between haloiodobenzenes and benzene and showed that phenanthroline
and its derivatives not only initiate these radical reactions like most of other ligands
(EDA, DMEDA, ethylene glycol, etc.), but also participate in the electron transfer
process of biaryl radical anion intermediates.
24

ACCEPTED MANUSCRIPT
Supporting Information
Ligand-controlled chemoselectivity in potassium tert-amylate-promoted
direct C-H arylation of unactivated benzene with aryl halides
Wei Liu,* Lige Xu
E-mail: liuwei307@hotmail.com
Table of Contents
1
Compounds NMR Spectrum
2-22
1

ACCEPTED MANUSCRIPT
4-methoxybiphenyl (3a)
2

ACCEPTED MANUSCRIPT
biphenyl (3b)
3

ACCEPTED MANUSCRIPT
4-methylbiphenyl (3c)
4

ACCEPTED MANUSCRIPT
3-methylbiphenyl (3d)
5