Transition-metal-free dehalogenation of aryl halides promoted by phenanthroline/potassium tert-butoxide

Article abstract of DOI:10.1016/j.tet.2017.01.002

Transition-metal-free dehalogenation of various aryl halides (iodides and bromides) can take place efficiently at 70–110?°C in the presence of a catalytic amount of 1, 10-phenanthroline and t-BuOK using THF or Dioxane as solvent. Control experiments indicated that radical transfer occurred between aryl radical and alkyl C[sbnd]H bond to generate alkyl radical.

Full text of DOI:10.1016/j.tet.2017.01.002

Accepted Manuscript
Transition-metal-free dehalogenation of aryl halides promoted by phenanthroline/
potassium tert-butoxide
Wei Liu, Fanyi Hou
PII:
S0040-4020(17)30002-9
10.1016/j.tet.2017.01.002
TET 28372
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 14 October 2016
Revised Date: 1 January 2017
Accepted Date: 3 January 2017
Please cite this article as: Liu W, Hou F, Transition-metal-free dehalogenation of aryl halides promoted
by phenanthroline/potassium tert-butoxide, Tetrahedron (2017), doi: 10.1016/j.tet.2017.01.002.
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
Transition-metal-free dehalogenation of aryl halides promoted by
phenanthroline/potassium tert-butoxide
Phen (0.2 eq.)/ t-BuOK (2 eq.)
X
H
o
R
THF or Dioxane, 70-110 C
R
X = I, Br
R = Me, OMe, Ph,
F, Cl, Br, CO Et, etc.
23 examples
up to 94% yield
2

ACCEPTED MANUSCRIPT
Transition-metal-free dehalogenation of aryl halides promoted
by phenanthroline/potassium tert-butoxide
Wei Liu* and Fanyi Hou
Lipid Chemistry, College of Food Science and Technology, Henan University of Technology, 100
Lianhua Street, Zhengzhou 450001, P. R. China
*Corresponding author.
E-mail address: liuwei307@hotmail.com (Wei Liu)
ABSTRACT: Transition-metal-free dehalogenation of various aryl halides (iodides
o
and bromides) can take place efficiently at 70-110 C in the presence of a catalytic
amount of 1, 10-phenanthroline and t-BuOK using THF or Dioxane as solvent.
Control experiments indicated that radical transfer occurred between aryl radical and
alkyl C-H bond to generate alkyl radical.
Keywords:
Dehalogenation; aryl halides; transition-metal-free; radical; alkoxy bases
1
. Introduction
Cross-coupling reactions catalyzed by various transition metals (eg. Pd, Rh, Ni, Cu,
Fe, Co, etc.) have become one of the most important topics in synthetic organic
1
chemistry during the past several decades. In recent years, the demand for green and
sustainable chemistry inspired organic chemists to develop transition-metal-free
2
version of reaction process in recent years.
In 2008, a t-BuOK promoted transition-metal-free cross-coupling between nitrogen
3
heterocycles and haloarenes under microwave irradiation has been firstly revealed. In
2
010, three research groups independently developed transition-metal-free
cross-coupling between unactivated arenes and aryl halides involving base-promoted
4
,5
homolytic aromatic substitution (HAS). In these processes, a catalytic amount of
1

ACCEPTED MANUSCRIPT
4
a,c
4b
nitrogen-containing bidentate ligands (eg. phenanthroline,
DMEDA ) could
efficiently promote the cross-coupling between aryl iodides/bromides with
unactivated arenes (eg. benzene) under t-butoxides (eg. t-BuOK) mediated conditions.
Since then, considerate attentions has been focused on developing new ligands or
6
catalysts toward this novel methodology. Meanwhile, this transition-metal-free
strategy has been successfully extended to other type of coupling reactions, such as
7
8
9
intramolecular cyclization , Heck-type coupling , carbonylation and so on.
Recently, great efforts have been devoted to develop new methods achieving the
1
0
11
dehalogenation of aromatic halides from the synthetic and environmental points of
view. Although numerous dehalogenation methods based on transition-metal-catalysis
1
2
13
14
15
(
Pd , Rh , Ni and Fe ) have been reported, example on transition-metal-free
version of dehalogenation of aryl halides is still rare up to now.
Owing to the synthetic importance of dehalogenation process and our continuous
6
g, q
interests on transition-metal-free radical cross-coupling reactions,
herein, we
report our results on this transition-metal-free dehalogenation of aryl halides
promoted by phenanthroline/potassium tert-butoxide (Scheme 1).
A. Previous work: Transition-metal-f ree direct arylation
Ar-H
Ligand/t-BuOK(Na)
X
Ar
Radical process
R
R
X = I, Br, etc.
B. Previous work: TM-catalyzed dehalogenation
TM
X
H
Reductant
R
R
X = I, Br, etc.
TMs = Pt, Pd, Rh, Ni, Fe, etc.
Reductants = H , NaBH , ROH, RMgX, RZnX, etc.
2
4
C. This work: Transition-metal-f ree dehalogenation
THF or Dioxane
Ligand/t-BuOK
X
H
Radical process
R
R
X = I, Br
Scheme 1. Previous TM-catalyzed dehalogenation and our work.
2
. Results and discussion
2

ACCEPTED MANUSCRIPT
We embarked on our research by testing the feasibility of the reaction of
4
-iodobiphenyl (1a) using dioxane as solvent (Table 1). In the presence of t-BuOK,
o
trace amount of dehalogenation product was observed at 100 C after 24 h (Table 1,
entry 1). Considering the role of ligands, two typical nitrogen-containing bidentate
ligands (DMEDA, phenanthroline) were tested for this transition-metal-free
dehalogenation reactions, and 0.2 equiv of phenanthroline (Phen) showed 100%
o
conversion of dehalogenation at 100 C (Table 1, entries 2-3). Decreasing the reaction
o
o
temperature from 100 C to 70 C led to lower yields (5-41%) (Table 1, entries 4-5).
Then other common alkyl C-H containing solvents were tested. To our surprise, the
combination of t-BuOK (4 equiv) and phen (0.2 equiv) could also produce 100%
conversion of dehalogenation using THF as solvent at a much lower temperature (70
o
C) (Table 1, entry 6). And further results showed that decreasing the amount of
t-BuOK from 4.0 equiv to 2.0 equiv would increase the yield slightly (Table 1, entries
6
-8). We next examined other common alkyl C-H solvents, such as diglyme,
o
cyclohexane, hexane, and dioxane under the same conditions (70 C), all of the
o
candicates exhibited less effciency than THF at 70 C (Table 1, entries 10-13).
Furthermore, other nitrogen-containing ligands were compared and phen was found to
be the most suitable ligand than 2,9-dimethyl-1,10-phenanthroline (Neo) and
2
,2'-bipyridine (Bipy) (Table 1, entries 14-15). It was worth noting that other weaker
4
c
bases, such as t-BuONa and KOH showed no effect on this transition-metal-free
o
dehalogenation reaction at 70 C (Table 1, entries 16-17). And control experiment
showed that reaction conducting for 12 h could afford only 81% conversion of 1a.
a
Table 1. Optimization of reaction conditions of dehalogenation.
3

ACCEPTED MANUSCRIPT
[
Cat.]/Base
I
H
Solvent, T, 24 h
1a
2a
o
entry [cat.] (eq.)/base (eq.)
None/t-BuOK (4.0)
solvent
temp. ( C) yield (%)b
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
Dioxane
100
100
100
70
<5
DMEDA (0.2)/t-BuOK (4.0) Dioxane
Phen (0.2)/t-BuOK (4.0) Dioxane
DMEDA (0.2)/t-BuOK (4.0) Dioxane
12
87 (100)
<5
Phen (0.2)/t-BuOK (4.0)
Phen (0.2)/t-BuOK (4.0)
Phen (0.2)/t-BuOK (3.0)
Phen (0.2)/t-BuOK (2.0)
Phen (0.2)/t-BuOK (1.0)
Phen (0.2)/t-BuOK (2.0)
Phen (0.2)/t-BuOK (2.0)
Phen (0.2)/t-BuOK (2.0)
Phen (0.2)/t-BuOK (2.0)
Neo(0.2)/t-BuOK (2.0)
Bipy (0.2)/t-BuOK (2.0)
Phen (0.2)/t-BuONa (2.0)
Phen (0.2)/KOH (2.0)
Dioxane
THF
70
41
70
92 (100)
THF
70
95 (100)
THF
70
96 (100)
THF
70
49
<5
32
0
0
1
2
3
4
5
6
7
Diglyme
70
Cyclohexane 70
Hexane
Dioxane
THF
70
70
70
70
70
70
43
91
<5
<5
0
THF
THF
THF
a
b
Standard reactions conditions: 1a (0.5 mmol), solvent (4.0 mL), 24 h, N2.
Calibrated GC yields were reported using hexadecane as the internal
standard; value in parentheses indicates the conversion of 1a.
With the optimal conditions (0.2 equiv of phen, 2.0 equiv of t-BuOK, THF as
o
solvent, 70 C) in hand, we investigated the dehalogenation of various aryl iodides
(Table 2). In general, electron-rich aryl iodides (1a-e) took place dehalogenation
reaction smoothly and afforded the corresponding dehalogenated products (2a-e) in
excellent yields (90-94%) (Table 2, entries 1-5). Sterically hindered aryl iodides, such
as
-iodo-2-methylbenzene were also suitable under the same reaction conditions and
afforded the corresponding dehalogenated products in good to excellent yields
85-90%), respectively (Table 2, entries 6-8). Moreover, electron-poor aryl iodides,
1-iodo-2,4-dimethoxybenzene
(1f),
1-iodo-2-methoxybenzene
and
1
(
such as ethyl 4-iodobenzoate (1i) could take place dehalogenation smoothly and
afforded the corresponding dehalogenated product (2i) in 73% yield (Table 2, entry
4

ACCEPTED MANUSCRIPT
9
).
Table 2. Transtion-metal-free dehalogenation of aryl iodides.
Phenanthroline (20 mol%)
t-BuOK (2.0 equiv)
I
H
o
THF, 70 C, 24 h, N
R
2
R
1
2
H
Me
H
H
Me
(
Entry 1, 2a, 94%*
)
(Entry 2, 2b, 90%
)
(Entry 3, 2b, 88%)
Me
Me
H
MeO
H MeO
H
OMe
(Entry 4, 2d, 92%
)
(Entry 5, 2e, 93%
)
(Entry 6, 2f, 90%*)
H
H
EtO C
H
2
OMe
Me
(
Entry 7, 2e, 85%
)
(Entry 8, 2b, 87%
)
(Entry 9, 2i, 73%*)
o
Reaction conditions: 1 (0.5 mmol), THF(4.0 mL), 70 C, 24 h, N .
2
Yields are determined by GC. *The yields reported are for
products isolated and purified by flash chromatography.
Encouraged by the above results, we focused on the reactivity and chemoselectivity
of various aryl iodides bearing halosubstituents (Br, Cl, F) under our optimal
conditions (Table 3). 1-fluoro-4-iodobenzene, 4-bromoiodobenzene and
3
-bromoiodobenzene could efficiently afford the corresponding mono-dehalogenated
products in 83-93% yields, respectively (Table 3, entries 1-3). Moving to other multi
haloarenes, 4-chloroiodobenzene, 3,4-dichloroiodobenzene and 3-chloroiodobenzene
could also undergo chemoselective dehalogenation and produced the desired products
in 88-91% yields, respectively (Table 3, entries 4-6).
Table 3. Dehalogenation of aryl iodides bearing halosubstituents.
5

ACCEPTED MANUSCRIPT
Phenanthroline (20 mol%)
t-BuOK (2.0 equiv)
I
H
o
X
THF, 70 C, 24 h, N2
X
1
2
F
H
Br
H
H
Br
(
Entry 1, 2j, 90%)
(Entry 2, 2k, 93%)
Cl
(Entry 3, 2k, 83%)
Cl
H
H
H
Cl
Cl
(
Entry 4, 2m, 91%)
(Entry 5, 2n, 88%*) (Entry 6, 2m, 90%)
o
Reaction conditions: 1 (0.5 mmol), THF (4.0 mL), 70 C, 24 h, N .
2
Yields are determined by GC. *The yields reported are for
products isolated and purified by flash chromatography.
Next, other unactive aryl halides, such as aryl bromides were examined as well.
o
4
-bromoanisole (3e) was less reactive at 70 C (Table 4). Considering the more
unactive aromatic C-Br bond in aryl halides, increasing the reaction temperature from
o
o
7
0 C to 100 C was conducted to promote the cleavage of aromatic C-Br bond, and
moderate conversion of 4-bromoanisole was observed (Table 4, entry 3). And
increased the amount of phen (40 mol%) and t-BuOK (3.0 equiv) led to 100%
conversion of 4-bromoanisole and produced the dehalogenation product in 86% yield
o
at 110 C (Table 4, entry 5). Moreover, the yield of dehalogenation product could be
up to 89% when decreasing the amount of t-BuOK (2.5 equiv) (Table 4, entry 6).
a
Table 4. Optimization of reaction conditions of dehalogenation of ArBr.
6

ACCEPTED MANUSCRIPT
Phenanthroline (X equiv)
t-BuOK (X equiv)
MeO
Br
MeO
H
THF, 24 h
3
e
2e
Conv. (%) Yield (%)
o
Entry Phen (equiv) t-BuOK (equiv) T ( C)
1
2
3
4
5
6
0.2
0.2
0.3
0.3
0.4
0.4
2.0
2.0
3.0
3.0
3.0
2.5
70
<5
0
100
100
120
110
110
12
<5
34
76
86
89
46
100
100
100
Reaction conditions: 3e (0.5 mmol), THF (4.0 mL), 24 h, N . Yields are
2
determined by GC.
Encouraged by the above results, other aryl bromides were examined and the
results were listed in Table 5. In general, electron-rich aryl bromides took place
dehalogenation smoothly and afforded the corresponding dehalogenated products in
good to excellent yields (84-90%) (Table 5, entries 1-5). Dihalide substrates, such as
1
-bromo-4-fluorobenzene, 1-bromo-4-chlorobenzene and 1-bromo-2-chlorobenzene
could both undergo chemoselective dehalogenation and produced the corresponding
products in 84-87% yields, respectively (Table 5, entries 6-8).
Table 5. Transtion-metal-free dehalogenation of aryl bromides.
Phenanthroline (40 mol%)
t-BuOK (2.5 equiv)
Br
H
o
THF, 110 C, 24 h
R
R
3
2
MeO
H
Me
H
H
H
Me
Me
(
Entry 1, 2e, 89%) (Entry 2, 2b, 90%) (Entry 3, 2b, 88%) (Entry 4, 2b, 84%)
Ph
H
F
H
Cl
H
H
Cl
Entry 5, 2a, 85%*) (Entry 6, 2j, 84%) (Entry 7, 2m, 87%)(Entry 8, 2m, 85%)
(
o
Reaction conditions: 3 (0.5 mmol), THF (4.0 mL), 110 C, 24 h, N . Yields
2
are determined by GC. *The yields reported are for products isolated.
7

ACCEPTED MANUSCRIPT
To gain some preliminary insights into the mechanism of such transition-metal-free
dehalogenation, we conducted a set of control experiments (Scheme 2). When the
reaction was conducted under air atmosphere, nearly no conversion of
1
-iodo-4-methoxybenzene (1e) was observed, which indicated that this reaction was
oxygen sensitive. On the other hand, the dehalogenation reaction was almost shut
down when 2,2,6,6-tetramethyl-1-piperidinoxyl (TEMPO) was added as radical
inhibitors. These results suggested that this transition-metal-free dehalogenation
5
,16
transformation involved a radical reaction mechanism.
dehalogenation of 1-iodo-4-methoxybenzene (1e) in THF-d8 gave a 84% yield of
-deuterioanisole (Scheme 3) (Figure S1), implying that aryl radical generated by
Moreover, the
4
reaction of ArI with Phen/t-BuOK abstracts a deuterium from THF-d8.
Phenanthroline (20 mol%)
t-BuOK (2.0 equiv)
MeO
I
MeO
H
o
THF, 70 C, 24 h
"
Conditions"
1e
2e
N2
93%
0%
Air
TEMPO (1.0 equiv.)
0%
Scheme 2. Control experiments for transition-metal-free dehalogenation.
D
Phen (20 mol%)
t-BuOK (2.0 equiv)
D
D
D
D
D
MeO
I +
MeO
D
o
7
0 C, 24 h, N
D
2
O
D
1e
2e'
4% (>95%-d)
THF-d
8
8
Scheme 3. Involvement of aryl radical intermediates.
Furthermore, we attempted to monitor the reaction between 4-bromoanisole and
THF in the presence of 1, 10-phenanthroline and t-BuOK (Figure S2). An apparent
induction period was observed, which suggested that 1, 10-phenanthroline was not the
1
7
“
true catalyst”. And the reaction mixture showed a dark purple colour after heating
o
at 110 C within half an hour (Figure S3), which indicated that
π
-electron-rich species
6
l
might be generated as the “true catalyst”.
6
s,18
On the basis of above results and previous studies , a plausible mechanism is
8

ACCEPTED MANUSCRIPT
proposed as shown in Scheme 4. An aryl halide radical anion (A) is generated from
aryl halides (1) by SET process in the presence of Phen/t-BuOK and converted to an
-
aryl radical (B) upon elimination of X . Aryl radical B reacts with THF to afford
product 2 and radical (C). From radical C, two possible pathways are presented. One
pathway is a deprotonation of radical C with the assistance of t-BuOK, followed by
another SET with 1 to form aryl halide radical anion (A) and 2,3-dihydrofuran. The
other pathway is a SET between radical C and 1 to produce cation E, followed by a
deprotonation by t-BuOK to give 2,3-dihydrofuran (4).
Initiation
Phen/t-BuOK
Ar-X
Ar-X
Ar
B
SET
-X
1
A
Propagation
O
Ar
Ar H
-
+
O
B
2
C
Path A
t-BuO-
+
Ar-X
+ Ar-X
O
PT
O
ET
O
C
D
1
4
A
Path B
t-BuO-
Ar-X
O
ET
O
O
PT
O
C
E
4
Scheme 4. Possible mechanism of this transition-metal-free dehalogenation.
. Conclusion
3
In conclusion, we have developed a transition-metal-free dehalogenation reaction
of various aryl halides in the presence of a catalytic amount of 1, 10-phenanthroline
and t-BuOK under mild conditions. Both aryl iodides and bromides could be
employed as substrate to afford the dehalogenation products in moderate to excellent
yields. Control experiments indicated that radical transfer occurred between aryl
9

ACCEPTED MANUSCRIPT
radical and alkyl C-H bond, and then alkyl radical generated in this process.
4
. Experimental section
4
.1 General Information
Analytical gas chromatography (GC) was performed using a Gas Chromatography
1
fitted with a flame ionization detector (FID). H NMR spectra were obtained at 300 or
5
00 MHz. The chemical shifts were quoted in parts per million (ppm) and referenced
1
3
to 0 ppm for internal tetramethylsilane (TMS). C NMR spectra were obtained at 75
or 125 MHz and referenced to the center line of a triplet at 77.0 ppm of CDCl . The
3
following abbreviations are used to describe peak patterns as appropriate: s = singlet,
d = doublet, t = triplet, m = multiplet. Coupling constants J were reported in hertz unit
(Hz). Thin layer chromatography (TLC) employed glass 0.25 mm silica gel plates.
Flash column chromatography was performed employing 200-300 mesh silica gel.
4
.2 General procedure for the dehalogenation of aryl iodides
A Schlenk tube was charged with aryl iodides (0.5 mmol), phen (18 mg, 0.1 mmol)
and t-BuOK (112 mg, 1.0 mmol) under an atmosphere of nitrogen at room
temperature, and then THF (4.0 mL) was added. The resulting mixture was stirred at
o
7
0 C for 24 h. After cooling to room temperature, the reaction mixture was quenched
and extracted with ethyl ether (10 ml×3). The organic layers were combined, dried
over Na SO and concentrated under reduced pressure, and then purified by silica gel
2
4
chromatograph to yield the desired dehalogenation product.
4
.3 General procedure for the dehalogenation of aryl bromides
A Schlenk tube was charged with aryl bromides (0.5 mmol), phen (36 mg, 0.2
mmol) and t-BuOK (140 mg, 1.25 mmol) under an atmosphere of nitrogen at room
temperature, and then THF (4.0 mL) was added. The resulting mixture was stirred at
o
1
10 C for 24 h. After cooling to room temperature, the reaction mixture was quenched
and extracted with ethyl ether (10 ml×3). The organic layers were combined, dried
over Na SO and concentrated under reduced pressure, and then purified by silica gel
2
4
1
0

ACCEPTED MANUSCRIPT
chromatograph to yield the desired dehalogenation product.
4
.4 Characterization data of product 2
4
b
1
biphenyl (2a) : Yield 94% (72.4 mg); white solid; H NMR (300 MHz, CDCl ): δ
3
1
3
7
.63 (d, J = 7.2Hz, 4H), 7.48 (t, J = 7.4Hz, 4H), 7.33 (t, J = 7.4Hz, 2H); C NMR (75
MHz, CDCl ): δ 141.2, 128.8, 127.3, 127.2. Anal. Calcd for C H : C, 93.46; H, 6.54.
3
12 10
Found: C, 93.35; H, 6.32.
19
1
toluene (2b) : colorless oil; H NMR (500 MHz, CDCl ): δ 7.26-7.23 (m, 3H), 7.16 (t,
3
1
3
J = 7.5Hz, 2H), 2.35 (s, 3H); C NMR (125 MHz, CDCl ): δ 137.9, 129.1, 128.3,
3
1
25.3, 21.5. Anal. Calcd for C H : C, 91.25; H, 8.75. Found: C, 91.07; H, 8.57.
7
8
1
9
1
o-xylene (2d) : colorless oil; H NMR (500 MHz, CDCl ): δ 7.13-7.07 (m, 4H), 2.25
3
13
(
s, 6H); C NMR (125 MHz, CDCl ): δ 136.5, 129.6, 125.9, 19.8. Anal. Calcd for
3
C H : C, 90.51; H, 9.49. Found: C, 90.35; H, 9.28.
8
10
1
2d
1
anisole (2e) : colorless oil; H NMR (500 MHz, CDCl ): δ 7.28 (t, J = 7.5Hz, 2H),
3
13
6
.94 (t, J = 7.0Hz, 1H), 6.90 (d, J = 9.5Hz, 2H), 3.79 (s, 3H); C NMR (125 MHz,
CDCl ): δ 159.4, 129.5, 120.7, 114.1, 55.1. Anal. Calcd for C H O: C, 77.75; H, 7.46.
3
7
8
Found: C, 77.65; H, 7.27.
1
2d
1
1
,3-dimethoxybenzene (2f)
: Yield 90% (62.1 mg); yellow oil; H NMR (500 MHz,
1
3
CDCl ): δ 7.18 (t, J = 8.0Hz, 1H), 6.52-6.47 (m, 3H), 3.79 (s, 6H); C NMR (125
3
MHz, CDCl ): δ 160.9, 129.9, 106.2, 100.5, 55.3. Anal. Calcd for C H O : C, 69.54;
3
8
10
2
H, 7.30. Found: 69.42; H, 7.14.
12d
1
ethyl benzoate (2i) : Yield 73% (54.8 mg); yellow oil; H NMR (500 MHz, CDCl ):
3
δ 8.04 (d, J = 1.5Hz, 2H), 7.54 (t, J = 8.5Hz, 1H), 7.40 (t, J = 7.5Hz, 2H), 3.79 (s, 6H),
1
3
4
1
6
.38 (q, J = 7.0Hz, 2H), 1.39 (t, J = 7.5Hz, 3H); C NMR (125 MHz, CDCl ): δ
3
66.6, 132.8, 130.5, 129.5, 128.3, 60.9, 14.3. Anal. Calcd for C H O : C, 71.98; H,
9
10
2
.71. Found: C, 71.81; H, 6.51.
1
9
1
fluorobenzene (2j) : colorless oil; H NMR (500 MHz, CDCl ): δ 7.32 (t, J = 11.0Hz,
3
1
3
2
H), 7.13-7.03 (m, 3H); C NMR (125 MHz, CDCl ): δ 163.9, 161.9, 129.9, 124.0,
3
1
15.3. Anal. Calcd for C H F: C, 74.99; H, 5.24. Found: C, 74.86; H, 5.01.
6 5
11

ACCEPTED MANUSCRIPT
1
9
1
bromobenzene (2k) : colorless oil; H NMR (500 MHz, CDCl ): δ 7.48 (t, J = 4.2Hz,
3
1
3
2
H), 7.29-7.20 (m, 3H); C NMR (125 MHz, CDCl ): δ 131.6, 130.1, 126.9, 122.6.
3
Anal. Calcd for C H Br: C, 45.90; H, 3.21. Found: C, 45.77; H, 3.11.
6
5
19
1
chlorobenzene (2m) : colorless oil; H NMR (500 MHz, CDCl ): δ 7.34-7.21 (m,
3
1
3
5
H); C NMR (125 MHz, CDCl ): δ 134.3, 129.7, 128.6, 126.4. Anal. Calcd for
3
C H Cl: C, 64.02; H, 4.48. Found: C, 63.84; H, 4.25.
6
5
1
9
1
1
,2-dichlorobenzene (2n) : Yield 88% (64.7 mg); yellow oil; H NMR (500 MHz,
1
3
CDCl ): δ 7.44 (d, J = 5.0Hz, 2H), 7.20 (d, J = 4.8Hz, 2H); C NMR (125 MHz,
3
CDCl ): δ 132.6, 130.5, 127.7. Anal. Calcd for C H Cl : C, 49.02; H, 2.74. Found: C,
3
6
4
2
C, 48.83; H, 2.56.
ACKNOWLEDGMENT
This work was supported by the National Natural Science Foundation of China (No.
1102036) and the Young-aged Backbone Teacher Funds of Henan Province of China
No. 2014GGJS-058).
2
(
ASSOCIATED CONTENT
Supporting Information. Optimization of reaction conditions and spectra of H
1
1
3
NMR and C NMR for products. This material is available free of charge via the
internet at http://pubs.acs.org.).
REFERENCES
(1) (a) D. Alberico, M. E. Scott, M. Lautens, Chem. Rev. 2007, 107, 174; (b) O.
Daugulis, H. Q. Do, D. Shabashov, Acc. Chem. Res. 2009, 42, 1074; (c) G. P.
McGlacken, L. M. Bateman, Chem. Soc. Rev. 2009, 38, 2447; (d) P. B. Arockiam, C.
Bruneau, P. H. Dixneuf, Chem. Rev. 2012, 112, 5879.
(2) For selected reviews on transition-metal-free coupling reactions, see: (a) A.
Bhunia, S. R. Yetra, A. T. Biju, Chem. Soc. Rev. 2012, 41, 3140; (b) V. P. Mehta, B.
Punji, RSC Adv. 2013, 3, 11957; (c) T. L. Chan, Y. Wu, P. Y. Choy, F. Y. Kwong,
1
2

ACCEPTED MANUSCRIPT
Chem. Eur. J. 2013, 19, 15802; (d) C.-L. Sun, Z.-J. Shi, Chem. Rev. 2014, 114, 9219.
(3) S. Yanagisawa, K. Ueda, T. Taniguchi, K. Itami, Org. Lett. 2008, 10, 4673.
(4) (a) C.-L. Sun, H. Li, D.-G. Yu, M. Yu, X. Zhou, X. Y. Lu, K. Huang, S. F. Zheng,
B.-J. Li, Z.-J. Shi, Nat. Chem. 2010, 2, 1044; (b) W. Liu, H. Cao, H. Zhang, H. Zhang,
K. H. Chung, C. He, H. B. Wang, F. Y. Kwong, A. Lei, J. Am. Chem. Soc. 2010, 132,
1
6737; (c) E. Shirakawa, K. Itoh, T. Higashino, T. Hayashi, J. Am. Chem. Soc. 2010,
32, 15537.
1
(5) A. Studer, D. P. Curran, Angew. Chem. Int. Ed. 2011, 50, 5018.
(6) (a) Y. T. Qiu, Y. H. Liu, K. Yang, W. K. Hong, Z. Li, Z. Y. Wang, Z. Y. Yao, S.
Jiang, Org. Lett. 2011, 13, 3556; (b) G.-P. Yong, W.-L. She, Y.-M. Zhang, Y.-Z. Li,
Chem. Commun. 2011, 47, 11766; (c) H. Liu, B. Yin, Z. Gao, Y. Li, H. Jiang, Chem.
Commun. 2012, 48, 2033; (d) W.-C. Chen, Y.-C. Hsu, W.-C. Shih, C.-Y. Lee, W.-H.
Chuang, Y.-F. Tsai, P. P.-Y Chen, T.-G. Ong, Chem. Commun. 2012, 48, 6702; (e) K.
Tanimoro, M. Ueno, K. Takeda, M. Kirihata, S. Tanimori, J. Org. Chem. 2012, 77,
7
844; (f) H. Zhao, J. Shen, J. Guo, R. Ye, H. Zeng, Chem. Commun. 2013, 49, 2323;
(g) W. Liu, F. Tian, X. Wang, H. Yu, Y. Bi, Chem. Commun. 2013, 49, 2983; (h) A.
Dewanji, S. Murarka, D. P. Curran, A. Studer, Org. Lett. 2013, 15, 6102; (i) B. Li, X.
Qin, J. You, X. Cong, J. Lan, Org. Biomol. Chem. 2013, 11, 1290; (j) S. Sharma, M
Kumar, V. Kumar, N. Kumar, Tetrahedron Lett. 2013, 54, 4868; (k) S. A, X. Liu, H. Li,
C. He, Y. Mu, Asian J. Org. Chem. 2013, 2, 857; (l) S. Zhou, G. M. Anderson, B.
Mondal, E. Doni, V. Ironmonger, M. Kranz, T. Tuttle, J. A. Murphy, Chem. Sci. 2014,
5, 476; (m) D. Ghosh, J.-Y. Lee, C.-Y. Liu, Y.-H. Chiang, H. M. Lee, Adv. Syn. Cat.
2014, 356, 406; (n) Y.-W. Zhu, W.-B. Yi, J.-L. Qian, C. Cai, ChemCatChem 2014, 6,
733; (o) B. S. Bhakuni, A. Yadav, S. Kumar, S. Kumar, New J. Chem. 2014, 38, 827;
(p) Y. Wu, P. Y. Choy, F. Y. Kwong, Org. Biomol. Chem. 2014, 12, 6820; (q) W. Liu,
L. Xu, Y. Bi, RSC Adv. 2014, 4, 44943; (r) Q. Song, D. Zhang, Q. Zhu, Y. Xu, Org.
Lett. 2014, 16, 5272; (s) S. Zhou, E. Doni, G. M. Anderson, R. G. Kane, S. W.
MacDougall, V. M. Ironmonger, T. Tuttle, J. A. Murphy, J. Am. Chem. Soc.
1
3

ACCEPTED MANUSCRIPT
2
014,136,17818.
(7) (a) D. S. Roman, Y. Takahashi, A. B. Charette, Org. Lett. 2011, 13, 3242; (b) C. L.
Sun, Y. F. Gu, W. P. Huang, Z. J. Shi, Chem. Commun. 2011, 47, 9813; (c) M.
Rueping, M. Leiendecker, A. Das, T. Poisson, L. Bui, Chem. Commun. 2011, 47,
1
0629; (d) B. S. Bhakuni, A. Kumar, S. J. Balkrishna, J. A. Sheikh, S. Konar, S.
Kumar, Org. Lett. 2012, 14, 2838; (e) S. De, S. Ghosh, S. Bhunia, J. A. Sheikh, A.
Bisai, Org. Lett. 2012, 14, 4466; (f) Y. Wu, S. M. Wong, F. Mao, T. L. Chan, F. Y.
Kwong, Org. Lett. 2012, 14, 5306; (g) K.-S. Masters, S. Bräse, Angew. Chem. Int. Ed.
2
2
013, 52, 866; (h) Wertjes, W. C.; Wolfe, L. C.; Waller, P. J.; Kalyani, D. Org. Lett.
013, 15, 5986; (i) B. S. Bhakuni, A. Yadav, S. Kumar, S. Patel, S. Sharma, S. Kumar,
J. Org. Chem. 2014, 79, 2944.
8) (a) E. Shirakawa, X. Zhang, T. Hayashi, Angew. Chem. Int. Ed. 2011, 50, 4671; (b)
(
C. L. Sun, Y. F. Gu, B. Wang, Z. J. Shi, Chem. Eur. J. 2011, 17, 10844; (c) J. F.
Guastavino, M. E. Budén, R. A. Rossi, J. Org. Chem. 2014, 79, 9104.
(9) H. Zhang, R. Shi, A. Ding, L. Lu, B. Chen, A. Lei, Angew. Chem. Int. Ed. 2012,
5
1, 12542.
(10) F. Alonso, I.P. Beletskaya, M. Yus, Chem. Rev. 2002, 102, 4009.
(11) M. L. Hitchman, R.A. Spackman, N.C. Ross, C. Agra, Chem. Soc. Rev. 1995, 24,
4
23.
(
12) (a) M.S. Viciu, G.A. Grasa, S.P. Nolan, Organometallics 2001, 20, 3607; (b) A.
Arcadi, G. Cerichelli, M. Chiarini, R. Vico, D. Zorzan, Eur. J. Org. Chem. 2004, 16,
404; (c) O. Navarro, N. Marion, Y. Oonishi, R. A. Kelly III, S. P. Nolan, J. Org.
Chem. 2006, 71, 685; (d) A. Bhattacharjya, P. Klumphu, B. H. Lipshutz, Org. Lett.
015, 17, 1122.
3
2
(13) (a) K. Fujita, M. Owaki, R. Yamaguchi, Chem. Commun. 2002, 2964; (b) M.
Buil, M. A. Esteruelas, S. Niembro, M. Olivan, L. Orzechowski, C. Pelayo, A.
Vallribera, Organometallics 2010, 29, 4375.
1
4

ACCEPTED MANUSCRIPT
(
14) (a) C. Desmarets, S. Kuhl, R. Schneider, Y. Fort, Organometallics 2002, 21, 1554;
b) S. Kuhl, R. Schneider, Y. Fort, Adv. Synth. Catal. 2003, 345, 341.
(
(15) W. M. Czaplik, S. Grupe, M. Mayer, A. J. Wangelin, Chem. Commun. 2010, 46,
6
350.
(
(
(
16) A. Studer, D. P. Curran, Nat. Chem. 2014, 6, 765.
17) J. Cuthbertson, V. J. Gray, J. D. Wilden, Chem. Commun. 2014, 50, 2575.
18) (a) L. Zhang, H. Yang, L. Jiao, J. Am. Chem. Soc. 2016, 138, 7151; (b) J. P.
Barham, G. Coulthard, K. J. Emery, E. Doni, F. Cumine, G. Nocera, M. P. John, L. E.
A. Berlouis, T. McGuire, T. Tuttle, J. A. Murphy, J. Am. Chem. Soc. 2016, 138, 7402.
(19) J. Moon, S. Lee, J. Organomet. Chem. 2009, 694, 473.
1
5