Palladium catalyzed-dehalogenation of aryl chlorides and bromides using phosphite ligands

Article abstract of DOI:10.1016/j.jorganchem.2008.10.052

The catalytic system based on Pd-phosphite for the dehalogenation reactions of aryl chlorides and bromides is described. The Pd-phosphite catalyst effectively promoted the dehalogenation of aryl halides to give dehalogenated products in moderate to excellent yields. The aryl chlorides required strong bases such as NaO^tBu for this transformation, whereas the aryl bromides were dehalogenated in the presence of weak bases such as Cs₂CO₃. This catalytic system exhibited tolerance to functional groups such as methoxy, amine, hydroxyl, ether, amide, benzyl and ketone groups. It also demonstrated chemoselectivity in that bromochlorobenzene was converted only to chlorobenzene.

Full text of DOI:10.1016/j.jorganchem.2008.10.052

Journal of Organometallic Chemistry 694 (2009) 473–477
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Note
Palladium catalyzed-dehalogenation of aryl chlorides and bromides using
phosphite ligands
*
Jeongju Moon, Sunwoo Lee
Department of Chemistry, Chonnam National University, 300 Yongbong-dong, Buk-gu, Gwangju 500-757, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
The catalytic system based on Pd–phosphite for the dehalogenation reactions of aryl chlorides and bro-
mides is described. The Pd–phosphite catalyst effectively promoted the dehalogenation of aryl halides to
give dehalogenated products in moderate to excellent yields. The aryl chlorides required strong bases
such as NaOtBu for this transformation, whereas the aryl bromides were dehalogenated in the presence
of weak bases such as Cs2CO3. This catalytic system exhibited tolerance to functional groups such as
methoxy, amine, hydroxyl, ether, amide, benzyl and ketone groups. It also demonstrated chemoselectiv-
ity in that bromochlorobenzene was converted only to chlorobenzene.
Received 16 September 2008
Received in revised form 25 October 2008
Accepted 31 October 2008
Available online 6 November 2008
Keywords:
Palladium
Phosphite
Ó 2008 Elsevier B.V. All rights reserved.
Dehalogenation
Aryl bromides
Aryl chlorides
1. Introduction
dehalogenated compounds. Numerous new dehalogenation meth-
ods using palladium [13–15], rhodium [16], iron [17] and nickel
Palladium catalyzed-transformation reactions have been widely
used in organic synthesis [1]. Among them, carbon–carbon bond
formation, one of the most powerful transformations, has been
extensively investigated over the past 30 years [2]. Recent develop-
ments in cross-coupling methodology allow aryl halides showing
high catalytic activities to be formed under milder conditions. Most
of them have been affected by the ligands. Generally, electron-rich
and bulky monoalkyl phosphines such as PtBu3 [3–5] and biphenyl
alkyl phosphines [6–8] showed high activities as the ligand in the
cross-coupling reaction. Moreover, a number of important devel-
opments with phosphine-free ligands such as N-heterocyclic carb-
enes have been reported [9]. However, they suffer some drawbacks
such as sensitivity to air or moisture in the case of phosphine li-
gands and the requirement for multistep synthesis in the case of
carbene. To address this problem, we employed a phosphite-con-
taining, sterically hindered group as the ligand, because phosphites
are less expensive and more stable to air and moisture than phos-
phines. They show good reactivities in Hiyama coupling reaction
and the homocoupling of aryl halides [10,11]. In the latter case,
we found that the dechlorination product was obtained as a
byproduct when aryl chlorides were used in the homocoupling.
Organohalogens are classified as pollutants due to their persis-
tent toxic effect [12]. Therefore, it is important to develop efficient
methods that transform them into less harmful chemicals such as
[18,19] catalysts have been reported. Palladium is the most com-
monly used transition metal in this transformation.
Recently, N-heterocyclic carbene ligands have been used for the
dehalogenation of aryl chlorides [20], while the triphenyl phos-
phine ligand, which was most often used as a ligand in the palla-
dium catalyzed-transformation, has been employed for the
dehalogenation of aryl halides and alpha-haloketones [21]. How-
ever, phosphite compounds have never before been used as ligands
in dehalogenation. Therefore, we decided to optimize the condition
for the dehalogenation of aryl halides using the palladium/phos-
phites catalytic system (Fig. 1).
We employed isopropanol, possessing a beta-hydrogen, as the
hydrogen source in a safer and simpler method than using molec-
ular hydrogen. Reactions of 4-chlorotoluene with palladium in iso-
propanol were initially conducted using various kinds of palladium
source and ligand, including phosphites. Table 1 summarizes our
preliminary results for these dechlorination reactions. As expected,
the ligand-free condition afforded dehalogenated product in low
yield (entry 1) and Pd2(dba)3 was the best palladium source among
the tested palladiums (entries 2–5). The phosphites showed better
reactivities than the phosphines did. Phosphite 1 was the best li-
gand, giving the desired product in almost quantitative yield with-
out byproduct derived from homocoupling reaction (entry 5).
Phosphites 2 and 3 afforded the dehalogenated product in good
yield, but gave a homocoupled compound (entries 6 and 7). How-
ever, P(OPh)3 showed good reactivity without the formation of
homocoupled product (entry 8). Interestingly, the chelating phos-
* Corresponding author. Tel.: +82 62 530 3385; fax: +82 62 530 3389.
E-mail address: sunwoo@chonnam.ac.kr (S. Lee).
0022-328X/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2008.10.052

474
J. Moon, S. Lee / Journal of Organometallic Chemistry 694 (2009) 473–477
tBu
tBu
Next, the above optimum catalytic system was tested on aryl
O
O
O
O
bromides for debromination. The data are summarized in Table
2. When 4-bromotoluene was treated with NaOtBu using Pd2(dba)3
and phosphite 1 as the ligand in i-PrOH, the debrominated product,
toluene, was obtained in 91% yield. However, the homocoupling
byproduct was also obtained in 4% yield (entry 1). To reduce the
amount of byproduct, several kinds of alcohol were screened as
solvents. Cyclohexanol afforded the desired product in high yield
and showed a trace amount of homocoupled product (entry 4).
The method using a strong base rarely addresses functional group
compatibility as well as selectivity. To address these problems, we
attempted to use a weak base rather than a strong base. When
Cs2CO3 was used as a base, the conversion yield was superior to
that of other weak bases such as K2CO3 and Na2CO3 (entries 5–
7). When the reaction temperature was increased in the presence
of Cs2CO3, the toluene product was obtained in almost quantitative
yield without any byproduct (entry 9). When the amount of cata-
lytic loading was decreased to 0.5 mol%, the product yield was
99% (entry 10), whereas at 0.1 mol% catalytic loading, the yield of
dehalogenated product was 60% (entry 11).
Based on the optimized condition, we investigated the scope of
the dehalogenation using phosphite 1 as the ligand for a series of
aryl chlorides and bromides having different electronic and steric
properties. The results for aryl chlorides are summarized in Table
3. Chlorobenzene and 4-chlorotoluene were completely converted
to dehalogenated product in high yields (entries 1 and 2). The
ortho-, meta- and para-chloroanisoles all showed high yields that
were independent of the substituent position (entries 3–5). This
reaction method showed the tolerance to functional groups such
as amino and hydroxy groups (entries 6 and 7). 1-Chloronaphtha-
lene was converted to naphthalene in 98% yield (entry 8).
In the case of aryl bromides, the reactions were carried out with
0.5 mol% palladium and 0.5 mol% ligand at 120 °C for 10 h. Cyclo-
hexanol and Cs2CO3 were employed as solvent and base, respec-
tively. The reaction is generalized for a variety of substrates, as
shown in Table 4.
tBu
tBu
Me
O
P
P
O
Me
tBu
tBu
tBu
2
O
O
P
O
tBu
tBu
tBu
tBu
O
O
tBu
O
P
P
O
tBu
tBu
O
O
1
3
Fig. 1. Phosphite ligands.
phine ligand 1,10-bis(diphenylphosphino)ferrocene (dppf) afforded
the dehalogenated product in very low yield (entry 11). Recently,
Muzart and coworkers showed that dppf was a suitable ligand
for dehalogenation using dimethylformamide as the hydride
source. However, in this reaction system, the low reactivity of
the chelating ligand is caused by blocking of the beta hydride elim-
ination step. Sterically demanding monophosphine showed low
activity (entry 12) and IPrÅHCl, which was reported by Nolan group,
afforded the dehalogenated product in high yield (entry 13). When
the amount of catalyst used was decreased to 1 mol%, the product
yield was very low (entry 15), and a minimum catalytic loading of
2.5 mol% was needed for full conversion (entry 14). The reactivity
of the dechlorination was dependent on the nature of the base.
The most effective base was NaOtBu, whereas other alkoxide bases
such as KOtBu, NaOMe and KOMe showed low product yield (en-
tries 16–18). Therefore, the optimized conditions for the dehalo-
genation of aryl chlorides were as follows: 1.25 mol% Pd2(dba)3,
2.5 mol% phosphite 1, and 1.2 equiv of NaOtBu in i-PrOH solvent
at 80 °C for 3 h.
Table 1
Optimization of conditions for dehalogenation of 4-chlorotoluene.a
Pd2(dba)3/Ligand
H3C
Cl
H3C
H
Base, i-PrOH
80oC, 3 h
Entry
Palladium
Ligand
Pd mol% (Pd/L = 1/1)
Base
Conv. b(%)
Productb (%)
Homoc (%)b
f
1
2
3
4
5
6
7
8
Pd(CH3CN)2Cl2
Pd(CH3CN)2Cl2
PdCl2
–
1
1
1
1
2
3
5
5
5
5
5
5
5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
1
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
KOtBu
35
67
65
30
66
60
94
99
95
76
92
74
24
23
45
99
99
12
43
27
4
–
f
–
f
–
f
Pd(OAc)2
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
Pd2(dba)3
95
–
f
100
100
100
98
76
30
25
45
100
100
15
–
2
11
f
P(OPh)3
PPh3
–
f
9
–
10
11
12
13
14
15
16
17
18
P(o-tol)3
2
f
Dppfd
–
f
PtBu3
–
f
IPrÅHCle
–
f
1
1
1
1
1
–
f
–
f
2.5
2.5
2.5
45
30
5
–
f
NaOMe
KOMe
–
f
–
a
Reaction conditions: 1.0 mmol CH3C6H4Cl, 3 mmol solvent.
b
c
d
e
f
Yields were determined by gas chromatography (GC) by comparison to an internal standard (naphthalene).
Homocoupled product is 4,40-dimethylbiphenyl.
1,10-Bis(diphenylphosphino)ferrocene.
1,3-Bis(2,6-diisopropylphenyl)imidazolium chloride.
No homocoupled product was found.

J. Moon, S. Lee / Journal of Organometallic Chemistry 694 (2009) 473–477
475
Table 2
Optimization of conditions for dehalogenation of 4-bromotoluene.a
Pd2(dba)3/1
H3C
Br
H3C
H
Base, Solvent
Temp, 10 h
Entry
Pd (mol%)
Temp (°C)
Base
Solvent
Conv. (%)
Productb (%)
Homoc (%)
1
2
3
4
5
6
7
8
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
0.5
0.1
80
80
80
80
80
80
80
100
120
120
120
NaOtBu
NaOtBu
NaOtBu
NaOtBu
Cs2CO3
K2CO3
Na2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
i-PrOH
MeOH
EtOH
100
82
94
100
60
43
13
80
100
100
62
91
63
90
97
52
35
9
72
99
99
60
4
11
2
d
Cyclohexanol
–
Cyclohexanol
Cyclohexanol
Cyclohexanol
Cyclohexanol
Cyclohexanol
Cyclohexanol
Cyclohexanol
3
1
–
d
2
d
9
10
11
–
d
–
d
–
a
Reaction conditions: 1.0 mmol CH3C6H4Br, 3 mmol solvent.
Yields were determined by gas chromatography (GC) by comparison to an internal standard (naphthalene).
Homocoupled product is 4,40-dimethylbiphenyl.
b
c
d
No homocoupled product was found.
Table 3
The dehalogenation of aryl chlorides using palladium/phosphite catalyst.
Pd2(dba)3(1.25 mol%)
1 (2.5 mol%)
H
Cl
R
R
NaOtBu (1.2 equiv)
i-PrOH, 80 oC, 3 h
Entry
1
Aryl chloride
Conv. (%)
100
Yielda (%)
>99b
Entry
5
Aryl chloride
Conv. (%)
100
Yielda (%)
>99b
Cl
Cl
MeO
H2N
Cl
Cl
2
3
100
100
100
98
6
7
8
100
100
100
96
95
98
Me
Cl
Cl
>99b
>99b
OMe
Cl
HO
Cl
4
OMe
a
All compounds are characterized by comparison of gas chromatography (GC) analysis, 1H and 13C NMR spectra with authentic samples or literature data.
Almost quantitative yield.
b
Bromobenzene, 4-bromotoluene and 1-bromo-4-tert-butylben-
was converted to the biphenyl in 99% yield (entry 13). 2-Bromo-
biphenyl, which is more sterically hindered, showed low conver-
sion and low yield. Nevertheless, its yield was increased to 99%
when NaOtBu was used as the base instead of Cs2CO3 (entry
14). In the case of 2-bromothiophene, the yields of conversion
and product were low when Cs2CO3 was used as the base. How-
ever, when NaOtBu was used as the base, 2-bromothiophene was
completely converted to thiophene in 72% yield and produced
bithiophene as the byproduct in 10% yield (entry 15). The reactiv-
ity of 3-bromopyridine was higher than that of 2-bromopyridine.
2-Bromopyridine and 3-bromopyridine resulted in homocoupled
products as byproduct in 7% and 15% yield, respectively (entries
16 and 17). This reaction condition exhibited chemoselectivity
zene were converted to the corresponding debrominated products
in high yields (entries 1–3, respectively). 3-Bromoanisole showed
moderate yield even though the conversion was high, and the
homocoupled product was not found in gas chromatography (GC)
(entry 4). However, 4-bromoanisole afforded 4,40-dimethoxybi-
phenyl as byproduct in 5% yield (entry 5). Even sterically
demanding substrates were converted to the desired product in
high yields (entries 6 and 7). In a similar method to that of aryl
chloride, this reaction method provided the tolerance to func-
tional group such as amino, nitro, hydroxyl and ether (entries
8–11). 2-Bromo-6-methoxynaphthalene was transformed to 2-
methoxynaphthalene in 95% yield (entry 12). 4-Bromobiphenyl

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J. Moon, S. Lee / Journal of Organometallic Chemistry 694 (2009) 473–477
Table 4
The dehalogenation of aryl bromides using palladium/phosphite catalyst.a
Pd2(dba)3(0. 25 mol%)
1 (0.5 mol%)
H
Br
R
R
Cs2CO3 (1.2 equiv)
Cyclohexanol, 120 oC, 10 h
Entry
1
Aryl bromide
Conv. (%)
100
Yield (%)
98
Entry
12
Aryl bromide
Conv. (%)
100
Yield (%)
95
Br
Br
MeO
Br
Br
2
3
4
5
6
100
100
98
95
99
13
14
15
16
17
100
50 (100)d
40 (100)d
63
99
46(99)d
38(72)d,e
43f
Br
Me
tBu
Br
Br
S
78b
78c
84
Br
OMe
Br
Br
N
98
MeO
Me
Br
Br
N
90
98
65g
Me
Me
Br
Br
7
8
9
87
84
85
80
85
18
19
20
99
99
88
89
98
Me
Me
Cl
Br
Br
Me2N
Cl
Br
Br
O
O
100
100
O2N
HO
N
H
Br
Br
10
100
90
61b
21
22
100
100
99
N
Ph
Me
Br
Br
O
O
11
85
66b
O
All compounds are characterized by comparison of gas chromatography analysis, 1H and 13C NMR spectra with authentic samples or literature data.
a
b
c
d
e
f
No homocoupled product was found in gas chromatography (GC).
5% Homocoupled byproduct.
NaOtBu was used as base instead of Cs2CO3.
10% Homocoupled byproduct.
7% Homocoupled product.
15% Homocoupled product.
g
to aryl bromide. 3- and 4-Chlorobromobenzenes were converted
ing amide and ketone groups also afforded the corresponding
debrominated products in moderate to excellent yields without
reducing the carbonyl group (entries 20–22).
As shown in Scheme 1, when the dehalogenation of fluoroben-
zene was carried out under reaction condition that was used for
to chlorobenzene. Bromotoluene and benzene were not found in
the reaction mixture, confirming that only debromination oc-
curred (entries 18 and 19). Yus’ group did not achieve the halogen
chemoselectivity using copper catalyst [22]. The substrates hav-

J. Moon, S. Lee / Journal of Organometallic Chemistry 694 (2009) 473–477
477
Pd2(dba)3(1.25 mol%)
1 (2.5 mol%)
NaOtBu (1.2 equiv)
i-PrOH, 80 oC
Ar
X
Ar
H
H
F
L
Pd(0)
Ar
Pd(II)
Ar
20% yield
L
L
Pd(II)
X
Scheme 1. Palladium-catalyzed defluorination.
H
O
Ar
Pd2(dba)3(0. 25 mol%)
Ligand (0.5 mol%) or no Ligand
O
L
Pd(II)
O
H
H
Br
tBu
Cs2CO3 (1.2 equiv)
tBu
X
Cyclohexanol, 120 oC
Fig. 3. General mechanism of Pd-catalyzed dehalogenation.
100
80
60
40
20
0
phites accelerated the reductive elimination steps. Further
mechanistic studies of the reactivity of phosphite ligand are in
progress in our laboratory.
Phosphite 1
PPh3
no ligand
In conclusion, we demonstrated that the sterically hindered
phosphites exhibited good reactivities as ligands in the dehalogen-
ation of aryl bromides and chlorides. To the best of our knowledge,
this is the first report of the use of phosphite as a ligand in dehalo-
genation reactions. Aryl chloride required 2.5 mol% catalyst and a
strong base, while 0.5 mol% catalytic loading was sufficient for
the debromination of aryl bromide in the presence of a weak base.
Aryl bromides bearing functional groups such as alkyl, alkoxy, hy-
droxyl, ether, chloro, phenyl, amide, benzyl and ketone can be
transformed to the corresponding debrominated products in high
yields.
0
2
4
6
8
10
12
Reaction Time (h)
Fig. 2. Reaction rate of debromination with phosphite 1 and PPh3.
Acknowledgment
This work was supported by the Korea Research Foundation
Grant Funded by the Korean Government (MOEHRD, Basic Re-
search Promotion Fund) (KRF-2006-003-C-00178).
dechlorination, the yield of defluorinated product, benzene, was
only 20% as determined by GC. This low yield was attributed to
the strong bond formed between carbon and fluorine atoms.
We compared the reaction rates of the phosphite ligand 1 and
PPh3 in the debromination of 1-bromo-4-tert-butylbenzene. As
shown in Fig. 2, phosphite 1 showed better catalytic activity than
PPh3. In addition, the debromination without ligand showed very
low reactivity.
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products in all case of Table
mechanism.
4 supported the proposed
The phosphorus atom of phosphite 1 is more electron-poor
than that of triphenylphosphine. However, the former had better
reactivity than the latter, as shown in Fig. 2, which is contrary to
the general belief that electron-rich ligands accelerate the rate of
oxidative addition of aryl halides [24]. It is generally believed that
the rate determining step for dehalogenation is the oxidative
addition of aryl halides. However, in this case, we believe that
the phosphite ligand exerted much greater effect on both the beta
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hydride elimination and the reductive elimination steps. The
p
acceptor phosphite ligand accelerated the beta hydride elimina-
tion step while the sterically bulky substituted group in phos-