Iron-catalyzed dechlorination of aryl chlorides

Article abstract of DOI:10.1246/cl.2004.1356

Electron-rich aryl chlorides such as chloroanisole, chloroaniline, and chlorotoluene were dechlorinated by Grignard reagents in the presence of a catalytic amount of iron chlorides. This is in sharp contrast to the cross-coupling reactions of electron-poor aryl chlorides with Grignard reagents.

Full text of DOI:10.1246/cl.2004.1356

1356
Chemistry Letters Vol.33, No.10 (2004)
Iron-Catalyzed Dechlorination of Aryl Chlorides
Haiqing Guo, Ken-ichiro Kanno, and Tamotsu Takahashiꢀ
Catalysis Research Center, and Graduate School of Pharmaceutical Sciences, Hokkaido University, and SORST,
Japan Science and Technology Corporation(JST), Sapporo 001-0021
(Received July 12, 2004; CL-040817)
Electron-rich aryl chlorides such as chloroanisole, chloro-
aniline, and chlorotoluene were dechlorinated by Grignard re-
agents in the presence of a catalytic amount of iron chlorides.
This is in sharp contrast to the cross-coupling reactions of elec-
tron-poor aryl chlorides with Grignard reagents.
Table 2. Iron-catalyzed dechlorination of 4-chloroanisole
FeXn (10 mol%)
n-BuMgCl
MeO
MeO
Cl
THF
Time
/h
Yielda
/%
Entry
1
Catalyst n-BuMgCl
Temp
/equiv.
/°C
Dechlorination of aryl chlorides is important target not only
in organic chemistry but also in environmental chemistry.1 Sev-
eral catalytic systems have been reported using Pd(0)/KOMe,
[Rh]/HSiEt3, Ni(0)/i-PrONa, and other systems for dechlorina-
tion of aryl chlorides.2–9
Our group has reported selective dehalogenation of aryl hal-
ides using Cp2ZrCl2 or Cp2TiCl2 as a catalyst with Grignard re-
agents.9 In particular, the combination of cat. Cp2TiCl2/RMgX
was efficient as a catalyst system for dechlorination of aryl chlor-
ides. During our further investigations, we surveyed the combi-
nation of transition metal chlorides and Grignard reagents for
dechlorination of aryl chlorides. In this paper we would like to
report a new system of iron catalyst/Grignard reagent for de-
chlorination of aryl chlorides.
FeCl3
3.0
50
24
84
FeCl2
2
3
3.0
3.0
50
50
48
48
93
61
Fe(acac)2
4
5
FeCl3
FeCl3
2.0
3.0
50
rt
24
24
57
33
aYields were determined by GC analyses.
much lower than that of iron catalyst under these conditions.
In order to optimize the reaction conditions, several types of
iron salts, reaction temperature, and the amount of n-BuMgCl
were tested as shown in Table 2. Iron chlorides FeCln (n ¼ 2
or 3) were better than Fe(acac)2 (Entries 1–3). Reducing the
amount of the Grignard reagent significantly lowered the product
yield (Entry 4). When the reaction was carried out at room tem-
perature, the yield remarkably decreased (Entry 5). In the ab-
sence of iron salts, the reaction did not proceed.
Table 1. MCln-catalyzed dechlorination of 4-chloroanisole
with n-BuMgCl
Catalyst (10 mol%)
n-BuMgX (3.0 equiv.)
Table 3 summarizes the results of the FeCl3-catalyzed dech-
lorination reactions of a series of aryl chlorides with several
kinds of Grignard reagents. The dechlorination of 3- or 4-chloro-
anisole with a series of alkyl Grignard reagents gave anisole in
high yields (Entries 1–4). When n-C12H25MgBr was employed
for the reaction, 1-dodecene was formed in 107% GC yield based
on 3-chloroanisole (Entry 5). On the other hand, in the cases of
MeMgCl and PhCH2MgCl without ꢀ-hydrogen, anisole was ob-
tained only in 21 and 41% yield, respectively (Entries 6 and 7). It
would suggest that the existence of ꢀ-hydrogen on the Grignard
reagents is necessary for this reaction to proceed efficiently.
For dechlorination of 4-chlorotoluene, 2-chloroaniline, and 2-
chloronaphthalene, the desired products were formed in good
to high yields (Entries 9–11). Double dechlorination of 3,4-
dichlorotoluene was also examined with FeCl3 (20 mol %) and
n-BuMgCl (6.0 equiv.) to afford toluene in 85% yield (Entry 12).
MeO
Cl
MeO
THF, 50 °C
Yield/%a
Catalyst
Entry
Time/h
VCl3
CrCl3
MnCl2
FeCl3
CoCl2
CuCl2
ZnCl2
MoCl5
CdCl2
LaCl3
1
2
48
48
24
24
48
48
24
24
24
24
45
53
6
3
4
84
29
27
0
5
6
7
8
2
Recently Furstner et al. have reported that simple iron salts
¨
9
0
such as FeCln, Fe(acac)n (n ¼ 2, 3) were highly efficient cata-
lysts for cross-coupling reactions of alkyl Grignard reagents with
aryl chlorides.10 In sharp contrast, no coupling products were de-
tected in the present reactions. Probably, the reason for such dif-
ference can be attributed to the electronic properties of the em-
ployed aryl chlorides. For the cross coupling reaction, electron-
deficient substituents are required on aryl chlorides, whereas the
reduction proceeds efficiently with electron-donating group on
aryl chlorides.
10
0
aYields were determined by GC analyses.
A series of transition metal chlorides (10 mol %) were exam-
ined for dechlorination reaction of 4-chloroanisole with n-
BuMgCl (3 equiv.) in THF at 50 ꢁC. The results are summarized
in Table 1. Interestingly, FeCl3 showed the highest catalytic ac-
tivity among them and anisole was obtained in 84% yield after
24 h (Entry 4). The activities of the other metal chlorides were
A proposed mechanism for the iron-catalyzed dechlorina-
Copyright Ó 2004 The Chemical Society of Japan

Chemistry Letters Vol.33, No.10 (2004)
1357
Table 3. FeCl3-catalyzed dechlorination of aryl chlorides
It seems that a key intermediate is the complex 3. When the
aryl group is substituted with electron-withdrawing group, re-
ductive elimination pathway is favored to give the cross cou-
pling product. On the other hand, electron-donating groups on
the aryl rings would increase the electron density of the iron
atom in the intermediate 3. It is well known that such electronic
effect is unfavorable for reductive elimination.11 Consequently,
ꢀ-H elimination of the alkyl group would proceed instead of re-
ductive elimination to afford the corresponding dechlorinated
arene in the present reaction.
It is worth noting that the iron-catalyst shows significant re-
activity even with MeMgCl or PhCH2MgCl. It is remarkable
contrast to the titanocene-catalyzed reaction, which did not work
for the dechlorination at all with such Grignard reagents.9b The
fact would suggest the existence of another reaction pathway
in the present dechlorination, such as radical reaction.12
RMgX (3.0 equiv.), FeCl3 (10 mol%)
Ar-Cl
Ar-H
THF, 50 °C
Entry
1
RMgX
Time/h
48
Product
MeO
Aryl Chloride
Yield/%a
94
MeO
Cl
Cl
i-PrMgBr
tert-BuMgCl
PhCH2CH2MgCl
n-BuMgCl
MeO
MeO
48
24
24
24
48
24
24
48
48
6
90
89
91
74
41
21
9
2
MeO
MeO
MeO
3
Cl
Cl
Cl
4
MeO
MeO
MeO
5
n-C12H25MgBr
PhCH2MgCl
MeMgCl
MeO
MeO
Cl
Cl
Cl
6
References
1
7
MeO
MeO
Me
MeO
MeO
Me
`
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VinylMgBr
Cl
95
91
66
85
9
n-BuMgCl
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2
3
4
5
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n-BuMgCl
H2N
10
11
12b
H2N
Cl
Cl
n-BuMgCl
Cl
n-BuMgCl
48
Me
Me
aYields were determined by GC analyses. bThe reaction was
carried out with 6 equiv. of BuMgCl and 20 mol % of FeCl3.
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Cl
H
+
[Fe(MgCl)2]
R
R
1
MgCl2
Me
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´
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¨
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BuMgCl
Scheme 1.
tion of aryl chloride with Grignard reagent is shown in Scheme 1.
This is based on the iron-catalyzed cross-coupling reaction pro-
posed by Furstner et al.10a,b The catalyst, FeCl3, is reduced by
BuMgCl to generate an ate complex 1, which is active enough
to react with an aryl chloride to form an aryliron complex 2. Fur-
ther reaction of 2 with BuMgCl produces a diorganoiron com-
plex 3. Finally, ꢀ-H elimination followed by reductive elimina-
tion affords a reduced arene.
11 J. P. Collman, L. S. Hegedus, J. R. Norton, and R. G. Finke,
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¨
Published on the web (Advance View) September 18, 2004; DOI 10.1246/cl.2004.1356