New efficient preparation of functionalized arylzinc or thienylzinc compounds from aryl or thienyl chlorides using cobalt catalysis

Article abstract of DOI:10.1055/s-2005-872250

A new chemical method is described for the preparation of aryl or thienyl zinc intermediates from their corresponding aromatic or thienyl chlorides in a mixture of acetonitrile-pyridine, using cobalt catalysis. This procedure allows for the synthesis of a

Full text of DOI:10.1055/s-2005-872250

LETTER
2171
New Efficient Preparation of Functionalized Arylzinc or Thienylzinc
Compounds from Aryl or Thienyl Chlorides Using Cobalt Catalysis
P
C
reparation of
F
u
o
nctionalized
r
A
rylzin
i
c
or Thi
n
enylzinc Co
n
mpounds e Gosmini,* Muriel Amatore, Stéphanie Claudel, Jacques Périchon
Laboratoire d’Electrochimie, Catalyse et Synthèse Organique, UMR 7582, Université Paris 12-CNRS, 2 Rue Henri Dunant, 94320 Thiais,
France
Fax +(33)149781148; E-mail: gosmini@glvt-cnrs.fr
Received 21 June 2005
More recently, we have established that readily available
Abstract: A new chemical method is described for the preparation
cobalt halide and zinc dust are convenient for the facile
of aryl or thienyl zinc intermediates from their corresponding aro-
matic or thienyl chlorides in a mixture of acetonitrile–pyridine, us-
ing cobalt catalysis. This procedure allows for the synthesis of a
chemical preparation of arylzinc species from the corre-
8
sponding bromides or iodides in acetonitrile. This new
variety of functionalized arylzinc species from reactive arylchlo- and versatile process favourably compares with known
rides or chlorothiophenes in good to excellent yields. Some of these chemical processes and could be applied to the prepara-
arylzinc compounds have been coupled with aromatic bromides us-
tion of 3-thienylzinc bromide in a single operation from 3-
ing palladium catalysis.
bromothiophene. However, the results obtained with aryl-
chlorides were disappointing.
Key words: cobalt halide, catalysis, zinc, thiophenes, aromatic
chlorides
Here, we wish to report a new chemical reaction aimed at
preparing aromatic zinc species from aromatic or thienyl
chlorides. Aromatic chlorides are generally inexpensive
and readily available substrates compared to the corre-
sponding bromides and iodides.
The utility of arylzinc compounds in organic synthesis has
been recognized for a long time. Their remarkable func-
tional group tolerance allows the synthesis of functional-
In acetonitrile, the reduction of CoBr leads to a Co(I) spe-
ized cross-coupling products without the need for
protecting groups. These polyfunctional zinc reagents can
2
cies which does not react with the C–Cl bond at room tem-
perature. At 50 °C, ArCl is partially converted into
ArZnCl; the entire starting compound does not react due
to the disproportionation of Co(I). The effect upon addi-
tion of various ligands on the aryl chloride/arylzinc con-
version has been examined in order to decrease the rate of
disproportionation. In fact, some recent electrochemical
studies have shown that the use of additives, such as vinyl
acetate and methyl vinyl ketone, stabilize the electrogen-
erated Co(I) in acetonitrile–pyridine.9 Unfortunately,
these ligands as well as adiponitrile do not stabilize Co(I)
in acetonitrile. Nevertheless, the formation of chemical
arylzinc compounds from aryl chlorides was successful
1
be readily prepared either by direct insertion of zinc or by
nucleophilic catalysis of the iodine–zinc exchange reac-
2
tion from aryl iodides. From aryl chlorides or bromides,
the preparation of these organozinc species was formerly
3
possible though transmetallation of organolithium or
4
Grignard reagents using zinc halides. However, such a
procedure could only be applied to compounds bearing re-
active functional groups (CO, CN, COOR etc.), provided
that the reaction was carried out at low temperature. This
drawback was circumvented by synthesizing the orga-
nozinc species from aryl bromides using activated zinc
5
(
Rieke’s zinc), but the difficulty of handling this reagent
using CoBr in a mixture of acetonitrile–pyridine as de-
makes this procedure very sensitive to reaction condi-
tions.
2
scribed in our electrochemical process (just aryl bromide
or iodide could react in acetonitrile). The presence of py-
ridine is required to avoid the fast disproportionation of
Co(I) and allow its oxidative addition into the C–Cl bond.
Under these conditions (in the presence of pyridine),
yields are higher at room temperature or at 50 °C than in
pure acetonitrile even at 50 °C. These yields and the con-
sumption of ArCl depend on the amount of pyridine. It has
been shown that an acetonitrile–pyridine ratio of 12:8 has
given the best yields. In these conditions, yields of
ArZnCl depend on the amount of catalyst, the reaction
temperature and solvents. The study was performed with
p-CNC H Cl (Equation 1, Table 1).
In our laboratory, several years ago, we successfully syn-
thesized functionalized arylzinc compounds from aryl ha-
lides, bromides as well as chlorides, using simple
electrochemical methods. These electrosynthetic methods
6
7
involve a nickel or more recently a cobalt catalyst asso-
ciated with the electroreduction of aromatic halides in an
undivided cell using the sacrificial anode process under
mild conditions. The use of cobalt allowed us to achieve
both the synthesis of organozinc reagents using a wide
variety of solvents and to use a less toxic catalyst than
nickel.
6
4
SYNLETT 2005, No. 14, pp 2171–2174
0
2
.0
9
.2
0
0
5
Advanced online publication: 03.08.2005
DOI: 10.1055/s-2005-872250; Art ID: G16805ST
©
Georg Thieme Verlag Stuttgart · New York

2
172
C. Gosmini et al.
LETTER
CN
1
) AllylCl (0.3 equiv), MeCN, CF3CO2H, r.t., 3 min
) py, CoBr2 (0.03 or 0.23 equiv), T °C ,
CoBr2
0.1 equiv)
+
Zn
(3 equiv)
(
2
ZnCl
NC
Cl (1 equiv)
Equation 1
Table 1 Influence of Various Parameters on the Formation of p-CNC H ZnCl
4
6
Entry
Solvent (12:8)
Amount of CoBr (mol%)
Temperature
Reaction time (h)
GC yield of ArZnCl (%)
2
1
2
3
4
5
CH CN–Pyridine
13
13
33
33
33
r.t.
23
6
78
3
CH CN–Pyridine
50 °C
r.t.
54 (ArH = 35)
82
3
CH CN–Pyridine
4
3
CH CN–Pyridine
50 °C
r.t.
2
60 (ArAr = 20)
traces
3
DMF–Pyridine
24
9
Reaction times depend both on the amount of CoBr and stable as in DMF–pyridine. As a consequence, the rate of
2
temperature. At the same temperature, an increased of disproportionation of Co(I) as well as the rate constant be-
amount of CoBr decreases the reaction time (Table 1, en- tween the electrogenerated Co(I) and aryl halides were
2
tries 1 and 3 or entries 2 and 4) and results in a slight im- lower. Therefore, reactions are carried out in acetonitrile–
provement in the yields. Increasing the temperature pyridine from various functionalized aryl chlorides with
decreases the reaction time but lower yields are obtained. 33 mol% of CoBr at room temperature, in order to ensure
2
Acetonitrile was also replaced by DMF, however, only moderate reaction rates and to improve the yields
traces of the corresponding arylzinc species are observed (Equation 2, Table 2).
after 24 hours at room temperature (Table 1, entry 5). This
Arylzinc chlorides are readily prepared by the reaction of
aryl chlorides with commercially available zinc dust acti-
was not surprising considering that reduction of CoBr in
2
acetonitrile–pyridine led to a Co(I) species about twice as
vated by traces of acid (CF COOH) in the presence of
3
1
) AllylCl (0.3 equiv), MeCN, CF3CO2H, r.t., 3 min
CoBr2
0.1 equiv)
Zn
(3 equiv)
+
FG
ZnCl
(
2) py, CoBr2 (0.23 equiv), r.t.,
FG
(1 equiv)
Cl
Equation 2
Table 2 Formation of Organozinc Species from Functionalized Aryl Chlorides
Entry
FG-C H Cl
ArZnCl (%)
ArCl recovered (%)
Reaction time (h)
ArH
ArAr
6
4
FG
1
2
3
4
5
6
7
8
9
H
95
45
82
78
84
69
75
0
0
0
0
0
0
0
0
0
0
0
22
31
4
5
55
11
13
16
17
18
13
14
9
0
0
p-MeO
p-CN
m-CN
o-CN
p-CF3
7
5
9
2
0
23
4
7
p-MeCO
o-MeCO
p-MeCO2
p-MeSO2
7
4
87
5
81
91
4
1
0
4
0
Synlett 2005, No. 14, 2171–2174 © Thieme Stuttgart · New York

LETTER
Preparation of Functionalized Arylzinc or Thienylzinc Compounds
2173
CoBr (0.33 equiv) in acetonitrile–pyridine at room tem- Some aromatic organozinc species mentioned in Table 2
2
perature. As described in our previous work, addition of have been cross-coupled with different activated aryl bro-
allyl chloride in a preliminary step makes the introduction mides (1 equiv vs. ArCl) in the presence of a catalytic
2
+
of hydroscopic ZnBr unnecessary, Zn salts being gen- amount of PdCl (PPh ) .The organozinc species obtained
2
2
3 2
erated in situ in this preliminary step. The resulting orga- from methyl p-chlorobenzoate (Table 2, entry 9) was cou-
nozinc species are converted into aromatic iodide by the pled with p-bromobenzonitrile at room temperature in
addition of iodine. The amount of aromatic iodide is mea- 77% yield. Conversely, the coupling between p-CN-
sured by GC using an internal reference (alkane).
PhZnCl (Table 2, entry 3) and ethyl p-bromobenzoate
gave only a 25% yield under the same conditions. In fact,
the organozinc species from p-ethyl bromobenzoate was
formed. On the other hand, a 48% yield of coupled prod-
uct was isolated from o-CNPhZnCl (Table 2, entry 5) and
ethyl p-bromobenzoate. In conclusion, the amount of cou-
pling product depends on the nature of the arylzinc chlo-
ride and in some cases, this coupling could be
quantitative. Some studies are in progress to achieve the
cross-coupling of such arylzinc compounds with various
aromatic halides.
This new method generally gives the expected organozinc
species in good to excellent yields with aryl chlorides sub-
stituted by an electron-withdrawing group (Table 2, en-
tries 3, 4, 5, 6, 7, 9, 10). Even with unactivated
chlorobenzene derivatives the corresponding organozinc
compound is detected, which is contrary to our electro-
chemical methods (Table 2, entries 1–2); however, the re-
action times are increased. This indicates that Co(I) reacts
too slowly with unactivated chlorobenzene derivatives
under these conditions. Moreover, no organozinc com-
pound is detected with o-chloroacetophenone (Table 2, In the following series of experiments, we tried to apply
entry 8), surprisingly, o-chloroacetophenone resulted in a the standard method described for aromatic chlorides to
dimerized adduct. The complexation of cobalt with the chlorothiophenes (Equation 3).
carbonyl group should avoid the transmetallation reac-
The results concerning chlorothiophenes are reported in
tion. With other reagents, it can be pointed out that the po-
Table 3 and show that the preceding method affords orga-
sition of the substituent has again a slight influence on the
nozinc species in good to excellent yields (Table 3, entries
yields as revealed in Table 2 (entries 3–5). However, the
1
, 3). Chlorothiophenes were reactive towards Co(I) at
reaction rate decreases when a substituent is placed at the
ortho-position. This method also allows for the formation
of arylzinc species from aryl bromides in the same yields
as obtained in pure acetonitrile. Unfortunately the reaction
time increases; for instance, ethyl p-bromobenzoate gives
room temperature but the reaction is particularly long es-
pecially with 3-chlorothiophene. In fact, this last com-
pound is less reactive than 2-chlorothiophene. However to
improve the reaction times, the medium was heated at
5
0 °C. Under these conditions, yields were good to excel-
8
0% yield of the corresponding arylzinc in 15 minutes in
lent (Table 3, entries 2, 4).
acetonitrile whereas 81% yield of ArZnBr is obtained in
three hours in a mixture of acetonitrile–pyridine.
In order to confirm our estimated yields of thienylzinc
species, we have coupled these compounds with ethyl p-
1) AllylCl (0.3 equiv), MeCN, CF3CO2H, r.t., 3 min
S
CoBr2
+
Zn
(0.1 equiv)
(3 equiv)
S
ZnCl
2) py, CoBr2 (0.23 equiv), r.t.,
(1 equiv)
Cl
Equation 3
Table 3 Formation of Organozinc Species from Chlorothiophenes
Entry
1
Chlorothiophene
Temperature
r.t.
Reaction time (h)
7
ThiopheneZnCl
80
Cl-Thiophene recovered (%)
0
S
Cl
2
3
S
50 °C
r.t.
2
88
67
0
5
Cl
S
24
Cl
S
4
50 °C
4
80
0
Cl
Synlett 2005, No. 14, 2171–2174 © Thieme Stuttgart · New York

2
174
C. Gosmini et al.
LETTER
bromobenzoate using PdCl (PPh ) as catalyst. Starting References
2
3 2
from 2- or 3-thienylchloride, the corresponding biaryls are
obtained in 74% yield in the two cases when the corre-
sponding thienylzinc species are prepared at 50 °C
(
(
(
(
(
1) Ikegami, R.; Koresawa, A.; Shibata, T.; Takagi, K. J. Org.
Chem. 2003, 68, 2195.
2) Kneisel, F. F.; Dochnahl, M.; Knochel, P. Angew. Chem. Int.
Ed. 2004, 43, 1017.
(
Table 3, entries 2, 4).
3) Tucker, C. E.; Majid, T. N.; Knochel, P. J. Am. Chem. Soc.
To our knowledge, there is no example of any direct ver-
satile chemical synthesis of thienylzinc compounds from
chlorothiophenes.
1
992, 114, 3983.
4) Krasovskiy, A.; Knochel, P. Angew. Chem. Int. Ed. 2004, 43,
333.
5) (a) Zhu, L.; Wehmeyer, R. M.; Rieke, R. D. J. Org. Chem.
3
These results show that this new chemical method gives
the expected organozinc species in good yields from aryl
or thienyl chlorides. With chloropyridines, the corre-
sponding zinc species have unfortunately been obtained in
only low yields up to now. Some studies are still in
progress to extend the process to these compounds.
1991, 56, 1445. (b) Rieke, R. D. Aldrichimica Acta 2000,
33, 52.
(
6) (a) Sibille, S.; Ratovelomanana, V.; Périchon, J. J. Chem.
Soc., Chem. Commun. 1992, 283. (b) Gosmini, C.; Nédélec,
J.-Y.; Périchon, J. Tetrahedron Lett. 1997, 38, 1941.
(7) (a) Gosmini, C.; Rollin, Y.; Nédélec, J.-Y.; Périchon, J. J.
Org. Chem. 2000, 65, 6024. (b) Fillon, H.; Gosmini, C.;
Nédélec, J.-Y.; Périchon, J. Tetrahedron Lett. 2001, 42,
In conclusion, we have established that cobalt(II) bromide
associated with pyridine can be used for the simple, high-
yielding preparation of a broad range of functionalized
aryl or thienyl zinc species starting from readily available
corresponding chlorides, these species being so far ob-
tained by transmetallation.
3843. (c) Fillon, H.; Le Gall, E.; Gosmini, C.; Périchon, J.
Tetrahedron Lett. 2002, 43, 5941.
(8) (a) Fillon, H.; Gosmini, C.; Périchon, J. J. Am. Chem. Soc.
2003, 125, 3867. (b) Kazmierski, I.; Gosmini, C.; Paris, J.-
M.; Périchon, J. Tetrahedron Lett. 2003, 44, 6417.
9) Buriez, O.; Nédélec, J.-Y.; Périchon, J. J. Electroanal.
Chem. 2001, 506, 162.
(
Acknowledgment
The authors gratefully acknowledge the financial support provided
by Rhodia.
Synlett 2005, No. 14, 2171–2174 © Thieme Stuttgart · New York