Cobalt-catalyzed vinylation of functionalized aryl halides with vinyl acetates

Article abstract of DOI:10.1002/ejoc.200400897

A new method for the preparation of styrene derivatives is described on the basis of the activation of aryl halides by low-valent cobalt species. A combination of CoII bromide and 2,2′-bipyridine is suitable as catalyst for the cross-coupling reaction of a wide range of aromatic halides (X = Cl, Br, I), mostly bearing sensitive moieties, with vinyl acetates. These reactions proceed under mild conditions in the presence of the appropriate reducing agent to afford α-substituted styrene compounds in satisfactory to high yields. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005.

Full text of DOI:10.1002/ejoc.200400897

SHORT COMMUNICATION
Cobalt-Catalyzed Vinylation of Functionalized Aryl Halides with
Vinyl Acetates
Muriel Amatore,[a] Corinne Gosmini,*[a] and Jacques Périchon[a]
Keywords: Catalysis / Cobalt / Cross-coupling / Styrene / Vinylation
A new method for the preparation of styrene derivatives is
described on the basis of the activation of aryl halides by
low-valent cobalt species. A combination of CoII bromide and
2,2Ј-bipyridine is suitable as catalyst for the cross-coupling
reaction of a wide range of aromatic halides (X = Cl, Br, I),
mostly bearing sensitive moieties, with vinyl acetates. These
reactions proceed under mild conditions in the presence of
the appropriate reducing agent to afford α-substituted sty-
rene compounds in satisfactory to high yields.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
scales. Moreover, this process involves a large quantity of
2,2Ј-bipyridine. This paper focuses on a new chemical
method for the vinylation of aryl halides using vinyl ace-
tates (Scheme 1).[13] This reaction relies on our recent find-
ings and demonstrates that in some cases a purely chemical
procedure may be derived from an initial electrochemical
approach, though requiring some important modifica-
tions.[14] Indeed low-valent cobalt may be generated by
chemical reduction of cobalt halide and efficiently activate
aryl halides to form the corresponding “aryl-cobalt” species
prone to undergo cross-coupling with vinyl acetates.
This allows the replacement of expensive metal catalysts
by cheap cobalt salts. Furthermore, aryl bromides, chlorides
and obviously iodides substituted by electron-donating or
-withdrawing groups result suitable, leading usually to short
reactions times. We wish to report here the finalization of
this reaction and to establish its versatility with several aryl
halides and vinyl acetates.
Introduction
Vinylation of aryl halides is a convenient route for syn-
thesis of styrene derivatives. The Heck reaction is a com-
mon method[1] for their preparation, as well as classical pal-
ladium-catalyzed cross-coupling of vinylic stannanes,[2] si-
lanes[3] and boronic acids[4] with aryl halides. Other meth-
ods using organometallic reagents such as alkenylgallium[5]
and vinylaluminium compounds[6] allow the formation of
these useful derivatives. However, all these reactions gen-
erally require palladium catalysts. Styrene derivatives can
also be obtained by cross-coupling vinyl halides with aryl-
boronic acids[7a] or aryl Grignard reagents.[7b] Because of
their poor reactivity, simple vinyl acetates are not often
used for these cross-coupling reactions. Heck was the first
to report cross-coupling of “phenylpalladium chloride” and
vinyl acetate, but only few traces of styrene were observed,
the major products being substituted 2-arylaldehydes and
ketones.[8] Daves et al. described the direct palladium-cata-
lyzed vinylation from vinyl acetate and 5-iodopyrimidines[9]
or iodobenzene.[10] Nevertheless, poor yields of the corre-
sponding styrene derivative were isolated. Cross-coupling
from reactive phenylvinyl acetate and various aryl halides
affords better yields of trans-stilbenes[11] in a single step, yet,
palladium catalysis is still required. In 2001, we described a
cobalt-catalyzed electrochemical vinylation of aryl halides
with vinyl acetates.[12] These reactions involved aryl bro-
mides and chlorides and led to styrene derivatives in good
yields. Although this electrochemical reaction compares fa-
vorably with known chemical process, its use is not general-
ized since electrochemical methods are often viewed as be-
ing difficult to handle and are not generally used on larger
Results and Discussion
We first investigated the reaction between methyl p-chlo-
robenzoate and isopropenyl acetate under the reaction con-
ditions described in Scheme 1. The corresponding aryl-vinyl
compound was synthesized in the presence of 5 mol%
CoBr2(2,2Ј-bipyridine) in a mixture of DMF/pyridine at
50 °C (GC yield 86%). The reducing metal was activated
by traces of acid. The amount of the coupling product was
determined by GC with internal alkane as the standard ref-
erence. The conversion was complete within 3.5 h. Two by-
products could be observed, the reduction product ArH
and the homo-coupling product Ar–Ar. A mixture of aceto-
nitrile/pyridine as reported in the electrochemical ap-
proach[12] could also be used. However, in this case, 40
mol% of CoBr2 and 40 mol% of 2,2Ј-bipyridine were re-
[a] Laboratoire dЈElectrochimie, Catalyse et Synthèse Organique,
UMR 7582, Université Paris 12-C.N.R.S.
2 rue Henri Dunant, 94320 Thiais, France
E-mail: gosmini@glvt-cnrs.fr
Eur. J. Org. Chem. 2005, 989–992
DOI: 10.1002/ejoc.200400897
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
989

M. Amatore, C. Gosmini, J. Périchon
SHORT COMMUNICATION
Scheme 1. General procedure for the cobalt-catalyzed cross-coupling process.
quired to achieve a similar efficiency (5 h, GC yield 84%). yields were obtained when the reaction was carried out at
The use of pyridine as co-solvent is not indispensable, but room temperature, but the reaction time increased in a two
it provides a spectacular acceleration. For example, in pure timefold. At 80 °C, the reaction time decreased but the pro-
DMF, only 55% of aryl chloride was converted to coupling portion of byproducts resulted higher. Using two equiva-
product in 8 h. This may be tentatively rationalized by con- lents of vinyl acetate at 50 °C afforded necessary the coup-
sidering that pyridine may play a stabilizating effect on the ling product with a short reaction time of 2h. Trifluoro-
“aryl-cobalt” species. However, the coupling product was acetic acid was required to activate the manganese powder.
not observed in neat pyridine as the solvent. The efficiency Iodine and acetic acid were also tested but resulted in less
of the reaction also depends on the amounts of catalyst and efficient activation.
2,2Ј-bipyridine (Table 1).
We have thus extended the vinyl acetate coupling process
to various aryl chlorides with isopropenyl acetate according
to Scheme 1. Due to the low reactivity of C–Cl bond, these
halides had to be activated by an electron-withdrawing
group on the aromatic nucleus in order to react with re-
duced cobalt to form “arylcobalt” species. Results are re-
ported in Table 2.
Table 1. Reaction efficiency upon using different amounts of
CoBr2/2,2Ј-bipyridine catalyst for cross-coupling of methyl p-chlo-
robenzoate with isopropenyl acetate (DMF/pyridine, 50 °C).
Entry
CoBr2
(mol %)
Bpy
(mol %)
Time
(h)
Conversion
(GC %)
1
2
3
4
5
10.0
10.0
10.0
2.5
0
68
3,5
1,5
6
19
84
80
10
86
5.0
10.0
2.5
5.0
Table 2. Cross-coupling of isopropenyl acetate with different aryl
chlorides (5 mol% CoBr2(2,2Ј-bipyridine), Mn, DMF/pyridine,
50 °C, unless stated otherwise).
5.0
3,5
Entry
ArCl
Yield (%)
(conversion 100%)
The use of 2,2Ј-bipyridine was essential for the coupling
reaction (Table 1, entry 1). However, when the reaction was
carried out with one or two equivalents of cobalt bromide
versus 2,2Ј-bipyridine, conversion of para-methylchloroben-
zoate and reaction time were the same (Table 1, entries 2,
5). Thus cobalt salt excess versus 2,2Ј-bipyridine did not
interfere in the catalytic process. In fact, only one equivalent
of 2,2Ј-bipyridine was necessary, being presumably enough
to stabilize CoIor0 species in the medium. Similar results
were observed with 10 mol% of the equimolar complex
CoBr2(2,2Ј-bipyridine) though leading to a noticeable in-
crease of the reaction rate (Table 1, entry 3). Conversely,
poor yields were obtained with only 2,5 mol% of this com-
1
2
3
4
5
6
7
8
p-MeOCOC6H4Cl
o-MeOCOC6H4Cl
m-MeOCOC6H4Cl
p-MeCOC6H4Cl
o-MeCOC6H4Cl
p-NCC6H4Cl
75
1
0[a]
2
3
4
5
6
7
8
56[a,b]
65
27[a]
76
o-NCC6H4Cl
m-NCC6H4Cl
73
63[c]
[a] GC yield. [b] Reaction required 10 mol% CoBr2(2,2Ј-bipyridine)
and compound 3 was difficult to separate from ArH. [c] Reaction
run at 80 °C.
Satisfactory yields were observed when the electron-with-
plex (Table 1, entry 4). Several reducing metals were investi- drawing substituent was in para or meta position. The ortho
gated showing that manganese seeming the most suitable substitution with an ester or a carbonyl group prevented
for this system. Thus poor yields were observed with other the formation of the coupling product reflecting steric
reducing metals, e.g. Al or Mg. Similarly, though Zn was requirements and involvement of chelation. Indeed, a nitrile
able to reduce the cobalt complex, this led to the corre- group in ortho position did not affect the cross coupling.
sponding aromatic organozinc chloride as byproduct.[15]
The reactivity of aryl bromides was also investigated. The
The use of 10 equivalents of Mn versus ArCl was necessary coupling reactions took place with good yields with isopro-
to observe a fast conversion with good yields, yet decreasing penyl acetate. The increased C–Br bond reactivity allowed
its relative amount led to increasing reaction times. Never- good yields even in the presence of electron-donating
theless, the use of only 2 equivalents of Mn afforded the groups. Results are reported in Table 3. Again, the ortho
coupling product but required longer reaction time. Similar position was not very compatible with this process.
990
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2005, 989–992

Cobalt-Catalyzed Vinylation of Functionalized Aryl Halides
SHORT COMMUNICATION
Table 3. Cross-coupling of isopropenyl acetate with different aryl powder, which needs to be previously activated by acid
traces. As shown in our previous work where CoI is stabi-
bromides (5 mol% CoBr2(2,2Ј-bipyridine), Mn, DMF/pyridine,
50 °C, unless stated otherwise).
lized by vinyl acetate in acetonitrile/pyridine,[17] cobalt spe-
Entry
ArBr
Yield (%)
(Conversion 100%)
cies is also probably coordinated to vinyl acetate. The low-
valent cobalt most likely reacts with aryl halide by oxidative
addition to form an “arylcobalt” species. This species could
undergo a substitution reaction with the carbon attached
to the acetate group after ligand exchange. (Scheme 2). The
electronically preferred direction of addition appears to fav-
our a transfer of the aryl group onto the carbon attached
to the ester group. This suggests the involvement of the a
six centers transition state [C] in which the aryl group is
well-positioned to be added on the most substituted carbon
atom of the double bond. With vinyl ethers instead of vinyl
acetates, no reaction was occurred. In this last case, the for-
mation of the six centers transition state is not possible, this
confirms our hypothesis. Once styrene derivative released,
cobalt is reduced again by the excess of Mn to regenerate
CoIor0 catalyst. Electrochemical studies are still in progress
in order to establish more soundly the mechanism of this
chemical reaction and to identify the “arylcobalt” species.
1
2
3
4
5
6
7
8
p-MeOC6H4Br
o-MeOC6H4Br
m-MeOC6H4Br
p-AcOC6H4Br
p-NMe2C6H4Br
p-MeOCOC6H4Br
o-EtOCOC6H4Br
m-EtOCOC6H4Br
p-MeCOC6H4Br
p-NCC6H4Br
78
48[a,b]
81
9
10
11
12
13
1
14
15
4
74
44[c]
75
0[a]
82[a,d]
51
9
10
11
42[a]
16[a]
6
7
o-NCC6H4Br
[a] GC yields. [b] Reaction required 10 mol% CoBr2(2,2Ј-bipyri-
dine). [c] Compound 13 was recrystallized from methanol. [d] Com-
pound 15 was difficult to separate from ArH.
Aryl iodides such as p-iodoanisole and ethyl p-iodoben-
zoate could be coupled with isopropenyl acetate. However,
the corresponding “arylcobalt” species were too reactive in
the medium leading essentially to the formation of ArH and
Ar–Ar.[16]
The process was finally extended to halopyridines and
isopropenyl acetate. The cross coupling reaction was ef-
ficient with 3- and 4-halopyridines notably with chloropyri-
dines. The 3-chloropyridine could be coupled in 83% yield
(compound 22) with 5 or 10 mol% of CoBr2(2,2Ј-bipyri-
dine). However, the reaction time was increased with 5
mol% (24 h instead of 4.5 h). The more reactive 4-chloro-
pyridine hydrochloride led to 67% yield (compound 23)
with only 5 mol% of catalyst within 4 h. On the other hand,
the major product was the reduction one upon using the
more activated 3- and 4-bromopyridines. Table 4 demon-
strates the scope of the reaction upon using various vinyl
acetates and different aryl halides.
Table 4. Coupling between different vinyl acetates and aryl halides
in the cobalt-catalyzed cross-coupling (5 mol% CoBr2(2,2Ј-bipyri-
dine), Mn, DMF/pyridine, 50 °C).
Scheme 2. Mechanism proposal for the vinylation of aryl halides
with vinyl acetates.
Conclusions
In conclusion, we have developed a Co-catalyzed chemi-
cal process devoted to the preparation of aryl-vinyl com-
pounds from various aryl or heteroaryl halides and vinyl
acetates. This catalytic process using CoBr2(2,2Ј-bipyridine)
appears extremely suitable as catalyst for a broad range of
[a] GC yields.
Yields were lower than with isopropenyl acetate. These aryl chlorides and bromides bearing an electron-donating
differences in reactivity may reflect in the one hand the or withdrawing group. To the best of our knowledge, this is
poor solubility of vinyl acetate in the medium and its trend the first palladium-free direct preparation of α-substituted
towards polymerization and, on the other hand, the steric styrene derivatives with satisfactorily good yields. More-
bulk of cyclopentenyl acetate.
over, this very versatile process compares favourably with
From a mechanistic point of view, CoII associated to the procedures using palladium catalysis since aryl bro-
2,2Ј-bipyridine is reduced either in CoI or 0 by manganese mides and chlorides do not bring difficulties in the cross-
Eur. J. Org. Chem. 2005, 989–992
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
991

M. Amatore, C. Gosmini, J. Périchon
SHORT COMMUNICATION
(14), 143769-34-0; ethyl 3-isopropenylbenzoate (15), 105640-23-1;
methyl 4-ethenylbenzoate (16), 1076-96-6; methyl 4-(cyclopent-1-
enyl)benzoate (17), 579472-58-5; 4-ethenylbenzonitrile (18), 3435-
51-6; 4-(cyclopent-1-enyl)benzonitrile (19), 19936-20-0; 4-meth-
oxystyrene (20), 637-69-4; 4-(cyclopent-1-enyl)-1-methoxybenzene
(21), 709-12-6; 3-isopropenylpyridine (22), 15825-89-5, 4-isopro-
penylpyridine (23), 17755-30-5.
coupling. Work is now in progress to elucidate the mecha-
nism of this reaction.
Experimental Section
GC analysis was carried out using a gas chromatograph Varian
3300 provided with a 25-m CPSIL5CB capillary column. Mass
spectra were recorded with a GCQ Thermoelectron spectrometer
coupled to a gas chromatograph Varian (25-m CPSIL5CB/MS cap-
illary column). Column chromatography was performed on silica
gel 60, 70-230 mesh with pentane/ether as eluent. 1H, and 13C spec-
tra were recorded in CDCl3 at 200 and 400 MHz. All solvents and
reagents were purchased and used without further purification. No
inert atmosphere was required.
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1. Typical Procedure for Vinylation of Aryl Halides: To a solution of
DMF (15 mL) and pyridine (2 mL) were successively added CoBr2
(0.025 mmol, 55 mg), 2,2Ј-bipyridine (0.025 mmol, 39 mg) and
manganese powder (50 mmol, 2.75 g). Aryl halide (5 mmol) and
vinyl acetate (10 mmol) were then introduced into the solution. The
medium was activated by traces of trifluoroacetic acid (100 µL) and
stirred at 50 °C until aryl halide was consumed. The amount of the
corresponding coupling product was measured by GC by using an
internal reference (dodecane, 200 µL). The reaction mixture was
poured into a solution of 2 n HCl (40 mL) and extracted with di-
ethyl ether (3 × 40 mL). The organic layer was washed with a satu-
rated solution of NaCl (20 mL) and dried with MgSO4. Evapora-
tion of diethyl ether and purification by column chromatography
on silica gel (pentane/diethyl ether) afforded the styrene derivatives
that were characterized by NMR (1H, 13C) and mass spectrometry.
2. Typical Vinylation Procedure for Cyano-, Aminoaryl Halides and
Pyridyl Halides (Compounds 6, 7, 8, 13, 22, 23): The procedure for
vinylation of cyano-, aminoaryl halides and halopyridines was the
same as for the other aryl halides except for the standard work-up
procedure. The reaction mixture was filtered through Celite, poured
into a saturated solution of NH4Cl (40 mL) and extracted with
diethyl ether (3 × 40 mL). The organic layer was washed with satu-
rated solution of NaCl (20 mL) and dried over MgSO4. Evapora-
tion of diethyl ether and purification by column chromatography
on silica gel (pentane/diethyl ether) afforded the styrene derivatives
that were characterized by NMR (1H, 13C) and mass spectrometry.
[12] a) P. Gomes, C. Gosmini, J. Périchon, Tetrahedron 2003, 59,
2999–3002; b) P. Gomes, C. Gosmini, J. Périchon, PCT Int.
WO 03/004729 A3, January 16, 2003.
[13] P. Gomes, C. Gosmini, J. Périchon, PCT Int. WO 2004/065336
A1, August 5, 2004. For details see the Experimental Section.
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1045; b) P. Gomes, C. Gosmini, J. Périchon, Fr. 2826982, July
3, 2001; c) H. Fillon, C. Gosmini, J. Périchon, J. Am. Chem.
Soc. 2003, 125, 3867–3870; d) H. Fillon, C. Gosmini, J.
Périchon, PCT Int. WO 03/004504 A1, January, 16, 2003.
[15] Unpublished results.
[16] With p-iodoanisole and ethyl p-iodobenzoate, we observed
respectively 41% (GC yield) and only few traces of the corre-
sponding coupling products. This work was not optimized be-
cause aryl bromides and chlorides were best candidates for this
cross-coupling reaction and it was more interesting to develop
a process using less expensive starting materials.
3. CAS Registry Numbers (Provided by the Authors): methyl 4-iso-
propenylbenzoate (1), 26581-23-7; methyl 2-isopropenylbenzoate
(2), 62291-44-5; 1-(4-isopropenylphenyl)ethanone (4), 5359-04-6; 4-
isopropenylbenzonitrile (5), 19956-03-7; 2-isopropenylbenzonitrile
(6), 23877-63-6; 3-isopropenylbenzonitrile (7), 53097-35-1; 1-iso-
propenyl-4-trifluoromethylbenzene (8), 55186-75-9; 4-isopropenyl-
1-methoxybenzene (9), 1712-69-2; 2-isopropenyl-1-methoxyben-
zene (10), 10278-02-1; 3-isopropenyl-1-methoxybenzene (11),
25108-57-0; 4-isopropenylphenyl acetate(12), 2759-56-0; 4-isoprop-
enyldimethylaniline (13), 25108-56-9; ethyl 2-isopropenylbenzoate
[17] O. Buriez, J.-Y. Nédelec, J. Périchon, J. Electroanal. Chem.
2001, 506, 162–169.
Received December 21, 2004
992
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2005, 989–992