Cobalt-catalyzed direct electrochemical cross-coupling between aryl or heteroaryl halides and allylic acetates or carbonates

Article abstract of DOI:10.1021/jo026421b

The electroreduction of a mixture of functionalized aromatic or heteroaromatic bromides or chlorides and allylic compounds such as acetates or carbonates in an electrochemical cell fitted with a sacrificial iron anode affords, in the presence of cobalt halide associated with pyridine as ligand in acetonitrile or DMF, the corresponding coupling product in good yields.

Full text of DOI:10.1021/jo026421b

Palladium complexes have proven to be the most
versatile catalyst. The discovery of these catalysts in
allylic substitution is one of the milestones in organic
synthesis. Although the advent of Pd(0) has solved a
number of industrial problems, this catalyst has a major
limitation: the cost of Pd becomes prohibitive for indus-
trial application when the catalytic turnover is low.
Hence, developing new catalytic systems are of par-
ticular importance. As a matter of fact, Mo,8 Zr,9 Pt,10
and Rh11 complexes have been studied. In most cases,
only very reactive substrates such as allylic carbonates
provide good yields.
Coba lt-Ca ta lyzed Dir ect Electr och em ica l
Cr oss-Cou p lin g betw een Ar yl or Heter oa r yl
Ha lid es a n d Allylic Aceta tes or Ca r bon a tes
Paulo Gomes, Corinne Gosmini,* and J acques Pe´richon
Laboratoire d’Electrochimie, Catalyze et Synthe`se
Organique, UMR 7582, Universite´ Paris 12sCNRS, 2,
Rue Henri Dunant, F-94320 Thiais, France
gosmini@glvt-cnrs.fr
Received September 9, 2002
A few years ago, in our laboratory, the electrochemical
reduction of aryl halide and allylic compounds12 was
reported in DMF in the presence of a catalytic amount
of NiBr2-2,2′-bipyridine at 60 °C. This method presents
two major drawbacks: (1) Elimination of nickel is now
recommended for environmental reasons. (2) Allylic
acetate must be introduced slowly all along the electroly-
sis since the oxidative addition of electrogenerated Ni0-
bpy is faster on allylic compounds than on aryl halides.
Recently, we have discovered a more simple catalytic
system involving cobalt halides used in DMF-pyridine
or acetonitrile-pyridine mixtures. This catalyst allowed
us to achieve the electrochemical synthesis of mono-13 and
dizinc14 species and was applied to the synthesis of
arylpyridines,15 arylpyrimidines,16 and even conjugate
addition of aromatic halides onto activated olefins17 using
the sacrificial anode process.
Previously, Iqbal18 has described that allylation of 1,3-
dicarbonyl compounds could be achieved with allyl
acetates in the presence of catalytic amounts of cobalt-
(II) chloride in 1,2-dichloroethane in high yields.
We describe in this paper the scope of this electro-
chemical procedure using the cobalt-pyridine complex
in DMF or acetonitrile in the field of arylation of allylic
acetate and derivatives (eq 1) from aryl bromides or
chlorides. We first studied the coupling reaction between
aryl bromides substituted by electron-donating or electron-
withdrawing groups and allyl acetate catalyzed by cobalt
bromide in acetonitrile/pyridine mixture (v/v ) 9/1).
Abstr a ct: The electroreduction of a mixture of functional-
ized aromatic or heteroaromatic bromides or chlorides and
allylic compounds such as acetates or carbonates in an
electrochemical cell fitted with a sacrificial iron anode
affords, in the presence of cobalt halide associated with
pyridine as ligand in acetonitrile or DMF, the corresponding
coupling product in good yields.
In tr od u ction
The arylallyl skeleton is the basic structure of many
natural products1 like estragol (p-CH3O-C6H4CH2CHd
CH2), eugenol (2-CH3O-C6H4OH-4-CH2CHdCH2), osmo-
rhyzol (1,3-di-CH3O-C6H4-4-CH2CHdCH2), etc. Substi-
tution reactions of allylic halides with aromatic organo-
metallic reagents have provided an important route for
the synthesis of these allylic compounds. However, a
large class of useful compounds is hardly accessible from
aromatic Grignard reagents,2 i.e., those bearing a reactive
functional group such as aldehydes, esters, ketones, or
nitriles on the aromatic nuclei. Alternatively, arylzinc
compounds are convenient reagents owing to their high
functional group tolerance and their good reactivity in
the presence of the soluble salt CuCN‚2LiCl.3 Using this
approach, Knochel reported the coupling reaction be-
tween arylzinc reagents and various electrophiles,4 namely,
allylic halides. In the same manner, arylpalladium spe-
cies prepared in situ from arylmercuric and palladium-
(II) salts can react with allylic halides at room temper-
ature to produce allylaromatic compounds.5 Although
organomercuric reagents exhibit a good functional group
compatibility, their high toxicity is well-known.
(8) (a) Trost, B. M.; Merlic, C. A. J . Am. Chem. Soc. 1990, 112, 9590.
(b) Malkov, A. V.; Baxendale, I. R.; Dvorak, D.; Mansfield, D. J .;
Kocovsky, P. J . Org. Chem. 1999, 64, 2737.
(9) (a) Temple, J . S.; Schwartz, J . J . Am. Chem. Soc. 1980, 102, 7382.
(b) Temple, J . S.; Riediker, M.; Schwartz, J . J . Am. Chem. Soc. 1982,
104, 1310.
(10) Kurosawa, H.; Ogoshi, S.; Kawasaki, Y.; Murai, S.; Miyoshi,
M.-a.; Ikeda, I. J . Am. Chem. Soc. 1990, 112, 2813.
(11) Tsuji, J .; Minami, I.; Shimizu, I. Tetrahedron Lett. 1984, 25,
5157.
Allylic stannanes can be prepared from allylic acetates
derivatives6 and coupled with aryl halides by a palladium
catalysis.7 In that case, the best results were obtained
from aryl bromides.
(12) Durandetti, M.; Ne´de´lec, J .-Y.; Pe´richon, J . J . Org. Chem. 1996,
61, 1748.
(13) (a) Gosmini, C.; Rollin, Y.; Pe´richon, J . Patent application 99/
08480, France, J uly 1, 1999. (b) Gosmini, C.; Rollin, Y.; Ne´de´lec, J .-Y.;
Pe´richon, J . J . Org. Chem. 2000, 65, 6024.
(14) Fillon, H.; Gosmini, C.; Ne´de´lec, J .-Y.; Pe´richon, J . Tetrahedron
Lett. 2001, 42, 3843.
(15) Gosmini, C.; Ne´de´lec, J .-Y.; Pe´richon, J . Tetrahedron Lett. 2000,
41, 5039.
(16) Gosmini, C.; Ne´de´lec, J .-Y.; Pe´richon, J . Tetrahedron Lett. 2000,
41, 201.
(17) Gomes, P.; Gosmini, C.; Ne´de´lec, J .-Y.; Pe´richon, J . Tetrahedron
Lett. 2000, 41, 3385.
(18) Maikap, G. C.; Madhava Reddy, M.; Mukhopadhyay, M.; Bhatia,
B.; Iqbal, J . Tetrahedron 1994, 50, 9145.
(1) Wenkert, E.; Fernandes, J . B.; Michelotti, E. L.; Swindell, C. S.
Synthesis 1983, 701.
(2) (a) Kharasch, M. S.; Reinmuth, O. In Grignard Reactions of
Nonmetallic Substances; Coustable: London, 1954. (b) Hayashi, T.;
Konishi, M.; Yokota, K.-i.; Kumada, M. J . Chem. Soc., Chem. Commun.
1981, 313. (c) Hayashi, T.; Konishi, M.; Yokota, K.-i.; Kumada, M. J .
Organomet. Chem. 1985, 285, 359.
(3) Zhu, L.; Wehmeyer, R. M.; Rieke, R. D. J . Org. Chem. 1991, 56,
1445.
(4) Knochel, P.; Singer, R. D. Chem. Rev. 1993, 93, 2117.
(5) Heck, R. F. J . Am. Chem. Soc. 1968, 90, 5531.
(6) Kosugi, M.; Sasazawa, K.; Shimizu, Y.; Migita, T. Chem. Lett.
1977, 301.
(7) Tsuji, J . Tetrahedron 1986, 42, 4361.
10.1021/jo026421b CCC: $25.00 © 2003 American Chemical Society
Published on Web 12/20/2002
1142
J . Org. Chem. 2003, 68, 1142-1145

TABLE 1. Cou p lin g Rea ction betw een Su bstitu ted Ar yl
Br om id es a n d Allyl Aceta te
The mechanism is complex and should involve the
transitory electrogenerated Co(I)-pyridine species, closely
associated with allyl and its oxidative addition on aryl
halide. Electroanalytical investigations are in progress,
and results will be soon reported.
Resu lts a n d Discu ssion
All reactions are conducted in a one-compartment cell
already described,19 using a consumable iron anode and
a stainless steel cathode. Commercial solvents are used
without purification. The ionic conductivity of the me-
dium is ensured by addition of NBu4BF4 as supporting
electrolyte. Electrolyses are run at constant current
intensity of 0.2 A (0.01 A/cm2), at 50 °C, and under an
inert atmosphere of argon. They are quenched after total
consumption of ArX. The cathodic potential during the
electrolysis remains at ca. -1.1 V/SCE, which is the
potential of formation of the Co(I) complex from CoX2-
pyridine20 in the acetonitrile medium. In a typical experi-
ment, 50 mL of a mixture of solvent (45 mL of acetonitrile
or DMF and 5 mL of pyridine) containing 7.5 mmol of
ArBr (0.15 M), 20 mmol of allyl acetate (0.4 M), 1 mmol
of CoBr2 (0.02 M), and 0.5 mmol of NBu4BF4 (0.01 M)
was introduced in the cell. Results obtained in acetoni-
trile-pyridine from phenyl bromides substituted by an
electron-donating or electron-withdrawing groups and
allyl acetate are reported in Table 1.
a
Isolated yields, based on initial ArBr.
starting compounds are converted into ArAr in the case
of p-bromoacetophenone and into ArH in the case of
p-bromobenzamide. The coupling with m-bromochlo-
robenzene (Table 1, entry 9) shows that only the carbon-
bromine bond is reactive toward allyl acetate. Neverthe-
less, electroreductive coupling reaction can be extended
to aryl chlorides providing that we modify the conditions
described before.
In our case, allylic substrate is totally introduced in
the cell at the beginning of the electrolysis, unlike the
electrochemical process using nickel complex as cata-
lyst.12 All the starting product ArBr is consumed at 4F/
mol.
Several metals can be used as anodes such as alumi-
num and zinc, but iron gives better yields in coupling
product. In the absence of pyridine as cobalt-ligand in
acetonitrile or DMF, only a small amount of arylallyl is
formed, the major product being ArH. In fact, we have
reported in a previous paper the efficiency of pyridine to
stabilize the electrogenerated active cobalt species.21
Results are similar if the electrolysis is carried out at
50 or 70 °C, but the coupling yield decreases if the
reaction is carried out at room temperature.
These results show that this new method gives high
yields of coupling product from aryl bromides substituted
either by electron-withdrawing (Table 1, entries 1-10)
or electron-donating (Table 1, entry 11) groups. Further-
more, the yields do not depend on the position of the
functional group on the aromatic nucleus (Table 1, entries
1 and 8 or entries 2 and 10). With a ketone (Table 1, entry
3) or with an amide (Table 1, entry 5) as substituent,
lower yields are obtained in this standard condition. The
Then, we studied the coupling reaction between aryl
chlorides and allyl acetate. In the conditions used previ-
ously with aryl bromides, i.e., 1 mmol of cobalt bromide
catalyst for 7.5 mmol of aromatic halide and 20 mmol of
allyl acetate, aryl chloride is not totally consumed. By
use of a larger amount of CoBr2 (0.2 equiv per equiv of
ArCl), all the aromatic chloride is consumed, but the
reaction proceeds slowly. To increase the reaction rate,
0.4 equiv of CoBr2 per ArCl was introduced in the
medium and allyl acetate is introduced in lower amounts
(2 equiv per ArCl).
Reaction conditions are reported in eq 2 and results
in Table 2.
Aryl chlorides substituted by an electron-withdrawing
group (Table 2, entries 12-15) give good to high yields
even in the case of ortho-substituted aryl chloride. With
o-chloroacetophenone (Table 2, entry 15), 50% yield of
allylic product is isolated, with the byproduct being ArH.
(19) Chaussard, J .; Folest, J . C.; Ne´de´lec, J .-Y.; Pe´richon, J .; Sibille,
S.; Troupel, M. Synthesis 1990, 5, 369.
(20) Buriez, O.; Ne´de´lec, J .-Y.; Pe´richon, J . J . Electroanal. Chem.
2001, 506, 162.
(21) Buriez, O.; Cannes, C.; Ne´de´lec, J .-Y.; Pe´richon, J . J . Electroa-
nal. Chem. 2000, 495, 57.
J . Org. Chem, Vol. 68, No. 3, 2003 1143

TABLE 2. Cou p lin g Rea ction betw een Su bstitu ted Ar yl
Ch lor id es a n d Allyl Aceta te
TABLE 4. Cou p lin g Rea ction betw een Heter oa r om a tic
Ha lid es a n d Allyl Meth a cr yla te
a
Isolated yields, based on initial HetArX.
yields poorly depend on the ester leaving group (Table
2, entry 14 and Table 3, entries 19-20), but with the
methacrylate one, the yield is slightly higher, probably
due to the conjugated double bond.
a
Isolated yields, based on initial ArCl.
TABLE 3. Cou p lin g Rea ction betw een Ar om a tic
Ha lid es a n d Va r iou s Allylic Ester s
The regiochemistry of the reaction has also been
studied with crotyl and cinnamyl acetates (Table 3,
entries 21-23). With the crotyl acetate, a mixture of the
SN2 and SN2′ allylic products is observed. However, the
major product formed in this reaction is the unbranched
product 15 (SN2) like the electrochemical process using
a nickel complex catalysis described in our laboratory.12
With cinnamyl acetate, the only product formed is the
linear one 17 (Table 3, entry 22) due to the steric
hindrance of phenyl group on the double bond. Neverthe-
less, with this allylic acetate, the aryl halide must be
reactive (ArBr). Indeed, aryl chloride substituted by an
electron-withdrawing group (Table 3, entry 23) is not
reactive enough toward the bulky allyl-cobalt complex
and generates ArH. As a matter of fact, electrolysis of
allylic acetates without aromatic halide in the medium
leads to the dimerization of the allylic moiety and, in a
minor way, to the reduction products of allylic substrates.
Work is still in progress to elucidate the mechanism of
the carbon-carbon bond formation in this process.
We have extended this process to the coupling between
several heteroaromatic halides with allyl methacrylate
according to eq 3 which gave the best results with
a
Isolated yields, based on initial ArX.
However, if the substituent is an electron-donating group
(Table 2, entries 16 and 17), only traces of the coupling
product are obtained, and the main product formed is
also ArH. Only 15% of ArCl is consumed. In this case,
Co(I) associated to allylic acetate reacts too slowly with
ArCl. The main reaction was found to be the oxidative
addition of Co(I) to allyl acetate generating the corre-
sponding hexadiene.
This process can also be extended to aryl iodides but
their higher reactivity leads to a higher formation of the
dimer ArAr during the electrolysis.
The reactions involving substituted allylic derivatives
generally give the linear or branched products due to
allylic transposition. The ratio of the R- and γ-allylation
depends on the nature of the organometallic intermedi-
ates.7 So, we have attempted to study the influence of
the groups born by both the allylic bond or the ester
leaving group. Results are reported in Table 3.
aromatic halides. The conditions are similar to those used
with aromatic halides. With a chlorine atom, the amounts
of CoBr2 should be higher than that obtained with a
bromine, owing to the lower reactivity of aryl chlorides.
Results are reported in Table 4.
The yields depend on the reactivity of each heteroaro-
matic halide. 2-Bromothiophene, which is more reactive
versus 3-bromothiophene,22 mainly leads to the reduction
product (Table 4, entry 25). The reaction provides good
yields (70 and 63%) with 3-bromothiophene and 2-chlo-
We have first studied the effect of the ester leaving
group (Table 3, entries 1-3). Good yields are obtained
with allyl methacrylate (Table 3, entries 18-19). The
(22) Schulz, E.; Fahmi, K.; Lemaire, M. Acros Org. Acta 1995, 1,
10.
1144 J . Org. Chem., Vol. 68, No. 3, 2003

formed on silica gel 60, 70-230 mesh. 1H, 13C, and 19F spectra
were recorded in CDCl3 at 200 MHz with TMS as an internal
standard.
TABLE 5. Cou p lin g Rea ction betw een Su bstitu ted Ar yl
Ha lid es a n d Allyl Meth yl ca r bon a te
The electrochemical cell has been described previously.19 All
solvents and reagents were purchased and used without further
purification. DMF, acetonitrile, and pyridine were stored under
argon. Cobalt bromide was used as obtained commercially.
Gen er a l P r oced u r e for th e Cou p lin g of Ar yl Br om id es
w ith Allyl Aceta te. In an undivided cell using a consumable
iron anode and a stainless steel grid as the cathode, CoBr2 (0.219
g, 1 mmol), ArBr (7.5 mmol), and allyl acetate (2.002 g, 20 mmol)
were placed in a mixture solvent of acetonitrile/pyridine or
dimethylformamide/pyridine (45 mL/5 mL). The ionic conductiv-
ity of the medium is ensured by addition of NBu4BF4 (0.165 g,
0.5 mmol) as supporting electrolyte. The solution was electro-
lyzed under argon and heated at 50 °C at current constant
intensity of 0.2 A (0.01 A/cm2) until aryl bromide wholly reacted.
The solution was hydrolyzed with HCl (2 N) and extracted with
diethyl ether, the organic layer was washed with brine and dried,
and the solvent was evaporated under vacuum. Coupling
products were isolated by column chromatography on silica gel
with pentane/ether as eluent.
a
Isolated yields, based on initial ArX.
rothiophene (less reactive than 2-bromothiophene) (Table
4, entries 24 and 26). In the case of 4-chloroquinaldine
(Table 4, entry 27), isomerization of the allylic product
takes place and leads to the arylvinyl product in a good
yield (69%).
Gen er a l P r oced u r e for th e Cou p lin g of Ar yl Ch lor id es
w ith Allyl Aceta te. The procedure used for aryl chlorides is
the same as that for aryl bromides excepted for amounts of CoBr2
(0.438 g, 2 mmol), ArCl (5 mmol), and allyl acetate (1.001 g, 10
mmol).
Allyl methyl carbonate can also react with aryl bro-
mides or chlorides according to eq 4. Results are reported
Registr y Nu m ber s (P r ovid ed by th e Au th or s): 4-allyl-
benzoic acid ethyl ester (1), 19819-94-4; 4-allyl-benzonitrile (2),
51980-05-3; 1-(4-allyl-phenyl)ethanone (3), 62929-84-5;
1-allyl-4-trifluoromethyl-benzene (4), 1813-97-4; 4-allyl-ben-
zamide (5), 104699-51-6; 1-allyl-4-fluoro-benzene (6), 1737-
16-2; 1-allyl-3-trifluoromethyl-benzene (7), 1813-96-3; 3-allyl-
benzoic acid ethyl ester (8), 372510-70-8; 1-allyl-3-chloro-
benzene (9), 3840-17-3; 2-allyl-benzonitrile (10), 61463-61-
4; 1-allyl-4-methoxy-benzene (11), 140-67-0; 4-allyl-benzoic
acid methyl ester (12), 20849-84-7; 1-(2-allyl-phenyl)etha-
none (13), 64664-07-9; 1-allyl-naphthalene (14), 2489-86-3;
4-but-2-enyl-benzoic acid methyl ester (15), 161112-49-8; 3-al-
lyl-thiophene (18), 33934-92-8; 2-allyl-thiophene (19), 20849-
87-0.
P r od u ct An a lysis. 4-(1-Methyl-allyl)-benzoic Acid Methyl
Ester (16). Yield: 19%. 1H NMR (200 MHz) δ (ppm): 7.96 (d,
2H, J ) 8.0 Hz), 7.39 (d, 2H, J ) 8.0 Hz), 5.52 (m, 1H), 5.04 (m,
2H), 3.87 (s, 3H), 3.40 (m, 1H), 1.33 (d, 3H, J ) 7.0 Hz). 13C
NMR (50 MHz) δ (ppm): 166.7, 150.7, 146.4, 132.6, 128.8, 128.0,
113.6, 51.6, 43.0, 22.2. MS. m/z (%): 190 (22) [M], 175 (21), 159
(28), 132 (12), 131 (100), 129 (17), 116 (18), 115 (28), 91 (30). IR
(neat): 3000, 1720, 1610 cm-1. Anal. Calcd for C12H14O2: C,
75.76; H, 7.42; O, 16.82. Found: C, 74.74; H, 7.08; O, 15.93.
4-(3-Phenyl-prop-2-enyl)-benzoic Acid Ethyl Ester (17). Yield:
52%. 1H NMR (200 MHz) δ (ppm): 8.01 (d, 2H, J ) 8.2 Hz),
7.24 (m, 7H), 6.47 (d, 1H, J ) 15.8 Hz), 6.33 (td, 1H, J ) 15.8
and 6.2 Hz), 4.38 (q, 2H, J ) 7.1 Hz), 3.59 (d, 2H, J ) 6.2 Hz),
1.39 (t, 3H, J ) 7.1 Hz). 13C NMR (50 MHz) δ (ppm): 166.5,
145.6, 145.4, 137.1, 131.7, 129.7, 128.6, 128.5, 128.0, 127.2, 126.1,
60.7, 39.2, 14.2. MS. m/z (%): 266 (45) [M], 237 (30), 221 (21),
193 (100), 192 (23), 178 (33), 115 (62). IR (neat): 3040, 3000,
1730, 1620 cm-1. Anal. Calcd for C18H18O2: C, 79.91; H, 6.85;
O, 12.31. Found: C, 79.70; H, 6.82; O, 12.48.
in Table 5.
Allyl carbonates have been shown to be very reactive
allylic substrates.8-11 Good yields are obtained with aryl
bromides substituted by either an electron-donating
group (Table 5, entry 28) or electron-withdrawing allyl
carbonates (Table 5, entry 29). The reaction with ethyl
4-bromobenzoate gives 53% of the expected allylic product
and 26% of arylallyl resulting from a trans-esterification
reaction due to the high reactivity of methyl carbonate
group in nucleophilic substitutions. However, with an
aryl chloride (even activated by an electron-withdrawing
substituent) (Table 5, entry 30), the yield is lower. In this
case, allylic substrate is too reactive toward Co(I) species
and gives the hydrogenation and dimerization products.
Attempts with allylic halides (bromides or chlorides)
gave few coupling products. In that case, Co(I) reacts very
quickly with these species leading to hexadiene.
In conclusion, we have discovered a new cobalt-
catalyzed coupling reaction23 of various functionalized
aryl or heteroaryl halides with different allylic substrates
(especially acetates). The corresponding arylallyls are
obtained in good yields. This simple experimental pro-
cedure appears to be a mild and useful method for the
synthesis of various arylallyl compounds. This catalytic
reaction is a convenient route for the nucleophilic sub-
stitution with aryl halides. Studies are now in progress
to elucidate the electrochemical reaction mechanism.
2-Methyl-4-(prop-2-enyl)-quinoline (20). Yield: 69%. 1H NMR
(200 MHz) δ (ppm): 7.91 (m, 2H), 7.51 (m, 1H), 7.31 (m, 1H),
7.12 (s, 1H), 6.87 (dd, 1H, J ) 15.5 and 1.6 Hz), 6.25 (m, 1H),
2.58 (s, 3H), 1.85 (dd, 3H, J ) 6.7 and 1.6 Hz). 13C NMR (50
MHz) δ (ppm): 158.4, 147.9, 143.6, 132.6, 129.1, 128.7, 125.8,
125.3, 124.4, 123.3, 117.9, 25.0, 18.9. MS, m/z (%): 184 (19) [M
+ 1], 183 (100) [M], 181 (12), 169 (48), 168 (37), 167 (18). IR
(neat): 2940, 1600 cm-1. Anal. Calcd for C13H13N: C, 85.21; H,
7.15; N, 7.64. Found: C, 85.23; H, 7.35; N, 7.42.
Exp er im en ta l Section
GC analysis was carried out using a 25-m capillary column.
Mass spectra were recorded with a spectrometer coupled to a
gas chromatograph (30 m). Column chromatography was per-
Ack n ow led gm en t. We gratefully acknowledge the
financial support provided by Rhodia industry.
(23) Fillon, H.; Gosmini, C.; Pe´richon, J . Patent application 01/
08808, France, J uly 3, 2001.
J O026421B
J . Org. Chem, Vol. 68, No. 3, 2003 1145