Nickel-catalyzed direct electrochemical cross-coupling between aryl halides and activated alkyl halides

Article abstract of DOI:10.1021/jo9518314

The electrochemical reduction of a mixture of aryl halides and activated alkyl halides in DMF in the presence of catalytic amount of NiBr₂bipy leads to cross-coupling products in good to high yields. The method applies to the synthesis of α-aryl ketones, α-aryl esters, and allylated compounds from readily available organic halides. Optimization of the process has been obtained by slowly adding the most reactive organic halide (usually the activated alkyl halide) during the electrolysis which is best conducted at 70 °C when aryl bromides are involved.

Full text of DOI:10.1021/jo9518314

1748
J . Org. Chem. 1996, 61, 1748-1755
Nick el-Ca ta lyzed Dir ect Electr och em ica l Cr oss-Cou p lin g betw een
Ar yl Ha lid es a n d Activa ted Alk yl Ha lid es
Muriel Durandetti,* J ean-Yves Ne´de´lec, and J acques Pe´richon
Laboratoire d’Electrochimie, Catalyse et Synthe`se Organique, UMR 28 CNRS, 2,
rue Henri-Dunant 94320 Thiais, France
Received October 11, 1995X
The electrochemical reduction of a mixture of aryl halides and activated alkyl halides in DMF in
the presence of catalytic amount of NiBr2bipy leads to cross-coupling products in good to high yields.
The method applies to the synthesis of R-aryl ketones, R-aryl esters, and allylated compounds from
readily available organic halides. Optimization of the process has been obtained by slowly adding
the most reactive organic halide (usually the activated alkyl halide) during the electrolysis which
is best conducted at 70 °C when aryl bromides are involved.
In tr od u ction
unless a catalyst (usually a nickel complex) is used, with,
however, modest yields.6 Organozinc compounds can also
be used, in the presence of a nickel complex as catalyst,
but these reactions are not widely applicable.
Aryl compounds, like R-aryl ketones, R-aryl esters, or
allylated aryl derivatives, are of high interest due to their
versatile properties as pharmaceuticals, agrochemicals,
perfumes, etc. Many synthetic strategies are available
to prepare these compounds, but the most straightfor-
ward approach is the direct introduction of the aryl group
on the substate. Selective one-step reductive cross-
coupling between aryl halides and alkyl halides (eq 1)
has never been achieved efficiently, as far as we know.
Over the past decade, research in these laboratories
has developed new methods of electroreductive C-C
bond-forming reactions based on the use of a sacrificial
anode,7 eventually in the presence of a catalyst. Notably,
we have found that cross-coupling between aryl halides
and activated alkyl halides, R-chloro ketones (eq 2),
R-chloro esters (eq 3), or allylic derivatives (eq 4), can be
easily carried out with a simple electrosynthesis using
nickel-bipyridine complexes as catalysts in N,N-dimeth-
ylformamide (DMF).
Such coupling requires the preliminary preparation of
an organometallic, either ArM or RM, which is then
reacted with the other organic halide, eventually in the
presence of transition metal catalyst. Grignard organo-
metallics are often involved in these reactions. However,
they cannot be prepared from organic halides having
sensitive functional groups. Zinc organometallics are less
reactive and often prepared from the corresponding
organomagnesium compound.
The coupling reaction between arylmagnesium bro-
mides and activated alkyl halides is more or less efficient.
Thus the coupling with allylic bromides occurs in good
yield. However, the reaction is not regioselective, and
two isomeric products are formed from for example crotyl
bromide.1 Pd-,2 Ni-,3 or Cu-4 catalysis of these reactions
can both increase the reaction rate and control the
regioselectivity. Alternatively, the allylation reaction can
be carried out from organozinc intermediates and in the
presence of a transition metal catalyst.5
Since the publication of some preliminary results,8,9 the
process has been both optimized on the basis of a better
understanding of the reaction mechanism and extended
to a wide range of organic halides. Here we present a
full account of these reactions.
Resu lts a n d Discu ssion
Op tim iza tion of th e Cr oss-Cou p lin g. The elec-
troreduction of a mixture of an aryl halide and an
R-chloro ketone or R-chloro ester, in the absence of
catalyst, does not afford the expected cross-coupling
product. We only obtain the reduction products from the
alkyl halide RX, namely RH and RR. On the contrary,
as previously shown,8 aryl iodides or activated aryl
bromides couple electroreductively with an R-chloro ester
The direct reaction of ArMgX with R-halo carbonyls,
esters or ketones, only leads to addition to the carbonyl,
X Abstract published in Advance ACS Abstracts, February 15, 1996.
(1) Kharash, M. S.; Reinmuth, O. Grignard Reactions of Nonmetallic
Substances; Coustable: London, 1954.
(2) (a) Heck, R. F. J . Am. Chem. Soc. 1968, 90, 5531. (b) Bumagin,
N. A.; Kasatkin, A.; Beletskaya, I. P. Bull. Acad. Sci. USSR 1984, 33,
1696.
(3) (a) Wenkert, E.; Fernandes, J . B.; Michelotti, E. L.; Swindell, C.
S. Synthesis 1983, 701. (b) Okamura, H.; Takei, H. Tetrahedron Lett.
1979, 20, 3425.
(4) (a) Kosugi, M.; Sasazawa, K.; Shimizu, Y.; Migita, T. Chem. Lett.
1977, 301. (b) Suzuki, S.; Shiono, M.; Fujita, Y. Synthesis 1983, 804.
(5) (a) Matsushita, H.; Negishi, E. I. J . Am. Chem. Soc. 1981, 103,
2882. (b) Negishi, E. I.; Chatterjee, S.; Matsushita, H. Tetrahedron
Lett. 1981, 22, 3737. (c) Pelter, A.; Rowlands, M.; Clements, G.
Synthesis 1987, 1, 51. (d) Zhu, L.; Wehmeyer, R. M.; Rieke, R. D. J .
Org. Chem. 1991, 56, 1445.
(6) Amano, T.; Yoshikawa, K.; Sano, T.; Ohuchi, Y.; Shiono, M.;
Ishiguro, M.; Fujita, Y. Synth. Commun. 1986, 16, 499.
(7) Chaussard, J .; Folest, J . C.; Ne´de´lec, J . Y.; Pe´richon, J .; Sibille,
S.; Troupel, M. Synthesis 1990, 1, 369.
(8) Conan, A.; Sibille, S.; d’Incan, E.; Pe´richon, J . J . Chem. Soc.,
Chem. Commun. 1990, 48.
(9) Durandetti, M.; Sibille, S.; Ne´de´lec, J .-Y.; Pe´richon, J . Synth.
Commun. 1994, 2, 145.
0022-3263/96/1961-1748$12.00/0 © 1996 American Chemical Society

Direct Electrochemical Cross-Coupling
J . Org. Chem., Vol. 61, No. 5, 1996 1749
more rapidly to Ni(0) than aryl halides.12 We also found
that the cross-coupling does not occur at all with the more
reactive alkyl bromides. This clearly indicates that for
the cross-coupling to occur it should involve, as the key
step, the formation of a σ-arylnickel intermediate (Scheme
1, step 1). The formation of RNiX likely occurs in all
cases (Scheme 1, step 2); it can, however, be minimized
by keeping the ArX/RX molar ratio elevated over the
duration of electrolysis by slow addition of RX. We must
also avoid forming biaryl (Scheme 1, step 4), so the excess
of ArX must be kept within a certain range. We found
an optimum addition rate of 5 mmol/h via a syringe pump
to keep a ArX/RX molar ratio of ca. 15 in the cell.
Sch em e 1
used in excess at room temperature, in the presence of a
catalytic amount (5-10%) of NiBr2bipy (bipy ) 2,2′-
bipyridine) and a zinc or aluminum anode. However,
when the electrolysis is carried out with PhBr, the cross-
coupling does not occur and RR is first formed and then
biphenyl after consumption of RX. Improvements were
obtained as follows: the running of the reaction at 70 °C
from a mixture of PhBr and RX afforded 5-10% of cross-
coupling, and high yields were obtained by slowly adding
RX, during the electrolysis at elevated temperature.
Thus at 70 °C and with a slow addition of the R-chloro
carbonyl the reaction between bromobenzene and, re-
spectively, chloropropanone and methyl 2-chloropropi-
onate gave 62% of phenylacetone and 70% of methyl
phenylacetate. With aryl iodides, and if the R-halo ester
or the R-halo ketone is added slowly, the reaction is best
carried out at room temperature. Also, electron-with-
drawing groups on the aromatic ring slightly favor the
cross-coupling, as compared to electron-releasing sub-
stituents, though the influence of the nature of the
substituent on Ar is not very large.
We already mentioned that with aromatic bromides,
yields of cross-coupling increased with the reaction
temperature. This means that the rate of the oxidative
addition of Ni(0) increases more rapidly with the temper-
ature for ArBr than for RX. Indeed the activation energy
for the oxidative addition of Ni(0) to PhBr and to ClCH2-
COCH3 was found to be, respectively, 76 kJ mol-1 and
28 kJ mol-1
.
(NiBr2bipy + bipy) was found to be less reactive than
NiBr2bipy (only 30% of m-CF3PhCH2COCH3 was ob-
tained in the electroreductive cross-coupling between
m-CF3PhBr and ClCH2COCH3 with NiBr2bipy2 instead
of 80% with NiBr2bipy), and with Ni(BF4)2bipy3 ArX was
not consumed. This can be explained by the decrease of
the rate constant of the oxidative addition of ArX to Ni(0)
with added bipy. As a consequence, when the ratio
bipyridine/nickel is increased, the formation of RNiX
prevails (Scheme 1, step 2) over the formation of ArNiX
(Scheme 1, step 1) and R-R and RH are mainly formed.
Changing 1,10-phenanthroline (phen) for bipyridine does
not change the chemical yields: the reaction between PhI
and ClCH(CH3)CO2Me gave 70% cross-coupling with
NiBr2bipy and 73% with NiCl2(phen). With NiBr2(PPh3)2
or NiBr2diphos in DMF, the oxidative addition to ArX is
too slow, and the Ni0 zero species only reacts with RX.
The effect of the nature of the metal used as anode
material on the chemical and faradaic yields of 1-phenyl-
2-propanone from iodobenzene and chloroacetone at room
temperature was also studied and found not to be a
highly critical factor in the process. Thus the yield of
1-phenyl-2-propanone was 54% with a zinc anode and
53% with an aluminum anode, but 39% with a magne-
sium anode. The decrease in the chemical yield with a
magnesium anode can be explained by the occurrence of
side reactions at the electroeroded metal.7 To sum up,
the kind of the electrogenerated ion does not greatly
affect the chemical yield. This may rule out a trans-
metalation reaction, as described in other reactions.13
To gain further insight into the mechanism of the
coupling step between ArNiX and RX (Scheme 1, step
3), we have undertaken voltametric studies of this cross-
coupling process.12 Here again, two processes may occur,
as outlined in Scheme 2.
Other features of these reactions are worth noting: for
a given ArX, the efficiency of the cross-coupling also
depends on the nature of X in RX and on the RX vs ArX
molar ratio. Thus the coupling reaction between PhI and
ClCH2CO2Me is efficiently performed at room tempera-
ture by slow (5 mmol/h) addition of 1.2 equiv of the R-halo
ester. On the contrary, only the reduction of the R-halo
ester occurs when BrCH2CO2Me is used instead of ClCH2-
CO2Me, even with a very slow addition of methyl bro-
moacetate. Similarly, allylation reactions are more
efficently performed with allylic acetates than with the
corresponding chlorides, while no cross-coupling occurs
with allylic bromides.
The reactions were usually conducted at constant
current density, and we found that during the electroly-
ses the potential of the working electrode remained
constant at ca -1.2 V/SCE, which corresponds to the
reduction of Ni(II) to Ni(0) 10
The subsequent step is an
.
oxidative addition of Ni(0) to one of the two organic
halides. There are indeed two possible competitive
pathways, i.e. the formation of ArNiX and the formation
of RNiX (Scheme 1). Rate constants value for the
reaction of Ni(0) (electrogenerated from NiBr2bipy) with
typical organic halides in DMF was obtained by the
method described by Nicholson and Shain11 which is
based on the measurement of the ratio of the intensity
ArNiX can be reduced to ArNi (Scheme 2, step 1),
which would then react by oxidative addition with RX
(Scheme 2, step 2). The coupling product results from
the reductive elimination reaction (Scheme 2, step 3).
However, an exhaustive electrolysis of a mixture PhI/
ClCH2COCH3 in the molar ratio 15/1 conducted at -1
of cyclic voltametry peaks of the Ni(II)/Ni(0) system in the
[RX]
presence of various amounts of RX vs Ni (iox/ired
)
as
compared the system in the absence of RX (iox/ired)0. It
them comes out that R-chloro carbonyls compounds add
(12) Results to be published.
(13) (a) Durandetti, S.; Sibille, S.; Pe´richon, J . J . Org. Chem. 1989,
54, 2198. (b) Conan, A.; Sibille, S.; Pe´richon, J . J . Org. Chem. 1991,
56, 2018. (c) Sibille, S.; Ratovelomanana, V.; Pe´richon, J . J . Chem. Soc.,
Chem. Commun. 1992, 283.
(10) Rollin, Y.; Troupel, M.; Tuck, D.; Pe´richon J . J . Organomet.
Chem. 1986, 303, 131.
(11) Nicholson, R. S.; Shain, I. Anal. Chem. 1964, 36, 706.

1750 J . Org. Chem., Vol. 61, No. 5, 1996
Durandetti et al.
Sch em e 2
notably amphetamine-like drugs. They can be prepared
in two or more steps from aryl compounds (halides,16
boranes,17 or azo sulfides18 ) from benzylic compounds,19
or from aromatic aldehydes.20 They can also be easily
obtained using the method reported here (eq 2).
Results for the electrochemical coupling reaction be-
tween chloroacetone and aryl iodides or bromides under
the standard reaction conditions defined above are given
in Table 1. Reactions involving aryl iodides were run at
room temperature and those with aryl bromides were run
at 70 °C. Because of the high reactivity of chloroacetone
with Ni(0), the addition of 2-4 equiv of chloroacetone with
respect to ArX was needed to totally consume ArX.
We can see that the chemical yields are good to
excellent and that they are roughly identical from both
types of aryl halides. As mentioned above there is no
great influence of the ring substituent on the yield.
However, with two electron-releasing groups the yields
are low. Also, the functional compatibility is worth
noting, illustrated here with the ester group. If the
substituent is at the ortho position, like with methyl
2-iodobenzoate, the yield was good regardless of the steric
hindrance. A lactone was formed as a secondary product
by cyclocondensation (eq 5).
V/SCE yielded the heterocoupling product nearly quan-
titatively. This indicates that the reduction of ArNiX is
not necessary for the coupling reaction to occur. In
keeping with this, a previous report showed that ArNiX-
(PPh3)2 prepared electrochemically from ArX and NiBr2-
(PPh3)2 in the presence of exces of PPh3 reacts with
R-chloro esters in the absence of electricity to give the
corresponding R-aryl ester.14 A second oxidative addition
between ArNiX and RX could then be postulated, thus
leading to ArRNiX2 which is formally a Ni(IV) species
(Scheme 2, step 4). We were unable to detect such an
intermediate by electrochemical analysis. An alternative
route would involve an electron transfer between these
two species leading to ArNiX•+RX•- (scheme 2, step 5) as
already proposed by Hegedus15a for the coupling of
π-allylnickel bromide and alkyl iodide and more recently
by Yamamoto(15b) for the coupling of arylnickel(II) and
alkyl iodide. This would involve the formation of a
radical from RX which would then react with ArNiX to
give nickel species ArRNiX. (Scheme 2, step 6), as
through step 7. To test this hypothesis we ran some
reactions involving chiral methyl chloropropionate. This
resulted in the formation of a racemic R-aryl ester. We
can then conclude that there is more than one reaction
mechanism, and the main mechanism leading to the
cross-coupling depends on the experimental conditions,
notably the cathode potential. A full mechanistic inves-
tigation will be reported.12
The investigation of the effect of the various param-
eters led us to employ the following experimental proce-
dure. Freshly distilled DMF (40 mL), Bu4NBF4 (0.6
mmol), NiBr2bipy (1 mmol), ArX (10 mmol), and a portion
of RX (ca. 0.3 mmol) were introduced into a one-
compartment cell fitted with an Al or Zn rod as the anode,
and a nickel or stainless-steel-sponge, or carbon fiber as
the cathode (cathode area: ca 20 cm2). RX was added
constantly to the solution via a syringe pump at a rate
of 5 mmol/h up to the disappearance of ArX, monitored
by GC, and the electricity was supplied at constant
current intensity of 0.2-0.25 A under argon. Reactions
involving aryl iodides were run at room temperature and
those with bromides at 70 °C. The electrolyses were
usually run until the aromatic halide was totally con-
sumed.
The method can be used with other R-chloro ketones
such as 3-chloro-2-butanone and 2-chloroacetophenone.
Results are given in Table 2.
Results are generally good. The excess of ketone vs
ArX needed with 3-chloro-2-butanone is less than for
chloroacetone. This is due to a decrease of the rate
constant of the oxidative addition of Ni(0)bipy with
3-chloro-2-butanone as compared to chloroacetone.
With 2-chloroacetophenone the reaction should be run
at a cathode potential of ca -1.1 V/SCE because this
chloroketone is easily reduced (E1/2 ) -1.4 V/SCE). For
that reason the reactions were conducted at a slightly
lower current intensity (i e 0.2 A) than for the other
reagents.
(b) Ar yla tion of r-Ch lor o Ester s. Nonsteroidal
antiinflammatory arylacetic and R-arylpropionic acids are
one of the largest class of drugs. Many routes to the
various structures of therapeutic interest have been
described, from either a benzylic21 or an aromatic deriva-
Syn th etic Ap p lica tion s. (a ) Ar yla tion of r-Ch lor o
Keton es. Arylacetones and R-aryl ketones are key
intermediates in the synthesis of many target molecules,
(16) Bunnett, J . F. Acc. Chem. Res. 1978, 11, 413.
(17) Brown, H. C.; Nambu, H.; Rogic, M. M. J . Am. Chem. Soc. 1969,
91, 6852.
(18) (a) Dell’Erba, C.; Novi, M.; Petrillo, G.; Tavani, C. Tetrahedron
1992, 48, 325. (b) Dell’Erba, C.; Novi, M.; Petrillo, G. Tavani, C.
Tetrahedron 1994, 50, 3529.
(19) D’Incan, E.; Sibille, S.; Pe´richon, J . Tetrahedron Lett. 1986, 27,
4175.
(20) Binovic, K.; Vrancea, S. Chim. Ther. 1968, 5, 313.
(21) Bakshi, S. P.; Turner, E. E. J . Chem. Soc. 1961, 171.
(14) Folest, J . C.; Pe´richon, J .; Fauvarque, J . F.; J utand, A. J .
Organometal. Chem. 1988, 342, 259.
(15) (a) Hegedus, L. S.; Miller, L. L. J . Am. Chem. Soc. 1975, 97,
459. (b) Kim, Y. J .; Sato, R.; Maruyama, T.; Osakada, T.; Yamamoto,
T. J . Chem. Soc., Dalton Trans. 1994, 943.

Direct Electrochemical Cross-Coupling
J . Org. Chem., Vol. 61, No. 5, 1996 1751
Ta ble 1. Electr or ed u ctive Cr oss-Cou p lin gs betw een Ar yl Ha lid es a n d ClCH2COCH3
tive,22 or by rearrangement of propiophenone.23 We
already described the electrochemical carboxylation of
benzylic halides.24 The method described here offers an
interesting alternative leading directly to the ester of the
desired arylacetic and R-arylpropionic acid (eq 3). Re-
sults are given in Table 3.
Methyl chloroacetate is slightly less reactive than
chloroacetone toward Ni(0). The reactions can then be
conducted in the presence of 2 equiv or less of the chloro
ester relative to the aryl halide. The yields are good to
excellent and do not seem to greatly depend on the nature
of the ring substituent.
The method can also be applied to alkenyl bromides.
Thus, as a preliminary study, the direct coupling between
â-bromostyrene and R-chloro esters proceeds in good yield
(eq 6). The stereochemical aspect has not been investi-
gated yet.
(c) Ar yla tion of Allylic Der iva tives. The arylallyl
skeleton is the basic structure of many natural products(3a)
like estragol (p-CH3O-C6H4CH2CHdCH2), eugenol (2-
CH3O-C6H4OH-4-CH2CHdCH2), methyleugenol (1,2-di-
CH3O-C6H4-4-CH2CHdCH2), osmorhyzol (1,3-di-CH3O-
C6H4-4-CH2CHdCH2), etc. It is also a useful building
block. Substitution reactions of allylic halides with
aromatic organometallic reagents have provided an
important route for the synthesis of these allylic com-
pounds.1-3,5
(22) (a) Millard, A. A.; Rathke, M. W. J . Am. Chem. Soc. 1977, 99,
4833. (b) Fauvarque, J . F.; J utand, A. J . Organomet. Chem. 1977, 132,
C17. (c) Fauvarque, J . F.; J utand, A. J . Organomet. Chem. 1979, 177,
273. (d) Yamanaka, H.; An-naka, M.; Kondo, Y.; Sakamoto, T. Chem.
Pharm. Bull. 1985, 33, 4309. (e) Klingstedt, T.; Frejd, T. Organome-
tallics 1983, 2, 598.
(23) Rieu, J . P.; Boucherle, A.; Cousse, H. Mouzin, G. Tetrahedron
1986, 42, 4095.
(24) Sock, O.; Troupel, M.; Pe´richon, J . Tetrahedron Lett. 1985, 26,
1509.
Cross-coupling reactions between aromatic halides and
allylic derivatives were performed with two kinds of
allylic compounds: allylic chloride and allylic acetate. The
results are summarized in Table 4.
Reactions involving allylic derivatives generally give

1752 J . Org. Chem., Vol. 61, No. 5, 1996
Durandetti et al.
Ta ble 2. Electr or ed u ctive Cr oss-Cou p lin gs betw een Ar yl Ha lid es a n d r-Ch lor o Keton es
two isomeric products due to allylic transposition: this
is also observed in the reactions reported here (eq 7).
mopropene (Table 5, entries 5-7) was introduced initially
(10 mmol) into the cell with the aromatic bromide and
then constantly added to the solution during the elec-
trolysis with a syringe pump at a rate of 5 mmol/h, at
room temperature. Unreacted vinylic bromide was re-
covered at the end of the electrolysis. The stereochemical
aspect has not yet been investigated. Methyl â-bro-
mopropionate (Table 5, entry 4) was introduced initially
into the cell, and bromobenzene was added slowly (ca. 4
mmol/h) to the electrolytic solution containing BrCH2-
CH2CO2Me. A great amount of benzene was formed
along with the cross-coupling product.
However, contrary to many other methods, the major
product formed in these reactions is the unbranched
product a , and the ratio of the two products is about 9:1
(Table 4, entries 4-6).
Identical or better results were obtained with allylic
acetates than with allylic chlorides. The oxidative ad-
dition of Ni(0)bipy is faster with allylic chlorides than with
allylic acetates, so the competition in the formation of
RNiX or ArNiX is in favor of RNiX in the reaction with
allylic chlorides.
We can notice that an aromatic chloride, when acti-
vated by an electron-withdrawing group, can couple with
allyl acetate in medium yield, at 70 °C (Table 4, entry
2).
(d ) Ar yla tion of Oth er Or ga n ic Ha lid es. R-Chlo-
ropropiononitrile, benzyl chloride, methyl â-bromopropi-
onate, and 1-bromopropene can also participate in such
cross-coupling reactions (Table 5), though the procedure
has to be adapted to each case.
Con clu sion
We have reported in this paper a staightforward
method of efficient cross-coupling of aryl and alkyl
halides, enabling the preparation of valuable target
molecules such as R-aryl esters or R-aryl ketones. The
scope of the method is wide concerning the type of organic
halides involved: besides aryl and activated alkyl halides,
alkenyl or alkyl halides can also be interestingly used.
The method is also of large functional tolerance as
regards the substituents on the aromatic ring. In addi-
tion, because of the use of a simple undivided electrolytic
cell and sacrificial anode,25 a possible scale up of the
process can be envisaged.
R-Chloropropiononitriles (Table 5, entry 1) or benzyl
chloride (Table 5, entries 2-3) react under the same
procedure as for R-chloro esters or R-chloro ketones. The
less reactive methyl â-bromopropionate and 1-bromopro-
pene required a modified experimental procedure. 1-Bro-
The important part played by the nickel catalysis in
the electroreductive coupling of aromatic halide with
(25) Chausard, J .; Troupel, M.; J acob, G.; J uhasz, J . P. J . Appl.
Electrochem. 1989, 19, 345.

Direct Electrochemical Cross-Coupling
J . Org. Chem., Vol. 61, No. 5, 1996 1753
Ta ble 3. Electr or ed u ctive Cr oss-Cou p lin gs betw een Ar yl Ha lid es a n d r-Ch lor o Ester s
pressure. The reaction products were identified by the usual
techniques. 1H, 19F, 13C NMR spectra were recorded at 200
alkyl halide has been clearly demonstrated. The best
catalysts for these reactions are NiBr2bipy and NiBr2-
phen. The optimization of the cross-coupling reactions
has led to a fine tuning of the experimental parameters
1
MHz. TMS served as an internal standard for H or 13C NMR
spectra. For 19F NMR spectra, CFCl3 served as an external
standard. Mass spectra were recorded with an ITD spectrom-
eter coupled to a gas chromatograph (DB1, 30 m). High
resolution mass spectra were performed by the Service Central
de Spectrome´trie de Masse (C.N.R.S., Lyon).
P r ep a r a tion of Ni(II) Com p lexes. NiBr2bipy,26 Ni(BF4)2-
bipy3,27 NiBr2(PPh3)2,28 and NiCl2diphos29 were prepared ac-
cording to literature methods.
(concentration, temperature). Metallic ions (Al3+ or Zn2+
)
derived from the anode do not have a vital role in these
reactions with respect to either the efficiency or the
selectivity. Notably, a transmetalation reaction can be
ruled out. A full study of the reaction mechanism will
be published separately.
P r ep a r a tion of Cr otyl Aceta te. We mixed 43 mL of crotyl
alcohol, 95 mL of acetic anhydride, and a catalytic amount of
(dimethylamino)pyridine (DMAP). A mixture of pyridine-
CH2Cl2 (40 mL:40 mL) was added slowly, and the solution was
allowed to react for 30 min at 0 °C. When all the pyridine
was added, the mixture was set at room temperature. Then
the reaction mixture was poured into 30 mL of 4 N HCl and
was extracted with diethyl ether (3 × 30 mL). The combined
Exp er im en ta l section
Nickel bromide, nickel tetrafluoroborate, and 2-2′-bipyri-
dine were used as obtained commercially. NBu4BF4 was dried
by heating overnight at 70 °C in vacuum.
A zinc, magnesium, or aluminum rod was used as the anode.
The cathode was made of carbon fiber or nickel- or stainless-
steel-sponge. Other reagents were generally used as received.
N,N-Dimethylformamide was distilled in the presence of
copper sulfate under reduced pressure and was dried over
molecular sieves (3 Å). DMF (analytical grade) was just dried
over molecular sieves. N-methylpyrrolidone was distilled in
the presence of alcoholic potassium hydroxide under reduced
(26) Uchino, M.; Asagi, K.; Yamamoto, A. Ikeda, S. J . Organomet.
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(28) Venanzi, L. J . Chem. Soc. 1958, 719.
(29) Van Hecke, G. R.; Horrocks, W. W. Inorg. Chem. 1966, 5, 1968.

1754 J . Org. Chem., Vol. 61, No. 5, 1996
Durandetti et al.
Ta ble 4. Electr or ed u ctive Cr oss-Cou p lin gs betw een Ar yl Ha lid es a n d Allylic Com p ou n d s
Ta ble 5. Electr or ed u ctive Cr oss-Cou p lin gs betw een Ar yl Ha lid es a n d Oth er Or ga n ic Ha lid es
extracts were washed with dilute aqueous HCl to ensure the
complete removal of pyridine, with aqueous NaHCO3 to remove
acetic acid, and finally with water. The extracts were dried
(MgSO4), and the solvent was removed under reduced pres-
sure. We obtained 57 g of crotyl acetate (100%). 1H NMR
(CDCl3): 1.7 (d, J ) 5 Hz, 3H); 2.1 (s, 3H); 4.6 (d, J ) 5 Hz,
2H); 5.7 (m, 2H).
Gen er a l P r oced u r e for th e Electr osyn th esis. The
electrolysis cell has already been described.7 It was fitted with
a nickel-sponge cathode (20 cm2) and a zinc or aluminum rod
(1 cm diameter) anode. To a DMF solution (40 mL) containing
0.6 mmol of NBu4BF4 and 1 mmol of NiBr2bipy were added
the aromatic halide (10 mmol) and the R-chloro ester or the
R-chloro ketone or the allylic derivative (ca. 0.3 mmol).
Reactions were performed at room temperature (aromatic
iodide) or at 70 °C (aromatic bromide), under argon. The
electrolysis (i ) 250 mA or 200 mA for the coupling with
2-chloroacetophenone) was monitored by GC and was run until
the aromatic halide was totally consumed (2-6 h). The
reactions were then quenched with 4 N HCl (or 2 N to aryl
esters) and extracted with diethyl ether (3 × 40 mL). The
combined extracts were washed with water (5 × 40 mL) to
ensure complete removal of DMF. The extracts were dried
(MgSO4), and solvent was removed under reduced pressure.
The product was isolated by silica-gel columm chromatography
eluted with 90:10 or 85:15 pentane/diethyl ether.
Ch a r a cter iza tion of th e P r od u cts. Benzoic acid, 4-(2-
oxopropyl)-methyl ester (5): 1H NMR (CDCl3, 200 MHz) δ 2.17

Direct Electrochemical Cross-Coupling
J . Org. Chem., Vol. 61, No. 5, 1996 1755
(3H, s), 3.77 (2H, s), 3.89 (3H, s), 7.27 and 8 (2H each, AA′-
BB′ system J ) 8.2 Hz); 13C NMR (CDCl3, 50.3 MHz) 29.2 (1C,
CH3), 50.2 (1C, CH2), 51.7 (1C, CH3), 128.6 (1C, arom), 129.2
(2C, arom), 129.6 (2C, arom), 139.1 (1C, arom), 166.4 (1C, CO2),
204.8 (1C, CO); MS 192 (M), 161 (M - 31), 149 (M - 43, base),
135 (M - 57), 118 (M - (31 + 43)), 90.
(22);39 benzeneacetic acid, R-methyl-3-(trifluoromethyl)-methyl
ester (23);40 benzeneacetic acid, R-methyl-4-(trifluoromethyl)-
methyl ester (24);40 benzeneacetic acid, 4-cyano-methyl ester
(25);8 benzeneacetic acid, 4-cyano-R-methyl-methyl ester (26);41
benzeneacetic acid, 4-(dimethylamino)-methyl ester (27);42
benzeneacetic acid, R-methyl-4-methyl-methyl ester (28);39
4-methoxybenzeneacetic acid, R-methyl-methyl ester (29);39
1-naphthylacetic acid, R-methyl-methyl ester (30);43 [2-(6-
methoxynaphthyl)]acetic acid, R-methyl-methyl ester (31);44
3-butenoic acid, 4-phenyl-methyl ester (32);45 3-butenoic acid,
2-methyl-4-phenyl-methyl ester (33);8 1-(2-propenyl)-3-(tri-
fluoromethyl)benzene (34);46 1-(2-propenyl)-4-(trifluorometh-
yl)benzene (35);47 1-(2-butenyl)-4-methoxybenzene (37a );3a
1-methoxy-4-(1-methyl-2-propenyl)benzene (37b);48 benzene,
1-fluoro-4-(phenylmethyl) (39);49 thiophene, 2-(phenylmethyl)
(40);50 benzenepropanoic acid, methyl ester (41);51 benzene,
1-(1-propenyl)-3-(trifluoromethyl) (42);46 benzonitrile, 4-(1-
propenyl) (43).52
3-(3-Acetylp h en yl)-2-bu ta n on e (14): 1H NMR (CDCl3, 200
MHz) δ 1.43 (3H, d, J ) 6.99 Hz), 2.09 (3H, s), 2.62 (3H, s),
3.89 (1H, q, J ) 6.99 Hz), 7.45-7.51 and 7.86-7.91(4H, m);
13C NMR (CDCl3, 50.3 MHz) δ 17.0 (1C, CH3), 26.3 (1C, CH3),
28.2 (1C, CH3), 53.0 (1C, CH), 127.1 (1C, arom), 127.4 (1C,
arom), 129 (1C, arom), 132.1 (1C, arom), 137.5 (1C, arom), 141
(1C, arom), 197.4 (1C, CO), 207.7 (1C, CO); high resolution
MS 190.1 (M), 175.1 (M - 15), 148.1 (M - 43), 105.1, 43.0
(base).
Ben zen ea cetic a cid , 4-flu or o-m eth yl ester (21): 1H
NMR (CDCl3, 200 MHz) δ 3.59 (2H, s), 3.69 (3H, s), 6.96-
7.04 (2H, m), 7.20-7.27 (2H, m); 19F NMR (CDCl3, 188.3 MHz):
δ -115.52 (1F, m)/CFCl3; MS 168 (M), 109 (M - 59, base).
2-[3-(Tr iflu or om eth yl)p h en yl]p r op ion on itr ile (38): 1H
NMR (CDCl3, 200 MHz) δ 1.64 (3H, d, J ) 7.3 Hz), 4.02 (1H,
q, J ) 7.3 Hz), 7.47-7.66 (4H, m); 13C NMR (CDCl3, 50.3 MHz)
δ 20.9 (1C, CH3), 30.9 (1C, CH), 120.9 (1C, CN), 123.5 (1C,
arom, q, J CCCF ) 3.78 Hz), 123.8 (1C, CF3, q, J CF ) 272.33 Hz),
124.9 (1C, arom, q, J CCCF ) 3.72 Hz), 129.7 (1C, arom), 130.2
(1C, arom), 131.3 (1C, arom, q, J CCF ) 32.48 Hz), 138.3 (1C,
arom); 19F NMR (CDCl3, 188.3 MHz) δ -62.66 (3F, s)/CFCl3;
high resolution MS 199.1 (M), 184.1 (M - 15, base), 145.1,
130.1 (M - 69).
The following products were characterized by comparison
of their GC and spectral data with those for commercially
available samples: 1-phenyl-2-propanone (1); 1-(4-fluorophen-
yl)-2-propanone (2); 1-[3-(Trifluoromethyl)phenyl]-2-propanone
(3); 1-(4-methoxyphenyl)-2-propanone (6); methyl phenylac-
etate (19); 1-methoxy-4-(2-propenyl)benzene (36); benzene,
1-methoxy-4-(1-propenyl) (44).
The following compounds were identified by comparison of
their physical and spectral data with those given in the cited
references: Benzoic acid, 2-(2-oxopropyl)-methyl ester (4a );30
3-methylisocoumarin (4b);31 1-(3-methoxyphenyl)-2-propanone
(7);18a 1-(1,3-benzodioxol-5-yl)-2-propanone (8);32 1-(2,5-Di-
methoxyphenyl)-2-propanone (9);33 2-(4-Fluorophenyl)-1-phen-
ylethanone (10);34 3-(4-Fluorophenyl)-2-butanone (11);35 2-[3-
(Trifluoromethyl)phenyl]-1-phenylethanone (12);34 3-[3-(Tri-
fluoromethyl)phenyl]-2-butanone (13);20 3-(4-cyanophenyl)-2-
butanone (15);36 2-(4-methoxyphenyl)-1-phenylethanone (16);37
3-(4-methoxyphenyl)-2-butanone (17);35 3-(3-pyridyl)-2-bu-
tanone (18);38 Benzeneacetic acid, R-methyl-methyl ester
(20);39 Benzeneacetic acid, 4-fluoro-R-methyl-methyl ester
Ack n ow led gm en t. We gratefully acknowledge the
CNRS (UMR 28) for financial support, and the Minis-
te`re de l’Enseignement Supe´rieur et de la Recherche for
a fellowship to M.D.
Registr y Nu m ber s (p r ovid ed by th e a u th or ). (1), 103-
79-7; (2), 459-03-0; (3), 21906-39-8; (4a ), 7115-18-6; (4b),
25539-21-7; (5), 22744-50-9; (6), 122-89-9; (7), 3027-13-2; (8),
4676-39-5; (9), 14293-24-4; (10), 347-91-1; (11), 79341-86-9;
(12), 30934-66-8; (13), 21906-07-0; (15), 79341-85-8; (16),
24845-40-7; (17), 7074-12-6; (18), 66702-67-8; (19), 101-41-7;
(20), 31508-44-8; (21), 34837-84-8; (22), 50415-71-9; (23) (-),
145983-12-6; (24), 125670-61-3; (25), 52798-01-3; (26), 125670-
62-4; (27), 6767-29-9; (28), 79443-97-3; (29), 50415-73-1; (30),
72221-62-6; (31), 30012-51-2; (32), 29891-75-5; (33), 94041-
87-9; (34), 1813-96-3; (35), 1813-97-4; (36), 140-67-0; (37a ),
18322-84-4; (37b), 18272-83-8; (39), 587-79-1; (40), 13132-15-
5; (41), 103-25-3; (42) (E), 588879-30-4; (42) (Z), 154309-36-
1; (43), 140675-27-0; (43) (E), 74254-13-0; (44), 4180-23-8.
J O9518314
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