Nickel-catalyzed electrochemical arylation of activated olefins

Article abstract of DOI:10.1002/1099-0690(20021)2002:1<105::AID-EJOC105>3.0.CO;2-J

Nickel-catalyzed electrochemical conjugate additions of substituted aryl bromides to activated olefins under recently optimized reaction conditions are reported. Good to high yields were obtained, whatever the nature of substituents in the meta- and para-positions of the benzene ring. In the ortho-substituted series, yields were good with electron-donating substituents, but low with electron-withdrawing groups. The activation of aryl chlorides and the sequential functionalization of aryl dihalides were also investigated.

Full text of DOI:10.1002/1099-0690(20021)2002:1<105::AID-EJOC105>3.0.CO;2-J

FULL PAPER
Nickel-Catalyzed Electrochemical Arylation of Activated Olefins
[a]
[a]
[a]
[a]
´
´ ´
Sylvie Condon,* Daniel Dupre, Gilles Falgayrac, and Jean-Yves Nedelec
Keywords: Addition / Catalysis / Electrochemistry / Nickel / Olefins
Nickel-catalyzed electrochemical conjugate additions of sub-
stituted aryl bromides to activated olefins under recently ing substituents, but low with electron-withdrawing groups.
optimized reaction conditions are reported. Good to high The activation of aryl chlorides and the sequential func-
tho-substituted series, yields were good with electron-donat-
yields were obtained, whatever the nature of substituents in tionalization of aryl dihalides were also investigated.
the meta- and para-positions of the benzene ring. In the or-
Introduction
the catalyst precursor being reduced in situ either by
zinc[8Ϫ10] or electrochemically.[11] We recently reported that
the electrochemical arylation of activated olefins can be effi-
ciently performed with either nickel[12] or cobalt[13] catalysts
in the presence of the cheap pyridine ligand, in combination
with the sacrificial anode procedure.[14] In the nickel-cata-
lyzed electrochemical arylation[12] of activated olefins
(Scheme 1), the low-valent nickel is generated in situ by
cathodic reduction of NiBr2, in an undivided cell provided
with an iron rod as the sacrificial anode.
Functionalized aryl rings occur both in natural sub-
stances and in biologically active molecules of pharmaceut-
ical or agrochemical interest. Activation of aryl halides by
the preparation of organometallic reagents or by metal
transition catalysis are attractive routes for introduction of
aryl moieties onto a substrate through coupling or addi-
tion reactions.
In conjugate addition reactions,[1] the use either of organ-
ocuprate reagents[2] or of organometallic reagents in the
presence of copper salts[3] are the classic methods for re-
gioselective 1,4-addition. These procedures require, as a
preliminary step, the preparation of air- and/or moisture-
sensitive organometallic reagents (such as organolithium or
organomagnesium) and the reaction usually has to be car-
ried out at controlled temperatures to ensure both the
stability of the reagent and the regioselectivity of the addi-
tion. Moreover, the yields reported in the literature are of-
ten based on the addition step, without mention of the
overall yields. There are also problems when the organo-
metallic reagent derives from a precursor bearing sensitive
functional groups such as ketone, ester, or nitrile. Recent
studies have shown ways to circumvent the low functional
group tolerance, either through the use of activated magnes-
ium[4] at Ϫ78 °C (Rieke magnesium) or through the pre-
paration of functionalized organometallic compounds by
halogen/metal exchange[5,6] either at low (magnesium)[6] or
at very low (lithium)[6] temperatures, eventually followed by
transmetallation with ZnBr2 or CuX (X ϭ CN, I) prior to
treatment[6,7] with an electrophile. One-step chemical or
electrochemical procedures, then, remain of high interest.
Homogeneous catalysis involving transition metal com-
plexes has already been proposed as a valuable alternative,
Scheme 1
Although the mechanism of this reaction remains to be
clarified, it may be pointed out that pyridine, which is used
as a co-solvent, probably interacts, along with the activated
olefin, with the active zero-valent nickel species generated
at ca. Ϫ1 V/SCE, thus preventing precipitation of the metal
(Scheme 2). The reaction thus most probably proceeds
through an organonickel complex, which arises through ox-
idative addition of aryl halide (ArX) to the nickel catalyst,
followed by an insertion reaction.
Scheme 2
[a]
`
Laboratoire d’Electrochimie, Catalyse et Synthese Organique,
The fate (Scheme 3) of the resulting organonickel com-
plex is still unclear. Iron ions released by the oxidation of
the sacrificial anode may undergo a transmetallation reac-
´
CNRS Ϫ Universite Paris XII Ϫ UMR 7582,
2 rue Henri Dunant 94320 Thiais, France
E-mail: condon@glvt-cnrs.fr
Eur. J. Org. Chem. 2002, 105Ϫ111
WILEY-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002
1434Ϫ193X/02/0101Ϫ0105 $ 17.50ϩ.50/0
105

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S. Condon, D. Dupre, G. Falgayrac, J. Y. Nedelec
FULL PAPER
tion (path A). Alternatively, the species may be protonated
in situ by residual water present in the solvent to afford the
final product (path B). It is worth noting that completely
anhydrous solvent is not required, and that the rate and the
yield of the reaction are not affected by a quantity of added
water (1 equiv. vs. ArX).
Table 1. Comparative study of the influence of the nature and of
the position of the substituent on the aryl bromide
Scheme 3
[a]
50% of starting material recovered after a passage of 5.3 F per
This straightforward and versatile electrochemical
method is characterized by mild reaction conditions, high
regioselectivity, and high tolerance towards sensitive func-
tional groups on the aromatic ring. In our first report,[12]
however, the yields were moderate, and not optimized, and
only a few aryl halides were studied.
Here we wish to report on the scope of the reaction. This
includes a study devoted to the influence of the nature and
the position of the substituents on the aromatic rings. The
activation of aryl chlorides has also been examined, as has
the extension of the procedure to the asymmetrical al-
kylation of aryl dihalides.
mol of ArX.
versus SCE. Results are reported in Table 1. High chemical
yields were obtained from reagents with either electron-do-
nating or electron-withdrawing substituents in the meta- or
para-positions in the benzene ring after consumption of ca.
2.2 F per mol of aryl halide.
Activation of ortho-substituted derivatives was usually
more critical. In this procedure, activation of ortho-substi-
tuted aryl bromides and their use in the conjugate addition
reaction was feasible to some extent. Indeed, yields were
good for substrates with electron-donating substituents
(Table 1, Entries 1, 2), but very low with electron-with-
drawing substituents (Table 1, Entries 3Ϫ6). This has al-
ready been observed in some catalyzed coupling reactions,
and remains unexplained.[16] In addition, different behavior
was observed in the latter series. o-Bromobenzonitrile was
largely recovered after passage of a charge of 5.3 F per mol
of ArX (Entry 3). This means that one step in the catalytic
cycle was too slow, and a electrochemical side-reaction,
such as the reduction of metallic salts released by oxidation
of the iron rod, had occurred. On the other hand, with
CO2Et, COCH3, or CF3 as the ring substituent, ArX was
consumed (Entries 4Ϫ6) after passage of a charge of 4.3 F
per mol of ArX. The main side reaction was the reduction
of ArBr into ArH. With 2-bromoacetophenone (Scheme 4),
2-acetyl-3-methylindene (14)[17] was formed (26%, isolated
yield) along with 15% of the desired product 12a (Table 1,
Entry 5) and acetophenone. With ethyl 2-bromobenzoate
Results and Discussion
1. Study of the Influence of the Nature and Position of a
Functional Group on the Aromatic Ring in Nickel-
Catalyzed Arylation of Methyl Vinyl Ketone
The study was carried out with aryl bromides, with
methyl vinyl ketone (MVK) as Michael acceptor. All the
reactions were performed according to the general method
previously described for the arylation of activated olefins.
They were conducted in an undivided cell[14] provided with
an iron rod as the anode, and a nickel grid as the cathode,
under argon, in commercial solvents used without further
purification. The ionic conductivity was ensured by
Bu4NBr and Bu4NI added to the reaction mixture. An im-
provement on the previously reported procedure[12] for
nickel-catalyzed alkenylation[15] of activated olefins was
found in the form of a short pre-electrolysis at room tem-
perature, involving the oxidation of the iron anode along
with the reduction of 1,2-dibromoethane in N,N-dimethyl-
formamide (DMF)/pyridine, prior to the electrolysis of the
mixture of the reagents and the catalyst precursor. After-
wards, the electrolysis of the solution containing the aryl
bromide, MVK, and the catalyst precursor was run at 70
°C under a constant current intensity of 0.1 A, until full
consumption of the aryl halide. The cathode potential
throughout the electrolysis was between Ϫ0.9 and Ϫ1 V Scheme 4
106
Eur. J. Org. Chem. 2002, 105Ϫ111

Nickel-Catalyzed Electrochemical Arylation of Activated Olefins
FULL PAPER
Table 2. Nickel-catalyzed electrochemical arylation of activated ol-
efins under optimized reaction conditions
Scheme 5
(Scheme 5), we obtained mainly the dehalogenated com-
pound 15 along with traces of the cyclic diketone 16 (7%
GC yield).
The nickel-catalyzed electrochemical procedure described
here thus enables substituted aryl bromides to be activated
and used synthetically without any need to protect sensitive
functional groups. Even hydroxy groups are tolerated with-
out any protection. Hence, the reaction between 3-bromo-
phenol and MVK yielded 4-(3-hydroxyphenyl)propan-2-
one in 75% yield.
In the runs above, the amount of NiBr2·3H2O was set
to 10 mol% vs. ArBr without optimization. Regarding the
optimum amount of NiBr2·3H2O required, it is first import-
ant to point out that the cathodic reaction is the reduction
of NiII and NiI into Ni0, which enters the catalytic cycle
[a]
Reactions were conducted with aryl bromide (7.5 mmol), activ-
ated olefin (2.5 equiv.), and NiBr2·3H2O (0.1 equiv.) in DMF/pyrid-
through the oxidative addition with ArX. This means that ine (9:1) at 70 °C at constant current density (0.3 A/dm2). [b] DMF/
pyridine (9:1) replaced by DMF/AN (1:1).
the overall reaction rate is current-dependent as long as the
concentration of the precursors of Ni0 is high enough, for
a given current density. This is actually ensured with at least
5% of NiBr2 vs. ArBr for the reaction between 4-bromoace-
Table 3. Influence of temperature and solvents in nickel(0)-cata-
tophenone and MVK when conducted at I ϭ 0.1 A. Thus,
chemical and Faradaic yields were 90% (isolated) and ca.
80%, respectively, with 5% of nickel salt. At below 2.5% of
NiBr2 and still at 0.1 A, a reasonable 83% chemical yield
could still be reached but after over-electrolysis correspond-
ing to a 66% Faradaic yield.
lyzed conjugate addition of methyl 4-chlorobenzoate to MVK
The above reaction conditions are also suitable for effici-
ently performing the arylation of other activated olefins,
such as ethyl acrylate (Table 2, Entries 3Ϫ5) or acrylonitrile
(Table 2, Entry 6). However, alkyl substituents on the
double bond of the activated olefin tended to slow down
the rate of the reaction to a rather large extent, and low
yields of ca. 25% were obtained with methyl crotonate,
methyl methacrylate, and also with cyclohexenone. A se-
cond carboxy group on the carbonϪcarbon double bond
was favorable, as observed with dimethyl maleate (Table 2,
Entry 7). Another solvent combination, DMF/acetonitrile
(AN) (1:1) already used in the previously studied alkenyl-
ation[15] and also mediated by nickel catalysis, could be ap-
plied to the arylation reaction. The reported comparative
results (Table 2) showed that DMF/AN was a good altern-
ative to DMF/pyridine, and even more favorable for the re-
action between 4-bromoacetophenone and acrylonitrile
(Table 2, Entry 6).
[a]
DMF/pyridine (9:1) and DMF/AN (1:1) were used.
reactive under the optimized reaction conditions described
above. Attempts to activate them were thus carried out by
a study of the reaction between methyl 4-chlorobenzoate
and MVK. The results are reported in Table 3. We first
found that raising the reaction temperature to 100 °C
(Table 3, Entry 4) favored the oxidative addition of aryl
chlorides to Ni0, and thus promoted the catalytic cycle,
whereas most of the starting material was recovered at 70
°C (Table 3, Entries 1Ϫ2). A solvent effect was also ob-
2. Nickel-Catalyzed Conjugate Addition Reaction of Aryl
Chlorides to Methyl Vinyl Ketone
Because of their low cost compared to aryl bromides, aryl served. Indeed, the reaction was fully completed only in
chlorides are of considerable interest, and recent papers re- DMF/pyridine (Table 3, Entries 5 and 7). We also found
fer to their use in palladium- or nickel-catalyzed coupling that the Bu4NBr/Bu4NI as supporting electrolyte can be ad-
reactions.[23,24Ϫ27] Aryl chlorides were found to be poorly vantageously replaced by the cheaper salt NaBr (Table 3,
Eur. J. Org. Chem. 2002, 105Ϫ111
107

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S. Condon, D. Dupre, G. Falgayrac, J. Y. Nedelec
FULL PAPER
aryl chloride were recovered (36% of chloroanisole, 44% of
chlorotoluene) with electron-rich aryl chlorides (Table 4,
Entries 1, 2).
Table 4. Scope of aryl chlorides in the conjugate addition reaction
to methyl vinyl ketone
3. Extension of the Procedure to the Dialkylation Reaction
This study was extended to dibromobenzenes, with the
goal of achieving sequential additions. Results are reported
in Table 5. The feasibility of dialkylation of dibromobenz-
enes was first carried out with MVK as sole substrate. 1,3-
Dibromobenzene and 1,4-dibromobenzene (Table 5, Entries
1, 2) showed approximately the same reactivity, and satisfy-
ing yields of the expected dialkylated product were ob-
tained. 1,2-Dibromobenzene gave 4-(2-bromophenyl)butan-
2-one (35% isolated yield) as the main product when treated
under the same reaction conditions as for 1,3- and 1,4-di-
bromobenzene. Most of the 1,2-dibromobenzene was con-
sumed and only traces of 2-(3-oxobutylphenyl)butan-2-one
were detected by GC.
For unsymmetrical dialkylation of dibromobenzene, the
second olefin used was ethyl acrylate, which is also a good
Michael acceptor in the arylation process (Table 2, Entries
3Ϫ5). The reaction was conducted in one-pot fashion, and
the two olefins were added sequentially to limit the amount
of symmetrical dialkylated products, the second one being
Entries 4 and 5), which is worth considering in an industrial introduced into the cell after most of the dibromobenzene
process. Table 4 reports the results obtained with various had been converted into its monobromo derivative and
aryl chlorides.
while the amount of symmetrical dialkylated compound
Unlike in the aryl bromide series, a striking influence of was less than 10% (GC analysis). Obtained yields of the
the substituent on the aromatic ring was observed. Whereas desired product were moderate, due to the inevitable forma-
yields were good with the electron-poor aryl chlorides tion of the two symmetrically dialkylated compounds. The
(Table 4, Entries 3Ϫ6) and the courses of the reaction were yield of the reaction was not influenced by the order of
similar to those observed for aryl bromides, medium yields introduction (Table 5, Entries 3, 4) of the two olefins. In
were obtained and significant amounts of the unreactive order to limit the amount of symmetrical dialkylated com-
Table 5. Polyfunctionalization of aryldihalides by sequential conjugate addition
[a]
[b]
t indicates reaction time before addition of the second olefin. Reaction conducted at constant current intensity (0.1 A).
108
Eur. J. Org. Chem. 2002, 105Ϫ111

Nickel-Catalyzed Electrochemical Arylation of Activated Olefins
FULL PAPER
pounds, the second olefin was introduced in excess with re- groups, but is also quite efficient with electron-rich reagents.
spect to the first one (Table 5, Entries 4, 5). Thus, sequential Aryl chlorides can also be activated at a higher temperature,
treatment of 1,3-dibromobenzene with ethyl acrylate and but their use is restricted to the electron-poor aryl chlorides.
MVK afforded the dissymmetrical dialkylated compound Most importantly, this conjugate addition reaction is a one-
30 as the main product (Table 5, Entry 5), along with the step procedure that can be used advantageously for the pre-
two symmetrical dioxo and diester compounds (in 12 and paration of biologically active substances from commer-
6% isolated yield, respectively). For comparative purposes, cially available starting materials. Thus, 4-(4-methoxyphen-
the preparation of ethyl 3-[3-(3-oxobutyl)phenyl]propanoate yl)butan-2-one (9c)[20] is the insect attractant for the scara-
(30) in two steps afforded a 57% isolated yield of ethyl 3- baeid subfamily Rutelinae, while 4-(2-methoxyphenyl)bu-
(3-bromophenyl)propanoate in the first step and, after sub- tan-2-one (9a)[20] is a key intermediate en route to the
sequent treatment with MVK, 80% of 30 in an overall bronchospasmolytically active [(arylalkyl)amino](hydroxy-
45% yield.
phenyl)ethanols. Arylsuccinates[34] are intermediates for the
We also tried to achieve better control in the selectivity preparation of building blocks involved in the synthesis of
of the sequential addition by performing the reaction with anti-inflammatory agents, and 4-(6-methoxy-2-naphthyl)-
1-bromo-4-chlorobenzene (31) (Scheme 6). The bromide butan-2-one (18) (Nabumeton)[28,35] is a nonsteroidal anti-
substituent was replaced selectively on treatment with ethyl inflammatory drug usually prepared in four steps in about
acrylate at 60 °C in DMF/pyridine media, and ethyl 3-(4- 40% yield.
chlorophenyl)propanoate (32) was isolated in 74% yield. At-
The arylation reactions described above were routinely
tempts to induce it to react further with MVK under the performed in small undivided cells (volume 40 mL) charged
reaction conditions described above for the activation of with 7Ϫ15 mmol of the aryl halide and 2.5 equiv. of the
aryl chlorides, however, were unsuccessful.
activated olefin. The reaction can also be carried out quite
efficiently in an electrochemical flow cell. In a typical run,
the reaction between 4-bromoanisole (170 mmol) and butyl
acrylate (420 mmol) in DMF/picoline (9:1) at 80 °C yielded
28 g (70% yield) of the addition product in a 90% Faradaic
yield. A detailed study of the various parameters related to
further scaling-up is underway in collaboration with Elec-
´
tricite de France.
Scheme 6
Experimental Section
Recently, we described another procedure[32] for electro-
reductive coupling of aryl halides with activated olefins
with [bis(2-pyridyl)amine]nickel complexes. These com-
plexes enable bromides to be activated at room temperature
in ethanol, a safe and inexpensive solvent. When the reac-
tion between ethyl 3-(4-chlorophenyl)propanoate (32) and
MVK was conducted under these conditions,[32] however,
either at room temperature or at 60 °C, only a small amount
of desired product 33 was obtained (20% GC yield). When
the electrolysis was conducted until full consumption of the
starting reagents, mostly the dehalogenated compound
was formed.
All solvents and reagents were purchased from commercial sources
and used as received. DMF and AN were stored under argon. GC
analysis was carried out on a 25-m DB-1 capillary column. Column
chromatography was performed on silica gel, 70Ϫ230 mesh. H1,
13C, and 19F NMR spectra were recorded with a Bruker AC 200
(200 MHz) spectrometer. Mass spectra were obtained with a GCQ
Thermoquest spectrometer coupled to a chromatograph fitted with
a 25-m CPSIL5 CB capillary column. Elemental analyses were car-
ried out by the Service Central de Microanalyses (CNRS, Lyon).
The electrochemical cell has been described previously.[14] IR spec-
tra were measured with a Perkin Elmer 283B spectrophotometer;
neat for liquid compounds and in CHCl3 for solid compounds.
General Procedure for the Arylation of Electron-Deficient Olefins:
Under argon, in an undivided cell equipped with a nickel grid (area
30 cm2) as the cathode and an iron rod as the anode, tetrabutylam-
monium bromide (0.34 mmol) and tetrabutylammonium iodide
Conclusions
Activation of functionalized aryl halides by nickel cata- (0.21 mmol) or NaBr (1.50 mmol) as supporting electrolytes were
dissolved in a mixture of DMF (27 mL) and pyridine (3 mL). A
short electrolysis was conducted in the presence of 1,2-dibromo-
ethane (0.90 mmol) at constant current density (0.3 A dmϪ2) and at
room temperature over 30 min to generate a small amount of iron
ions. The current was then turned off. NiBr2·3H2O (0.75 mmol,
164 mg) and the activated olefin (18.75 mmol) was added, and the
mixture was heated at 70 °C (when aryl bromide was used) or 100
°C (when aryl chloride was used) after the addition of the aryl
halide (7.5 mmol). The electrosynthesis was run at constant current
density (0.3 A dmϪ2). The reaction was monitored by GC and
lysis under mild reaction conditions thus results in the
formation of functionalized arylnickel intermediates, which
add regioselectively to activated olefins. Under the optim-
ized reaction conditions, neither homocoupling of the aryl
halide, nor the Heck reaction are observed. The main side-
product is the dehalogenated (reduced) aryl compound. No
protection of sensitive functional groups is required. Fur-
thermore, the significant results obtained (Table 1) with the
aryl bromide series demonstrate that the reaction is not
confined to aryl bromides possessing electron-withdrawing stopped after the aryl bromide was consumed. An average charge
Eur. J. Org. Chem. 2002, 105Ϫ111 109

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S. Condon, D. Dupre, G. Falgayrac, J. Y. Nedelec
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1
of 2.5 F molϪ1 was used in most reactions described in Tables 1Ϫ4.
The mixture was then hydrolyzed with hydrochloric acid (1 ,
30 mL) and diluted with diethyl ether (50 mL). The aqueous layer
Ethyl 4-(3-Oxobutyl)benzoate (11c): H NMR (200 MHz, CDCl3):
1
δ ϭ 1.31 (t, J ϭ 7.10 Hz, 3 H, CH3), 2.08 (s, 3 H, CH3), 2.70 (m,
1
2 H, CH2), 2.88 (m, 2 H, CH2), 4.29 (q, J ϭ 7.10 Hz, 2 H, CH2),
was extracted with diethyl ether (2 ϫ 50 mL) and the combined 7.18 (d, 1J ϭ 8.20 Hz, 2 H), 7.88 (d, 1J ϭ 8.20 Hz, 2 H). 13C NMR
organic layers were washed with water and saturated NaCl solu-
tion, then dried with MgSO4. The oil thus obtained was purified
by column chromatography to give desired compound.
(50.321 MHz, CDCl3): δ ϭ 14.1, 29.3, 29.8, 44.2, 60.6, 128.1 (2 C),
129.5, 146.3, 166.2, 207.0. MS; m/z (%): 220, 205, 174 (100), 149,
131, 105. IR: ν˜ ϭ 3020, 1730, 1720, 1600, 1450, 900 cmϪ1
.
4-(3-Acetylphenyl)butan-2-one (12b): 1H NMR (200 MHz, CDCl3):
δ ϭ 1.80 (s, 3 H, CH3), 2.20 (s, 3 H, CH3), 2.53 (m, 4 H, 2 ϫ CH2),
7.05 (m, 2 H), 7.42 (m, 2 H). 13C NMR (50.321 MHz, CDCl3): δ ϭ
26.1, 28.9, 29.5, 44.2, 125.8, 127.6, 128.3, 132.8, 136.9, 141.3, 197.6,
General Procedure for the Sequential Addition Reaction from Aryl
Dihalides: Under argon, in an undivided cell equipped with a nickel
grid (area 30 cm2) as the cathode and an iron rod as the anode,
tetrabutylammonium bromide (0.34 mmol) and tetrabutylammo-
nium iodide (0.21 mmol) as supporting electrolytes were dissolved
in a mixture of DMF (27 mL) and pyridine (3 mL). 1,2-Dibromo-
ethane (0.90 mmol) was introduced. After a short electrolysis run
at constant current density (0.3 A dmϪ2) and at room temperature
for 30 min, the current was turned off and NiBr2·3H2O (0.75 mmol,
164 mg) and the first activated olefin (1.5 to 2.5 equiv.) were added.
The mixture was heated at 70 °C after introduction of dibromoben-
zene (7.5 mmol). The electrosynthesis was run at constant current
density (0.3 A dmϪ2). The second olefin was introduced into the
cell together with a small portion of NiBr2·3H2O (0.37 mmol,
82 mg) when most of the dibromobenzene had been consumed, to
give its monobromo derivative, and the proportion of the symmet-
rically dialkylated compound did not exceed 10% (uncorrected GC
yield). The reaction was monitored by GC and terminated after
full consumption of the monobromo derivative. The mixture was
then hydrolyzed with hydrochloric acid (1 , 30 mL) and diluted
with diethyl ether (50 mL). The aqueous layer was extracted with
diethyl ether (3 ϫ 50 mL), the combined organic layers were
washed with water and saturated NaCl solution and dried with
MgSO4, and the solvent was evaporated. The crude product thus
obtained was purified by column chromatography.
˜
206.8. MS; m/z (%): 191 (100), 175, 147, 77. IR: ν ϭ 3020, 1730,
1690, 1610, 1590, 1490, 1450, 800 cmϪ1
.
1
4-(4-Acetylphenyl)butan-2-one (12c): H NMR (200 MHz, CDCl3):
1
δ ϭ 2.07 (s, 3 H, CH3), 2.50 (s, 3 H, CH3), 2.67 (t, J ϭ 7.00 Hz,
2 H, CH2), 2.84 (t, 1J ϭ 7.00 Hz, 2 H, CH2), 7.21 (d, 1J ϭ 7.18 Hz,
2 H), 7.81 (d, 1J ϭ 7.18 Hz, 2 H). 13C NMR (50.321 MHz, CDCl3):
δ ϭ 26.2, 29.3, 29.7, 44.1, 128.3 (2C), 135.0, 146.7, 197.3, 206.8.
MS; m/z (%): 191 (100), 190, 175, 147. IR: ν˜ ϭ 3080, 1730, 1690,
1610 cmϪ1. C12H14O2: calcd. C 75.76, H 7.42; found C 75.98, H
7.46.
4-(2-Trifluoromethylphenyl)butan-2-one (13a): 1H NMR (200 MHz,
1
CDCl3): δ ϭ 2.04 (s, 3 H, CH3), 2.64 (t, J ϭ 7.70 Hz, 2 H, CH2),
1
2.96 (t, J ϭ 7.70 Hz, 2 H, CH2), 7.14Ϫ7.52 (m, 4 H). 19F NMR
(CDCl3): δ ϭ Ϫ59.60. MS; m/z (%): 216, 197, 196, 133 (100). IR:
Ϫ1
˜
ν ϭ 3020, 1730, 1610, 1590, 1500, 1450, 1320, 770 cm
.
C11H11OF3: calcd. C 61.10, H 5.12; F, 26.36; found C 60.77, H
5.18; F, 26.24.
4-(4-Trifluoromethylphenyl)butan-2-one (13c): 1H NMR (200 MHz,
CDCl3): δ ϭ 2.20 (s, 3 H, CH3), 2.84 (m, 2 H, CH2), 3.01 (m, 2 H,
1
CH2), 7.36 (d, J ϭ 8.00 Hz, 2 H), 7.58 (d, 1J ϭ 8.00 Hz, 2 H). 19F
1
4-(3-Methylphenyl)butan-2-one (8b): H NMR (200 MHz, CDCl3):
NMR (CDCl3): δ ϭ Ϫ62.24. MS; m/z (%): 217, 216 (100), 197,
δ ϭ 2.06 (s, 3 H, CH3), 2.26 (s, 3 H, CH3), 2.64Ϫ2.84 (m, 4 H, 2 ϫ
CH2), 6.90Ϫ6.94 (m, 3 H), 7.11 (m, 1 H). 13C NMR (50.321 MHz,
CDCl3): δ ϭ 21.1, 29.4, 29.7, 44.9, 125.0, 126.6, 128.1, 128.8, 137.7,
133. IR: ν ϭ 1730, 1330, 820 cmϪ1. C11H11F3O: calcd. C 61.10, H
˜
5.12; F, 26.36; found C 60.66, H 5.23; F, 25.78.
˜
140.7, 207.6. MS; m/z (%): 162, 147, 119 (100), 105, 91. IR: ν ϭ
Ethyl 3-(6-Methoxy-2-naphthalenyl)propanoate (20): M.p. 75.3 °C
(ref.[29] 76 °C). 1H NMR (200 MHz, CDCl3): δ ϭ 1.13 (t, 1J ϭ
3020, 1730, 1720, 780 cmϪ1
.
1
1
7.12 Hz, 3 H, CH3), 2.59 (t, J ϭ 7.72 Hz, 2 H, CH2), 2.99 (t, J ϭ
7.72 Hz, 2 H, CH2), 3.75 (s, 3 H, CH3), 4.05 (q, 1J ϭ 7.12 Hz, 2
H, CH2), 7.00Ϫ7.58 (m, 6 H). 13C NMR (50.321 MHz, CDCl3):
δ ϭ 14.1, 30.9, 35.8, 55.0, 60.2, 105.6, 118.7, 126.3, 126.9, 127.4,
128.9, 129.0, 133.2, 135.7, 157.3, 172.7. MS; m/z (%): 258, 184,
171 (100).
3-(3-Oxobutyl)benzonitrile (10b): 1H NMR (200 MHz, CDCl3): δ ϭ
2.09 (s, 3 H, CH3), 2.82 (m, 4 H, 2 ϫ CH2), 7.28 Ϫ7.43 (m, 4 H).
13C NMR (50.321 MHz, CDCl3): δ ϭ 28.6, 29.5, 43.7, 111.8, 118.6,
129.0, 129.4, 131.6, 132.8, 142.5, 206.4. MS; m/z (%): 174 (100),
173, 158, 131, 130, 116, 103, 77. IR: ν˜ ϭ 3080, 3020, 2240, 1730,
1720, 1600, 1580, 1500, 800 cmϪ1. C11H11NO: calcd. C 76.27, H
6.40, N 8.08; found C 76.25, H 6.42, N 8.09.
4-[3-(3-Oxobutyl)phenyl]butan-2-one (27): 1H NMR (200 MHz,
CDCl3): δ ϭ 1.96 (s, 6 H, 2 ϫ CH3), 2.48Ϫ2.76 (m, 8 H, 4 ϫ CH2),
6.80 (m, 3 H), 7.00 (m, 1 H). 13C NMR (50.321 MHz, CDCl3): δ ϭ
207.4, 140.9, 128.3, 128.0, 125.7, 44.6, 29.6, 29.3.
4-(3-Oxobutyl)benzonitrile (10c): M.p. 53.2 °C. 1H NMR
(200 MHz, CDCl3): δ ϭ 2.17 (s, 3 H, CH3), 2.80 (t, J ϭ 6.81 Hz,
1
2 H, CH2), 2.97 (t, 1J ϭ 6.81 Hz, 2 H, CH2), 7.31 (d, 1J ϭ 8.20 Hz,
2 H), 7.59 (d, 1J ϭ 8.20 Hz, 2 H). 13C NMR (50.321 MHz, CDCl3):
δ ϭ 29.2, 29.6, 43.6, 109.4, 118.6, 128.9, 131.8, 146.6, 206.4. MS;
m/z (%): 174 (100), 131, 130, 116, 103. IR: ν˜ ϭ 3030, 2220, 1730,
1600, 1500, 820 cmϪ1. C11H11NO: calcd. C 76.27, H 6.40, N 8.08;
found C 76.57, H 6.39, N 8.27.
4-[4-(3-Oxobutyl)phenyl]butan-2-one (28): M.p. 55.8 °C (ref.[33]
1
53.5Ϫ55 °C). H NMR (200 MHz, CDCl3): δ ϭ 2.06 (s, 6 H, 2 ϫ
CH3), 2.55 Ϫ2.81 (m, 8 H, 4 ϫ CH2), 7.00 (s, 4 H). 13C NMR
(50.321 MHz, CDCl3): δ ϭ 207.5, 138.4, 128.1, 44.8, 29.7, 29.0.
˜
MS; m/z (%): 218, 201, 161, 160, 117 (100). IR: ν ϭ 3020, 1720,
1520, 1450 cmϪ1. C14H18O2: calcd. C 77.03, H 8.31; found C 77.05,
H 8.36.
1
Ethyl 3-(3-Oxobutyl)benzoate (11b): H NMR (200 MHz, CDCl3):
1
δ ϭ 1.42 (t, J ϭ 7.11 Hz, 3 H, CH3), 2.18 (s, 3 H, CH3), 2.82 (m,
2 H, CH2), 2.98 (m, 2 H, CH2), 4.40 (q, J ϭ 7.11 Hz, 2 H, CH2), Ethyl 3-[4-(3-Oxobutyl)phenyl]propanoate (29): 1H NMR
1
7.40 (m, 2 H), 7.91 (m, 2 H). 13C NMR (50.321 MHz, CDCl3): δ ϭ (200 MHz, CDCl3): δ ϭ 1.15 (t, J ϭ 7.13 Hz, 3 H, CH3), 2.05 (s,
1
14.1, 29.1, 29.6, 44.4, 60.6, 127.0, 128.2, 129.0, 130.4, 132.7, 141.1, 3 H), 2.51 (t, 1J ϭ 7.73 Hz, 2 H, CH2), 2.61Ϫ2.87 (m, 6 H, 3 ϫ
166.2, 206.9. MS; m/z (%): 220, 205, 174 (100), 149, 131, 105. IR: CH2), 4.04 (q, J ϭ 7.13 Hz, 2 H, CH2), 7.03 (s, 4 H). 13C NMR
1
Ϫ1
˜
ν ϭ 3020, 1730, 1720, 1600, 1450, 750 cm
.
(50.321 MHz, CDCl3): δ ϭ 207.4, 172.5, 138.6, 138.0, 128.1 (4 C),
Eur. J. Org. Chem. 2002, 105Ϫ111
110

Nickel-Catalyzed Electrochemical Arylation of Activated Olefins
FULL PAPER
[13]
[14]
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[16]
[17]
´ ´
´
P. Gomes, C. Gosmini, J. Y. Nedelec, J. Perichon, Tetrahedron
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60.0, 44.7, 35.6, 30.2, 29.6, 29.0, 13.9. IR: ν˜ ϭ 1740, 1720, 800
cmϪ1. C15H20O3: calcd. C 72.55, H 8.12; found C 72.60, H 8.08.
´ ´
´
J. Chaussard, J. C. Folest, J. Y. Nedelec, J. Perichon, S. Sibille,
Ethyl 3-[3-(3-Oxobutyl)phenyl]propanoate (30): 1H NMR
M. Troupel, Synthesis 1990, 369Ϫ380.
1
´
´ ´
´
S. Condon-Gueugnot, D. Dupre, J. Y. Nedelec, J. Perichon,
Synthesis 1997, 1457Ϫ1460.
(200 MHz, CDCl3): δ ϭ 1.09 (t, J ϭ 7.13 Hz, 3 H, CH3), 1.98 (s,
1
3 H, CH3), 2.45 (t, J ϭ 7.73 Hz, 2 H, CH2), 2.55 Ϫ2.81 (m, 6 H,
1
A. Aranyos, D. W Old, A. Kiyomori, J. P. Wolfe, J. P. Sadighi,
S. L. Buchwald, J. Am. Chem. Soc. 1999, 121, 4369Ϫ4378.
2-Acetyl-3-methylindene was characterized on the basis of the
following data: 1H NMR: δ ϭ 7.70 (m, 2 H), 7.50 (m, 2 H),
3 ϫ CH2), 3.98 (q, J ϭ 7.13 Hz, 2 H, CH2), 6.88 (m, 3 H), 7.05
(m, 1 H). 13C NMR (50.321 MHz, CDCl3): δ ϭ 207.5, 172.6, 141.0,
140.6, 128.4, 128.1, 126.0, 125.9, 60.1, 44.8, 35.7, 30.7, 29.8, 29.5,
˜
14.0. MS; m/z (%): 249, 230, 203, 184, 174, 160 (100). IR: ν ϭ 1740,
1
3.80 (m, CH2), 2.67 (t, J ϭ 2.46 Hz, 3 H, CH3ϪCϭC), 2.57
1720, 800 cmϪ1. C15H20O3: calcd. C 72.55, H 8.12; found C 72.06,
H 8.07.
(s, 3 H, CH3). 13C NMR: δ ϭ 196.36, 149.66, 145.10, 142.85,
137.32, 127.77, 126.49, 123.70, 121.30, 38.85, 29.86, 12.63.
Mass (IE); m/z (%): 172, 157, 129 (100).
Ethyl 3-(4-Chlorophenyl)propanoate (32): 1H NMR (200 MHz,
CDCl3): δ ϭ 1.15 (t, 3 H, J ϭ 7.15 Hz), 2.52 (t, 2 H, J ϭ 7.61 Hz),
2.84 (t, 2 H, J ϭ 7.61 Hz), 4.04 (q, 2 H, J ϭ 7.15 Hz), 7.03Ϫ7.20
(m, 4 H). 13C NMR (50.321 MHz, CDCl3): δ ϭ 13.9, 29.9, 35.4,
60.1, 128.2, 129.4, 131.7, 138.8, 172.2. MS; m/z (%): 212, 214. IR:
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Eur. J. Org. Chem. 2002, 105Ϫ111
111