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H. Fillon et al. / Tetrahedron Letters 43 (2002) 5941–5944
pling reactions between these organozinc reagents and
acetyl chloride were realized using palladium(II) cata-
lyzed, or copper(I) mediated, classical conditions.
remains unconverted and the organozinc yield decreases
in about 10%. The use of cobalt chloride instead of
cobalt bromide leads to a lower yield (65%) and again
to a partial consumption of the aromatic halide. We
have shown that 15% amount of cobalt bromide was
the lower range in order to obtain an efficient conver-
sion to the organozinc species since using 10% amount
of this salt gives rise to the preferential formation of the
hydro-dehalogenation product of the starting material
(ArH, 70%).
Recently, electrochemical studies carried out in our
laboratory have shown that the addition of vinyl ace-
tate or methyl vinyl ketone as ligand to a mixture of
acetonitrile and pyridine could enhance Co(I) stability.9
It has been noticed that in our previously described
conditions7 of electrosynthesis of aromatic organozinc
species, the presence of pyridine remained crucial even
in the presence of those ligands. Aiming to discard
pyridine in our electrosynthesis reaction mixtures, its
nucleophilic properties being in some cases a drawback
when electrophilic species are added to electrolyses
mixtures, other reaction conditions have thus been
studied. It has been possible to show, towards several
electrochemical studies, that the presence of a stoichio-
metric amount of zinc bromide, which was electrogen-
erated, had a very promising effect on Co(I) lifetime.
Thus, because the Co(I) lifetime is considered the key
point in the catalytic process of aromatic organozinc
compounds formation,10 we thought that we could
eliminate pyridine if zinc bromide was present in suffi-
cient amount in the reaction mixture. Several elec-
trosynthesis attempts were realized11 (Scheme 1).
Then we used the optimized conditions described above
to convert aromatic halides bearing electron donating
groups to the related organozinc species.
It is noteworthy that in all cases yields vary from
moderate to good. The position of the substituent has
only a slight influence on yields and in all cases, the sole
byproduct is the hydro-dehalogenation product of the
starting aromatic halide (ArH), the dimerization
product (ArꢀAr) being always absent. Such a behaviour
has previously been reported when reactions are carried
out with such donating groups.
Our study was then extended to aromatic halides bear-
ing electron withdrawing groups. The results are sum-
marized in Table 2.
First, using acetonitrile as a solvent, we chose to exam-
ine the effect of the addition of various ligands on the
formation of the organozinc species stemming from
ethyl 4-bromobenzoate. Results are reported in Table 1.
It can be pointed out that the position of the sub-
stituent has again a slight influence on yields as
revealed by assays in entries 13–15. Yields are fairly
good except for p-fluoro-bromobenzene which leads to
a 43% yield but in that case, the starting material is not
totally consumed (entry 11). Curiously, no dimerization
products are detected when a nitrile group is connected
to the phenyl moiety while in the presence of pyridine,
a non negligible part of the self coupling product is
obtained.7 An interesting effect resulting from the
absence of pyridine in the electrolysis medium can be
observed when p-chloro-bromobenzene is used as start-
ing compound. Indeed, electrolyses of 2-chloro-bro-
mobenzene, conducted in the acetonitrile/pyridine
mixture, had afforded mono- and dizincation products
after a charge of 2 and 4 F per mol of substrate was
passed, respectively, the carbonꢀbromide bond being
metallated first.12 When acetonitrile is solely used, this
carbonꢀbromide bond remains reactive as attested by
the formation of the monozincation compound (entry
10) but no dizincation product could be observed when
an additional charge of 2 F per mol of substrate was
passed. This behaviour could be generalized to aro-
The main point to note is that the use of an additional
ligand is useless because similar yields are obtained in
entries 4–6. Moreover, the reaction yield seems to be
very sensitive to ligand amount as shown by compari-
son of entries 3 and 4. Considering the fact that the
presence of an additional ligand does not raise the
reaction yield and could have negative effects if the
optimal amount is not present in the reaction mixture,
we decided to work without any ligand in the following
electrosyntheses.
Several other parameters such as solvent, cathode
nature, halide in the cobalt salts and amount of catalyst
have been studied. The use of dimethylformamide
(DMF) or dimethylacetamide (DMAC) instead of ace-
tonitrile does not lead to organozinc species formation
when these solvents are used without addition of pyri-
dine. When a nickel foam cathode is used instead of a
stainless steel grid, a part of the starting material
Table 1. Influence of the nature of additive associated with 45 mL of acetonitrile
Entry
Additive
ArZnX (%)a
ArH (%)
ArAr (%)
Conv. (%)
1
2
3
4
5
6
Phenylsulfonyl acetonitrile 1 equiv./CoBr2
Adiponitrile 1 equiv./CoBr2
Vinyl acetate 1 equiv./CoBr2
Vinyl acetate 2 equiv./CoBr2
Methyl vinyl ketone 0.5 equiv./CoBr2
–
52
61
48
75
77
76
34
37
28
25
17
17
0
0
0
0
7
7
86
100
76
100
100
100
a The obtained arylzinc halides are converted into the corresponding aryl iodide by addition of iodine.