Published on Web 03/08/2003
New Chemical Synthesis of Functionalized Arylzinc
Compounds from Aromatic or Thienyl Bromides under Mild
Conditions Using a Simple Cobalt Catalyst and Zinc Dust
Hyacinthe Fillon, Corinne Gosmini,* and Jacques Pe´richon
Contribution from the Laboratoire d’Electrochimie, Catalyze et Synthe`se Organique,
UMR 7582 CNRS-UniVersite´ Paris 12 2, rue Henry-Dunant 94320 Thiais, France
Received October 15, 2002; E-mail: gosmini@glvt-cnrs.fr
Abstract: A new chemical method for the preparation of arylzinc intermediates is described in acetonitrile,
on the basis of the activation of aryl bromides by low-valent cobalt species arising from the reduction of
cobalt halide by zinc dust. This procedure allows for the synthesis of a variety of functionalized aryl- and
thienylzinc species in good to excellent yields. The versatility and the simplicity of that original method
represent an alternative to most known procedures.
Introduction
Among the numerous topics developed in our laboratory, the
synthesis of organozinc reagents is of current interest. In the
past few years, arylzinc compounds have been successfully
synthesized from aryl bromides or chlorides in high yields under
mild conditions by two electrochemical procedures. The former
one was based on the catalytic activity of a nickel complex in
DMF as solvent.8 More recently, we have developed a simpler
catalytic system involving cobalt halides in DMF or acetonitrile
associated to pyridine.9 The use of cobalt allowed us both to
achieve the synthesis of organozinc reagents using the sacrificial
anode process with a wide variety of solvents and to use a less
toxic catalyst. To develop a pyridine-free process, the last
electrochemical process has been carried out in pure acetonitrile
from aryl bromides.10 These electrochemical methods favorably
compare with known chemical processes. Yet all of the
electrochemical reactions are generally considered as being more
difficult to handle than conventional chemical methods. Thus,
electrochemical syntheses are poorly applied by organic chem-
ists, and, although they were found successful on the laboratory
scale, they are not used on a larger (industrial) scale.
The preparation of functionalized organometallic compounds
has been the subject of increased research activity over the past
decades,1 due to the versatility of such key intermediates in
organic synthesis. Indeed, organozinc species have received
much attention because of their mildness resulting in high
functional group compatibility.2 Numerous methods devoted to
carbon-zinc bond formation have been developed. Prior to the
discovery of Rieke zinc,3 zinc was found unreactive toward
alkyl, vinyl, and aryl bromides or chlorides except in the well-
known Reformatsky reaction.4 The preparation of these organo-
zinc compounds was formerly achieved only by a transmeta-
lation reaction of a zinc halide from preformed organolithium
or magnesium counterparts. Although some functionalized
magnesium reagents have been prepared via an iodine-
magnesium exchange,5 they need to be transmetalated with
copper or zinc to undergo the cross-coupling reaction. Organo-
lithium compounds can also bear a reactive group, providing
they are prepared at low temperature.6 Alternatively, Rieke
reported on a general approach for preparing highly reactive
metals such as zinc by reducing the corresponding metal halide.7
This Rieke zinc is generally reactive toward aryl or heteroaryl
bromides at elevated temperature but reacts neither on aryl
chlorides nor on some aryl bromides (e.g., 3-bromothiophene).
Despite its indisputable synthetic utility, the use of such activated
zinc requires specific conditions together with careful handling.
Given the importance of arylzinc species in chemical
synthesis, we developed a new chemical reaction aimed at
preparing aromatic zinc species. This process relies on our recent
discoveries and demonstrates that in some cases a purely
chemical reaction could be extended from our initial electro-
chemical process. Indeed, we have established that chemical
reducing agents could advantageously replace electricity for the
preparation of arylzinc compounds catalyzed by cobalt in
acetonitrile.11 The low-valent cobalt generated from the chemical
(1) (a) Boudier, A.; Bromm, L. O.; Lotz, M.; Knochel, P. Angew. Chem., Int.
Ed. 2000, 39, 4414. (b) Rieke, R. D.; Hanson, M. V. Tetrahedron 1997,
53, 1925.
(2) (a) Knochel, P.; Singer, R. D. Chem. ReV. 1993, 93, 2117. (b) Knochel,
P.; Jones, P. In Organozinc Reagents, A Practical Approach; Harwood, L.
M., Moody, C. J., Eds.; Oxford University Press: Oxford, 1999.
(3) Zhu, L.; Wehmeyer, R. M.; Rieke, R. D. J. Org. Chem. 1991, 56, 1445.
(4) Reformatsky, S. Ber. Dtsch. Chem. Ges. 1887, 20, 1210.
(5) Jensen, A. E.; Dohle, W.; Sapountzis, Y.; Lindsay, D. M.; Vu, V. A.;
Knochel, P. Synthesis 2002, 4, 565.
(8) Sibille, S.; Ratovelomanana, V.; Perichon, J. J. Chem. Soc., Chem. Commun.
1992, 283.
(9) Gosmini, C.; Rollin, Y.; Nedelec, J.-Y., Pe´richon, J. J. Org. Chem. 2000,
65, 6024.
(10) Fillon, H.; Le Gall, E.; Gosmini, C.; Pe´richon, J. Tetrahedron Lett. 2002,
(6) Tucker, C. E.; Majid, T. N.; Knochel, P. J. Am. Chem. Soc. 1992, 114,
3983.
43, 5941.
(11) Fillon, H.; Gosmini, C.; Pe´richon, J. Patent application in France (4. july
(7) Rieke, R. D. Aldrichimica Acta 2000, 33, 52.
2001) n°01/08880.
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10.1021/ja0289494 CCC: $25.00 © 2003 American Chemical Society
J. AM. CHEM. SOC. 2003, 125, 3867-3870
3867