Electrosynthesis of functionalized 2-arylpyridines from functionalized aryl and pyridine halides catalyzed by nickel bromide 2,2'-bipyridine complex

Article abstract of DOI:10.1016/S0040-4039(00)00760-7

2-Arylpyridines substituted on aryl and/or on pyridine nuclei can be obtained in good to high yields in one step by electroreduction of mixtures of the corresponding aryl and pyridyl halides using the sacrificial iron anode process and a nickel 2,2'-bipyr

Full text of DOI:10.1016/S0040-4039(00)00760-7

Tetrahedron Letters 41 (2000) 5039±5042
Electrosynthesis of functionalized 2-arylpyridines from
functionalized aryl and pyridine halides catalyzed by nickel
bromide 2,20-bipyridine complex
Corinne Gosmini,* Jean Yves Nedelec and Jacques Perichon
Á
Laboratoire d'Electrochimie, Catalyse et Synthese Organique, UMR 7582, CNRS, 2, Rue Henri Dunant,
94320 Thiais, France
Received 21 March 2000; accepted 10 May 2000
Abstract
2-Arylpyridines substituted on aryl and/or on pyridine nuclei can be obtained in good to high yields in
one step by electroreduction of mixtures of the corresponding aryl and pyridyl halides using the sacri®cial
iron anode process and a nickel 2,20-bipyridine complex catalyst in DMF as solvent. # 2000 Elsevier
Science Ltd. All rights reserved.
Arylpyridine sub-units form the basic structure of a large variety of biologically active com-
pounds, notably agrochemicals. Further reactions from these biaryls to the ®nal product require
the presence, on one or the two rings, of functional groups such as ester, nitrile, nitro, or acyl
groups. Modern chemical methods of metal-catalyzed cross-coupling o€er various routes to prepare
these biaryls from readily available aryl- and pyridylhalides.1 However, they all require the pre-
liminary formation of an organometallic intermediate, and this is hardly compatible with the
presence of electrophilic functional groups. Even soft organometallics of zinc, tin, or boron are
usually obtained by transmetallation from organo-magnesium or -lithium reagents. Therefore, in
many cases, one has to introduce functional groups after the cross-coupling.2
There is still a need for more simple and more versatile cross-coupling methods. In relation to
this, we have already reported in a previous paper3 the electrochemical synthesis of 2-arylpyridines
bearing substituent on the aryl ring. The ®rst one involves the electrochemical preparation of an
aryl zinc species followed by its reaction with 2-chloropyridine, these two steps being catalyzed by
the same nickel-2,20-bipyridine (bpy) complex. An alternative more simple method was also used.
It consists of the electroreduction of a 1:1 mixture of the two organic halides in the presence of a
* Corresponding author. Fax: 33(0)1 49 78 11 48; e-mail: gosmini@glvt-cnrs.fr
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00760-7

5040
catalytic amount of NiBr2bpy in DMF as solvent (Eq. (1)). The eciency of this route makes it
the most convenient method to prepare 2-arylpyridine compounds.
ꢀ1†
Results and discussion: In this former study we found that the use of a zinc anode was preferable
when the substituent on the aryl halide is an electron-withdrawing group (EWG). More recently,
however, we found that the use of an iron anode instead of zinc was also quite convenient in the
coupling of aryl halides with 2-chloropyrimidine.4 Therefore, we revisited our previous results for
Eq. (1). Results for some model reactions are shown in Table 1. We can see that the yields of the
coupling product are increased by about 15% when iron is used instead of zinc as the anode.
Table 1
Comparison of the use of iron or zinc anode in the nickel±bpy
catalyzed electrochemical arylation of 2-halopyridine by EWG-
substituted aryl halides
On the basis of these improvements we investigated the electrochemical coupling between
substituted 2-halopyridine and substituted aryl halides using an iron anode and NiBr2bpy as
catalyst according to Eq. (2). Results are reported in Table 2.
ꢀ2†
The presence of an electron-donating substituent on 2-chloro- or 2-bromo-pyridine does not
signi®cantly change their reactivity. So, in this case, and whether the functional group on the aryl
bromide is electron-donating or electron-withdrawing, chloro- or bromo-pyridine can be used,
and the cross-coupling product is obtained in good yield. We have already observed that 2-chloro-
pyridines substituted by an electron-withdrawing group are more reactive toward electro-
generated zero-valent nickel than 2-chloropyridine.5 Therefore, the coupling of EGW-substituted

5041
Table 2
Ni-catalyzed electrochemical cross-coupling between substituted 2-halopyridine and substituted aryl halides
2-chloropyridines with aryl bromides occurs only when the aryl ring is substituted by electron-
withdrawing group. In the case of an electron-donating group on the aromatic ring, the use of the
corresponding iodo compound is required. This is in keeping with the postulated mechanism,
where the aryl halide should react faster than the pyridyl halide with the Ni(0) to lead selectively
to the cross-coupling product.3 A reverse order of reactivity leads mostly to the formation of
the bipyridine. In similar reaction conditions, the cross-coupling occurred in good yield between
3-bromothiophene and ethyl 2-chloronicotinate. All these reactions were conducted with an iron
rod as the consumable anode. We could con®rm in several cases the advantage of using this metal.
For example, the yield of D was 73 and 55% with, respectively, iron and zinc as the anode material.

5042
The coupling procedure is as follows: The reactions were performed under an inert atmosphere
of argon at 60ꢁC, in commercial DMF without puri®cation. The ionic conductivity is ensured by
NBu4BF4 (0.01 M), as the supporting electrolyte. In a typical experiment, 50 ml of DMF, 7.5
mmol ArX (0.15 M), 1 mmol NiBr2Bpy (0.02M) and 7.5 mmol halo pyridine (0.15 M) were
introduced in the cell. The electrolysis was conducted at constant current intensity of 0.2 A in an
undivided cell (0.01 A/cm2) using an iron sacri®cial anode and a nickel foam cathode. The reaction
was stopped after consumption of 2.2 F per mol ArX corresponding to complete consumption of
the starting reagents. The cathodic potential during the electrolysis was constant between ^1.2 V
and ^1.3 V/SCE.
In conclusion, we have shown that the use of a consumable iron anode combined with chemical
catalysis by NiBr2bpy is very ecient to perform, in one step, the cross-coupling between sub-
stituted 2-halopyridine and substituted aryl halides.
References
1. Negishi, E.-I.; Suzuki, A.; Mitchell, T. N.; Knochel, P.; Hiyama, T. In Metal-Catalyzed Cross-Coupling Reactions;
Diedederich, F.; Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998, chapters 1, 2, 4, 9 and 10, pp. 1, 49, 167, 387,
421.
2. Browne, L. J.; Gude, C.; Rodriguez, H.; Steele, R. E.; Bhatnager, A. J. Med. Chem. 1991, 34, 725±736.
3. Gosmini, C.; Lasry, S.; Nedelec, J. Y.; Perichon, J. Tetrahedron 1998, 54, 1289±1298.
4. Gosmini, C.; Nedelec, J. Y.; Perichon, J. Tetrahedron Lett. 2000, 41, 201±203.
5. Unpublished results.