Cobalt-catalyzed electrochemical cross-coupling of functionalized phenyl halides with 4-chloroquinoline derivatives

Article abstract of DOI:10.1016/S0040-4039(00)01936-5

A novel electrochemical procedure allowing the synthesis of various 4-phenylquinoline derivatives in satisfactory to high yields is described. This method relies on a cobalt-catalyzed cross-coupling reaction of functionalized phenyl halides with 4-chloroquinoline derivatives and is conducted in a one-compartment cell using the sacrificial anode process.

Full text of DOI:10.1016/S0040-4039(00)01936-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 267–269
Cobalt-catalyzed electrochemical cross-coupling of functionalized
phenyl halides with 4-chloroquinoline derivatives
Erwan Le Gall, Corinne Gosmini,* Jean-Yves Ne´de´lec and Jacques Pe´richon
Laboratoire d’Electrochimie, Catalyse et Synthe`se Organique, LECSO, CNRS, UMR 7582, 2–8 rue Henri Dunant,
94320 Thiais, France
Received 3 October 2000; accepted 30 October 2000
Abstract—A novel electrochemical procedure allowing the synthesis of various 4-phenylquinoline derivatives in satisfactory to
high yields is described. This method relies on a cobalt-catalyzed cross-coupling reaction of functionalized phenyl halides with
4-chloroquinoline derivatives and is conducted in a one-compartment cell using the sacrificial anode process. © 2000 Elsevier
Science Ltd. All rights reserved.
Formation of CꢀC bonds has long been recognized as
one of the most challenging features in organic chem-
istry. In the field of biaryl synthesis, numerous works
were directed towards cross-coupling reactions between
‘activated’ aromatic compounds, which could be for
instance aryl halides. Among several catalytic
processes1 which have been developed during the last
decades, the Suzuki reaction2 involving arylboronic
acids and aryl halides has widely been employed.3,4
applied to the synthesis of rarely-described 4-phenyl-
quinoline derivatives.
Considering several works devoted to the catalytic acti-
vation of aromatic halides by electroreduced cobalt
chloride, in progress in this laboratory,7 we undertook
to scan other possibilities provided by this catalyst and
decided to focus our attention on the synthesis of these
4-phenylquinoline derivatives. Thus, we wish to de-
scribe herein a new powerful tool for this purpose,
consisting of the cobalt chloride-catalyzed electrochemi-
cal cross-coupling reactions of phenyl halides and 4-
chloroquinoline derivatives.
In a previous paper, we reported the efficient nickel-cat-
alyzed electrochemical cross-coupling of 2-chloropyridi-
nes with aryl halides.5 Only slight modifications of this
procedure allowed the efficient synthesis of 2-
phenylpyrimidines and pyrazines,6 e.g. it was shown
that the nature of the anode played a major role and
that the presence of FeBr2 at the beginning of the
electrolysis was necessary for the cross-coupling reac-
tion to occur. However, the scope of these reactions
was minimized insofar as these procedures could not be
First, we tried to define standard conditions for all
electrolyses. A typical electrolysis medium was found to
be a mixture of acetonitrile, dimethylformamide and
pyridine in the presence of a catalytic amount of cobalt
chloride. The presence of pyridine proved to be essen-
tial for the coupling reaction to occur providing the
Scheme 1.
* Corresponding author. Fax: (33) 1 49 78 11 48; e-mail: gosmini@glvt-cnrs.fr
0040-4039/01/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01936-5

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E. Le Gall et al. / Tetrahedron Letters 42 (2001) 267–269
experimental evidence that DMF and MeCN were un-
able to stabilize electroreduced cobalt. Several attempts
towards cross-coupling reactions between phenyl
halides and 4-chloroquinoline derivatives were realized
according to general conditions given in Scheme 1.
dimethylformamide (5 ml) and pyridine (5 ml) were
added using a syringe. To the solution were added
anhydrous cobalt chloride (2.6 mmol, 0.26 equiv.) and
tetrabutylammonium tetrafluoroborate (0.2 g) in order
to raise the conductivity of the electrolysis medium. The
4-chloroquinoline derivative (10 mmol, 1 equiv.) and
the functionalized halogenobenzene (10–20 mmol, 1–2
equiv.) were added and a constant current intensity of
0.2 A was applied until complete disappearance of the
Typical procedure: The electrochemical cell,8 fitted with
an iron rod as the anode and a stainless steel grid as the
cathode, was flushed with argon. Acetonitrile (40 ml),
Table 1. Cobalt-catalyzed cross-coupling of phenyl halides with 4-chloroquinoline derivatives

E. Le Gall et al. / Tetrahedron Letters 42 (2001) 267–269
269
Acknowledgements
starting 4-chloroamine had occurred (range 2000–4000
C). The mixture was then poured into 50 ml of a
saturated ammonium chloride solution. After evapora-
tion of acetonitrile under reduced pressure, sodium
chloride was added to the aqueous layer, which was
extracted with 3×100 ml diethyl ether. The organic
layer was dried over magnesium sulfate and evaporated
to dryness. The resulting oil was purified using silica gel
chromatography with diethyl ether and pentane as the
eluent to afford the analytically-pure 4-phenylquinoline
derivative in 48–81% yield.9
The authors thank Aventis for financial support.
References
1. Stanforth, S. P. Tetrahedron 1997, 54, 263–303.
2. Miayaura, N.; Yamagi, T.; Suzuki, A. Synth. Commun.
1981, 11, 513–519.
3. Ali, N. M.; McKillop, A.; Mitchell, M. B.; Rebelo, R. A.;
Wallbank, P. J. Tetrahedron 1992, 48, 8117–8126.
4. Lohse, O.; Thevenin, P.; Waldvogel, E. Synlett 1999, 45–
48.
It should be pointed out that the choice of an iron rod
as the anode was of crucial importance for the effi-
ciency of the electrochemical process. Indeed, the use of
metallic rods other than an iron rod as the anode
invariably led to failure. This observation clearly indi-
cates that ferrous salts that are released during the
electrolysis participate in the catalytic process. Never-
theless, it should be mentioned that in that case and
contrary to the coupling of chloropyrimidines with aryl
halides,6 preelectrolyses furnishing FeBr2 at the begin-
ning of the electrolyses were not realized. The results
are listed in Table 1.
5. Gosmini, C.; Lasry, S.; Ne´de´lec, J. Y.; Pe´richon, J. Tetra-
hedron 1998, 54, 1289–1298.
6. Gosmini, C.; Ne´de´lec, J. Y.; Pe´richon, J. Tetrahedron Lett.
2000, 41, 201–203.
7. (a) Patent Application 99/08480, France, July 1, 1999. (b)
Gosmini, C.; Rollin, Y.; Ne´de´lec, J. Y.; Pe´richon, J. J.
Org. Chem. 2000, 65, 6024–6026.
8. Troupel, M.; Rollin, Y.; Sock, O.; Meyer, G.; Pe´richon, J.
Nouv. J. Chim. 1986, 11, 593–599.
9. Physical data for selected compounds. 4-(2-Methylquino-
4-yl)benzoic acid ethyl ester 1a: 1H NMR (CDCl3, 200
MHz) l (ppm): 1.37 (t, J=7 Hz, 3H), 2.72 (s, 3H), 4.37
(q, J=7 Hz, 2H), 7.16 (s, 1H), 7.20–7.70 (m, 5H), 8.03 (d,
J=8.5 Hz, 1H), 8.13 (d, J=8 Hz, 2H). 13C NMR(CDCl3,
50 MHz) l (ppm): 14.33, 25.30, 61.11, 121.98, 124.56,
125.15, 125.96, 129.14, 129.48, 129.68, 130.37, 142.57,
147.29, 148.33, 158.40, 166.10. MS, m/z (relative intensity):
291 (M, 100), 263 (M−28, 32), 246 (M−45, 45), 218
(M−73, 31). Analysis calcd for C19H17NO2: C, 78.35; H,
5.84; N, 4.81; O, 10.99. Found: C, 78.41; H, 5.91; N, 4.89;
O, 10.90. 4-(4-Methoxyphenyl)quinaldine 1c: 1H NMR
(CDCl3, 200 MHz) l (ppm): 2.69 (s, 3H), 3.81 (s, 3H), 6.97
(d, J=9 Hz, 2H), 7.13 (s, 1H), 7.28–7.40 (m, 3H), 7.60 (t,
J=7.5 Hz, 1H), 7.82 (d, J=8 Hz, 1H), 8.00 (d, J=8 Hz,
1H). 13C NMR (CDCl3, 50 MHz) l (ppm): 25.34, 55.29,
114.00, 122.12, 125.24, 125.61, 125.67, 129.06, 129.19,
130.36, 130.73, 148.16, 148.52, 158.44, 159.80. MS, m/z
(relative intensity): 249 (M, 100), 234 (M−15, 20), 206
(M−43, 12). Analysis calcd for C17H15NO: C, 81.92; H,
6.02; N, 5.62; O, 6.43. Found: C, 81.39; H, 5.98; N, 5.67;
O, 6.47.
It is worth noting that both electron donating and
withdrawing groups (entries 1–4) allow coupling prod-
ucts to be obtained in satisfactory yields. These results
can be slightly improved by using iodinated rather than
brominated benzenes when an electron donating group
is connected to the phenyl moiety (entries 5 and 6) but,
in this case, increased amounts of the starting com-
pound have to be used and lead to the rise of biaryl
formation. This method can be extended to other aro-
matic amines than quinaldine. Indeed, 4-chloroquino-
line (entry 7) and 4-chloro-2-phenylquinoline (entry 8)
react in the same fashion providing the desired cross-
coupling products in 48 and 65% yields, respectively.
In conclusion, we reported in this paper the efficient
and versatile synthesis of rarely described 4-
phenylquinoline derivatives. These compounds are ob-
tained in satisfactory to high yields starting from
commercially available compounds and using a particu-
larly simple electrochemical procedure.
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