Palladium-catalysed phenylation of heteroaromatics in water or methylformamide under microwave irradiation

Article abstract of DOI:10.1016/S0040-4039(00)02026-8

Rapid and efficient palladium-catalysed phenylation of heteroaromatic halides take place under focused microwave irradiation in water of monomethylformamide.

Full text of DOI:10.1016/S0040-4039(00)02026-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 635–637
Palladium-catalysed phenylation of heteroaromatics in water or
methylformamide under microwave irradiation
Didier Villemin,a,* Mar´ıa Jose´ Go´mez-Escalonillab and Jean-Francois Saint-Claira
aEcole Nationale Supe´rieure d’Inge´nieurs de Caen, ISMRA, Equipe associe´e au CNRS, Universite´ de Caen,
F-14050 Caen, France
bFac. de Ciencias, Universidad de Castilla-La Mancha, 45071 Toledo, Spain
Received 20 September 2000; accepted 10 November 2000
Abstract—Rapid and efficient palladium-catalysed phenylation of heteroaromatic halides takes place under focused microwave
irradiation in water or monomethylformamide. © 2001 Elsevier Science Ltd. All rights reserved.
The Suzuki reaction1 is widely used in the synthesis of
mamide (DMF, m=36.7) or dimethylacetamide
(DMAC, m=37.8). Thus, the coupling of microwave
natural heterocyclic compounds such as alkaloids.2 Lig-
andless palladium-catalysed Suzuki reaction on phenyl
halides in aqueous media was described by Bumagin et
al.3 Recently, it was published4 that microwave irradia-
tion allows the activation of homogenous palladium-
catalysed reaction, showing that the rate of the reaction
is accelerated affording faster and cleaner chemical
conversions.
and MMF is very strong and high temperatures can be
obtained very quickly.
Because of this, we decided to carry out the Suzuki
coupling reaction between different heterocycles and
sodium tetraphenylborate in water or MMF as solvent
under focused microwave irradiation.
It is well known that water or polar solvents are
particularly interesting to dissolve polar molecules, such
as heterocycles. This kind of solvent absorbs
microwaves very efficiently,5 so we decided to explore
the possibility for the Suzuki reaction of an heterocyclic
halide in water or polar solvents under focused
microwave irradiation.
All reactions were performed in a Teflon closed vessel
(Ace pressure tube) under an argon atmosphere. We
have used for the irradiation a resonance cavity Micro-
Energie-Syste`me (MES) at 2450 MHz as described.9
The reactions also take place with the easy and com-
mercially available Prolabo Synthewave 402.
The products obtained were identified by 1H, 13C
NMR, mass spectroscopy by comparison with spectral
data in the literature. The results obtained with differ-
ent heterocyclic halides are presented in Table 1. Some
products were previously obtained from halides by
organometallic reactions catalysed by transition
metals.10–13 Comparison with literature is not easy
In this communication, we have used stable and com-
mercially available sodium tetraphenylborate6 as
phenylation reagent of heteroaromatic halides with a
phosphine free-palladium catalyst according to the con-
ditions of Bumagin described for aromatic halides3
(Scheme 1).
We have used water and monomethylformamide
(MMF) as solvents. To our knowledge, MMF has not
been used previously in a Suzuki coupling. MMF has a
high boiling point (183°C) and is more polar (m=182.5)
than water (m=78.5) and other amides used in
microwave activated reactions7 such as dimethylfor-
* Corresponding author. Fax: (33) 231 45 28 77; e-mail: didier.
villemin@ismra.fr
Scheme 1.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)02026-8

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D. Villemin et al. / Tetrahedron Letters 42 (2001) 635–637
Table 1. Phenylation catalysed by palladium under mono-mode microwave irradiation8 HetArX/(C6H5)BNa/Pd(OAc)/
Na2CO3=100/27/175/1
because of the variety of organometallics used. In an
experiment (no. 2) we obtained a final temperature of
105°C in water and 195°C in MMF. The reaction
performed for 12 min in a preaheated oil bath (105°C
for H2O and 195°C for MMF) gave, respectively, yields
of 42 and 53%. In general, under microwave irradiation
better yields were obtained in MMF, perhaps because
the temperature gradient and the ionisation of solvent
are higher. According to the stoichiometry and the
yields, it would appear that the four phenyl groups of
the sodium tetraphenylboronate are available for
phenylation.
References
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In conclusion, commercially available and non-toxic
sodium tetraphenylborate can be used in water or
monomethylformamide for a rapid and efficient phenyl-
ation of heteroaromatic halide under mono-mode
microwave irradiation.
Acknowledgements
We are grateful to a grant (J.C.C.M.) funding a stu-
dentship to M. J. Go´mez.

D. Villemin et al. / Tetrahedron Letters 42 (2001) 635–637
637
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