D. Villemin, F. Caillot / Tetrahedron Letters 42 (2001) 639–642
641
References
with an organometallic reagent in slight excess, in order
to reduce the palladium(II) into palladium(0). In the
case of Heck and Trost reactions (Table 3), a stable
complex of palladium (0), [Pd2(dba)3] was used. In the
Suzuki reaction and all solventless palladium-catalysed
reactions described, the most important factor, in order
to obtain a good yield, is to have a good dispersion of
palladium complex A on KF-Al2O3. This dispersion
was obtained by grinding the palladium catalyst with
KF-Al2O3 before the reaction. In all palladium-
catalysed reactions performed without solvent under
microwave, we were unable to create reproducible
results using a domestic microwave oven. This result
was probably due to several factors: the small dimen-
sion of the sample irradiated (1–3 g of support), the
poor control of the power and the irregular distribution
of microwave irradiation. To eliminate these factors a
mono-mode microwave with accurate emission control
was used which gave reproducible results. We have
used a mono-mode Prolabo Synthewave 402 cavity.8
1. Heck, R. F. Palladium Reagents in Organic Synthesis,
Academic Press, 1995. Tsuji, J. Palladium Reagents and
Catalysts: Innovations in Organic Synthesis, Wiley, 1995.
Cornils, B.; Hermann, W. A. Applied Homogeneous
Catalysis with Organometallic Compounds V.C.H. 1996.
Malleron, J. L.; Fiaud, J.-C.; Legros, J.-Y. Handbook of
Palladium-Catalysed Reactions, Academic Press, 1997.
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Chem. Commun. 1989, 386–387. Bram, G.; Loupy, A.,
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cited.
4. Larhed, M.; Hoshino, M.; Hadida, S.; Curran, D. P.;
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Larhed, M.; Hallberg, A. J. Org. Chem. 1996, 61, 9582–
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603, 2–5.
The Stille reaction, the reactions of Heck (Table 3, N°
9–10) and the Trost–Tsuji reaction (Table 3, N° 11–14)
were carried out and produced good yields under simi-
lar conditions.
The main advantage of this new methodology in the
case of Stille reaction, is that the organotin residue
remains adsorbed on the solid support (probably as
fluorotin polymer). An elution with acetonitrile pro-
duced pure Stille reaction product, so the classical
purification of the product (generally treatment with a
fluoride) before biological tests is not necessary in this
case.
5. For a recent review on reactions under microwave irra-
diation without solvent: Varma, R. S. Green Chem.
1999, 43–55.
6. Bumagin, N. A.; Bykov, V. V. Tetrahedron 1997, 53,
14437–14450.
7. Although the reaction of Heck was described with a
little quantity of triethylamine7 as solvent under
microwave: DiazOrtiz, A.; Prieto, P.; Vazquez, E. Syn-
lett 1997, 269–270. Copper-palladium catalysed
Sonogoshira reaction in solventlesss conditions was also
recently described: Kabalka, G. W.; Wong, L.; Nam-
boodiri, V.; Pagni, R. M. Tetrahedron Lett. 2000, 41,
5151–5154.
8. For a recent review under mono-mode microwave irra-
diation, see: Loupy, A.; Petit, A.; Hamelin, J.; Texier-
Boullet, F.; Jacquault, P.; Mathe´, D. Synthesis, 1998,
1213–1234.
The reactions were carried out under an inert atmo-
sphere (argon), however some of them (Suzuki, Stille)
may be carried out in air.9 In all the reactions a slight
decrease of the yield11 has been observed [e.g.: under air
the yields were respectively: N° 1 (95%), N° 2 (90%), N°
7 (50%), N° 12 (93%)]. The analyses of Suzuki, Stille
and Trost–Tsuji reaction products showed that prod-
ucts eluted with poorly polar solvent (toluene) resulted
in products free of metals (boron, tin or palladium).
However, with acetonitrile some traces of palladium are
observed. The comparison of yields with classical heat-
ing using a preheated oil bath has showed that reac-
tions under microwave were faster. However the yields
obtained were comparable only if the classical heating
was prolonged. The increase of speed under microwave
irradiation was attributed to a more direct transfer of
heat.
9. Typical procedure (Suzuki reaction): 0.1 mmol Pd(OAc)2
and 1 mmol of ArB(OH)2 were mixed with a grinder
(IKA A-10) with 1 g of KF-Al2O3 (prepared according
to Ref. 10). Subsequently the mixture was placed in a
pressure tube under argon and then 1 mmol of the ArI
was added. The tube was irradiated with a Prolabo
Synthewave 402. After the reaction was completed, the
solid was extracted with toluene or acetonitrile and the
solvent was evaporated in a vacuum. The residue was
purified by flash chromatography on silica.
In summary, we have demonstrated that it is possible to
use KF-Al2O3 as a base without solvent under mono-
mode microwave irradiation in classical palladium-
catalysed reactions. The simplicity of experimental
conditions, the resistance shown towards oxidation in
the open atmosphere, the favourable safety aspects, the
significant yields, rapid reaction times make this an
ideal procedure for the preparation of small amounts of
products.