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LETTER
our hands the catalyst could be conveniently stored under
nitrogen in an air tight container and furthermore we
found it unnecessary to pre-soak the catalyst with solvent,
as is required for polystyrene-based supports, therefore
providing a solvent-free environment.
Acknowledgment
The helpful advice from Dr Neil Williams and the assistance of J.M.
in the project are gratefully acknowledged.
References
(1) Kirschnig, A.; Monenschein, H.; Wittenberg, R. Angew.
Chem. Int. Ed. 2001, 40, 650.
(2) Clapham, B.; Reger, T. S.; Janda, K. D. Tetrahedron 2001,
57, 4637.
(3) Uozumi, Y.; Nakai, Y. Org. Lett. 2002, 4, 2997.
(4) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(5) Gonthier, E.; Breinbauer, R. Synlett 2003, 1049.
(6) (a) Sonogashira, K. J. Organomet. Chem. 2002, 653, 46.
(b) Rossi, R.; Carpita, A.; Bellina, F. Org. Prep. Proced. Int.
1995, 129.
(7) Neckars, D. C. J. Chem. Educ. 1975, 52, 695.
(8) Lin, C.-A.; Luo, F.-T. Tetrahedron Lett. 2003, 44, 7565.
(9) Brase, S.; Gil, C.; Knepper, K. Bioorg. Med. Chem. 2002,
10, 2415.
Scheme 2
(10) Siemsen, P.; Livingstone, R. C.; Diederich, F. Angew. Chem.
Int. Ed. 2000, 39, 2632.
(11) Aldrich reference 36, 425-8.
(12) Angeletti, A.; Canepa, C.; Martinetti, G.; Venturello, P. J.
Chem. Soc., Perkin Trans. 1 1989, 105.
(13) Matrex Silica 60 (37-70 mesh).
The coupling reaction between terminal alkynes and a
number of aryl iodides were readily accomplished on a 1
mmol scale using 1 mol% of the tethered catalyst 3
(Scheme 2). These reaction conditions provided highly
reproducible yields in short reaction times.22 A reduction
in the quantity of catalyst used, to 0.5 mol% resulted in
longer reaction times from 10 minutes (78% conversion)
to 50 minutes (90% conversion).
(14) Clark, J. H. Chemistry of Waste Minimisation; Chapman and
Hall: Glasgow, 1995.
(15) Price, P. M.; Clark, J. H.; Macquarrie, D. J. J. Chem. Soc.,
Dalton Trans. 2000, 101.
(16) Clark, J. H.; Macquarrie, D. J. Chem. Commun. 1998, 853.
(17) (a) Hallmann, K.; Macedo, E.; Nordstrom, K.; Moberg, C.
Tetrahedron: Asymmetry 1999, 10, 4037. (b) Zhang, T. Y.;
Allen, M. J. Tetrahedron Lett. 1999, 40, 5813. (c) Terrett,
N. K. Comb. Chem. Online 2003, 5, 43.
(18) Djakovitch, L.; Rollet, P. Tetrahedron Lett. 2004, 45, 1367.
(19) These studies were conducted on a Mettler TG50
Thermogravimetric Analyser. The decomposition weight
loss was measured over the range 200–650 °C at a
temperature rate increase of 20.0 °C min–1.
As a footnote to this project23 we found that after filtration
and washing with toluene the catalyst could be recycled in
a further coupling reaction. However, we observed a re-
duction in the yield of the coupled product and an increase
in the reaction time.
In summary, these preliminary studies have focused upon
Sonogashira coupling reactions between a number of aryl
iodides and alkynes using a novel silica-supported palla-
dium catalyst. As well as the observed stability of the sup-
ported catalyst over several months, under an inert
atmosphere, we found that our procedure offers signifi-
cant advantages over applications involving other sup-
ported catalysts. These include readily reproducible, rapid
and high yielding reactions. The absence of copper, as a
co-catalyst, is of considerable importance for industrial
preparation of drug-like molecules where copper contam-
inants require additional purification processes. The role
of piperidine as both a base and a solvent in reduced quan-
tities, compared to other reported copper-free reaction
conditions, confirms the environmentally friendly nature
of this series of reactions. Unlike polystyrene-based sup-
ports there is no need to pre-swell the catalyst in a solvent,
which essentially removes the requirement for any addi-
tional solvent to be employed during the coupling reaction
itself. The efficiency of this procedure coupled with the
environmentally ‘friendly’ reaction conditions employed
provides an alternative methodology to the more tradi-
tional coupling techniques.
(20) Leadbetter, N. E.; Tominack, B. J. Tetrahedron Lett. 2003,
44, 8653.
(21) Representative Experimental Procedure: the Synthesis
of Diphenylacetylene.
To a small dry glass tube/flask charged with a magnetic
stirrer bar, iodobenzene (0.204 g, 1.0 mmol) and phenyl-
acetylene (0.102 g, 1.0 mmol) was added piperidine (0.256
g, 3.0 mmol) and catalyst 3 (0.015 g). The reaction vessel
was sealed with a septum and heated to a temperature of
70 °C on an oil bath with constant stirring. After about 10
min the contents were cooled and decanted into a separating
funnel. The residual supported catalyst was washed with
Et2O (3 × 10 cm3) and the washings added to the separating
funnel. Then, H2O (20 mL) was added to the separating
funnel and the organic layer was separated neutralised, by
washing with dilute HCl (15% v/v), washed with H2O
(2 × 15 mL), dried over anhyd MgSO4 and the organic
solvent removed, in vacuo, to afford the crude product
(0.1602 g, 90%). This was characterised by GC-MS which
confirmed that the yield of diphenylacetylene (85%), IR and
NMR spectroscopy using an authentic sample for reference
purposes.
(22) The yields of coupled products obtained from reactions
involving supported palladium catalysts are often superior to
those obtained from the corresponding homogeneous
reaction.
At the present time we are attempting to develop the scope
and extent of this chemistry in other related areas.
(23) This work was carried out by A. Al-Saardi as part of an
MChem undergraduate final year project at Kingston
University.
Synlett 2005, No. 3, 487–488 © Thieme Stuttgart · New York