TETRAHEDRON
LETTERS
Tetrahedron Letters 43 (2002) 9365–9368 Pergamon
A copper- and amine-free Sonogashira-type coupling procedure
catalyzed by oxime palladacycles
Diego A. Alonso, Carmen Na ´jera* and M
a
Carmen Pacheco
Departamento de Quı ´mica Orga ´nica, Facultad de Ciencias, Universidad de Alicante, Apdo. 99, 03080 Alicante, Spain
Received 24 September 2002; revised 14 October 2002; accepted 16 October 2002
Abstract—Oxime palladacycle derived from 4,4-dichlorobenzophenone was found to promote the Sonogashira reaction of aryl
iodides and aryl bromides with terminal acetylenes using 1 equivalent of tetrabutylammonium acetate in organic solvents generally
in 1 h at 110°C and in high TONs (up to 72000). © 2002 Elsevier Science Ltd. All rights reserved.
Cross-coupling reactions of acetylenes with aryl or
alkenyl halides or triflates in the presence of a palla-
dium salt or complex, copper iodide and an amine, are
extensively used in organic chemistry and materials
science for the preparation of internal alkynes and
enynes.
1
Thus, the Sonogashira reaction is used in
numerous syntheses of natural products, for instance,
enediyne antibiotics,
2
as well as in the preparation of
liquid crystals, conducting polymers and other engi-
neering materials.
3
In order to simplify the Sonogashira
reaction protocol, several important aspects have to be
improved. First, to eliminate the use of copper(I) iodide
as co-catalyst, because it induces homocoupling reac-
tions (Glaser-type reactions) of terminal alkynes to
diynes in the presence of oxygen.
4
Second to also avoid,
is the use of the amine. Its presence, either as solvent or
in stoichiometric amounts for the elimination of the
HX formed in the reaction, seems vital but largely
depends on the type of substrates to be coupled. Fur-
thermore, and from an economical point of view, to
employ lower catalyst loadings, which is a very impor-
tant feature because of the high loadings (1–5 mol%)
usually required when typical catalysts such as
Pd(PPh
3
)
2
Cl
2
, Pd(PPh
3
)
4
or Pd
2
(dba)
3
are employed.
Another facet to improve is the ability to perform this
reaction in air using reagent-grade chemicals and
solvents.
Copper-free methodologies have recently been
described employing amines as solvents as in the case of
palladium(0) complexes such as Pd(PPh
3
)
4
in piperidine
or pyrrolidine.
5
The only example using a palladacycle
6
in a copper-free protocol, is Herrmanns phospha-pal-
ladacycle which is performed in triethylamine and only
worked with phenylacetylene as sp counterpart.
7
On the
other hand, the catalytic system Pd
2
(dba)
3
8
promotes
the copper-free Sonogashira reaction of aryl bromides
at room temperature,
9
but the air-unstable tris-tert -
butylphosphane has to be used as co-catalyst. Stoichio-
metric amounts of silver(I) oxide for aryl iodides, and
tetrabutylammonium fluoride (TBAF) or tetra-
butylammonium hydroxide (TBAOH)
10
for aryl bro-
mides, have been used as activators in the first
described copper- and amine-free procedure.
11
Very
recently, phenylacetylene has been coupled with aryl
chlorides under harsh conditions in the presence of
ZnCl
2
as additive and Cs
2
CO
3
as base, employing 5
mol% of the phosphinito palladium pincer complex
PdCl[C
6
H
3
(OPPr
i
2
)
2
-2,6].
12
Scheme 1.
Keywords : alkynes; coupling reactions; palladium catalysis.
* Corresponding author. Fax: +34-96-5903549; e-mail: cnajera@ua.es
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII:S0040-4039(02)02335-3