COMMUNICATION
One single catalyst, Pd(OAc)2, for two sequential very different steps:
allylic alcohol oxidation–Heck reaction. Access to functionalised
a,b-unsaturated ketonesw
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b
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Frederic Batt, Christel Gozzi* and Fabienne Fache*
Received (in Cambridge, UK) 20th June 2008, Accepted 19th August 2008
First published as an Advance Article on the web 30th September 2008
DOI: 10.1039/b810538c
A single addition of the catalyst, Pd(OAc)2, was realised to
mediate two transformations as different as allylic alcohol
oxidation under O2 and C–C bond formation of the Heck type,
to give substituted a,b-unsaturated ketones without intermediate
purification.
Fig. 1 Sequential allylic alcohol oxidation–Heck reaction.
According to current synthetic requirements, effective and
environmentally benign procedures are particularly welcome.
Among them, tandem or sequential reactions are especially
interesting because they limit the amount of solvent used by
reducing the number of costly workups as well as purification
procedures and are less time-consuming.1 In numerous cases, a
transition metal catalyst presents in the reaction mixture, is
efficient in one of the consecutive steps, but acts as a spectator
in the other steps.2 Much more interesting are transition metal
catalysed syntheses which rely on a single catalyst for several
steps.3 This has been reported for tandem reactions as different
as cross metathesis–intramolecular hydroarylation with Ru,4
deprotection–heterocyclisation with Pd5 or Sonogashira–
heteroannulation with Pd/C.6 With this in mind, we have
developed a strategy for a rapid construction of functionalised
a,b-unsaturated ketones starting from allylic alcohol and
using 3% Pd(OAc)2 added in the first step and able to mediate
two transformations as different as the oxidation of allylic
alcohols and the Heck reaction.
initially used in the oxidation procedure turned out to be a good
solvent. The first step, the oxidation, was thus performed at 70 1C
and was finished after around 4 h. Then, the halogenated
derivative and 1.1 equiv. of Et3N were added and the reaction
mixture was heated for four additional hours. After addition of
water, extraction with diethyl ether and column chromatography
on silica, the product was obtained with good isolated yields
(41–60% for the two consecutive reactions, 64–77% for each
separately). It is noteworthy that the Heck reaction was
performed under air atmosphere.
Different sources of Pd(II) have been tested: with PdCl2 and
PdCl4Na2, 20 h were needed for the overall oxidation of
product 1a instead of 2 h with Pd(OAc)2 but the Heck reaction
with 2a was finished in 6 h, leading to the same products. With
PdCl2(PPh3)2 no oxidation occurred. Pd(OAc)2 was chosen for
the rest of our study.z
In the case of aryl bromide, no reaction occurred even
though triphenylphosphine was added in the second step.
When 25% of nBu4NI was added, only 10% of bromobenzene
was converted into product 3a. When 1equiv. or 2 equiv.
nBu4NI–bromobenzene was added, no reaction occurred.
Several iodoaryl compounds have been tested with success.
Results are displayed in Table 1.y
In the course of our study on green methods for organic
transformations, we published a selective method for the
oxidation of allylic alcohols using oxygen with a catalytic
amount of Pd(OAc)2 and Et3N.7 With these results in hand,
we examined the possibility of performing a second reaction,
catalysed by Pd(OAc)2 but without addition of more
palladium. The Heck reaction seemed to be a good candidate
(Fig. 1).8
In the case of disubstituted aryl iodides, whatever the nature
of the second group (electron donating group, entry 3 or
electron withdrawing group, entry 4) good isolated yields were
obtained. In the case of a diiodo aromatic compound, two
Heck reactions were performed which shows the great reac-
tivity of our palladium, which has thus realised three steps.
The lack of reactivity of bromine derivatives in our conditions
makes it possible to limit the reaction to the carbon bearing an
iodo atom (entry 6) with the possibility of performing other
chemistry on the bromine site. Aniline derivatives were also
used with success, leading to potential precursors of indoles
(entry 7).9 Finally, our conditions are also compatible with
different protecting groups such as silyl (entry 10) or benzyl
(entry 11), leading to polyfunctionalised compounds.
First of all we had to adjust our reaction conditions as the
Heck reaction was usually described in polar solvent.
Dimethylacetamide (DMA) instead of the mixture THF–toluene
a
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Universite de Lyon, Universite Lyon 1, ICBMS, equipe Cheops,
CNRS, UMR 5246, Baˆt. Raulin, 43 Bd du 11 Nov. 1918, 69622
Villeurbanne cedex, France. E-mail: fache@univ-lyon1.fr;
Fax: +33 472448136; Tel: +33 472448521
b Universite´ de Lyon, Laboratoire de Chimie Organome´tallique de
´
Surface (LCOMS), Ecole Superieure de Chimie, Physique,
Electronique de Lyon (CPE Lyon), 43 Bd du 11 Nov. 1918, BP
82077, 69616 Villeurbanne cedex, France. E-mail: gozzi@cpe.fr;
Fax: +33 472431669; Tel: +33 472431826
w Electronic supplementary information (ESI) available: Experimental
details. See DOI: 10.1039/b810538c
In conclusion, we have shown that it is possible to use one
single amount of catalyst to perform in a one-pot sequential
ꢀc
This journal is The Royal Society of Chemistry 2008
5830 | Chem. Commun., 2008, 5830–5832
Batt, Frederic
