4740
L. Joucla et al. / Tetrahedron Letters 49 (2008) 4738–4741
I
Pd/C (2 mol%), AcONa.3H2O (3,0 éq.)
BF3K
+
Solvent, 100°C, 24 h
Br
Br
NMP GC-Yield: 68%
NMP/H2O (1/1) GC-Yield: 81%
Scheme 3. Selective heterogeneously Pd-catalysed vinylation of 4-bromoiodobenzene.
Unexpectedly when referring to previous reports,19,20 we
observed that the free o-iodophenol (Table 2, entry 3) showed
higher reactivity than the corresponding alkylated compound
(Table 2, entry 4). Therefore, this result opens the route to green
processes (i.e., atom economy procedure) for the synthesis of vinyl-
phenol derivatives as it avoids the protective steps.
As predictable, aryl iodides bearing electron withdrawing group
at para position show enhanced reactivity as complete conversion
was achieved even at 80 °C (Table 2, entry 5).
Similarly, several aryl bromides were studied. Under such reac-
tion conditions (Pd/C 2 mol %, AcONaÁ3H2O, NMP) moderate to
good conversions were achieved (Table 2, entries 7–12). Notice-
ably, the 3- and 4-bromonitrobenzene derivatives gave high con-
versions within 24 h (Table 2, entries 8 and 9), whereas lower
reactivity was observed for the ortho derivative (Table 2, entry 7)
that was attributed to steric hindrance. Aryl bromides bearing
weakly electron withdrawing groups such as a nitrile (Table 2,
entry 10) or a ketone (Table 2, entry 11) at para position gave,
unexpectedly, low conversions (i.e., ꢀ45%). Similarly, electron
donating group at para position gave poor conversions even at
140 °C (Table 2, entries 12–14). In those cases dehalogenation
was observed in relatively high rate (6–19%).
100
80
60
40
20
0
Standard run
Hot-filtration run
Hot filtration at ca. 40% conversion
0
50
100
150
200
Time (min)
Figure 1. Leaching of active Pd-species in solution using the Pd:C catalyst. Residual
catalytic activity after hot filtration at ca. 40% conversion versus standard
catalytic run
.
tration method: a catalytic run was started as for a standard
reaction, and at ca. 40% conversion, the reaction mixture was fil-
tered through a warmed Celite pad to afford a clear filtrate. The
clear filtrate was then treated as the usual catalytic test, and its
composition was followed by GC and compared to that of a stan-
dard catalytic run. Figure 1 shows clearly that the catalytic activity
observed is mainly due to dissolved active Pd-species since after
removal of the heterogeneous catalyst by hot filtration the conver-
sion raised from 40% to 70% over 3 h.25
The role played by the solvent is not clear. While for the aryl
bromides the use of NMP/H2O (1/1) instead of NMP as solvent
has no or negative influence on the reaction rate (Table 2, entries
7, 10, 13), it improves noticeably the conversion of 4-iodoanisole
(58% and 95% conversion, respectively, Table 2, entry 6).
Accounting the lower reactivity of aryl bromides versus iodides,
we investigated the iodo/bromo selectivity starting from 4-bro-
moiodobenzene. As expected
a
full selectivity towards the
In conclusion, we reported for the first time an efficient
heterogeneously palladium catalysed vinylation of aryl iodides
and bromides. Using common reaction conditions (Pd/C 2 mol %,
AcONaÁ3H2O, NMP or NMP/H2O), the vinylation gave good to full
conversions with high selectivities towards the expected
vinylaromatic.
From an environmental point of view, the most interesting out-
come came from the full iodo/bromo selectivity leading to direct
and selective formation of bromovinyl compounds and the applica-
bility to OH-free phenols avoiding protection/deprotection steps
for the synthesis of vinylphenol derivatives.
Some results suggest that the reaction rate depends not only on
electronic factors but also on steric hindrance. Chelating effects of
palladium centre by ortho substitutents after oxidative addition
accounting for some of the reactivities observed could not be
discarded (e.g., Table 2, entries 2–4 and 7).
corresponding 4-bromovinylbenzene was achieved at 100 °C
(Scheme 3). The reaction gave 68% GC-yield when carried out in
NMP and 81% GC-yield in NMP/H2O (1/1) leading in that case to
58% isolated yield due to its high volatility. Such syntheses of
halovinylderivatives were to date only possible using the proce-
dure reported by Genêt and co-workers16,17 as aryliodides and
arylbromides react equally under the procedure reported by
Molander and co-workers.19,20
When using heterogeneous palladium catalysts, the questions
regarding the reuse and the leaching of active Pd-species in solu-
tion should be addressed. The recycling was examined for the cou-
pling reaction of 4-bromonitrobenzene under optimised reaction
conditions (Pd/C 2 mol %, AcONaÁ3H2O, NMP) over 16 h. The fol-
lowing procedure was performed: after the first run of the catalyst,
the reaction mixture was allowed to cool to room temperature and
the catalyst was separated by centrifugation, washed with NMP/
H2O (1:1), twice with NMP and allowed to dry at room tempera-
ture for 24 h. The recycled palladium catalyst was then used with-
out any regeneration under the same reaction conditions as the
fresh catalyst. The procedure was repeated up to 5 runs without
any loss of activity.
Current investigations are in progress to optimise further the
heterogeneous catalytic systems for lower reactive aryl bromides.
Acknowledgements
GC thanks the ‘Ministère de l’Education Nationale, de l’Enseign-
ement Supérieur et de la Recherche’ for a grant and LJ thanks
the CNRS for a grant. We gratefully acknowledge the ‘Programme
Leaching was examined for the coupling reaction of 4-bromoni-
trobenzene under optimised reaction conditions using the hot-fil-