932
J . Org. Chem. 2002, 67, 932-934
High ly Ch em oselective Hyd r ogen olysis of Iod oa r en es
Nicolas Faucher, Yves Ambroise, J ean-Christophe Cintrat, Eric Doris, Florence Pillon, and
Bernard Rousseau*
Service des Molecules Marque´es, CEA/ Saclay, 91191 Gif sur Yvette, France
bernard.rousseau@cea.fr
Received October 1, 2001
The catalytic hydrodehalogenation reaction using molecular hydrogen and Pd/C has been revisited.
It is shown that the speed of removal of halogen increases with increasing electronegativity I < Br
< Cl. Nevertheless, selective dehydrohalogenation in compounds containing other reducible functions
can be achieved only with iodine and not with bromine or chlorine. Selective deiodination of
iodobenzophenone could be accomplished without reducing the carbonyl group. Hydrogenolysis of
azidoiodoaromatic compounds to the corresponding azido compounds is high yielding. This selectivity
was exploited for the labeling of benzophenone- and azido-containing compounds by deuterium
and tritium.
In tr od u ction
tive reactions with trans-1-phenyl-1-propene, under the
following conditions: methanol, 10% Pd/C, triethylamine
(10 equiv), H2 (1 atm). We first verified that the stirring
speed was sufficiently high (1400 rpm) to ensure that the
reduction occurred under kinetic conditions. When the
reactions were carried out separately, the reduction of
trans-1-phenyl-1-propene was the fastest (3 min), the
reduction of iodobenzene the slowest (40 min), while
chlorobenzene and bromobenzene were reduced respec-
tively in 6 and 14 min. When iodobenzene and trans-1-
phenyl-1-propene were reacted competitively, the reduc-
tion of trans-1-phenyl-1-propene was delayed and iodo-
benzene reacted first (Figure 1a). The same competitive
reaction was carried out with bromobenzene versus trans-
1-phenyl-1-propene (Figure 1b). In this case, no selectiv-
ity was observed. The olefin reduction and the bromoben-
zene hydrogenolysis took place simultaneously. When
chlorobenzene and trans-1-phenyl-1-propene were re-
acted competitively, the olefin was first and selectively
reduced (Figure 1c).
Selectivity in organic chemistry is a major asset during
the synthesis of complex molecules, and the development
of chemoselective reactions provides a powerful tool for
organic chemists.1 We have recently revisited the cata-
lytic hydrogenolysis of iodoarenes using hydrogen and
Pd/C.2 We have shown that when an iodoaryl compound
and an olefin were separately subjected to reducing
conditions, the double bond was transformed faster. But,
when these two groups were reacted together (whether
borne by the same molecule or not), the selectivity
obtained was unexpected. The less reactive iodoarene was
selectively reduced while the more reactive double bond
was unaffected. We have shown, for the first time, that
the chemoselectivity of this reaction is controlled by the
high affinity of the iodinated compound for the catalyst.
Herein we describe further results in the study of the
hydrodehalogenation reaction, in particular concerning
the effect on the chemoselectivity of varying the halogen
(I, Br, Cl). We show that the chemoselectivity of this
reaction versus double-bond hydrogenation strongly de-
pends on the halogen. In addition, we demonstrate that
the catalytic hydrogenolysis of iodoarenes is compatible
with easily reducible functional groups such as ben-
zophenone and aryl azide. We took advantage of this
chemoselectivity to develop a general method to label
benzophenone- and aryl azide-containing compounds
with deuterium and tritium.
These experiments clearly show that the selective
removal of a halogen is extremely dependent on the
halogen. When the hydrogenolysis was carried out sepa-
rately, the speed of removal of halogens increased with
increasing electronegativity. Chlorine was removed faster
than bromine and bromine faster than iodine. When the
reaction was carried out in the presence of an easily
reducible substrate (trans-1-phenyl-1-propene), the less
reactive iodobenzene was selectively reduced. Selectivity
was obtained only in the case of the iodo compound. As
we have recently demonstrated, the selectivity can be
explained by a marked adsorption of the aryl iodide on
the catalyst.
Resu lts a n d Discu ssion
Hydrodehalogenation of chloro-, bromo-, and iodoben-
zene was carried out individually as well as in competi-
(1) (a) Yamakawa, M.; Ito, H.; Noyori, R. J . Am. Chem. Soc. 2000,
122, 1466-1478. (b) Carren˜o, M. C.; Ruano, J . L. G.; Urbano, A.;
Remor, C. Z.; Arroyo, Y. J . Org. Chem. 2000, 65, 453-458. (c) Saito,
S.; Nakagawa, S.; Koizumi, T.; Hirayama, K.; Yamamoto, Y. J . Org.
Chem. 1999, 64, 3975-3978. (d) Shibata, I.; Moriuchi-Kawagami, T.;
Tanizawa, D.; Suwa, T.; Sugiyama, E.; Matsuda, H.; Baba, A. J . Org.
Chem. 1998, 63, 383-385. (e) Yasuda, M.; Hayashi, K.; Katoh, Y.;
Shibata, I.; Baba, A. J . Am. Chem. Soc. 1998, 120, 715-721. (f)
Ohkuma, T.; Ooka; H.; Ikariya, T.; Noyori, R.; J . Am. Chem. Soc. 1995,
117, 10417-10418. (g)Yanagisawa, A.; Inoue, H.; Morodome, M.;
Yamamoto, H. J . Am. Chem. Soc. 1993, 115, 10356-10357.
To investigate the synthetic utility of this reaction,
iodine was selectively removed from substrates bearing
a benzophenone or an azido moiety. It is well-known that
these two groups are easily reduced by Pd and molecular
hydrogen.3
Benzophenone compounds: The high-yielding hydro-
genolysis of 1a and 1b show that the position of the iodine
atom on the aromatic ring has no influence (Table 1).
Even in the presence of other easily reducible functions
(2) Ambroise, Y.; Mioskowski, C.; Dje´ga-Mariadassou, G.; Rousseau,
B. J . Org. Chem. 2000, 65, 7183-7186.
10.1021/jo0109669 CCC: $22.00 © 2002 American Chemical Society
Published on Web 01/15/2002