ORGANIC
LETTERS
2001
Vol. 3, No. 13
1997-1999
Palladium-Catalyzed Cross-Coupling
Reaction of Organoindiums with Aryl
Halides in Aqueous Media
Kazuaki Takami, Hideki Yorimitsu, Hiroshi Shinokubo, Seijiro Matsubara, and
Koichiro Oshima*
Department of Material Chemistry, Graduate School of Engineering, Kyoto UniVersity,
Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
Received April 12, 2001
ABSTRACT
Diaryl-, divinyl-, and dialkylindium proved to be stable in aqueous media and to undergo a palladium-catalyzed cross-coupling reaction with
aryl halides in aqueous THF. Treatment of 3-iodophenol with diphenylindium compound, generated from indium trichloride and two equimolar
amounts of a phenyl Grignard reagent, in aqueous media under palladium catalysis provided the corresponding coupling product in excellent
yield. Divinyl- and diethylindium can be used for the coupling reaction in the presence of water. A wide range of functional groups, including
a hydroxy group and a formyl group, are compatible with this reaction.
The palladium-catalyzed cross-coupling reaction is one of
the most important methodologies in organic synthesis.1 The
Suzuki-Miyaura coupling of organoboranes with organic
halides has attracted much attention because of the low
toxicity and easy handling of boron reagents as well as good
functional group compatibility under the reaction conditions.2
On the other hand, the cross-coupling reaction with orga-
noindium compounds has not been widely studied.3 A recent
report3a,e shows that triorganoindium can efficiently transfer
the three organic groups on the metal. Therefore, studies of
this attractive cross-coupling reaction with organoindium are
warranted.
organic solvents.4 Among them, allylic indium provides a
powerful tool for allylation of carbonyl compounds in
aqueous media.5,6 The usefulness of allylindium in water was
well illustrated in the synthesis of (+)-3-deoxy-D-glycero-
D-galacto-nonulosonic acid (KDN), starting from unprotected
D-mannose.7 Here we wish to report the cross-coupling
reaction of organoindiums with aryl halides in aqueous
media.8,9 This study disclosed that diaryl-, divinyl-, and
dialkylindium species are available in the presence of water,
similar to allylic indium.
First, we examined the coupling reaction of triphenylin-
(4) (a) Li, C.-J.; Chan, T.-H. Organic Reactions in Aqueous Media; John
Wiley & Sons: New York, 1997. (b) Grieco, P. A. Organic Synthesis in
Water; Blackie Academic & Professional: London, 1998. (c) Lubineau,
A.; Auge, J. In Modern SolVents in Organic Synthesis; Knochel, P., Ed.;
Springer-Verlag: Berlin Heidelberg, 1999.
There is increasing recognition that organic reactions
carried out in water may offer advantages over those in
(1) (a) Metal-Catalyzed Cross-Coupling Reactions; Diederich, F., Stang,
P. J., Eds.; Wiley-VCH: Weinheim, 1998. (b) Heck, R. F. Palladium
Regents in Organic Syntheses; Academic Press: New York, 1985. (c) Tsuji,
J. Palladium Reagents and Catalysts. InnoVations in Organic Synthesis;
Wiley: Chichester, U.K., 1996.
(2) (a) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457-2483. (b)
Suzuki, A., in ref 1a, Chapter 2.
(3) (a) Pe´rez, I.; Pe´rez Sestelo, J.; Sarandeses, L. A. Org. Lett. 1999, 1,
1267-1269. (b) Gelman, D.; Schumann, H.; Blum, J. Tetrahedron Lett.
2000, 41, 7555-7558. (c) Fujiwara, N.; Yamamoto, Y. J. Org. Chem. 1999,
64, 4095-4101. (d) Hirashita, T.; Yamamura, H.; Kawai, M.; Araki, S.
Chem. Commun. 2001, 387-388. (e) Pe´rez, I.; Pe´rez Sestelo, J.; Sarandeses,
L. A. J. Am. Chem. Soc. 2001, 123, 4155-4160.
(5) Review on the use of indium in organic synthesis; Cintas, P. Synlett
1995, 1087-1096.
(6) (a) Li, C.-J.; Chan, T.-H. Tetrahedron Lett. 1991, 32, 7017-7020.
(b) Araki, S.; Jin, S.; Idou, Y.; Butsugan, Y. Bull. Chem. Soc. Jpn. 1992,
65, 1736-1738.
(7) (a) Chan, T.-H.; Li, C.-J. J. Chem. Soc., Chem. Commun. 1992, 747-
748. (b) Li, C.-J. Chem. ReV. 1993, 93, 2023-2035.
(8) For reviews on transition metal-catalyzed coupling reactions in
aqueous media, see refs 4a, Chapter 5.5, and 4c, Chapter 2.
(9) Palladium-catalyzed Ullmann-type reductive coupling reaction of aryl
halides was reported: Venkatraman, S.; Li, C.-J. Org. Lett. 1999, 1, 1133-
1135.
10.1021/ol015975i CCC: $20.00 © 2001 American Chemical Society
Published on Web 06/07/2001