7232
J . Org. Chem. 1996, 61, 7232-7233
potassium fluoride in N,N-dimethylformamide at 120 °C,
furnishing the corresponding unsymmetrical biaryls
(Table 1). In most cases, no significant side products such
as symmetrical biaryls arising from the homocoupling
reactions were observed.6d However, reduction of the Si-
Ar bonds occurred in some cases, producing volatile
aromatic compounds (Table 1, entries 3-5). Since a wide
range of functional groups on the aromatic rings of both
the coupling partners could be tolerated under the
reaction conditions, aryl chlorides containing cyano,
acetyl, fluoro, and trifluoromethyl groups were easily
involved in the reactions (Table 1, entries 1-6). Con-
sidering the commercial availabilities of a variety of
arylchlorosilanes,11 this method would be of great value
as a convenient route to functionalized unsymmetrical
biaryls from inexpensive aryl chlorides.12
A series of trialkylphosphine-palladium complexes
were found to be highly effective in catalyzing the cross-
coupling reactions of aryl chlorides. The highest yields
of the coupled products were obtained by using [(i-Pr3P)2-
PdCl2] as a catalyst. In some cases, catalytic activity of
[(dcpe)PdCl2] (dcpe ) Cy2PCH2CH2PCy2)13 was compa-
rable (Table 1, entry 2). In contrast to the excellent
catalytic activity of trialkylphosphine-palladium com-
plexes, triphenylphosphine-palladium complexes such as
(PPh3)4Pd and (PPh3)2PdCl2 exhibited negligible catalytic
activity.
The structure of the silyl groups of arylchlorosilanes
slightly influences the rate of the cross-coupling reac-
tions. For instance, the reactivities of (dichloro)(methyl)-
(4-methoxyphenyl)silane and (dichloro)[bis(4-methoxy-
phenyl)]silane in the coupling reactions with 4-chloro-
benzonitrile were comparable to that of (dichloro)(ethyl)-
(4-methoxyphenyl)silane (Table 1, entries 6-8). How-
ever, (trichloro)(4-methoxyphenyl)silane in the same
reaction was slightly less reactive, giving the coupled
product in lower yield even under the longer reaction
time (Table 1, entry 9).
Cr oss-Cou p lin g Rea ction s of Ar yl Ch lor id es
w ith Or ga n och lor osila n es: High ly
Effective Meth od s for Ar yla tion or
Alk en yla tion of Ar yl Ch lor id es
Ken-ichi Gouda, Emiko Hagiwara,
Yasuo Hatanaka,*,† and Tamejiro Hiyama‡
Sagami Chemical Research Center, 4-4-1 Nishiohnuma,
Sagamihara, Kanagawa, 229, J apan, and Research
Laboratory of Resources Utilization, Tokyo Institute of
Technology, 4259 Nagatsuda, Midori-ku, Yokohama 226,
J apan
Received J une 13, 1996 (Revised Manuscript Received J uly 30,
1996 )
The transition-metal-catalyzed cross-coupling reactions
of aryl halides with organometallic reagents1 have been
demonstrated to be a highly effective and practical
method for preparing a number of valuable aromatic
products such as aromatic polymers,2 liquid crystals,3 and
natural products containing aryl parts.4 Among various
aryl halides, aryl chlorides should be the most attractive
candidates for industrial applications of these reactions,
because they are inexpensive and easily available in bulk
quantities compared with aryl bromides and iodides.
Thus, transition-metal-catalyzed activation and trans-
formation of the inert Cl-C bonds in aryl chlorides has
been one of the most challenging problems in synthetic
chemistry.5 However, unlike bromo and iodo analogs,
aryl chlorides are usually unreactive in the cross-coupling
reactions with organometallic reagents6 except for the
nickel-catalyzed alkylation using alkyl Grignard re-
agents.7
We report herein the first successful examples of
alkenylation and arylation of aryl chlorides by means of
the cross-coupling reactions using organochlorosilanes
(Scheme 1).8
Sch em e 1a
(5) Grushin, V. V.; Alper, H. Chem. Rev. 1994, 94, 1047.
(6) (a) Sekiya, A.; Ishikawa, N. J . Organomet. Chem. 1976, 118, 349.
(b) Zemmbayashi, M.; Tamao, K.; Kumada, M. Tetrahedron Lett. 1975,
1719. (c) Mitchell, M. B.; Wallbank, P. J . Tetrahedron Lett. 1991, 32,
2273. (d) Ikoma, Y.; Taya, F.; Ozaki, E.; Higuchi, S.; Naoi, K.; Fuji-i,
K. Synthesis 1990, 147. Heteroarylchlorides with activated Ar-Cl
bonds (e.g., chloropyrizines) can undergo the palladium-catalyzed cross-
coupling reactions with Grignard reagents: Minato, A.; Suzuki, K.;
Tamao, K.; Kumada, M. J . Chem. Soc., Chem. Commun. 1984, 511.
(7) (a) Tamao,K.; Sumitani, K.; Kumada, M. J . Am. Chem. Soc. 1972,
94, 4374. (b) Tamao, K.; Sumitani, K.; Kiso, Y.; Zembayashi, M.;
Fujioka, A.; Kodama, S.; Nakajima, I.; Minato, A.; Kumada, M. Bull.
Chem. Soc. J pn. 1976, 49, 1958.
RSi + ClAr
-8 RAr
Pd cat/F
a
R ) aryl, alkenyl; Si ) SiCl3, Si(R)Cl2, SiEtCl2, SiMeCl2, SiMe2Cl.
A series of alkenyl- and arylchlorosilanes have been found
to undergo the palladium-catalyzed cross-coupling reac-
tions with aryl chlorides in the presence of a fluoride salt,
giving alkenylarenes or unsymmetrical biaryls in good
yields.9
(8) The cross-coupling reactions of arylboronic acid with chloroben-
zonitirile have been briefly reported: Poetsch, E.; Meyer, V. Abstracts
of Papers, Seventh IUPAC Symposium on Organometallic Chemistry
Directed towards Organic Synthesis, Kobe, J apan, 1993; S-20.
(9) Aryl- and alkenylhalosilanes undergo the palladium-catalyzed
cross-coupling reactions with organic halides and triflates in the
presence of a fluoride salt, which activates the Si-C bonds of the silicon
reagents by forming an anionic pentacoordinate silicate to promote
the transmetalation with a palladium catalyst; see: (a) Hatanaka, Y.;
Goda, K.; Okahara, Y.; Hiyama, T. Tetrahedron 1994, 28, 8301. For
reviews on the cross-coupling reactions of organosilicon compounds,
see: (b) Hatanaka, Y.; Hiyama, T. Synlett 1991, 845. (c) Hiyama, T.;
Hatanaka, Y. Pure Appl. Chem. 1994, 66, 1471. (d) Chuit, C.; Corriu,
R. J . P.; Reye, C.; Young, J . C. Chem. Rev. 1993, 93, 1371. (e) Horn, K.
A. Chem. Rev. 1995, 95, 1317.
(10) This complex was prepared by treating PdCl2(PhCN)2 with
i-Pr3P in dry benzene: Turio, A.; Giacometti, G. Ric. Sci. 1960, 30,
1051.
(11) Pawlenko, S. Organosilicon Chemistry; Walter de Gruyter:
Berlin, 1986; Chapter 4.
(12) For reviews on the synthesis of biaryls, see: (a) Bringmann,
G.; Walter, R.; Weirich, R. Angew. Chem., Int. Ed. Engl. 1990, 29, 977.
(b) Sainsbury, M. Tetrahedron 1980, 36, 3327.
(13) Diversi, P.; Ingrosso, G.; Lucherini, A.; Lumini, T.; Marchett,
F.; Adovasio, V.; Nardelli, M. J . Chem. Soc., Dalton Trans. 1988, 133.
The cross-coupling reactions of aryl chlorides with
arylchlorosilanes smoothly proceeded in the presence of
a catalytic amount of [(i-Pr3P)2PdCl2] (0.5 mol%)10 and
† Present address: Department of Organic Chemistry, National
Institute of Materials and Chemical Research, Tsukuba, Ibaraki 305,
J apan.
‡ Tokyo Institute of Technology.
(1) (a) Heck, R. F. Palladium Reagents in Organic Synthesis;
Academic Press: London, 1985. (b) Kalinin, V. N. Synthesis 1992, 413
and references cited therein.
(2) (a) Rehahn, M.; Schlu¨ter, A. D.; Wegner, G. Makromol. Chem.
1990, 191, 1991. (b) Wallow, T. I.; Novak, B. M. J . Am. Chem. Soc.
1991, 113, 7411. (c) Bochmann, M.; Kelly, K. J . Chem. Soc., Chem.
Commun. 1989, 532.
(3) Poetsch, E.; Meyer, V.; Bo¨ttcher, H. Ger. Pat. DE3736489, 1987;
Chem. Abstr. 1990, 112, 88951a.
(4) (a) Schmitd, U.; Meyer, R.; Leitenberger, V.; Lieberknecht, A.
Angew. Chem., Int. Ed. Engl. 1989, 28, 929. (b) Tamao, K.; Kodama,
S.; Nakajima, I.; Kumada, M.; Minato, A.; Suzuki, K. Tetrahedron 1982,
38, 3347. (c) Muller, D.; Fleury, J . Tetrahedron Lett. 1991, 32, 2229.
(d) Tius, M. A.; Gomez-Galeno, J .; Gu, X.; Zaidi, J . H. J . Am. Chem.
Soc. 1991, 113, 5775.
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