Efficient cross-coupling reactions of aryl chlorides and bromides with phenyl- or vinyltrimethoxysilane mediated by a palladium/imidazolium chloride system

Article abstract of DOI:10.1021/ol005956t

diagram presented A combination of palladium acetate and the imidazolium salt IPr-HCI (1, IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) has proven to be highly efficient in the cross coupling reactions of aryl bromides and electron-deficient aryl chlorides with phenyltrimethoxysilane or vinyltrimethoxysilane. The catalytic performance of this system was found to be comparable to that of systems using PCy₃ and P(o-tol)3.

Full text of DOI:10.1021/ol005956t

ORGANIC
LETTERS
2000
Vol. 2, No. 14
2053-2055
Efficient Cross-Coupling Reactions of
Aryl Chlorides and Bromides with
Phenyl- or Vinyltrimethoxysilane
Mediated by a Palladium/Imidazolium
Chloride System
Hon Man Lee and Steven P. Nolan*
Department of Chemistry, UniVersity of New Orleans, New Orleans, Louisiana 70148
snolan@uno.edu
Received April 16, 2000
ABSTRACT
A combination of palladium acetate and the imidazolium salt IPr‚HCl (1, IPr ) 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene) has proven to
be highly efficient in the cross coupling reactions of aryl bromides and electron-deficient aryl chlorides with phenyltrimethoxysilane or
vinyltrimethoxysilane. The catalytic performance of this system was found to be comparable to that of systems using PCy3 and P(o-tol)3.
Pd-catalyzed C-C bond formation is one of the most
fundamental and important reactions in organic synthesis.1
It represents the key step in a wide range of preparative
organic processes, from the synthesis of natural products2
to supramolecular chemistry and material science.3 Common
methodologies used are the palladium mediated coupling of
organic halides or halide equivalents with Grignard reagent4
(Kumada reaction), organotin5 (Stille reaction) or organobo-
ron6 reagents (Suzuki reaction) where monodentate phos-
phines are usually employed as ancillary ligands.
The use of silicon-derived compounds as transmetalation
reagents has attracted much attention as a viable option to
these processes for its low cost, easy availability, nontoxic
byproducts, and stability to many reaction conditions.7 High
catalyst and phosphine loading are usually required to
produce high yields for unactivated aryl halides using this
methodology.
(1) (a) Trost, B. M.; Verhoeven, T. R. In ComprehensiVe Organometallic
Chemistry; Wilkinson, G., Stone, F. G. A., Abel, E. W., Eds.; Pergamon:
Oxford, Vol. 8, 1982; pp 799-938. (b) Heck, R. F. Palladium Reagents in
Organic Synthesis; Academic Press: New York, 1985. (c) Tsuji, J.
Palladium Reagents and Catalysis; Wiley: Chichester, 1995. (d) Tsuji, J.
Synthesis 1990, 739.
(2) (a) Torssell, K. G. B. Natural Product Chemistry; Wiley: Chichester,
1983. (b) Thomson, R. H. The Chemistry of Natural Products; Blackie and
Son: Glasgow, 1985.
Nucleophilic N-heterocyclic carbenes, or so-called “phos-
phine mimics”, have attracted considerable attention as
T.; Kagotani, M.; Tajika, M.; Kumada, M. J. Am. Chem. Soc. 1982, 104,
180. (h) Hayashi, T.; Konishi, M.; Kobori, Y.; Kumada, M.; Higuchi, T.;
Hirotsu, K. J. Am. Chem. Soc. 1984, 106, 158. (i) Sofia, A.; Karlstrom, E.;
Itami, K.; Backvall, J.-E. J. Org. Chem. 1999, 64, 1745. (j) Busacca, C.
A.; Erikccon, M. C.; Fiaschi, R. Tetrahedron Lett. 1999, 40, 3101. (k) Miller,
J. A.; Farrell, R. P. Tetrahedron Lett. 1998, 39, 7275. (l) for a review, see:
Kumada, M. Pure Appl. Chem. 1980, 52, 669.
(5) (a) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508. (b) Farina,
V.; Krishnamurthy, V.; Scott, W. J. Org. React. 1998, 50, 1. (c) Mitchell,
T. N. in Metal-catalyzed Cross-coupling Reactions; Diederich, F., Stang,
P. J., Eds.; Wiley-VCH: Weinhein, 1998; pp 167-202 and references
therein.
(3) (a) Roncali, J. Chem. ReV. 1992, 92, 711. (b) Yamamura, K.; Ono,
S.; Ogoshi, H.; Masuda, H.; Kuroda, Y. Synlett 1989, 18.
(4) (a) Yamamura, M.; Moritani, I.; Murahashi, S. J. Organomet. Chem.
1975, 91, C39. More examples for Kumada reaction: (b) Tamao, K.; Kiso,
Y.; Sumitani, K.; Kumada, M. J. Am. Chem. Soc. 1972, 94, 9268. (c) Sekiya,
A.; Ishikawa, N. J. Organomet. Chem. 1976, 118, 349. (d) Tamao, K.;
Sumitani, K.; Kisa, Y.; Zambayashi, M.; Fujioka, A.; Kodama, A.;
Nakajima, I.; Minato, A.; Kumada, M. Bull. Chem. Soc. Jpn. 1976, 49,
1958. (e) Widdowson D. A.; Zhang, Y.-Z. Tetrahedron 1986, 42, 2111. (f)
Minato, A.; Tamao, K.; Hayashi, T.; Suzuki, K.; Kumada, M. Tetrahedron
Lett. 1981, 22, 5319. (g) Hayashi, T.; Konishi, M.; Fukushima, M.; Mise,
(6) (a) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457. (b) Suzuki,
A. in Metal-catalyzed Cross-coupling Reactions; Diederich, F., Stang, P.
J., Eds.; Wiley-VCH: Weinhein, 1998; pp 49-97 and references therein.
10.1021/ol005956t CCC: $19.00 © 2000 American Chemical Society
Published on Web 06/17/2000

possible alternatives for the widely used phosphine ligands
in homogeneous catalysis.8 Recently, we and others have
found that the combination of Pd2(dba)3 or Pd(OAc)2 and
IPr‚HCl (1) (IPr ) 1,3-bis(2,6-diisopropylphenyl)imidazol-
2-ylidene) or IMes‚HCl (2) (IMes ) bis-(1,3-(2,4,6-tri-
methylphenyl)imidazol-2-ylidene) was highly efficient in
Suzuki coupling,9 Kumada coupling10 and amination of aryl
chlorides.11 Therefore, it was of interest to expand the scope
of these catalytic systems to silicon-derived reagents as the
coupling partner. We now wish to report the use of Pd(II)/
IPr.HCl in the cross coupling reaction of aryl halides with
phenyltrimethoxysilane. A preliminary study on vinylation
of aryl bromides using vinyltrimethoxysilane had also been
performed.
substrate 4-bromoacetophenone, quantitative conversion was
obtained in less than 1 h (entry 3). Longer reaction times
were required for electron-neutral aryl bromides (entries
1-2).
The catalytic system also proved to be highly efficient for
electron-deficient aryl chlorides (entries 6-7). Complete
conversion was readily obtained for 4-chloroacetophenone,
although a slightly longer reaction time compared with the
bromo-analogue was required, which is consistent with the
general trend that aryl chlorides are less reactive than aryl
bromides as observed in Stille,5 Suzuki6 and Kumada
coupling.4 It is worth mentioning that by using a Pd(II)/PPh3
or P(o-toly)3 system, 4-chloroacetophenone could not be
activated in the coupling reaction with phenytrimethoxysilane.7a
Subsequently a more sophisticated phosphine (Buchwald’s
ligand)14 and high catalyst loading were required to provide
moderate yields of the desired product. In the present system,
coupling involving the electron deficient 4-chlorobenzonitrile
gave quantitative conversion in 2 h (entry 7).
Treatment of aryl halide (1 equiv) with phenyltrimethoxy-
silane (2 equiv) in the presence of 3 mol % of Pd(OAc)2
and 3 mol % of IPr‚HCl in 1,4-dioxane/THF at 80 °C was
found to lead to coupling products12 (Table 1).13 In general,
In contrast to our findings in Suzuki9a and Kumada
coupling,10 the catalyst/ligand system was not suitable for
electron-neutral or electron-donating aryl chlorides in silox-
ane cross coupling reactions (entries 4-5). The reaction with
4-chlorotoluene gave only a 29% yield of cross-coupled
product in 4 h. Attempt to prolong the reaction time did not
lead to an increase in yield. Presumably, the catalytic system
degenerated after 4 h which was consistent with the observa-
tion of palladium black deposition. A 19% isolated yield of
biaryl product was obtained for 4-chloroanisole (entry 4).
As illustrated in Table 2, the siloxane cross coupling
technology based on the Pd(II)/IPr‚HCl is also applicable to
Table 1. Pd-IPr-Catalyzed Cross-Coupling of Aryl Halides
with Phenyltrimethoxysilane
entry
X
R
time (h)
yielda (%)
1
2
3
4
5
6
7
Br
Br
Br
Cl
Cl
Cl
Cl
H
Me
3
6
1
17
4
3
100
93b
100
19c
29
COMe
OMe
Me
COMe
CN
100
100
2
Table 2. Pd-IPr-Catalyzed Cross-Coupling of 2-Chloro- and
2-Bromopyridine with Phenyltrimethoxysilane
a GC yields. b 60 °C; 3 equiv of PhSi(OMe)3. c Isolated yield.
excellent yields of cross-coupled products were obtained for
aryl bromides (entries 1-3). In fact, for the electron-deficient
(7) (a) Mowery, M. E.; DeShong, P. Org. Lett. 1999, 1, 2137. (b)
Mowery, M. E.; DeShong, P. J. Org. Chem. 1999, 64, 1684. (c) Mowery,
M. E.; DeShong, P. J. Org. Chem. 1999, 64, 3266. (d) Brescia, M.-R.;
DeShong, P. J. Org. Chem. 1998, 63, 3156. (e) Pilcher, A. S.; DeShong, P.
J. Org. Chem. 1996, 61, 6901. (f) Denmark, S. E.; Wu, Z. Org. Lett. 1999,
1, 1495. (g) Denmark, S. E.; Choi, J. Y. J. Am. Chem. Soc. 1999, 121,
5821. (h) Horn, K. A. Chem. ReV. 1995, 95, 1317. (i) Chuit, C.; Corriu, R.
J. P.; Reye, C.; Young, J. C. Chem. ReV. 1993, 93, 1317. (j) Gouda, K.;
Hagiwara, E.; Hatanaka, Y.; Hiyama, T. J. Org. Chem. 1996, 61, 7232. (k)
Hagiwara, E.; Gouda, K.; Hatanaka, Y.; Hiyama, T. Tetrahedron Lett. 1997,
38, 439.
(8) (a) Regitz, M. Angew. Chem., Int. Ed. Engl. 1996, 35, 725. (b)
Arduengo, A. J., III.; Krafczyk, R. Chem Zeit. 1998, 32, 6. (c) Herrmann,
W. A.; Ko¨cher, C. Angew. Chem., Int. Ed. Engl. 1997, 36, 2163. (d) Dullius,
J. E. L.; Suarez, P. A. Z.; Einloft, S.; de Souza, R. F.; Dupont, J.; Fischer,
J.; De Cian, A. Organometallics 1998, 17, 815.
(9) (a) Zhang, C.; Huang, J.; Trudell, M. L.; Nolan, S. P. J. Org. Chem.
1999, 64, 3804. (b) Bo¨hm, V. P. W.; Gsto¨ttmayr, C. W. K.; Weskamp, T.;
Hermann, W. A. J. Organomet. Chem. 2000, 595, 186.
(10) Huang, J.; Nolan, S. J. Am. Chem. Soc. 1999, 121, 9889.
(11) Huang, J.; Grasa, G.; Nolan, S. P. Org. Lett. 1999, 1, 1307.
(12) Application of these conditions to the substrate 4-bromotoluene
resulted in small amount of homocoupled product formation. By lowering
the temperature to 60 °C and using 3 equiv of phenyltrimethoxysilane, the
amount of homocoupled product was effectively reduced. These conditions
are general for all other substrates described in this study.
entry
X
time (h)
yield (%)
1
2
Br
Cl
7
7.5
81a
81b
a Isolated yield. b GC yield.
heteroaryl halides. Using 2-bromopyridine as substrate gave
81% yield of 2-phenylpyridine in 7 h (entry 1). The chloro-
(13) General procedure for cross coupling reactions: Under an
atmosphere of argon 1,4-dioxane (3 mL), aryl halide (1.0 mmol), phenyl-
trimethoxysilane (2.0 mmol) and TBAF (2 mL, 2.00 mmol) were added in
turn to a screw-capped vial with a septum charged with Pd(OAc)2 (6.7 mg,
0.03 mmol), 1 (13 mg, 0.03 mmol), and a magnetic stirring bar. The vial
was placed in an 80 °C oil bath and stirred. The reaction was monitored by
GC. In some cases, the yields were determined by GC using biphenyl as
internal standard. The mixture was then allowed to cool to room temperature.
The reaction was quenched (30 mL H2O) and extracted (4 × 30 mL Et2O).
The organic layers were dried over MgSO4, concentrated in vacuo and then
purified by flash chromatography. All coupling products were found to be
1
identical by H NMR with literature data.
(14) Buchwald’s ligand ) 2-(Dicyclohexylphosphino)biphenyl.
2054
Org. Lett., Vol. 2, No. 14, 2000

analogue gave an identical yield (entry 2). It is worth noting
that this latter reaction using 4-chloropyridine has not
previously been reported in silicon-derived coupling reactions
using phosphines as ancillary ligands.7a
Table 4. Pd-IPr Catalyzed Coupling of 4-Bromo-acetophenone
with Vinyltrimethoxysilane
As stated above, common C-C bond coupling technolo-
gies employed phosphines as ancillary ligand. Thus, it was
of interest to compare the catalytic performances of the
imidazolylidene ligands IPr and IMes with the commonly
employed phosphines in siloxane cross coupling. As shown
in Table 3, both PCy3 and P(o-tolyl)3 are highly effective in
entry
X
time (h)
conversion (%)
1
2
Br
Cl
8
18
100
100
Table 3. Effect of Ancillary Ligand for the Pd-IPr-Catalyzed
Cross-Coupling of 4-Bromotoluene with Phenyltrimethoxysilane
methodology could find applications as a substitute for Stille
coupling where the generated tin byproducts are environ-
mentally undesirable.
In summary, the Pd/imidazolium chloride system has been
successfully extended to the siloxane cross coupling meth-
odology. The Pd(II)/IPr‚HCl system is highly efficient in
activating aryl bromides and electron-deficient aryl chlorides.
Investigations into the use of other siloxane derivatives and
applications to pharmaceutical intermediate synthesis are
ongoing.
entry
Pd
L
time (h)
yielda (%)
1
2
3
4
Pd (0)
Pd (0)
Pd (II)
Pd (II)
PCy3
1.5
1
2
100b
100b
60c
P(o-tol)3
IMes‚HCl
IPr‚HCl
6
93c
a GC yield. b 80 °C; 2 equiv of PhSi(OMe)3. c 60 °C; 3 equiv of
PhSi(OMe)3.
the coupling reaction of 4-bromotoluene with phenyltri-
methoxysilane (entries 1-2). Comparable catalytic activity
could also be obtained with IPr‚HCl, although a slightly
longer reaction time was required (entry 4). Consistent with
previous findings, IMes‚HCl, with a smaller steric bulk, was
less efficient than IPr‚HCl (entry 3).
Figure 1. Imadazolium salts.
A preliminary study was performed to see if the catalytic
system Pd(II)/IPr‚HCl could also mediate the coupling
reaction of aryl halides with vinyltrimethoxysilane to produce
substituted styrene. A similar protocol to the preparation of
biaryls using phenyltrimethoxysilane was employed. As
shown in entry 1 of Table 4, the coupling reaction of
4-bromoacetophenone with vinyltrimethoxysilane to 4-
acetylstyrene was completed in 8 h. Reaction with the chloro-
analogue required a longer reaction time to reach completion
(entry 2). These early results show great promise as the
Acknowledgment. The National Science Foundation
(CHE-9985213) and Alberarle Corporation are gratefully
acknowledged for support of this research.
Supporting Information Available: Experimental pro-
cedures, details of reaction conditions, and spectroscopic and
analytic data for the products. This material is available free
of charge via the Internet at http://pubs.acs.org.
OL005956T
Org. Lett., Vol. 2, No. 14, 2000
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