C-C coupling reactions of aryl bromides and arylsiloxanes in water catalyzed by palladium complexes of phosphanes modified with crown ethers

Article abstract of DOI:10.1021/ol061221y

The complexes [PdCl₂L₂], where L is a crown-ether-containing triarylphosphane, catalyze the formation of biaryls from arylsiloxanes and aryl bromides with high yields In water as solvent and under air. The water-insoluble catalysts [PdCl₂(PhCN)2] and [PdCl ₂(PPh₃)₂] are also efficient, although they decompose more quickly to form black Pd⁰.

Full text of DOI:10.1021/ol061221y

ORGANIC
LETTERS
2006
Vol. 8, No. 16
3517-3520
C−C Coupling Reactions of Aryl
Bromides and Arylsiloxanes in Water
Catalyzed by Palladium Complexes of
Phosphanes Modified with Crown Ethers
AÄ lvaro Gordillo, Ernesto de Jesu´s,* and Carmen Lo´pez-Mardomingo
Departamento de Qu´ımica Orga´nica and Departamento de Qu´ımica Inorga´nica,
UniVersidad de Alcala´, 28871 Alcala´ de Henares (Madrid), Spain
ernesto.dejesus@uah.es
Received May 18, 2006
ABSTRACT
The complexes [PdCl2L2], where L is a crown-ether-containing triarylphosphane, catalyze the formation of biaryls from arylsiloxanes and aryl
bromides with high yields in water as solvent and under air. The water-insoluble catalysts [PdCl2(PhCN)2] and [PdCl2(PPh3)2] are also efficient,
although they decompose more quickly to form black Pd0.
The palladium-catalyzed aryl-aryl cross-coupling reaction
is a simple, efficient, and versatile route to the formation of
carbon-carbon bonds that is commonly used in modern
organic synthesis1 to give complex products in a one-step
reaction between an aryl halide and an organometallic
species, for instance, an organoborane (Suzuki)2 or orga-
nostannane reagent (Stille reaction).3 Organosilanes are
remarkable for their low toxicity, environmental benignity,
and high chemical stability, and these advantages can be
reinforced by using water as a cheap, nontoxic, and nonflam-
mable solvent.4 Hiyama showed 20 years ago that trans-
metalation of organosilanes takes place smoothly after their
activation with the fluoride anion.5 Subsequent developments6
showed that sodium hydroxide is an effective promoter7 that
is able to activate the coupling of arylsiloxanes6b,8 in water-
containing organic solvents.9 Recently, Wolf and Lerebours
have described a NaOH-promoted coupling method for the
(4) (a) Cornils, B.; Herrmann, W. A. Aqueous-Phase Organometallic
Catalysis: Concepts and Applications, 2nd ed.; Wiley-VCH: Weinheim,
Germany, 2004. (b) Joo´, F.; Katho´, AÄ . J. Mol. Catal. A 1997, 116, 3-26.
(c) Genet, J. P.; Savignac, M. J. Organomet. Chem. 1999, 576, 305-317.
(d) Li, C.-J. Chem. ReV. 2005, 105, 3095-3165.
(5) (a) Hatanaka, Y.; Hiyama, T. J. Org. Chem. 1988, 53, 918-920. (b)
Hatanaka, Y.; Fukushima, S.; Hiyama, T. Chem. Lett. 1989, 1711-1714.
(c) Hiyama, T. In Metal-Catalyzed Cross-Coupling Reactions; Diederich,
F., Stang, P. J., Eds.; Wiley-VCH: Weinheim, Germany, 1998; Chapter
10. (d) Hiyama, T. J. Organomet. Chem. 2002, 653, 58-61 and references
therein.
(6) (a) Denmark, S. E.; Sweis. R. F. In Metal-Catalyzed Cross-Coupling
Reactions, 2nd ed.; de Meijere, A., Diederich, F., Eds.; Wiley-VCH:
Weinheim, Germany, 2004; Chapter 4. (b) Handy, C. J.; Manoso, A. S.;
McElroy, W. T.; Seganish, W. M.; DeShong, P. Tetrahedron 2005, 61,
12201-12225. (c) Denmark, S. E.; Sweis, R. F. Acc. Chem. Res. 2002, 35,
835-846. (d) Denmark, S. E.; Ober, M. H. Aldrichimica Acta 2003, 36,
75-85.
(1) (a) Hassan, J.; Se´vignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M.
Chem. ReV. 2002, 102, 1359-1470. (b) Echavarren, A. M.; Cardenas, D.
J. In Metal-Catalyzed Cross-Coupling Reactions, 2nd ed.; de Meijere, A.,
Diederich, F., Eds.; Wiley-VCH: Weinheim, Germany, 2004; Chapter 1.
(2) (a) Suzuki, A. J. Organomet. Chem. 1999, 576, 147-168. (b) Suzuki,
A. Chem. ReV. 1995, 95, 2457-2483. (c) Herrmann, W. In Applied
Homogeneous Catalysis with Organometallic Compounds, 2nd ed.; Cornils,
B., Herrmann, W. A., Eds.; Wiley-VCH: Weinheim, Germany, 2002; pp
591-598.
(7) Hagiwara, E.; Gouda, K.; Hatanaka, Y.; Hiyama, T. Tetrahedron Lett.
1997, 38, 439-442.
(8) (a) Tamao, K.; Kobayashi, K.; Ito, Y. Tetrahedron Lett. 1989, 30,
6051-6054. (b) Shibata, K; Miyazawa, K.; Goto, Y. Chem. Commun. 1997,
1309-1310. (c) Mowery, M. E.; DeShong, P. J. Org. Chem. 1999, 64,
1684-1688. (d) Mowery, M. E.; DeShong, P. Org. Lett. 1999, 1, 2137-
2140.
(3) (a) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508-524.
(b) Espinet, P.; Echavarren, A. M. Angew. Chem., Int. Ed. 2004, 43, 4704-
4734 and references therein.
10.1021/ol061221y CCC: $33.50
© 2006 American Chemical Society
Published on Web 07/01/2006

synthesis of biaryls in water using arylsiloxanes and aryl
halides with a Pd catalyst of formula [{(tBu)2P(OH)-
(tBu)2PO}PdCl]2.10
Table 1. Screening of Cross-Coupling Reaction Conditions in
Watera
We have probed the efficiency of the [PdCl2L2] complexes
Pd*1 and Pd*2, where L is a crown-ether-modified triph-
enylphosphane ligand (Scheme 1), in the Stille cross-coupling
mol %
entry catalyst [Pd]
temp reaction ratio yield
baseb
(°C) time (h)c 1:2
(%)d
Scheme 1. Pd Catalysts and Aqueous Hiyama-type
1
2
3
4
5
6
7
8
9
Pd*1
Pd*1
Pd*1
Pd*2
Pd*2
Pd*1
Pd*1
Pd*2
Pd*2
Pd*1
Pd*1
1
1
1
1
1
1
1
1
TBAF
140
18
18
18
18
1:2
1:2
1:2
1:2
1:2
1:1.2 96
1:1.2 96
1:1.2 72e
1:1.2 90
1:1.2 92
10e
51e
96
96
96
Cross-Coupling Reactions
K2CO3 140
NaOH 140
NaOH 140
NaOH 140
NaOH 140
1.5
1.5
1.5
1.5
18
1.5
1.5
KOH
140
NaOH 100
NaOH 100
NaOH 140
NaOH 140
1
0.5
0.1
10
11
1:1.2
6e
a In a typical experiment, a mixture of 1.0 mmol of aryl bromide,
1.2 equiv of aryltrimethoxysilane, and 1 mol % of Pd catalyst were
stirred under air in 5.0 mL of 0.50 M NaOH at 140 °C for 1.5 h.
The products were purified by flash chromatography (silica gel,
hexane/ethyl acetate).
a See footnote to Scheme 1 and Supporting Information for other general
conditions. b Five milliliters of an aqueous 0.5 M solution. c Reagents were
mixed at room temperature with vigorous stirring. The reaction time was
measured from the moment at which the tabulated temperature was reached.
d Yields of isolated product. e Incomplete conversion.
of aryl iodides and trichlorostannanes in water.11 Despite the
low water solubility of these Pd complexes, good activities
were observed for such reactions under the reported condi-
tions (1 M KOH, 1% Pd, 100 °C). Taking into account these
results, we decided to test Pd*1 and Pd*2 in aqueous
Hiyama-type cross-coupling reactions between trialkoxyar-
ylsilanes and aryl bromides under conditions based on those
described by Wolf (Scheme 1).10 These catalysts were found
to be more active than those previously described and
allowed the synthesis of biaryls in excellent yields with lower
Pd loadings and shorter reaction times.
The reaction between 3-bromopyridine and trimethylphe-
nylsiloxane was studied as a model to determine the standard
conditions for the cross-coupling between aryl bromides and
arylsiloxanes in water (Table 1). Sodium hydroxide was
found to be a better activator than tetrabutylammonium
fluoride (TBAF) or potassium carbonate (entries 1-3), giving
3-phenylpyridine as a liquid of high purity without traces of
reagents (1H NMR evidence). In contrast, a conversion of
only 10 and 50% of 3-bromopyridine was observed when
TBAF or K2CO3, respectively, was used under the same
conditions. Potassium hydroxide gave results similar to those
obtained with sodium hydroxide (compare entries 6 and 7).
No appreciable differences were found between the activity
of Pd*1 and Pd*2, which differ only in the number of crown
ether groups per phosphane ligand (entries 3 and 4). Both
yellow complexes were completely soluble at the concentra-
tion and temperature of the reaction (140 °C), affording
yellow-orange solutions that lose their color during the
course of the reaction. We found that a 20% excess of
arylsiloxane was enough to obtain good yields in most cases
(entry 6) instead of the 1:2 ratio of aryl halide to arylsiloxane
used previously.10 However, a greater excess of siloxane
enhances the yields with inactivated aryl bromides (see
below). Essentially quantitative yields were obtained after
1.5 h at 140 °C (entry 5), although longer reaction times
were needed to achieve high yields when the reaction
temperature was decreased to 100 °C (entries 8 and 9).
Nevertheless, and despite the slower kinetics, conversions
of about 90-92% were obtained at 100 °C. The optimal
catalyst loading is situated in the range of 0.5 to 1 mol %
(compare entries 6, 10, and 11).
We also tested the viability of recycling the palladium
catalysts. After a first run using Pd*2 under the standard
conditions of entry 6, the reaction products were extracted
with pentane at room temperature, and the aqueous solution
was reused for a second run, which gave only a 10% yield
of product. This is probably due, in part, to the low water
solubility of the active catalyst at room temperature. In fact,
a pale-grayish solid was observed at the pentane/water
interface, which was found to catalyze the reaction with a
65% yield after separation.
The standard conditions selected above were applied to
synthesize a series of biaryls in water using Pd*2 as catalyst
(Table 2). Thus, 3-bromopyridine was efficiently coupled
to para-substituted phenylsiloxanes, independently of the
electronic nature of the substituent in the para position
(electron-withdrawing, electron-neutral, or electron-donating,
entries 1-4). However, the reaction of 2-bromopyridine with
trimethoxyphenylsilane gave lower yields of the desired
biaryl product (entry 5), probably due to the sensitivity of
the 2-position of the pyridine ring to a nucleophilic attack
in the basic medium. Fused heterocycles, such as 3-bromo-
(9) Murata, M.; Shimazaki, R.; Watanabe, S.; Masuda, Y. Synthesis 2001,
2231-2233.
(10) Wolf, C.; Lerebours, R. Org. Lett. 2004, 6, 1147-1150.
(11) Fresneda, J.; de Jesu´s, E.; Lo´pez-Mardomingo, C. Eur. J. Inorg.
Chem. 2005, 1468-1476.
3518
Org. Lett., Vol. 8, No. 16, 2006

11 and 12), whose yields decrease considerably when the
reactions are carried out under an inert atmosphere. For
instance, 4-bromo-N,N-dimethylaniline produced about 80%
of the heterocoupled and 15-20% of the homocoupled
products after 5 h of reaction in the presence of 2 equiv of
arylsiloxane under argon. In contrast, essentially quantitative
yields of only N,N-dimethylbiphenyl-4-amine were achieved
under the same conditions in air. The disminution of
homocoupled products in aerobic conditions is unexpected.
Oxygen is known to induce homocoupling in Suzuki reac-
tions, for instance.12 The presumed catalytic cycle involves
double organoboron transmetalation, reductive elimination
of the biaryl, and reoxidation of the Pd0 center with oxygen.
Symmetrical biaryls can be synthesized by Pd-catalyzed
oxidative homocoupling of organostannanes or organoboron
derivatives using oxygen as oxidant.13 It is interesting to
highlight that the presence of oxygen in the hydrosilylation
of olefins catalyzed by Pt enhances the conversion and
prevents olefin bond isomerization. It has been proposed that
oxygen breaks up the multinuclear Pt species that are
responsible for the isomerization and supplies monometallic
compounds, which are the active species in the hydrosily-
lation.14
Table 2. Cross-Coupling Reactions of Arylsiloxanes with Aryl
Bromides Catalyzed by Pd*2 in Watera
It is also surprising that the reaction of para-iodotoluene
with trimethoxyphenylsilane afforded yields as low as 20%
after 22 h at 140 °C. para-Iodoaniline did not react at all
under the same conditions. The same Pd complex catalyzes
the Stille reaction between these iodoaryls and PhSnCl3 in
water with nearly quantitative yields.11 On the other hand,
the reaction of 3-chloropyridine with trimethoxyphenylsilane
was unsuccessful. After addition of the chloride and the
catalyst at room temperature, the color of the aqueous
solution immediately turned intense orange and a copious
precipitate of Pd black was observed after warming.
In our previous work on the Stille reaction,11 we observed
that complexes without water-solubilizing groups, such as
[PdCl2(PPh3)2], produced remarkable conversions, although
lower than those obtained with the crown ether phosphane
complexes. Interestingly, the yields obtained at 140 °C for
the Hiyama model reaction using [PdCl2(PPh3)2], [PdCl2-
(PhCN)2], or mixtures of [PdCl2(PhCN)2] and PPh3 as the
catalysts were nearly quantitative and comparable to those
produced by Pd*1 or Pd*2 (Table 3, entries 2-5). In
contrast, the yield obtained at 100 °C with [PdCl2(PPh3)2]
was appreciably lower than that obtained with Pd*2 (45-
50% versus 72%; entry 1 of Table 3 and entry 8 of Table
1). An important difference between both series of catalysts
is that the insoluble catalysts decompose appreciably to give
a copious and fine dispersion of Pd black even before
reaching the reaction temperature (140 °C), whereas no
apparent formation of metallic Pd0 is observed with crown
ether phosphane complexes at 100 or 140 °C. The presence
a See footnote to Scheme 1 and Supporting Information for other general
conditions. b Yields of isolated product. c Traces of products resulting from
the homocoupling of the aryl bromide were also found. d Two equivalents
of arylsiloxane and 5 h of reaction time were used; incomplete conversion
(75% of p-bromoaniline).
quinoline or 4-bromoisoquinoline, were also coupled with
trimethoxyphenylsilane in excellent yields (entries 6 and 7).
The electronic influence of the substituent on the aryl
bromide was also studied. Both electron-withdrawing (entries
8-10) and electron-donating substituents (entries 11 and 12)
gave excellent yields. The steric influence of the ortho
substitution in 2-bromoacetophenone is low (compare entries
9 and 10), and the conversion was complete without the need
for the high Pd loadings required in other cases.8d The yields
obtained for 4-bromoaniline under the standard conditions
were negligible, but they increased to a modest 25% with
longer reaction times and higher arylsiloxane to aryl bromide
ratios (entry 13 and footnote d). It is worth mentioning that
all the preparations were carried out under air because, under
anaerobic conditions, the yields of cross-coupling products
often decreased and the formation of homocoupled products
was favored. This is especially relevant with inactivated aryl
bromides containing electron-donating substituents (entries
(12) Miyaura, N. In Metal-Catalyzed Cross-Coupling Reactions, 2nd ed.;
de Meijere, A., Diederich, F., Eds.; Wiley-VCH: Weinheim, Germany,
2004; Chapter 2.
(13) See, for example: (a) Yoshida, H.; Yamaryo, Y.; Ohshita, J.; Kunai,
A. Tetrahedron Lett. 2003, 44, 1541. (b) Shirakawa E.; Nakao, Y.; Murota,
Y.; Hiyama, T. J. Organomet. Chem. 2003, 670, 132 and references therein.
(14) See, for instance: Stein, J.; Lewis, L. N.; Gao, Y.; Scott, R. A. J.
Am. Chem. Soc. 1999, 121, 3693-3703 and references therein.
Org. Lett., Vol. 8, No. 16, 2006
3519

the formation of C-C bonds,17 although it has been
postulated that metal colloids could, on occasion, be acting
as the source of Pd0 molecular catalysts.18 Kinetic studies
have shown an induction period of about 30 min for the
reaction catalyzed by PPh3 and Pd*n complexes under the
standard conditions. Furthermore, the activity of these
complexes drops drastically in the presence of metallic
mercury (Hg drop test). However, neither of these experi-
ments provides irrefutable evidence of a heterogeneous
process. In addition, the isolation of a pale-grayish solid after
the first run with Pd*2 (see above) that is able to catalyze a
second run could be indicative of molecular catalysis.
In summary, the complexes Pd*1 and Pd*2 catalyze the
formation of biaryls from arylsiloxanes and aryl bromides
in only water as solvent. Yields generally in the range of
90-98% are obtained for both activated and inactivated aryl
bromides using Pd loadings of 1 mol % and reaction times
of 1.5 h, both of which are better than those described
previously.10 The reactions are compatible with air, and in
addition, yields are significantly increased by its presence.
The viability of catalyst recycling has been shown for Pd*2,
but practical problems arise from its poor solubility in water
at room temperature. The water-insoluble catalysts [PdCl2-
(PhCN)2] and [PdCl2(PPh3)2] are also notably efficient, but
they produce lower yields in cross-coupling products with
inactivated aryl bromides. Moreover, they decompose more
quickly to form inactive Pd black, thus precluding catalyst
reuse. In our opinion, the water solubility of the crown ether
phosphanes is responsible for the enhanced stability of Pd*1
and Pd*2 under these reaction conditions. Our current efforts
are directed at further expanding the reaction scope to other
substrates and elucidating the nature of the catalyst.
Table 3. Catalysis with Water-Insoluble Pd Precursorsa
a Conditions: 1 mmol of aryl bromide, 1.2 mmol of arylsiloxane, 5 mL
of 0.5 M NaOH, 1.5 h. See footnote to Scheme 1 and Supporting Information
for other general conditions. b Yields of isolated product. c Incomplete
conversion. d Complete conversion, homocoupled product was also found.
e Formation of Pd black was observed.
of progressively higher concentrations of the PPh3 ligand
retards the precipitation of Pd (entries 3-5), but the yields
were only modified when a large excess of triphenylphos-
phane was used, which hampered the reaction (entry 6).
Crown ether catalysts are, however, significantly more
efficient in the coupling of electron-donating aryl bromides
(compare, respectively, entries 7 and 8 in Table 3 with entries
11 and 12 in Table 2).
These results raise the question of the nature of the
catalysis, that is, heterogeneous (bulk Pd or metal nanopar-
ticles) or homogeneous (molecular). It is well-established
that palladium(II) complexes, such as [PdCl2(PR3)2], are
reduced to Pd0 complexes under conditions similar to those
employed here.15 The comparable activity of soluble and
insoluble complexes might be due to the generation of the
same common active species, either metallic or molecular,
independently of the Pd precatalyst used. Deposition of Pd0
was not usually observed in the reactions with Pd*n, and
the Pd black formed from the insoluble complexes was found
to be inactive as a catalyst. Nevertheless, the process can
appear to be homogeneous if the catalyst consists of soluble
metal nanoparticles.16 Pd nanoclusters are able to catalyze
Acknowledgment. This work was supported by the
Spanish DGI-Ministerio de Educacio´n y Ciencia (Project
CTQ2005-00795/BQU and FPU grant to A.G.) and the
Comunidad de Madrid (Project S-0505-PPQ-0328).
Supporting Information Available: Experimental pro-
cedures and spectroscopic data for all compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL061221Y
(17) See, for example: (a) Reetz, M. T.; Breinbauer, R.; Wanninger, K.
Tetrahedron Lett. 1996, 37, 4499-4502. (b) Reetz, M. T.; de Vries, J. G.
Chem. Commun. 2004, 1559-1563. (c) Eberhard, M. R. Org. Lett. 2004,
6, 2125-2128.
(18) Trzeciak, A. M.; Zio´lkowski, J. J. Coord. Chem. ReV. 2005, 249,
2308-2322.
(15) Grushin, V. V.; Alper, H. Organometallics 1993, 12, 1890-1901.
(16) Widegren, J.; Finke, R. G. J. Mol. Catal. A: Chem. 2003, 198,
317-341.
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