Palladium-Catalyzed Cross-Coupling Reaction of Silicone with Aryl Chlorides

Article abstract of DOI:10.1055/s-2003-41413

The palladium-catalyzed cross-coupling reaction of silicone, poly(diorganosiloxane), with aryl chlorides in the presence of K ₂CO₃/H₂O as an activator proceeds to afford the biaryl derivatives in moderate to excellent yields. A wide range of aryl chlorides bearing an electron-donating or electron-withdrawing substituent on the aromatic ring are tolerated. The amount of K₂CO₃ relative to silicone significantly influences the reaction. Treatment of silicone with K₂CO₃/H₂O at r.t. for 1 hour prior to the addition of the palladium catalyst and an aryl chloride is necessary.

Full text of DOI:10.1055/s-2003-41413

1850
LETTER
Palladium-Catalyzed Cross-Coupling Reaction of Silicone with Aryl Chlorides
C
ross-Coupling
o
Reaction of
o
Silicone
w
it
r
h Aryl
C
u
hlorides Koike, Atsunori Mori*
Chemical Resources Laboratory, Tokyo Institute of Technology, Nagatsuta, Yokohama 226-8503, Japan
Fax +81(45)9245224; E-mail: amori@res.titech.ac.jp
Received 01 July 2003
product 3a in 65% yield (entry 2). Moreover, it is effective
Abstract: The palladium-catalyzed cross-coupling reaction of sili-
cone, poly(diorganosiloxane), with aryl chlorides in the presence of
K2CO3/H2O as an activator proceeds to afford the biaryl derivatives
in moderate to excellent yields. A wide range of aryl chlorides
to stir the silicone 1 in the presence of TBAF/H2O at r.t.
for 1 hour before the addition of the palladium catalyst
and 2a to accomplish the cross-coupling reaction giving
bearing an electron-donating or electron-withdrawing substituent 3a in 78% yield (entry 3). On the other hand, we detected
on the aromatic ring are tolerated. The amount of K2CO3 relative to
no coupling product with the palladium catalyst in the ab-
silicone significantly influences the reaction. Treatment of silicone
sence of a phosphine ligand or Pd(PPh3)4 (entries 4 and 5).
with K2CO3/H2O at r.t. for 1 hour prior to the addition of the palla-
These results are explained in terms of the lower reactivity
dium catalyst and an aryl chloride is necessary.
of aryl chlorides compared to that of aryl iodides toward a
palladium complex.7 Ethereal solvent such as 1,4-dioxane
Key words: palladium, cross coupling, silicone, aq potassium
carbonate, aryl chlorides
was similarly effective for the biaryl formation to furnish
the desired coupling product in 81% yield (entry 6). Low-
ering the temperature to 70 °C also caused cross coupling
We have recently reported that silicone, poly(diorgano-
to give 3a in 46% yield (entry 7) and increasing the
siloxane), participates in the palladium-catalyzed cross-
amount of TBAF (2 equiv) resulted in lowering the yield
coupling reaction of aryl iodides in the presence of
of 3a (entry 8).
silver(I) oxide (Ag2O) or tetrabutylammonium fluoride
(TBAF) as an activator.1 This newly developed organo-
silicon reagent is also available for the rhodium-catalyzed
carbon-carbon bond-forming reaction of a,b-unsaturated
carbonyl compounds.2 These results demonstrated the
synthetic utility of polysiloxane as a novel organosilicon
reagent similar to silanols, silanediols, silanetriols, and
other silane reagents.3 Aryl chlorides are one of the most
Scheme 1
attractive substrates for the transition metal-catalyzed
Table 1 Palladium-Catalyzed Cross-Coupling Reaction of 1-Chlo-
cross-coupling reaction due to the lower cost compared to
ro-4-methoxybenzenea
aryl bromide or iodide counterparts.4 Thus, our interest
directed to modify the reaction protocol of silicone in or-
der to cross-couple with aryl chlorides. In this paper, we
describe a practical palladium-mediated biaryl-forming
reaction of siloxane reagents with aryl chlorides.
Entry Cat. Pd
Solvent
Temp/°C %Yield of 3ab
1c
2
PdCl2(PCy3)2
toluene
120
120
120
120
120
100
70
0
65
78
0
PdCl2(PCy3)2
PdCl2(PCy3)2
Pd2dba3
toluene
Initially, we performed the reaction of poly(phenylmeth-
ylsiloxane) (1)1b with 1-chloro-4-methoxybenzene (2a) in
the presence of 5 mol% of PdCl2(PCy3)2,5 which poss-
essed electron-donating and bulky phosphine ligands and
was shown to be effective for several cross-coupling reac-
tions of aryl chlorides, using TBAF6 as a common activat-
ing reagent for organosilicon compounds (Scheme 1).
According to the procedure for the previously reported
cross-coupling reaction of aryl iodides,1a the reaction was
carried out using an equimolar amount of TBAF relative
to the silicon atom of 1 in toluene at 120 °C for 39 hours.
However, no coupling product was obtained at all
(Table 1, entry 1). Dramatic improvement was observed
by addition of water to afford the desired cross-coupling
3d
4e
5
toluene
toluene
Pd(PPh3)4
toluene
0
6
PdCl2(PCy3)2
PdCl2(PCy3)2
PdCl2(PCy3)2
1,4-dioxane
1,4-dioxane
1,4-dioxane
81
46
61
7
8f
100
a Unless otherwise noted, the reaction was carried out using 1 (1.5
mmol/unit), 2a (0.3 mmol), 5 mol% of palladium catalyst, and TBAF
(1.5 mmol) in the presence of water (0.5 mL) for 39 h.
b The yield was determined by 1H NMR using diphenylmethane as an
internal standard.
c The reaction was performed in the absence of water.
d Stirring 1 with TBAF at r.t. for 1 h before starting reaction.
e Pd2dba3 (2.5 mol%) was employed.
SYNLETT 2003, No. 12, pp 1850–1852
2
9
.0
9
.2
0
0
3
f TBAF (3.0 mmol) was used.
Advanced online publication: 28.08.2003
DOI: 10.1055/s-2003-41413; Art ID: U12403st.pdf
© Georg Thieme Verlag Stuttgart · New York

LETTER
Cross-Coupling Reaction of Silicone with Aryl Chlorides
1851
We next investigated the effect of additive and found that Under our optimized reaction conditions, various aryl
fluoride-free cross-coupling reaction was achieved. The chlorides were treated with 1 to provide the corresponding
results are summarized in Table 2. CsCO3 can be em- coupling products in moderate to excellent yields. As il-
ployed for this reaction to produce the cross-coupling lustrated in Table 3, aryl chlorides bearing an electron-
product in 73% yield (entry 1). It should be noted that use donating or electron-withdrawing substituent on the aro-
of K2CO3 lead to the complete consumption of 2a giving matic ring underwent the coupling reaction in good yields.
the 4-methoxybiphenyl (3a) in quantitative yield (entry Sterically hindered aryl chloride 2c was also tolerated
3).8 The reaction with K2CO3 also proceeded at lower to produce the corresponding product 3c in 43% yield
temperature (100 °C) in 1,4-dioxane (entry 5). Another in- (entry 2). A heteroaromatic substrate such as 2-chloro-
organic activator such as NaOH was applicable (entry 6). quinoline (2g) reacted to afford 3g in 68% yield (entry 6).
On the other hand, no coupling product was obtained Poly[methyl(2-phenylethenyl)siloxane] (4), which was
when Ag2O was employed (entry 7). This result could be prepared by hydrosilylation of poly(methylhydrosil-
ascribed to the inferior interaction ability between silver oxane) (PMHS),1a served as a substrate for the alkenyl-
and chloride compared with the iodide case.3c A decrease ation to afford stilbene derivatives in good yields (entries
in the amount of K2CO3 from 2.0 equivalents to 1.0 equiv- 7 and 8).
alent relative to 1 was found to be less effective giving a
smaller amount of the cross-coupling product (entry 2).
Table 3 Cross-Coupling of Silicone with Aryl Chloridesa
Similarly, the reaction was suppressed to some extent
with increasing the amount of K2CO3 from 2.0 equiva-
lents to 3.0 equivalents (entry 4). Consequently, the
present reaction was found to be significantly influenced
by the amount of activator employed.
Entry Silicone
1
Aryl chloride
%Yieldb
92
Table 2 Effect of Additive for the Cross-Coupling of Siliconea
2
1
43
Entry
Additive
Cs2CO3
K2CO3
K2CO3
K2CO3
K2CO3
NaOH
Ag2O
Additive/silicone %Yield of 3ab
1
2
3
4
5c
6
7
2
1
2
3
2
2
1
73
65
3
1
1
53
>99
70
4c
>99
64
5
6
1
1
77
68
>99
0
a Unless otherwise mentioned, the reaction was carried out in 3 mL of
toluene and 0.5 mL of water at 120 °C for 39 h.
b Estimated by 1H NMR.
c The reaction was performed in 1,4-dioxane/H2O at 100 °C.
During the course of our study on the palladium-mediated
cross-coupling reaction of silicone, we suggested that a
certain oligomer, which was formed in situ by the activa-
tion of silicone with TBAF, might be involved in the
cross-coupling reaction.1 Thus, we examined favorable
activating conditions of 1 with K2CO3. When 1 was treat-
ed with aq K2CO3 at 120 °C for 1 h before addition of pal-
7
8
97
70
4
2f
a Unless otherwise specified, the reaction was performed in toluene
(3mL) for 29–48 h at 120 °C using silicone (1.5 mmol ; per unit), aryl
chloride (0.3 mmol), 5 mol% of PdCl2(PCy3), and 3 mmol of K2CO3
ladium catalyst and 2a, only 25% of the cross-coupling H2O.
b Determined by 1H NMR analysis using diphenylmethane as an inter-
product was obtained. Addition of all reagents in one por-
tion was also ineffective (10% yield). Moreover, the reac-
tion was completely inhibited in the absence of water
because of the low solubility of K2CO3 in toluene. These
results imply that stirring the mixture of silicone and aq
K2CO3 at r.t. for 1 h before addition of the palladium cat-
alyst and an aryl chloride plays an important role in form-
ing the active oligosiloxane to promote the cross-coupling
reaction effectively.
nal standard.
c The reaction was carried out using TBAF (1.5mmol) in 1,4-dioxane
at 100 °C.
In general, electron-deficient aryl chlorides are more reac-
tive than electron-rich counterparts because the oxidative
addition of the former will occur faster.7 Nevertheless, the
obtained results were rather unusual in that activated aryl
Synlett 2003, No. 12, 1850–1852 © Thieme Stuttgart · New York

1852
T. Koike, A. Mori
LETTER
2137. (g) Mowery, M. E.; DeShong, P. J. Org. Chem. 1999,
64, 1684. (h) Denmark, S. E.; Wehrli, D. Org. Lett. 2003, 5,
1357; and references cited therein. (i) Mori, A.; Danda, Y.;
Fujii, T.; Hirabayashi, K.; Osakada, K. J. Am. Chem. Soc.
2001, 123, 10774. (j) For a review: Organosilicon
Compounds in Cross-Coupling Reactions, see: Hiyama, T.
In Metal-Catalyzed Cross-Coupling Reactions; Diederich,
F.; Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998, 421.
(4) Recent palladium-catalyzed cross-coupling reaction of aryl
chlorides using organometallic reagents, see: (a) Old, D.
W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1998,
120, 9722. (b) Littke, A. F.; Schwarz, L.; Fu, G. C. Angew.
Chem. Int. Ed. 1998, 37, 3387. (c) Zhang, C.; Huang, J.;
Trudell, M. L.; Nolan, S. P. J. Org. Chem. 1999, 64, 3804.
(d) Littke, A. F.; Fu, G. C. Angew. Chem. Int. Ed. 1999, 38,
2411. (e) Wolfe, J. P.; Buchwald, S. L. Angew. Chem. Int.
Ed. 1999, 38, 2413. (f) Hagiwara, E.; Gouda, K.; Hatanaka,
Y.; Hiyama, T. Tetrahedron Lett. 1997, 38, 439. (g) Gouda,
K.; Hagiwara, E.; Hatanaka, Y.; Hiyama, T. J. Org. Chem.
1996, 61, 7232.
chlorides like 2f or 2g still remained after 48 h (entries 5
and 6) although unactivated chloroarenes such as 2b was
completely consumed within 29 h under analogous
conditions to give the coupling product in superior yields
(entry 1). Such a phenomenon was also observed when 2a
or 2f was used as a coupling partner of the cross-coupling
reaction with alkenylsiloxane (after stirring for 48 h).
These results suggest that rate-determining step of the
reaction using K2CO3 between silicone and activated
chloroarenes may not be oxidative addition of the aryl
chloride but transmetalation of the organic group of the
silicone reagent.9
In conclusion, we have shown that aryl chlorides that are
less expensive substrate than aryl iodides or bromides are
effective for the cross-coupling reaction of silicone.
Aqueous K2CO3, which is an inexpensive and weak inor-
ganic base, affected cross coupling of aryl chlorides with
silicone. Although the present reaction requires high tem-
perature, silicone would be an attractive reagent due to
their ease of handling, low toxicity, and a low cost com-
pared to another main group organometallic reagent such
as boron or tin.
(5) PdCl2(PCy3)2 was prepared according to the literature
procedure, see : Grushin, V. V.; Alper, H. Organometallics
1993, 12, 1890.
(6) Available from Aldrich Chemicals Co. as TBAF·xH2O.
(7) (a) Grushin, V. V.; Alper, H. Chem. Rev. 1994, 94, 1047.
(b) Littke, A. F.; Fu, G. C. Angew. Chem. Int. Ed. 2002, 41,
4176.
(8) Typical Experimental Procedure for the Cross-Coupling
Reaction: To a toluene (3 mL) solution of [Ph(Me)SiO]n (1,
204 mg, 1.5 mmol) was added K2CO3 (414 mg, 3.0 mmol) in
water (0.5 mL). After stirring at r.t. for 1 h, 1-chloro-4-
methoxybenzene (2a, 43 mg, 0.3 mmol) and PdCl2(PCy3)2
(11 mg, 0.015 mmol) were added and then the resulting
yellow mixture was stirred at 120 °C for 39 h. After cooling
the mixture to r.t., the organic layer was separated and
aqueous layer was extracted with Et2O (2 × 10 mL). The
combined organic layer was washed with 1 M HCl (10 mL),
sat. aq NaHCO3 (10 mL), and brine (10 mL) and then dried
over anhyd MgSO4. Removal of the solvent left a crude oil,
which was purified by chromatography on silica gel (reverse
phase, MeOH–H2O = 3:1) to yield 52.5 mg of 4-methoxy-
biphenyl (95%).
Acknowledgement
This work was supported by a Giant-in-aid for Scientific Research
(No. 13650915) from Japan Society for the Promotion of Science.
References
(1) (a) Mori, A.; Suguro, M. Synlett 2001, 845. (b) Average
mol. wt of 1 employed is ca. 2500-2700.
(2) Koike, T.; Du, X.; Mori, A.; Osakada, K. Synlett 2002, 301.
(3) (a) Hirabayashi, K.; Kawashima, J.; Nishihara, Y.; Mori, A.;
Hiyama, T. Org. Lett. 1999, 1, 299. (b) Hirabayashi, K.;
Kondo, T.; Toriyama, F.; Nishihara, Y.; Mori, A. Bull.
Chem. Soc. Jpn. 2000, 73, 985. (c) Nishihara, Y.;
Ikegashira, K.; Hirabayashi, K.; Ando, J.-i.; Mori, A.;
Hiyama, T. J. Org. Chem. 2000, 65, 1780. (d) Fujii, T.;
Koike, T.; Mori, A.; Osakada, K. Synlett 2002, 295.
(e) Fujii, T.; Koike, T.; Mori, A.; Osakada, K. Synlett 2002,
298. (f) Mowery, M. E.; DeShong, P. Org. Lett. 1999, 1,
(9) The related mechanism has also been proposed in the Stille
coupling reaction of chloroarenes: Bedford, R. B.; Cazin, C.
S. J.; Hazelwood, S. L. Chem. Commun. 2002, 2608.
Synlett 2003, No. 12, 1850–1852 © Thieme Stuttgart · New York