Intramolecularly activated vinylsilanes: Fluoride-free cross-coupling of (Z)-β-(trialkylsilyl)acrylic acids

Article abstract of DOI:10.1055/s-2004-836033

The fluoride-free palladium-catalyzed cross-coupling reaction of trialkyl(vinyl)silanes activated by the intramolecular pentacoordination of carboxylic acid at the Z-β-position is described.

Full text of DOI:10.1055/s-2004-836033

176
LETTER
Intramolecularly Activated Vinylsilanes: Fluoride-Free Cross-Coupling of
(Z)-b-(Trialkylsilyl)acrylic Acids
Intramolecularly
A
ctiv
i
ated
V
t
s
Institute of Health Biosciences, The University of Tokushima Graduate School, Sho-machi 1, Tokushima 770-8505, Japan
Fax +81(88)6337294; E-mail: shindo@ph.tokushima-u.ac.jp.
Received 13 October 2004
R1
R2
Si
R1
R2
Ar
Abstract: The fluoride-free palladium-catalyzed cross-coupling re-
action of trialkyl(vinyl)silanes activated by the intramolecular pen-
tacoordination of carboxylic acid at the Z-b-position is described.
Pd
Previous
methods
+
Ar-I
(F–)
X
Me2
X = F, Cl, OR, OH, H, 2-Py, 2-thienyl, Bn
Key words: alkenes, carboxylic acids, cross-coupling, palladium,
silicon
OH
R1
R2
CO2H
Ar
R1
R2
Pd
O
Our
Method
+
Ar-I
The palladium-catalyzed Hiyama coupling of organosili-
con compounds with organic halides is an important
method for producing carbon-carbon bonds. Unlike some
organometallic reagents employed in cross-coupling pro-
cesses, organosilicon compounds are usually easier to
handle and/or possess low toxicity.1 Since trialkyl-substi-
tuted alkenylsilanes generally are extremely stable to
chemical manipulation prior to fluoride activation, they
do not readily undergo productive cross-coupling.1,2 Al-
kenylsilanes with heteroatom substituents are essential for
efficient reactivity, but they are sensitive to acidic or basic
hydrolysis.1,3 In recent years, the alkenylsilanes with 2-
non-F
SiMe3
Scheme 1 Palladium-catalyzed cross-coupling of organosilicon
compounds.
by Pd2(dba)3·CHCl3 provided the desired cross-coupling
product 2a along with fair amounts of the undesired pro-
todesilylation product 3a. To facilitate the cross-coupling
process, various additives were surveyed with
Pd2(dba)3·CHCl3. We found that when Cs2CO3 was em-
ployed as an activator, the coupling product 2a was ob-
tained in good yield (Table 1, entry 1).5d The ligands
[PPh3, 7%; P(o-tolyl)3, 29%; P(2-furyl)3, 17%; P(OEt)3,
9%; AsPh3, 43%] were not effective in the cross-coupling
reaction with 4-chloro-iodobenzene (Table 1, entry 5).
pyridyl,4a
2-thienyl,4b
benzyl,4c
hydride4d
and
silacyclobutane4e,f have been used in palladium-catalyzed
cross-coupling (Scheme 1). However, a common limita-
tion of the aforementioned silicon based coupling reac-
tions is the use of fluoride as the promoter, which would
be incompatible in a complex molecule synthesis where
one of the coupling partners contained silyl protective
groups. The development of a mild and convenient, non-
fluoride promoted system would therefore be highly de-
sirable.5 Herein, we describe a fluoride-free palladium-
catalyzed cross-coupling reaction of (Z)-b-(trialkyl-
silyl)acrylic acids activated by intramolecular pentacoor-
dination to silicon.
With the optimized reaction conditions [Pd2(dba)3·CHCl3/
Cs2CO3 in DME at 60 °C] in hand, we then investigated
the scope and limitations of the reaction with a variety of
aryl iodides (Table 1).9 The 4-substituted aryl iodides
containing electron-withdrawing substituents exhibited
similar reactivity to that of iodobenzene (entries 3 and 5).
In contrast, the use of substrates with an electron-donating
group resulted in relatively low yields (entries 6 and 7)
while the other (Z)-b-(trimethylsilyl)acrylic acids (1b–e)
gave similar products in good to moderate yields (entry 8–
12). The use of Pd(Pt-Bu3)2 instead of Pd2(dba)3·CHCl3
also gave coupling products (entries 2, 4, 11, and 12).10 As
for 1d, Pd(Pt-Bu3)2 was clearly superior to
Pd2(dba)3·CHCl3 (entries 10 and 11). Pd(Pt-Bu3)2 was also
highly suitable for the reaction of 1e (entry 12), since use
of Pd2(dba)3·CHCl3 resulted in only the protodesilylation
product. In all cases, the reaction conditions were depen-
dent on the substrates. It is worth noting that even with
these sterically hindered alkenylsilanes, cross-coupling
still proceeded.11
Recently, we found a direct electrophilic cleavage of a sil-
icon-carbon bond activated by intramolecular pentacoor-
dination of the carbonyl oxygen to (Z)-b-silylacrylic
acids,6 prepared by stereoselective olefination of acylsi-
lanes with ynolates.7 This result, which can be considered
as an activation method for intrinsically stable C-Si
bonds, led us to postulate that (Z)-b-(trialkylsilyl)carbox-
ylic acids would undergo cross-coupling reactions with
aryl halides to afford tetrasubstituted olefins.8
Initial investigation of the cross-coupling of (Z)-b-(tri-
methylsilyl)acrylic acid 1a with iodobenzene catalyzed
The cross-coupling reaction did not occur at all using the
methyl ester of 1a and trimethyl(vinyl)silane 4, indicating
perhaps that the presence of a carboxylic acid at the Z-b-
SYNLETT 2005, No. 1, pp 0176–0178
Advanced online publication: 29.11.2004
DOI: 10.1055/s-2004-836033; Art ID: U28104ST
0
5.
0
1.
2
0
0
5
© Georg Thieme Verlag Stuttgart · New York

LETTER
Intramolecularly Activated Vinylsilanes
177
Table 1 Cross-Coupling Reaction of (Z)-b-(Trimethylsilyl)acrylic Acid 1 with Aryl Halide
A : Pd2(dba)3
•CHCl3
R1
CO2H
R1
CO2H
R1
CO2H
H
+
+
Ar-I
B : Pd(PtBu3)2
R2
SiMe3
R2
Ar
R2
1
2
3
Entry
1
1
R1
R2
Ar
Methoda
2
Yield (%) of 2 Yield (%) of 3b
1a
1a
1a
1a
1a
1a
1a
1b
1c
1d
1d
1e
Me
Me
Me
Me
Me
Me
Me
Bu
i-Pr
Ph
Bn
Bn
Bn
Bn
Bn
Bn
Bn
Me
Me
Me
Me
Ph
A
B
A
B
A
A
A
A
A
A
B
B
2a
2a
2b
2b
2c
2d
2e
2f
72
51
65
50b
66
46
47
58
46
40
73
70
6
15
3
2
Ph
3
4-CF3C6H4-
4-CF3C6H4-
4-ClC6H4-
4-MeOC6H4-
4-MeC6H4-
Ph
4
9
5
7
6
7
7
3
8
4
9
Ph
2g
2h
2h
2i
4
10
11
12
Ph
15
15
29
Ph
Ph
Ph
4-MeOC6H4-
Ph
a Method A: The reactions were performed at 60 °C using 1 (1.0 equiv), aryl halide (1.5 equiv), Cs2CO3 (5.0 equiv), and Pd2(dba)3·CHCl3 (5
mol%) in DME. Method B: The reactions were performed at 60 °C using 1 (1.0 equiv), aryl halide (1.5 equiv), aq Cs2CO3 (5.0 M, 5.0 equiv),
and Pd(Pt-Bu3)2 (5 mol%) in THF.
b Determined by 1H NMR.
position is important for efficient reactivity. We propose to carbon-carbon bond formation to produce tetrasubsti-
that coordination of the carboxylate anion to the silicon tuted alkenes (Scheme 3).
center may increase the pentacoordinate siliconate
concentration, which accelerates transmetallation
(Scheme 2). Although it is possible that an intramolecular
transmetallation through the alkoxypalladium complex 5
is involved,12 we have not yet clarified the detailed
mechanism.
Ph
CO2H
Ph
Br
NBS
LiOAc
Ph
Ph
CH3CN/ H2O
microwave
MeO
6
2i
MeO
92% (Z:E = 5:95)
OH
O
Scheme 3 Transformation of carboxylic acid to alkenyl halide.
R1
R2
R1
R2
Ar-Pd-I
Base
O
O
2
We also investigated the synthesis of tamoxifen, which is
one of the most important drugs in clinical use today for
the treatment of breast cancer (Scheme 4).14 Using the
Stille coupling of 6, followed by selective hydrogenation
of 7 with Wilkinson’s catalyst, we were able to produce
the alkene 8, which is the intermediate in the synthesis of
(Z)-tamoxifen reported by Miller.15
transmetallation
Me
Me
SiMe3
Si
Me
1
O
R1
R2
Me
O
Pd-Ar
Bn
SiMe3
SiMe3
4
5
Ph
Ph
Scheme 2 Proposed mechanism.
a
b
6
Ph
Ph
To show the synthetic utility of our methodology, we next
examined the transformation of the coupling products.
Carboxylic acid 2i underwent a modified Hunsdiecker re-
MeO
MeO
7
8
Scheme
4
Reagents and conditions: (a) Tributylvinyltin,
action with NBS13 to afford the bromoalkene 6, which is a Pd2(dba)3·CHCl3, P(2-furyl)3, DMF, 80 °C, 68% (Z:E = 94:6); (b)
RhCl(PPh3)3, H2, benzene, r.t., 64% (Z:E = 97:3).
useful intermediate since alkenyl halides can be subjected
Synlett 2005, No. 1, 176–178 © Thieme Stuttgart · New York

178
M. Shindo et al.
LETTER
(6) Shindo, M.; Matsumoto, K.; Shishido, K. Angew. Chem. Int.
Ed. 2004, 43, 104.
(7) (a) Shindo, M.; Matsumoto, K.; Mori, S.; Shishido, K. J. Am.
Chem. Soc. 2002, 124, 6840. For reviews on ynolates, see:
(b) Shindo, M. Synthesis 2003, 2275. (c) Shindo, M. Chem.
Soc. Rev. 1998, 27, 367.
(8) Takeda reported a copper(I) tert-butoxide-promoted cross-
coupling reaction of (Z)-b-(trimethylsilyl)allylic alcohols
with aryl and alkenyl halides. See: Taguchi, H.; Ghoroku,
K.; Tadaki, M.; Tsubouchi, A.; Takeda, T. J. Org. Chem.
2002, 67, 8450.
(9) General Procedure for the Cross-Coupling Reaction of a
(Z)-b-(Trimethylsilyl)acrylic Acid 1a with Iodobenzene.
To a solution of 1a (35 mg, 0.141 mmol) and Cs2CO3 (230
mg, 0.705 mmol) in DME (10 mL) were added sequentially
iodobenzene (43 mg, 0.211 mmol) and Pd2 (dba)3·CHCl3 (7
mg, 0.00705 mmol) at room temperature. After the mixture
was stirred at 60 °C for 22 h, the solvents were evaporated to
give a residue, which was diluted with CH2Cl2 and acidified
with 6 M HCl (aq). The mixture was extracted with CH2Cl2,
and the combined organic layer was washed with H2O and
brine, and dried over MgSO4. The organic phase was
concentrated in vacuo to give a crude product, which was
purified by silica gel column chromatography (hexane–
EtOAc, 10–25%) to afford 27 mg of a mixture of 2a (72%)
and 3a (6%). After recrystallization from CCl4–hexane,
compound 2a was isolated as colorless needles. (Z)-2-
Methyl-3,4-diphenyl-2-butenoic acid (2a):6 mp 107.6–108.0
°C. 1H NMR (400 MHz, CDCl3): d = 2.14 (s, 3 H), 3.83 (s, 2
H), 7.01–7.08 (m, 4 H), 7.13–7.24 (m, 6 H). IR (CHCl3):
3062, 1691 cm–1.
In conclusion, we have developed a fluoride-free cross-
coupling reaction of (Z)-b-(trialkylsilyl)acrylic acids with
aryl iodides. These results demonstrate the synthetic util-
ity of the C-Si bond activation by intramolecular pentaco-
ordination to silicon. We have also demonstrated that the
coupling products can be transformed into alkenyl ha-
lides, which are useful for the preparation of multisubsti-
tuted alkenes. Since (Z)-b-(trimethylsilyl)acrylic acids are
extremely stable and easily prepared by olefination of
acylsilanes with ynolates, this process should have great
synthetic potential.
Acknowledgment
This work was supported in part by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports, Science
and Technology, Japan. We also thank the Japan Society for the
Promotion of Science (JSPS) for a research fellowship.
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Synlett 2005, No. 1, 176–178 © Thieme Stuttgart · New York