Improved synthesis of aryltrialkoxysilanes via treatment of aryl Grignard or lithium reagents with tetraalkyl orthosilicates

Article abstract of DOI:10.1021/jo048667h

General reaction conditions for the synthesis of aryl(trialkoxy)silanes from aryl Grignard and lithium reagents and tetraalkyl orthosilicates (Si(OR)₄) have been developed. Ortho-, meta-, and para-substituted bromoarenes underwent efficient metalation and silylation at low temperature to provide aryl siloxanes. Mixed results were obtained with heteroaromatic substrates: 3-bromothiophene, 3-bromo-4-methoxypyridine, 5-bromoindole, and N-methyl-5-bromoindole underwent silylation in good yield, whereas a low yield of siloxane was obtained from 2-bromofuran, and 2-bromopyridine failed to give silylated product. The synthesis of siloxanes via organolithium and magnesium reagents was limited by the formation of di- and triarylated silanes (Ar ₂Si(OR)₂ and Ar₃SiOR, respectively) and dehalogenated (Ar-H) byproducts. Silylation at low temperature gave predominantly monoaryl siloxanes, without requiring a large excess of the electrophile. Optimal reaction conditions for the synthesis of siloxanes from aryl Grignard reagents entailed addition of arylmagnesium reagents to 3 equiv of tetraethyl- or tetramethyl orthosilicate at -30 °C in THF. Aryllithium species were silylated using 1.5 equiv of tetraethyl- or tetramethyl orthosilicate at -78 °C in ether.

Full text of DOI:10.1021/jo048667h

Improved Synthesis of Aryltrialkoxysilanes via Treatment of Aryl
Grignard or Lithium Reagents with Tetraalkyl Orthosilicates
Amy S. Manoso, Chuljin Ahn,† Arash Soheili, Christopher J. Handy, Reuben Correia,
W. Michael Seganish, and Philip DeShong*
Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742
deshong@umd.edu
Received August 2, 2004
General reaction conditions for the synthesis of aryl(trialkoxy)silanes from aryl Grignard and lithium
reagents and tetraalkyl orthosilicates (Si(OR)4) have been developed. Ortho-, meta-, and para-
substituted bromoarenes underwent efficient metalation and silylation at low temperature to provide
aryl siloxanes. Mixed results were obtained with heteroaromatic substrates: 3-bromothiophene,
3-bromo-4-methoxypyridine, 5-bromoindole, and N-methyl-5-bromoindole underwent silylation in
good yield, whereas a low yield of siloxane was obtained from 2-bromofuran, and 2-bromopyridine
failed to give silylated product. The synthesis of siloxanes via organolithium and magnesium
reagents was limited by the formation of di- and triarylated silanes (Ar2Si(OR)2 and Ar3SiOR,
respectively) and dehalogenated (Ar-H) byproducts. Silylation at low temperature gave predomi-
nantly monoaryl siloxanes, without requiring a large excess of the electrophile. Optimal reaction
conditions for the synthesis of siloxanes from aryl Grignard reagents entailed addition of
arylmagnesium reagents to 3 equiv of tetraethyl- or tetramethyl orthosilicate at -30 °C in THF.
Aryllithium species were silylated using 1.5 equiv of tetraethyl- or tetramethyl orthosilicate at
-78 °C in ether.
SCHEME 1
Introduction
The metal-catalyzed cross-coupling reaction for the
formation of carbon-carbon bonds between unsaturated
centers is an indispensable synthetic tool for the prepara-
tion of useful industrial and pharmaceutical materials.
Of the many combinations of organometallic nucleophiles
and organic electrophiles in the literature,1-3 the Stille4
(organostannane) and Suzuki-Miyaura5 (organoborane)
coupling methodologies are the most widely employed for
the synthesis of unsymmetrical biaryl derivatives and
substituted alkenes due to the generally excellent yields,
high stereoselectivities, and superior functional group
tolerance (Scheme 1). Nonetheless, arylsilane derivatives
have emerged as powerful alternatives to conventional
arylmetalloids for the Pd(0)-catalyzed aryl-aryl coupling
reaction with organohalides and organo(pseudo)halides.
Aryl silanes avoid the inherent limitations associated
with traditional methodologies: the Stille tin reagents
and byproducts are toxic, and the Suzuki boron reagents
can be difficult to synthesize and purify.
Previous studies from our group6-14 and others15-22
have shown that a variety of silicon derivatives undergo
fluoride-mediated, Pd(0)-catalyzed aryl group transfer
(6) Mowery, M. E.; DeShong, P. J. Org. Chem. 1999, 64, 1684-1688.
(7) Mowery, M. E.; DeShong, P. J. Org. Chem. 1999, 64, 3266-3270.
(8) Mowery, M. E.; DeShong, P. Org. Lett. 1999, 1, 2137-2140.
(9) Handy, C. J.; Mowery, M. E.; DeShong, P. Pure Appl. Chem.
2000, 72, 1655-1658.
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8109.
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1143.
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6795.
* To whom correspondence should be addressed. Tel: 301-405-1892.
Fax: 301-314-9121.
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1478.
† Current address: Department of Chemistry, Changwon National
University, Changwon 641-1870, Korea.
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Commun. 1997, 14, 1309-1310.
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10.1021/jo048667h CCC: $27.50 © 2004 American Chemical Society
Published on Web 10/26/2004
J. Org. Chem. 2004, 69, 8305-8314
8305

Manoso et al.
SCHEME 2
siloxanes via the organometallic approach has several
advantages, including the commercial availability, low
cost, and ease of handling and storage of tetraalkoxy-
orthosilicates.43 The use of SiCl4 as the silicon electrophile
is of limited practicality for a number of reasons that
include (a) moderate to poor product yield for the overall,
two-step conversion, (b) the difficult transfer and han-
dling of moisture-sensitive reagents and intermediates,
and (c) multiple substitution results in the formation of
difficult to separate byproducts.26,30 In the past, large
quantities of electrophile (20+-fold excess) have been
employed to mitigate polyarylation; however, this leads
to difficulties in product isolation and HCl contamina-
tion.30 Treatment of the arylmetalloid with Cl-Si(OR)3
should favor the formation of monoaryl siloxanes by
preferential displacement of chloride from silicon.30,35-37
As reported in the literature, not only are the yields
somewhat better than the SiCl4/alcoholysis technique, but
the reaction involves a single step from the formation of
the organometalloid.37 However, use of Cl-Si(OR)3 as the
silicon electrophile still has several significant draw-
backs: (1) unlike SiCl4, Cl-Si(OR)3 compounds are not
commercially available and are tedious to prepare;44-46
(2) while less reactive than the tetrachloride, chloro-
(trialkoxy)silane reagents still require careful handling
to avoid hydrolysis of the reactive Si-Cl bond; and (3)
surprisingly, even when excess electrophile is used or low
temperatures are employed, over-arylation of silicon
occurs, resulting in inseparable di- and triarylated byprod-
ucts.30,43 Typically, the reaction of organometallic re-
agents with alkoxy silanes is more selective than the
reaction with chlorosilanes.43 Treatment of the arylmet-
alloid with the less reactive electrophile Si(OEt)4 should
favor the formation of monoaryl siloxanes because alkox-
ide is more difficult to displace from silicon than chloride.
For our studies, 4-methoxyphenylmagnesium bromide
was selected as the initial nucleophile to be inves-
tigated in the metalation methodology (Table 1). The in-
expensive, commercially available electrophiles tetra-
methyl orthosilicate (Si(OMe)4), tetraethyl orthosilicate
(Si(OEt)4), and tetrachlorosilane (SiCl4) were each evalu-
ated for their efficacy in the formation of the Si-Ar bond.
The results are summarized in Table 1. The temperature
at which the Grignard reagent was added to the electro-
phile had a marked effect on the reaction. As seen in
entries 1, 4, and 5, at temperatures above -30 °C a sig-
nificant amount of the diaryl(dialkoxy)silane impurity 4
was formed, although no triaryl(alkoxy)silane was ob-
served over the tested temperature range. The remainder
of the reaction mixture was anisole, which resulted from
the aqueous quench of unreacted arylmagnesium bro-
mide. However, longer reaction time or elevated temper-
reactions. These earlier reports have demonstrated the
relative mildness, wide-ranging functional group compat-
ibility, and ease of workup of the siloxane-based cross-
coupling process. However, the primary limitation of the
siloxane protocol is the synthesis of the aryl siloxane
reagents. Existing methods for the synthesis of aryl
siloxanes fall into two categories: (1) treatment of an aryl
Grignard or lithium reagent with a silicon electrophile
(Scheme 2) and (2) silylation of an aryl iodide or bromide
by triethoxysilane (H-Si(OEt)3) in the presence of a
Pd(0)23,24 or Rh(I)25 catalyst. The metalloid reaction, as
presently constituted, is limited by the generally inferior
yields of siloxane, most likely due to competing formation
of di- and triarylated products (over-arylation). A general
method for the synthesis of arylsiloxanes from aryl-
lithium or magnesium reagents has not been reported,
nor has a systematic study of this reaction been per-
formed. We recently reported the preparation of ortho-
substituted aryl siloxanes using directed orthometalation
protocols.14 The goal of the study reported herein was to
develop a practical, general synthetic technique for the
synthesis of aryl(trialkoxy)silanes utilizing standard
organometallic reagents generated from the correspond-
ing aryl halide by metal-halogen exchange.
Results and Discussion
Traditionally, the synthesis of aryl siloxanes has been
accomplished by the treatment of Grignard or organo-
lithium reagents with either SiCl4 (followed by
alcoholysis),16,26-34 Cl-Si(OR)3,30,35-37 or Si(OR)4.16,29,34,36,38-42
The use of Si(OR)4 for the one-step preparation of aryl-
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Jutzi, P. J. Organomet. Chem. 1996, 521, 177-184.
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Chemistry; John Wiley & Sons: New York, 2000.
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8306 J. Org. Chem., Vol. 69, No. 24, 2004

Improved Synthesis of Aryltrialkoxysilanes
TABLE 1. Optimization of the Synthesis of
Arylsiloxanes Using 4-Methoxyphenyl Magnesium
Bromide
Only trace amounts of diaryl(dialkoxy)silane contami-
nants were observed for all entries. Again, the remaining
yield was of reduced (dehalogenated) aryl halide. As
expected, tetramethyl orthosilicate and tetraethyl ortho-
silicate worked equally well (entries 1 and 2, 6 and 7).
Surprisingly, the results were comparable with o-, m-,
and p-substituted anisyl and tolyl Grignard reagents
(entries 2-4, and 7-9, respectively); all yields were
approximately 80%. Also, 3,4-(methylenedioxy)bromoben-
zene underwent smooth conversion to the siloxane (entry
5, 74% yield). This result contradicts the findings of Selin
and co-workers, who observed acceptable yields of o- and
p- but not m-(triethoxysilyl)toluene. The reaction condi-
tions employed by Selin entailed addition of the Grignard
reagent to 2.0 equiv of tetraethyl orthosilicate at reflux.38
Several researchers have reported acceptable yields of
arylsiloxane using Barbier reaction conditions, the in situ
formation of the reactive Grignard intermediate in the
presence of the silicon electrophile.36,47-49 Ideally, Barbier
conditions are a method of controlling multiple substitu-
tion at silicon, because the Grignard reagent is im-
mediately consumed and never present in excess. For
example, Shea and co-workers combined magnesium
metal, a crystal of iodine, and 4 equiv of tetraethyl
orthosilicate and THF and brought the mixture to re-
flux.48 A solution of p-bromoanisole in THF was then
added slowly, and the mixture was allowed to reflux for
12 h; a 74% isolated yield of 4-(triethoxysilyl)anisole
was obtained without mention of byproducts. This re-
sult was not reproducible in our laboratories: under iden-
tical Barbier reaction conditions, only 50% yield at 80%
conversion was achieved; although no diarylated silane
was observed, the remaining yield was of reduced arene.
In continuing pursuit of our goal of synthesizing a
variety of highly functionalized siloxane derivatives for
use in aryl coupling reactions, we turned our efforts to
determining the scope and limitations of the synthesis
of aryl siloxanes from lithium reagents. For our studies,
4-lithiotoluene (Table 3) was selected as the initial nu-
cleophile for investigation of the formation of the Si-Ar
bond. The electrophile tetraethyl orthosilicate (Si(OEt)4)
was chosen for initial study, in lieu of tetramethyl ortho-
silicate (Si(OMe)4), which freezes at the low temperatures
required for the formation of aryllithium reagents, or
tetrachlorosilane (SiCl4), because the subsequent alco-
holysis step had proven to be problematic (low yielding
and complicated by polymerization). Both ether and THF
were evaluated for their suitability in the silylation of
aryllithium intermediates, although ether was the sol-
vent of choice for practical reasons. The higher-boiling
THF was preferred for the Grignard protocol because it
allowed for heating the reaction to initiate formation of
the Grignard reagent. The more reactive lithium reagents
rapidly decompose at ambient temperatures and do not
require higher-boiling solvents. The results of the sily-
lation reactions are shown in Table 3.
conditionsa
silane/equiv
yield (%)b,c
entry
T (°C)
3
4
1
2
3
4
5
6
7
8
Si(OMe)4/3.0
Si(OMe)4/3.0
Si(OMe)4/1.5
Si(OEt)4/3.0
Si(OEt)4/3.0
Si(OEt)4/3.0
Si(OEt)4/1.5
Si(Cl)4/3.0d
25
-30
-30
0
-10
-30
-30
-30
47
76
65
72
70
83
76
70d
47
3
4
23
23
3
2
3
a Reactions of p-methoxy magnesium bromide 2 (1.0 equiv) with
Si(OR)4 or SiCl4 (1.5 to 3.0 equiv) were allowed to stir at the given
temperature in THF. The reaction mixture was stirred at the
indicated temperature for 1 h and then at room temperature for
12 h. b GC yields were calculated using an internal standard
(naphthalene); see Experimental Section. c Remainder of the
product was anisole. d Yield of 4-(triethoxysilyl)anisole (3). The
crude, concentrated 4-(trichlorosilyl)anisole was converted to the
siloxane 3 by dropwise addition of the chlorosilane to EtOH/
pyridine at 0 °C.
ature did not improve the yield. In addition, the amount
of anisole remained constant regardless of the electro-
phile. It is likely that reduction occurs at least in part
during the in situ formation of the Grignard reagent.
The best result was obtained when the Grignard
reagent was treated at -30 °C with 3.0 equiv of the
electrophile Si(OEt)4 (83% yield, Table 1, entry 6); under
identical reaction conditions, Si(OMe)4 (76% yield, entry
2) and SiCl4 (followed by alcoholysis) (70%, entry 8) also
performed well (the yields were determined by GC
analysis). In contrast, Shibata observed a 60% yield of
siloxane using the two-step SiCl4/alcoholysis method for
the silylation of p-(4-propylcyclohexyl)phenylmagnesium
bromide but only a 35% yield of siloxane via direct
silylation with Si(OMe)4.16 The reaction conditions em-
ployed by Shibata were addition of the Grignard reagent
to 1.5 equiv of silane at 0 °C.16 In our study, a 2-fold
decrease in the concentration of the electrophile slightly
decreased the yield of the desired monoarylated silane
but surprisingly did not stimulate the formation of
diarylated byproduct (Table 1, entries 3 and 7).
Preliminary studies using commercial phenylmagne-
sium bromide indicated that increasing the concentration
of the electrophile from 3 to 5 to 30 equiv did not improve
the reaction outcome and only served to complicate
product isolation. Little reaction improvement was ob-
served with alternative ether solvents, and poor results
were obtained with toluene or hexane. Ultimately, THF
rather than lower-boiling Et2O was employed as the
solvent in order to facilitate in situ formation of the
Grignard reagent (which required heating to progress
efficiently).
(47) Jacob, S.; Popall, M.; Froehlich, L.; Kahlenberg, F.; Olma, K.
Patent: Procedure for Preparation of Styryl-Functionalized Silanes
(Fraunhofer-Gesellschaft zur Foerderung der Angewandten Forschung
e.V., Germany). Denmark Patent 10159859, 2001; Chem Abstr. 2003,
138, 899915.
(48) Pak, J. J.; Greaves, J.; McCord, D. J.; Shea, K. J. Organome-
tallics 2002, 21, 3552-3561.
(49) Blomberg, C. The Barbier Reaction and Related One-Step
Processes, 1st ed.; Springer-Verlag: Heidelberg, 1993.
To demonstrate the scope of the Grignard reaction, a
variety of substituted aryl bromides was examined (Table
2). The isolated yields obtained in our laboratories were
generally better than those reported in the literature.
J. Org. Chem, Vol. 69, No. 24, 2004 8307

Manoso et al.
TABLE 2. Synthesis of Aryl(trialkoxy)silanes Using Grignard Reagents
a Reactions of arylmagnesium bromide 2 (1.0 equiv) with Si(OEt)4 or Si(OMe)4 (3.0 equiv) were allowed to stir at -30 °C in THF for
1 h and then at room temperature for 12 h. b Yields of 3 are after distillation (purity > 95%). The remainder of the product was of the
reduced (dehalogenated) arene.
TABLE 3. Optimization of the Synthesis of
Arylsiloxanes Using 4-Lithiotoluene
although diarylated silane 4 was formed. As in the
Grignard reaction, reduction (dehalogenation) of the
starting material also was observed. At low temperature,
the reaction was essentially insensitive to the solvent
(Et2O and THF were tolerated, entries 4 and 5) and only
a small excess of the electrophile was needed (1.5-3.0
equiv were equally effective, entries 5 and 6).
The best result was obtained when the lithium reagent
in ether was added to 3.0 equiv of the electrophile
Si(OEt)4 at -78 °C (86% yield, entry 6). Experience
garnered applying these reaction conditions to other
substrates would show that more than 1.5 equiv was
unnecessary to achieve the optimum yield of siloxane.
The electrophile and the lithium reagent were allowed
to stir at -78 °C until the reaction ceased to progress.
Quenching the reaction at -78 °C before allowing the
mixture to slowly warm to room-temperature mitigated
formation of di- and triarylated byproducts.
To demonstrate the scope of the optimized silylation
reaction, a variety of substituted aryl bromides were
examined (Table 4). Only trace amounts of diaryl-
(dialkoxy)silane contaminants were observed for most
entries; again, the remaining yield was of reduced
(dehalogenated) aryl halide. The best results were ob-
tained with less reactive (less electron-rich) aryllithium
derivatives: the less electron-rich tolyl series (entries
1-3) and electron-neutral phenyl (entry 4) outperformed
the more electron-rich anisyl/thioanisyl series (entries
5-8). Bearing two electron-donating substituents, the
3,4-(methylenedioxy)phenyllithium intermediate (entry
9) proved to be highly reactive: the major product was
the diarylated silane. Reducing the temperature to -110
°C or increasing the concentration of Si(OEt)4 failed to
improve the yield. Note that the analogous Grignard
conditionsa
yield (%)b,c
entry
equiv of Si(OEt)4
solvent
T (°C)
3
4
5
1
2
3
4
5
6
1.5
1.5
1.5
1.5
1.5
3.0
THF
THF
Et2O
THF
Et2O
Et2O
0
-30
-30
-78
-78
-78
7
25
12
6
54
1
74
77
81
82
86
0
9
0
5
3
1
1
a Reactions of p-tolyllithium
2 (1.0 equiv) with Si(OEt)4
(1.5-3.0 equiv) were allowed to stir at the given temperature; the
reaction was complete in 1 h. b GC yields were calculated using
an internal standard (naphthalene); see Experimental Section.
c Remainder of the product was toluene.
Like the Grignard approach, the temperature at which
the lithium reagent was added to the electrophile dra-
matically effected the reaction outcome. As seen in
entries 1-3, at temperatures above -78 °C a significant
amount of the diaryl(dialkoxy)silane impurity 4 was
formed. In addition, trialkylated product 5 was observed.
Note that the analogous transformation employing Grig-
nard reagents did not lead to the formation of trialkylated
products, because of the significantly lower reactivity of
Grignard reagents. At 0 °C (entry 1), the major product
was tris-p-tolyl(ethoxy)silane (5). In contrast, at -30 °C
(entries 2 and 3) and -78 °C (entries 4-6), formation of
the trialkylated silane 5 was effectively suppressed,
8308 J. Org. Chem., Vol. 69, No. 24, 2004

Improved Synthesis of Aryltrialkoxysilanes
TABLE 4. Synthesis of Aryl(trialkoxy)silanes Using Lithium Reagents
a Reactions of aryllithium 2 (1.0 equiv) with Si(OEt)4 (1.5 equiv) were allowed to stir at -78 °C for 1 h in Et2O. b Yields of 3
are after distillation or chromatography (purity > 95%). c Major product was Ar2Si(OEt)2. d GC analysis indicated a 2:1:1 ratio of
mono-:di-:triarylalkoxysilanes.
reagent underwent clean silylation (Table 2, entry 5),
affording 74% yield of triethoxy(3,4-methylenedioxy-
phenyl)silane. Again, as with magnesium reagents, the
reaction using aryllithium intermediates was insensitive
to the position of substituents: o-, m-, and p-substituted
arenes underwent silylation with equal efficiency (Table
4, entries 1-3 and 5-8).
Mixed results were obtained for silylation of heteroaro-
matic systems (entries 10-15). For example, acceptable
yields of siloxane were obtained from the corresponding
bromothiophene and indole derivatives (entries 10-12),
whereas silylation of 2-bromofuran was inefficient and
2-bromopyridine failed to give any of the desired siloxane
(entries 13 and 14). The yield of 2-(triethoxysilyl)furan
was compromised by the formation of di- and triarylated
products, indicating that 2-lithiofuran was successfully
formed in situ but was highly reactive. In contrast,
attempted silylation of 2-bromopyridine led to exclusive
formation of pyridine, indicating successful formation of
the organolithium intermediate but unsuccessful silyla-
tion. The nearly quantitative formation of 2-lithiopyridine
under our reaction conditions was confirmed by capture
with the more reactive electrophiles TMS-Cl and benz-
aldehyde. In an effort to increase the nucleophilicity of
the pyridine metalloid, silylation of 3-bromo-4-methoxy-
pyridine (entry 15) was attempted with dramatic results.
The desired monopyridinyl siloxane was isolated in 25%
yield, in addition to significant quantities of dipyridinyl-
and tripyridinyl siloxanes.50
The results with pyridine derivatives were not surpris-
ing given the literature precedence. Using analogous
reaction conditions, Schmidbaur and co-workers synthe-
sized 2- and 3-(triethoxysilyl)pyridine in 10 and 16%
yield, respectively.51 Zeldin carefully examined the syn-
thesis of 3-pyridinyl-substituted ethoxysilane monomers,
focusing on the preparation of diethoxy(methyl)(3-pyridi-
nyl)silane (PyrSiMe2(OEt)).30 A variety of silicon electro-
philes were evaluated, most notably MeSiCl3 (followed
by alcoholysis), MeSi(OEt)2Cl, and MeSi(OEt)3, under
different metalation conditions. Three significant conclu-
sions were drawn: (1) MeSi(OEt)3 (3 equiv) was ideal for
the methyl(diethoxy)silylation of 3-pyridinylmagnesium
(50) Handy, C. J. Doctoral Dissertation, University of Maryland,
College Park, Maryland, 2002.
(51) Riedmiller, F.; Jockisch, A.; Schmidbaur, H. Organometallics
1998, 17, 4444-4453.
J. Org. Chem, Vol. 69, No. 24, 2004 8309

Manoso et al.
SCHEME 3
bromide, yielding 45% of the desired monosubstitution
product and no diarylated adduct; (2) in contrast, a
20-fold excess of MeSiCl3 was required to mitigate
multiple substitution by 3-lithiopyridine and, as with
MeSi(OEt)2Cl, still yielded a significant amount of the
diarylated silane and led to the formation of mixed
silanes and silicates; and (3) the use of pyridinyllithium
reagents led to the formation of a pentacoordinate anionic
species between the silane product and LiOEt formed in
the displacement reaction.30 Zeldin obtained the best
results when the pyridinyl Grignard reagent was gener-
ated under Barbier conditions; in fact, when the pre-
formed 3-pyridinylmagnesium bromide was treated with
MeSi(OEt)3, no reaction was observed.30 Given that
pyridinyl Grignard reagents are reputed to be unreactive
toward most electrophiles,52,53 Zeldin’s result is striking.
Unfortunately in our laboratories, using the Barbier
reaction conditions reported by Zeldin but substituting
Si(OEt)4 as the electrophile led to unsuccessful prepara-
tion of 3-(triethoxy)pyridine. The only products obtained
were the homocoupled product 3,3′-dipyridyl and pyri-
dine. Homocoupling (Wurtz-type coupling) is a common
side-reaction of organomagnesium reagents.54
With both Grignard and lithium reagents, the forma-
tion of di- and triarylated silanes was best controlled by
employing reduced reaction temperatures. In contrast,
change of solvent or the use of large excesses of the
electrophile had relatively little impact on the reaction
outcome. It is unlikely that the temperature effect
observed in the arylation is due solely to the attenuation
of organometalloid reactivity at reduced temperature.
Contrary to expectation, lower temperatures have been
shown to increase the reactivity of the organometallic
species toward electrophiles by causing deaggregation of
the organometalloid.54 This phenomenon would clearly
favor multiple arylation of the silane. Instead, a reduction
in diarylation was observed when the temperature was
reduced; therefore, the reactivity of the nucleophile must
not be greatly altered within the temperature range
studied. In fact, it has been observed that phenyllithium
does not change its aggregation state until temperatures
as low as -100 °C are reached.54
of a second aryl nucleophile on the pentacoordinate
silicate 7 to form hexacoordinate intermediate 9 or attack
on the tetracoordinate monoaryl silane 8.
Again, it was observed that at lower temperatures the
formation of diaryl products was minimal. We propose
that at reduced temperature, the pentacoordinate silicate
7 formed by initial attack of the metalloid reagent does
not decompose (with loss of alkoxide) to give the neutral
monoaddition product 8. The stable, anionic monoaryl
silicate 7 is less reactive than its neutral monoaryl silane
counterpart 8; in effect, the monoaryl silane 8 is “pro-
tected” as the pentacoordinate silane against multiple
arylation. This result is quite different than what has
been observed for chlorosilanes, where the analogous
pentacoordinate tetrachloroaryl silicate (Ar-SiCl4-) has
been found to be more reactive than the neutral tetra-
coordinate monoaryl silane (Ar-SiCl3).43,55,56
Conclusion
General reaction conditions for the synthesis of aryl-
(trialkoxy)silanes from aryl Grignard and lithium re-
agents and functionalized silanes have been developed.
Although examples in the literature have described the
use of a range of silicon electrophiles (including SiCl4 and
Cl-Si(OR)3), our studies have demonstrated that tet-
raalkyl orthosilicates (Si(OR)4) allow for the most direct
and convenient synthesis of arylsiloxanes in that they
are commercially available, inexpensive, and air and
moisture stable and generally give an excellent yield of
the desired siloxanes without subsequent transforma-
tions (i.e., conversion of the trichlorosilane to the silox-
ane). Using the reaction conditions developed herein, we
observed o-, m-, and p-substituted bromoarenes to un-
dergo efficient metalation and silylation. Mixed results
were obtained with heteroaromatic substrates: 3-bro-
mothiophene, 3-bromo-4-methoxypyridine, 5-bromoin-
dole, N-methyl-5-bromoindole all underwent silylation in
good yield, whereas low yields of siloxanes were obtained
from 2-bromofuran and 2-bromopyridine failed to be
silylated. The key feature of these reactions was the use
of low temperatures during addition of the orthosilicate,
which allowed for the formation of predominantly
monoarylated siloxanes, without requiring more than
1.5-3.0 equiv of the electrophile.
The relative rates of reaction of alkoxysilanes with
organometallic reagents follows the order of silane
electrophilicity Si(OEt)4 > RSi(OEt)3 > R2Si(OEt)2
>
R3Si(OEt); the same order is observed with chlorosi-
lanes.43 Given the relative reactivities, polyarylation
should be stoichiometrically controllable or mitigated by
slow addition of the organometallic reagent to the elec-
trophile. On the contrary, even at low temperature, with
less than 1 equiv of organometallic reagent, diarylated
and even triarylated byproducts are observed, suggesting
that factors other than organometalloid reactivity or
electrophile electronics are at play.55
The accepted mechanism of alkylation comprises for-
mation of pentacoordinate adduct 7 as shown in Scheme
3.43,55,56 Diarylation is the result of either direct attack
(52) French, H. E.; Sears, K. J. Am. Chem. Soc. 1951, 73, 469-470.
(53) Fischer, F. C.; Havinga, E. Recl. Trav. Chim. Pays-Bas. 1965,
84, 439-439.
The methodology reported above can be employed for
the synthesis of highly functionalized aryl siloxane
(54) Schlosser, M. In Organometallics in Synthesis A Manual, 2nd
ed.; Schlosser, M., Ed.; John Wiley and Sons: New York, 2002; p
1-352.
(55) Gilman, H.; Brannen, C. J. Am. Chem. Soc. 1951, 73, 4640-
4641.
(56) Corriu, R. J. P.; Gue´rin, C.; Moreau, J. J. E. Top. Stereochem.
1984, 15, 43-198.
8310 J. Org. Chem., Vol. 69, No. 24, 2004

Improved Synthesis of Aryltrialkoxysilanes
funnel. The amber solution was washed with 3 × 25 mL of
water, dried over MgSO4, filtered, and concentrated in vacuo.
Purification of the residue by bulb-to-bulb distillation yielded
the siloxane.
derivatives for the siloxane coupling technologies, and
we have recently reported initial studies for the synthesis
of the antitumor antibiotics streptonigrin and lavenda-
mycin.12 Additional studies in this area are underway,
and as always, the results will be reported in due course.
2-(Triethoxysilyl)anisole (Table 2, Entry 1). The general
procedure for synthesis of siloxanes from Grignard reagents
was followed using 2-bromoanisole (935 mg, 623 µL, 5.00
mmol), magnesium turnings (134 mg, 5.50 mmol), and tetra-
ethyl orthosilicate (3.13 g, 3.35 mL, 15.0 mmol) in THF. Bulb-
to-bulb distillation (125 °C, 0.5 Torr) afforded 1.19 g (88%) of
2-(triethoxysilyl)anisole as a colorless oil: IR (neat) 3067 (m),
2967 (s), 2922 (s, 2891 (s), 2829 (m), 2780 (w), 2762 (w), 1590
(s), 1569 (s), 1459 (s), 1241 (s) cm-1; 1H (NMR) (CDCl3) δ 1.21
(t, J ) 7.2, 9H), 3.79 (s, 3H), 3.84 (q, J ) 7.2, 6H), 6.83 (d, J
) 8.2, 1H), 6.95 (t, J ) 7.2, 1H), 7.38 (m, 1H), 7.63 (dd, J )
1.6, 7.2, 1H); 13C (NMR) (CDCl3) δ 18.2, 55.1, 58.7, 109.6, 119.2,
120.5, 132.2, 137.5, 164.3; MS (m/z) 271 (M+ + 1, 42), 225 (100),
195 (21), 181 (36), 139 (25), 119 (21), 91 (24), 77 (14); HRMS
for C13H23O4Si calcd 271.1366 (M+ + 1), found 271.1354.
2-(Trimethoxysilyl)anisole (Table 2, Entry 2). The
general procedure for synthesis of siloxanes from Grignard
reagents was followed using 2-bromoanisole (935 mg, 623 µL,
5.00 mmol), magnesium turnings (134 mg, 5.50 mmol), and
tetramethyl orthosilicate (2.28 g, 2.21 mL, 15.0 mmol) in THF.
Bulb-to-bulb distillation (125 °C, 0.5 Torr) afforded 948 mg
(83%) of 2-(trimethoxysilyl)anisole as a colorless oil: IR (neat)
2970 (s), 2920 (m), 1570 (m), 1486 (w), 1078 (s) cm-1; 1H (NMR)
(CDCl3) δ 3.61 (s, 9H), 3.80 (s, 3H), 6.87 (d, J ) 8.3, 1H), 6.97
(t, J ) 7.2, 1H), 7.42 (m, 1H), 7.59 (dd, J ) 1.7, 7.2, 1H); 13C
NMR (CDCl3) δ 50.4, 54.9, 109.4, 117.7, 120.3, 132.2, 137.0,
164.1; MS (m/z) 228 (100), 196 (61) 167 (55), 137 (18), 121 (44),
91 (45), 58 (29); HRMS for C10H16O4Si calcd 228.0818, found
228.0809.
Experimental Section
Optimization of the Synthesis of 4-(Triethoxysilyl)-
anisole Using 4-Bromomagnesium Anisole (Table 1). A
10 mL, three-neck, pear-shaped flask was fitted with an
addition funnel, a reflux condenser, a rubber septum, and a
stir bar. The flask was then charged with freshly washed
magnesium turnings (134 mg, 5.50 mmol), flame-dried under
vacuum, and back-filled with argon. THF (1.0 mL) was added
to the magnesium turnings via syringe. The addition funnel
was charged with 4-bromoanisole (935 mg, 628 µL, 5.00 mmol)
in 2.0 mL of THF. The reaction was initiated by addition of
5-10 drops of the bromoanisole solution to the magnesium
turnings with stirring, followed by gentle heating. The rest of
the bromoanisole solution was then added at such a rate that
the THF maintained a moderate reflux. Upon final addition,
the solution was allowed to stir at room temperature for 1 h,
at which point GC analysis of a quenched aliquot of the
reaction mixture indicated complete consumption of 4-bro-
moanisole. The 4-(bromomagnesium)anisole solution was then
transferred via cannula to a second flame-dried addition
funnel, to which was fitted a 50 mL round-bottom flask
containing the indicated silane (1.5-3.0 equiv) and the internal
standard naphthalene (64 mg, 0.50 mmol) in 10.0 mL of THF.
The silane solution was cooled to the indicated temperature,
and then the 4-(bromomagnesium)anisole solution was added
dropwise (1 drop per second). The solution was allowed to stir
at the indicated temperature for 1 h and then at room
temperature for 12 h. Progress was monitored by GC analysis
of aliquots of the quenched reaction mixture. GC response
factors relative to the internal naphthalene standard were
determined, and the observed percentages of products were
normalized accordingly. The reduced product anisole was
identified by comparison of the GC retention time to that of
an authentic sample. Diarylated products were identified by
GCMS; triarylated products were not observed. Aliquots of the
crude, concentrated 4-(trichlorosilyl)anisole were converted to
the siloxane by dropwise addition (1 drop per second) of the
chlorosilane to EtOH/pyridine at 0 °C.
General Procedure for Synthesis of Siloxanes from
Grignard Reagents (Table 2). Unless otherwise indicated,
all reactions were performed on a 5 mmol scale. A 10 mL,
three-neck, pear-shaped flask was fitted with an addition
funnel, a reflux condenser, a rubber septum, and a stir bar.
The flask was then charged with freshly washed magnesium
turnings (134 mg, 5.50 mmol), flame-dried under vacuum, and
back-filled with argon. THF (1.0 mL) was added to the
magnesium turnings via syringe. The addition funnel was
charged with the aryl halide (5.00 mmol) in 2.0 mL THF. The
reaction was initiated by addition of 5-10 drops of the aryl
halide solution to the magnesium turnings with stirring,
followed by gentle heating. The rest of the aryl halide solution
was then added at such a rate that the THF maintained a
moderate reflux. Upon final addition, the solution was allowed
to stir at room temperature until GC analysis of a quenched
aliquot of the reaction mixture indicated complete consumption
of aryl halide. The arylmagnesiumhalide solution was then
transferred via cannula to a second flame-dried addition
funnel, to which was fitted a 50 mL round-bottom flask
containing tetraethyl orthosilicate or tetramethyl orthosilicate
(15.00 mmol) in 10.0 mL of THF. The silane solution was
cooled to -30 °C, and then the 4-arylmagnesiumhalide solution
was added dropwise (1 drop per second). The solution was
allowed to stir at the indicated temperature for 1 h and then
at room temperature for 12 h. The crude reaction mixture was
then poured into 50 mL of pentane in a 200 mL separatory
3-(Triethoxysilyl)anisole (Table 2, Entry 3). The general
procedure for synthesis of siloxanes from Grignard reagents
was followed using 3-bromoanisole (935 mg, 633 µL, 5.00
mmol), magnesium turnings (134 mg, 5.50 mmol), and tetra-
ethyl orthosilicate (3.13 g, 3.35 mL, 15.0 mmol) in THF. Bulb-
to-bulb distillation (125 °C, 0.5 Torr) afforded 1.14 g (84%) of
3-(triethoxysilyl)anisole as a colorless oil: IR (neat) 2975 (s),
2927 (m), 2887 (m), 1572 (m), 1482 (w), 1410 (w), 1391 (w),
1284 (w), 1249 (m), 1234 (m), 1167 (m), 1078 (vs) cm-1 1H
;
(NMR) (CDCl3) δ 1.25 (t, J ) 7.0, 9H), 3.81 (s, 3H), 3.87 (q, J
) 7.0, 6H), 6.96-6.98 (m, 1H), 7.21-7.33 (m, 3H); 13C (NMR)
(CDCl3) δ 18.3, 55.1, 58.8, 116.1, 119.8, 127.1, 129.2, 132.4,
159.0; MS (m/z) 270 (100), 256 (12), 255 (70), 226 (28), 225
(64), 211 (23), 197 (13), 182 (11), 181 (41), 169 (37), 168 (13),
167 (29), 163 (10), 154 (16), 153 (27), 149 (22), 147 (61), 139
(20), 137 (14), 136 (55), 135 (95); HRMS for C13H22O4Si calcd
270.1287, found 270.1282.
4-(Triethoxysilyl)anisole (Table 2, Entry 4). The general
procedure for synthesis of siloxanes from Grignard reagents
was followed using 4-bromoanisole (935 mg, 626 µL, 5.00
mmol), magnesium turnings (134 mg, 5.50 mmol), and tetra-
ethyl orthosilicate (3.13 g, 3.35 mL, 15.0 mmol) in THF. Bulb-
to-bulb distillation (125 °C, 0.5 Torr) afforded 1.11 g (82%) of
4-(triethoxysilyl)anisole as a colorless oil: IR (neat) 2975 (s),
2926 (m), 2894 (m), 1597 (s), 1505 (m), 1282 (m), 1249 (m),
1167 (s), 1127 (vs), 1104 (vs), 1080 (vs) cm-1; 1H (NMR) (CDCl3)
δ 1.24 (t, J ) 7.0, 9 H), 2.34 (s, 3H), 3.86 (q, J ) 7.0, 6 H), 6.92
(d, J ) 8.6, 2 H), 7.61 (d, J ) 8.6, 2 H); 13C (NMR) (CDCl3) δ
18.1, 54.9, 58.6, 113.6, 122.0, 136.4, 161.4; MS (m/z) 270 (52),
255 (53), 225 (38), 211 (25), 181 (28), 169 (27), 149 (22), 147
(100), 135 (32); HRMS for C13H22O4Si calcd 270.1287, found
270.1261. The IR and 1H and 13C NMR data were identical to
published spectral data.23
4-(Triethoxysilyl)-1,2-(methylenedioxy)benzene (Table
2, Entry 5). The general procedure for synthesis of siloxanes
from Grignard reagents was followed using 4-bromo-1,2-
(methylenedioxy)benzene (1.01 g, 602 µL, 5.00 mmol), mag-
nesium turnings (134 mg, 5.50 mmol), and tetraethyl ortho-
silicate (3.13 g, 3.35 mL, 15.0 mmol) in THF. Bulb-to-bulb
J. Org. Chem, Vol. 69, No. 24, 2004 8311

Manoso et al.
distillation (125 °C, 0.5 Torr) afforded 1.00 g (74%) of 4-(tri-
ethoxysilyl)-1,2-(methylenedioxy)benzene as a colorless oil: IR
(CCl4) 2976 (s), 2926 (m), 2886 (s), 1613 (w), 1503 (w), 1487
(m), 1422 (m), 1237 (m), 1168 (m), 1080 (s), 1045 (m) cm-1; 1H
(NMR) (CDCl3) δ 1.24 (t, J ) 6.8, 9H), 3.85 (q, J ) 6.8, 6H),
5.95 (s, 2H), 6.86 (d, J ) 7.6, 1H), 7.12 (s, 1H), 7.19 (d, J )
7.6, 1H); 13C (NMR) (CDCl3) δ 18.1, 59.9, 100.8, 108.8, 114.2,
123.9, 129.6, 147.6, 149.7; MS (m/z) 284 (100), 239 (39), 226
(28), 211 (10), 195 (14), 183 (25), 167 (18), 153 (13), 149 (24),
148 (14), 147 (75), 135 (12); HRMS for C13H20O5Si calcd
284.1080, found 284.1083.
2-(Triethoxysilyl)toluene (Table 2, Entry 6). The gen-
eral procedure for synthesis of siloxanes from Grignard
reagents was followed using 2-bromotoluene (855 mg, 601 µL,
5.00 mmol), magnesium turnings (134 mg, 5.50 mmol), and
tetraethyl orthosilicate (3.13 g, 3.35 mL, 15.0 mmol) in THF.
Bulb-to-bulb distillation (125 °C, 0.5 Torr) afforded 1.03 g
(81%) of 2-(triethoxysilyl)toluene as a colorless oil: IR (CCl4)
magnesium turnings (134 mg, 5.50 mmol), and tetraethyl
orthosilicate (3.13 g, 3.35 mL, 15.0 mmol) in THF. Bulb-to-
bulb distillation (125 °C, 0.5 Torr) afforded 661 mg (55%) of
triethoxyphenylsilane as a colorless oil: spectral data is
reported above; IR (CCl4) 3140 (w), 2976 (s), 2928 (m), 2941
(m), 1431 (m), 1391 (m), 1129 (s), 1102 (s), 1094 (s), 1080 (s)
1
cm-1; H (NMR) (CDCl3) δ 1.25 (t, J ) 7.0, 9 H), 3.88 (q, J )
7.0, 6 H), 7.3-7.5 (m, 3 H), 7.6-7.8 (m, 2 H); 13C (NMR)
(CDCl3) δ 18.1, 58.7, 127.8, 130.2, 131.1, 134.7; MS (m/z) 240
(16), 195 (38), 181 (13), 162 (28), 147 (100), 139 (33), 135 (33);
HRMS for C12H20O3Si calcd 240.1182, found 240.1141. The IR
and 1H and 13C NMR data were identical to published spectral
data.23
Optimization of the Synthesis of 4-(Triethoxysilyl)-
toluene Using 4-Lithioanisole (Table 3). A solution of
n-BuLi (1.5 M in pentane, 3.33 mL, 5.00 mmol) was added
dropwise (1 drop per second) to a stirring solution of 4-bro-
motoluene (855 mg,615 µL, 5.00 mmol) in Et2O (15.0 mL) at
room temperature. After 1 h, the solution was cooled to -78
°C and added via cannula to a stirring solution of tetraethyl
orthosilicate (1.5-3.0 equiv) and the internal standard bi-
phenyl (77 mg, 0.50 mmol) in Et2O (15.0 mL) at -78 °C.
Progress was monitored by GC analysis of aliquots of the
quenched reaction mixture. GC response factors relative to the
internal standard were determined, and the observed percent-
ages of products were normalized accordingly. The reduced
product toluene was identified by comparison of the GC
retention time to that of an authentic sample. Poly-
arylated products were identified by GCMS.
General Procedure for Synthesis of Siloxanes from
Lithium Reagents Using n-BuLi (Table 4). Unless other-
wise indicated, all reactions were performed on a 5 mmol scale.
A solution of n-BuLi (1.6 M in pentane, 3.1 mL, 5.0 mmol)
was added dropwise (1 drop per second) to a stirring solution
of the aryl halide (5.00 mmol) in Et2O or THF (7.0 mL) at room
temperature. After 1 h, the solution was cooled to -78 °C and
added via cannula to a stirring solution of tetraethyl ortho-
silicate (1.56 g, 1.68 mL, 7.50 mmol) in Et2O or THF (7.0 mL)
at -78 °C. After 1 h, the reaction was quenched with H2O (5
drops) at -78 °C and allowed to slowly warm to room
temperature. The crude reaction mixture was then extracted
with 3 × 50 mL Et2O. The combined organic extracts were
dried over MgSO4, filtered, and concentrated in vacuo. The
residue was purified by either column chromatography or by
bulb-to-bulb distillation.
2-(Triethoxysilyl)toluene (Table 4, Entry 1). The gen-
eral procedure for synthesis of siloxanes from lithium reagents
was followed using n-BuLi (1.6 M in pentane, 3.1 mL, 5.0
mmol), 2-bromotoluene (855 mg, 601 µL, 5.00 mmol), and
tetraethyl orthosilicate (1.56 g, 1.68 mL, 7.50 mmol) in Et2O.
Bulb-to-bulb distillation (125 °C, 0.5 Torr) afforded 1.00 g
(79%) of 2-(triethoxysilyl)toluene as a colorless oil. Spectral
data is reported above.
3-(Triethoxysilyl)toluene (Table 4, Entry 2). The gen-
eral procedure for synthesis of siloxanes from lithium reagents
was followed using n-BuLi (1.6 M in pentane, 3.1 mL, 5.0
mmol), 3-bromotoluene (855 mg, 607 µL, 5.00 mmol), and
tetraethyl orthosilicate (1.56 g, 1.68 mL, 7.50 mmol) in Et2O.
Bulb-to-bulb distillation (125 °C, 0.5 Torr) afforded 903 mg
(71%) of 3-(triethoxysilyl)toluene as a colorless oil. Spectral
data is reported above.
3054, 2971, 2922, 2881, 1442, 1393, 1283, 1162, 1079 cm-1
;
1H NMR (CDCl3) δ 1.26 (t, J ) 7.0, 9H), 2.26 (s, 3H), 3.87 (q,
J ) 7.0, 6H), 7.17 (m, 2H), 7.32 (m, 1H), 7.74 (m, 1H); 13C
NMR (CDCl3) δ 18.2, 22.4, 58.5, 124.7, 129.7, 129.9, 130.5,
136.5, 144.5, MS (m/z) 254 (48), 209 (44), 208 (19), 162 (55),
147 (100), 119 (51), 91 (50), 79 (15); HRMS for C13H22O3Si calcd
1
254.1349, found 254.1338. The IR and H and 13C NMR data
were identical to published spectral data.38
2-(Trimethoxysilyl)toluene (Table 2, Entry 7). The
general procedure for synthesis of siloxanes from Grignard
reagents was followed using 2-bromotoluene (855 mg, 601 µL,
5.00 mmol), magnesium turnings (134 mg, 5.50 mmol), and
tetramethyl orthosilicate (2.28 g, 2.21 mL, 15.0 mmol) in THF.
Bulb-to-bulb distillation (125 °C, 0.5 Torr) afforded 754 mg
(71%) of 2-(trimethoxysilyl)toluene as a colorless oil: IR (neat)
3052 (w), 3008 (w), 2942 (s), 2840 (s), 1592 (m), 1471 (m), 1456
1
(m) cm -1; H NMR (CDCl3) δ 2.48 (s, 3H), 3.61 (s, 9H), 7.17
(m, 2H), 7.31 (m, 1H), 7.67 (d, J ) 7.5, 1H); 13C NMR (CDCl3)
δ 22.2, 50.4, 124.7, 128.4, 129.7, 130.6, 136.3, 144.4; MS (m/z)
212 (61), 151 (16), 121 (100), 60 (73); HRMS for C10H16O3Si
212.0869, found 212.0859.
3-(Triethoxysilyl)toluene (Table 2, Entry 8). The gen-
eral procedure for synthesis of siloxanes from Grignard
reagents was followed using 3-bromotoluene (855 mg, 607 µL,
5.00 mmol), magnesium turnings (134 mg, 5.50 mmol), and
tetraethyl orthosilicate (3.13 g, 3.35 mL, 15.0 mmol) in THF.
Bulb-to-bulb distillation (125 °C, 0.5 Torr) afforded 954 mg
(75%) of 3-(triethoxysilyl)toluene as a colorless oil: IR (neat)
2975 (s), 2926 (s), 2885 (s), 1577 (w), 1480 (w), 1442 (m), 1390
(m), 1295 (w), 1225 (w), 1167 (s), 1104 (vs), 1079 (vs) cm-1; 1H
(NMR) (CDCl3) δ 1.25 (t, J ) 7.2, 9H), 2.36 (s, 3H), 3.87 (q, J
) 7.2, 6H), 7.23-7.29 (m, 2H), 7.46-7.48 (m, 2H); 13C (NMR)
(CDCl3) δ 18.4, 21.7, 58.9, 128.0, 130.8, 131.4, 132.0, 135.6,
137.4; MS (m/z) 254 (41), 239 (6), 209 (52), 195 (6), 162 (44),
147 (100), 119 (53), 91 (42), 66 (6); HRMS for C13H22O3Si calcd
254.1338, found 254.1331.
4-(Triethoxysilyl)toluene (Table 2, Entry 9). The gen-
eral procedure for synthesis of siloxanes from Grignard
reagents was followed using 4-bromotoluene (855 mg, 638 µL,
5.00 mmol), magnesium turnings (134 mg, 5.50 mmol), and
tetraethyl orthosilicate (3.13 g, 3.35 mL, 15.0 mmol) in THF.
Bulb-to-bulb distillation (125 °C, 0.5 Torr) afforded 1.09 g
(86%) of 4-(triethoxysilyl)toluene as a colorless oil: IR (CCl4)
2975 (s), 2926 (m), 2885 (m), 1167(s), 1124 (vs), 1103 (vs), 1080
4-(Triethoxysilyl)toluene (Table 4, Entry 3). The gen-
eral procedure for synthesis of siloxanes from lithium reagents
was followed using n-BuLi (1.6 M in pentane, 3.1 mL, 5.0
mmol), 4-bromotoluene (855 mg, 638 µL, 5.00 mmol), and
tetraethyl orthosilicate (1.56 g, 1.68 mL, 7.50 mmol) in Et2O.
Bulb-to-bulb distillation (125 °C, 0.5 Torr) afforded 1.08 g
(81%) of 4-(triethoxysilyl)toluene as a colorless oil. Spectral
data is reported above.
1
(vs) cm -1; H (NMR) (CDCl3) δ 1.24 (t, J ) 7.0, 9 H), 2.36 (s,
3 H), 3.86 (q, J ) 7.0, 6 H), 7.19 (d, J ) 7.9, 2 H), 7.57(d, J )
7.9, 2 H); 13C (NMR) (CDCl3) δ 18.2, 21.5, 58.6, 127.4, 128.6,
134.8, 140.2; MS (m/z) 254 (23), 209 (38), 181 (5), 165 (16),
162 (30), 153 (19), 147 (100), 135 (17); HRMS for C13H22O3Si
calcd 254.1363, found 254.1338. The IR and 1H and 13C NMR
data were identical to published spectral data.23
Triethoxyphenylsilane (Table 2, Entry 10). The general
procedure for synthesis of siloxanes from Grignard reagents
was followed using bromobenzene (785 mg, 527 µL, 5.00 mmol),
Triethoxyphenylsilane (Table 4, Entry 4). The general
procedure for synthesis of siloxanes from lithium reagents was
followed using n-BuLi (1.6 M in pentane, 3.1 mL, 5.0 mmol),
8312 J. Org. Chem., Vol. 69, No. 24, 2004

Improved Synthesis of Aryltrialkoxysilanes
bromobenzene (785 mg, 527 µL, 5.00 mmol), and tetraethyl
orthosilicate (1.56 g, 1.68 mL, 7.50 mmol) in Et2O. Bulb-to-
bulb distillation (125 °C, 0.5 Torr) afforded 889 mg (74%) of
triethoxyphenylsilane as a colorless oil. Spectral data is
reported above.
2-(Triethoxysilyl)anisole (Table 4, Entry 5). The general
procedure for synthesis of siloxanes from lithium reagents was
followed using n-BuLi (1.6 M in pentane, 3.1 mL, 5.0 mmol),
2-bromoanisole (935 mg, 623 µL, 5.00 mmol), and tetraethyl
orthosilicate (1.56 g, 1.68 mL, 7.50 mmol) in Et2O. Bulb-to-
bulb distillation (125 °C, 0.5 Torr) afforded 811 mg (60%) of
2-(triethoxysilyl)anisole as a colorless oil. Spectral data is
reported above.
3-(Triethoxysilyl)anisole (Table 4, Entry 6). The general
procedure for synthesis of siloxanes from lithium reagents was
followed using n-BuLi (1.6 M in pentane, 3.1 mL, 5.0 mmol),
3-bromoanisole (935 mg, 633 µL, 5.00 mmol), and tetraethyl
orthosilicate (1.56 g, 1.68 mL, 7.50 mmol) in Et2O. Bulb-to-
bulb distillation (125 °C, 0.5 Torr) afforded 892 mg (66%) of
3-(triethoxysilyl)anisole as a colorless oil. Spectral data is
reported above.
4-(Triethoxysilyl)anisole (Table 4, Entry 7). The general
procedure for synthesis of siloxanes from lithium reagents was
followed using n-BuLi (1.6 M in pentane, 3.1 mL, 5.0 mmol),
4-bromoanisole (935 mg, 626 µL, 5.00 mmol), and tetraethyl
orthosilicate (1.56 g, 1.68 mL, 7.50 mmol) in Et2O. Bulb-to-
bulb distillation (125 °C, 0.5 Torr) afforded 906 mg (67%) of
4-(triethoxysilyl)anisole as a colorless oil. Spectral data is
reported above.
mL). The reaction mixture was stirred for 15 min and then
cooled to -78 °C. A solution of t-BuLi (1.7 M in pentane, 3.0
mL, 5.0 mmol) was then added via cannula. A white precipitate
immediately formed. The mixture was stirred for 10 min,
followed by dropwise (1 drop per second) addition of a solution
of tetraethyl orthosilicate (1.06 g, 1.13 mL, 5.08 mmol) in THF
(2 mL). The reaction mixture was stirred for 30 min at -78
°C and then allowed to slowly warm to room temperature. The
reaction mixture was poured into 10 mL of ice water and then
extracted with ether (3 × 15 mL). The combined organic
extracts were dried over MgSO4 and then concentrated in
vacuo. Column chromatography (4:1 hexanes/EtOAc) afforded
497 mg (70%) of 5-(triethoxysilyl)indole as a pale yellow oil:
TLC Rf ) 0.32 (4:1 hexanes/EtOAc); IR (CCl4) 3489 (s),
2976 (s), 2926 (m), 1885 (m) cm-1 1H NMR (CDCl3) δ 8.38
;
(br s, 1H), 8.03 (s, 1H), 7.48 (d, J ) 8.1 Hz, 1H), 7.39 (d,
J ) 8.1 Hz, 1H), 7.16 (t, J ) 2.6 Hz, 1H), 6.56 (s, 1H), 3.89 (q,
J ) 7.0, 6H), 1.26 (t, J ) 7.0, 9H); 13C NMR (CDCl3) δ 137.2,
128.5, 127.7, 127.6, 124.2, 120.0, 110.9, 102.7. 58.6, 18.2; MS
(m/z) 280 (70), 234 (42), 206 (14), 190 (21), 163 (100), 144 (78),
117 (58); HRMS for C14H21NO3Si calcd 280.1369, found
280.1381.
5-(Triethoxysilyl)-1-methyl-indole (Table 4, Entry 12).
A solution of t-BuLi (1.50 M in pentane, 3.76 mL, 5.64 mmol)
was added dropwise (1 drop per second) to a stirring solution
of 5-bromo-1-methylindole (987 mg, 4.70 mmol) in Et2O (10.0
mL) at -78 °C. After 15 min, the solution was added dropwise
(1 drop per second) via cannula to a solution of tetraethyl
orthosilicate (6.25 g, 6.69 mL, 30.0 mmol) in 5 mL of Et2O
cooled to -78 °C. After 1 h, the reaction was allowed to slowly
warm to room temperature. The reaction mixture was quenched
by the addition of 50 mL of water. The crude reaction mixture
was then extracted with 4 × 50 mL of Et2O. The combined
organic extracts were dried over Na2SO4, filtered, and con-
centrated in vacuo. Purification of the residue by flash chro-
matography (30 mm, 15 cm, 33% CH2Cl2/hexane) gave 840 mg
(60%) of 5-(triethoxysilyl)-1-methyl-indole as a yellow oil: TLC
Rf ) 0.37 (33% CH2Cl2/hexane); IR (CCl4) 2975 (s), 2923 (m),
2882 (m), 1611 (m), 1556 (s), 1518 (m), 1480 (m), 1104 (s), 1080
(s) cm-1; 1H NMR (CDCl3) δ 1.25 (t, J ) 7.2, 9H), 3.79 (s, 3H),
3.88 (q, J ) 7.2, 6H), 6.52 (d, J ) 2.8, 1H), 7.05 (d, J ) 2.8,
1H), 7.36 (d, J ) 7.9, 1H), 7.52 (d, J ) 7.9, 1H), 8.00 (s, 1H);
13C NMR (CDCl3) δ 18.2, 32.6, 58.5, 101.3, 108.9, 119.4, 127.3,
128.2, 128.6, 128.8, 137.9; MS (m/z) 294 (M+ + 1, 29), 293 (M+,
100), 278 (10), 131 (23). HRMS for C15H23NO3Si calcd 293.1447,
found 293.1439.
2-Furyltriethoxysilane (Table 4, Entry 13). A solution
of t-BuLi (1.50 M in pentane, 16.00 mL, 24.00 mmol) was
added dropwise (1 drop per second) to a stirring solution of
the furan (1.36 g, 1.46 mL, 20.0 mmol) and TMEDA (2.32 g,
3.02 mL, 20.0 mmol) in Et2O (40.0 mL) at 0 °C. After 2 h, the
solution was cooled to -78 °C and tetraethyl orthosilicate (6.25
g, 6.69 mL, 30.0 mmol) was added dropwise (1 drop per
second). After 1 h, the reaction was quenched with H2O (1 mL)
at -78 °C and allowed to slowly warm to room temperature.
The crude reaction mixture was then extracted with 2 × 200
mL Et2O. The combined organic extracts were dried over
MgSO4, filtered, and concentrated in vacuo. Purification of the
residue by flash chromatography (30 mm, 15 cm, 10% EtOAc/
hexanes) gave 1.01 g (22%) of 2-furyltriethoxysilane as a
colorless oil: TLC Rf ) 0.71 (10% EtOAc/hexane); IR (CCl4)
2974 (s), 2926 (s), 2891 (s), 1455 (m), 1390 (m), 1169 (s), 1100
(s), 1079 (s), 965 (m); 1H (NMR) (CDCl3) δ 1.23 (t, J ) 7.0,
9H), 3.87 (q, J ) 7.0, 6H), 6.39 (dd, J ) 1.3, 3.3, 1H), 6.87 (d,
J ) 3.3, 1H), 7.65 (d, J ) 1.3, 1H); 13C (NMR) (CDCl3) δ 18.1,
59.0, 109.3, 123.2, 147.4, 151.3; MS (m/z) 231 (M+ + 1, 5), 230
(M+, 28), 215 (100), 203 (14), 185 (28), 147 (80), 119 (52), 113
(55), 79 (47), 63 (27); HRMS for C10H18O4Si calcd 230.0979,
found 230.0974.
4-(Triethoxysilyl)thioanisole (Table 4, Entry 8). The
general procedure for synthesis of siloxanes from lithium
reagents was followed using n-BuLi (1.6 M in pentane, 6.1 mL,
9.8 mmol), 4-bromothioanisole (1.99 g, 9.80 mmol), and tetra-
ethyl orthosilicate (6.13 g, 6.56 mL, 29.4 mmol) in Et2O (20
mL). Extraction and flash chromatography (30 mm, 15 cm,
33% CH2Cl2/hexanes) afforded 1.40 g (50%) of 4-(triethoxysi-
lyl)thioanisole as a colorless oil: TLC Rf ) 0.25 (33% CH2Cl2/
hexanes); IR (CCl4) 2976 (m), 2925 (m), 1585 (m), 1487 (m),
1
1440 (m), 1103 (s), 1080 (s) cm-1; H NMR (CDCl3) δ 1.24 (t,
J ) 6.8, 9H), 2.48 (s, 3H), 3.86 (q, J ) 6.8, 6H), 7.25 (d, J )
7.9, 2H), 7.58 (d, J ) 7.9, 2H); 13C NMR (CDCl3) δ 15.0, 18.2,
58.7, 125.3, 126.7, 135.1, 141.4; MS (m/z) 287 (M+ + 1, 22),
286 (100), 241 (19), 227 (17), 195 (19), 147 (49), 124 (17), 119
(17); HRMS for C13H22O3SSi calcd 286.1059, found 286.1063.
4-(Triethoxysilyl)-1,2-(methylenedioxy)benzene (Table
4, Entry 9). The general procedure for synthesis of siloxanes
from lithium reagents was followed using n-BuLi (1.6 M in
pentane, 3.1 mL, 5.0 mmol), 4-bromo-1,2-(methylenedioxy)-
benzene (1.01 g, 602 µL, 5.00 mmol), and tetraethyl orthosili-
cate (1.56 g, 1.68 mL, 7.50 mmol) in Et2O. Bulb-to-bulb
distillation (125 °C, 0.5 Torr) afforded 427 mg (30%) of
4-(triethoxysilyl)-1,2-(methylenedioxy)benzene as a colorless
oil. Spectral data is reported above.
3-(Triethoxysilyl)thiophene (Table 4, Entry 10). The
general procedure for synthesis of siloxanes from lithium
reagents was followed using n-BuLi (1.6 M in pentane, 7.50
mL, 12.0 mmol), 3-bromothiophene (1.96 g, 1.12 mL, 12.0
mmol), and tetraethyl orthosilicate (7.50 g, 8.05 mL, 36.0
mmol) in Et2O (20 mL). Extraction and flash chromatography
(30 mm, 15 cm, 17% CH2Cl2/hexanes) gave 1.48 g (50%) of
3-(triethoxysilyl)thiophene as a colorless oil: TLC Rf ) 0.25
(17% CH2Cl2/hexanes); IR (CCl4) 2975 (m), 2926 (m), 1553 (m),
1
1542 (m), 1103 (s), 1081 (s) cm-1; H NMR (CDCl3) δ 1.24 (t,
J ) 7.2, 9H), 3.87 (q, J ) 7.2, 6H), 7.29 (d, J ) 4.8, 1H), 7.40
(dd, J ) 4.8, 2.0, 1H), 7.74 (d, J ) 2.0, 1H); 13C NMR (CDCl3)
δ 18.2, 58.7, 125.7, 131.7, 131.8, 135.5; MS (m/z) 247 (M+ + 1,
17), 246 (100), 202 (30), 201 (46), 158 (51), 145 (30), 135 (73);
HRMS for C10H18O3SSi calcd 246.0746, found 246.0743.
5-(Triethoxysilyl)indole (Table 4, Entry 11). To a solu-
tion of KH (35% dispersion in mineral oil, 292 mg, 2.55 mmol)
in THF (5.0 mL) was added dropwise (1 drop per second) a
solution of 5-bromoindole (498 mg, 2.54 mmol) in THF (5.0
5-Triethoxysilyl-2-methoxypyridine (Table 4, Entry
15). The general procedure for synthesis of siloxanes from
lithium reagents was followed using n-BuLi (1.4 M in pentane,
J. Org. Chem, Vol. 69, No. 24, 2004 8313

Manoso et al.
6.5 mL, 8.8 mmol), 5-bromo-2-methoxypyridine (1.66 g, 1.14
mL, 8.83 mmol), and tetraethyl orthosilicate (2.76 g, 2.95 mL,
13.3 mmol) in Et2O (20 mL). Extraction and flash chromatog-
raphy (9:1 hexanes/EtOAc) afforded 527 mg (22%) of 5-tri-
ethoxysilyl-2-methoxypyridine as a colorless oil: TLC Rf )
0.28 (9:1 hexanes/EtOAc); IR (CCl4) 2976 (s), 2927 (m), 2887
(m), 1589 (s), 1491 (w), 1442 (m), 1390 (w), 1356 (m), 1286 (s),
land for generous financial support. W.M.S. thanks the
Organic Division of the American Chemical Society for
a graduate fellowship (Proctor and Gamble). We also
thank Dr. Yiu-Fai Lam (NMR), Caroline Ladd (MS), and
Noel Whittaker (MS) for their assistance in obtaining
spectral data.
1082 (vs) cm-1 1H (NMR) (CD3CN) δ 1.20 (t, J ) 7.0, 9H),
;
3.83 (q, J ) 7.0, 6H), 3.87 (s, 3H), 6.73-6.75 (m, 1H), 7.76-
7.78 (m, 1H), 8.32-8.35 (m, 1H); 13C (NMR) (CD3CN) δ 18.6,
53.9, 59.5, 111.5, 130.8, 118.2, 145.5, 154.3, 166.5; MS (m/z)
272 (100), 240 (13), 226 (31), 170 (11), 163 (11), 136 (15), 119
(6), 91 (5), 79 (14); HRMS for C12H22ONSi calcd 272.1318,
found 272.1311.
Supporting Information Available: General experimen-
tal procedures and 1H NMR (400 MHz) spectra for all com-
pounds (these compounds were prepared using the lithiation
method). This material is available free of charge via the
Internet at http://pubs.acs.org.
Acknowledgment. We thank the National Cancer
Institute (C.A. 82169-01) and the University of Mary-
JO048667H
8314 J. Org. Chem., Vol. 69, No. 24, 2004