Studies toward terminal (fluoroalkyl)silanes. Investigation of diethylaminosulfur trifluoride (DAST) in exchange reactions with some terminal (hydroxyalkyl)silanes

Article abstract of DOI:10.1016/j.jfluchem.2013.12.011

Aiming at a convenient way toward the synthesis of terminal (fluoroalkyl)silanes, the effect of (diethylamino)sulfur trifluoride (DAST) on some terminal hydroxyalkylsilanes was investigated. Reaction of DAST with a substituted (hydroxyethyl)diphenylsilane led to the formation of the desired (2-fluoroethyl)diphenylsilane in considerable amounts although the competing elimination route was still the favored mechanism. This new reaction was studied under various parameters with the best conditions yielding the substitution product in a ratio of 1:4 over the undesired elimination product. In a different approach trying to optimize the outcome of the reaction, the presence of two bulky 2,4,6-trimethoxyphenyl (TMOP) groups on the silicon atom favored the elimination route.

Full text of DOI:10.1016/j.jfluchem.2013.12.011

Journal of Fluorine Chemistry 160 (2014) 20–28
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Studies toward terminal (fluoroalkyl)silanes. Investigation of
diethylaminosulfur trifluoride (DAST) in exchange reactions with
some terminal (hydroxyalkyl)silanes
a
b
a
Aristeidis Chiotellis a, , Svetlana V. Selivanova , Bernd Schweizer , Roger Schibli ,
*
Simon M. Ametamey a
a Center for Radiopharmaceutical Sciences of ETH, PSI and USZ, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH)
Zurich, Wolfgang Pauli Strasse 10, 8093 Zurich, Switzerland
b Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH) Zurich,
Wolfgang Pauli Strasse 10, 8093 Zurich, Switzerland
A R T I C L E I N F O
A B S T R A C T
Article history:
Aiming at a convenient way toward the synthesis of terminal (fluoroalkyl)silanes, the effect of
(diethylamino)sulfur trifluoride (DAST) on some terminal hydroxyalkylsilanes was investigated.
Reaction of DAST with a substituted (hydroxyethyl)diphenylsilane led to the formation of the desired
(2-fluoroethyl)diphenylsilane in considerable amounts although the competing elimination route was
still the favored mechanism. This new reaction was studied under various parameters with the best
conditions yielding the substitution product in a ratio of 1:4 over the undesired elimination product. In a
different approach trying to optimize the outcome of the reaction, the presence of two bulky 2,4,6-
trimethoxyphenyl (TMOP) groups on the silicon atom favored the elimination route.
ß 2014 Elsevier B.V. All rights reserved.
Received 25 September 2013
Received in revised form 3 December 2013
Accepted 27 December 2013
Available online 4 January 2014
Keywords:
DAST
Fluoroalkylsilanes
Silicon
Fluorination
Hydroxyalkylsilanes
1. Introduction
Nucleophilic fluorination of haloalkylsilanes with longer alkyl
chains proceeds in a similar manner, e.g. g-elimination takes place
Terminal fluoroalkylsilanes are sparingly available mainly
because they cannot be synthesized directly from the correspond-
ing haloalkylsilanes (halo including sulfonates) via nucleophilic
fluorination. In the case of halomethylsilanes, fluoride reacts by
attacking the silicon atom to give rearrangement – displacement
products arising from competitive migration of the silicon
substituents to the electrophilic carbon with displacement of
the halide atom [1–4] (Scheme 1). It is postulated that the reaction
proceeds via a pentacoordinated silicon intermediate and it has
been shown that migration is largely controlled by the ability of the
migrating group to bear a negative charge, which is acquired in the
transition state [5]. For haloethylsilanes, fluoride attacks again the
silicon atom, which results in C–Si bond cleavage and elimination
in the case of substituted 3-chloropropylsilanes to give substituted
cyclopropanes [11]. In all the aforementioned cases, fluoride
attacks preferentially the silicon atom rather than the electrophilic
carbon and no trace of fluoroalkylsilane is observed. Apparently,
the driving force for this effect is the formation of the extremely
strong Si–F bond.
Nevertheless, there are a few reports where fluoroalkylsilanes
were synthesized by direct nucleophilic substitution of corre-
sponding analogs bearing a suitable leaving group (chloride or
tosylate). These sparse examples include (fluoromethyl)trimethyl-
silane and (3-fluoropropyl)trimethylsilane [12,13]. The authors,
however, mentioned that in these cases there was also some
degree of rearrangement or elimination but the desired fluoroalk-
ylsilanes could be obtained in satisfactory yields. It seems that the
outcome of the two competing reactions (nucleophilic substitution
vs. elimination) (Scheme 2), is affected by the nature of the
substituents attached to the silicon atom. In all cases, the silicon
atom bears three electron donating methyl groups, which could
potentially reduce its electropositivity and thus its affinity for
fluoride, giving to the latter the opportunity to react with the
electrophilic carbon. On the other hand, electron withdrawing
of the leaving group from the
b-carbon (Scheme 2A) [6–10].
*
Corresponding author at: Center for Radiopharmaceutical Sciences ETH-PSI-
USZ, Department of Chemistry and Applied Sciences, Swiss Federal Institute of
Technology (ETH) Zurich, HCI H422, Wolfgang Pauli Strasse 10, 8093 Zurich,
Switzerland. Tel.: +41 44 6337472.
E-mail addresses: aristeidis.chiotellis@pharma.ethz.ch, achiotel@ethz.ch (A.
Chiotellis).
0022-1139/$ – see front matter ß 2014 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2013.12.011

A. Chiotellis et al. / Journal of Fluorine Chemistry 160 (2014) 20–28
21
Scheme 1. Rearrangement – displacement reaction of chloromethylsilanes by fluoride attack at the silicon center.
Scheme 2. Elimination vs. substitution in the case of ethylsilanes carrying a leaving group (LG) at 2-position.
groups seem to favor elimination. For example, in contrast to (3-
chloropropyl)trimethylsilane, no exchange of chlorine is observed
for (3-chloropropyl)trichlorosilane where the nucleophilic fluoride
attacks exclusively the electron-deficient silicon leading quantita-
phenyl groups on silicon could actually impede substitution by
increasing the electron deficiency of silicon when compared
to substituted (2-hydroxyethyl)dimethylsilanes. Treatment of
(diphenyl)divinylsilane 1 [18] (Scheme 3A) with 9-borabicy-
clo[3.3.1]nonane (9-BBN) followed by addition of aqueous solu-
tions of sodium hydroxide 3 M and hydrogen peroxide 30% gave
the corresponding bis(2-hydroxyethyl)silane 2 in good yield (76%).
Reaction of diol 2 with acetic anhydride in the presence of
triethylamine and catalytic amounts of DMAP afforded the
corresponding monoacetate compound 3 (50% yield). The reaction
of 3 with DAST in dichloromethane at ꢀ78 8C afforded a mixture of
fluorosilane 4 and the desired 2-fluoroethyl derivative 5 in 4.5:1
ratio (as shown by 1H NMR analysis of the crude mixture).
Efforts were made to shift the reaction in favor of the
substitution product 5. Various parameters were investigated,
including solvent, temperature and order of reagent addition. The
results are summarized in Table 1. For the same solvent tested
(dichloromethane), higher temperature favored the elimination
mechanism, as expected (entry 2). Performing the reaction near
the freezing point of dichloromethane (ꢁꢀ90 8C) caused precipi-
tation of 3 and the reaction was not evaluated. More polar solvents
like diglyme and ether readily promoted the elimination process
even at temperatures as low as ꢀ100 8C (entries 3 and 4). The best
results were obtained when using a non- polar, non-basic solvent,
e.g. trichlorofluoromethane (Freon-11) (entry 5). The use of even
less polar solvents (like hexane or pentane) was not examined due
to complete insolubility of 3 at the low temperatures used. Even
though trichlorofluoromethane gave repeatedly slightly better
ratios of the desired product, dichloromethane was chosen for
larger scale reactions for environmental reasons. Finally, the order
of addition of the reagents affected the reaction only marginally
(entries 6 and 7). Best results were obtained when DAST was added
neat to the solution of 3 (entry 1).
tively to g-elimination [12]. Although some degree of nucleophilic
fluorination is observed when three methyl groups are attached to
silicon, these are very difficult to cleave making thus further
derivatization of the resulting terminal fluoroalkylsilanes difficult.
We were interested in synthesizing substituted (2-fluoroethyl)-
diphenylsilanes as building blocks for larger organo-silicon mole-
cules within our medicinal chemistry research program. The only
known synthetic pathway to 2-fluoroethylsilanes is the free radical
chain reaction of vinylfluoride with trichloro- or trimethylsilanes, a
reaction which has a difficult setup and involves tedious purifica-
tions [14]. Clearly, a nucleophilic approach would be much more
convenient but no such reports are available in the literature, for
reasons mentioned above. Additionally, to our surprise, a search on
the Scifinder revealed only 10 examples of synthesized (2-
fluoroethyl)silanes. However, a report describing the direct conver-
sion of (3-hydroxypropyl)trimethylsilane to (3-fluoropropyl)tri-
methylsilane using the Yarovenko reagent [15] prompted us to
examine the reaction of the most commonly used dehydroxylating/
fluorinating agent, namely diethylaminosulfur trifluoride [16,17]
(DAST). To our knowledge, DAST has not yet been used in the
chemistry of organometalloid compounds, at least not for exchange
reactions. Moreover, in the case of the Yarovenko reagent, the
authors state that
g-elimination could partially be controlled by
lowering the temperature. The high reactivity of DAST allows
reactions at low temperatures (ꢀ78 8C), which could potentially
favor substitution over elimination. In this work, we report that
treatment of substituted (2-hydroxyethyl)diphenylsilane 3 with
DAST leads to (2-fluoroethyl)diphenylsilane 5 (Scheme 3), which
can readily be separated from the fluorosilane byproduct.
Although purification of the reaction mixture by column
chromatography was not possible (since the two compounds
exhibit no difference in polarity on the TLC in every solvent
mixture examined), separation was readily achieved by subjecting
the mixture to hydrolytic conditions with aqueous saturated
NaHCO3 solution in acetone. Fluorosilane 4 was quantitatively and
2. Results and discussion
We decided to study the effect of DAST directly on the desired
substituted (2-hydroxyethyl)diphenylsilane 3 even though we
were aware that the presence of the two electron withdrawing

22
A. Chiotellis et al. / Journal of Fluorine Chemistry 160 (2014) 20–28
Scheme 3. (A) Synthesis of (2-fluoroethyl)diphenylsilane 5 and further derivatization. Reagents and conditions: (a) 9-BBN 0.5 M, THF, r.t., 4 h then H2O, NaOH 3 M, H2O2 30%,
reflux, 3 h, 76%; (b) Ac2O, pyridine, DMAP(cat), DCM, 0 8C 30 min then r.t. 3 h, 50%; (c) DAST, DCM, ꢀ78 8C, 30 min; (d) PPh3/CBr4, DCM, 0 8C to r.t, 2 h, 96% for 30 or Tf2O,
pyridine, DCM, ꢀ5 8C, 30 min for 300; (e) KF/Kryptofix, MeCN, 0 8C or TBAF 1 M, THF, 0 8C for 30 and TBABF/KHF2, DCM, 0 8C for 300; (f) NaHCO3(sat)/acetone 1:1, r.t., 16 h, 10%
over two steps; (g) K2CO3, MeOH, r.t., 1 h, 95%; (h) PPh3, 2-nitroimidazole, DIAD, THF, r.t., 16 h, 92%. (B) Synthesis of hydroxymethylanalogue 11. Reagents and conditions: (i)
AcONa, DMF, 100 8C, 6 h, 90%; (j) K2CO3, MeOH, r.t., 1 h, 19%; (k) DAST, DCM, ꢀ78 8C, 30 min, unidentified products.
cleanly converted to the corresponding silanol 6, while the 2-
fluoroethyl derivative 5 remained unaffected. Since polarity of the
silanol differs significantly, product 5 was easily purified by
column chromatography with a total yield of 10% over two steps.
Compound 5 remains stable for a long time at room temperature
with no sign of spontaneous elimination of the fluorine atom and it
can be easily manipulated for further reactions. Treatment with
potassium carbonate in MeOH resulted solely in cleavage of the
acetate group to yield the free alcohol 7 in 95% yield. The free
alcohol was then coupled to the hypoxia targeting agent 2-
nitroimidazole under Mitsunobu reaction conditions to yield
compound 8. In the same way, building block 7 could be coupled to
other molecules of biological interest.
[15]. It is also worth saying that nucleophilic fluorination of
bromide 30 with KF/Kryptofix in MeCN or TBAF in THF and reaction
of triflate 300 with the much less basic TBABF/KHF2 [19] exclusively
resulted in b-elimination, as expected. Although the overall yield of
5 is low (10%), this method could be an alternative approach in the
synthesis of terminal (fluoroethyl)silanes, compared to the already
mentioned radical reaction with vinyl fluoride especially since it
involves an easier experimental setup, cheap and easy to handle
starting materials, avoidance of tedious distillations and the
possibility for further derivatization. The latter could be achieved
by cleaving the phenyl groups with trifluoromethanesulfonic acid
[20,21] and converting to the corresponding chlorosilanes,
although this possibility was not investigated here since we were
interested in keeping the bulky lipophilic phenyl groups on the
silicon atom.
To our knowledge, this is the first example where a (2-
fluoroethy)lsilane is synthesized directly from the corresponding
(2-hydroxyethyl)silane via an exchange reaction. Notably, the use
of the Yarovenko reagent on (2-hydroxyethyl)trimethylsilane
The exchange reaction with DAST was additionally tested on
(hydroxymethyl)silanes in order to examine whether this reaction
would lead to (fluoromethyl)silanes. Compound 11 was synthesized
from 9 [22] as a direct analog of 3 (Scheme 3B). However, in this case,
resulted, according to the authors, exclusively in
b-elimination
with ethylene and (trimethyl)fluorosilane as the sole products
Table 1
Investigation of different conditions of the DAST fluorination reaction with substrate 3.
Entrya
Order of reagents addition
Solvent
Temperature
Ratiob (fluorosilane/
2-fluoroethylsilane)
1
2
3
4
5
6
7
DAST added neat to a solution of 3
Dichloromethane
Dichloromethane
Diglyme
ꢀ78 8C
ꢀ20 8C
ꢀ50 8C
ꢀ100 8C
ꢀ78 8C
ꢀ78 8C
ꢀ78 8C
4.5:1
9.1:1
15.2:1
9:1
DAST added neat to a solution of 3
DAST added neat to a solution of 3
DAST added neat to a solution of 3
Ether
DAST added neat to a solution of 3
Trichlorofluoromethane (Freon-11)
Dichloromethane
Dichloromethane
4.0:1
5.4:1
5.0:1
DAST added as solution in DCM to a solution of 3
Solution of compound 3 added to solution of DAST
a
Experimental conditions (molarity of reaction, quantities of reagents, workup method) were kept constant in every attempt for comparable results.
Determined by 1H NMR analysis of the crude reaction after workup.
b

A. Chiotellis et al. / Journal of Fluorine Chemistry 160 (2014) 20–28
23
the reaction of 11 with DAST led only to unidentified products with
no trace of the desired (fluoromethyl)diphenylsilane.
reacting with acetic anhydride in the presence of pyridine and
catalytic amounts of DMAP in dichloromethane (48% yield).
Compound 15 was then reacted with DAST using the optimal
conditions determined for substrate 3. Unfortunately, the reaction
afforded solely the elimination product, fluorosilane 17. The
reaction was not further investigated since the best experimental
parameters failed to give even a trace of the desired (fluor-
oethyl)silane. Besides, we wanted to investigate how a typical
nucleophilic substitution reaction would proceed when silicon
bears two TMOP groups. For this reason, the sulfonate 16 was
synthesized from 15 by treatment with mesyl chloride in the
presence of triethylamine in 90% yield. The unstable mesyl
compound was quickly reacted with KF/kryptofix in dry acetoni-
trile to deliver exclusively fluorosilane 17 and silanol 18. Our
hypothesis that TMOP groups would facilitate substitution over
elimination was not supported by the experimental data (Fig. 1).
Derivative 20 was synthesized as a model compound in order to
examine in which way would nucleophilic fluorination proceed if
TMOP groups were attached to (chloromethyl)silanes (Scheme 4B).
(Dichloro)bischloromethylsilane 19 [27] was treated with two
equivalents of freshly prepared TMOP-Li in hexane to yield
compound 20 in 65% yield. Surprisingly, 20 did not undergo any
changes when subjected to treatment with KF/Kryptofix in acetoni-
trile. It was also unreactive toward other nucleophiles such as AcOK
in DMF even at temperatures as high as 150 8C. A possible
explanation for this unexpected inertness derives from X-ray
analysis (Fig. 2), which shows that the oxygen atoms of the methoxy
groups are positionedin the nearproximityand atthebacksideofthe
chloromethyl carbon (Fig. 2), probably shielding it effectively from
the approaching nucleophile (in the concept of an SN2 mechanism).
All the afore-mentioned literature data concerning nucleophilic
fluorination of terminal haloalkylsilanes (or hydroxysilanes)
suggest that the nature of the silicon substituents must also
influence the outcome of the new reaction under investigation.
Electron donating groups (e.g. alkyl groups) are expected to favor
substitution by reducing the electropositivity of silicon while
electron withdrawing substituents (e.g. halides) are most likely to
promote elimination by increasing the electron deficiency of the
silicon atom making it thus more prone to attack by fluoride. Our
interest was to examine the outcome of the DAST fluorination
reaction with a different substitution on the silicon atom. The
2,4,6-trimethoxyphenyl (TMOP) group, has recently been reported
to be an effective protecting group in organosilicon chemistry [23–
26]. Its main advantages include high stability under basic
conditions and easy cleavage under very mild acidic conditions.
We envisioned that the bulky TMOP substituents would sterically
hinder the attack of fluoride on silicon and redirect it toward the
easily accessible electrophilic carbon. Besides, it was hypothesized
that the electron donating effect of the three methoxy groups of
TMOP would make the silicon atom less electron deficient which
would favor the substitution route, when compared to its phenyl
analog 3. Moreover, the TMOP group should be much more easily
cleavable than the phenyl groups, which could be an advantage for
medicinal chemistry applications (easier derivatization).
The synthesis of compound 15 (the direct TMOP analog of 3)
was accomplished as depicted in Scheme 4A. The two chlorine
atoms on (dichloro)divinylsilane 12 [18] were substituted with
TMOP groups by reacting 12 with two equivalents of freshly
prepared TMOP-Li [23] to give 13 in good yield (80%), which was
additionally structurally characterized by single-crystal X-ray
diffraction. Hydroboration of 13 with 9-BBN and subsequent
oxidation with hydrogen peroxide 30% under basic conditions
provided the corresponding bis(2-hydroxyethyl)silane 14 in 80%
yield. The diol was converted to its monoacetate analog 15 by
3. Conclusion
We conclude that DAST can be useful for the synthesis of some
terminal (fluroethyl)silanes as exemplified by the synthesis of
(2-fluoroethyl)diphenylsilane 5 starting from the corresponding
Scheme 4. Synthesis of TMOP protected silanes. Reagents and conditions: (a) TMEDA, n-BuLi, hexane, 20 8C, 16 h; (b) TMOP-Li, hexane, 0 8C for 10 min then r.t. 1 h, 80%; (c) 9-
BBN 0.5 M, THF, r.t., 3 h then H2O, NaOH 3 M, H2O2 30%, 0 8C to reflux, 3 h, 80%; (d) Ac2O, pyridine, DMAP(cat), DCM, 0 8C 30 min then r.t. 3 h, 48%; (e) MsCl, Et3N, DCM, ꢀ30 8C to
ꢀ3 8C within 2 h, 90%; (f) KF/Kryptofix, MeCN, r.t., 2 h, 17% (17) and 26% (18); (g) DAST, DCM, ꢀ78 8C, 30 min; (h) TMOP-Li, hexane, 0 8C for 10 min then r.t. 1 h, 65%; (i) KF/
Kryptofix, MeCN, r.t. no reaction; (j) AcONa, DMF, 150 8C, no reaction.

24
A. Chiotellis et al. / Journal of Fluorine Chemistry 160 (2014) 20–28
Fig. 1. ORTEP drawing and numbering scheme for 13 (thermal ellipsoids drawn at 40% probability).
Fig. 2. ORTEP drawing and numbering scheme for 20 (thermal ellipsoids drawn at 40% probability). Geometry shows the methoxy group oxygens positioned in the close
˚
proximity of the targeted electrophilic carbons (2.782 and 2.854 A).
hydroxyl compound. This substitution reaction is of scientific
interest since it directly and conveniently leads to a not easily
accessible class of compounds circumventing the copious radical
reaction with vinylfluoride, the only known reaction which leads to
(2-fluoroethyl)silanes. To our knowledge, compound 5 is also the
first compound to be synthesized via an exchange reaction with
DAST where other nucleophilic fluorinating agents (KF/Kryptofix,
TBABF/KHF2, Yarovenko reagent) for the same or similar synthons
failed to give any trace of the corresponding (2-fluoroethyl)silane.
The substitution path seems to be favored at a low temperature
and using a non-polar solvent. Substitution of the two phenyl
groups with the bulky and easily cleavable TMOP groups failed to
give any trace of the corresponding (2-fluoroethyl)silane which
shows the strong influence of the silicon substituents on the
outcome of the reaction. Other groups, presumably electron
donating ones, could potentially lead to more favorable ratios of
substitution over elimination.
(Diphenyl)divinylsilane 1 [18], (diphenyl)bischloromethylsilane
9 [22], (dichloro)divinylsilane 12 [18], and (dichloro)bischloro-
methylsilane 19 [27] were synthesized by following published
protocols with slight modifications. All solvents used for reactions
were purchased as anhydrous grade from Acros Organics (puriss.,
dried over molecular sieves, H2O < 0.005%) and were used without
further purification unless otherwise stated. Solvents for extrac-
tions, column chromatography and thin layer chromatography
(TLC) were purchased as commercial grade. All non aqueous
reactions were performed under an argon atmosphere using flame-
dried glassware and standard syringe/septa techniques. In general,
reactions were magnetically stirred and monitored by TLC
performed on Merck TLC glass sheets (silica gel 60 F254). Spots
were visualized with UV light (l = 254 nm) or through staining
with anisaldehyde solution or basic aq. KMnO4 solution and
subsequent heating. Chromatographic purification of products was
performed using Fluka silica gel 60 for preparative column
chromatography (particle size 40–63
mm). Reactions at 0 8C were
4. Experimental
carried out in an ice/water bath. Reactions at ꢀ78 8C were carried
out in a dry ice/acetone bath.
4.1. Materials and methods
Nuclear magnetic resonance (NMR) spectra were recorded in
CDCl3 or C6D6 on a Bruker Av-400 spectrometer at room tempera-
All reagents and starting materials were purchased from
commercial suppliers and used without further purification.
ture. The measured chemical shifts are reported in
residual signal of the solvent was used as the internal standard
d (ppm) and the

A. Chiotellis et al. / Journal of Fluorine Chemistry 160 (2014) 20–28
25
(CDCl3 1H:
d
= 7.26 ppm, 13C:
d
= 77.0 ppm, C6D6: 1H:
d
= 7.16 ppm,
column chromatography (hexane/ethyl acetate 7:3) afforded 2.4 g
(50%) of monoacetate 3 as a colorless viscous oil. 1H NMR
13C: = 128.39 ppm). For the 19F NMR spectra, CFCl3(=0.00 ppm)
d
was used as the internal standard. All 13C NMR spectra were
measured with complete proton decoupling. 1H and 13C NMR peaks
werefully assigned for all new compounds. Analysisand assignment
of the 1H NMR data were supported by 1H, 1H COSY and 13C, 1H HSQC
experiments. The assignment of the ambiguous C-2/5 and C-4 in the
case of the TMOP analogs, was established through the observation
of long range heteronuclear coupling with the protons of their
corresponding methoxy groups in 13C, 1H HMBC experiments. The
numbering of the TMOP atoms is shown in Scheme 2. For compound
8 the chemical shift of the carbon N–CH55CH–N of the imidazole ring
was differentiated from its geminal one on the basis of its
heteronuclear long range coupling with the SiCH2CH2N protons.
Data of NMR spectra are reported as follows: s = singlet, d = doublet,
t = triplet, m = multiplet, dd = doublet of doublets, dt = doublet of
triplets, dq = doublet of quartets, br = broad signal. The coupling
constant J is reported in Hertz (Hz). Mass spectra were recorded on a
Waters Micromass Autospec Ultima (EI-sector) or a Varian Ionspec
Ultima (MALDI/ESI-FT-ICR) (both MS service of Laboratory of
Organic Chemistry (LOC) at the ETH Zurich).
(400 MHz, CDCl3): d 7.57–7.47 (m, 4 H, SiC6H5), 7.45–7.32 (m, 6 H,
SiC6H5), 4.20 (t, J = 8.4 Hz, 2 H, SiCH2CH2OAc), 3.80 (t, J = 8.3 Hz, 2
H, SiCH2CH2OH), 1.93 (s, 3 H, –O(C55O)CH3), 1.52–1.66 (m, 5 H,
HOCH2CH2SiCH2CH2OAc). 13C NMR (100 MHz, CDCl3):
d 171.1 (–
O(C55O)CH3), 134.7, 134.3, 129.7 and 128.1 (SiC6H5), 61.9
(SiCH2CH2Oac), 59.5 (SiCH2CH2OH), 21.0 (SiCH2CH2OAc), 18.2
(SiCH2CH2OH), 14.1 (–O(C55O)CH3). ESI-QTOF MS m/z calculated
for C18H22O3Si [M+Na]+ 337.1230, found 337.1227.
4.2.3. 2-((2-Bromoethyl)diphenylsilyl)ethyl acetate (30)
Triphenylphosphine (690 mg, 2.44 mmol) was added to an ice
cold solution of 3 (640 mg, 2.04 mmol) in dichloromethane
(10 ml) and after 10 min of stirring carbon tetrabromide (1.01 g,
3.05 mmol) was added in three portions within 5 min. The bright
yellow solution that formed was allowed to reach room
temperature where it was stirred for 2 h. The reaction mixture
was then diluted with DCM and washed once with aq. NaHCO3
(sat), followed by water (1ꢂ) and brine (1ꢂ), dried over sodium
sulfate, filtered and evaporated to dryness. The crude oil that
resulted was purified by flash column chromatography using
hexane/ethyl acetate (95:5) to provide the title compound as a
4.2. Chemistry
clear, colorless oil (740 mg, 96%). 1H NMR (400 MHz, CDCl3):
d
4.2.1. 2,20-(Diphenylsilanediyl)diethanol (2)
7.53–7.35 (m, 10 H, SiC6H5), 4.18 (t, JH = 8 Hz, 2 H, SiCH2CH2OAc),
3.58–3.50 (m, 2 H, SiCH2CH2Br), 1.99–1.92 (m, 5 H, SiCH2CH2Br
and –O(C55O)CH3), 1.59 (t, J = 8 Hz, 2 H, SiCH2CH2OAc). 13C NMR
A solution of diphenyldivinylsilane 1 (4.8 g, 20.3 mmol) in
30 ml THF was added dropwise to a 0.5 M solution of 9-
borabicyclo[3.3.1]nonane in THF (42.6 mmol, 85 ml) and the
resulting mixture was stirred at room temperature for 4 h,
followed by the addition of water (16.2 ml) and 3 M aqueous
sodium hydroxide solution (16.2 ml). Subsequently, aqueous
hydroxide peroxide solution (30 wt%, 16.2 ml) was added drop-
wise at 0 8C within 15 min and the reaction mixture was heated to
reflux for 3 h. Upon cooling to 20 8C, the aqueous layer was
saturated with potassium carbonate, the organic layer was
removed and the aqueous layer was extracted with ethyl acetate
(3ꢂ 20 ml). The combined organic phases were dried over
anhydrous potassium carbonate, filtered and concentrated to
dryness. The crude was dissolved in dichloromethane (80 ml),
placed at 4 8C for 4 h and then at ꢀ25 8C for 18 h. The precipitated
crystalline cyclooctane-1,5-diol was filtered off (5.1 g) and washed
with cold dichloromethane. The filtrate and washings were
combined and the solvent was removed under reduced pressure.
The residue was purified by gravity column chromatography on
silica gel using ethyl acetate. The fractions containing the product
were combined and solvents were removed under reduced
pressure to give 2 in 76% yield as a colorless viscous oil (4.2 g)
which solidified upon standing at room temperature. 1H NMR
(100 MHz, CDCl3): d 171.0 (–O(C55O)CH3), 134.6, 133.0, 130.1 and
128.3 (SiC6H5), 61.5 (SiCH2CH2OAc), 30.3 (SiCH2CH2Br), 20.9
(SiCH2CH2OAc), 20.5 (SiCH2CH2Br), 13.6 (–O(C55O)CH3). ESI-
QTOF MS m/z calculated for C18H21BrO2Si [M+Na]+ 399.0392,
found 399.0388.
Reaction conditions for subsequent fluorination: Potassium
fluoride (28 mg, 0.47 mmol) was suspended to a solution of 30
(160 mg, 0.42 mmol) in acetonitrile (15 ml) at 0 8C, followed by the
addition of Kryptofix1 (176 mg, 0.47 mmol) in three portions
within 5 min. During the addition, bubbling was observed. After
30 min, the reaction was allowed to reach room temperature and
was diluted with ethyl acetate and washed with water and brine,
dried over sodium sulfate and evaporated to dryness. The crude
was analyzed by 1H NMR where only fluorosilane 4 was detected.
In a different reaction, 30 was dissolved in THF and TBAF 1 M in THF
was added at 0 8C resulting again only in fluorosilane 4.
4.2.4. 2-(Diphenyl(2-(((trifluoromethyl)sulfonyl)oxy)ethyl)silyl)ethyl
acetate (300)
Triflic anhydride (0.14 ml, 227 mg, 0.805 mmol) was added
dropwise within 3 min to a solution of 3 (230 mg, 0.73 mmol) and
(400 MHz, CDCl3):
d
7.56–7.49 (m, 4 H, SiC6H5), 7.43–7.33 (m, 6 H,
pyridine (70 ml, 69.4 mg, 0.88 mmol) in dichloromethane (2 ml) at
SiC6H5), 3.83 (t, J = 7.6 Hz, 4 H, SiCH2CH2OH), 1.64 (br, 2 H,
SiCH2CH2OH), 1.58 (t, J = 7.6 Hz, 4 H, SiCH2CH2OH). 13C NMR
ꢀ5 8C. The pink solution that resulted was stirred at 0 8C for
30 min. The solution was then diluted with cold DCM, washed once
with cold HCI 1 M and dried shortly over magnesium sulfate. The
dichloromethane was evaporated with a stream of Argon to a
volume of approximately 5 ml which was used for the next step
without further purification due to the high sensitivity of the
triflate.
(100 MHz, CDCl3):
d 134.9, 134.7, 129.6 and 128.0 (SiC6H5), 59.5
(SiCH2CH2OH), 18.1 (SiCH2CH2OH). ESI-QTOF MS m/z calculated
for C16H20O2Si [M+Na]+ 295.1125, found 295.1125.
4.2.2. 2-((2-Hydroxyethyl)diphenylsilyl)ethyl acetate (3)
To an ice cold solution of 2 (4.2 g, 15.42 mmol), triethylamine
(3.12 g, 30.8 mmol) and DMAP (19 mg, 1.56 mmol) in dichlor-
omethane (30 ml), acetic anhydride (1.73 ml, 18.34 mmol) was
added dropwise within 10 min. The resulting reaction mixture
was stirred for 30 min at 0 8C and then for 3 h at room temperature.
The reaction mixture was then diluted with dichloromethane
(30 ml) and washed with saturated aqueous sodium hydrogen
carbonate solution (1ꢂ 30 ml), water (1ꢂ 30 ml) and brine (1ꢂ
30 ml). The organic phase was dried over sodium sulfate, filtered
and concentrated to dryness. Purification of the residue by flash
Reaction conditions for fluorination with TBABF/KHF2: The above
mentioned solution was cooled at 0 8C and KHF2 (17.1 mg,
0.22 mmol) was added, followed by the dropwise addition of
TBABF (247 mg, 0.88 mmol, dried at 100 8C for 15 min under high
vacuum before use) as a solution in 2 ml dichloromethane. The
reaction was stirred for 3 h at 0 8C and then was allowed to reach
room temperature and washed with water and brine. It was then
dried over sodium sulfate, filtered and evaporated to dryness. NMR
analysis of the crude revealed no trace of the desired 2-
fluoroethylsilane 5.

26
A. Chiotellis et al. / Journal of Fluorine Chemistry 160 (2014) 20–28
4.2.5. 2-((2-Fluoroethyl)diphenylsilyl)ethyl acetate (5)
stirred for 16 h. After this time the solvent was removed under
reduced pressure and the residue was chromatographed on silica
gel using ethyl acetate/hexane 8:2–7:3 as eluent system to yield
compound 8 as a yellow oil (227 mg, 92%). 1H NMR (400 MHz,
A solution of 3 (2.4 g, 7.63 mmol) in dry DCM (65 ml) was
cooled to ꢀ78 8C and DAST (1.48 g, 9.16 mmol) was added
dropwise within 20 min. The reaction mixture was stirred at
ꢀ78 8C for 30 min before being quenched by the addition of
NaHCO3 5% solution (10 ml). After reaching room temperature, the
aqueous layer was removed and the organic phase was washed
with 5% NaHCO3 solution (2ꢂ 30 ml), brine (1ꢂ 70 ml), dried over
sodium sulfate, filtered and evaporated to dryness under reduced
pressure. The crude oil was dissolved in acetone (16 ml), sat.
NaHCO3 solution (16 ml) was added and the reaction mixture was
stirred for 16 h. After this time, water was added (20 ml) and the
solution was extracted with ether (3ꢂ 30 ml). The organic fractions
were combined and dried over sodium sulfate, filtered and
concentrated under vacuum. The crude was purified by flash
chromatography with hexane/ethyl acetate 9:1 to yield 242 mg
CDCl3):
d 7.58–7.39 (m, 10 H, SiC6H5), 7.07 (d, J = 1 Hz, 1 H, N–
2
CH55CH–N), 7.00 (d, J = 1 Hz, 1 H, N–CH = CHN), 4.64 (dt, JF–
H = 48 Hz, JH–H = 8 Hz, 2 H, SiCH2CH2F), 4.47–4.40 (m, 2 H,
3
SiCH2CH2N), 1.86–1.79 (m, 2 H, SiCH2CH2N, partially overlapping
3
3
with SiCH2CH2F), 1.75 (dt, JF–H = 23.1 Hz, JH–H = 8 Hz, 2 H,
SiCH2CH2F). 13C NMR (100 MHz, CDCl3):
144.5 (N–C(NO2)–N),
134.6, 132.5, 130.3 and 128.5 (SiC6H5), 128.4 (N–CH55CH–N) 125.1
d
1
2
(N–CH55CH–N), 81.4 (d, JC–F = 166.4 Hz), 47.2, 16.7, 15.9 (d, JC–
F = 20 Hz). 19F NMR (376 MHz, CDCl3):
H = 48 Hz, JF–H = 23.1 Hz, 1 F). ESI-QTOF MS m/z calculated for
19H20FN3O2Si [M+Na]+ 392.1201, found 392.1198.
d
ꢀ202.9 (septet, JF–
2
3
C
(10%) of the desired 2-fluoroethylsilane 5 as a colorless oil. 1H NMR
4.2.9. (Diphenylsilanediyl)bis(methylene) diacetate (10)
Sodium acetate (5.83 g, 71.1 mmol) was added to a solution of
(diphenyl)bischloromethylsilane 9 (2 g, 7.11 mmol) in DMF
(14 ml) and the suspension was heated at 100 8C for 6 h. After
cooling, water was added (50 ml) and the reaction was extracted
with ethyl acetate (3ꢂ 25 ml). The combined organic layers were
dried under sodium sulfate, filtered and evaporated to dryness. The
crude was purified by flash column chromatography on silica with
hexane/ethyl acetate 9:1 to afford the title compound (2.1 g, 90%)
as a clear oil which solidified upon standing at room temperature.
2
(400 MHz, CDCl3):
F = 48.2 Hz, JH–H = 8.3 Hz, 2 H, SiCH2CH2F), 4.21 (t, JH–H = 8 Hz, 2
d
7.58–7.33 (m, 10 H, SiC6H5), 4.59 (dt, JH–
3
3
3
H, SiCH2CH2OAc), 1.88 (s, 3 H, –O(C55O)CH3), 1.75 (dt, JF–
3
3
H = 20.2 Hz, JH–H = 8.3 Hz, 2 H, SiCH2CH2F), 1.57 (t, JH–H = 8 Hz,
2 H, SiCH2CH2OAc). 13C NMR (100 MHz, CDCl3):
171.0 (–
d
1
O(C55O)CH3), 134.6, 133.5, 129.9 and 128.2 (SiC6H5), 81.6 (d, JC–
F = 166 Hz, SiCH2CH2F), 61.7 (SiCH2CH2OAc), 20.9 (SiCH2CH2OAc),
2
16.4 (d, JC–F = 18.4 Hz, SiCH2CH2F), 14.1 (–O(C55O)CH3). 19F NMR
(376 MHz, CDCl3):
d
ꢀ201.3 to ꢀ201.7 (m, 1 F). ESI-QTOF MS m/z
calculated for C18H21FO2Si [M+Na]+ 339.1187, found 339.1191.
1H NMR (400 MHz, CDCl3):
(m, 6 H, SiC6H5), 4.38, (s, 4 H, SiCH2OAc), 2.00 (s, 6 H, –O(C55O)CH3).
13C NMR (100 MHz, CDCl3):
171.5 (–O(C55O)CH3), 135.06, 130.8,
d 7.61–7.56 (m, 4 H, SiC6H5), 7.49–7.37
4.2.6. (2-(Hydroxydiphenylsilyl)ethyl acetate) (6)
d
Silanol 6 was isolated by increasing the polarity of the eluent to
130.4 and 128.2 (SiC6H5), 53.3 (SiCH2OAc), 20.7 (–O(C55O)CH3).
ESI-QTOF MS m/z calculated for C18H20O4Si [M+Na]+ 351.1023,
found 351.1023.
hexane/ethyl acetate 8:2: 1H NMR (400 MHz, CDCl3):
d 7.64–7.58
(m, 4 H, SiC6H5), 7.46–7.34 (m, 6 H, SiC6H5), 4.31 (t, J = 8.1 Hz, 2 H,
SiCH2CH2OAc), 3.21 (s, 1 H, SiOH), 1.86 (s, 3 H, –O(C55O)CH3), 1.61
(t, J = 8.1 Hz, 2 H, SiCH2CH2OAc). 13C NMR (100 MHz, CDCl3):
d
4.2.10. ((Hydroxymethyl)diphenylsilyl)methyl acetate (11)
171.5 (–O(C55O)CH3), 135.4, 134.0, 130.1 and 128.0 (SiC6H5), 61.5
(SiCH2CH2OAc), 20.9 (SiCH2CH2OAc), 16.2 (–O(C55O)CH3). ESI-
QTOF MS m/z calculated for C16H18O3Si [M+Na]+ 309.0917, found
309.0923.
Potassium carbonate (207 mg, 1.5 mmol) was added to a
solution of 10 (1 g, 3.04 mmol) in methanol (25 ml) and the
solution was stirred for 1 h at room temperature. The reaction was
then filtered and the filtrate was partitioned between water
(40 ml) and ethyl acetate (40 ml). The organic layer was separated
and the aqueous phase was extracted with ethyl acetate (2ꢂ
40 ml). The combined organic layers were washed with brine,
dried under sodium sulfate, filtered and evaporated to dryness
under reduced pressure. The crude was purified by flash column
chromatography using hexane/ethyl acetate 8:2 to yield com-
pound 11 (166 mg, 19%) as a clear colorless oil. 1H NMR (400 MHz,
4.2.7. 2-((2-Fluoroethyl)diphenylsilyl)ethanol (7)
To a solution of 5 (240 mg, 0.76 mmol) in methanol (4 ml) at
room temperature was added potassium carbonate (110 mg,
0.80 mmol) in one portion. After stirring for 1 h, the reaction
mixture was quenched with water (6 ml) and extracted with ethyl
acetate (3ꢂ 5 ml). The combined organic layers were washed with
brine (10 ml) and dried over anhydrous sodium sulfate. The solvent
was removed under reduced pressure and the residue was purified
by flash chromatography to afford 7 as a colorless oil (197 mg,
CDCl3):
4.42, (s, 2 H, SiCH2OAc), 3.98 (s, 2 H, SiCH2OH), 2.02 (s, 3 H, –
O(C55O)CH3), 1.85 (br, 1 H, SiCH2OH). 13C NMR (100 MHz, CDCl3):
d 7.63–7.58 (m, 4 H, SiC6H5), 7.48–7.36 (m, 6 H, SiC6H5),
d
95%). 1H NMR (400 MHz, CDCl3):
d
7.56–7.35 (m, 10 H, SiC6H5),
172.1 (–O(C55O)CH3), 135.08, 131.4, 130.3 and 128.2 (SiC6H5), 54.3
(SiCH2OAc), 52.0 (SiCH2OH), 20.8 (O(C55O)CH3). ESI-QTOF MS m/z
calculated for C16H18O3Si [M+Na]+ 309.0917, found 309.0917.
2
3
4.64 (dt, JF–H = 48 Hz, JH–H = 8 Hz, 2 H, SiCH2CH2F), 3.80 (t,
J = 8.0 Hz, 2 H, SiCH2CH2OH), 1.75 (t, 3JF–H = 20.1 Hz, 3JH–H = 8 Hz, 2
H, SiCH2CH2F), 1.57 (t, J = 8.0 Hz, 2 H, SiCH2CH2OH), 1.34 (br, 1 H,
SiCH2CH2OH). 13C NMR (100 MHz, CDCl3):
d
134.7, 134.1, 129.8
4.2.11. Bis(2,4,6-trimethoxyphenyl)divinylsilane (13)
1
and 128.1 (SiC6H5), 81.9 (SiCH2CH2F, d, JC–F = 167.8 Hz), 59.4
To a solution of 1,3,5-trimethoxybenzene (2 g, 11.89 mmol) and
TMEDA (1.42 g, 12.22 mmol) in dry n-hexane (14.1 ml) under
vigorous stirring, was added dropwise a 2.5 M solution of n-
butyllithium in hexanes (5 ml, 12.5 mmol) within 8 min at 20 8C.
The resulting suspension of TMOP-Li was stirred at room
temperature for another 16 h and then added dropwise at 0 8C
within 10 min to a stirred solution of dichlorodivinylsilane 12
(0.91 g, 5.94 mmol) in dry n-hexane (5.7 ml). The reaction mixture
was allowed to warm to room temperature and stirred for an
additional hour. The reaction was quenched by slowly adding
saturated NH4Cl (7 ml) at 0 8C. Water (25 ml) and ethyl acetate
(15 ml) were added and the organic layer was separated. The
aqueous phase was washed with ethyl acetate (2ꢂ 20 ml) and the
2
(SiCH2CH2OH), 18.3 (SiCH2CH2OH), 15.9 (SiCH2CH2F, d, JC–
F = 17.9 Hz). 19F NMR (376 MHz, CDCl3):
d
ꢀ201.2 (septet, JF–
2
3
H = 48 Hz, JF–H = 20.1 Hz, 1 F). ESI-QTOF MS m/z calculated for
C
16H19FOSi [M+Na]+ 297.1081, found 297.1074.
4.2.8. 1-(2-((2-Fluoroethyl)diphenylsilyl)ethyl)-2-nitro-1H-
imidazole (8)
Triphenylphosphine (229 mg, 0.87 mmol) was added to a
solution of
7
(184 mg, 0.67 mmol) and 2-nitroimidazole
(98.5 mg, 0.87 mmol) in THF (30 ml). After stirring for 15 min at
room temperature, DIAD (180 mg, 0.87 mmol) was added drop-
wise within 10 min and the clear yellow solution that formed was

A. Chiotellis et al. / Journal of Fluorine Chemistry 160 (2014) 20–28
27
combined organic layers were washed with water (1ꢂ 25 ml) and
brine (1ꢂ 25 ml), dried over Na2SO4, filtered and concentrated
under reduced pressure. The crude was purified using flash
chromatography with hexane/ethyl acetate 9:1 to yield 13 as a
white solid (1.98 g, 80%). Crystals, suitable for X-ray crystallogra-
phy, were obtained by slow evaporation from CH2Cl2/hexane. 1H
d 170.8 (–O(C55O)CH3), 166.7 (C-2/C-6), 163.8 (C-4), 106.1 (C-1),
91.4 (C-3/C-5), 64.8 (SiCH2CH2OAc), 61.5 (SiCH2CH2OH), 55.3 (o-
OCH3), 55.0 (p-OCH3), 23.4 (SiCH2CH2OH), 21.3 (–OCOCH3), 19.3
(SiCH2CH2OAc). HRMS: calculated for 461.0948 (M+H) found
461.0945.
NMR (400 MHz, C6D6):
d
7.24 (dd, 3Jtrans = 20.3 Hz, 3Jcis = 14.3 Hz, 2
4.2.14. 2-((2-((Methylsulfonyl)oxy)ethyl)bis(2,4,6-
H, CH55CH2), 6.17 (dd, 3Jcis = 14.3 Hz, 2Jgem = 4.1 Hz, 2 H, CH55CHH),
6.09 (s, 4 H, H-3/H-5), 5.99 (dd, 3Jtrans = 20.3 Hz, 2Jgem = 4.1 Hz, 2 H,
CH55CHH), 3.38 (s, 6 H, p-OCH3), 3.29 (s, 12 H, o-OCH3). 13C NMR
trimethoxyphenyl)silyl)ethyl acetate (16)
To a solution of 15 (120 mg, 0.24 mmol) and triethylamine
(0.13 ml, 0.93 mmol) in dichloromethane (1.6 ml) a solution of
methanesulfonylchloride (31 mg, 0.27 mmol) in dichloromethane
(0.2 ml) was added dropwise at ꢀ30 8C within 1 min. The reaction
mixture was stirred for 2 h during which time, the temperature
reached ꢀ3 8C. The solvent was removed with a stream of argon
and the residue was quickly chromatographed on silica gel using
benzene/ethyl acetate/triethylamine (80:20:5) as the eluent. The
fractions of interest were combined and the solvents were
removed under reduced pressure at 30 8C to yield 16 (125 mg,
90%). The compound decomposes rapidly at room temperature but
it is stable for a few days at ꢀ25 8C as a solution in benzene. 1H
(100 MHz, C6D6):
d 167.1 (C-2/C-6), 163.9 (C-4), 140.9 (CH55CH2),
129.4 (CH55CH2), 106.5 (C-1), 91.8 (C-3/C-5), 55.5 (o-OCH3), 55.0
(p-OCH3). ESI-QTOF MS m/z calculated for C22H28O6Si [M+H]+
417.1728, found 417.1726.
4.2.12. 2,20-(Bis(2,4,6-trimethoxyphenyl)silanediyl)diethanol (14)
A solution of 13 (1.98 g, 4.75 mmol) in THF (16 ml) was added to
a 0.5 M solution of 9-borabicyclo[3.3.1]nonane (20 ml, 9.98 mmol)
and the resulting mixture was stirred at room temperature for 3 h,
followed by the addition of water (4 ml) and a 3 M aqueous sodium
hydroxide solution (4 ml). Subsequently,
a
30 wt% aqueous
NMR (400 MHz, C6D6): d 6.00 (s, 4 H, H-3/H-5), 4.67 (m, 2 H,
hydrogen peroxide solution (4 ml) was added dropwise at 0 8C
within 10 min and the reaction mixture was heated to reflux for
3 h. Upon cooling to 20 8C, the aqueous layer was saturated with
potassium carbonate, the organic layer was removed and the
aqueous layer was extracted with ethyl acetate (3ꢂ 10 ml). The
combined organic phases were dried over anhydrous potassium
carbonate, filtered and concentrated to dryness. The crude was
dissolved in dichloromethane (20 ml), placed at 4 8C for 2 h and
then at ꢀ25 8C for 16 h. The precipitated cyclooctane-1,5-diol was
filtered off (1.1 g) and washed with cold dichloromethane. The
filtrates were combined and the solvent was removed under
reduced pressure. The residue was purified by flash column
chromatography on silica gel starting with ether to remove the rest
of cyclooctane-1,5-diol following by ether/ethanol 7:3 to elute the
desired compound. The fractions containing the product were
combined and the solvents were removed under reduced pressure
to give the title compound as a colorless viscous oil (1.73 g, 80%),
which solidified upon standing at room temperature. 1H NMR
SiCH2CH2OMs), 4.51 (m, 2 H, SiCH2CH2OAc), 3.36 (s, 6 H, p-OCH3),
3.27 (s, 12 H, o-OCH3), 2.25 (s, 3 H, –OSO2CH3), 2.09 (m, 2 H,
SiCH2CH2OMs), 1.96 (m, 2 H, SiCH2CH2OAc), 1.74 (s, 3 H, –
OCOCH3). 13C NMR (100 MHz, C6D6):
d 170.8 (–OCOCH3), 166.7 (C-
2/C-6), 164.1 (C-4), 104.6 (C-1), 91.3 (C-3/C-5), 71.9 (SiCH2-
CH2OMs), 64.2 (SiCH2CH2OAc), 55.3 (o-OCH3), 55.0 (p-OCH3), 37.3
(–OSO2CH3), 21.3 (–OCOCH3), 20.6 (SiCH2CH2OMs), 19.3 (SiCH2-
CH2OAc). Note: Due to the instability of the compound, HRMS was
not possible.
4.2.15. 2-(Fluorobis(2,4,6-trimethoxyphenyl)silyl)ethyl acetate (17)
To a solution of 16 (56 mg, 0.098 mmol) and Kryptofix 222
(37 mg, 0.098 mmol) in dry acetonitrile (0.3 ml), potassium
fluoride (5.7 mg, 0.098 mmol) was added in one portion at 0 8C.
The reaction mixture was allowed to reach room temperature and
was stirred for 2 h. The reaction was diluted with ethyl acetate
(5 ml) and washed with water (1ꢂ 2 ml) and brine (1ꢂ 2 ml), dried
over sodium sulfate, filtered and concentrated to dryness. The
crude was chromatographed on silica gel with benzene/ethyl
acetate 9:1 to yield fluorosilane 17 (8 mg, 17%) and silanol 18
(400 MHz, C6D6):
d 6.04 (s, 4 H, H-3/H-5), 3.99 (t, J = 7.9 Hz, 4 H,
SiCH2CH2OH), 3.37 (s, 6 H, p-OCH3), 3.23 (s, 12 H, o-OCH3), 1.93 (t,
J = 7.9 Hz, 4 H, SiCH2CH2OH), 1.22 (br, 2 H, OH). 13C NMR
(12 mg, 26%). Compound 17: 1H NMR (400 MHz, C6D6):
d 6.02 (s, 4
(100 MHz, C6D6):
d
166.5 (C-2/C-6), 163.4 (C-4), 106.1 (C-1),
H, H-3/H-5), 4.76 (m, 2 H, SiCH2CH2OAc), 3.33 (s, 6 H, p-OCH3), 3.32
(s, 12 H, o-OCH3), 2.20–2.12 (m, 2 H, SiCH2CH2OAc), 1.70 (s, 3 H, –
91.2 (C-3/C-5), 61.1 (SiCH2CH2OH), 55.2 (o-OCH3), 55.1 (p-OCH3),
22.9 (SiCH2CH2OH). ESI-QTOF MS m/z calculated for C22H32O8Si
[M+Na]+ 475.1764, found 475.1762.
OCOCH3). 19F NMR (376.5 MHz, C6D6):
d
ꢀ159.0 (t, 3JF–H = 6.9 Hz).
Compound 18: 1H NMR (400 MHz, C6D6):
d 6.01 (s, 4 H, H-3/H-5),
4.90 (m, 2 H, SiCH2CH2OAc), 3.33 (s, 6 H, p-OCH3), 3.27 (s, 12 H, o-
OCH3), 2.24 (t, 3J = 8.7 Hz, 2 H, SiCH2CH2OAc), 1.70 (s, 3 H, –
OCOCH3).
4.2.13. 2-((2-Hydroxyethyl)bis(2,4,6-trimethoxyphenyl)silyl)ethyl
acetate (15)
To an ice cold solution of 14 (1.73 g, 3.82 mmol), pyridine
(0.62 ml, 7.67 mmol) and DMAP (56 mg, 0.46 mmol) in dichlor-
omethane (14 ml), acetic anhydride (0.4 ml, 4.24 mmol) was
added dropwise within 10 min. The resulting reaction mixture
was stirred at 0 8C for 30 min and at room temperature for 3 h.
The mixture was diluted with ethyl acetate (50 ml) and washed
with a 10% aqueous copper sulfate solution (3ꢂ 20 ml), water
(1ꢂ 30 ml), saturated aqueous sodium hydrogen carbonate (1ꢂ
30 ml) and brine (1ꢂ 30 ml). The organic phase was dried over
sodium sulfate, filtered and concentrated to dryness. Purification
of the residue by flash column chromatography (hexane/ethyl
acetate 5:5) afforded monoacetate 15 as a colorless viscous
4.2.16. Bis(chloromethyl)bis(2,4,6-trimethoxyphenyl)silane (20)
1,3,5-Trimethoxybenzene (922 mg, 5.48 mmol) was dissolved
in a mixture of TMEDA (656 mg, 5.65 mmol) and dry n-hexane
(6.5 ml). To this solution and under vigorous stirring, a 2.5 M
solution of n-butyllithium in hexane (2.3 ml, 5.75 mmol) was
added dropwise at 20 8C within 5 min. The resulting suspension of
TMOP-Li was stirred at room temperature for another 16 h and
then added dropwise at 0 8C within 10 min to a stirred solution of
(dichloro)bischloromethylsilane 19 (517 mg, 2.61 mmol) in dry n-
hexane (2.5 ml). The reaction mixture was allowed to warm to
room temperature and stirred for an additional hour. The reaction
was quenched by slowly adding saturated NH4Cl solution (5 ml) at
0 8C. Water (20 ml) and ethyl acetate (10 ml) were added and the
organic layer was separated. The aqueous phase was washed with
ethyl acetate (2ꢂ 15 ml) and the combined organic layers were
washed with water (1ꢂ 20 ml) and brine (1ꢂ 20 ml), dried over
liquid (0.91 g, 48%). 1H NMR (400 MHz, C6D6):
d 6.02 (s, 4 H, H-3/
H-5), 4.60 (m, 2 H, SiCH2CH2OAc), 3.96 (t, J = 7.8 Hz, 2 H,
SiCH2CH2OH), 3.36 (s, 6 H, p-OCH3), 3.26 (s, 12 H, o-OCH3), 2.06
(m, 2 H, SiCH2CH2OAc), 1.92 (t, J = 7.8 Hz, 2 H, SiCH2CH2OH), 1.73
(s, 3 H, –OCOCH3), 1.12 (br, 1 H, OH). 13C NMR (100 MHz, C6D6):

28
A. Chiotellis et al. / Journal of Fluorine Chemistry 160 (2014) 20–28
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Na2SO4, filtered and concentrated under reduced pressure. The
crude was purified by flash chromatography with hexane/ethyl
acetate 8:2 to yield 785 mg of 20 a white solid (65%). Crystals,
suitable for X-ray crystallography, were obtained by slow
evaporation from CH2Cl2/hexane. 1H NMR (400 MHz, C6D6):
5.96 (s, 4 H, H-3/H-5), 4.15 (s, 4 H, SiCH2Cl), 3.31 (s, 6 H, p-OCH3),
3.17 (s, 12 H, o-OCH3). 13C NMR (100 MHz, C6D6):
167.1 (C-2/C-6),
d
d
164.5 (C-4), 103.0 (C-1), 91.5 (C-3/C-5), 55.3 (o-OCH3), 55.0 (p-
OCH3), 31.5 (-CH2Cl). MALDI MS m/z calculated for C20H27Cl2O6Si
[M+H]+ 461.0954, found 461.0948.
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4.3. Crystallography
X-ray analyses for 13 and 20 were performed on a Bruker Apex
II Duo diffractometer at 100 K. Crystallographic data of C22H28O6Si
(13) and C20H26Cl2O6Si (20) have been deposited with the
Cambridge Crystallographic Data Center with deposition numbers
CCDC 956644 and CCDC 956645 respectively and can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif.
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