Enhanced nucleophilic fluorination and radiofluorination of organosilanes appended with potassium-chelating leaving groups

Article abstract of DOI:10.1016/j.jfluchem.2013.12.005

Here we aimed to explore the feasibility of enhancing the fluorination of organosilanes by appending potassium-chelating groups to the substrates. For this purpose, eight organosilanes were prepared in which a linear or cyclic leaving group, with putative

Full text of DOI:10.1016/j.jfluchem.2013.12.005

Journal of Fluorine Chemistry 158 (2014) 48–52
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Enhanced nucleophilic fluorination and radiofluorination of
organosilanes appended with potassium-chelating leaving groups
Mohammed H. Al-huniti a, Shuiyu Lu b, Victor W. Pike b, , Salvatore D. Lepore
*
a,**
a Department of Chemistry, Florida Atlantic University, Boca Raton, FL 33431, United States
b Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1003, United States
A R T I C L E I N F O
A B S T R A C T
Article history:
Here we aimed to explore the feasibility of enhancing the fluorination of organosilanes by appending
potassium-chelating groups to the substrates. For this purpose, eight organosilanes were prepared in
which a linear or cyclic leaving group, with putative potassium-chelating ability, was attached
covalently to a congested silicon atom via an ether linkage to serve as a potential nucleophilic assisting
leaving group (NALG). Organosilicon-NALGs with expected strong potassium-chelating capability
enhanced reactions with potassium fluoride in acetonitrile to produce organofluorosilanes without any
need to separately add phase transfer reagent. Similar rate enhancements were also observed with
cyclotron-produced [18F]fluoride ion (t1/2 = 109.7 min, b+ = 97%) in the presence of potassium carbonate
in MeCN–0.5% H2O. This study found that metal-chelating NALG units can accelerate fluorination and
radiofluorination reactions at sterically crowded silicon atoms.
Received 30 October 2013
Received in revised form 9 December 2013
Accepted 14 December 2013
Available online 19 December 2013
Keywords:
Chelating leaving group
Fluoroorganosilane
Fluorine-18
Fluorination
ß 2013 Elsevier B.V. All rights reserved.
Radiofluorination
1. Introduction
metabolic instability by incorporating bulky iso-propyl or tert-
butyl groups near the silicon atom [6], and to reduce overall
We have shown that the appendage of particular metal-
chelating leaving groups to substrates is capable of facilitating
nucleophilic substitution reactions, where the halide nucleophile
originates from a metal salt [1] or titanium(IV) complex [2]. We
dubbed such groups as ‘nucleophile assisting leaving groups’
(NALGs), arguing that the observed rate enhancements afforded by
these new nucleofuges are primarily due to stabilizing interactions
between substrates and metal-nucleophile pairs to lower transi-
tion state energies [3]. More recently, we have applied NALGs to
expedite the formation of C–18F bonds in potential radiotracers for
molecular imaging with positron emission tomography (PET) [4].
The exploitation of organosilanes as superb [18F]fluoride ion
acceptors has emerged as an interesting strategy for the rapid
introduction of cyclotron-produced no-carrier-added (NCA) fluo-
rine-18 (t1/2 = 109.7 min; b+ = 97%) into potential PET radiotracers
[5]. Nevertheless, [18F]organofluorosilanes have not yet been
widely used in PET because of certain shortcomings, such as
lipophilicity by introducing charged or hydrophilic groups at an
aromatic linker [7]. Moreover, small molecule [18F]organofluor-
osilanes have been developed as labeling synthons [8] for
preparing macromolecular PET radiotracers, especially peptides
and proteins. Low molecular weight [18F]organosilanes are also
now appearing as PET radiotracers [9].
Existing techniques for the radiofluorination of organosilyl
groups require forcing conditions, which include an acidic reaction
medium, elevated temperature and polar solvent (e.g., DMSO). For
example, the radiofluorinations of some ethoxysilanes were
recently achieved with a solution of [18F]fluoride ion-quaternary
ammonium salt in 2% acetic acid–DMSO at 90 8C for 23 min
[10,11]. In most radiofluorination reactions, K+–kryptofix 2.2.2
(K+–K 2.2.2), K+–18-crown-6 or another bulky cation is used as a
necessary phase transfer agent [12]. Such phase transfer com-
plexes react slowly with organosilanes, especially if the silicon
atom is bonded to bulky organic groups for the purpose of
ultimately avoiding rapid hydrolysis in vivo [6]. Alternative
radiolabeling by 18F/19F exchange reactions, either in labeling
synthons [13] or preformed macromolecular substrates [6a,8b],
does not have wide utility because the resultant PET radiotracers
have low specific activity.
susceptibility to Si–18
lipophilicity. Recently, however progress has been made to reduce
F bond hydrolysis in vivo, and high
*
Corresponding author.
Here we aimed to explore the utility of NALGs for enhancing the
fluorination and radiofluorination of organosilanes. We found that
organosilanes that bear a linear or cyclic leaving group with
**
Corresponding author. Tel.: +1 301 594 5986.
E-mail addresses: pikev@mail.nih.gov (V.W. Pike), slepore@fau.edu
(S.D. Lepore).
0022-1139/$ – see front matter ß 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2013.12.005

M.H. Al-huniti et al. / Journal of Fluorine Chemistry 158 (2014) 48–52
49
expected strong potassium-chelating ability, enhance fluorination
reactions with potassium fluoride or radiofluorination with NCA
[
strategy appears valuable for preparing non-radioactive organo-
fluorosilanes but requires further development to be useful for
preparing NCA PET radiotracers in adequate amounts due to the
limited solubility of NCA [18F]fluoride ion in the absence of
separate phase transfer agent.
organosilane substrate at room temperature in acetonitrile-d3
(1.0 mL) with potassium fluoride as the limiting reagent
(0.5 equiv.) in the absence of any separate phase transfer agent.
Under these conditions potassium fluoride was initially in a
suspension, but became completely dissolved after 10–15 min.
Substrate 1, containing a linear oligoether moiety and consequent-
ly a potential potassium-chelating leaving group, failed to give
detectable amounts of the desired organofluorosilane product 9
after 30 min. However, in the presence of excess potassium
fluoride (4 equiv.), substrate 1 was quantitatively converted into 9
after 6 h. Under identical conditions, substrate 2, containing a
linear leaving group expected to be incapable of potassium
chelation, yielded no 9 and remained inert even after 6 h.
18F]fluoride ion in the presence of potassium carbonate. The NALG
2. Results and discussion
2.1. Fluorination with potassium fluoride
2.1.1. Fluorination in the absence of 18-crown-6
We next examined substrates 3–5 and 6–8. The silicon atoms in
these substrates are variously congested with alkyl and phenyl
groups and carry one of three types of alkoxide leaving group.
Gratifyingly, substrate 3, containing a metal-chelating hydroxy-
methyl-18-crown-6 leaving group, reacted with potassium fluo-
ride in anhydrous acetonitrile-d3 to give tert-butyldiphenylsilyl
fluoride (TBDPSF, 10) in 59% yield after 30 min and in quantitative
yield after 2.3 h. By contrast, compound 4, containing a linear
methoxy triethylene oxide leaving group, failed to give any of the
organofluorosilane 10 at 30 min. Not surprisingly, substrate 5,
Our initial experiments to investigate the effect of metal-
chelating leaving groups on the yields of fluorinations of
organosilanes used non-radioactive potassium fluoride (Table 1).
Except where noted, all reactions were conducted with 0.1 M
Table 1
Fluorination of organosilanes with diverse alkoxide leaving groups.
possessing
a simple methoxy leaving group, also gave no
measurable organofluorosilane, even after 6 h. Similarly, substrate
6 gave 11 in 79% yield in 30 min, but 7 and 8 did not give any
measurable organofluorosilane 11 under the same conditions.
.
2.1.2. Fluorination in the presence of 18-crown-6
In view of the preceding results, the reactivity of substrates 1–8
toward fluoride ion in the presence of an added phase transfer
agent 18-crown-6 (18-C-6) was also assessed. Remarkably, only
substrates 3 and 6 gave no yield of fluorinated product, in stark
contrast to the high yield obtained in the absence of 18-C-6
described above. Here the added 18-C-6 presumably chelated all
available potassium ion, but this complex was unable to react
effectively at the sterically crowded silicon center (i.e., any NALG
effect was negated). Other substrates gave similar results.
Substrates 4 and 5 gave organofluorosilane 10 in low (10%) and
moderate (33%) yields with the assistance of 18-C-6. Substrates 7
and 8 needed the assistance of 18-C-6 to produce organofluor-
osilane 11 in good yields (72 and 77%, respectively).
Entry
Substrate
Product
Conversion
(%)a
Alone
0
18-C-6
1
9
20b
2
3
9
0
13
0
10
59
4
10
0
10
2.2. Radiofluorination with [18F]fluoride ion in the presence of
potassium carbonate
5
6
10
11
0
33
0
2.2.1. Radiofluorination in the absence of K 2.2.2
For the radiofluorination of substrates 3–5 in the absence of K
2.2.2, the substrate was dissolved first in the desired solvent. The
solution was then transferred to a V-vial that contained NCA
‘anhydrous potassium [18F]fluoride’, prepared by drying cyclotron-
produced aqueous [18F]fluoride ion in the presence of potassium
carbonate through conventional additions and azeotropic
removals of acetonitrile. In anhydrous acetonitrile, 3 gave 70–
80% decay-corrected radiochemical yield (RCY) based on the
radioactivity that entered liquid phase. However, the drying of
79
7
11
11
0
0
72
77
[
18F]fluoride ion in the absence of phase transfer agent resulted in
less than 5% dissolution of the starting radioactivity in acetonitrile
for this reaction. The radiofluorination of 4 and 5 gave only trace
amounts of radioactive product. Again, in both cases, only very low
proportions of starting activity (ꢀ1%) were solubilized for reaction.
Inclusion of a low concentration of water (0.5%, v/v) in the
solvent increased the dissolution of [18F]fluoride ion from 4 to 31%.
However, further increase in water content (up to 5%, v/v),
although increasing the solubilization of [18F]fluoride ion, also
reduced its reactivity, thereby reducing overall RCY. Therefore, to
8
a
All fluorinations were carried out at 0.1 M substrate conc. in anhydrous
acetonitrile-d3 (1.0 mL) at room temperature. Percent conversion, based on
potassium fluoride as limiting reagent, was measured with 1H NMR.
b
In the presence of excess potassium fluoride (4 equiv.), substrate
1 was
quantitatively converted into 9 after 6 h.

50
M.H. Al-huniti et al. / Journal of Fluorine Chemistry 158 (2014) 48–52
100
60
40
20
0
0.36 mM K2CO3
80
5
3
4
8
7
6
3
9.0 mM K2CO3
60
6
7
8
40
20
0
1.8 mM K2CO3
3
4
5
0
20
40
60
80 100 120 140
0
10
20
30
40
50
Time (min)
Time (min)
Fig. 2. RCYs versus time for the radiofluorinations of 3–8 in the presence of K2CO3
and K 2.2.2 in anhydrous acetonitrile at room temperature. Substrate concentration
was 5 mM; K2CO3 concentration was 3.6 mM.
Fig. 1. RCYs versus time for the radiofluorinations of substrates 3–8 in the presence
of the stated concentration of K2CO3 in acetonitrile containing 0.5% water at room
temperature (in the absence of K 2.2.2). Substrate concentration was 5 mM.
compare the reactivity of each organosilane-NALG, radiofluorina-
tion was carried out under identical conditions of 1.8 mM K2CO3 in
acetonitrile containing 0.5% water at room temperature (Fig. 1).
Radiofluorination of 3 for just 2 min gave [18F]10 in a moderate
yield from solubilized [18F]fluoride ion (35%). However, thereafter
the yield gradually decreased showing that product was degrading.
Substrates 4 and 5 were not so reactive under these conditions;
each gave [18F]10 in less than 5% yield after 45 min. Hence, the
organosilicon-NALG having a cyclic crown ether component (3),
rather than a linear oligoether components (4 and 5), was clearly
most effective for promoting radiofluorination. This finding
accords with results from the non-radioactive fluorination
reactions.
obtained from substrates 6–8. Yields from 7 and 8 reached plateaus
at about 45 min whereas the yield from 6 always slowly increased.
Reactions in borosilicate glass or polypropylene vials gave identical
results. The highest yields were obtained for the substrates 5 and 8,
featuring not a metal-chelating leaving group but a methyloxy unit
(Fig. 2). These results mirror those obtained with non-radioactive
potassium fluoride. They may be understood on the basis that K
2.2.2 likely chelates K+ more effectively than the leaving groups
thereby preventing close interaction of potassium ion with
substrate. The larger metal-chelating groups might also impart
some steric hindrance under these conditions.
2.3. Mechanistic considerations
We suspected that [18F]10 was labile to base. Lowering the
concentration of potassium carbonate from 1.8 mM to 0.36 mM in
the radiofluorination of 3 reduced decomposition of product and
led to 50% yield in 20 min at room temperature (Fig. 1). To our
knowledge, this is the fastest silicon radiofluorination ever
reported without the use of a phase transfer agent, such as K
2.2.2. The yields of [18F]10 from 4 and 5 improved slightly to near
10% when the concentration of potassium carbonate was reduced.
The effect of base concentration on the radiofluorination of 6
was somewhat different. The substrate and the product, [18F]11,
were much more stable to high base concentration. Radio-
fluorination of 6–8 in the absence of K 2.2.2 was performed in
acetonitrile containing 0.5% water, but using an optimally high
K2CO3 concentration (9 mM; Fig. 1). The highest yield (45%) for this
substrate group was obtained from 6. Yields for 7 and 8 were 33
and 30% for 45-min reaction time, respectively. Thus, once again, a
substrate containing a cyclic crown ether as NALG unit (6)
appeared most reactive.
We postulate that the 18-C-6-CH2O- leaving group enhances
the reaction rate, at least in part, by positioning the fluoride ion
near to its silicon target (entropic advantage). The reaction then
proceeds through the well-established pentacoordinate silicon
anion intermediate (Scheme 1) [14]. This anionic intermediate is
likely stabilized by a potassium cation positioned nearby due to
chelating interactions with the chelating leaving group. Others
have shown that an 18-C-6/K+ counter ion is capable of stabilizing
pentacoordinate silicon anion [15]. Computational studies suggest
that the pentacoordinate silicon atom prefers to distribute
negative charge to its substituents [16], thus we expect stabilizing
ionic interactions with the oxygen of the leaving group.
2.2.2. Radiofluorination in the presence of K 2.2.2
In order to establish the effect of potassium-chelating leaving
group on the reactivity of compounds 3–8 toward NCA radio-
fluorination, reactions were also conducted in the presence of
anhydrous K 2.2.2/K18F in acetonitrile, at room temperature
(Fig. 2). In these experiments, K 2.2.2 was in molar excess over
K+ (1.8:1). An aliquot of reaction mixture was quenched in
MeCN–H2O (1:1, v/v) and then analyzed with reversed phase
radio-HPLC.
[
18F]tert-Butyldiphenylsilyl fluoride ([18F]10) was obtained
from substrates 3–5. Yields from starting [18F]fluoride ion peaked
after 20 min. [18F]Biphenyldiisopropylsilyl fluoride ([18F]11) was
Scheme 1. Likely mechanism for rate enhancement in silicon fluorination using a
crown ether leaving group.

M.H. Al-huniti et al. / Journal of Fluorine Chemistry 158 (2014) 48–52
51
3. Conclusions
127.9, 72.7 72.2, 71.0, 70.9, 70.8, 63.6, 59.3, 27.0, 19.4. ESI–HRMS
calc. for C23H34O4Si [M+Na]+: 425.2119. Found: 425.2126.
Our findings, especially with compounds having leaving groups
containing crown ether units (substrates 3 and 6), demonstrate
that potassium-chelating units enhance fluoride substitution at
silicon centers. However, this reactivity was undermined in NCA
radiochemistry by the difficulty of solubilizing NCA K18F in the
reaction solvent. This problem needs to be surmounted in future
work. We also suspect that different linkers connecting a crown
ether moiety to a silicon center can be found to maximize metal
involvement in the transition state for faster fluorination.
4.2.5. tert-Butyl(methoxy)diphenylsilane (5)
Yield = 84%. 1H NMR (400 MHz, CDCl3):
d
7.74–7.73 (m, 4H),
7.47–7.43 (m, 6H), 3.57 (s, 3H), 1.08 (s, 9H). 13C NMR (CDCl3,
150.92 MHz, 25 8C):
d 135.7, 133.7, 129.8, 127.9, 52.4, 27.0, 19.4.
CI–HRMS calc. for C17H22OSi [(M+H)-CH3OH]+: 239.1256. Found:
239.1251.
4.2.6. ((1,4,7,10,13,16-Hexaoxacyclooctadecan-2-yl)methoxy)-
([1,10-biphenyl]-4-yl)diisopropylsilane (6)
4. Experimental
Yield = 68%. 1H NMR (400 MHz, CDCl3):
d
7.61–7.27 (m, 6H),
7.47–7.43 (m, 2H), 7.37–7.35 (m, 1H), 3.86–3.63 (m, 25H), 1.33–1.27
(m, 2H), 1.08–1.03 (m, 12H). 13C NMR (100 MHz, CDCl3):
141.8,
4.1. General procedure for silylation of alcohols
d
141.0, 135.1, 132.9, 128.7, 127.3, 127.1, 126.3, 80.2, 71.6, 70.9, 70.8,
70.7, 70.7, 70.6, 70.6, 70.6, 70.5, 70.1, 63.7, 17.4, 17.3, 12.0. ESI–
HRMS calc. for C31H48O7Si [M+Na]+: 583.3062. Found: 583.3078.
In an oven-dried vial under argon atmosphere, alcohol
(1.0 mmol) was dissolved in dichloromethane (5 mL) to which
was added imidazole (2.0 mmol). This solution was then stirred in
an ice-bath for 10 min. Silyl chloride (2.0 mmol) was then added
and the reaction was allowed to warm to room temperature. After
completion, volatiles were removed under reduced pressure and
the crude mixture was purified with silica gel chromatography
using hexanes/EtOAc as eluent.
4.2.7. 12-([1,10-Biphenyl]-4-yl)-12-isopropyl-13-methyl-2,5,8,11-
tetraoxa-12-silatetradecane (7)
Yield = 91%. 1H NMR (400 MHz,CDCl3):
d 7.65–7.58 (m, 6H),
7.47–7.43 (m, 2H), 7.37–7.35 (m, 1H), 3.94 (t, J = 5.6 Hz, 2H), 3.69
(m, 8H), 3.35 (m, 2H), 3.37 (s, 3H), 1.34–1.26 (m, 2H), 1.09 (d,
J = 7.6 Hz, 6H), 1.04 (m, J = 7.6 Hz, 6H). 13C NMR (100 MHz, CDCl3):
4.2. General procedure for fluorination
d
141.8, 141.0, 135.1, 128.2, 127.3, 127.1, 126.2, 72.6, 71.9, 70.8,
70.7, 70.6, 63.3, 59.0, 17.4, 17.3, 12.02. ESI–HRMS calc. for
25H38O4Si [M+Na]: 453.2432. Found: 453.2447.
In an oven-dried vial purged with argon, silyl ether (0.10 mmol)
was dissolved in anhydrous acetonitrile-d3 (0.1 M solution, 1.0 mL)
and stirred at room temperature for 5 min. Finely powdered
anhydrous potassium fluoride (0.5 mmol) was then added to the
stirred solution resulting initially in a suspension and then a
homogeneous mixture after 10–15 min. After KF addition, the
reaction was stirred at room temperature for 30 min (overall time)
and then directly analyzed by 1H NMR. Percent conversion to silyl
fluoride product was calculated based on the limiting reagent KF
using the proton integration of an alkyl (tBu and iPr) group present
on silicon in both starting material and product.
C
4.2.8. [1,10-Biphenyl]-4-yldiisopropyl(methoxy)silane (8)
Yield = 90%. 1H NMR (400 MHz, CDCl3):
7.64–7.60 (m, 6H),
7.46–7.43 (m, 2H), 7.37–7.35 (m, 1H), 3.64 (s, 3H), 1.37–1.29 (m,
2H), 1.10 (d, J = 7.2 Hz, 6H), 1.05 (d, J = 7.2 Hz, 6H). 13C NMR
d
(100 MHz, CDCl3): d 141.6, 141.0, 135.1, 132.7, 128.7, 127.3, 127.1,
126.3, 52.1, 17.5, 17.3, 11.95. CI–HRMS calc. for C19H26Osi [M+H]+:
299.1831. Found: 299.1844.
4.2.9. [1,10-Biphenyl]-4-ylfluorodiisopropylsilane (11)
Yield = 81%. 1H NMR (400 MHz, CDCl3):
d
7.67–7.56 (m, 6H),
7.48–7.41 (m, 2H), 7.39–7.32 (m, 1H), 1.37–1.25 (m, 2H), 1.12–1.05
(m, 12H). 13C NMR (100 MHz, CDCl3):
141.5, 134.9, 134.3, 134.3,
129.0, 128.8, 127.7, 127.5, 127.3, 127.1, 127.0, 126.5, 126.1, 17.8,
17.6, 16.7 (d, JC–F = 2 Hz), 16.5, 13.8, 12.2 (d, JC–F = 14 Hz). CI–HRMS
calc. for C18H23FSi [M+H]+: 287.1631. Found: 287.1635.
4.2.1. 2-Methyl-2-phenyl-3,6,9,12-tetraoxa-2-silatridecane (1)
Yield = 61%. 1H NMR (400 MHz, CDCl3):
d
7.58–7.56 (m, 2H),
7.37–7.34 (m, 3H), 3.74 (t, J = 5.2 Hz, 2H), 3.63–3.61 (m, 6H), 3.55–
3.52 (m, 4H), 3.36 (s, 3H), 0.38 (s, 6H). 13C NMR (100 MHz, CDCl3):
d
d
138.0, 133.7, 129.8, 128.0, 72.6, 72.1, 70.8, 70.8, 70.7, 62.6, 59.2,
ꢁ1.5. MS calc. for C15H26O4Si [M+H]+: 299.17. Found: 299.61.
4.3. Radiochemistry
4.2.2. (Heptyloxy)dimethyl(phenyl)silane (2)
Yield = 71%. 1H NMR (400 MHz, CDCl3):
d
7.62–7.61 (m, 2H),
7.42–7.40 (m, 3H), 3.62 (t, J = 6.6, 2H), 1.56(m, 2H), 1.29 (m, 8H), 0.91
(t, J = 6.7, 3H), 0.41(s, 6H); 13C NMR (100 MHz, CDCl3):
138.3, 133.7,
Cyclotron-produced NCA [18F]fluoride ion (30–100 mCi) in
[
18O]water (60–250
(0.7
K2CO3 (0.1–3.6
m
L) was mixed with stock K2CO3/K 2.2.2
mol and 2.6 mmol in 9:1 MeCN:H2O mixture) or aqueous
mol), then dried by four cycles of azeotropic
d
m
129.8, 128.0, 63.4, 32.9, 32.1, 29.4, 26.0, 22.9, 14.4, ꢁ1.5. APCI_TOF-
m
MS calc. for C15H26OSi [M+H]+: 251.1826. Found: 251.1825.
evaporation with acetonitrile (0.65 mL for each addition) at 110 8C
using a robot-based automation module [17]. All reactions were
performed at room temperature. For radiochemical studies with K
4.2.3. ((1,4,7,10,13,16-Hexaoxacyclooctadecan-2-yl)methoxy)-(tert-
butyl)diphenylsilane (3)
2.2.2, substrate (1
(200 L) were added to a glass vial to form a clear solution. For
radiochemical studies without K 2.2.2, substrate (1 mol) was
dissolved in the MeCN containing H2O (0.5–5%, v/v, 200 L), and
the solution transferred to the V-vial that contained dried K18F. For
both types of experiment, an aliquot (10 L) of reaction mixture
was sampled at a designated time and quenched in a mixture of
H2O:MeCN (1:1, v/v, 500 L). A portion of the quenched aqueous
solution (20 L) was injected onto a reverse phase HPLC (Luna,
C18, 10
m
mol) and anhydrous 18Fꢁ/K+–K 2.2.2 in MeCN
Yield = 97%. 1H NMR (400 MHz, CDCl3):
d
7.67 (m, 4H), 7.39–7.32
m
(m, 6H), 3.65 (m, 25H), 1.04 (s, 9H). 13C NMR (100 MHz, CDCl3):
d
m
135.5, 135.4, 133.3, 133.3, 129.5, 127.5, 127.5, 79.9, 71.0, 70.7, 70.5,
70.6, 70.6, 70.5, 70.5, 70.5, 70.4, 69.9, 63.3, 26.6, 19.1. ESI–HRMS calc.
for C29H44O7Si [M+Na]+: 555.2749. Found: 555.2754.
m
m
4.2.4. 13,13-Dimethyl-12,12-diphenyl-2,5,8,11-tetraoxa-12-
m
silatetradecane (4)
m
Yield = 74%. 1H NMR (400 MHz, CDCl3):
d
ppm 7.70–7.67 (m,
4H), 7.42–7.36 (m, 6H) 3.81 (t, J = 4 Hz, 2H), 3.67–3.52 (m, 10H),
3.37 (s, 3H), 1.05 (s, 9H). 13C NMR (100 MHz):
135.8, 133.9, 129.8,
m
m, 250 mm ꢂ 4 mm) for analysis with UV-absorbance
(254 nm) and radioactivity detectors. The mobile phase was a
mixture of 25 mM aqueous ammonium formate (A) and MeCN (B),
d

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Acknowledgments
This work was supported by a grant from the National Institute of
Mental Health (MH087932). We also acknowledge the National
Science Foundation Division of Undergraduate Education (NSF-
0311369) forthe 400 MHz NMR used in this study. SL and VWP were
supported by the Intramural Research Program of the National
Institutes of Health (NIMH). The authors are grateful to the NIH
Clinical PET Center for the cyclotron production of fluorine-18.
(b) A.P. Kostikov, J. Chin, K. Orchowski, S. Niedermoser, M.M. Kovacevic, A. Aliaga,
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Appendix A. Supplementary data
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