Si- and C-functional organosilicon building blocks for synthesis based on 4-Silacyclohexan-1-ones containing the silicon protecting groups MOP (4-Methoxyphenyl), DMOP (2,6-Dimethoxyphenyl), or TMOP (2,4,6-Trimethoxyphenyl)

Article abstract of DOI:10.1021/acs.joc.5b00774

4-Silacyclohexan-1-ones 1a-1c, 4-silacyclohexan-1-one oximes 2a-2c, 1,4-azasilepan-7-ones 3a-3c, 1,4-azasilepanes 4a-4c, and 2-bromo-4-silacyclohexan-1-ones 5a and 5b were prepared in multistep syntheses, starting from trimethoxypropylsilane. All of these compounds represent C-functional (R₂C=O, R₂C=N-OH, R-NH(C=O)-R, R₂NH, or R₃C-Br) silicon-containing heterocycles that contain Si-MOP, Si-DMOP, or Si-TMOP moieties (MOP = 4-methoxyphenyl; DMOP = 2,6-dimethoxyphenyl; TMOP = 2,4,6-trimethoxyphenyl), which can be cleaved under mild conditions by protodesilylation. As a proof of principle, compounds 3a-3c were transformed quantitatively and selectively into the chlorosilane 6 (treatment with hydrogen chloride in dichloromethane). Thus, the C- and Si-functional compounds 1a-1c, 2a-2c, 3a-3c, 4a-4c, 5a, and 5b represent versatile building blocks for synthesis.

Full text of DOI:10.1021/acs.joc.5b00774

Subscriber access provided by Yale University Library
Article
Si- and C-Functional Organosilicon Building Blocks for
Synthesis Based on 4-Silacyclohexan-1-ones Containing the
Silicon Protecting Groups MOP (4-Methoxyphenyl), DMOP
(2,6-Dimethoxyphenyl), or TMOP (2,4,6-Trimethoxyphenyl)
Marcel Geyer, Olle Karlsson, Johannes Armin Baus, Eric Wellner, and Reinhold Tacke
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b00774 • Publication Date (Web): 30 Apr 2015
Downloaded from http://pubs.acs.org on May 15, 2015
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Si- and C-Functional Organosilicon Building Blocks for Synthesis Based on
4-Silacyclohexan-1-ones Containing the Silicon Protecting Groups MOP
(4-Methoxyphenyl), DMOP (2,6-Dimethoxyphenyl), or TMOP (2,4,6-Tri-
methoxyphenyl)
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[a]
[b]
[a]
[b]
Marcel Geyer , Olle Karlsson , Johannes A. Baus , Eric Wellner , and Reinhold
[
a]
Tacke *
[
[
a] Institut für Anorganische Chemie, Universität Würzburg, Am Hubland, D-97074
Würzburg, Germany
b] AstraZeneca R&D Mölndal, CVMD Innovative Medicines, Pepparedsleden 1, SE-43183
Mölndal, Sweden
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ABSTRACT: The 4-silacyclohexan-1-ones 1a–1c, 4-silacyclohexan-1-one oximes 2a–2c,
1,4-azasilepan-7-ones 3a–3c, 1,4-azasilepanes 4a–4c, and 2-bromo-4-silacyclohexan-1-ones
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a and 5b were prepared in multistep syntheses, starting from trimethoxypropylsilane. All
these compounds represent C-functional (R C=O, R C=N‒OH, R‒NH(C=O)‒R, R NH, or
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R C‒Br) silicon-containing heterocycles that contain Si‒MOP, Si‒DMOP, or Si‒TMOP
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moieties (MOP = 4-methoxyphenyl, DMOP = 2,6-dimethoxyphenyl, TMOP = 2,4,6-
trimethoxyphenyl), which can be cleaved under mild conditions by protodesilylation. As a
proof of principle, compounds 3a–3c were transformed quantitatively and selectively into the
chlorosilane 6 (treatment with hydrogen chloride in dichloromethane). Thus, the C- and Si-
functional compounds 1a–1c, 2a–2c, 3a–3c, 4a–4c, 5a, and 5b represent versatile building
blocks for synthesis.
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
INTRODUCTION
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In context with our systematic studies on silicon-based drugs, we have been interested in
the development of new silicon-containing building blocks for synthesis, such as 4-
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silapiperidines, 4-silacyclohexan-1-ones, and other classes of organosilicon compounds. In
continuation of these studies, we have now succeeded in synthesizing a series of new 4-
silacyclohexan-1-ones (1a–1c), 4-silacyclohexan-1-one oximes (2a–2c), 1,4-azasilepan-7-
ones (3a–3c), 1,4-azasilepanes (4a–4c), and 2-bromo-4-silacyclohexan-1-ones (5a and 5b)
that contain the silicon protecting groups MOP (4-methoxyphenyl), DMOP (2,6-
dimethoxyphenyl), or TMOP (2,4,6-trimethoxyphenyl). In previous studies, we have
demonstrated that these three methoxy-substituted phenyl groups can be easily removed from
the silicon atom of a given MOP-, DMOP-, or TMOP-silane via protodesilylation under very
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mild conditions to give the corresponding chloro- or methoxysilane. Thus, compounds 1a–
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c, 2a–2c, 3a–3c, 4a–4c, 5a, and 5b can be regarded as versatile building blocks for synthesis
that can undergo (i) a variety of transformations at their C-functional group and (ii) selective
cleavage reactions of their Si‒MOP, Si‒DMOP, and Si‒TMOP moieties. Here we report on
the syntheses and characterization of 1a–1c, 2a–2c, 3a–3c, 4a–4c, 5a, and 5b. The syntheses
of 2a–2c, 3a–3c, 4a–4c, 5a, and 5b are based on a sequence of transformations of the keto
group of 1a–1c. As a proof of principle, we have also studied the cleavage of the Si‒MOP,
Si‒DMOP, and Si‒TMOP moieties of 3a–3c (formation of the corresponding chlorosilane 6).
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RESULTS AND DISCUSSION
Syntheses. Compounds 1a–1c, 2a–2c, 3a–3c, and 4a–4c were prepared in multistep
syntheses according to Scheme 1, starting from trimethoxypropylsilane (7). Thus, treatment of
with (4-methoxyphenyl)magnesium bromide, (2,6-dimethoxyphenyl)lithium, or (2,4,6-
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trimethoxyphenyl)lithium afforded the corresponding dimethoxydiorganylsilanes 8a–8c,
which upon reaction with vinylmagnesium chloride furnished the respective
divinyldiorganylsilanes 9a–9c. In the next step, compounds 9a–9c were transformed into the
corresponding 4-silacyclohexan-1-ones 1a–1c by using a synthetic method developed by H.
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C. Brown, J. A. Soderquist, et al. The 4-silacyclohexan-1-one oximes 2a–2c were
synthesized by treatment of 1a–1c with hydroxylamine hydrochloride and sodium carbonate.
Sequential treatment of 2a–2c with sodium carbonate and benzenesulfonyl chloride yielded
the corresponding 1,4-azasilepan-7-ones 3a–3c. Finally, reduction of 3a–3c with lithium
aluminum hydride, followed by aqueous workup, afforded the 1,4-azasilepanes 4a–4c.
Compounds 1a–1c, 2a–2c, and 3a–3c were isolated as colorless crystalline solids,
whereas compounds 4a–4c, 8a–8c, and 9a–9c were isolated as colorless liquids (for the
yields, see Scheme 1).
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Scheme 1. Syntheses of Compounds 1a–1c, 2a–2c, 3a–3c, and 4a–4c
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The 2-bromo-4-silacyclohexan-1-ones 5a and 5b were synthesized according to Scheme
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by treatment of the 4-silacyclohexan-1-ones 1a and 1b with 0.5 molar equivalents of 5,5-
dibromobarbituric acid (in this context, see ref 7) and were isolated in 41% (5a) and 53% (5b)
yield, respectively, as colorless oils. Both compounds were obtained as a mixture of two
diastereomers (molar ratios: 5a, 1:3.8; 5b, 1:1.1). All attempts to prepare the analogous
TMOP-substituted derivative of 5a and 5b, starting from 1c and using the same synthetic
method and the same experimental parameters failed, due to side reactions of the reactive Si‒
TMOP moiety (side products could not be identified).
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Scheme 2. Syntheses of Compounds 5a and 5b
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As a proof of principle, the MOP, DMOP, and TMOP protecting groups of the 1,4-
azasilepan-7-ones 3a–3c were removed by treatment with hydrogen chloride in
dichloromethane at 20 °C to give the corresponding 4-chloro-1,4-azasilepan-7-one 6 (Scheme
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). According to the different reactivities of the Si–MOP, Si–DMOP, and Si–TMOP
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moieties, different reaction times were necessary for these transformations (for details, see
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the Experimental Section). The cleavage reactions were monitored by H, C, and Si NMR
spectroscopic studies (see the Supporting Information; Figures S1‒S9). In all cases,
quantitative and selective cleavage reactions were observed to give 6 and the respective
cleavage products H‒MOP, H‒DMOP, and H‒TMOP.
Scheme 3. Syntheses of Compound 6
The identities of the new compounds 1a–1c, 2a–2c, 3a–3c, 4a–4c, 5a, 5b, 8a–8c, and
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a–9c were established by NMR spectroscopic studies ( H, C, Si) and elemental analyses
(C, H, N) or mass spectrometric investigations (ESI-HRMS). In addition, compounds 3a and
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NMR spectroscopic studies ( H, C, Si).
Crystal Structure Analyses. Compounds 3a and 3b were structurally characterized by
single-crystal X-ray diffraction. The crystal data and the experimental parameters used for the
crystal structure analyses are given in the Supporting Information (Table S1). The molecular
structures of 3a and 3b are depicted in Figures 1 and 2. All the bond lengths and angles of
these compounds are in the expected ranges and do not need any further discussion; however,
the conformations of 3a and 3b deserve a brief discussion. Both compounds adopt a chair
conformation of the seven-membered ring in the crystal. In the case of 3b, the bulky 2,6-
dimethoxyphenyl group occupies an equatorial position, whereas the less bulky 4-
methoxyphenyl group of 3a is found in an axial site. This finding is in agreement with the
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crystal structures of a series of 4-silacyclohexan-1-ones and 4-silapiperidines with chair
conformation, where the more bulky silicon-bound substituents also occupy an equatorial site.
Figure 1. Molecular structure of 3a in the crystal
Figure 2. Molecular structure of 3b in the crystal
(probability level of displacement ellipsoids 50%).
(probability level of displacement ellipsoids 50%).
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CONCLUSION
With the syntheses of compounds 1a–1c, 2a–2c, 3a–3c, 4a–4c, 5a, and 5b, a series of new
classes of silicon-containing C-functional heterocycles with an Si‒MOP, Si‒DMOP, or Si‒
TMOP moiety have been made available. These compounds were prepared in convenient
multistep syntheses, starting from trimethoxypropylsilane, and were characterized by NMR
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spectroscopic studies ( H, C, Si) and elemental analyses (C, H, N) or mass-spectrometric
studies (ESI-HRMS). Compounds 3a and 3b were additionally studied by single-crystal X-ray
diffraction. With their C-functional R C=O (1a–1c, 5a, 5b), R C=N‒OH (2a–2c), R‒
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NH(C=O)‒R (3a–3c), R NH (4a–4c), and R C‒Br moieties (5a, 5b), these compounds
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represent versatile building blocks for synthesis.
The transformations 1a–1c → 2a–2c → 3a–3c → 4a–4c and 1a/1b → 5a/5b at the
aforementioned C-functional groups already demonstrate the synthetic potential of these
silicon-containing heterocycles. In addition to their C-functional groups, these compounds
also contain an Si-functional Si‒MOP, Si‒DMOP, or Si‒TMOP moiety that can be cleaved
under mild conditions by protodesilylation to give other Si-functionalities. As a proof of
principle, compounds 3a‒3c were transformed quantitatively and selectively by treatment
with hydrogen chloride in dichloromethane into the corresponding chlorosilane 6. Thus, with
their C- and Si-functionalities, the title compounds can be regarded as versatile building
blocks for synthesis. As heterocyclic skeletons play a very important role in medicinal
chemistry, the C- and Si-functional silicon-containing heterocycles 1a–1c, 2a–2c, 3a–3c, 4a–
4c, 5a, and 5b represent promising building blocks for the design of new silicon-based drugs.
For example, 5a and 5b have already been used as starting materials for the synthesis of a
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series of GPR81 agonists with a thiazol skeleton, such as 10 and 11. Furthermore, it should
be mentioned that 4,4-dimethyl-1,4-azasilepane (12) has recently been demonstrated to be an
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Scheme 4. Chemical Structures of Compounds 10‒12
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EXPERIMENTAL SECTION
General Procedures. All syntheses in organic solvents were carried out under a dry
argon or nitrogen atmosphere. The organic solvents used were dried and purified according to
standard procedures and stored under dry argon. The commercial starting materials and
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reagents were used without further purification. The H (500 MHz), C (125.7 MHz), and
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Si (99.3 MHz) NMR spectra were recorded at 23 °C using CDCl , CD Cl , or C D as the
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solvent. Chemical shifts (ppm) were determined relative to internal CHCl ( H, δ 7.24 ppm;
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CDCl ), CHDCl ( H, δ 5.32 ppm; CD Cl ), C HD ( H, δ 7.28 ppm; C D ), CDCl ( C,
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external TMS ( Si, δ 0 ppm; CD Cl , CDCl , C D ). Analysis and assignment of the H and
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C NMR spectroscopic data was supported by H, H gradient-selected COSY along with
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C, H gradient-selected HMQC and HMBC experiments. Assignment of the C NMR
spectroscopic data was additionally supported by DEPT 135 experiments. Coupling constants
are given as their absolute values. GC/MS spectra were recorded using solutions in
dichloromethane. High-resolution mass spectra were recorded using solutions in
dichloromethane (GC-FI-TOF-MS) or methanol (ESI).
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-(4-Methoxyphenyl)-4-propyl-4-silacyclohexan-1-one (1a). 9-Borabicyclo[3.3.1]nonane
(11.0 g, 45.1 mmol of the 9-BBN dimer) was added in a single portion at 20 °C to a stirred
solution of 9a (9.00 g, 38.7 mmol) in n-heptane (150 mL), and the resulting mixture was
heated under reflux for 2 h. The reaction mixture was then cooled to 20 °C, borane dimethyl
sulfide complex (3.24 g, 42.6 mmol) was added in a single portion, and the resulting mixture
was heated under reflux for 2 h. Subsequently, the mixture was cooled to 0 °C, methanol (8
mL) was added dropwise within 10 min, and the resulting solution was then stirred at 20 °C
for 1 h. The volatile components were removed under reduced pressure at 40 °C, and the oily
residue was dissolved in tetrahydrofuran (100 mL), followed by the addition of
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dichloromethyl methyl ether (6.68 g, 58.1 mmol) in a single portion at 0 °C. Subsequently, a 1
M solution of lithium tert-butoxide in tetrahydrofuran (194 mL, 194 mmol) was added
dropwise at 0 °C within 30 min, and the reaction mixture was stirred at 0 °C for 10 min and
then at 20 °C for 1 h, followed by sequential addition of ethanol (50 mL), water (50 mL), and
sodium hydroxide (4.65 g, 116 mmol). The resulting mixture was cooled to 0 °C, and an
aqueous solution of hydrogen peroxide (35 weight%, 33.9 mL) was added dropwise within 30
min. The mixture was then stirred at 20 °C for 16 h, followed by the addition of water (200
mL). The organic phase was separated, the aqueous layer was extracted with diethyl ether (3
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×
100 mL) and discarded, the combined organic extracts were dried over anhydrous sodium
sulfate, and the solvent was removed under reduced pressure. The residue was purified by
automated flash column chromatography on silica gel (Biotage SNAP cartridge, KP-Sil, 340
g; eluent, n-heptane/ethyl acetate (8/2 v/v)), followed by bulb-to-bulb distillation in vacuo
(142‒144 °C/0.1 mbar) to furnish 1a in 71% yield as a colorless crystalline solid (7.21 g, 27.5
1
mmol). H NMR (500.0 MHz, CD Cl ): δ 0.82−0.89 (m, 2 H; SiCH CH CH ), 0.93−0.99 (m,
2
2
2
2
3
3
H; SiCH CH CH ), 1.11–1.19 and 1.21–1.29 (m, 4 H; SiCH CH C), 1.34−1.44 (m, 2 H;
2 2 3 2 2
SiCH CH CH ), 2.45−2.58 (m, 4 H; SiCH CH C), 3.81 (s, 3 H; C H OCH ), 6.93−6.95 (m, 2
2
2
3
2
2
6
4
3
13
H; H-2/H-6, C H OCH ), 7.48−7.50 ppm (m, 2 H; H-3/H-5, C H OCH ). C NMR
6
4
3
6
4
3
(
125.7 MHz, CD Cl ): δ 8.5 (SiCH CH C), 16.4 (SiCH CH CH ), 17.7 (SiCH CH CH ), 18.3
2 2 2 2 2 2 3 2 2 3
(SiCH CH CH ), 38.2 (SiCH CH C), 55.4 (C H OCH ), 114.2 (C-3/C-5, C H OCH ), 126.8
2
2
3
2
2
6
4
3
6
4
3
(C-1, C H OCH ), 135.7 (C-2/C-6, C H OCH ), 161.2 (C-4, C H OCH ), 214.3 ppm
6 4 3 6 4 3 6 4 3
2
9
+
(
SiCH CH C). Si NMR (99.3 MHz, CD Cl ): δ −7.1 ppm. HRMS: m/z [M + H] calcd for
2
2
2
2
C H O Si: 263.1467; found: 263.1484.
15
22
2
4
-(2,6-Dimethoxyphenyl)-4-propyl-4-silacyclohexan-1-one (1b). Compound 1b was
synthesized by using the same procedure as described for the preparation of 1a, starting from
b (20.0 g, 76.2 mmol). The product was purified by automated flash column
9
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chromatography on silica gel (Biotage SNAP cartridge, KP-Sil, 340 g; eluent, n-heptane/ethyl
acetate (8/2 v/v)), followed by bulb-to-bulb distillation in vacuo (156‒158 °C/0.1 mbar) to
1
furnish 1b in 83% yield as a colorless crystalline solid (18.6 g, 63.6 mmol). H NMR
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
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2
3
4
5
6
7
8
9
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1
2
3
4
5
6
7
8
9
0
(
500.0 MHz, CD Cl ): δ 0.85−0.90 (m, 2 H; SiCH CH CH ), 0.90−0.95 (m, 3 H;
2 2 2 2 3
SiCH CH CH ), 1.14–1.22 and 1.32–1.38 (m, 4 H; SiCH CH C), 1.38−1.46 (m, 2 H;
2
2
3
2
2
3
SiCH CH CH ), 2.47−2.53 (m, 4 H; SiCH CH C), 3.75 (s, 6 H; C H (OCH ) ), 6.52 (d, J
HH
2
2
3
2
2
6
3
3 2
3
=
8.3 Hz, 2 H; H-3/H-5, C H (OCH ) ), 7.31 ppm (t, J = 8.3 Hz, 1 H; H-4, C H (OCH ) ).
6 3 3 2 HH 6 3 3 2
1
3
C NMR (125.7 MHz, CD Cl ): δ 10.9 (SiCH CH C), 17.1 (SiCH CH CH ), 18.0
2
2
2
2
2
2
3
(
SiCH CH CH ), 18.3 (SiCH CH CH ), 38.7 (SiCH CH C), 55.5 (C H (OCH ) ), 103.7 (C-
2 2 3 2 2 3 2 2 6 3 3 2
3
/C-5, C H (OCH ) ), 110.8 (C-1, C H (OCH ) ), 132.3 (C-4, C H (OCH ) ), 166.1 (C-2/C-6,
6 3 3 2 6 3 3 2 6 3 3 2
29
C H (OCH ) ), 215.7 ppm (SiCH CH C). Si NMR (99.3 MHz, CD Cl ): δ −7.6 ppm.
6
3
3 2
2
2
2
2
+
HRMS: m/z [M + H] calcd for C H O Si: 293.1573; found: 293.1584.
1
6
24
3
4
-Propyl-4-(2,4,6-trimethoxyphenyl)-4-silacyclohexan-1-one (1c). Compound 1c was
synthesized by using the same procedure as described for the preparation of 1a, starting from
c (16.0 g, 54.7 mmol). The product was purified by automated flash column chromatography
9
on silica gel (Biotage SNAP cartridge, KP-Sil, 340 g; eluent, n-heptane/ethyl
acetate/triethylamine (80/20/5 v/v/v)), followed by bulb-to-bulb distillation in vacuo (189‒
1
90 °C/0.3 mbar) to furnish 1c in 61% yield as a colorless crystalline solid (10.8 g, 33.5
1
mmol). H NMR (500.0 MHz, CD Cl ): δ 0.82−0.87 (m, 2 H; SiCH CH CH ), 0.90−0.95 (m,
2
2
2
2
3
3
H; SiCH CH CH ), 1.10–1.18 and 1.31–1.39 (m, 4 H; SiCH CH C), 1.34−1.42 (m, 2 H;
2 2 3 2 2
SiCH CH CH ), 2.46−2.51 (m, 4 H; SiCH CH C), 3.73 (s, 6 H; o-OCH , C H (OCH ) ), 3.81
2
2
3
2
2
3
6
2
3 3
13
(s, 3 H; p-OCH , C H (OCH ) ), 6.09 ppm (s, 2 H; H-3/H-5, C H (OCH ) ). C NMR
3
6
2
3 3
6
2
3 3
(
125.7 MHz, CD Cl ): δ 11.0 (SiCH CH C), 17.3 (SiCH CH CH ), 18.0 (SiCH CH CH ),
2 2 2 2 2 2 3 2 2 3
1
8.3 (SiCH CH CH ), 38.8 (SiCH CH C), 55.4 (p-OCH , C H (OCH ) ), 55.6 (o-OCH ,
2 2 3 2 2 3 6 2 3 3 3
C H (OCH ) ), 90.6 (C-3/C-5, C H (OCH ) ), 102.1 (C-1, C H (OCH ) ), 164.1 (C-4
6
2
3 3
6
2
3 3
6
2
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C H (OCH ) ), 167.0 (C-2/C-6, C H (OCH ) ), 215.8 ppm (SiCH CH C). Si NMR
6
2
3 3
6
2
3 3
2
2
+
(
99.3 MHz, CD Cl ): δ −8.3 ppm. HRMS: m/z [M + H] calcd for C H O Si: 323.1679;
2
2
17 26
4
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
found: 323.1665.
0
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6
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8
9
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4
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7
8
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9
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2
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4
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6
7
8
9
0
4
-(4-Methoxyphenyl)-4-propyl-4-silacyclohexan-1-one Oxime (2a). Hydroxylamine
hydrochloride (530 mg, 7.63 mmol) and sodium carbonate (1.21 g, 11.4 mmol) were added in
a single portion each at 20 °C to a stirred solution of 1a (1.00 g, 3.81 mmol) in a mixture of
acetonitrile (40 mL) and water (40 mL), and the reaction mixture was then stirred at 20 °C for
16 h. Subsequently, dichloromethane (100 mL) and a saturated aqueous sodium hydrogen
carbonate solution (50 mL) were added sequentially, the organic layer was separated, and the
aqueous layer was extracted with dichloromethane (3 × 30 mL) and discarded. The combined
organic extracts were dried over anhydrous sodium sulfate, the solvent was removed under
reduced pressure, and the residue was purified by column chromatography on silica gel (40‒
6
3 μm, 100 g; eluent, n-hexane/ethyl acetate (8/2 v/v)) to furnish 2a in 73% yield as a
1
colorless crystalline solid (772 mg, 2.78 mmol). H NMR (500.1 MHz, CD Cl ): δ 0.78−0.83
2
2
(
m, 2 H; SiCH CH CH ), 0.92−0.96 (m, 3 H; SiCH CH CH ), 0.96–1.04 and 1.06–1.17 (m, 4
2 2 3 2 2 3
H; SiCH CH C), 1.32−1.41 (m, 2 H; SiCH CH CH ), 2.36−2.57 and 2.77−2.85 (m, 4 H;
2
2
2
2
3
SiCH CH C), 3.88 (s, 3 H; C H OCH ), 6.91−6.95 (m, 2 H; H-2/H-6, C H OCH ), 7.44−7.49
2
2
6
4
3
6
4
3
1
3
(m, 2 H; H-3/H-5, C H OCH ), 8.01 ppm (br. s, 1 H; OH). C NMR (125.7 MHz, CD Cl ):
6 4 3 2 2
δ 8.1 and 10.1 (SiCH CH C), 16.5 (SiCH CH CH ), 17.7 (SiCH CH CH ), 18.4
2
2
2
2
3
2
2
3
(
SiCH CH CH ), 21.4 and 29.2 (SiCH CH C), 55.3 (C H OCH ), 114.1 (C-2/C-6,
2 2 3 2 2 6 4 3
C H OCH ), 127.4 (C-1, C H OCH ), 135.7 (C-3/C-5, C H OCH ), 161.1 (C-4, C H OCH ),
6
4
3
6
4
3
6
4
3
6
4
3
2
9
163.5 ppm (SiCH CH C). Si NMR (99.3 MHz, CD Cl ): δ −6.2 ppm. Anal. Calcd for
2
2
2
2
C H NO Si: C, 64.94; H, 8.36; N, 5.05. Found: C, 65.2; H, 8.6; N, 5.3.
15
23
2
4
-(2,6-Dimethoxyphenyl)-4-propyl-4-silacyclohexan-1-one Oxime (2b). Compound 2b
was synthesized by using the same procedure as described for the preparation of 2a, starting
1
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2
2
2
2
2
2
2
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6
from 1b (1.00 g, 3.42 mmol). The product was purified by column chromatography on silica
gel (40‒63 μm, 100 g; eluent, n-hexane/ethyl acetate (8/2 v/v)) to furnish 2b in 67% yield as a
1
colorless crystalline solid (708 mg, 2.30 mmol). H NMR (500.1 MHz, CD Cl ): δ 0.80−0.85
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
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1
2
3
4
5
6
7
8
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2
3
4
5
6
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2
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4
5
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7
8
9
0
(
m, 2 H; SiCH CH CH ), 0.89−0.93 (m, 3 H; SiCH CH CH ), 1.01–1.10 and 1.18–1.26 (m, 4
2 2 3 2 2 3
H; SiCH CH C), 1.26−1.38 (m, 2 H; SiCH CH CH ), 2.34−2.47 and 2.59−2.74 (m, 4 H;
2
2
2
2
3
3
SiCH CH C), 3.74 (s, 6 H; C H (OCH ) ), 6.50 (d, J = 8.3 Hz, 2 H; H-3/H-5,
HH
2
2
6
3
3 2
3
C H (OCH ) ), 7.28 (t, J = 8.3 Hz, 1 H; H-4, C H (OCH ) ), 8.10 ppm (br. s, 1 H; OH).
6
3
3 2
HH
6
3
3 2
1
3
C NMR (125.7 MHz, CD Cl ): δ 10.2 and 12.6 (SiCH CH C), 17.1 (SiCH CH CH ), 18.0
2
2
2
2
2
2
3
(
SiCH CH CH ), 18.3 (SiCH CH CH ), 21.8 and 29.4 (SiCH CH C), 55.5 (C H (OCH ) ),
2 2 3 2 2 3 2 2 6 3 3 2
1
03.7 (C-3/C-5, C H (OCH ) ), 111.4 (C-1, C H (OCH ) ), 132.1 (C-4, C H (OCH ) ), 164.7
6 3 3 2 6 3 3 2 6 3 3 2
29
(SiCH CH C), 166.0 ppm (C-2/C-6, C H (OCH ) ). Si NMR (99.3 MHz, CD Cl ): δ −6.6
2
2
6
3
3 2
2
2
ppm. Anal. Calcd for C H NO Si: C, 62.50; H, 8.20; N, 4.56. Found: C, 62.7; H, 8.1; N, 4.5.
1
6
25
3
4
-Propyl-4-(2,4,6-trimethoxyphenyl)-4-silacyclohexan-1-one Oxime (2c). Compound 2c
was synthesized by using the same procedure as described for the preparation of 2a, starting
from 1c (1.00 g, 3.10 mmol). The product was purified by column chromatography on silica
gel (40‒63 μm, 100 g; eluent, n-hexane/ethyl acetate (8/2 v/v)) to furnish 2c in 34% yield as a
1
colorless crystalline solid (354 mg, 1.05 mmol). H NMR (500.1 MHz, CD Cl ): δ 0.76−0.82
2
2
(
m, 2 H; SiCH CH CH ), 0.88−0.93 (m, 3 H; SiCH CH CH ), 0.97–1.06 and 1.15–1.24 (m, 4
2 2 3 2 2 3
H; SiCH CH C), 1.26−1.37 (m, 2 H; SiCH CH CH ), 2.33−2.46 and 2.59−2.72 (m, 4 H;
2
2
2
2
3
SiCH CH C), 3.72 (s, 6 H; o-OCH , C H (OCH ) ), 3.80 (s, 3 H; p-OCH , C H (OCH ) ),
2
2
3
6
2
3 3
3
6
2
3 3
1
3
6
.08 (s, 2 H; H-3/H-5, C H (OCH ) ), 8.01 ppm (br. s, 1 H; OH). C NMR (125.7 MHz,
6 2 3 3
CD Cl ): δ 10.3 and 12.7 (SiCH CH C), 17.2 (SiCH CH CH ), 18.0 (SiCH CH CH ), 18.3
2
2
2
2
2
2
3
2
2
3
(
SiCH CH CH ), 21.8 and 29.5 (SiCH CH C), 55.4 (o-OCH , C H (OCH ) ), 55.5 (p-OCH ,
2 2 3 2 2 3 6 2 3 3 3
C H (OCH ) ), 90.6 (C-3/C-5, C H (OCH ) ), 102.7 (C-1, C H (OCH ) ), 163.9 (C-4,
6
2
3 3
6
2
3 3
6
2
3 3
29
C H (OCH ) ), 164.7 (SiCH CH C), 167.0 ppm (C-2/C-6, C H (OCH ) ). Si NMR
6
2
3 3
2
2
6
2
3 3
1
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(
99.3 MHz, CD Cl ): δ −7.2 ppm. Anal. Calcd for C H NO Si: C, 60.50; H, 8.06; N, 4.15.
2
2
17 27
4
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Found: C, 60.4; H, 8.4; N, 3.9.
4
-(4-Methoxyphenyl)-4-propyl-1,4-azasilepan-7-one (3a)
.
Sodium carbonate (848 mg,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
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8
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4
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8
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2
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9
0
8
.00 mmol) was added in a single portion at 20 °C to a stirred solution of 2a (2.11 g, 7.61
mmol) in a mixture of acetonitrile (100 mL) and water (100 mL), and the resulting mixture
was then cooled to 0 °C, followed by dropwise addition of benzenesulfonyl chloride (2.68 g,
1
5.2 mmol) within 5 min. After the addition was complete, the reaction mixture was warmed
to 20 °C and stirred for 24 h. Subsequently, dichloromethane (100 mL) and a saturated
aqueous sodium hydrogen carbonate solution (50 mL) were added sequentially, the organic
layer was separated, and the aqueous layer was extracted with dichloromethane (3 × 50 mL)
and discarded. The combined organic extracts were dried over anhydrous sodium sulfate, the
solvents were removed under reduced pressure, and the residue was purified by automated
flash column chromatography on silica gel (Biotage SNAP cartridge, KP-Sil, 100 g; eluent,
dichloromethane/methanol (97/3 v/v)). The resulting colorless oil was crystallized from n-
hexane/ethyl acetate (9/1 v/v; slow cooling of a saturated boiling solution to 20 °C), and the
product was isolated by filtration and dried in vacuo to furnish 3a in 73% yield as a colorless
1
crystalline solid (1.54 g, 5.55 mmol). H NMR (500.0 MHz, CDCl ): δ 0.70−0.77 (m, 2 H;
3
SiCH CH CH ), 0.87−0.92 (m, 3 H; SiCH CH CH ), 0.96−1.10 (m, 2 H; SiCH CH C),
2
2
3
2
2
3
2
2
1.13−1.25 (m, 2 H; SiCH CH N), 1.25−1.34 (m, 2 H; SiCH CH CH ), 2.49−2.58 (m, 2 H;
2
2
2
2
3
SiCH CH C), 3.32−3.44 (m, 2 H; SiCH CH N), 3.79 (s, 3 H; C H OCH ), 6.44 (br. s, 1 H;
2
2
2
2
6
4
3
NH), 6.88−6.93 (m, 2 H; H-2/H-6, C H OCH ), 7.37−7.42 ppm (m, 2 H; H-3/H-5,
6
4
3
13
C H OCH ). C NMR (125.7 MHz, CDCl ): δ 7.6 (SiCH CH C), 14.6 (SiCH CH CH ), 16.6
6
4
3
3
2
2
2
2
3
(
SiCH CH N), 17.1 (SiCH CH CH ), 18.2 (SiCH CH CH ), 28.5 (SiCH CH C), 38.3
2 2 2 2 3 2 2 3 2 2
(
SiCH CH N), 55.0 (C H OCH ), 113.9 (C-2/C-6, C H OCH ), 126.3 (C-1, C H OCH ),
2 2 6 4 3 6 4 3 6 4 3
2
9
1
35.3 (C-3/C-5, C H OCH ), 160.7 (C-4, C H OCH ), 178.5 ppm (SiCH CH C). Si NMR
6
4
3
6
4
3
2
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4
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5
5
5
5
5
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6
+
(
99.3 MHz, CDCl ): δ −4.9 ppm. HRMS: m/z [M + H] calcd for C H NO Si: 278.1576;
3
15 23
2
found: 278.1580.
4
-(2,6-Dimethoxyphenyl)-4-propyl-1,4-azasilepan-7-one (3b). Compound 3b was
synthesized by using the same procedure as described for the preparation of 3a, starting from
a (2.20 g, 7.16 mmol). The product was purified by automated flash column chromatography
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
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1
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4
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7
8
9
0
2
on silica gel (Biotage SNAP cartridge, KP-Sil, 100 g; eluent, dichloromethane/methanol (97/3
v/v)). The resulting colorless oil was crystallized from diethyl ether (slow cooling of a
saturated boiling solution to −20 °C), and the product was isolated by filtration and dried in
1
vacuo to furnish 3b in 66% yield as a colorless crystalline solid (1.45 g, 4.72 mmol). H NMR
(
500.0 MHz, CDCl ): δ 0.80−0.86 (m, 2 H; SiCH CH CH ), 0.87−0.92 (m, 3 H;
3 2 2 3
SiCH CH CH ), 1.00−1.15 (m, 2 H; SiCH CH C), 1.25−1.34 (m, 2 H; SiCH CH N),
2
2
3
2
2
2
2
1
.33−1.42 (m, 2 H; SiCH CH CH ), 2.50−2.63 (m, 2 H; SiCH CH C), 3.36−3.50 (m, 2 H;
2 2 3 2 2
3
SiCH CH N), 3.73 (s, 6 H; C H (OCH ) ), 6.01 (br. s, 1 H; NH), 6.48 (d, J = 8.3 Hz, 2 H;
2
2
6
3
3 2
HH
3
13
H-3/H-5, C H (OCH ) ), 7.28 ppm (t, J = 8.3 Hz, 1 H; H-4, C H (OCH ) ). C NMR
6
3
3 2
HH
6
3
3 2
(
125.7 MHz, CDCl ): δ 10.0 (SiCH CH C), 16.8 (SiCH CH CH ), 17.2 (SiCH CH N), 17.5
3 2 2 2 2 3 2 2
(SiCH CH CH ), 18.3 (SiCH CH CH ), 28.9 (SiCH CH C), 39.1 (SiCH CH N), 55.1
2
2
3
2
2
3
2
2
2
2
(
C H (OCH ) ), 103.4 (C-3/C-5, C H (OCH ) ), 110.7 (C-1, C H (OCH ) ), 132.0 (C-4,
6 3 3 2 6 3 3 2 6 3 3 2
29
C H (OCH ) ), 165.5 (C-2/C-6, C H (OCH ) ), 179.2 ppm (SiCH CH C). Si NMR
6
3
3 2
6
3
3 2
2
2
+
(99.3 MHz, CDCl ): δ −5.0 ppm. HRMS: m/z [M + H] calcd for C H NO Si: 308.1676;
3
16 25
3
found: 308.1690.
4
-Propyl-4-(2,4,6-trimethoxyphenyl)-1,4-azasilepan-7-one (3c). Compound 3c was
synthesized by using the same procedure as described for the preparation of 3a, starting from
c (2.21 g, 6.55 mmol). The product was purified by automated flash column chromatography
on silica gel (Biotage SNAP cartridge, KP-Sil, 100 g; eluent,
dichloromethane/methanol/triethylamine (97/3/5 v/v/v)). The resulting colorless oil was
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crystallized from n-hexane (slow cooling of a saturated boiling solution to 20 °C), and the
product was isolated by filtration and dried in vacuo to furnish 3c in 41% yield as a colorless
1
crystalline solid (903 mg, 2.68 mmol). H NMR (500.0 MHz, C D ): δ 0.99−1.04 (m, 2 H;
6
6
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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SiCH CH CH ), 1.05−1.08 and 1.28−1.37 (m, 2 H; SiCH CH C), 1.09−1.14 (m, 3 H;
2
2
3
2
2
SiCH CH CH ), 1.34−1.42 and 1.62−1.70 (m, 2 H; SiCH CH N), 1.48−1.58 (m, 2 H;
2
2
3
2
2
SiCH CH CH ), 2.68−2.76 and 2.79−2.87 (m, 2 H; SiCH CH C), 3.09−3.24 (m, 2 H;
2
2
3
2
2
SiCH CH N), 3.31 (s, 6 H; o-OCH , C H (OCH ) ), 3.48 (s, 3 H; p-OCH , C H (OCH ) ),
2
2
3
6
2
3 3
3
6
2
3 3
1
3
6.10 (s, 2 H; H-3/H-5, C H (OCH ) ), 6.58 ppm (br. s, 1 H; NH). C NMR (125.7 MHz,
6
2
3 3
C D ): δ 10.7 (SiCH CH C), 17.75 (SiCH CH CH ), 17.76 (SiCH CH N), 18.0
6
6
2
2
2
2
3
2
2
(
SiCH CH CH ), 18.6 (SiCH CH CH ), 29.5 (SiCH CH C), 38.8 (SiCH CH N), 54.5 (o-
2 2 3 2 2 3 2 2 2 2
OCH , C H (OCH ) ), 54.7 (p-OCH , C H (OCH ) ), 90.8 (C-3/C-5, C H (OCH ) ), 102.8
3
6
2
3 3
3
6
2
3 3
6
2
3 3
(C-1, C H (OCH ) ), 164.1 (C-4, C H (OCH ) ), 166.9 (C-2/C-6, C H (OCH ) ), 177.9 ppm
6 2 3 3 6 2 3 3 6 2 3 3
2
9
+
(
SiCH CH C). Si NMR (99.3 MHz, C D ): δ −5.5 ppm. HRMS: m/z [M + Na] calcd for
2
2
6
6
C H NO Si: 360.1607; found: 360.1592.
17
27
4
4
-(4-Methoxyphenyl)-4-propyl-1,4-azasilepane (4a). A 1 M solution of lithium aluminum
hydride in tetrahydrofuran (4.97 mL, 4.97 mmol of LiAlH ) was added dropwise at 0 °C
4
within 5 min to a stirred solution of 3a (690 mg, 2.49 mmol) in diethyl ether (50 mL), and the
reaction mixture was then stirred at 20 °C for 2 h. Subsequently, diethyl ether (50 mL) and
water (50 mL) were added sequentially, the organic layer was separated, and the aqueous
layer was extracted with diethyl ether (3 × 30 mL) and discarded. The combined organic
extracts were dried over anhydrous sodium sulfate, the solvent was removed under reduced
pressure, and the residue was purified by automated flash column chromatography on silica
gel (Biotage SNAP cartridge, KP-Sil, 50 g; eluent, ethyl acetate/triethylamine, (95/5 v/v)),
followed by bulb-to-bulb distillation in vacuo to furnish 4a in 80% yield as a colorless oil
1
(
521 mg, 1.98 mmol); bp 125−126 °C/0.1 mbar. H NMR (500.0 MHz, C D ): δ 0.97−1.04
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(
m, 2 H; SiCH CH CH ), 1.01−1.07 (m, 2 H; SiCH CH CH N), 1.10−1.17 (m, 3 H;
2
2
3
2
2
2
SiCH CH CH ), 1.16 (br. s, 1 H; NH), 1.20−1.37 (m, 2 H; SiCH CH N), 1.50−1.60 (m, 2 H;
2
2
3
2
2
SiCH CH CH ), 1.74−1.85 (m, 2 H; SiCH CH CH N), 2.62−2.75 (m, 2 H; SiCH CH CH N),
2
2
3
2
2
2
2
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
2
.85−2.96 (m, 2 H; SiCH CH N), 3.48 (s, 3 H; C H OCH ), 7.01−7.06 (m, 2 H; H-2/H-6,
2 2 6 4 3
1
3
C H OCH ), 7.63−7.68 ppm (m, 2 H; H-3/H-5, C H OCH ). C NMR (125.7 MHz, C D ): δ
6
4
3
6
4
3
6
6
1
1
2.4 (SiCH CH CH N), 17.2 (SiCH CH N), 18.1 (SiCH CH CH ), 18.5 (SiCH CH CH ),
2 2 2 2 2 2 2 3 2 2 3
8.8 (SiCH CH CH ), 27.7 (SiCH CH CH N), 46.0 (SiCH CH N), 52.1 (SiCH CH CH N),
2
2
3
2
2
2
2
2
2
2
2
54.5 (C H OCH ), 113.9 (C-2/C-6, C H OCH ), 130.7 (C-1, C H OCH ), 135.8 (C-3/C-5,
6
4
3
6
4
3
6
4
3
29
C H OCH ), 160.7 ppm (C-4, C H OCH ). Si NMR (99.4 MHz, C D ): δ 0.0 ppm. HRMS:
6
4
3
6
4
3
6
6
+
m/z [M + H] calcd for C H NOSi: 264.1784; found: 264.1801.
1
5
25
4-(2,6-Dimethoxyphenyl)-4-propyl-1,4-azasilepane (4b). Compound 4b was synthesized
by using the same procedure as described for the preparation of 4a, starting from 3b (468 mg,
1
.52 mmol). The product was purified by automated flash column chromatography on silica
gel (Biotage SNAP cartridge, KP-Sil, 25 g; eluent, ethyl acetate/triethylamine (95/5 v/v)),
followed by bulb-to-bulb distillation in vacuo to furnish 4b in 78% yield as a colorless oil
1
(348 mg, 1.19 mmol); bp 128−129 °C/0.01 mbar. H NMR (500.0 MHz, C D ): δ 1.13−1.18
6
6
and 1.54−1.60 (m, 2 H; SiCH CH CH N), 1.15−1.19 (m, 3 H; SiCH CH CH ), 1.19−1.22 (m,
2
2
2
2
2
3
2
H; SiCH CH CH ), 1.24 (br. s, 1 H; NH), 1.40−1.47 and 1.73−1.80 (m, 2 H; SiCH CH N),
2 2 3 2 2
1.64−1.72 (m, 2 H; SiCH CH CH ), 1.86−2.04 (m, 2 H; SiCH CH CH N), 2.77−2.83 and
2
2
3
2
2
2
2
.87−2.94 (m, 2 H; SiCH CH CH N), 3.08−3.20 (m, 2 H; SiCH CH N), 3.45 (s, 6 H;
2 2 2 2 2
3
3
C H (OCH ) ), 6.42 (d, J = 8.3 Hz, 2 H; H-3/H-5, C H (OCH ) ), 7.26 ppm (t, J = 8.3
6
3
3 2
HH
6
3
3 2
HH
13
Hz, 1 H; H-4, C H (OCH ) ). C NMR (125.7 MHz, C D ): δ 15.0 (SiCH CH CH N), 18.6
6
3
3 2
6
6
2
2
2
(
(
(
SiCH CH N), 18.8 (SiCH CH CH ), 19.6 (SiCH CH CH ), 20.1 (SiCH CH CH ), 28.2
2 2 2 2 3 2 2 3 2 2 3
SiCH CH CH N), 46.1 (SiCH CH N), 51.7 (SiCH CH CH N), 54.7 (C H (OCH ) ), 103.8
2
2
2
2
2
2
2
2
6
3
3 2
C-3/C-5, C H (OCH ) ), 114.6 (C-1, C H (OCH ) ), 131.1 (C-4, C H (OCH ) ), 165.6 ppm
6
3
3 2
6
3
3 2
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+
(
C-2/C-6, C H (OCH ) ). Si NMR (99.4 MHz, C D ): δ −0.3 ppm. HRMS: m/z [M + H]
6 3 3 2 6 6
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
calcd for C H NO Si: 294.1889; found: 294.1872.
1
6
27
2
4
-Propyl-4-(2,4,6-trimethoxyphenyl)-1,4-azasilepane (4c). Compound 4c was
synthesized by using the same procedure as described for the preparation of 4a, starting from
c (590 mg, 1.75 mmol). The product was purified by automated flash column
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
3
chromatography on silica gel (Biotage SNAP cartridge, KP-Sil, 25 g; eluent, ethyl
acetate/triethylamine (95/5 v/v)) to furnish 4c in 55% yield as a colorless oil (311 mg, 961
1
µmol). H NMR (500.0 MHz, C D ): δ 1.14−1.20 and 1.54−1.60 (m, 2 H; SiCH CH CH N),
6
6
2
2
2
1
1
.18−1.22 (m, 3 H; SiCH CH CH ), 1.19−1.23 (m, 2 H; SiCH CH CH ), 1.39−1.48 and
2 2 3 2 2 3
.73−1.80 (m, 2 H; SiCH CH N), 1.49 (br. s, 1 H; NH), 1.66−1.77 (m, 2 H; SiCH CH CH ),
2
2
2
2
3
1.77−2.07 (m, 2 H; SiCH CH CH N), 2.83−2.89 and 2.92−2.99 (m, 2 H; SiCH CH CH N),
2
2
2
2
2
2
3
.12−3.35 (m, 2 H; SiCH CH N), 3.42 (s, 6 H; o-OCH , C H (OCH ) ), 3.51 (s, 3 H; p-OCH ,
2 2 3 6 2 3 3 3
1
3
C H (OCH ) ), 6.17 ppm (s, 2 H; H-3/H-5, C H (OCH ) ). C NMR (125.7 MHz, C D ): δ
6
2
3 3
6
2
3 3
6
6
1
2
5.1 (SiCH CH CH N), 18.6 (SiCH CH N), 18.9 (SiCH CH CH ), 19.6 (SiCH CH CH ),
2 2 2 2 2 2 2 3 2 2 3
0.1 (SiCH CH CH ), 28.2 (SiCH CH CH N), 46.3 (SiCH CH N), 51.8 (SiCH CH CH N),
2
2
3
2
2
2
2
2
2
2
2
54.6 (p-OCH , C H (OCH ) and o-OCH , C H (OCH ) ), 90.8 (C-3/C-5, C H (OCH ) ),
3
6
2
3 3
3
6
2
3 3
6
2
3 3
1
05.7 (C-1, C H (OCH ) ), 163.5 (C-4 C H (OCH ) ), 166.6 ppm (C-2/C-6, C H (OCH ) ).
6 2 3 3 6 2 3 3 6 2 3 3
2
9
+
Si NMR (99.4 MHz, C D ): δ −0.7 ppm. HRMS: m/z [M + H] calcd for C H NO Si:
6
6
17 29
3
324.1990; found: 324.1985.
2
-Bromo-4-(4-methoxyphenyl)-4-propyl-4-silacyclohexan-1-one (5a). 5,5-Dibromo-
barbituric acid (163 mg, 570 µmol) was added at 20 °C in a single portion to a solution of 1a
(300 mg, 1.14 mmol) in diethyl ether (30 mL), and the resulting mixture was then stirred at
2
0 °C for 24 h. The liquid phase of the reaction mixture was separated from the precipitate
barbituric acid) by means of a syringe, and the solvent was removed under reduced pressure.
Subsequently, diethyl ether (20 mL) and water (20 mL) were added sequentially, the organic
(
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layer was separated, and the aqueous layer was extracted with diethyl ether (3 × 10 mL) and
discarded. The combined organic extracts were dried over anhydrous sodium sulfate, the
solvent was removed under reduced pressure, and the product was purified by column
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
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8
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0
chromatography on silica gel (40‒63 μm, 50 g; eluent, n-hexane/dichloromethane (1/1 v/v)) to
1
furnish 5a in 41% yield as a colorless oil (160 mg, 469 µmol). H NMR (500.1 MHz, CD Cl ;
2
2
data for two diastereomers (molar ratio 1:3.8) marked with A (major isomer) and B (minor
A
B
A
B
isomer)): δ 0.82−0.87 and 0.95−1.00 (m, 2 H; SiCH CH CH ), 0.90−0.95 and 0.98−1.02
2
2
3
A
B
A
(m, 3 H; SiCH CH CH ), 1.21–1.29 and 1.31–1.38 (m, 2 H; SiCH CH C), 1.30−1.36 and
2
2
3
2
2
B
B
A
A
B
1
.40−1.47 (m, 2 H; SiCH CH CH ), 1.76−1.83 , 1.81−1.88 , 2.02−2.08 , and 2.12−2.19
2 2 3
A
B
A
B
(
m, 2 H; SiCH CH(Br)C), 2.54−2.62 , 2.66−2.73 , 2.79−2.85 , and 2.81−2.86 (m, 2 H;
2
B
A
A
B
SiCH CH C), 3.80 and 3.82 (s, 3 H; C H OCH ), 4.86−4.91 and 5.00−5.05 (m, 1 H;
2
2
6
4
3
B
A
B
SiCH CH(Br)C), 6.91−6.95 and 6.97−7.00 (m, 2 H; H-2/H-6, C H OCH ), 7.41−7.45 and
2
6
4
3
A
13
7
.51−7.54 ppm (m, 2 H; H-3/H-5, C H OCH ). C NMR (125.8 MHz, CD Cl ; data for two
6 4 3 2 2
B
diastereomers (molar ratio 1:3.8) marked with A (major isomer) and B (minor isomer)): δ 9.4
A
B
A
A
B
and 9.7 (SiCH CH C), 15.6 and 16.9 (SiCH CH CH ), 17.4 and 17.7 (SiCH CH CH ),
2
2
2
2
3
2
2
3
A
B
B
A
B
A
1
8.1 and 18.3 (SiCH CH CH ), 24.4 and 25.1 (SiCH CH(Br)C), 36.4 and 36.8
2
2
3
2
B
A
B
A
B
(
SiCH CH C), 55.40 and 55.44 (C H OCH ), 56.3 and 56.5 (SiCH CH(Br)C), 114.2
2
2
6
4
3
2
A
A
B
B
A
and 114.5 (C-3/C-5, C H OCH ), 124.7 and 125.1 (C-1, C H OCH ), 135.69 and 135.70
6
4
3
6
4
3
B
A
B
A
(C-2/C-6, C H OCH ), 161.5 and 161.6 (C-4, C H OCH ), 204.2 and 204.3 ppm
6
4
3
6
4
3
2
9
(
SiCH CH C). Si NMR (99.4 MHz, CD Cl ; data for two diastereomers (molar ratio 1:3.8)
2
2
2
2
B
A
marked with A (major isomer) and B (minor isomer)): δ −6.9 and −5.8 ppm. Anal. Calcd
for C H BrO Si: C, 52.78; H, 6.20. Found: C, 52.9; H, 6.0.
1
5
21
2
2
-Bromo-4-(2,6-dimethoxyphenyl)-4-propyl-4-silacyclohexan-1-one (5b). Compound
b was synthesized by using the same procedure as described for the preparation of 5a,
starting from 1b (1.00 g, 3.42 mmol). The product was purified by column chromatography
5
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on silica gel (40‒63 μm, 100 g; eluent, n-hexane/ethyl acetate (9/1 v/v)) to furnish 5b in 53%
1
yield as a colorless oil (675 mg, 1.82 mmol). H NMR (500.1 MHz, CD Cl ; data for two
2
2
diastereomers (molar ratio 1:1.1) marked with A (major isomer) and B (minor isomer)): δ
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
A
B
A
B
0
.85−0.90 and 0.92−0.96 (m, 2 H; SiCH CH CH ), 0.88−0.92 and 0.93−0.98 (m, 3 H;
2 2 3
A
B
A
SiCH CH CH ), 1.12–1.21 and 1.34–1.43 (m, 2 H; SiCH CH C), 1.27−1.42 and
2
2
3
2
2
B
A
B
B
A
1
.46−1.58 (m, 2 H; SiCH CH CH ), 1.66−1.73 , 1.90−1.98 , 2.21−2.27 , and 2.38−2.44
2 2 3
A
B
A
B
(
m, 2 H; SiCH CH(Br)C), 2.57−2.64 , 2.62−2.70 , 2.72−2.79 , and 2.75−2.84 (m, 2 H;
2
B
A
B
A
SiCH CH C), 3.74 and 3.79 (s, 6 H; C H (OCH ) ), 5.02−5.08 and 5.10−5.16 (m, 1 H;
2
2
6
3
3 2
B
A
3
B
SiCH CH(Br)C), 6.50 and 6.55 (d, J = 8.3 Hz, 2 H; H-3/H-5, C H (OCH ) ), 7.32 and
2
HH
6
3
3 2
A
3
13
7
.36 ppm (t, J = 8.3 Hz, 1 H; H-4, C H (OCH ) ). C NMR (125.8 MHz, CD Cl ; data
HH 6 3 3 2 2 2
for two diastereomers (molar ratio 1:1.1) marked with A (major isomer) and B (minor
B
A
B
A
A
B
isomer)): δ 12.1 and 12.3 (SiCH CH C), 16.5 and 17.3 (SiCH CH CH ), 17.8 and 17.9
2
2
2
2
3
A
B
B
A
B
(
SiCH CH CH ), 18.1 and 18.2 (SiCH CH CH ), 27.1 and 27.8 (SiCH CH(Br)C), 37.1
2
2
3
2
2
3
2
A
B
A
B
A
and 37.3 (SiCH CH C), 55.5 and 55.6 (C H (OCH ) ), 58.2 and 58.5 (SiCH CH(Br)C),
2
2
6
3
3 2
2
B
A
A
B
B
1
03.7 and 103.8 (C-3/C-5, C H (OCH ) ), 108.9 and 109.5 (C-1, C H (OCH ) ), 132.8
6 3 3 2 6 3 3 2
A
B
A
B
and 132.9 (C-4, C H (OCH ) ), 165.7 and 166.0 (C-2/C-6, C H (OCH ) ), 205.1 and
6
3
3 2
6
3
3 2
A
29
2
05.4 ppm (SiCH CH C). Si NMR (99.4 MHz, CD Cl ; data for two diastereomers (molar
2 2 2 2
B
A
ratio 1:1.1) marked with A (major isomer) and B (minor isomer)): δ −7.1 and −6.5 ppm.
Anal. Calcd for C H BrO Si: C, 51.75; H, 6.24. Found: C, 51.7; H, 6.4.
1
6
23
3
4
-Chloro-4-propyl-1,4-azasilepan-7-one (6). Method I. Gaseous hydrogen chloride was
passed through a solution of 3a (70 mg, 252 µmol) in dichloromethane (5 mL) at 20 °C for 15
min, and the reaction mixture was then stirred at 20 °C for 15 min, until the cleavage of the
MOP protecting group was complete (monitored by GC/MS analysis). The volatile
components (including most of the methoxybenzene) were removed under reduced pressure,
and the residue was demonstrated by NMR spectroscopic studies to be a mixture of 6 and
2
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traces of methoxybenzene (see Figures S1−S3 in the Supporting Information). H NMR
(
500.1 MHz, CD Cl ): δ 0.89−0.95 (m, 2 H; SiCH CH CH ), 0.96−1.01 (m, 3 H;
2
2
2
2
3
SiCH CH CH ), 1.17−1.22 (m, 2 H; SiCH CH N), 1.20−1.26 (m, 2 H; SiCH CH C),
2
2
3
2
2
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
.41−1.50 (m, 2 H; SiCH CH CH ), 2.76−2.85 (m, 2 H; SiCH CH C), 3.65−3.71 (m, 2 H;
2 2 3 2 2
13
SiCH CH N), 9.43 ppm (br. s, 1 H; NH). C NMR (125.8 MHz, CD Cl ): δ 12.1
2
2
2
2
(
SiCH CH C), 16.3 (SiCH CH CH ), 17.3 (SiCH CH CH ), 17.6 (SiCH CH CH ), 19.1
2 2 2 2 3 2 2 3 2 2 3
29
(
SiCH CH N), 25.9 (SiCH CH C), 38.6 (SiCH CH N), 182.2 ppm (SiCH CH C). Si NMR
2
2
2
2
2
2
2
2
(99.4 MHz, CD Cl ): δ 29.9 ppm.
2
2
Method II. Gaseous hydrogen chloride was passed through a solution of 3b (110 mg,
3
58 µmol) in dichloromethane (10 mL) at 20 °C for 5 min, and the reaction mixture was then
stirred at 20 °C for 10 min, until the cleavage of the DMOP protecting group was complete
monitored by GC/MS analysis). The volatile components (including parts of the 1,3-
(
dimethoxybenzene) were removed under reduced pressure, and the residue was demonstrated
by NMR spectroscopic studies to be a 1:0.8 mixture of 6 and 1,3-dimethoxybenzene (see
1
Figures S4−S6 in the Supporting Information). H NMR (500.1 MHz, CD Cl ): δ 0.89−0.94
2
2
(
m, 2 H; SiCH CH CH ), 0.96−1.03 (m, 3 H; SiCH CH CH ), 1.16−1.21 (m, 2 H;
2 2 3 2 2 3
SiCH CH N), 1.19−1.25 (m, 2 H; SiCH CH C), 1.42−1.52 (m, 2 H; SiCH CH CH ),
2
2
2
2
2
2
3
2
.76−2.85 (m, 2 H; SiCH CH C), 3.61−3.68 (m, 2 H; SiCH CH N), 3.76 (s, 6 H;
2 2 2 2
C H (OCH ) ), 6.43−6.46 (m, 1 H; H-2, C H (OCH ) ), 6.47−6.51 (m, 2 H; H-4/H-6,
6
4
3 2
6
4
3 2
1
3
C H (OCH ) ), 7.14−7.19 (m, 1 H; H-5, C H (OCH ) ), 9.26 ppm (br. s, 1 H; NH). C NMR
6
4
3 2
6
4
3 2
(
125.8 MHz, CD Cl ): δ 12.1 (SiCH CH C), 16.3 (SiCH CH CH ), 17.5 (SiCH CH CH ),
2 2 2 2 2 2 3 2 2 3
17.6 (SiCH CH CH ), 19.2 (SiCH CH N), 26.0 (SiCH CH C), 38.3 (SiCH CH N), 55.5
2
2
3
2
2
2
2
2
2
(
C H (OCH ) ), 100.6 (C-2, C H (OCH ) ), 106.3 (C-4/C-6, C H (OCH ) ), 130.1 (C-5,
6 4 3 2 6 4 3 2 6 4 3 2
2
9
C H (OCH ) ), 161.3 (C-1/C-3, C H (OCH ) ), 181.6 ppm (SiCH CH C). Si NMR
6
4
3 2
6
4
3 2
2
2
(
99.4 MHz, CD Cl ): δ 30.1 ppm.
2 2
2
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Method III. Gaseous hydrogen chloride was passed through a solution of 3c (95 mg,
81 µmol) in dichloromethane (7 mL) at 20 °C for 1 min, and the reaction mixture was then
stirred at 20 °C for 10 min, until the cleavage of the TMOP protecting group was complete
2
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
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2
2
2
3
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3
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3
4
4
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4
4
4
4
4
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5
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6
0
1
2
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5
6
7
8
9
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1
2
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4
5
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7
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9
0
1
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7
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9
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2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(monitored by GC/MS analysis). The volatile components were removed under reduced
pressure, and the residue was demonstrated by NMR spectroscopic studies to be a 1:1 mixture
1
of 6 and 1,3,5-trimethoxybenzene (see Figures S7−S9 in the Supporting Information). H
NMR (500.1 MHz, CD Cl ): δ 0.88−0.94 (m, 2 H; SiCH CH CH ), 0.97−1.02 (m, 3 H;
2
2
2
2
3
SiCH CH CH ), 1.14−1.19 (m, 2 H; SiCH CH N), 1.17−1.23 (m, 2 H; SiCH CH C),
2
2
3
2
2
2
2
1
.42−1.51 (m, 2 H; SiCH CH CH ), 2.68−2.80 (m, 2 H; SiCH CH C), 3.56−3.65 (m, 2 H;
2 2 3 2 2
SiCH CH N), 3.75 (s, 9 H; C H (OCH ) ), 6.07 (s, 3 H; C H (OCH ) ), 8.42 ppm (br. s, 1 H;
2
2
6
3
3 3
6
3
3 3
1
3
NH). C NMR (125.8 MHz, CD Cl ): δ 12.3 (SiCH CH C), 16.4 (SiCH CH CH ), 17.7
2
2
2
2
2
2
3
(SiCH CH CH ), 18.0 (SiCH CH CH ), 19.3 (SiCH CH N), 26.6 (SiCH CH C), 38.2
2 2 3 2 2 3 2 2 2 2
(
SiCH CH N), 55.6 (C H (OCH ) ), 93.1 (C-2/C-4/C-6, C H (OCH ) ), 162.0 ppm (C-1/C-
2
2
6
3
3 3
6
3
3 3
29
3/C-5, C H (OCH ) ), 180.9 ppm (SiCH CH C). Si NMR (99.4 MHz, CD Cl ): δ 29.9 ppm.
6
3
3 3
2
2
2
2
Trimethoxypropylsilane (7). This compound was commercially available.
Dimethoxy(4-methoxyphenyl)propylsilane (8a). A 1 M solution of (4-methoxy-
phenyl)magnesium bromide in tetrahydrofuran (128 mL, 128 mmol of p-MeOC H MgBr)
6
4
was added dropwise at 20 °C within 3 h to a stirred solution of 7 (20.0 g, 122 mmol) in
diethyl ether (200 mL), and stirring was then continued at 20 °C for 16 h. The resulting
precipitate was filtered off, washed with diethyl ether (3 × 100 mL), and discarded. The
filtrate and wash solutions were combined, the solvents were removed under reduced pressure,
and the residue was purified by bulb-to-bulb distillation in vacuo to furnish 8a in 67% yield as
1
a colorless liquid (19.7 g, 82.0 mmol); bp 99−100 °C/0.3 mbar. H NMR (500.0 MHz,
CD Cl ): δ 0.79−0.86 (m, 2 H; SiCH CH CH ), 0.91−0.99 (m, 3 H; SiCH CH CH ),
2
2
2
2
3
2
2
3
1
.35−1.46 (m, 2 H; SiCH CH CH ), 3.54 (s, 6 H; SiOCH ), 3.81 (s, 3 H; C H OCH ),
2 2 3 3 6 4 3
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6
.90−6.97 (m, 2 H; H-2/H-6, C H OCH ), 7.49−7.58 ppm (m, 2 H; H-3/H-5, C H OCH ). C
6 4 3 6 4 3
NMR (125.7 MHz, CD Cl ): δ 15.1 (SiCH CH CH ), 16.7 (SiCH CH CH ), 18.0
2
2
2
2
3
2
2
3
(SiCH CH CH ), 50.7 (SiOCH ), 55.3 (C H OCH ), 113.9 (C-2/C-6, C H OCH ), 124.8 (C-1,
2
2
3
3
6
4
3
6
4
3
0
1
2
3
4
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0
1
2
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4
5
6
7
8
9
0
29
C H OCH ), 136.2 (C-3/C-5, C H OCH ), 161.7 ppm (C-4, C H OCH ). Si NMR
6
4
3
6
4
3
6
4
3
+
(
99.3 MHz, CD Cl ): δ −15.9 ppm. HRMS: m/z [M] calcd for C H O Si: 240.1182; found:
2 2 12 20 3
2
40.1168.
(
2,6-Dimethoxyphenyl)dimethoxypropylsilane (8b). A 2.5 M solution of n-butyllithium in
hexanes (53.6 mL, 134 mmol of n-BuLi) was added dropwise at 20 °C within 1 h to a stirred
mixture of 1,3-dimethoxybenzene (16.8 g, 122 mmol), N,N,N`,N`-tetramethylenediamine
(
TMEDA; 15.6 g, 134 mmol), and n-pentane (60 mL). The resulting suspension of DMOP−Li
was stirred at 20 °C for 16 h and then added to a stirred solution of 7 (20.0 g, 122 mmol) in
diethyl ether (80 mL) at 20 °C within 1 h, and the reaction mixture was stirred at 20 °C for a
further 16 h. The resulting precipitate was filtered off, washed with diethyl ether (3 × 100 mL),
and discarded. The filtrate and wash solutions were combined, the solvents were removed
under reduced pressure, and the residue was purified by bulb-to-bulb distillation in vacuo to
furnish 8b in 58% yield as a colorless liquid (19.1 g, 70.6 mmol); bp 108−109 °C/0.2 mbar.
1
H NMR (500.0 MHz, CD Cl ): δ 0.78−0.88 (m, 2 H; SiCH CH CH ), 0.92−0.99 (m, 3 H;
2
2
2
2
3
SiCH CH CH ), 1.36−1.46 (m, 2 H; SiCH CH CH ), 3.52 (s, 6 H; SiOCH ), 3.78 (s, 6 H;
2
2
3
2
2
3
3
3
3
C H (OCH ) ), 6.54 (d, J = 8.2 Hz, 2 H; H-3/H-5, C H (OCH ) ), 7.34 ppm (t, J = 8.2
6
3
3 2
HH
6
3
3 2
HH
13
Hz, 1 H; H-4, C H (OCH ) ). C NMR (125.7 MHz, CD Cl ): δ 16.7 (SiCH CH CH ), 18.2
6
3
3 2
2
2
2
2
3
(
SiCH CH CH ), 18.3 (SiCH CH CH ), 50.9 (SiOCH ), 55.7 (C H (OCH ) ), 103.8 (C-3/C-5,
2 2 3 2 2 3 3 6 3 3 2
C H (OCH ) ), 109.4 (C-1, C H (OCH ) ), 133.0 (C-4, C H (OCH ) ), 166.2 ppm (C-2/C-6,
6
3
3 2
6
3
3 2
6
3
3 2
29
+
C H (OCH ) ). Si NMR (99.4 MHz, CD Cl ): δ −16.7 ppm. HRMS: m/z [M] calcd for
6
3
3 2
2
2
C H O Si: 270.1287; found: 270.1264.
13 22
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Dimethoxypropyl(2,4,6-trimethoxyphenyl)silane (8c). A 2.5 M solution of n-butyllithium
in hexanes (62.4 mL, 156 mmol of n-BuLi) was added dropwise at 20 °C within 1 h to a
stirred mixture of 1,3,5-trimethoxybenzene (25.0 g, 149 mmol), TMEDA (18.1 g, 156 mmol),
and n-pentane (150 mL). The resulting suspension of TMOP−Li was stirred at 20 °C for 16 h
and then added to a stirred solution of 7 (23.2 g, 141 mmol) in diethyl ether (150 mL) at 20 °C
within 1 h, and the reaction mixture was stirred at 20 °C for a further 16 h. The resulting
precipitate was filtered off, washed with diethyl ether (3 × 100 mL), and discarded. The
filtrate and wash solutions were combined, the solvents were removed under reduced pressure,
and the residue was purified by bulb-to-bulb distillation in vacuo to furnish 8c in 72% yield as
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
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31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
a colorless liquid (30.3 g, 101 mmol); bp 121−122 °C/0.2 mbar. H NMR (500.0 MHz,
CD Cl ): δ 0.75−0.84 (m, 2 H; SiCH CH CH ), 0.91−0.96 (m, 3 H; SiCH CH CH ),
2
2
2
2
3
2
2
3
1
.33−1.44 (m, 2 H; SiCH CH CH ), 3.49 (s, 6 H; SiOCH ), 3.76 (s, 6 H; o-OCH ,
2 2 3 3 3
C H (OCH ) ), 3.82 (s, 3 H; p-OCH , C H (OCH ) ), 6.09 ppm (s, 2 H; H-3/H-5,
6
2
3 3
3
6
2
3 3
1
3
C H (OCH ) ).
C NMR (125.7 MHz, CD Cl ): δ 16.8 (SiCH CH CH ), 18.3
2 2 2 2 3
6
2
3 3
(
SiCH CH CH ), 18.4 (SiCH CH CH ), 50.8 (SiOCH ), 55.6 (p-OCH , C H (OCH ) ), 55.7
2 2 3 2 2 3 3 3 6 2 3 3
(
o-OCH , C H (OCH ) ), 90.6 (C-3/C-5, C H (OCH ) ), 101.1 (C-1, C H (OCH ) ), 164.5
3 6 2 3 3 6 2 3 3 6 2 3 3
2
9
(
C-4 C H (OCH ) ), 167.3 ppm (C-2/C-6, C H (OCH ) ). Si NMR (99.3 MHz, CD Cl ): δ
6 2 3 3 6 2 3 3 2 2
+
−
16.3 ppm. HRMS: m/z [M] calcd for C H O Si: 300.1393; found: 300.1400.
14 24 5
(4-Methoxyphenyl)propyldivinylsilane (9a). A 1.9 M solution of vinylmagnesium chloride
in tetrahydrofuran (77.0 mL, 146 mmol of CH =CHMgCl) was added dropwise at 20 °C
2
within 2 h to a stirred solution of 8a (14.0 g, 58.2 mmol) in diethyl ether (200 mL), and the
reaction mixture was then stirred at 20 °C for 16 h. Subsequently, diethyl ether (200 mL) and
water (200 mL) were added sequentially, the organic layer was separated, and the aqueous
layer was extracted with diethyl ether (3 × 100 mL) and discarded. The combined organic
extracts were dried over anhydrous sodium sulfate, the solvents were removed under reduced
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pressure, and the residue was purified by bulb-to-bulb distillation in vacuo to furnish 9a in
1
8
1% yield as a colorless liquid (11.0 g, 47.3 mmol); bp 94−96 °C/0.2 mbar. H NMR
(500.0 MHz, CD Cl ): δ
0.91−0.95 (m, 2 H; SiCH CH CH ), 0.95−1.00 (m, 3 H;
2 2 3
2
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
SiCH CH CH ), 1.38−1.47 (m, 2 H; SiCH CH CH ), 3.80 (s, 3 H; C H OCH ), 5.75 ( ),
2
2
3
2
2
3
6
4
3
A
3
2
3
6.12 ( ), and 6.28 ( ) (CH =CH H , J = 20.3 Hz, J = 3.9 Hz, J = 14.7 Hz, 6 H),
M
X
X
A
M
AX
AM
MX
13
6
.91 (m, 2 H; H-2/H-6, C H OCH ), 7.44 ppm (m, 2 H; H-3/H-5, C H OCH ). C NMR
6 4 3 6 4 3
(
125.7 MHz, CD Cl ): δ 15.9 (SiCH CH CH ), 17.1 (SiCH CH CH ), 18.5 (SiCH CH CH ),
2 2 2 2 3 2 2 3 2 2 3
5
1
5.3 (C H OCH ), 113.9 (C-2/C-6, C H OCH ), 126.6 (C-1, C H OCH ), 134.7 (SiCH=CH ),
6 4 3 6 4 3 6 4 3 2
29
35.7 (C-3/C-5, C H OCH ), 136.6 (SiCH=CH ), 161.1 ppm (C-4, C H OCH ). Si NMR
6
4
3
2
6
4
3
+
(99.4 MHz, CD Cl ): δ −17.4 ppm. HRMS: m/z [M] calcd for C H OSi: 232.1283; found:
2
2
14 20
2
32.1271.
(2,6-Dimethoxyphenyl)propyldivinylsilane (9b). Compound 9b was synthesized by using
the same procedure as described for the preparation of 9a, starting from 8b (5.00 g, 18.5
mmol). The product was purified by bulb-to-bulb distillation in vacuo to furnish 9b in 88%
1
yield as a colorless liquid (4.27 g, 16.3 mmol); bp 98−100 °C/0.1 mbar. H NMR (500.0 MHz,
CD Cl ): δ 0.93−0.97 (m, 2 H; SiCH CH CH ), 0.98−1.02 (m, 3 H; SiCH CH CH ),
2
2
2
2
3
2
2
3
1
6
8
.33−1.43 (m, 2 H; SiCH CH CH ), 3.72 (s, 6 H; C H (OCH ) ), 5.67 ( ), 5.96 ( ), and
2
2
3
6
3
3 2
A
M
3
2
3
3
.42 ( ) (CH =CH H , J = 20.4 Hz, J = 3.9 Hz, J = 14.6 Hz, 6 H), 6.51 (d, J
=
X
X
A
M
AX
AM
MX
HH
3
.3 Hz, 2 H; H-3/H-5, C H (OCH ) ), 7.30 ppm (t, J = 8.3 Hz, 1 H; H-4, C H (OCH ) ).
6
3
3 2
HH
6
3
3 2
1
3
C NMR (125.7 MHz, CD Cl ): δ 16.9 (SiCH CH CH ), 18.1 (SiCH CH CH ), 18.6
2
2
2
2
3
2
2
3
(
SiCH CH CH ), 55.5 (C H (OCH ) ), 104.1 (C-3/C-5, C H (OCH ) ), 111.2 (C-1,
2 2 3 6 3 3 2 6 3 3 2
C H (OCH ) ), 130.9 (SiCH=CH ), 132.3 (C-4, C H (OCH ) ), 138.3 (SiCH=CH ), 166.0
6
3
3 2
2
6
3
3 2
2
29
ppm (C-2/C-6, C H (OCH ) ). Si NMR (99.3 MHz, CD Cl ): δ −20.5 ppm. HRMS: m/z
6
3
3 2
2
2
+
[
M] calcd for C H O Si: 262.1389; found: 262.1389.
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Propyl(2,4,6-trimethoxyphenyl)divinylsilane (9c). Compound 9c was synthesized by using
the same procedure as described for the preparation of 9a, starting from 8c (23.0 g, 76.6
mmol). The product was purified by bulb-to-bulb distillation in vacuo to furnish 9c in 80%
10
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16
17
18
19
20
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22
23
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38
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41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
yield as a colorless liquid (17.9 g, 61.2 mmol); bp. 120−121 °C/0.3 mbar. H NMR
(
500.0 MHz, CD Cl ): δ 0.92−0.96 (m, 2 H; SiCH CH CH ), 0.94−0.98 (m, 3 H;
2 2 2 2 3
SiCH CH CH ), 1.30−1.40 (m, 2 H; SiCH CH CH ), 3.70 (s, 6 H; o-OCH , C H (OCH ) ),
2
2
3
2
2
3
3
6
2
3 3
3
3
.80 (s, 3 H; p-OCH , C H (OCH ) ), 5.65 ( ), 5.94 ( ), and 6.39 ( ) (CH =CH H , J
3
6
2
3 3
A
M
X
X
A
M
AX
2
3
= 20.4 Hz, J = 4.0 Hz, J = 14.6 Hz, 6 H), 6.08 ppm (s, 2 H; H-3/H-5, C H (OCH ) ).
AM
MX
6
2
3 3
13
C NMR (125.7 MHz, CD Cl ): δ 17.1 (SiCH CH CH ), 18.1 (SiCH CH CH ), 18.6
2
2
2
2
3
2
2
3
(
SiCH CH CH ), 55.47 (p-OCH , C H (OCH ) ), 55.53 (o-OCH , C H (OCH ) ), 91.0 (C-
2 2 3 3 6 2 3 3 3 6 2 3 3
3
1
/C-5, C H (OCH ) ), 102.5 (C-1, C H (OCH ) ), 130.7 (SiCH=CH ), 138.6 (SiCH=CH ),
6
2
3 3
6
2
3 3
2
2
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64.1 (C-4 C H (OCH ) ), 166.9 ppm (C-2/C-6, C H (OCH ) ). Si NMR (99.3 MHz,
6
2
3 3
6
2
3 3
+
CD Cl ): δ −20.2 ppm. HRMS: m/z [M + H] calcd for C H O Si: 293.1573, found:
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16 24
3
2
93.1558.
Crystal Structure Analyses. Suitable single crystals of 3a and 3b were obtained directly
from the respective syntheses. The crystals were mounted in inert oil (perfluoropolyalkyl
ether) on a glass fiber and then transferred to the cold nitrogen gas stream of the
diffractometer (graphite-monochromated Mo radiation, λ = 0.71073 Å). The structures were
Kα
solved by direct methods (SHELXS-2013) and refined by full-matrix least-squares methods
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on F for all unique reflections (SHELXL-2013). SHELXLE was used as refinement GUI.
A riding model was employed in the refinement of the CH hydrogen atoms. CCDC-1052862
3a) and CCDC-1052863 (3b) contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge from the Cambridge Crystallographic Data Centre
via www.ccdc.cam.ac.uk/data_request/cif.
(
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
ASSOCIATED CONTENT
Supporting Information
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Data for the crystal structure analyses of compounds 3a and 3b (Table S1); H, C, and Si
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NMR spectra of the mixtures 6/H−MOP, 6/H−DMOP, and 6/H−TMOP (Figures S1−S9); H,
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C, and Si NMR spectra of compounds 1a–1c, 2a–2c, 3a–3c, 4a–4c, 5a, 5b, 8a–8c, and
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a–9c (Figures S10−S69). This material is available free of charge via the Internet at
http://pubs.acs.org.

AUTHOR INFORMATION
Corresponding Author
E-mail: r.tacke@uni-wuerzburg.de
*
Notes
The authors declare no competing financial interest.
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