Synthesis of 4-silacyclohexan-1-ones and (4-silacyclohexan-1-yl)amines containing the silicon protecting groups MOP (4-methoxyphenyl), DMOP (2,4-dimethoxyphenyl), or TMOP (2,4,6-trimethoxyphenyl): Versatile Si- and C-functional building blocks for synthesis

Article abstract of DOI:10.1021/om401208y

The 4-silacyclohexanones 1-6 were prepared in convenient multistep syntheses, starting from MeSi(OMe)₃ and PhSi(OMe)₃, respectively. Cleavage of the 4-methoxyphenyl (MOP), 2,6-dimethoxyphenyl (DMOP), and 2,4,6-trimethoxyphenyl (TMOP) protecting groups of 4-6 by treatment with HCl/Et₂O in CH₂Cl₂ at 20 C gives the 4-chloro-4-silacyclohexanone 13. Reductive amination of 1-6 with NH₃ or i-PrNH₂ yields the respective (4-silacyclohexan-1-yl)amines 7-12. Compounds 1-12 and all new precursors synthesized were characterized by elemental analyses (C, H, N) or mass spectrometric investigations (ESI-HRMS) and by NMR spectroscopic studies (¹H, ¹³C, ²⁹Si). Compounds 1, 3, 5, and 6 and the precursors (MeO)₂SiPh(TMOP) (21) and (CH₂=CH)₂SiPh(TMOP) (27) were additionally characterized by single-crystal X-ray diffraction. Compounds 1-12 with their Si- and C-functional groups represent versatile building blocks for synthesis.

Full text of DOI:10.1021/om401208y

Article
pubs.acs.org/Organometallics
Synthesis of 4‑Silacyclohexan-1-ones and (4-Silacyclohexan-1-
yl)amines Containing the Silicon Protecting Groups MOP (4-
Methoxyphenyl), DMOP (2,4-Dimethoxyphenyl), or TMOP (2,4,6-
Trimethoxyphenyl): Versatile Si- and C‑Functional Building Blocks for
Synthesis
Markus Fischer, Christian Burschka, and Reinhold Tacke*
Institut fur Anorganische Chemie, Universitat Wurzburg, Am Hubland, D-97074 Wurzburg, Germany
̈
̈
̈
̈
S
* Supporting Information
ABSTRACT: The 4-silacyclohexanones 1−6 were prepared in convenient
multistep syntheses, starting from MeSi(OMe)3 and PhSi(OMe)3, respectively.
Cleavage of the 4-methoxyphenyl (MOP), 2,6-dimethoxyphenyl (DMOP), and
2,4,6-trimethoxyphenyl (TMOP) protecting groups of 4−6 by treatment with
HCl/Et2O in CH2Cl2 at 20 °C gives the 4-chloro-4-silacyclohexanone 13.
Reductive amination of 1−6 with NH3 or i-PrNH2 yields the respective (4-
silacyclohexan-1-yl)amines 7−12. Compounds 1−12 and all new precursors
synthesized were characterized by elemental analyses (C, H, N) or mass
spectrometric investigations (ESI-HRMS) and by NMR spectroscopic studies
(1H, 13C, 29Si). Compounds 1, 3, 5, and 6 and the precursors (MeO)2SiPh-
(TMOP) (21) and (CH2CH)2SiPh(TMOP) (27) were additionally
characterized by single-crystal X-ray diffraction. Compounds 1−12 with their Si- and C-functional groups represent versatile
building blocks for synthesis.
INTRODUCTION
■
Cyclohexanones and cyclohexylamines are important building
blocks in the synthesis of drugs. As part of our ongoing studies
on silicon-based drugs,1,2 we have been interested in the
development of versatile silicon-containing building blocks for
synthesis, such as 4-((2-halogeno-5-pyridyl)dimethylsilyl)-
phenylboronic acids,3 (2-halogeno-5-pyridyl)dimethyl(oxiran-
2-ylmethyl)silanes,4 4-silapiperidines,5 and other classes of
organosilicon compounds. In continuation of these studies, we
have now succeeded in synthesizing a series of new 4-
silacyclohexanones and (4-silacyclohexan-1-yl)amines that
contain the silicon protecting groups MOP (4-methyoxyphen-
yl), DMOP (2,4-dimethoxyphenyl), or TMOP (2,4,6-trime-
thoxyphenyl). In previous studies, we have demonstrated that
these protecting groups can be easily removed from the silicon
atom via protodesilylation under mild conditions.6 Therefore,
the Si−MOP, Si−DMOP, and Si−TMOP moieties can also be
regarded as Si-functional groups. As a proof of principle, we
also report here on the cleavage of the MOP, DMOP, and
TMOP groups of 4−6 to give the 4-chloro-4-silacyclohexanone
13. With the transformations of 4−6 into 7−12 via a reductive
amination, we have also made use of the second functional
group (keto group) of the 4-silacyclohexanones described
herein.
Received: December 19, 2013
Published: February 11, 2014
© 2014 American Chemical Society
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RESULTS AND DISCUSSION
Syntheses. The 4-silacyclohexanones 1−6 were synthesized
according to Scheme 1, starting from trimethoxymethylsilane
Scheme 2. Syntheses of Compounds 7−13
■
Scheme 1. Syntheses of Compounds 1−6
for these transformations (for details, see the Experimental
Section). In all cases, quantitative and selective cleavage
reactions were achieved to give the respective mixtures 13/H-
1
MOP, 13/H-DMOP, and 13/H-TMOP. The H, 13C, and 29Si
NMR spectra and GC/MS spectra of these mixtures are
depicted in the Supporting Information (Figures S1−S15). In
contrast to our earlier studies, where the cleavage of the MOP,
DMOP, and TMOP protecting groups was performed in
diethyl ether, in this study dichloromethane was used as the
dominating solvent (see the Experimental Section). It is
interesting to note that the usage of dichloromethane speeds
up the cleavage reaction significantly.
The identities of the new compounds 1−12, 17−21, and
23−27 were established by NMR spectroscopic studies (1H,
13C, 29Si) and elemental analyses (C, H, N) or mass
spectrometric investigations (ESI-HRMS). The 1:1 mixtures
of 13/H-MOP, 13/H-DMOP, and 13/H-TMOP were
characterized by NMR spectroscopic studies (1H, 13C, 29Si)
and GC/MS investigations (see the Supporting Information).
In addition, compounds 1, 3, 5, 6, 21, and 27 were studied by
crystal structure analyses.
(14) and trimethoxyphenylsilane (15), respectively. Thus,
treatment of 14 and 15 with (4-methoxyphenyl)magnesium
bromide, (2,6-dimethoxyphenyl)lithium, or (2,4,6-trimethox-
yphenyl)lithium afforded the corresponding dimethoxydiorga-
nylsilanes 16−21, which upon reaction with vinylmagnesium
chloride furnished the respective divinyldiorganylsilanes 22−
27. In the last step, compounds 22−27 were transformed into
the corresponding 4-silacyclohexanones 1−6 by using a
synthetic method developed by Brown, Soderquist, et al.8
Compounds 1−6 were isolated as colorless crystalline solids
(yields: 1, 74%; 2, 73%; 3, 82%; 4, 79%; 5, 80%; 6, 81%),
whereas 16−27 were obtained as colorless liquids (yields: 16,
71%; 17, 71%; 18, 77%; 19, 70%; 20, 68%; 21, 67%; 22, 70%;
23, 72%; 24, 75%; 25, 90%; 26, 76%; 27, 70%).
The (4-silacyclohexan-1-yl)amines 7−12 were synthesized by
reductive amination according to Scheme 2, starting from the
respective 4-silacyclohexanones 4−6.8 Thus, treatment of 4−6
with ammonia or isopropylamine in an autoclave under an
atmosphere of hydrogen, in the presence of Raney nickel,
afforded the corresponding amines 7−12, which were isolated
as colorless liquids (yields: 7, 73%; 8, 61%; 9, 79%; 10, 77%;
11, 74%; 12, 81%).
Crystal Structure Analyses. Compounds 1, 3, 5, 6, 21,
and 27 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 1, 3, 5, 6, 21, and 27 are depicted in Figures 1−6. All the
bond lengths and angles of these compounds are in the
expected ranges and do not need any further discussion;
however, the structural features of the 4-silacyclohexanones 1,
3, 5, and 6 deserve a brief discussion.9 Except for one of the two
crystallographically independent molecules of 5 (twist con-
formation), all the compounds studied adopt a chair
conformation in the crystal. In the case of 3, 5, and 6, the
bulky 2,6-dimethoxyphenyl and 2,4,6-trimethoxyphenyl group,
respectively, occupy an equatorial position. In contrast, the less
bulky 4-methoxyphenyl group of 1 is found in an axial site.
As a proof of principle, the MOP, DMOP, and TMOP
protecting groups of the 4-silacyclohexanones 4−6 were
removed by treatment with hydrogen chloride/diethyl ether
in dichloromethane at 20 °C to give the corresponding 4-
chloro-4-silacyclohexanone 13 (Scheme 2). According to the
different reactivities of the Si−MOP, Si−DMOP, and Si−
TMOP moieties,6c different reaction conditions were applied
1
NMR Studies. The H, 13C, and 29Si NMR spectroscopic
studies confirmed the identities of the new silicon compounds
synthesized. Moreover, they revealed some insight into the
stereochemistry of the 4-silacyclohexane derivatives studied.
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Figure 1. Molecular structure of 1 in the crystal (probability level of
displacement ellipsoids 50%).
Figure 3. Molecular structures of the two crystallographically
independent molecules in the crystal of 5 (probability level of
displacement ellipsoids 50%).
Figure 2. Molecular structure of 3 in the crystal (probability level of
displacement ellipsoids 50%).
The results of the crystal structure analyses of compounds 1,
3, 5, and 6 suggest that the 4-silacyclohexanones 1−6 and 13
also adopt a chair conformation in solution. As shown in
Scheme 3, two conformers of this type have to be considered,
and it is likely to assume that the conformer with the most
bulky substituent in equatorial position is the dominating
species. For compounds 1−6 and 13, only one set of resonance
1
signals was observed in the H, 13C, and 29Si NMR spectra,
indicating a rapid chair-to-chair inversion on the NMR time
scale.
A totally different stereochemistry was observed for the (4-
silacyclohexan-1-yl)amines 7−12. In the case of compounds 7
and 8, two sets of resonance signals each were observed in the
1H, 13C, and 29Si NMR spectra, with intensity ratios of 1:1.1
and 1:1.6, respectively. These two sets of resonance signals can
be assigned to the two diastereomers shown in Scheme 4. As
the steric demand of the phenyl and 4-methoxyphenyl group is
very similar, an NMR spectroscopic differentiation between the
two chair conformations of the diastereomers of 7 and 8 is not
possible under the experimental conditions applied. However,
in the case of compounds 9−12, four sets of resonance signals
were observed in the NMR spectra, indicating the presence of
two diastereomers each, the two conformers of which are stable
on the NMR time scale. The population ratios of these four
species are as follows: 9, 1:2.1:7.5:9.4; 10, 1:1.1:2.2:3.5; 11,
1:1.3:23:28; 12, 1:1.7:3.2:5.1. These ratios reflect the different
steric demand of the unsubstituted and substituted phenyl
groups and of the unsubstituted and substituted amino groups.
Figure 4. Molecular structure of 6 in the crystal (probability level of
displacement ellipsoids 50%).
CONCLUSION
■
With the synthesis of compounds 1−6, a new class of 4-
silacyclohexanones with a Si−MOP, Si−DMOP, or Si−TMOP
moiety was made available. These compounds were prepared
by a convenient multistep synthesis, starting from trimethoxy-
methylsilane and trimethoxyphenylsilane, respectively. The
MOP, DMOP, and TMOP protecting groups can be easily
removed via protodesilylation under mild conditions. As a
proof of principle, compounds 4−6 were converted quantita-
tively and selectively into the corresponding 4-chloro-4-
silacyclohexanone 13 by treatment with hydrogen chloride/
diethyl ether at 20 °C. With the transformations of the 4-
silacyclohexanones 1−6 into the corresponding (4-silacyclohex-
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an-1-yl)amines 7−12 via a reductive amination, the keto group
of 1−6 was also demonstrated to be a useful functional group
for further conversions. In conclusion, both the 4-silacyclohex-
anones 1−6 and the (4-silacyclohexan-1-yl)amines 7−12 with
their Si- and C-functional groups represent versatile building
blocks for synthesis.
EXPERIMENTAL SECTION
■
General Procedures. All syntheses in organic solvents were
carried out under dry argon. The organic solvents used were dried and
purified according to standard procedures and stored under dry argon.
Starting materials and reagents were purchased from ABCR, Acros, or
Aldrich and were used without further purification. Bulb-to-bulb
distillations were accomplished by using a Buchi GKR-50 glass oven
̈
apparatus. Melting points were determined with a Buchi B-540 melting
̈
point apparatus using samples in open glass capillaries. The H, 13C,
1
and 29Si NMR spectra were recorded at 23 °C on a Bruker Avance 500
NMR spectrometer (1H, 500.1 MHz; 13C, 125.8 MHz; 29Si, 99.4
MHz) using CDCl3 or CD2Cl2 as the solvent. Chemical shifts (ppm)
were determined relative to internal CHCl3 (1H, δ 7.24 ppm; CDCl3),
CHDCl2 (1H, δ 5.32 ppm; CD2Cl2), CDCl3 (13C, δ 77.0 ppm;
CDCl3), CD2Cl2 (13C, δ 53.8 ppm; CD2Cl2), or external TMS (29Si, δ
Figure 5. Molecular structure of 21 in the crystal (probability level of
displacement ellipsoids 50%).
0 ppm; CDCl3, CD2Cl2). Analysis and assignment of the H and 13C
1
1
NMR spectroscopic data was supported by H,1H gradient selected
COSY along with 13C,1H gradient selected HMQC and HMBC
experiments. Assignment of the 13C NMR spectroscopic data was
additionally supported by DEPT 135 experiments. Coupling constants
are given as their absolute values. GC/MS studies were performed
using a Varian 450-GC gas chromatograph with a capillary column
from Varian of the type FactorFour VF-5 ms (column length, 30 m;
column inside diameter, 0.25 mm; flow rate, 1.0 mL min−1; injector,
split ratio 1:80, 220 °C; carrier gas, He) and a Varian 320-MS SQ mass
spectrometer (70 eV). HRMS spectra were recorded on a Bruker
MicrOTOF mass spectrometer using solutions in methanol (ESI).
Elemental analyses were performed by using a VarioMicro apparatus
(Elementar Analysensysteme GmbH) or a EURO EA elemental
analyzer (EuroVector).
4-(4-Methoxyphenyl)-4-methyl-4-silacyclohexan-1-one (1). 9-
Borabicyclo[3.3.1]nonane (11.7 g, 47.9 mmol of the 9-BBN dimer)
was added in a single portion at 20 °C to a stirred solution of 22 (8.89
g, 43.5 mmol) in n-hexane (120 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 (3.64 g, 47.9 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 30 min, and the resulting solution
was then stirred at 20 °C for 1 h. The volatile components were
removed under reduced pressure at 30 °C, and the oily residue was
dissolved in tetrahydrofuran (120 mL), followed by the addition of
dichloromethyl methyl ether (7.50 g, 65.2 mmol) in a single portion at
0 °C. Subsequently, a solution of lithium tert-butoxide (prepared from
tert-butanol (16.1 g, 217 mmol) in tetrahydrofuran (85 mL) and a 2.5
M solution of n-butyllithium in hexanes (96 mL; 240 mmol of n-
BuLi)) was added dropwise at 0 °C within 45 min, and the reaction
mixture was stirred at 0 °C for 10 min and then at 20 °C for a further
45 min. The reaction mixture was then treated with ethanol (33 mL),
water (35 mL), and sodium hydroxide (5.28 g, 132 mmol), the
resulting mixture was cooled to 0 °C, and an aqueous solution of
hydrogen peroxide (30 weight %, 40 mL) was added dropwise within
30 min. The mixture was warmed to 20 °C within 30 min, stirred at
this temperature for 16 h, and then heated under reflux for 1 h.
Subsequently, water (75 mL) and diethyl ether (60 mL) were added at
20 °C, the organic layer was separated, and the aqueous layer was
extracted with diethyl ether (3 × 60 mL) and discarded. The
combined organic phases were dried over anhydrous sodium sulfate,
the organic solvents were removed under reduced pressure, and the
residue was purified by bulb-to-bulb distillation (147−149 °C/0.2
mbar). The resulting solid distillate was recrystallized from diethyl
ether (slow cooling of a saturated boiling solution to −20 °C), and the
Figure 6. Molecular structure of 27 in the crystal (probability level of
displacement ellipsoids 50%).
Scheme 3. Chair-to-Chair Inversion of Compounds 1−6 and
13 in Solution
Scheme 4. Structures of the Two Chair Conformations of the
Two Diastereomers of Compounds 7−12 in Solution
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product was isolated by filtration and dried in vacuo (0.005 mbar, 20
°C, 4 h) to give 1 in 74% yield as a colorless crystalline solid (7.58 g,
4-(2,6-Dimethoxyphenyl)-4-phenyl-4-silacyclohexan-1-one (5).
Compound 5 was synthesized by using the same procedure as
described for the preparation of 1, starting from 26 (16.8 g, 56.7
mmol). The product was purified by bulb-to-bulb distillation (253−
254 °C/1.2 mbar), and the resulting solid distillate was recrystallized
from n-hexane/ethyl acetate (1:1 v/v; slow cooling of a saturated
boiling solution to −20 °C). The product was isolated by filtration and
dried in vacuo (0.005 mbar, 20 °C, 5 h) to give 5 in 80% yield as a
1
32.3 mmol); mp 35 °C. H NMR (CD2Cl2): δ 0.38 (s, 3 H; SiCH3),
1.06−1.15 and 1.20−1.30 (m, 4 H; SiCH2CH2C), 2.49−2.59 (m, 4 H;
SiCH2CH2C), 3.81 (s, 3 H; C6H4OCH3), 6.92−6.96 (m, 2 H; H-3/H-
5, C6H4OCH3), 7.48−7.52 ppm (m, 2 H; H-2/H-6, C6H4OCH3). 13
C
NMR (CD2Cl2): δ −3.8 (SiCH3), 10.1 (SiCH2CH2C), 38.2
(SiCH2CH2C), 55.4 (C6H4OCH3), 114.1 (C-3/C-5, C6H4OCH3),
127.7 (C-1, C6H4OCH3), 135.5 (C-2/C-6, C6H4OCH3), 161.3 (C-4,
C6H4OCH3), 214.2 ppm (SiCH2CH2C). 29Si NMR (CD2Cl2): δ −7.8
ppm. Anal. Calcd for C13H18O2Si: C, 66.62; H, 7.74. Found: C, 66.42;
H, 7.93.
1
colorless crystalline solid (14.8 g, 45.3 mmol); mp 86 °C. H NMR
(CD2Cl2): δ 1.53−1.72 (m, 4 H; SiCH2CH2C), 2.51−2.65 (m, 4 H;
SiCH2CH2C), 3.73 (s, 6 H; C6H3(OCH3)2), 6.54 (d, 3JHH = 8.3 Hz, 2
H; H-3/H-5, C6H3(OCH3)2), 7.30−7.37 (m, 2 H; H-3/H-5, C6H5),
3
4-(2,6-Dimethoxyphenyl)-4-methyl-4-silacyclohexan-1-one (2).
Compound 2 was synthesized by using the same procedure as
described for the preparation of 1, starting from 23 (10.2 g, 43.5
mmol). The product was purified by bulb-to-bulb distillation (159−
160 °C/0.2 mbar), and the resulting solid distillate was recrystallized
from n-hexane/ethyl acetate (1:1 v/v; slow cooling of a saturated
boiling solution to −20 °C). The product was isolated by filtration and
dried in vacuo (0.005 mbar, 20 °C, 4 h) to give 2 in 73% yield as a
7.32−7.38 (m, 1 H; H-4, C6H5), 7.35 (t, JHH = 8.3 Hz, 1 H; H-4,
C6H3(OCH3)2), 7.59−7.64 ppm (m, 2 H; H-2/H-6, C6H5). 13C NMR
(CD2Cl2): δ 11.4 (SiCH2CH2C), 38.7 (SiCH2CH2C), 55.6
(C6H3(OCH3)2), 104.0 (C-3/C-5, C6H3(OCH3)2), 109.8 (C-1,
C6H3(OCH3)2), 128.0 (C-3/C-5, C6H5), 129.3 (C-4, C6H5), 132.9
(C-4, C6H3(OCH3)2), 134.4 (C-2/C-6, C6H5), 137.6 (C-1, C6H5),
166.0 (C-2/C-6, C6H3(OCH3)2), 214.9 ppm (SiCH2CH2C). 29Si
NMR (CD2Cl2): δ −14.4 ppm. Anal. Calcd for C19H22O3Si: C, 69.90;
H, 6.79. Found: C, 69.78; H, 6.79.
1
colorless crystalline solid (8.39 g, 31.7 mmol); mp 49 °C. H NMR
(CD2Cl2): δ 0.35 (s, 3 H; SiCH3), 1.08−1.18 and 1.37−1.48 (m, 4 H;
4-Phenyl-4-(2,4,6-trimethoxyphenyl)-4-silacyclohexan-1-one (6).
Compound 6 was synthesized by using the same procedure as
described for the preparation of 1, starting from 27 (18.5 g, 56.7
mmol). The product was purified by bulb-to-bulb distillation (237−
240 °C/0.4 mbar), and the resulting solid distillate was recrystallized
from n-hexane/ethyl acetate (1:1 v/v; slow cooling of a saturated
boiling solution to −20 °C). The product was isolated by filtration and
dried in vacuo (0.005 mbar, 20 °C, 4 h) to give 6 in 81% yield as a
SiCH2CH2C), 2.45−2.60 (m, 4 H; SiCH2CH2C), 3.76 (s, 6 H;
3
C6H3(OCH3)2, 6.53 (d, JHH = 8.3 Hz, 2 H; H-3/H-5,
3
C6H3(OCH3)2), 7.32 ppm (t, JHH = 8.2 Hz, 1 H; H-4,
C6H3(OCH3)2). 13C NMR (CD2Cl2): δ −2.4 (SiCH3), 12.1
(SiCH2CH2C), 38.6 (SiCH2CH2C), 55.5 (C6H3(OCH3)2), 103.8 (C-
3/C-5, C6H3(OCH3)2), 111.4 (C-1, C6H3(OCH3)2), 132.4 (C-4,
C6H3(OCH3)2), 165.9 (C-2/C-6, C6H3(OCH3)2), 215.6 ppm
(SiCH2CH2C). 29Si NMR (CD2Cl2): δ −9.2 ppm. Anal. Calcd for
C14H20O3Si: C, 63.60; H, 7.62. Found: C, 63.43; H, 7.77.
1
colorless crystalline solid (16.4 g, 46.0 mmol); mp 74 °C. H NMR
(CD2Cl2): δ 1.49−1.66 (m, 4 H; SiCH2CH2C), 2.49−2.62 (m, 4 H;
SiCH2CH2C), 3.71 (s, 6 H; o-OCH3, C6H2(OCH3)3), 3.81 (s, 3 H; p-
OCH3, C6H2(OCH3)3), 6.10 (s, 2 H; H-3/H-5, C6H2(OCH3)3),
7.29−7.34 (m, 2 H; H-3/H-5, C6H5), 7.31−7.34 (m, 1 H; H-4, C6H5),
7.56−7.61 ppm (m, 2 H; H-2/H-6, C6H5). 13C NMR (CD2Cl2): δ
11.4 (SiCH2CH2C), 38.8 (SiCH2CH2C), 55.5 (o-OCH3,
C6H2(OCH3)3), 55.6 (p-OCH3, C6H2(OCH3)3), 90.8 (C-3/C-5,
C6H2(OCH3)3), 101.1 (C-1, C6H2(OCH3)3), 128.0 (C-3/C-5,
C6H5), 129.2 (C-4, C6H5), 134.3 (C-2/C-6, C6H5), 138.1 (C-1,
C6H5), 164.6 (C-4, C6H2(OCH3)3), 167.0 (C-2/C-6, C6H2(OCH3)3),
215.1 ppm (SiCH2CH2C). 29Si NMR (CD2Cl2): δ −15.0 ppm. Anal.
Calcd for C20H24O4Si: C, 67.38; H, 6.79. Found: C, 67.35; H, 6.86.
(4-(4-Methoxyphenyl)-4-phenyl-4-silacyclohexan-1-yl)amine (7).
A suspension of activated Raney nickel in water (50 weight %, 1.00 g
of suspension, 8.52 mmol of Raney nickel) was washed with methanol
(3 × 10 mL), and the resulting powder was resuspended in methanol
(10 mL). This suspension and a 7 M solution of ammonia in methanol
(3.37 mL; 23.6 mmol of ammonia) were added sequentially in single
portions at 20 °C to a stirred solution of 4 (1.00 g, 3.37 mmol) in
methanol (20 mL), and the resulting mixture was heated in an
autoclave at 100 °C under an atmosphere of hydrogen (30 bar) for 16
h. The mixture was then cooled to 20 °C and filtered through a pad of
Celite, followed by elution with methanol (3 × 20 mL). The filtrate
and the eluates were combined, the volatile components were removed
under reduced pressure, and the oily residue was dissolved in diethyl
ether (100 mL). Subsequently, a 2 M solution of hydrogen chloride in
diethyl ether (2.00 mL, 4.00 mmol of HCl) was added at 0 °C within
10 min (formation of a precipitate), and the resulting suspension was
then stirred at 0 °C for 30 min and at 20 °C for a further 2 h. The solid
was separated by centrifugation (2300g, 5 min, 20 °C), and the
supernatant was discarded. Subsequently, the solid was resuspended in
diethyl ether (15 mL) and again isolated by centrifugation (2300g, 5
min, 20 °C). This procedure was repeated, and the product was then
recrystallized from acetone/diethyl ether (5:1 v/v; slow cooling of a
saturated boiling solution to −20 °C), isolated by filtration, and dried
in vacuo (0.005 mbar, 20 °C, 3 h) to give 7·HCl in 78% yield as a
colorless crystalline solid (879 mg, 2.63 mmol). Subsequently, a two-
phase mixture of 7·HCl (879 mg, 2.63 mmol), a 1 M aqueous solution
of sodium hydroxide (18.0 mL, 18.0 mmol of NaOH), and diethyl
ether (50 mL) was stirred at 20 °C for 30 min. The organic phase was
4-Methyl-4-(2,4,6-trimethoxyphenyl)-4-silacyclohexan-1-one (3).
Compound 3 was synthesized by using the same procedure as
described for the preparation of 1, starting from 24 (20.0 g, 75.6
mmol). The product was purified by bulb-to-bulb distillation (243−
245 °C/0.1 mbar), and the resulting solid distillate was recrystallized
from n-pentane/diethyl ether (1:1 v/v; slow cooling of a saturated
boiling solution to −20 °C). The product was isolated by filtration and
dried in vacuo (0.005 mbar, 20 °C, 5 h) to give 3 in 82% yield as a
1
colorless crystalline solid (18.3 g, 62.2 mmol); mp 57 °C. H NMR
(CD2Cl2): δ 0.32 (s, 3 H; SiCH3), 1.05−1.13 and 1.34−1.43 (m, 4 H;
SiCH2CH2C), 2.44−2.57 (m, 4 H; SiCH2CH2C), 3.74 (s, 6 H; o-
OCH3, C6H2(OCH3)3), 3.81 (s, 3 H; p-OCH3, C6H2(OCH3)3), 6.09
ppm (s, 2 H; H-3/H-5, C6H2(OCH3)3). 13C NMR (CD2Cl2): δ −2.2
(SiCH3), 12.2 (SiCH2CH2C), 38.6 (SiCH2CH2C), 55.5 (o-OCH3,
C6H2(OCH3)3), 55.6 (p-OCH3, C6H2(OCH3)3), 90.6 (C-3/C-5,
C6H2(OCH3)3), 102.7 (C-1, C6H2(OCH3)3), 164.1 (C-4,
C6H2(OCH3)3), 166.8 (C-2/C-6, C6H2(OCH3)3), 215.7 ppm
(SiCH2CH2C). 29Si NMR (CD2Cl2): δ −9.8 ppm. Anal. Calcd for
C15H22O4Si: C, 61.19; H, 7.53. Found: C, 61.23; H, 7.46.
4-(4-Methoxyphenyl)-4-phenyl-4-silacyclohexan-1-one (4). Com-
pound 4 was synthesized by using the same procedure as described for
the preparation of 1, starting from 25 (15.1 g, 56.7 mmol). The
product was purified by bulb-to-bulb distillation (262−263 °C/1.6
mbar), and the resulting solid distillate was recrystallized from n-
hexane/ethyl acetate (1:1 v/v; slow cooling of a saturated boiling
solution to −20 °C). The product was isolated by filtration and dried
in vacuo (0.005 mbar, 20 °C, 4 h) to give 4 in 79% yield as a colorless
crystalline solid (13.3 g, 44.9 mmol); mp 58 °C. 1H NMR (CD2Cl2): δ
1.45−1.54 (m, 4 H; SiCH2CH2C), 2.57−2.64 (m, 4 H; SiCH2CH2C),
3.81 (s, 3 H; C6H4OCH3), 6.93−6.98 (m, 2 H; H-3/H-5,
C6H4OCH3), 7.35−7.43 (m, 2 H; H-3/H-5, C6H5), 7.38−7.45 (m,
1 H; H-4, C6H5), 7.48−7.53 (m, 2 H; H-2/H-6, C6H4OCH3), 7.55−
7.60 ppm (m, 2 H; H-2/H-6, C6H5). 13C NMR (CD2Cl2): δ 9.2
(SiCH2CH2C), 38.3 (SiCH2CH2C), 55.4 (C6H4OCH3), 114.3 (C-3/
C-5, C6H4OCH3), 125.4 (C-1, C6H4OCH3), 128.5 (C-3/C-5, C6H5),
130.1 (C-4, C6H5), 134.8 (C-2/C-6, C6H5), 135.5 (C-1, C6H5), 136.3
(C-2/C-6, C6H4OCH3), 161.5 (C-4, C6H4OCH3), 213.6 ppm
(SiCH2CH2C). 29Si NMR (CD2Cl2): δ −12.6 ppm. Anal. Calcd for
C18H20O2Si: C, 72.93; H, 6.80. Found: C, 72.53; H, 7.19.
1024
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Organometallics
Article
separated, the aqueous layer was extracted with diethyl ether (3 × 50
mL) and discarded, and the combined organic phases were dried over
anhydrous sodium sulfate. The solvent was removed under reduced
pressure, and the residue was purified by bulb-to-bulb distillation in
vacuo to give 7 in 73% yield (with respect to 4) as a colorless oil (728
an autoclave at 100 °C under an atmosphere of hydrogen (30 bar) for
24 h. The mixture was then cooled to 20 °C and filtered through a pad
of Celite, followed by elution with methanol (3 × 20 mL). The filtrate
and the eluates were combined, the volatile components were removed
under reduced pressure, and the residue was purified by bulb-to-bulb
distillation in vacuo to give 9 in 79% yield as a colorless oil (413 mg,
1
mg, 2.45 mmol); bp 253−254 °C/0.6 mbar. H NMR (CD2Cl2; data
1
1.26 mmol); bp 267−279 °C/0.3 mbar. H NMR (CD2ACl2; data for
for two conformers (molar ratio 1:1.1); the dominating conformer is
marked with an A, the minor conformer with a B): δ 1.03−1.14A,B (m, 2
H; SiCHHCH2C), 1.39−1.49A,B (m, 2 H; SiCHHCH2C), 1.40−
1.52A,B (m, 2 H; SiCH2CHHC), 2.03−2.12A,B (m, 2 H;
SiCH2CHHC), 2.75−2.83A,B (m, 1 H; SiCH2CH2CH), 3.79A and
3.83B (s, 3 H; C6H4OCH3), 6.88−6.92A and 6.97−7.01B (m, 2 H; H-
3/H-5, C6H4OCH3), 7.31−7.37B and 7.39−7.44A (m, 2 H; H-3/H-5,
C6H5), 7.33−7.37B and 7.40−7.44A (m, 1 H; H-4, C6H5), 7.39−7.43A
and 7.56−7.60B (m, 2 H; H-2/H-6, C6H4OCH3), 7.47−7.51B and
7.62−7.68A ppm (m, 2 H; H-2/H-6, C6H5); signal for NH2 not
detected. 13C NMR (CD2Cl2; data for two conformers (molar ratio
1:1.1); the dominating conformer is marked with an A, the minor
conformer with a B): δ 9.5A,B (SiCH2CH2C), 34.13B and 34.14A
(SiCH2CH2C), 53.2A and 53.3B (SiCH2CH2C), 55.31A and 55.33B
(C6H4OCH3), 114.0A and 114.2B (C-3/C-5, C6H4OCH3), 126.1B and
128.0A (C-1, C6H4OCH3), 128.1B and 128.3A (C-3/C-5, C6H5),
129.47B and 129.54A (C-4, C6H5), 134.6B and 134.9A (C-2/C-6, C6H5),
136.09A and 136.4B (C-2/C-6, C6H4OCH3), 136.13A and 137.9B (C-1,
C6H5), 161.08A and 161.14B ppm (C-4, C6H4OCH3). 29Si NMR
(CD2Cl2; data for two conformers (molar ratio 1:1.1); the dominating
conformer is marked with an A, the minor conformer with a B): δ
−14.0A,B ppm. Anal. Calcd for C18H23NOSi: C, 72.68; H, 7.79; N,
4.71. Found: C, 72.36; H, 7.74; N, 4.72.
D
four species (molar ratio 1:2.1:7.5:9.4) marked from to
with
decreasing concentration): δ 0.93−1.04A, 1.01−1.08C, 1.08−1.19B, and
1.13−1.18D (m, 2 H; SiCHHCH2C), 1.29−1.42B, 1.44−1.57A,D, and
1.67−1.74C (m, 2 H; SiCH2CHHC), 1.54−1.63A, 1.55−1.62C, 1.70−
1.72D, and 1.63−1.72B (m, 2 H; SiCHHCH2C), 1.94−2.05A, 1.97−
2.05C, 1.98−2.08B, and 2.07−2.14D (m, 2 H; SiCH2CHHC), 2.62−
C
D
2.71B, 2.76−2.84A, signals for
and
not detected (m, 1 H;
SiCH2CH2CH), 3.64C and 3.72A,B,D (s, 6 H; C6H3(OCH3)2), 6.485B,
6.493D, 6.537C, and 6.547A (d, 3JHHA = 3JHHB = 3JHHC = 3JHHD = 8.3 Hz;
2 H, H-3/H-5, C6H3(OCH3)2), 7.25−7.36A,B,C,D (m, 2 H; H-3/H-5,
C6H5), 7.26−7.35A,B,C,D (m, 1 H; H-4, C6H5), 7.28B, 7.335C, 7.342A,
3
A
3
B
3
C
3
D
and 7.35D (t, JHH = JHH = JHH = JHH = 8.3 Hz, 1 H; H-4,
C6H3(OCH3)2), 7.46−7.50C,D, 7.49−7.58A, and 7.64−7.72B ppm (m, 2
H; H-2/H-6, C6H5); signal for NH2 not detected. 13C NMR (CD2Cl2;
A
D
data for four species (molar ratio 1:2.1:7.5:9.4) marked from to
with decreasing concentration): δ 10.6C, 11.1D, 11.8A, and 12.1B
(SiCH2CH2C), 33.2C, 34.0D, 34.3A, and 35.1B (SiCH2CH2C), 52.9A
and 53.6B, signals for and not detected (SiCH2CH2C), 55.4C,
55.46A,D, and 55.51B (C6H3(OCH3)2), 103.91B, 103.94A, 104.1D, and
104.2C (C-3/C-5, C6H3(OCH3)2), 110.2C, 110.3A, 110.5D, and 112.1B
(C-1, C6H3(OCH3)2), 127.73A, 127.77C, 127.87B, and 127.90D (C-3/
C-5, C6H5), 128.8A,B,C,D (C-4, C6H5), 132.3B, 132.38D, 132.44A, and
132.5C (C-4, C6H3(OCH3)2), 134.0D, 134.2C, 134.4A, and 134.7B (C-
2/C-6, C6H5), 138.3B, 138.8D, 139.1C, and 139.2A (C-1, C6H5), 165.8B,
166.1D, 166.3C, and 166.4A ppm (C-2/C-6, C6H3(OCH3)2). 29Si NMR
(CD2Cl2; data for four species (molar ratio 1:2.1:7.5:9.4) marked from
C
D
Isopropyl(4-(4-methoxyphenyl)-4-phenyl-4-silacyclohexan-1-yl)-
amine (8). Compound 8 was synthesized by using the same procedure
as described for the preparation of 7, starting from 4 (1.00 g, 3.37
mmol) and using isopropylamine (1.40 g, 23.7 mmol) instead of the 7
M solution of ammonia in methanol. The product was purified by
bulb-to-bulb distillation in vacuo to give 8 in 61% yield as a colorless
oil (700 mg, 2.06 mmol); bp 253−254 °C/0.3 mbar. 1H NMR
(CD2Cl2; data for two conformers (molar ratio 1:1.6); the dominating
conformer is marked with an A, the minor conformer with a B): δ
to with decreasing concentration): δ −16.3B, −15.0C, −14.9A, and
A
D
−12.4D ppm. HRMS (ESI): m/z calcd for [M + H]+ 328.1727, found
328.1727.
Isopropyl(4-(2,4-dimethoxyphenyl)-4-phenyl-4-silacyclohexan-1-
yl)amine (10). Compound 10 was synthesized by using the same
procedure as described for the preparation of 9, using a suspension of
activated Raney nickel in water (50 weight %, 500 mg of suspension,
4.26 mmol of Raney nickel), isopropylamine (674 mg, 11.4 mmol),
and a solution of 5 (530 mg, 1.62 mmol) in methanol (20 mL). The
reaction mixture was heated in an autoclave at 100 °C under an
atmosphere of hydrogen (35 bar) for 27 h, and the product was
purified by bulb-to-bulb distillation in vacuo to give 10 in 77% yield as
3
A
1.01−1.10A,B (m, 2 H; SiCHHCH2C), 1.018A and 1.020B (d, JHH
=
B
3JHH = 6.2 Hz, 6 H; CH(CH3)2), 1.34−1.42A,B (m, 2 H;
SiCHHCH2C), 1.40−1.50A,B (m, 2 H; SiCH2CHHC), 2.01−2.09A,B
(m, 2 H; SiCH2CHHC), 2.60−2.68A,B (m, 1 H; SiCH2CH2CH),
3
A
3
B
2.927A and 2.931B (sept, JHH = JHH = 6.2 Hz, 1 H; CH(CH3)2),
3.79A and 3.81B (s, 3 H; C6H4OCH3), 6.87−6.91A and 6.93−6.97B (m,
2 H; H-3/H-5, C6H4OCH3), 7.30−7.36B and 7.36−7.40A (m, 2 H; H-
3/H-5, C6H5), 7.33−7.36B and 7.36−7.41A (m, 1 H; H-4, C6H5),
7.39−7.43A and 7.51−7.55B (m, 2 H; H-2/H-6, C6H4OCH3), 7.47−
7.50B and 7.58−7.62A ppm (m, 2 H; H-2/H-6, C6H5); signal for NH
not detected. 13C NMR (CD2Cl2; data for two conformers (molar
ratio 1:1.6); the dominating conformer is marked with an A, the minor
conformer with a B): δ 9.15A and 9.18B (SiCH2CH2C), 23.7A,B
(C(CH3)2), 31.15A and 31.18B (SiCH2CH2C), 45.3A and 45.4B
(C(CH3)2), 55.33A and 55.34B (C6H4OCH3), 55.5A and 55.6B
(SiCH2CH2C), 113.9A and 114.1B (C-3/C-5, C6H4OCH3), 126.6B
and 128.0A (C-1, C6H4OCH3), 128.1B and 128.3A (C-3/C-5, C6H5),
129.4B and 129.5A (C-4, C6H5), 134.7B and 134.9A (C-2/C-6, C6H5),
136.1A and 136.4B (C-2/C-6, C6H4OCH3), 136.5A and 137.9B (C-1,
C6H5), 161.06A and 161.10B ppm (C-4, C6H4OCH3). 29Si NMR
(CD2Cl2; data for two conformers (molar ratio 1:1.6); the dominating
conformer is marked with an A, the minor conformer with a B): δ
−13.0A,B ppm. HRMS (ESI): m/z calcd for [M + H]+ 340.2091, found
340.2088.
1
a colorless oil (462 mg, 1.25 mmol); bp 273−275 °C/0.2 mbar. H
NMR (CD2Cl2; data for four species (molar ratio 1:1.1:2.2:3.5)
A
D
marked from to with decreasing concentration): δ 0.98−1.04C,D
3
B
3
A
(m), 1.00B (d, JHH = 6.2 Hz), and 1.02A (d, JHH = 6.2 Hz) (6 H;
CH(CH3)2), 0.98−1.06A, 1.00−1.08C, 1.07−1.16B, and 1.10−1.18D
(m, 2 H; SiCHHCH2C), 1.47−1.56A, 1.53−1.61C, 1.59−1.67B, and
1.62−1.69D (m, 2 H; SiCHHCH2C), 1.26−1.37B, 1.47−1.57D, 1.48−
1.60A, and 1.66−1.75C (m, 2 H; SiCH2CHHC), 1.92−2.01A, 1.96−
2.05C, 2.04−2.13B, 2.07−2.14D (m, 2 H; SiCH2CHHC), 2.49−2.57B,D
and 2.64−2.71A,C (m, 1 H; SiCH2CH2CH), 2.89−2.98C,D (m), 2.934B
3
B
3
A
(sept, JHH = 6.2 Hz), and 2.938A (sept, JHH = 6.2 Hz) (1 H;
CH(CH3)2), 3.711A, 3.714C,D, and 3.719B (s, 6 H; C6H3(OCH3D)2),
3
A
3
B
3
C
3
6.480B, 6.482D, 6.52A, and 6.54C (d, JHH = JHH = JHH = JHH
=
8.3 Hz, 2 H; H-3/H-5, C6H3(OCH3)2), 7.24−7.34A,B,C,D (m, 2 H; H-
3/H-5, C6H5), 7.24−7.36 (m, 1 H; H-4, C6H3(OCH3)2), 7.26−
7.33A,B,C,D (m, 1 H; H-4, C6H5), 7.51−7.57A,C and 7.63−7.68B,D ppm
(m, 2 H; H-2/H-6, C6H5); signal for NH not detected. 13C NMR
(CD2Cl2; data for four species (molar ratio 1:1.1:2.2:3.5) marked from
A to D with decreasing concentration): δ 10.5C, 11.0D, 11.3A, and 12.1B
(SiCH2CH2C), 23.4A,B,C,D (C(CH3)2), 31.0A 32.0B, 33.1C, and 34.0D
(SiCH2CH2C), 45.4A,B,C,D (C(CH3)2), 55.0A,C and 56.3B,D
(SiCH2CH2C), 55.5A,B,C,D (C6H3(OCH3)2), 103.9A,B,C,D (C-3/C-5,
C6H3(OCH3)2), 110.2C, 110.6A, 111.6D, and 112.1B (C-1,
C6H3(OCH3)2), 127.75A, 127.78C, 127.8B, and 127.9D (C-3/C-5,
C6H5), 128.81B, 128.83A, 128.92C, and 128.93D (C-4, C6H5), 132.3B,
(4-(2,4-Dimethoxyphenyl)-4-phenyl-4-silacyclohexan-1-yl)amine
(9). A suspension of activated Raney nickel in water (50 weight %, 500
mg of suspension, 4.26 mmol of Raney nickel) was washed with
methanol (3 × 10 mL), and the resulting powder was resuspended in
methanol (10 mL). This suspension and a 7 M solution of ammonia in
methanol (1.60 mL; 11.2 mmol of ammonia) were added sequentially
in single portions at 20 °C to a stirred solution of 5 (520 mg, 1.59
mmol) in methanol (20 mL), and the resulting mixture was heated in
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Article
132.39A,D, and 132.5C (C-4, C6H3(OCH3)2), 134.41A, 134.42C, 134.6D,
and 134.7B (C-2/C-6, C6H5), 138.1D, 138.4B, 138.7C, and 139.2A (C-1,
C6H5), 165.8B, 166.0D, and 166.3A,C ppm (C-2/C-6, C6H3(OCH3)2).
29Si NMR (CD2Cl2; data for four species (molar ratio 1:1.1:2.2:3.5)
6.070D, 6.11A, and 6.12C (s, 2 H; H-3/H-5, C6H2(OCH3)3), 7.26−
7.35A,B,C,D (m, 2 H; H-3/H-5, C6H5), 7.28−7.34A,B,C,D (m, 1 H; H-4,
C6H5), 7.51−7.59A,C and 7.63−7.69B,D ppm (m, 2 H; H-2/H-6,
C6H5); signal for NH not detected. 13C NMR (CD2Cl2; data for four
species (molar ratio 1:1.7:3.2:5.1) marked from A to D with decreasing
concentration): δ 10.7C, 11.1D, 11.4A, and 12.2B (SiCH2CH2C),
23.7A,B,C,D (C(CH3)2), 31.17A, 32.22B, 33.24C, and 34.0D
(SiCH2CH2C), 45.3A,B,C,D (C(CH3)2), 55.1A,C and 56.3B,D
(SiCH2CH2C), 55.43A,C and 55.47B,D (o-OCH3, C6H2(OCH3)3),
55.53A,B,C,D (p-OCH3, C6H2(OCH3)3), 90.76D, 90.78B, and 90.80A,C
(C-3/C-5, C6H2(OCH3)3), 101.5C, 102.0A, 103.1D, and 103.6B (C-1,
C6H2(OCH3)3), 127.73A, 127.75C, 127.79B, and 127.9D (C-3/C-5,
marked from A to D with decreasing concentration): δ −16.2D, −15.2B,
−15.1C, and −14.2A ppm. HRMS (ESI): m/z calcd for [M + H]+
370.2197, found 370.2192.
(4-Phenyl-4-(2,4,6-trimethoxyphenyl)-4-silacyclohexan-1-yl)-
amine (11). Compound 11 was synthesized by using the same
procedure as described for the preparation of 9, using a suspension of
activated Raney nickel in water (50 weight %, 1.50 g of suspension,
12.8 mmol of Raney nickel), a 7 M solution of ammonia in methanol
(4.29 mL, 30.0 mmol of ammonia), and a solution of 6 (1.52 g, 4.26
mmol) in methanol (30 mL). The reaction mixture was heated in an
autoclave at 100 °C under an atmosphere of hydrogen (100 bar) for
16 h, and the product was purified by bulb-to-bulb distillation in vacuo
to give 11 in 74% yield as a colorless oil (1.13 g, 3.16 mmol); bp 248−
C6H5), 128.68B, 128.73A, 128.81D, and 128.82C (C-4, C6H5), 134.4A,C
,
134.58D, and 134.56B (C-2/C-6, C6H5), 138.6D, 139.0B, 139.2C, and
139.7A (C-1, C6H5), 164.0B, 164.12D, 164.14A, and 164.2C (C-4,
C6H2(OCH3)3), 166.80B, 166.81D, 167.24A, and 167.25C ppm (C-2/C-
6, C6H2(OCH3)3). 29Si NMR (CD2Cl2; data for four species (molar
ratio 1:1.7:3.2:5.1) marked from A to D with decreasing concentration):
δ −16.7D, −15.7B, −15.5C, and −14.6A ppm. HRMS (ESI): m/z calcd
for [M + H]+ 400.2303, found 400.2303.
1
250 °C/0.02 mbar. H NMR (CD2Cl2; data for four species (molar
ratio 1:1.3:23:28) marked from A to D with decreasing concentration):
δ 0.91−1.01A, 0.99−1.06C, 1.07−1.15D, and 1.07−1.16B (m, 2 H;
SiCHHCH2C), 1.47−1.55C, 1.53−1.60A, 1.59−1.66D, and 1.60−1.68B
(m, 2 H; SiCHHCH2C), 1.30−1.40B, 1.33−1.43D, 1.45−1.56A, and
1.58−1.68C (m, 2 H; SiCH2CHHC), 1.95−2.03C, 1.96−2.04A, 1.98−
2.06B, and 2.08−2.13D (m, 2 H; SiCH2CHHC), 2.63−2.71B and 2.75−
4-Chloro-4-phenyl-4-silacyclohexan-1-one (13). Method I. A 2 M
solution of hydrogen chloride in diethyl ether (4.05 mL, 8.10 mmol of
HCl) was added in a single portion at 20 °C to a stirred solution of 4
(40.0 mg, 135 μmol) in dichloromethane (10 mL), and the reaction
mixture was then stirred at 20 °C for 60 h, until the cleavage of the
MOP protecting group was complete (by GC/MS analysis). The
volatile components were removed under reduced pressure, and the
residue was demonstrated by NMR spectroscopic and GC/MS studies
to be a mixture of 13 and methoxybenzene (see Figures S1−S5 in the
C
D
2.83A, signals for and not detected (m, 1 H; SiCH2CH2CH),
3.715B and 3.718A, signals for and not detected (s, 6 H; o-OCH3,
C6H2(OCH3)3), 3.79B, 3.80D, 3.82C, and 3.83A (s, 3 H; p-OCH3,
C6H2(OCH3)3), 6.07B, 6.08D, 6.11C, and 6.13A (s, 2 H; H-3/H-5,
C6H2(OCH3)3), 7.26−7.31A,C and 7.30−7.36B,D (m, 2 H; H-3/H-5,
C6H5), 7.28−7.34A,B,C,D (m, 1 H; H-4, C6H5), 7.40−7.55A,C and 7.65−
7.70B,D ppm (m, 2 H; H-2/H-6, C6H5); signal for NH2 not detected.
13C NMR (CD2Cl2; data for four species (molar ratio 1:1.3:23:28)
C
D
1
Supporting Information). H NMR (CD2Cl2): δ 1.47−1.60 (m, 4 H;
SiCH2CH2C), 2.58−2.68 and 2.76−2.85 (m, 4 H; SiCH2CH2C), 3.79
(s, 0.28 H; C6H5OCH3), 6.87−6.98 (m, 0.18 H; H-2/H-6,
C6H5OCH3), 6.93−6.98 (m, 0.09 H; H-4, C6H5OCH3), 7.25−7.31
(m, 0.19 H; H-3/H-5, C6H5OCH3), 7.43−7.49 (m, 2 H; H-3/H-5,
C6H5), 7.49−7.54 (m, 1 H; H-4, C6H5), 7.65−7.70 ppm (m, 2 H; H-
2/H-6, C6H5). 13C NMR (CD2Cl2): δ 13.3 (SiCH2CH2C), 37.5
(SiCH2CH2C), 55.4 (C6H5OCH3), 114.3 (C-2/C-6, C6H5OCH3),
120.9 (C-4, C6H5OCH3), 128.7 (C-3/C-5, C6H5), 129.7 (C-3/C-5,
C6H5OCH3), 131.5 (C-4, C6H5), 132.9 (C-1, C6H5), 133.8 (C-2/C-6,
C6H5), 161.5 (C-1, C6H5OCH3), 211.7 ppm (SiCH2CH2C). 29Si
NMR (CD2Cl2): δ 15.2 ppm.
A
D
marked from to with decreasing concentration): δ 11.0C, 11.7D,
11.9A, and 12.1B (SiCH2CH2C), 30.1C, 31,1D, 34.5A, and 35.2B
(SiCH2CH2C), 53.1A and 53.6B, signals for and not detected
(SiCH2CH2C), 55.4A,B,C,D (o-OCH3, C6H2(OCH3)3), 55.45B.D and
55,52A,C (p-OCH3, C6H2(OCH3)3), 90.75B,D and 90.79A,C (C-3/C-5,
C6H2(OCH3)3), 101.5A, 102.0C, 103.3D, and 103.6B (C-1,
C6H2(OCH3)3), 127.70A, 127.72C, 127.80C, and 127.82B (C-3/C-5,
C
D
C6H5), 128.71B and 128.73A, signals for and not detected (C-4,
C
D
C6H5), 134.35A, 134.38C, 134.59D, and 134.62B (C-2/C-6, C6H5),
138.9B and 139.7A, signals for and not detected (C-1, C6H5),
164.04B, 164.04D, 164.1C, and 164.2A (C-4, C6H2(OCH3)3), 166.75B,
166.80D, 167.2C, and 167.3A ppm (C-2/C-6, C6H2(OCH3)3). 29Si
NMR (CD2Cl2; data for four species (molar ratio 1:1.3:23:28) marked
from A to D with decreasing concentration): δ −16.9B, −15.7D, −15.3A,
and −14.8C. Anal. Calcd for C20H27NO3Si: C, 67.19; H, 7.61; N, 3.92.
Found: C, 67.17; H, 7.65; N, 3.89.
C
D
Method II. A 2 M solution of hydrogen chloride in diethyl ether
(650 μL, 1.30 mmol of HCl) was added in a single portion at 20 °C to
a stirred solution of 5 (85.0 mg, 260 μmol) in dichloromethane (10
mL), and the reaction mixture was stirred at 20 °C for 30 min, until
the cleavage of the DMOP protecting group was complete (by GC/
MS analysis). The volatile components were removed under reduced
pressure, and the residue was demonstrated by NMR spectroscopy and
GCIMS studies to be an equimolar mixture of 13 and 1,3-
dimethoxybenzene (see Figures S6−S10 in the Supporting Informa-
tion). 1H NMR (CD2Cl2): δ 1.47−1.60 (m, 4 H; SiCH2CH2C), 2.58−
2.68 and 2.76−2.85 (m, 4 H; SiCH2CH2C), 3.78 (s, 6 H;
C6H4(OCH3)2), 6.45−6.48 (m, 1 H; H-2, C6H4(OCH3)2), 6.48−
6.52 (m, 2 H; H-4/H-6, C6H4(OCH3)2), 7.15−7.21 (m, 1 H; H-5,
C6H4(OCH3)2), 7.44−7.50 (m, 2 H; H-3/H-5, C6H5), 7.50−7.55 (m,
1 H; H-4, C6H5), 7.67−7.71 ppm (m, 2 H; H-2/H-6, C6H5). 13C
NMR (CD2Cl2): δ 13.3 (SiCH2CH2C), 37.5 (SiCH2CH2C), 55.6
(C6H4(OCH3)2), 100.7 (C-2, C6H4(OCH3)2), 106.4 (C-4/C-6,
C6H4 (OCH3 )2 ), 128.8 (C-3/C-5, C6 H5), 130.2 (C-5,
C6H4(OCH3)2), 131.5 (C-4, C6H5), 132.9 (C-1, C6H5), 133.9 (C-2/
C-6, C6H5), 161.3 (C-1/C-3, C6H4(OCH3)2), 211.7 ppm
(SiCH2CH2C). 29Si NMR (CD2Cl2): δ 15.2 ppm.
Isopropyl(4-phenyl-4-(2,4,6-trimethoxyphenyl)-4-silacyclohexan-
1-yl)amine (12). Compound 12 was synthesized by using the same
procedure as described for the preparation of 9, using a suspension of
activated Raney nickel in water (50 weight %, 500 mg of suspension,
4.26 mmol of Raney nickel), isopropylamine (662 mg, 11.2 mmol),
and a solution of 6 (570 mg, 1.60 mmol) in methanol (20 mL). The
reaction mixture was heated in an autoclave at 100 °C under an
atmosphere of hydrogen (50 bar) for 16 h, and the product was
purified by bulb-to-bulb distillation in vacuo to give 12 in 81% yield as
1
a colorless oil (520 mg, 1.30 mmol); bp 285−287 °C/0.5 mbar. H
NMR (CD2Cl2; data for four species (molar ratio 1:1.7:3.2:5.1)
A
D
marked from to with decreasing concentration): δ 0.98−1.04C,D
3
B
3
A
(m), 1.00B (d, JHH = 6.2 Hz), and 1.02A (d, JHH = 6.2 Hz) (6 H;
CH(CH3)2), 0.96−1.05A,C, 1.06−1.15B, and 1.08−1.16D (m, 2 H;
SiCHHCH2C), 1.45−1.53A, 1.52−1.59C, 1.57−1.65B, and 1.60−1.66D
(m, 2 H; SiCHHCH2C), 1.26−1.36B, 1.46−1.58A, 1.48−1.58D, and
1.66−1.74C (m, 2 H; SiCH2CHHC), 1.92−2.01A, 1.98−2.05C, 2.04−
2.11B, and 2.07−2.13D (m, 2 H; SiCH2CHHC), 2.49−2.57B,D and
2.63−2.71A,C (m, 1 H; SiCH2CH2CH), 2.89−2.98C,D (m), 2.93B (sept,
Method III. A 2 M solution of hydrogen chloride in diethyl ether
(70.0 μL, 140 μmol of HCl) was added in a single portion at 20 °C to
a stirred solution of 6 (50.0 mg, 140 μmol) in dichloromethane (10
mL), and the reaction mixture was then stirred at 20 °C for 5 min,
until the cleavage of the TMOP protecting group was complete (by
GC/MS anaylsis). The solvents were removed under reduced
pressure, and the residue was demonstrated by NMR spectroscopy
and GCIMS studies to be an equimolar mixture of 13 and 1,3,5-
3JHHB = 6.2 Hz), and 2.94A (sept, JHHA = 6.2 Hz) (1 H; CH(CH3)2),
3
3.71A,B, 3.715D, and 3.717C (s, 6 H; o-OCH3, C6H2(OCH3)3), 3.792B,
3.793D, 3.820A, and 3.824C (s, 3 H; p-OCH3, C6H2(OCH3)3), 6.069B,
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Article
1
trimethoxybenzene (see Figures S11−S15 in the Supporting
Information). 1H NMR (CD2Cl2): δ 1.47−1.60 (m, 4 H;
SiCH2CH2C), 2.58−2.68 and 2.76−2.85 (m, 4 H; SiCH2CH2C),
3.75 (s, 9 H; C6H3(OCH3)3), 6.08 (s, 3 H; H-2/H-4/H-6,
C6H3(OCH3)3), 7.44−7.50 (m, 2 H; H-3/H-5, C6H5), 7.50−7.55
(m, 1 H; H-4, C6H5), 7.67−7.71 ppm (m, 2 H; H-2/H-6, C6H5). 13C
NMR (CD2Cl2): δ 13.3 (SiCH2CH2C), 37.5 (SiCH2CH2C), 55.6
(C6H3(OCH3)3), 93.1 (C-2/C-4/C-6, C6H3(OCH3)3), 128.8 (C-3/C-
5, C6H5), 131.5 (C-4, C6H5), 132.9 (C-1, C6H5), 133.9 (C-2/C-6,
C6H5), 162.0 (C-1/C-3/C-5, C6H3(OCH3)3), 211.8 ppm
(SiCH2CH2C). 29Si NMR (CD2Cl2): δ 15.2 ppm.
Trimethoxymethylsilane (14). This compound was commercially
available.
Trimethoxyphenylsilane (15). This compound was commercially
available.
Dimethoxy(4-methoxyphenyl)methylsilane (16). This compound
mbar. H NMR (CD2Cl2): δ 3.61 (s, 6 H; SiOCH3), 3.81 (s, 3 H;
C6H4OCH3), 6.92−6.97 (m, 2 H; H-3/H-5, C6H4OCH3), 7.36−7.42
(m, 2 H; H-3/H-5, C6H5), 7.41−7.47 (m, 1 H; H-4, C6H5), 7.55−7.60
(m, 2 H; H-2/H-6, C6H4OCH3), 7.61−7.66 ppm (m, 2 H; H-2/H-6,
C6H5). 13C NMR (CD2Cl2): δ 51.0 (SiOCH3), 55.4 (C6H4OCH3),
114.0 (C-3/C-5, C6H4OCH3), 123.6 (C-1, C6H4OCH3), 128.2 (C-3/
C-5, C6H5), 130.6 (C-4, C6H5), 133.2 (C-1, C6H5), 135.1 (C-2/C-6,
C6H5), 136.7 (C-2/C-6, C6H4OCH3), 161.9 ppm (C-4, C6H4OCH3).
29Si NMR (CD2Cl2): δ −28.9 ppm. Anal. Calcd for C15H18O3Si: C,
65.66; H, 6.61. Found: C, 65.57; H, 6.42.
(2,4-Dimethoxyphenyl)dimethoxyphenylsilane (20). A 2.5 M
solution of n-butyllithium in hexanes (154 mL, 385 mmol of n-
BuLi) was added dropwise at 20 °C within 1 h to a stirred mixture of
1,3-dimethoxybenzene (48.4 g, 350 mmol), TMEDA (44.7 g, 385
mmol), and n-hexane (150 mL). The resulting suspension was stirred
at 20 °C for 16 h and then added to a stirred solution of 15 (69.4 g,
350 mmol) in diethyl ether (250 mL) at 20 °C within 1 h, and stirring
was 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 fractional
distillation in vacuo to give 20 in 68% yield as a colorless liquid (72.9
was synthesized according to ref 5 (71% yield).
(2,6-Dimethoxyphenyl)dimethoxymethylsilane (17). A 2.5 M
solution of n-butyllithium in hexanes (160 mL, 400 mmol of n-
BuLi) was added dropwise at 20 °C within 1 h to a stirred mixture of
1,3-dimethoxybenzene (50.8 g, 368 mmol), N,N,N′,N′-tetramethyl-
enediamine (TMEDA; 46.9 g, 404 mmol), and n-hexane (170 mL).
The resulting suspension was stirred at 20 °C for 16 h and then added
to a stirred solution of 14 (50.0 g, 367 mmol) in diethyl ether (170
mL) at 20 °C within 1 h, and the reaction mixture was then heated
under reflux for 2 h. The resulting precipitate was filtered off, washed
with diethyl ether (3 × 70 mL), and discarded. The filtrate and wash
solutions were combined, the solvents were removed under reduced
pressure, and the residue was purified by fractional distillation in vacuo
to give 17 in 71% yield as a colorless liquid (63.4 g, 262 mmol); bp 87
1
g, 239 mmol); bp 172 °C/0.8 mbar. H NMR (CD2Cl2): δ 3.60 (s, 6
H; SiOCH3), 3.69 (s, 6 H; C6H3(OCH3)2), 6.56 (d, JHH = 8.3 Hz, 2
3
H; H-3/H-5, C6H3(OCH3)2), 7.28−7.37 (m, 2 H; H-3/H-5, C6H5),
3
7.31−7.39 (m, 1 H; H-4, C6H5), 7.38 (t, JHH = 8.3 Hz, 1 H; H-4,
C6H3(OCH3)2), 7.57−7.61 ppm (m, 2 H; H-2/H-6, C6H5). 13C NMR
(CD2Cl2): δ 51.2 (SiOCH3), 55.8 (C6H3(OCH3)2), 104.2 (C-3/C-5,
C6H3(OCH3)2), 108.2 (C-1, C6H3(OCH3)2), 127.7 (C-3/C-5, C6H5),
129.7 (C-4, C6H5), 133.6 (C-4, C6H3(OCH3)2), 134.4 (C-2/C-6,
C6H5), 136.2 (C-1, C6H5), 166.4 ppm (C-2/C-6, C6H3(OCH3)2). 29Si
NMR (CD2Cl2): δ −29.8 ppm. Anal. Calcd for C16H20O4Si: C, 63.13;
H, 6.62. Found: C, 63.06; H, 6.42.
1
°C/0.3 mbar. H NMR (CD2Cl2): δ 0.32 (s, 3 H; SiCH3), 3.51 (s, 6
3
H; SiOCH3), 3.78 (s, 6 H; C6H3(OCH3)2), 6.54 (d, JHH = 8.3 Hz, 2
3
H; H-3/H-5, C6H3(OCH3)2), 7.34 ppm (t, JHH = 8.3 Hz, 1 H; H-4,
C6H3(OCH3)2). 13C NMR (CD2Cl2): δ −1.4 (SiCH3), 50.7
(SiOCH3), 55.8 (C6H3(OCH3)2), 103.9 (C-3/C-5, C6H3(OCH3)2),
109.8 (C-1, C6H3(OCH3)2), 133.1 (C-4, C6H3(OCH3)2), 166.1 ppm
(C-2/C-6, C6H3(OCH3)2). 29Si NMR (CD2Cl2): δ −15.3 ppm. Anal.
Calcd for for C11H18O4Si: C, 54.52; H, 7.49. Found: C, 54.57; H 7.45.
Dimethoxymethyl(2,4,6-trimethoxyphenyl)silane (18). A 2.5 M
solution of n-butyllithium in hexanes (161 mL, 403 mmol of n-BuLi)
was added dropwise at 20 °C within 1 h to a stirred mixture of 1,3,5-
trimethoxybenzene (61.8 g, 367 mmol), TMEDA (46.9 g, 404 mmol),
and n-hexane (170 mL). The resulting suspension was stirred at 20 °C
for 16 h and then added to a stirred solution of 14 (50.0 g, 367 mmol)
in diethyl ether (170 mL) at 20 °C within 1 h, and the reaction
mixture was then 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 fractional distillation in vacuo to give 18 in 77% yield as a
Dimethoxyphenyl(2,4,6-trimethoxyphenyl)silane (21). A 2.5 M
solution of n-butyllithium in hexanes (154 mL, 386 mmol of n-BuLi)
was added dropwise at 20 °C within 1 h to a stirred mixture of 1,3,5-
trimethoxybenzene (58.9 g, 350 mmol), TMEDA (44.7 g, 385 mmol),
and n-hexane (150 mL). The resulting suspension was stirred at 20 °C
for 16 h and then added to a stirred solution of 15 (69.4 g, 350 mmol)
in diethyl ether (250 mL) at 20 °C within 1 h, and stirring was
continued 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 give 21 in 67% yield as a colorless oil
(78.5 g, 235 mmol); bp 164−165 °C/0.1 mbar. 1H NMR (CD2Cl2): δ
3.58 (s, 6 H; SiOCH3), 3.67 (s, 6 H; o-OCH3, C6H2(OCH3)3), 3.83 (s,
3 H; p-OCH3, C6H2(OCH3)3), 6.11 (s, 2 H; H-3/H-5,
C6H2(OCH3)3), 7.28−7.36 (m, 2 H; H-3/H-5, C6H5), 7.30−7.38
(m, 1 H; H-4, C6H5), 7.55−7.61 ppm (m, 2 H; H-2/H-6, C6H5). 13C
NMR (CD2Cl2): δ 51.1 (SiOCH3), 55.6 (p-OCH3, C6H2(OCH3)3),
55.7 (o-OCH3, C6H2(OCH3)3), 90.9 (C-3/C-5, C6H2(OCH3)3), 99.8
(C-1, C6H2(OCH3)3), 127.6 (C-3/C-5, C6H5), 129.6 (C-4, C6H5),
134.4 (C-2/C-6, C6H5), 136.6 (C-1, C6H5), 165.0 (C-4,
C6H2(OCH3)3), 167.6 ppm (C-2/C-6, C6H2(OCH3)3). 29Si NMR
(CD2Cl2): δ −29.4 ppm. Anal. Calcd for C17H22O5Si: C, 61.05; H,
6.63. Found: C, 60.86; H, 6.60.
1
colorless liquid (76.9 g, 282 mmol); bp 128 °C/0.3 mbar. H NMR
(CD2Cl2): δ 0.29 (s, 3 H; SiCH3), 3.49 (s, 6 H; SiOCH3), 3.77 (s, 6
H; o-OCH3, C6H2(OCH3)3), 3.82 (s, 3 H; p-OCH3, C6H2(OCH3)3),
6.10 ppm (s, 2 H; H-3/H-5, C6H2(OCH3)3). 13C NMR (CD2Cl2): δ
−1.4 (SiCH3), 50.6 (SiOCH3), 55.6 (p-OCH3, C6H2(OCH3)3), 55.7
(o-OCH3, C6H2(OCH3)3), 90.7 (C-3/C-5, C6H2(OCH3)3), 101.6 (C-
1, C6H2(OCH3)3), 164.5 (C-4, C6H2(OCH3)3), 167.2 ppm (C-2/C-6,
C6H2(OCH3)3). 29Si NMR (CD2Cl2): δ −15.0 ppm. Anal. Calcd for
C12H20O5Si: C, 52.92; H, 7.40. Found: C, 52.90; H, 7.44.
(4-Methoxyphenyl)methyldivinylsilane (22). This compound was
synthesized according to ref 5 (70% yield).
Dimethoxy(4-methoxyphenyl)phenylsilane (19). A solution of (4-
methoxyphenyl)magnesium bromide (prepared from magnesium
turnings (7.66 g, 315 mmol) and 1-bromo-4-methoxybenzene (58.9
g, 315 mmol) in tetrahydrofuran (200 mL)) was added dropwise at 20
°C within 1 h to a stirred solution of 15 (59.5 g, 300 mmol) in diethyl
ether (220 mL), and stirring was continued at 20 °C for 16 h. The
resulting precipitate was filtered off, washed with diethyl ether (3 ×
150 mL), and discarded. The filtrate and wash solutions were
combined, the solvents were removed under reduced pressure, and the
residue was purified by fractional distillation in vacuo to give 19 in
70% yield as a colorless liquid (57.9 g, 211 mmol); bp 131 °C/0.1
(2,6-Dimethoxyphenyl)methyldivinylsilane (23). A solution of
vinylmagnesium chloride in tetrahydrofuran (15 weight % CH2
CHMgCl, d = 0.97 g mL−1; 236 mL, 396 mmol of CH2CHMgCl)
was added dropwise at 20 °C within 30 min to a stirred solution of 17
(45.7 g, 189 mmol) in tetrahydrofuran (100 mL), and the reaction
mixture was heated under reflux for 1 h. The mixture was then cooled
to 20 °C, followed by the addition of n-pentane (150 mL). 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 fractional distillation in vacuo to give 23 in
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Organometallics
Article
72% yield as a colorless liquid (32.2 g, 137 mmol); bp 78 °C/0.1 mbar.
1H NMR (CD2Cl2): δ 0.48 (s, 3 H; SiCH3), 3.74 (s, 6 H;
C6H3(OCH3)2), 5.69 (δA), 5.95 (δM), and 6.45 (δX) (6 H; CHX
CHAHM, 3JAX = 20.4 Hz, 2JAM = 3.8 Hz, 3JMX = 14.5 Hz), 6.52 (d, 3JHH
= 8.3 Hz, 2 H; H-3/H-5, C6H3(OCH3)2), 7.30 ppm (t, 3JHH = 8.3 Hz,
1 H; H-4, C6H3(OCH3)2). 13C NMR (CD2Cl2): δ −2.9 (SiCH3), 55.6
(C6H3(OCH3)2), 104.1 (C-3/C-5, C6H3(OCH3)2), 111.6 (C-1,
C6H3(OCH3)2), 130.8 (SiCHCH2), 132.3 (C-4, C6H3(OCH3)2),
139.4 (SiCHCH2), 165.8 ppm (C-2/C-6, C6H3(OCH3)2). 29Si
NMR (CD2Cl2): δ −21.7 ppm. Anal. Calcd for for C13H18O2Si: C,
66.62; H, 7.74. Found: C, 66.67; H, 7.73.
Methyl(2,4,6-trimethoxyphenyl)divinylsilane (24). A solution of
vinylmagnesium chloride in tetrahydrofuran (15 weight % CH2
CHMgCl, d = 0.97 g mL−1; 236 mL, 396 mmol of CH2CHMgCl)
was added dropwise at 20 °C within 45 min to a stirred solution of 18
(51.3 g, 188 mmol) in tetrahydrofuran (120 mL), and the reaction
mixture was heated under reflux for 1 h. The mixture was then cooled
to 20 °C, followed by the addition of n-pentane (200 mL). 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 give 24 in
75% yield as a colorless oil (37.3 g, 141 mmol); bp 128 °C/0.1 mbar.
1H NMR (CD2Cl2): δ 0.43 (s, 3 H; SiCH3), 3.72 (s, 6 H; o-OCH3,
C6H2(OCH3)3), 3.80 (s, 3 H; p-OCH3, C6H2(OCH3)3), 5.67 (δA),
residue was purified by bulb-to-bulb distillation in vacuo to give 26 in
76% yield as a colorless liquid (38.0 g, 128 mmol); bp 138 °C/0.1
1
mbar. H NMR (CD2Cl2): δ 3.63 (s, 6 H; C6H3(OCH3)2), 5.64 (δA),
6.10 (δM), and 6.64 (δX) (6 H; CHXCHAHM, 3JAX = 20.3 Hz, 2JAM
=
3
3
3.9 Hz, JMX = 14.4 Hz), 6.55 (d, JHH = 8.3 Hz, 2 H; H-3/H-5,
C6H3(OCH3)2), 7.27−7.34 (m, 2 H; H-3/H-5, C6H5), 7.29−7.36 (m,
3
1 H; H-4, C6H5), 7.36 (t, JHH = 8.3 Hz, 1 H; H-4, C6H3(OCH3)2),
7.46−7.52 ppm (m, 2 H; H-2/H-6, C6H5). 13C NMR (CD2Cl2): δ
55.6 (C6H3(OCH3)2), 104.4 (C-3/C-5, C6H3(OCH3)2), 110.3 (C-1,
C6H3(OCH3)2), 127.6 (C-3/C-5, C6H5), 128.9 (C-4, C6H5), 132.9 (C-
4, C6H3(OCH3)2), 133.0 (SiCHCH2), 135.1 (C-2/C-6, C6H5),
137.0 (C-1, C6H5), 137.2 (SiCHCH2), 166.1 ppm (C-2/C-6,
C6H3(OCH3)2). 29Si NMR (CD2Cl2): δ −24.9 ppm. Anal. Calcd for
C18H20O2Si: C, 72.93; H, 6.80. Found: C, 73.02; H, 6.80.
Phenyl(2,4,6-trimethoxyphenyl)divinylsilane (27). A solution of
vinylmagnesium chloride in tetrahydrofuran (15 weight % CH2
CHMgCl, d = 0.97 g mL−1; 147 mL, 247 mmol of CH2CHMgCl)
was added dropwise at 20 °C within 45 min to a stirred solution of 21
(39.1 g, 117 mmol) in tetrahydrofuran (90 mL), and the reaction
mixture was heated under reflux for 1 h. The mixture was then cooled
to 20 °C, followed by the addition of n-pentane (100 mL) and water
(150 mL). The organic layer was separated, the aqueous layer was
extracted with dichloromethane (3 × 100 mL) and discarded, and the
combined organic phases were dried over anhydrous sodium sulfate.
The organic solvents were removed under reduced pressure, and the
residue was purified by bulb-to-bulb distillation in vacuo to give 27 in
70% yield as a colorless oil (26.7 g, 81.8 mmol); bp 172−173 °C/0.2
5.93 (δM), and 6.42 (δX) (6 H; CHXCHAHM, 3JAX = 20.4 Hz, 2JAM
=
3.9 Hz, 3JMX = 14.5 Hz), 6.08 ppm (s, 2 H; H-3/H-5, C6H2(OCH3)3).
13C NMR (CD2Cl2): δ −2.8 (SiCH3), 55.5 (o-OCH3, C6H2(OCH3)3),
55.6 (p-OCH3, C6H2(OCH3)3), 90.9 (C-3/C-5, C6H2(OCH3)3), 102.9
(C-1, C6H2(OCH3)3), 130.5 (SiCHCH2), 139.7 (SiCHCH2),
164.1 (C-4, C6H2(OCH3)3), 166.8 ppm (C-2/C-6, C6H2(OCH3)3).
29Si NMR (CD2Cl2): δ −22.1 ppm. Anal. Calcd for C14H20O3Si: C,
63.60; H, 7.62. Found: C, 63.62; H, 7.69.
1
mbar. H NMR (CD2Cl2): δ 3.62 (s, 6 H; o-OCH3, C6H2(OCH3)3),
3.83 (s, 3 H, p-OCH3, C6H2(OCH3)3), 5.63 (δA), 6.08 (δM), and 6.61
(δX) (6 H; CHXCHAHM, 3JAX = 20.4 Hz, 2JAM = 3.9 Hz, 3JMX = 14.5
Hz), 6.12 (s, 2 H; H-3/H-5, C6H2(OCH3)3), 7.27−7.33 (m, 2 H; H-
3/H-5, C6H5), 7.29−7.35 (m, 1 H; H-4, C6H5), 7.45−7.51 ppm (m, 2
H; H-2/H-6, C6H5). 13C NMR (CD2Cl2): δ 55.5 (o-OCH3,
C6H2(OCH3)3), 55.6 (p-OCH3, C6H2(OCH3)3), 91.2 (C-3/C-5,
C6H2(OCH3)3), 101.5 (C-1, C6H2(OCH3)3), 127.6 (C-3/C-5,
C6H5), 128.8 (C-4, C6H5), 132.7 (SiCHCH2), 135.1 (C-2/C-6,
C6H5), 137.4 (C-1, C6H5), 137.5 (SiCHCH2), 164.6 (C-4,
C6H2(OCH3)3), 167.1 ppm (C-2/C-6, C6H2(OCH3)3). 29Si NMR
(CD2Cl2): δ −25.2 ppm. Anal. Calcd for C19H22O3Si: C, 69.90; H,
6.79. Found: C, 69.89; H, 6.80.
Crystal Structure Analyses. Suitable single crystals of 1, 3, 5, 6,
21, and 27 were obtained directly from the respective syntheses. The
crystals were mounted in inert oil (perfluoropolyalkyl ether, ABCR)
on a glass fiber and then transferred to the cold nitrogen gas stream of
the diffractometer (Stoe IPDS, graphite-monochromated Mo Kα
radiation (λ = 0.71073 Å)). The structures were solved by direct
methods (SHELXS-97).10 All non-hydrogen atoms were refined
anisotropically (SHELXL-97).10 A riding model was employed in the
refinement of the CH hydrogen atoms. CCDC-975473 (1), CCDC-
975474 (3), CCDC-975475 (5), CCDC-975476 (6), CCDC-975477
(21), and CCDC-975478 (27) contain the supplementary crystallo-
graphic 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.
(4-Methoxyphenyl)phenyldivinylsilane (25). A solution of vinyl-
magnesium chloride in tetrahydrofuran (15 weight % CH2CHMgCl,
d = 0.97 g mL−1; 183 mL, 307 mmol of CH2CHMgCl) was added
dropwise at 20 °C within 1 h to a stirred solution of 19 (40.0 g, 146
mmol) in tetrahydrofuran (150 mL), and the reaction mixture was
heated under reflux for 1 h. The mixture was then cooled to 20 °C,
followed by the addition of n-pentane (250 mL) and water (200 mL).
The organic layer was separated, the aqueous layer was extracted with
dichloromethane (3 × 100 mL) and discarded, and the combined
organic phases were dried over anhydrous sodium sulfate. The organic
solvents were removed under reduced pressure, and the residue was
purified by bulb-to-bulb distillation in vacuo to give 25 in 90% yield as
a colorless liquid (35.1 g, 132 mmol); bp 136 °C/0.1 mbar. 1H NMR
(CDCl3): δ 3.82 (s, 3 H; C6H4OCH3), 5.81 (δA), 6.26 (δM), and 6.50
(δX) (6 H; CHXCHAHM, 3JAX = 20.2 Hz, 2JAM = 3.7 Hz, 3JMX = 14.6
Hz), 6.92−6.96 (m, 2 H; H-3/H-5, C6H4OCH3), 7.33−7.40 (m, 2 H;
H-3/H-5, C6H5), 7.36−7.43 (m, 1 H; H-4, C6H5), 7.45−7.50 (m, 2 H;
H-2/H-6, C6H4OCH3), 7.52−7.57 ppm (m, 2 H; H-2/H-6, C6H5).
13C NMR (CDCl3): δ 55.0 (C6H4OCH3), 113.7 (C-3/C-5,
C6H4OCH3), 124.8 (C-1, C6H4OCH3), 127.8 (C-3/C-5, C6H5),
129.4 (C-4, C6H5), 134.2 (SiCHCH2), 134.6 (C-1, C6H5), 135.4 (C-
2/C-6, C6H5), 136.2 (SiCHCH2), 137.0 (C-2/C-6, C6H4OCH3),
160.8 ppm (C-4, C6H4OCH3). 29Si NMR (CDCl3): δ −20.8 ppm.
Anal. Calcd for C17H18OSi: C, 76.64; H, 6.81. Found: C, 76.63; H,
6.63.
(2,6-Dimethoxyphenyl)phenyldivinylsilane (26). A solution of
vinylmagnesium chloride in tetrahydrofuran (15 weight % CH2
CHMgCl, d = 0.97 g mL−1; 211 mL, 354 mmol of CH2CHMgCl)
was added dropwise at 20 °C within 45 min to a stirred solution of 20
(51.1 g, 168 mmol) in tetrahydrofuran (170 mL), and the reaction
mixture was heated under reflux for 1 h. The mixture was then cooled
to 20 °C, followed by the addition of n-pentane (200 mL) and water
(200 mL). The organic layer was separated, the aqueous layer was
extracted with dichloromethane (3 × 150 mL) and discarded, and the
combined organic phases were dried over anhydrous sodium sulfate.
The organic solvents were removed under reduced pressure, and the
ASSOCIATED CONTENT
* Supporting Information
■
S
Data for the crystal structure analyses of compounds 1, 3, 5, 6,
21, and 27 (Table S1) and 1H, 13C, and 29Si NMR spectra and
GC/MS spectra of the mixtures 13/H-MOP, 13/H-DMOP,
and 13/H-TMOP (Figures S1−S15). 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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Organometallics
Article
REFERENCES
■
(1) Reviews dealing with silicon-based drugs: (a) Tacke, R.; Linoh,
H. In The Chemistry of Organic Silicon Compounds; Patai, S., Rappaport,
Z., Eds.; Wiley: Chichester, U.K., 1989; Part 2, pp 1143−1206.
(b) Bains, W.; Tacke, R. Curr. Opin. Drug Discovery Dev. 2003, 6, 526−
543. (c) Showell, G. A.; Mills, J. S. Drug Discovery Today 2003, 8, 551−
556. (d) Mills, J. S.; Showell, G. A. Expert Opin. Investig. Drugs 2004,
13, 1149−1157. (e) Pooni, P. K.; Showell, G. A. Mini-Rev. Med. Chem.
2006, 6, 1169−1177. (f) Sieburth, S. McN.; Chen, C.-A. Eur. J. Org.
Chem. 2006, 311−322. (g) Gately, S.; West, R. Drug Dev. Res. 2007,
68, 156−163. (h) Franz, A. K. Curr. Opin. Drug Discovery Dev. 2007,
10, 654−671. (i) Meanwell, N. A. J. Med. Chem. 2011, 54, 2529−2591.
(j) Franz, A. K.; Wilson, S. O. J. Med. Chem. 2013, 56, 388−405.
(2) Selected publications dealing with silicon-based drugs:
(a) Lippert, W. P.; Burschka, C.; Gotz, K.; Kaupp, M.; Ivanova, D.;
̈
Gaudon, C.; Sato, Y.; Antony, P.; Rochel, N.; Moras, D.; Gronemeyer,
H.; Tacke, R. ChemMedChem 2009, 4, 1143−1152. (b) Tacke, R.;
Muller, V.; Buttner, M. W.; Lippert, W. P.; Bertermann, R.; Daiss, J.
̈
̈
O.; Khanwalkar, H.; Furst, A.; Gaudon, C.; Gronemeyer, H.
ChemMedChem 2009, 4, 1797−1802. (c) Johansson, T.; Weidolf, L.;
Popp, F.; Tacke, R.; Jurva, U. Drug Metab. Dispos. 2010, 38, 73−83.
(d) Tacke, R.; Nguyen, B.; Burschka, C.; Lippert, W. P.; Hamacher, A.;
Urban, C.; Kassack, M. U. Organometallics 2010, 29, 1652−1660.
(e) Tacke, R.; Bertermann, R.; Burschka, C.; Dorrich, S.; Fischer, M.;
̈
Muller, B.; Meyerhans, G.; Schepmann, D.; Wunsch, B.; Arnason, I.;
̈
̈
Bjornsson, R. ChemMedChem 2012, 7, 523−532.
(3) Troegel, D.; Moller, F.; Burschka, C.; Tacke, R. Organometallics
̈
2009, 28, 3218−3224.
(4) Troegel, D.; Moller, F.; Tacke, R. J. Organomet. Chem. 2010, 695,
̈
310−313.
(5) Fischer, M.; Tacke, R. Organometallics 2013, 32, 7181−7185; and
references therein.
(6) (a) Daiss, J. O.; Penka, M.; Burschka, C.; Tacke, R.
Organometallics 2004, 23, 4987−4994. (b) Daiss, J. O.; Barth, K. A.;
Burschka, C.; Hey, P.; Ilg, R.; Klemm, K.; Richter, I.; Wagner, S. A.;
Tacke, R. Organometallics 2004, 23, 5193−5197. (c) Popp, F.;
Natscher, J. B.; Daiss, J. O.; Burschka, C.; Tacke, R. Organometallics
̈
2007, 26, 6014−6028. (d) Tacke, R.; Popp, F.; Muller, B.; Theis, B.;
̈
Burschka, C.; Hamacher, A.; Kassack, M. U.; Schepmann, D.; Wunsch,
̈
B.; Jurva, U.; Wellner, E. ChemMedChem 2008, 3, 152−164.
(e) Troegel, D.; Walter, T.; Burschka, C.; Tacke, R. Organometallics
2009, 28, 2756−2761. (f) Tacke, R.; Nguyen, B.; Burschka, C.;
Lippert, W. P.; Hamacher, A.; Urban, C.; Kassack, M. U. Organo-
metallics 2010, 29, 1652−1660. (g) Laskowski, N.; Reis, E.-M.;
Kotzner, L.; Baus, J. A.; Burschka, C.; Tacke, R. Organometallics 2013,
̈
32, 3269−3278.
(7) (a) Carlson, B. A.; Brown, H. C. J. Am. Chem. Soc. 1973, 95,
6876−6877. (b) Carlson, B. A.; Katz, J.-J.; Brown, H. C. J. Organomet.
Chem. 1974, 67, C39−C42. (c) Soderquist, J. A.; Hassner, A. J. Org.
Chem. 1983, 48, 1801−1810. (d) Soderquist, J. A.; Shiau, F.-Y.;
Lemesh, R. A. J. Org. Chem. 1984, 49, 2565−2569. (e) Soderquist, J.
A.; Negron, A. J. Org. Chem. 1987, 52, 3441−3442. (f) Soderquist, J.
A.; Negron, A. J. Org. Chem. 1989, 54, 2462−2464. (g) Damour, D.;
Renaudon, A.; Mignani, S. Synlett 1995, 111−112.
(8) Gomez, S.; Peters, J. A.; Maschmeyer, T. Adv. Synth. Catal. 2002,
344, 1037−1057.
(9) For the first crystal structure analysis of a 4-silacyclohexanone,
see: Barnes, C. L.; Soderquist, J. A. Acta Crystallogr., Sect. C 1992, 48,
2222−2224.
(10) Sheldrick, G. M. Acta Crystallogr., Sect. A 2008, 64, 112.
1029
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