Sila-rhubafuran and derivatives: Synthesis and olfactory characterization of novel silicon-containing odorants

Article abstract of DOI:10.1021/om401070c

Sila-rhubafuran (1b), a silicon analogue of the grapefruit odorant rhubafuran (1a), was synthesized and isolated as a 1:1 mixture of two racemic diastereomers. In addition, the structurally related racemic C/Si pairs 2a/2b and 3a/3b were prepared. To get

Full text of DOI:10.1021/om401070c

Article
pubs.acs.org/Organometallics
Sila-rhubafuran and Derivatives: Synthesis and Olfactory
Characterization of Novel Silicon-Containing Odorants
Bettina Forster,† Rudiger Bertermann,† Philip Kraft,‡ and Reinhold Tacke*,†
̈
̈
†Institut fur Anorganische Chemie, Universitat Wurzburg, Am Hubland, D-97074 Wurzburg, Germany
̈
̈
̈
̈
‡
̈
Givaudan Schweiz AG, Fragrance Research, Uberlandstrasse 138, CH-8600 Dubendorf, Switzerland
̈
ABSTRACT: Sila-rhubafuran (1b), a silicon analogue of the grapefruit odorant
rhubafuran (1a), was synthesized and isolated as a 1:1 mixture of two racemic
diastereomers. In addition, the structurally related racemic C/Si pairs 2a/2b and
3a/3b were prepared. To get information about structure−odor relationships in
the domain of grapefruit odorants, the C/Si pairs 1a/1b, 2a/2b, and 3a/3b were
studied for their olfactory properties.
Scheme 1. Synthesis of (3SR,5SR)-1b/(3SR,5RS)-1b
INTRODUCTION
■
Rhubafuran (1a) is a synthetic grapefruit odorant with an
intense tangy rhubarb character and a green eucalyptus heart
much used in fruity and citrus accords.1,2 Bearing two
stereogenic centers in the tetrahydrofuran skeleton, commercial
rhubafuran (1a) is a mixture of two racemic diastereomers.
Preparation of the four enantiomerically enriched stereoisomers
of 1a by enzymatic catalysis3 proved the isomers (2R,4S)-1a
and (2S,4R)-1a to contribute most to the odor of the
commercial product, which consists of all four stereoisomers.
In continuation of our systematic studies on silicon-based
odorants,4,5 we have now succeeded in synthesizing sila-
rhubafuran (1b), a silicon analogue of 1a. In addition, we have
prepared the related C/Si pairs 2a/2b and 3a/3b. Sila-
rhubafuran (1b) was synthesized as a mixture of two racemic
diastereomers, and compounds 2a, 2b, 3a, and 3b were
prepared as racemates. Here we report on the synthesis of 1b,
2a, 2b, 3a, and 3b and the olfactory characterization of the C/Si
pairs 1a/1b, 2a/2b, and 3a/3b.
in 52% yield. Reduction of rac-6 with lithium aluminum
hydride, followed by aqueous workup, afforded rac-allyl-
(hydroxymethyl)methylphenylsilane (rac-7) in 79% yield. In
the last step, the 3-silatetrahydrofuran skeleton of 1b was
constructed by an intramolecular hydroalkoxylation of rac-7,
catalyzed by aluminum(III) trifluoromethanesulfonate
(Al(OTf)3), to give a 1:1 mixture of (3SR,5SR)-1b and
(3SR,5RS)-1b in 26% yield. This cyclization is based on a
method developed for intramolecular hydroalkoxylations of γ,δ-
unsaturated alcohols.6 However, to the best of our knowledge,
this method has not yet been applied to allyl(hydroxymethyl)-
silanes.
rac-2,2,4-Trimethyl-4-phenyltetrahydrofuran (rac-2a) was
synthesized according to Scheme 2, starting from rac-2-
phenylpropanal (rac-8). In the first step, compound rac-8 was
treated with 3-chloro-2-methylprop-1-ene, in the presence of
sodium hydroxide and tetra-n-butylammonium iodide, to
RESULTS AND DISCUSSION
■
Syntheses. Sila-rhubafuran (1b) was prepared according to
Scheme 1, starting from dichloro(chloromethyl)methylsilane
(4). In the first step, compound 4 was treated sequentially with
phenylmagnesium chloride and allylmagnesium chloride in a
one-pot synthesis to give rac-allyl(chloromethyl)-
methylphenylsilane (rac-5a) in 88% yield. Subsequent reaction
of rac-5a with sodium acetate, in the presence of 18-crown-6,
furnished rac-(acetoxymethyl)allylmethylphenylsilane (rac-6)
Received: November 4, 2013
© XXXX American Chemical Society
A
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[(phenylseleno)methyl]-3-silatetrahydrofuran ((3SR,5SR)-14/
(3SR,5RS)-14) in 63% yield. Treatment of this mixture with
tri-n-butylstannane,8 in the presence of 2,2′-azobis(2-methyl-
propionitrile) (AIBN), finally afforded the target compound
rac-2b in 42% yield.
Scheme 2. Synthesis of rac-2a
rac-2,2,5-Trimethyl-5-phenyltetrahydropyran (rac-3a) was
synthesized according to Scheme 4, starting from rac-8. In
Scheme 4. Synthesis of rac-3a
furnish rac-2,4-dimethyl-2-phenylpent-4-enal (rac-9) in 64%
yield. Reduction of rac-9 with lithium aluminum hydride,
followed by aqueous workup, afforded rac-2,4-dimethyl-2-
phenylpent-4-en-1-ol (rac-10) in 89% yield. In the last step,
the tetrahydrofuran skeleton of rac-2a was built up by an
intramolecular hydroalkoxylation6 of rac-10, catalyzed by
aluminum(III) trifluoromethanesulfonate, to give the target
compound rac-2a in 46% yield.
rac-3,5,5-Trimethyl-3-phenyl-3-silatetrahydrofuran (rac-2b)
was synthesized according to Scheme 3, starting from 4.
the first step, rac-18 was deprotonated with sodium hydride,
followed by treatment with 5-bromo-2-methylbut-2-ene, to
furnish rac-2,5-dimethyl-2-phenylhex-4-enal (rac-15) in 68%
yield. Reduction of rac-15 with lithium aluminum hydride,
followed by aqueous workup, afforded rac-2,5-dimethyl-2-
phenylhex-4-en-1-ol (rac-16) in 76% yield. An intramolecular
hydroalkoxylation6 of rac-16, catalyzed by aluminum(III)
trifluoromethanesulfonate, resulted in the formation of a
tetrahydropyran ring and provided the target compound rac-
3a in 43% yield.
Scheme 3. Synthesis of rac-2b
rac-3,6,6-Trimethyl-3-phenyl-3-silatetrahydropyran (rac-3b)
was synthesized according to Scheme 5, starting from 4. In
the first step, compound 4 was treated sequentially with
phenylmagnesium chloride and (3-methylbut-2-en-1-yl)magne-
sium chloride in a one-pot synthesis to afford rac-
(chloromethyl)methyl(3-methylbut-2-en-1-yl)phenylsilane
(rac-17) in 80% yield. Subsequent reaction of rac-17 with
Scheme 5. Synthesis of rac-3b
Thus, sequential treatment of 4 with phenylmagnesium
chloride and (2-methylprop-2-en-1-yl)magnesium chloride in
a one-pot synthesis afforded rac-(chloromethyl)methyl(2-
methylprop-2-en-1-yl)phenylsilane (rac-11) in 85% yield.
Subsequent reaction of rac-11 with sodium acetate, in the
presence of tetra-n-butylphosphonium chloride, furnished rac-
(acetoxymethyl)methyl(2-methylprop-2-en-1-yl)phenylsilane
(rac-12) in 71% yield. Reduction of rac-12 with lithium
aluminum hydride, followed by aqueous workup, afforded rac-
(hydroxymethyl)methyl(2-methylprop-2-en-1-yl)phenylsilane
(rac-13) in 93% yield. Treatment of rac-13 with chlorophe-
nylselane,7 in the presence of triethylamine, furnished a 1:1
mixture of (3SR,5SR)- and (3SR,5RS)-3,5-dimethyl-3-phenyl-5-
B
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Table 1. Olfactory Properties of (3SR,5SR)-1a/(3SR,5RS)-1a, (3SR,5SR)-1b/(3SR,5RS)-1b, rac-2a, rac-2b, rac-3a, and rac-3b
odor threshold
value
compound
olfactory properties
intense rhubarb and citrus character, with a green eucalyptus heart
[ng L−1 air]
0.68
(3SR/5SR)-1a/
(3SR/5RS)-1a
a
(3SR/5SR)-1b/
(3SR/5RS)-1b
green-fruity, fatty odor, with bergamot and linalyl acetate connotation and grapefruit as well as cassis facets in front of a floral-
powdery, magnolan-type background
18.1
a
rac-2a
intense citrus and grapefruit odor, pleasant bloomy and honey-like
11.8
7.58
rac-2b
rac-3a
rac-3b
agrestic odor in the direction of lavender, labienone ((6E)-2,4,4,7-tetramethylnona-6,8-dien-3-one) and methyl pamplemousse
(6,6-dimethoxy-2,5,5-trimethylhex-2-ene), with strong green chili pepper and tomato aspects, and a slightly rubbery character
fresh methyl pamplemousse odor, with a cardamom and agrumex effect (2-tert-butylcyclohexyl acetate) and slightly animalic
aspects in the direction of ambrinol (2,5,5-trimethyl-1,2,3,4,4a,5,6,7-octahydronaphthalen-2-ol)
18.9
2.50
green, bitter citrus-grapefruit-type odor, with slightly animalic and slightly dry, woody facets
a
Studied as a 1:1 mixture.
sodium acetate, in the presence of tetra-n-butylphosphonium
chloride, furnished rac-(acetoxymethyl)methyl(3-methylbut-2-
en-1-yl)phenylsilane (rac-18) in 75% yield. Reduction of rac-18
with lithium aluminum hydride, followed by aqueous workup,
afforded rac-(hydroxymethyl)methyl(3-methylbut-2-en-1-yl)-
phenylsilane (rac-19) in 98% yield. In the last step, the 3-
silatetrahydropyran skeleton of rac-3b was constructed by an
intramolecular hydroalkoxylation6 of rac-19, catalyzed by
aluminum(III) trifluoromethanesulfonate, to provide the target
compound 3b in 17% yield.
The identities of (3SR,5SR)-1b/(3SR,5RS)-1b, rac-2a, rac-
2b, rac-3a, rac-3b, rac-5−rac-13, (3SR,5SR)-14/(3SR,5RS)-14,
and rac-15−rac-19 were established by elemental analyses (C,
H) and NMR spectroscopic studies (1H, 13C, 29Si, 77Se). At first
glance, some of the yields of the target compounds appear
somewhat unsatisfactory; however, it is important to note that
we were aiming to prepare olfactorily pure products, which
sometimes was possible only at the expense of the yield.
Olfactory Characterization. Compounds (3SR,5SR)-1a/
(3SR,5RS)-1a (1:1 mixture; rhubafuran), (3SR,5SR)-1b/
(3SR,5RS)-1b (1:1 mixture; sila-rhubafuran), rac-2a, rac-2b,
rac-3a, and rac-3b were studied for their olfactory properties
(Table 1).
Upon sila-substitution, the typical intense rhubarb and citrus
character of rhubafuran (1a) with its green eucalyptus aspects
becomes greener and more fatty in tonality. While grapefruit
facets were still clearly discernible, the hesperidic, citrusy
aspects are less pronounced in the odor profile of sila-
rhubafuran (1b). With its bergamot and linalyl acetate
connotation, sila-rhubafuran (1b) is more herbaceous-warm
in lavender direction than minty-eucalyptus and distinctly fruity
with pronounced cassis (blackcurrant) facets. The dry-down of
1b even has a floral-powdery background recalling magnolan
(2,4-dimethyl-4,4a,5,9b-tetrahydroindeno[1,2-d][1,3]dioxine),
yet still in a green direction. In terms of odor detection
threshold, sila-rhubafuran (1b) is, with 18.1 ng L−1 air, over 25
times weaker than rhubafuran (1a), for which an odor
threshold value of 0.68 ng L−1 air was measured.
Addition of an additional methyl group to the tertiary
stereocenter of rhubafuran (1a; → 2a) eliminates the green-
minty eucalyptus facets and intensifies the citrus and grapefruit
character, while 2a shows pleasant floral-bloomy and honey-like
aspects as well. However, in terms of odor detection threshold,
compound 2a (11.8 ng L−1 air) is still almost 20 times weaker
than rhubafuran (1a). Introduction of an additional methyl
group in sila-rhubafuran (1b; → 2b) affects the odor in a
similar manner to that observed for 1a/2a in that the green
facets, i.e., green-fruity in this case, are eliminated. Thus, the
agrestic (i.e., “rural-Provenca
̧
l” from French “agreste”) character
in lavender direction comes to the fore as well as the grapefruit
character, which is established by the reminiscence of 2b with
labienone ((6E)-2,4,4,7-tetramethylnona-6,8-dien-3-one) and
methyl pamplemousse (6,6-dimethoxy-2,5,5-trimethylhex-2-
ene). Besides, there are spicy-vegetal aspects in the direction
of green chili peppers and tomatoes in the odor profile of 2b as
well as a slight rubbery note. Interestingly, now the sila-
analogue 2b (7.58 ng L−1 air) is slightly more intense in terms
of odor detection threshold than the parent carbon compound
2a.
This threshold inversion observed for the C/Si pair 2a/2b
becomes even more pronounced for the homologous C/Si pair
3a/3b, where the silicon compound 3b (2.50 ng L−1 air) is
almost eight times more powerful than the corresponding
carbon analogue 3a (18.9 ng L−1 air). For both compounds, the
grapefruit aspects are more pronounced again, and both share
also animalic, dry, and woody facets, in the case of 3a slightly
more camphoraceous, so recalling ambrinol (2,5,5-trimethyl-
1,2,3,4,4a,5,6,7-octahydronaphthalen-2-ol). With an agrumex
effect (2-tert-butylcyclohexyl acetate), also the top note of 3a is
more woody and camphoraceous, with additional spicy aspects
in the cardamom direction. The top note of 3b, however, is
green and bitter, the citrus character is clearly in the grapefruit
direction, and animalic, slightly dry, woody facets are present as
well. Floral, agrestic-lavender, and rhubarb elements are absent
in the smell of 3b.
CONCLUSIONS
■
With the preparation of sila-rhubafuran (1b), a silicon analogue
of the synthetic grapefruit odorant rhubafuran (1a), and the
structurally related C/Si pairs 2a/2b and 3a/3b, we have
succeeded in synthesizing a set of model compounds that allow
for an analysis of structure−odor relationships in the domain of
grapefruit odorants. To the best of our knowledge, sila-
rhubafuran (1b) and its derivatives 2b and 3b represent the first
silicon-based grapefruit odorants. For the construction of the 3-
silatetrahydrofuran skeleton of 1b and the 3-silatetrahydropyran
skeleton of 3b, a new synthetic method has been used, an
aluminum(III) trifluoromethane sulfonate-catalyzed intramo-
lecular hydroalkoxylation of allyl(hydroxymethyl)silanes.
The complex odor profile of rhubafuran (1a) with its
elements rhubarb/fruity, citrus/grapefruit, green, and agrestic/
lavender/eucalyptus depends on several structural elements as
was already apparent from the odor descriptions of the four
enantiomers of 1a by Brenna et al.,3 who found the unlike-
enantiomers (2R,4S)-1a and (2S,4R)-1a to represent the odor
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vector. The like-configured rhubafuran enantiomer (2S,4S)-1a
was even reported to possess cassis- and oxane-like odor
characteristics, which we also found for sila-rubafuran (1b).
The situation, thus, is even more complicated than in the case
of the tetrahydrofuran cassis odorant cassyrane and its dihydro
derivatives,9 where the 5R-configured enantiomers elicit
agrestic odor characters in the direction of rosemary, while
the 5S-isomers smell fruity and cassis-like.
Since only the lead compound rhubafuran (1a) displays a
pronounced rhubarb character, this fruity odor attribute cannot
be structurally assigned further to what has been reported for
the enantiomers of 1a.3 However, from our work it seems clear
that a gem-dimethyl group adjacent to the osmophoric ether-
oxygen atom diminishes or fully eliminates the green odor
characteristics and intensifies the grapefruit character.
So while we cannot draw conclusions on the rhubarb/fruity
side, the grapefruit character is increased by the gem-dimethyl
group and is most pronounced for 2a and 3b. In fact, the best
threshold value for a grapefruit odorant in this series was
obtained for the silicon compound 3b (2.50 ng L−1 air), where
the distance between the two quaternary centers appears to be
optimal for a grapefruit character. The flexible alignment of the
silicon compound 3b (black) and the carbon-based lower
homologue 2a (dark gray) on the grapefruit odorant methyl
pamplemousse (6,6-dimethoxy-2,5,5-trimethylhex-2-ene, light
gray) in Figure 1 could perhaps explain why, since the
isobutenyl tail of methyl pamplemousse superimposes perfectly
on the aromatic ring system of 2a and 3b.
EXPERIMENTAL SECTION
■
General Procedures. All reactions involving chemicals sensitive to
water and/or oxygen were carried out under dry argon. The organic
solvents used were dried and purified according to standard
procedures and stored under dry nitrogen. Flash chromatography
(pressure, 1.5 bar) was carried out using silica gel as the stationary
phase (35−70 μm, Merck). Medium-pressure liquid chromatography
(MPLC) was performed as follows: pressure, 16 bar; column, 50 × 2.5
cm; stationary phase, silica gel, YMC SL12S15, 15 μm; detector,
Knauer variable wavelength monitor. The 1H, 13C, 29Si, and 77Se NMR
spectra were recorded at 23 °C with a Bruker DRX-300 (1H, 300.1
MHz; 13C, 75.5 MHz; 29Si, 59.6 MHz) or Bruker Avance 500 NMR
spectrometer (1H, 500.1 MHz; 13C, 125.8 MHz; 29Si, 99.4 MHz; 77Se,
95.4 MHz) using CDCl3, CD2Cl2, or C6D6 as the solvent. Chemical
shifts (ppm) were determined relative to internal CHCl3 (1H, δ 7.24;
CDCl3), internal CDCl3 (13C, δ 77.0; CDCl3), internal CHDCl2 (1H,
δ 5.32; CD2Cl2), internal CD2Cl2 (13C, δ 53.8; CD2Cl2), internal
C6HD5 (1H, δ 7.28; C6D6), internal C6D6 (13C, δ 128.0; C6D6),
external TMS (TMS, 29Si, δ 0.0; CDCl3, CD2Cl2, C6D6), or external
Me2Se (5% (w/w) in C6D6, 77Se, δ 0; C6D6). Analysis and assignment
1
1
of the H NMR spectroscopic data were supported by H,1H COSY,
13C,1H HMQC, 13C,1H HMBC, and 29Si,1H HMQC (optimized for
2J(Si,H) = 7 Hz) experiments. The spin systems observed for the
compounds synthesized were analyzed by using the WIN-DAISY 4.05
software package.11 Coupling constants are given as their absolute
values. Assignment of the 13C NMR spectroscopic data was supported
by DEPT-135 and the aforementioned 13C,1H correlation experiments.
Elemental analyses were performed with a VarioMicro apparatus
(Elementar Analysensysteme GmbH). Olfactory evaluations of the
samples as 10% solutions in dipropylene glycol (DPG) and as 10%
solutions in ethanol (EtOH) on smelling blotters were performed by
at least two expert perfumers. The odor threshold values were
determined by GC−olfactometry. Different dilutions of the sample
substances were injected into a gas chromatograph in descending
order until the panelists evaluating in blind failed to detect the odor
impression at the correct retention time. The reported threshold
values are geometrical means of the different values reported by at
least three individual panelists.
Preparation of a 1:1 Mixture of (3SR,5SR)- and (3SR,5RS)-3,5-
Dimethyl-3-phenyl-3-silatetrahydrofuran ((3SR,5SR)-1b/
(3SR,5RS)-1b; Sila-rhubafuran). Aluminum(III) trifluoromethane-
sulfonate (370 mg, 780 μmol) was added at 20 °C in a single portion
to a stirred solution of rac-7 (3.00 g, 15.6 mmol) in dichloromethane
(50 mL). The reaction mixture was heated under reflux for 3 h and
was then cooled to 20 °C, followed by the addition of 1 M
hydrochloric acid (10 mL). The organic layer was separated, the
aqueous layer was extracted with diethyl ether (3 × 25 mL) and
discarded, the combined organic extracts were dried (Na2SO4), and
the solvent was removed under reduced pressure. The residue was
purified by column chromatography on silica gel (eluent, n-hexane/
ethyl acetate (98:2 v/v)) to furnish a 1:1 mixture of (3SR,5SR)-1b and
(3SR,5RS)-1b as a colorless liquid (780 mg, 4.06 mmol; 26% yield).
1H NMR (500.1 MHz, CD2Cl2; data for two diastereomers (molar
Figure 1. Flexible alignment of the grapefruit odorants methyl
pamplemousse (6,6-dimethoxy-2,5,5-trimethylhex-2-ene, light gray),
2a (dark gray), and 3b (black), employing the MOE 2012.10 software
package.10
The agrestic lavender facets of the silicon compounds 1b and
2b could also arise from such subtle spatial differences, but this
is far more speculative. While we could increase neither the
fruity/rhubarb aspects of rhubafuran (1a) nor its odor
threshold, we could, however, shift the odor characteristics of
1a in the grapefruit direction and gain a bit of insight into why
this happened. It would be interesting to test this hypothesis by
sila-substitution of the quaternary carbon atom of methyl
pamplemousse, since better performing grapefruit odorants
could result that way. In any case, the interesting change from
rhubafuran (1a) to pronounced citrus/grapefruit odorants with
gem-dimethyl groups proved sila-substitution and ring enlarge-
ment to be powerful tools for odorant design by fine-tuning
molecular geometries.
ratio, 1:1)): δ 0.53 (s, 3 H; SiCH3), 0.87 (δF), 1.28 (δM), 1.35 (δN),
3.23 (δX), 3.73 (δY), and 3.81 (δZ) (FMN3XYZ system,12 2J(F,M) =
2
3
3
14.4 Hz, J(X,Y) = 13.6 Hz, J(F,Z) = 10.3 Hz, J(M,Z) = 5.1 Hz,
3J(N,Z) = 6.0 Hz, J(F,Y) = 0.4 Hz, J(M,Y) = 0.3 Hz, J(Y,Z) = 0.6
Hz, 8 H; SiCHXHYOCHZ(C(HN)3)CHFHM), 0.54 (δA), 0.78 (δF),
1.37(δN), 1.37 (δM), 3.34 (δX), 3.66 (δY), and 3.90 (δZ) (A3FMN3XYZ
4
4
4
2
2
3
system, J(M,F) = 14.4 Hz, J(X,Y) = 13.7 Hz, J(F,Z) = 10.1 Hz,
3J(M,Z) = 5.2 Hz, J(N,Z) = 6.0 Hz, J(A,X) = 0.5 Hz, J(F,Y) = 0.4
3
4
4
Hz, 4 J(M,Y) 0.3 Hz, 4 J(Y,Z)
=
=
0.6 Hz, 11 H;
C(HA)3SiCHXHYOCHZ(C(HN)3)CHFHM), 7.38−7.42 (m, 6 H; H-
3/H-4/H-5, C6H5), 7.58−7.64 (m, 4 H; H-2/H-6, C6H5). 13C NMR
(125.8 MHz, CD2Cl2; data for two diastereomers (molar ratio, 1:1)): δ
−5.4 and −4.6 (SiCH3), 23.7 and 23.8 (CCH3), 24.0 and 24.1
(CH2CH), 60.9 and 61.4 (CH2O), 77.1 and 77.7 (CH2CH), 128.27
and 128.33 (C-3/C-5, C6H5), 129.8 and 129.9 (C-4, C6H5), 134.3 and
134.4 (C-2/C-6, C6H5), 136.4 and 136.8 (C-1, C6H5). 29Si NMR (99.4
D
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2
2
2
MHz, CD2Cl2; data for two diastereomers (molar ratio, 1:1)): δ 9.1
and 9.2. Anal. Calcd for C11H16OSi: C, 68.69; H, 8.38. Found: C,
68.74; H, 8.46. Odor description: green-fruity, fatty odor, with
bergamot and linalyl acetate connotation and grapefruit as well as
cassis facets in front of a floral-powdery, magnolan-type background;
odor threshold, 18.1 ng L−1 air.
system, J(A,B) = 13.6 Hz, J(M,N) = 13.6 Hz, J(X,Y) = 11.9 Hz,
3J(A,M) = 8.3 Hz, 3J(A,N) = 4.3 Hz, 3J(B,M) = 4.1 Hz, 3J(B,N) = 8.8
Hz, 4 J(M,X)
= = 1.4 Hz, 6 H;
1.3 Hz, 4 J(N,Y)
CHAHBCHMHNCCHXHY), 7.18−7.22 (m, 1 H; H-4, C6H5), 7.31−
7.35 (m, 2 H; H-3/H-5, C6H5), 7.42−7.44 (m, 2 H; H-2/H-6, C6H5).
13C NMR (125.8 MHz, CD2Cl2): δ 25.9 (CH3C(C6H5)), 26.2
Preparation of 2,2,4-Trimethyl-4-phenyltetrahydrofuran
(rac-2a). Aluminum(III) trifluoromethanesulfonate (186 mg, 392
μmol) was added at 20 °C in a single portion to a stirred solution of
rac-10 (1.50 g, 7.88 mmol) in dichloromethane (15 mL). The reaction
mixture was heated under reflux for 10 h and was then cooled to 20
°C, followed by the addition of 1 M hydrochloric acid (5 mL). The
organic layer was separated, the aqueous layer was extracted with
diethyl ether (3 × 10 mL) and discarded, the combined organic
extracts were dried (Na2SO4), and the solvent was removed under
reduced pressure. The residue was purified by MPLC on silica gel
(eluent, n-hexane/ethyl acetate (98:2 v/v); flow rate, 58 mL min−1;
detector wavelength, 254 nm) to furnish rac-2a as a colorless liquid
(C(CH3)CH3), 26.7 (C(CH3)CH3), 32.9 (CH2CH2C(CH3)2), 33.1
(CH2CH2C(CH3)2), 37.2 (CH3C(C6H5)), 69.9 (CCH2O), 71.2
(CH2CH2C(CH3)2), 126.1 (C-4, C6H5), 126.5 (C-2/C-6, C6H5),
128.5 (C-3/C-5, C6H5), 147.9 (C-1, C6H5). Anal. Calcd for C14H20O:
C, 82.30; H, 9.87. Found: C, 82.13; H, 9.82. Odor description: fresh
methyl pamplemousse odor, with a cardamom and agrumex effect and
slightly animalic aspects in the direction of ambrinol; odor threshold,
18.9 ng L−1 air.
Preparation of rac-3,6,6-Trimethyl-3-phenyl-3-sila-
tetrahydropyran (rac-3b). Aluminum(III) trifluoromethanesulfo-
nate (108 mg, 228 μmol) was added at 20 °C in a single portion to a
stirred solution of rac-19 (1.00 g, 4.54 mmol) in dichloromethane (15
mL). The reaction mixture was heated under reflux for 3 h and was
then cooled to 20 °C, followed by the addition of 1 M hydrochloric
acid (5 mL). The organic layer was separated, the aqueous layer was
extracted with diethyl ether (3 × 10 mL) and discarded, the combined
organic extracts were dried (Na2SO4), and the solvent was removed
under reduced pressure. The residue was purified by column
chromatography on silica gel (eluent, n-hexane/ethyl acetate (98:2
v/v)) to furnish rac-3b as a colorless liquid (170 mg, 771 μmol; 17%
1
(691 mg, 3.63 mmol; 46% yield). H NMR (500.1 MHz, CD2Cl2): δ
1.20 (s, 3 H; C(CH3)CH3), 1.40 (s, 3 H; C(CH3)CH3), 1.45 (δA),
2.02 (δM), 2.19 (δN), 3.90 (δX), and 4.02 (δY) (A3MNXY system,
2J(M,N) = 12.6 Hz, 2J(X,Y) = 8.6 Hz, 4J(A,N) = 0.6 Hz, 4J(A,Y) = 0.6
4
Hz, J(M,X) = 1.0 Hz, 7 H; CHMHNC(C(HA)3)CHXHY), 7.12−7.22
(m, 1 H; H-4, C6H5), 7.25−7.27 (m, 2 H; H-3/H-5, C6H5), 7.31−7.34
(m, 2 H; H-2/H-6, C6H5). 13C NMR (125.8 MHz, CD2Cl2): δ 29.0
(C(CH3)CH3), 29.7 (CH3C(C6H5)), 30.0 (C(CH3)CH3), 48.9
(CH3C(C6H5)), 52.8 (C(CH3)2CH2), 77.2 (CH2O), 81.2
(C(CH3)2), 126.2 (C-4, C6H5), 126.4 (C-2/C-6, C6H5), 128.7 (C-3/
C-5, C6H5), 148.9 (C-1, C6H5). Anal. Calcd for C13H18O: C, 82.06; H,
9.53. Found: C, 81.83; H, 9.53. Odor description: intense citrus and
grapefruit odor, pleasant bloomy and honey-like; odor threshold, 11.8
ng L−1 air.
1
yield). H NMR (500.1 MHz, CD2Cl2): δ 0.37 (s, 3 H; SiCH3), 0.92
(δA), 1.07 (δB), 1.77 (δM), 1.79 (δN2), 3.50 (δX), and 3.63 (δY)
2
2
(ABMNXY system, J(A,B) = 14.9 Hz, J(M,N) = 14.2 Hz, J(X,Y) =
3
3
3
15.2 Hz, J(A,M) = 4.3 Hz, J(A,N) = 9.0 Hz, J(B,M) = 9.9 Hz,
3J(B,N) = 4.6 Hz, 4J(A,X) = 0.9 Hz, 4J(B,Y) = 0.6 Hz, 6 H;
OCHXHYSiCHAHBCHMHN), 1.218 (s, 3 H; C(CH3)CH3), 1.222 (s, 3
H; C(CH3)CH3), 7.37−7.40 (m, 3 H; H-3/H-4/H-5, C6H5), 7.60−
7.62 (m, 2 H; H-2/H-6, C6H5). 13C NMR (125.8 MHz, CD2Cl2): δ
−5.6 (SiCH3), 6.6 (SiCH2CH2), 26.0 (C(CH3)CH3), 26.9 (C(CH3)-
CH3), 34.5 (SiCH2CH2), 55.2 (CH2O), 73.1 (C(CH3)2), 128.2 (C-3/
C-5, C6H5), 129.7 (C-4, C6H5), 134.3 (C-2/C-6, C6H5), 137.4 (C-1,
C6H5). 29Si NMR (99.4 MHz, CD2Cl2): δ −17.5. Anal. Calcd for
C13H20OSi: C, 70.85; H, 9.15. Found: C, 71.03; H, 9.19. Odor
description: green, bitter citrus-grapefruit-type odor, with slightly
animalic and slightly dry, woody facets; odor threshold, 2.50 ng L−1 air.
Dichloro(chloromethyl)methylsilane (4). This compound was
commercially available.
Preparation of rac-3,5,5-Trimethyl-3-phenyl-3-sila-
tetrahydrofuran (rac-2b). 2,2′-Azobis(2-methylpropionitrile) (1.08
g, 6.58 mmol) was added at 20 °C in a single portion to a stirred
solution of (3SR,5SR)-14/(3SR,5RS)-14 (3.50 g, 9.68 mmol) and tri-
n-butylstannane (5.08 g, 17.5 mmol) in benzene (40 mL). The mixture
was heated under reflux for 1 h and was then cooled to 20 °C, the
solvent was removed under reduced pressure, and the residue was
purified by column chromatography on silica gel (eluent, n-hexane/
ethyl acetate (9:1 v/v)) to furnish rac-2b as a colorless liquid (840 mg,
1
4.07 mmol; 42% yield). H NMR (500.1 MHz, CD2Cl2): δ 0.55 (s, 3
H; SiCH3), 1.09 (δA) and 1.17 (δB) (AB system, 2J(A,B) = 14.5 Hz, 2
H; SiCHAHBC), 1.31 (s, 3 H; C(CH3)CH3), 1.33 (s, 3 H;
Preparation of rac-Allyl(chloromethyl)methylphenylsilane
(rac-5). A 1.8 M solution of phenylmagnesium chloride in
tetrahydrofuran (22.5 mL, 40.5 mmol of PhMgCl) was added
dropwise at 0 °C within 1 h to a stirred solution of 4 (6.30 g, 38.5
mmol) in diethyl ether (120 mL). The resulting mixture was warmed
to 20 °C and stirred at this temperature for 20 min. Subsequently, a
1.7 M solution of allylmagnesium chloride in tetrahydrofuran (23.8
mL, 40.5 mmol of CH2CHCH2MgCl) was added dropwise at 0 °C
within 1.5 h. After the addition was complete, the mixture was warmed
to 20 °C and stirred at this temperature for 17 h, followed by
sequential addition of a saturated aqueous solution of ammonium
chloride (20 mL) and diethyl ether (20 mL). The resulting solid was
filtered off and discarded, the organic layer was separated, the aqueous
layer was washed with diethyl ether (3 × 25 mL) and discarded, the
combined organic extracts were dried (Na2SO4), and the solvent was
removed under reduced pressure. The residue was purified by column
chromatography on silica gel (eluent, n-hexane/ethyl acetate (98:2 v/
v)) to furnish rac-5 as a colorless liquid (7.14 g, 33.9 mmol; 88%
2
C(CH3)CH3), 3.49 (δA) and 3.58 (δB) (AB system, J(A,B) = 13.8
Hz, 2 H; SiCHAHBO), 7.38−7.41 (m, 3 H; H-3/H-4/H-5, C6H5),
7.61−7.63 (m, 2 H; H-2/H-6, C6H5). 13C NMR (125.8 MHz,
CD2Cl2): δ −4.1 (SiCH3), 28.2 (SiCH2C), 29.3 (C(CH3)CH3), 30.0
(C(CH3)CH3), 58.0 (SiCH2O), 81.7 (C(CH3)2), 128.3 (C-3/C-5,
C6H5), 129.8 (C-4, C6H5), 134.3 (C-2/C-6, C6H5), 136.9 (C-1, C6H5).
29Si NMR (99.4 MHz, CD2Cl2): δ 11.2. Anal. Calcd for C12H18OSi: C,
69.84; H, 8.79. Found: C, 69.53; H, 8.86. Odor description: agrestic
odor in the direction of lavender, labienone, and methyl
pamplemousse, with strong green chile pepper and tomato aspects
and a slightly rubbery character; odor threshold, 7.58 ng L−1 air.
Preparation of rac-2,2,5-Trimethyl-5-phenyl-
tetrahydropyran (rac-3a). Aluminum(III) trifluoromethanesulfo-
nate (197 mg, 415 μmol) was added at 20 °C in a single portion to a
stirred solution of rac-16 (1.68 g, 8.22 mmol) in dichloromethane (15
mL). The reaction mixture was heated under reflux for 10 h and was
then cooled to 20 °C, followed by the addition of 1 M hydrochloric
acid (5 mL). The organic layer was separated, the aqueous layer was
extracted with diethyl ether (3 × 10 mL) and discarded, the combined
organic extracts were dried (Na2SO4), and the solvent was removed
under reduced pressure. The residue was purified by column
chromatography on silica gel (eluent, n-hexane/ethyl acetate (98:2
v/v)) to furnish rac-3a as a colorless liquid (730 mg, 3.57 mmol; 43%
yield). 1H NMR (500.1 MHz, CD2Cl2): δ 1.15 (s, 3 H; C(CH3)CH3),
1.24 (s, 3 H; CH3CCH2O), 1.26 (s, 3 H; C(CH3)CH3), 1.36 (δA),
1.56 (δB), 1.79 (δM), 2.04 (δN), 3.59 (δX), and 3.91 (δY) (ABMNXY
1
yield). H NMR (500.1 MHz, CDCl3): δ 0.46 (s, 3 H; CH3), 1.98
(δA), 2.01 (δB), 4.96 (δM(E)), 5.00 (δN(Z)), and 5.84 (δX) (ABMNX
system, 2J(A,B) = 13.7 Hz, 2J(M(E),N(Z)) = 2.0 Hz, 3J(A,X) = 8.0 Hz,
3J(B,X) = 8.1 Hz, 3J(M(E),X) = 10.1 Hz, 3J(N(Z),X) = 17.0 Hz,
4
4
4J(A,M(E)) = 1.0 Hz, J(A,N(Z)) = 1.4 Hz, J(B,M(E)) = 1.0 Hz,
4J(B,N(Z)) = 1.4 Hz, 5 H; CHAHBCHXCHM(E)HN(Z)), 3.03 (δA)
and 3.08 (δB) (AB system, 2J(A,B) = 13.7 Hz, 2 H; CHAHBCl), 7.41−
7.47 (m, 3 H; H-3/H-4/H-5, C6H5), 7.58−7.60 (m, 2 H; H-2/H-6,
E
dx.doi.org/10.1021/om401070c | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
C6H5). 13C NMR (125.8 MHz, CDCl3): δ −6.5 (SiCH3), 20.2
(CH2CHCH2), 28.7 (CH2Cl), 114.8 (CH2CHCH2), 128.1 (C-3/
C-5, C6H5), 130.0 (C-4, C6H5), 133.3 (CH2CHCH2), 134.2 (C-2/
C-6, C6H5), 134.6 (C-1, C6H5). 29Si NMR (99.4 MHz, CDCl3): δ
−5.0. Anal. Calcd for C11H15ClSi: C, 62.68; H, 7.17. Found: C, 62.70;
H, 7.15.
organic layer was separated, the aqueous layer was extracted with
toluene (3 × 25 mL) and discarded, the combined organic extracts
were dried (Na2SO4), and the solvent was removed under reduced
pressure. The residue was purified by column chromatography on
silica gel13 (eluent, n-hexane/ethyl acetate (99:1 v/v)) to furnish rac-9
as a colorless liquid (2.71 g, 14.4 mmol; 64%). 1H NMR (300.1 MHz,
C6D6): δ 1.34 (s, 3 H; CH3C(C6H5)), 1.39 (δF), 2.63 (δA), 2.69 (δB),
Preparation of rac-(Acetoxymethyl)allylmethylphenylsilane
(rac-6). Compound rac-5 (7.14 g, 33.9 mmol) was added at 20 °C in a
single portion to a stirred mixture of sodium acetate (2.78 g, 33.9
mmol), 18-crown-6 (89.5 mg, 339 μmol), and N,N-dimethylforma-
mide (120 mL). The reaction mixture was heated under reflux for 17 h
and was then cooled to 20 °C. The solvent was removed under
reduced pressure, followed by sequential addition of water (60 mL)
and diethyl ether (60 mL). The organic layer was separated, the
aqueous layer was extracted with diethyl ether (3 × 35 mL) and
discarded, the combined organic extracts were dried (Na2SO4), and
the solvent was removed under reduced pressure. The residue was
purified by column chromatography on silica gel (eluent, n-hexane/
ethyl acetate (98:2 v/v)) to furnish rac-6 as a colorless liquid (7.31 g,
2
4.68 (δX(Z)), and 4.86 (δY(E)) (ABF3XY system, J(A,B) = 13.9 Hz,
4
4
2J(X(Z),Y(E)) = 2.2 Hz, J(A,X(Z)) = 0.9 Hz, J(B,X(Z)) = 1.0 Hz,
4J(F,X(Z)) = 0.9 Hz, 4J(F,Y(E)) = 1.5 Hz, 7 H; CHAHBC(C(HF)3)
CHX(Z)HY(E)), 7.13−7.21 (m, 5 H; C6H5), 9.42 (s, 1 H; CHO). 13C
NMR (75.5 MHz, C6D6): δ 18.5 (CH3C(C6H5)), 24.1 (CH2C-
(CH3)CH2), 44.4 (CH2C(CH3)CH2), 53.4 (CH3C(C6H5)),
115.5 (CH2C(CH3)CH2), 127.3 (C-4, C6H5), 127.5 (C-2/C-6 or
C-3/C-5, C6H5), 128.9 (C-2/C-6 or C-3/C-5, C6H5), 140.4 (C-1,
C6H5), 141.8 (CH2C(CH3)CH2), 200.6 (CHO). Anal. Calcd for
C13H16O: C, 82.94; H, 8.57. Found: C, 82.60; H, 8.74.
Preparation of rac-2,4-Dimethyl-2-phenylpent-4-en-1-ol
(rac-10). A solution of rac-9 (2.00 g, 10.6 mmol) in diethyl ether
(45 mL) was added dropwise at 0 °C within 30 min to a stirred
suspension of lithium aluminum hydride (402 mg, 10.6 mmol) in
diethyl ether (35 mL). The resulting mixture was stirred at 0 °C for 30
min, warmed to 20 °C, and then stirred at this temperature for 30 min.
Subsequently, a saturated aqueous solution of sodium sulfate (10 mL)
and diethyl ether (10 mL) were added carefully one after another. The
resulting solid was filtered off and discarded, the solvent was removed
under reduced pressure, and the residue was purified by column
chromatography on silica gel (eluent, n-hexane/ethyl acetate (9:1 v/
v)) to furnish rac-10 as a colorless liquid (1.79 g, 9.41 mmol; 89%
yield). 1H NMR (500.1 MHz, C6D6): δ 1.36 (δX), 3.52 (δA), and 3.63
(δB) (ABX system, 2J(A,B) = 10.7 Hz, 3J(A,X) = 2.0 Hz, 3J(B,X) = 0.9
Hz, 3 H; CHAHBOHX), 1.40 (s, 3 H; CH3C(C6H5)), 1.41 (δF), 2.36
(δA), 2.49 (δB), 4.74 (δX(Z)), and 4.89 (δY(E)) (ABF3XY system,
1
31.2 mmol; 92% yield). H NMR (300.1 MHz, CD2Cl2): δ 0.37 (s, 3
H; SiCH3), 1.90 (δA), 1.92 (δB), 4.90 (δM(E)), 4.93 (δN(Z)), and 5.81
2
2
(δX) (ABMNX system, J(A,B) = 12.6 Hz, J(M(E),N(Z)) = 2.1 Hz,
3J(A,X) = 8.0 Hz, 3J(B,X) = 8.1 Hz, 3J(M(E),X) = 10.1 Hz,
4
4
3J(N(Z),X) = 17.0 Hz, J(A,M(E)) = 1.0 Hz, J(A,N(Z)) = 1.4 Hz,
4J(B,M(E)) = 1.0 Hz, 4J(B,N(Z)) = 1.4 Hz, 5 H; CHAHBCHX
CHM(E)HN(Z)), 2.00 (s, 3 H; C(O)CH3), 4.00 (δA) and 4.01 (δB) (AB
system, 2J(A,B) = 14.4 Hz, 2 H; CHAHBO), 7.35−7.45 (m, 3 H; H-3/
H-4/H-5, C6H5), 7.53−7.59 (m, 2 H; H-2/H-6, C6H5). 13C NMR
(75.5 MHz, CD2Cl2): δ −6.6 (SiCH3), 20.8 (CH2CHCH2), 20.9
(C(O)CH3), 55.4 (CH2O), 114.4 (CH2CHCH2), 128.2 (C-3/C-5,
C6H5), 130.0 (C-4, C6H5), 134.0 (CH2CHCH2), 134.4(C-2/C-6,
C6H5), 135.3 (C-1, C6H5), 171.8 (C(O)CH3). 29Si NMR (59.6 MHz,
CD2Cl2): δ −7.3. Anal. Calcd for C13H18O2Si: C, 66.62, H, 7.74.
Found: C, 66.56; H, 7.72.
2
4
2J(A,B) = 13.5 Hz, J(X(Z),Y(E)) = 2.5 Hz, J(A,X(Z)) = 0.9 Hz,
4J(B,X(Z)) = 1.1 Hz, 4J(B,F) = 0.3 Hz, 4J(F,X(Z)) = 0.9 Hz,
4J(F,Y(E)) = 1.5 Hz, 7 H; CHAHBC(C(HF)3)CHX(Z)HY(E)), 7.14−
7.18 (m, 1 H; H-4, C6H5), 7.24−7.27 (m, 2 H; H-3/H-5, C6H5),
7.31−7.34 (m, 2 H; H-2/H-6, C6H5). 13C NMR (125.8 MHz, C6D6):
Preparation of rac-Allyl(hydroxymethyl)methylphenylsilane
(rac-7). A solution of rac-6 (6.00 g, 25.6 mmol) in diethyl ether (75
mL) was added dropwise at 0 °C within 30 min to a stirred suspension
of lithium aluminum hydride (972 mg, 25.6 mmol) in diethyl ether
(85 mL). The resulting mixture was stirred at 0 °C for 30 min, warmed
to 20 °C, and then stirred at this temperature for 30 min.
Subsequently, a saturated aqueous solution of sodium sulfate (15
mL) and diethyl ether (15 mL) were added carefully one after another.
The resulting solid was filtered off and discarded, the solvent was
removed under reduced pressure, and the residue was purified by bulb-
to-bulb distillation (oven temperature 100 °C, 0.03 mbar) to furnish
δ
21.9 (CH3C(C6H5)), 24.6 (CH2C(CH3)CH2), 43.2
(CH3C(C6H5)), 46.8 (CH2C(CH3)CH2), 72.0 (CH2O), 114.6
(CH2C(CH3)CH2), 126.2 (C-4, C6H5), 127.1 (C-2/C-6, C6H5),
128.4 (C-3/C-5, C6H5), 143.0 (CH2C(CH3)CH2), 145.8 (C-1,
C6H5). Anal. Calcd for C13H18O: C, 82.06; H, 9.53. Found: C, 82.00;
H, 9.89.
1
Preparation of rac-(Chloromethyl)methyl(2-methylprop-2-
en-1-yl)phenylsilane (rac-11). A 1.8 M solution of phenyl-
magnesium chloride in tetrahydrofuran (71.1 mL, 128 mmol of
PhMgCl) was added dropwise at 0 °C within 2 h to a stirred solution
of 4 (20.0 g, 122 mmol) in diethyl ether (400 mL). The resulting
mixture was warmed to 20 °C and stirred at this temperature for 30
min. Subsequently, a solution of (2-methylprop-2-en-1-yl)magnesium
chloride in tetrahydrofuran (freshly prepared from 3-chloro-2-
methylprop-1-ene (12.2 g, 135 mmol) and magnesium turnings
(13.1 g, 539 mmol) in tetrahydrofuran (200 mL)) was added dropwise
at 0 °C within 1.5 h. After the addition was complete, the mixture was
warmed to 20 °C and stirred at this temperature for 17 h, followed by
sequential addition of a saturated aqueous solution of ammonium
chloride (25 mL) and diethyl ether (25 mL). The resulting solid was
filtered off and discarded, the organic layer was separated, the aqueous
layer was washed with diethyl ether (3 × 25 mL) and discarded, the
combined organic extracts were dried (Na2SO4), and the solvent was
removed under reduced pressure. The residue was purified by column
chromatography on silica gel (eluent, n-hexane) to furnish rac-11 as a
colorless liquid (23.4 g, 104 mmol; 85% yield). 1H NMR (500.1 MHz,
CD2Cl2): δ 0.46 (s, 3 H; SiCH3), 1.63 (δF), 1.94 (δA), 1.98 (δB), 4.56
(δX(Z)), and 4.65 (δY(E)) (ABF3XY system, 2J(A,B) = 13.7 Hz,
rac-7 as a colorless liquid (3.89 g, 20.2 mmol; 79% yield). H NMR
(500.1 MHz, CD2Cl2): δ 0.36 (s, 3 H; CH3), 1.31 (br s, 1 H; OH),
1.91 (δA), 1.94 (δB), 4.91 (δM(E)), 4.97 (δN(Z)), and 5.88 (δX)
(ABMNX system, 2J(A,B) = 13.6 Hz, 2J(M(E),N(Z)) = 2.2 Hz,
3J(A,X) = 8.0 Hz, 3J(B,X) = 8.1 Hz, 3J(M(E),X) = 10.1 Hz,
4
4
3J(N(Z),X) = 17.0 Hz, J(A,M(E)) = 1.0 Hz, J(A,N(Z)) = 1.4 Hz,
4J(B,M(E)) = 1.0 Hz, 4J(B,N(Z)) = 1.4 Hz, 5 H; CHAHBCHX
2
CHM(E)HN(Z)), 3.639 and 3.641 (AB system, J(A,B) = 14.1 Hz, 2 H;
CHAHBO), 7.38−7.44 (m, 3 H; H-3/H-4/H-5, C6H5), 7.59−7.62 (m,
2 H; H-2/H-6, C6H5). 13C NMR (125.8 MHz, CD2Cl2): δ −6.9
(SiCH3), 20.7 (CH2CHCH2), 53.9 (CH2O), 114.1 (CH2CH
CH2), 128.2 (C-3/C-5, C6H5), 129.9 (C-4, C6H5), 134.6 (C-2/C-6,
C6H5), 134.7 (CH2CHCH2), 136.0 (C-1, C6H5). 29Si NMR (99.4
MHz, CD2Cl2): δ −7.4. Anal. Calcd for C11H16OSi: C, 68.69; H, 8.38.
Found: C, 68.31; H, 8.26.
rac-2-Phenylpropanal (rac-8). This compound was commercially
available.
Preparation of rac-2,4-Dimethyl-2-phenylpent-4-enal (rac-
9). A mixture of rac-8 (3.00 g, 22.4 mmol) and 3-chloro-2-methylprop-
1-ene (2.03 g, 22.4 mmol) was added dropwise at 60 °C within 3 h to
a stirred mixture of powdered sodium hydroxide (1.34 g, 33.5 mmol),
tetra-n-butylammonium iodide (82.7 mg, 224 μmol), water (2.69 mL),
and toluene (30 mL). After the addition was complete, the mixture
was stirred at 60 °C for 17 h and was then cooled to 20 °C, followed
by sequential addition of water (25 mL) and toluene (25 mL). The
4
4
2J(X(Z),Y(E)) = 2.2 Hz, J(A,X(Z)) = 1.1 Hz, J(B,X(Z)) = 1.0 Hz,
4J(F,X(Z)) = 0.8 Hz, 4J(F,Y(E)) = 1.5 Hz, 7 H; CHAHBC(C(HF)3)
2
CHX(Z)HY(E)), 3.065 (δA) and 3.08 (δB) (AB system, J(A,B) = 13.7
F
dx.doi.org/10.1021/om401070c | Organometallics XXXX, XXX, XXX−XXX

Organometallics
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Hz, 2 H; CHAHBCl), 7.37−7.43 (m, 3 H; H-3/H-4/H-5, C6H5), 7.56−
7.60 (m, 2 H; H-2/H-6, C6H5). 13C NMR (125.8 MHz, CD2Cl2): δ
−6.2 (SiCH3), 24.3 (CH2C(CH3)CH2), 25.4 (CH2C(CH3)
CH2), 29.5 (CH2Cl), 110.0 (CH2C(CH3)CH2), 128.2 (C-3/C-5,
C6H5), 130.1 (C-4, C6H5), 134.4 (C-2/C-6, C6H5), 135.3 (C-1, C6H5),
142.5 (CH2C(CH3)CH2). 29Si NMR (99.4 MHz, CD2Cl2): δ −5.1.
Anal. Calcd for C12H17ClSi: C, 64.11; H, 7.62. Found: C, 64.33; H,
7.80.
mL) and discarded. The combined organic extracts were dried
(Na2SO4), the solvent was removed under reduced pressure, and the
residue was purified by column chromatography on silica gel (eluent,
n-hexane/ethyl acetate (98:2 v/v)) to furnish (3SR,5SR)-14/
1
(3SR,5RS)-14 as a yellow liquid (2.20 g, 6.09 mmol; 63% yield). H
NMR (500.1 MHz, C6D6; data for two diastereomers (molar ratio,
1:1)): δ 0.37 (s, 3 H; SiCH3), 0.38 (s, 3 H; SiCH3), 0.98 (δA) and 1.60
(δB) (AB system, 2J(A,B) = 14.5 Hz, 2 H; SiCHAHBC), 1.17 (δA) and
1.40 (δB) (AB system, 2J(A,B) = 14.6 Hz, 2 H; SiCHAHBC), 1.45 (s, 3
H; CCH3), 1.51 (s, 3 H; CCH3), 3.310 (δA) and 3.312 (δB) (AB
system, 2J(A,B) = 11.7 Hz, 2 H; CCHAHBSe), 3.33 (δA) and 3.36 (δB)
(AB system, 2J(A,B) = 11.6 Hz, 2 H; CCHAHBSe), 3.50 (δA) and 3.77
(δB) (AB system, 2J(A,B) = 13.9 Hz, 2 H; SiCHAHBO), 3.60 (δA) and
Preparation of rac-(Acetoxymethyl)methyl(2-methylprop-2-
en-1-yl)phenylsilane (rac-12). Compound rac-11 (4.00 g, 17.8
mmol) was added at 20 °C in a single portion to a stirred mixture of
sodium acetate (3.65 g, 44.5 mmol), tetra-n-butylphosphonium
chloride (525 mg, 1.78 mmol), and N,N-dimethylformamide (60
mL). The reaction mixture was heated under reflux for 17 h and was
then cooled to 20 °C. The solvent was removed under reduced
pressure, followed by sequential addition of water (50 mL) and diethyl
ether (50 mL). The organic layer was separated, the aqueous layer was
extracted with diethyl ether (3 × 25 mL) and discarded, the combined
organic extracts were dried (Na2SO4), and the solvent was removed
under reduced pressure. The residue was purified by column
chromatography on silica gel (eluent, n-hexane/ethyl acetate (98:2
v/v)) to furnish rac-12 as a colorless liquid (3.14 g, 12.6 mmol; 71%
2
3.69 (δB) (AB system, J(A,B) = 13.9 Hz, 2 H; SiCHAHBO), 7.06−
7.14 (m, 6 H; H-3/H-4/H-5, SeC6H5), 7.29−7.31 (m, 6 H; H-3/H-4/
H-5, SiC6H5), 7.53−7.55 (m, 4 H; H-2/H-6, SiC6H5), 7.61−7.67 (m, 4
H; H-2/H-6, SeC6H5). 13C NMR (125.8 MHz, C6D6; data for two
diastereomers (molar ratio, 1:1)): δ −4.55 and −4.52 (SiCH3), 26.1
and 26.3 (SiCH2C), 27.1 and 27.6 (CCH3), 42.2 and 42.5 (CCH2Se),
58.0 and 58.2 (SiCH2O), 83.6 and 83.7 (CCH3), 126.56 and 126.64
(C-4, SeC6H5), 128.3 (4 C; C-3/C-5, SiC6H5), 129.1 and 129.2 (C-3/
C-5, SeC6H5), 129.80 and 129.83 (C-4, SiC6H5), 132.55 and 132.58
(C-1, SeC6H5), 132.8 and 132.9 (C-2/C-6, SeC6H5), 134.2 and 134.3
(C-2/C-6, SiC6H5), 136.1 and 136.2 (C-1, SiC6H5). 29Si NMR (99.4
MHz, C6D6; data for two diastereomers (molar ratio, 1:1)): δ 10.8 and
10.9. 77Se NMR (95.4 MHz, C6D6; data for two diastereomers (molar
ratio, 1:1)): δ 256.1 and 257.1. Anal. Calcd for C18H22OSeSi: C, 59.82;
H, 6.14. Found: C, 60.19; H, 6.39.
1
yield). H NMR (300.1 MHz, CD2Cl2): δ 0.41 (s, 3 H; SiCH3), 1.64
(δF), 1.91 (δA), 1.93 (δB), 4.55 (δX(Z)), and 4.65 (δY(E)) (ABF3XY
2
2
4
system, J(A,B) = 13.7 Hz, J(X(Z),Y(E)) = 2.3 Hz, J(A,X(Z)) = 1.1
Hz, 4J(B,X(Z)) = 1.0 Hz, 4J(F,X(Z)) = 0.8 Hz, 4J(F,Y(E)) = 1.5 Hz, 7
H; CHAHBC(C(HF)3)CHX(Z)HY(E)), 2.01 (s, 3 H; C(O)CH3), 4.01
2
(δA) and 4.03 (δB) (AB system, J(A,B) = 14.4 Hz, 2 H; CHAHBO),
7.38−7.40 (m, 3 H; H-3/H-4/H-5, C6H5), 7.56−7.59 (m, 2 H; H-2/
H-6, C6H5). 13C NMR (75.5 MHz, CD2Cl2): δ −6.1 (SiCH3), 20.9
(C(O)CH3), 24.7 (CH2C(CH3)CH2), 25.3 (CH2C(CH3)CH2),
55.6 (CH2O), 109.9 (CH2C(CH3)CH2), 128.2 (C-3/C-5, C6H5),
129.9 (C-4, C6H5), 134.4 (C-2/C-6, C6H5), 135.7 (C-1, C6H5), 142.6
(CH2C(CH3)CH2), 172.0 (C(O)CH3). 29Si NMR (59.6 MHz,
CD2Cl2): δ −7.5. Anal. Calcd for C14H20O2Si: C, 67.70; H, 8.12.
Found: C, 67.59; H, 7.96.
Preparation of rac-2,5-Dimethyl-2-phenylhex-4-enal (rac-
15). A solution of rac-8 (2.54 g, 18.9 mmol) in tetrahydrofuran (35
mL) was added dropwise at 20 °C within 30 min to a stirred
suspension of sodium hydride (505 mg, 21.0 mmol) in tetrahydrofuran
(35 mL), and the resulting mixture was stirred at 20 °C for 30 min.
Subsequently, 1-bromo-3-methylbut-2-ene (3.13 g, 21.0 mmol) was
added dropwise at 20 °C within 30 min. After the addition was
complete, the mixture was stirred at 20 °C for 30 min, followed by
sequential addition of water (25 mL) and diethyl ether (25 mL). The
organic layer was separated, the aqueous layer was extracted with
diethyl ether (3 × 25 mL) and discarded, the combined organic
extracts were dried (Na2SO4), and the solvent was removed under
reduced pressure. The residue was purified by column chromatog-
raphy on silica gel13 (eluent, n-hexane/ethyl acetate (98:2 v/v)),
followed by a second column-chromatographic purification on silica
gel (eluent, n-hexane/diethyl ether (99:1 v/v)) to furnish rac-15 as a
Preparation of rac-(Hydroxymethyl)methyl(2-methylprop-2-
en-1-yl)phenylsilane (rac-13). A solution of rac-12 (3.00 g, 12.1
mmol) in diethyl ether (45 mL) was added dropwise at 0 °C within 1
h to a stirred suspension of lithium aluminum hydride (460 mg, 12.1
mmol) in diethyl ether (45 mL). The resulting mixture was stirred at 0
°C for 30 min, warmed to 20 °C, and then stirred at this temperature
for 30 min. Subsequently, a saturated aqueous solution of sodium
sulfate (15 mL) and diethyl ether (15 mL) were added carefully one
after another. The resulting solid was filtered off and discarded, and
the solvent was removed under reduced pressure to furnish rac-13 as a
colorless liquid (2.32 g, 11.2 mmol; 93% yield). 1H NMR (300.1 MHz,
C6D6): δ 0.41 (s, 3 H; SiCH3), 0.67 (br s, 1 H; OH), 1.72 (δF), 1.92
(δA), 1.99 (δB), 4.77 (δX(Z)), and 4.83 (δY(E)) (ABF3XY system,
1
colorless liquid (2.61 g, 12.9 mmol; 68%). H NMR (500.1 MHz,
C6D6): δ 1.36 (s, 3 H; CH3C(C6H5)), 1.49 (δM(Z)), 1.61 (δN(E)), 2.66
2
(δA), 2.67 (δB), and 5.11 (δX) (ABM3N3X system, J(A,B) = 14.7 Hz,
3J(A,X) = 7.4 Hz, 3J(B,X) = 7.5 Hz, 4J(M(Z),X) = 1.4 Hz, 4J(N(E),X)
5
5
5
= 1.5 Hz, J(A,M(Z)) = 0.6 Hz, J(A,N(E)) = 1.1 Hz, J(B,M(Z)) =
2
4
2J(A,B) = 13.5 Hz, J(X(Z),Y(E)) = 2.3 Hz, J(A,X(Z)) = 1.1 Hz,
5
0.8 Hz, J(B,N(E)) = 1.3 Hz, 9 H; CHAHBCHXC(C(HN(E))3)C-
4J(B,X(Z)) = 1.0 Hz, 4J(F,X(Z)) = 0.8 Hz, J(F,Y(E)) = 1.4 Hz, 7 H;
(HM(Z))3), 7.13−7.17 (m, 1 H; H-4, C6H5), 7.18−7.25 (m, 4 H; H-2/
H-3/H-5/H-6, C6H5), 9.50 (s, 1 H; CHO). 13C NMR (125.8 MHz,
C6D6): δ 17.8 (CH2CHC(C(HM(Z))3)(C(HN(E))3)), 19.1 (CH3C-
(C6H5)), 25.8 (CH2CHC(C(HM(Z))3)(C(HN(E))3)), 34.9
(CH2CHC(CH3)2), 54.4 (CH3C(C6H5)), 119.4 (CH2CH
C(CH3)2), 127.2 (C-4, C6H5), 127.5 (C-2/C-6 or C-3/C-5, C6H5),
128.9 (C-2/C-6 or C-3/C-5, C6H5), 134.5 (CH2CHC(CH3)2),
140.6 (C-1, C6H5), 201.1 (CHO). Anal. Calcd for C14H18O: C, 83.12;
H, 8.97. Found: C, 82.82; H, 9.28.
4
CHAHBC(C(HF)3)CHX(Z)HY(E)), 3.52 (δA) and 3.55 (δB) (AB
system, 2J(A,B) = 13.9 Hz, 2 H; CHAHBO), 7.30−7.23 (m, 3 H; H-3/
H-4/H-5, C6H5), 7.62−7.67 (m, 2 H; H-2/H-6, C6H5). 13C NMR
(75.5 MHz, C6D6): δ −6.5 (SiCH3), 24.5 (CH2C(CH3)CH2), 25.3
(CH2C(CH3)CH2), 53.9 (CH2O), 109.6 (CH2C(CH3)CH2),
128.1 (C-3/C-5, C6H5), 129.6 (C-4, C6H5), 134.5 (C-2/C-6, C6H5),
136.6 (C-1, C6H5), 142.1 (CH2C(CH3)CH2). 29Si NMR (59.6
MHz, CD2Cl2): δ −8.0. Anal. Calcd for C12H18OSi: C, 69.84; H, 8.79.
Found: C, 69.78; H, 8.80.
Preparation of a 1:1 Mixture of (3SR,5SR)- and (3SR,5RS)-3,5-
Dimethyl-3-phenyl-5-[(phenylseleno)methyl]-3-silatetrahydro-
furan ((3SR,5SR)-14/(3SR,5RS)-14). Chlorophenylselane (1.86 g,
9.71 mmol) was added at −78 °C in small portions within 30 min to a
stirred solution of triethylamine (1.36 g, 13.4 mmol) and rac-13 (2.00
g, 9.69 mmol) in dichloromethane (25 mL). The resulting mixture was
stirred at −78 °C for 30 min, warmed to 20 °C, and then stirred at this
temperature for 2 h. Subsequently, a saturated aqueous solution of
sodium chloride (15 mL) was added, the organic layer was separated,
and the aqueous layer was extracted with dichloromethane (3 × 35
Preparation of rac-2,5-Dimethyl-2-phenylhex-4-en-1-ol (rac-
16). A solution of rac-15 (2.34 g, 11.6 mmol) in diethyl ether (25 mL)
was added dropwise at 0 °C within 1 h to a stirred suspension of
lithium aluminum hydride (441 mg, 11.6 mmol) in diethyl ether (20
mL). The resulting mixture was stirred at 0 °C for 30 min, warmed to
20 °C, and then stirred at this temperature for 30 min. Subsequently, a
saturated aqueous solution of sodium sulfate (5 mL) and diethyl ether
(5 mL) were added carefully one after another. The resulting solid was
filtered off and discarded, the solvent was removed under reduced
pressure, and the residue was purified by column chromatography on
silica gel (eluent, n-hexane/ethyl acetate (9:1 v/v)) to furnish rac-16 as
G
dx.doi.org/10.1021/om401070c | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
1
4
5
a colorless liquid (1.80 g, 8.81 mmol; 76% yield). H NMR (500.1
MHz, C6D6): δ 0.95 (δX), 3.56 (δA), and 3.66 (δB) (ABX system,
2J(A,B) = 10.8 Hz, 3J(A,X) = 2.8 Hz, 3J(B,X) = 1.8 Hz, 3 H;
CHAHBOHX), 1.38 (s, 3 H; CH3C(C6H5)), 1.61 (δM(Z)), 1.65 (δN(E)),
2.46 (δA), 2.52 (δB), and 5.17 (δX) (ABM3N3X system, 2J(A,B) = 14.5
Hz, 3J(A,X) = 8.0 Hz, 3J(B,X) = 6.6 Hz, 4J(M(Z),X) = 1.4 Hz,
4J(M(Z),X) = 1.4 Hz, J(N(E),X) = 1.5 Hz, J(A,M(Z)) = 0.8 Hz,
5J(A,N(E)) = 0.8 Hz, 5J(B,M(Z)) = 0.8 Hz, 5J(B,N(E)) = 1.2 Hz, 9 H;
CHAHBCHXC(C(HM(Z))3)C(HN(E))3), 2.00 (s, 3 H; C(O)CH3),
2
3.988 and 3.990 (AB system, J(A,B) = 14.6 Hz, 2 H; CHAHBO),
7.36−7.42 (m, 3 H; H-3/H-4/H-5, C6H5), 7.52−7.58 (m, 2 H; H-2/
H-6, C6H5). 13C NMR (125.8 MHz, CD2Cl2): δ −6.4 (SiCH3), 14.9
(CH2CHC(CH3)2), 17.7 (CH2CHC(C(HM(Z))3)(C(HN(E))3)),
20.9 (C(O)CH3), 25.8 (CH2CHC(C(HM(Z))3)(C(HN(E))3)), 55.6
(CH2O), 118.4 (CH2CHC(CH3)2), 128.2 (C-3/C-5, C6H5), 129.8
(C-4, C6H5), 130.8 (CH2CHC(CH3)2), 134.4 (C-2/C-6, C6H5),
135.9 (C-1, C6H5), 171.8 (C(O)CH3). 29Si NMR (99.4 MHz,
CD2Cl2): δ −6.5. Anal. Calcd for C15H22O2Si: C, 68.65; H, 8.45.
Found: C, 68.49; H, 8.47.
4J(N(E),X) = 1.5 Hz, J(A,M(Z)) = 0.6 Hz, J(A,N(E)) = 1.1 Hz,
5
5
5J(B,M(Z)) = 0.8 Hz, 5J(B,N(E)) = 1.2 Hz, 9 H; CHAHBCHX
C(C(HN(E))3)C(HM(Z))3), 7.17−7.21 (m, 1 H; H-4, C6H5), 7.28−7.32
(m, 2 H; H-3/H-5, C6H5), 7.37−7.39 (m, 2 H; H-2/H-6, C6H5). 13C
NMR (125.8 MHz, C6D6): δ 17.9 (CH2CHC(C(HM(Z))3)(C-
(HN(E))3), 22.1 (CH3C(C6H5)), 25.9 (CH2CHC(C(HM(Z))3)-
(C(HN(E))3)), 37.0 (CH2CHC(CH3)2), 44.0 (CH3C(C6H5)), 71.7
(CH2O), 120.9 (CH2CHC(CH3)2), 126.2 (C-4, C6H5), 127.1 (C-2/
C-6, C6H5), 128.3 (C-3/C-5, C6H5), 133.3 (CH2CHC(CH3)2),
145.8 (C-1, C6H5). Anal. Calcd for C14H20O: C, 82.30; H, 9.87.
Found: C, 82.17; H, 9.86.
Preparation of rac-(Hydroxymethyl)methyl(3-methylbut-2-
en-1-yl)phenylsilane (rac-19). A solution of rac-18 (1.50 g, 5.72
mmol) in diethyl ether (25 mL) was added dropwise at 0 °C within 1
h to a stirred suspension of lithium aluminum hydride (217 mg, 5.72
mmol) in diethyl ether (20 mL). The resulting mixture was stirred at 0
°C for 30 min, warmed to 20 °C, and then stirred at this temperature
for 30 min. Subsequently, a saturated aqueous solution of sodium
sulfate (5 mL) and diethyl ether (5 mL) were added carefully one after
another. The resulting solid was filtered off and discarded, and the
solvent was removed under reduced pressure to furnish rac-19 as a
colorless liquid (1.24 g, 5.63 mmol; 98% yield). 1H NMR (500.1 MHz,
CD2Cl2): δ 0.33 (s, 3 H; SiCH3), 1.31 (s, 1 H; OH), 1.57 (δM(Z)), 1.71
(δN(E)), 1.75 (δA), 1.80 (δB), and 5.22 (δX) (ABM3N3X system,
2J(A,B) = 14.2 Hz, 3J(A,X) = 8.4 Hz, 3J(B,X) = 8.5 Hz, 4J(M(Z),X) =
Preparation of rac-(Chloromethyl)methyl(3-methylbut-2-
en-1-yl)phenylsilane (rac-17). A 1.8 M solution of phenyl-
magnesium chloride in tetrahydrofuran (32.3 mL, 58.1 mmol of
PhMgCl) was added dropwise at 0 °C within 1 h to a stirred solution
of 4 (9.06 g, 55.4 mmol) in diethyl ether (200 mL). The resulting
mixture was warmed to 20 °C and then stirred at this temperature for
30 min. Subsequently, a solution of (3-methylbut-2-en-1-yl)-
magnesium chloride in tetrahydrofuran (freshly prepared from 1-
chloro-3-methylbut-2-ene (6.66 g, 63.7 mmol) and magnesium
turnings (6.97 g, 287 mmol) in tetrahydrofuran (200 mL)) was
added dropwise at 0 °C within 1.5 h to the reaction mixture. After the
addition was complete, the mixture was warmed to 20 °C and then
stirred at this temperature for 17 h, followed by sequential addition of
a saturated aqueous solution of ammonium chloride (25 mL) and
diethyl ether (25 mL). The resulting solid was filtered off and
discarded, the organic layer was separated, the aqueous layer was
washed with diethyl ether (3 × 25 mL), the combined organic extracts
were dried (Na2SO4), and the solvent was removed under reduced
pressure. The residue was purified by column chromatography on
silica gel (eluent, n-hexane/ethyl acetate (98:2 v/v)) to furnish rac-17
1.4 Hz, 4J(N(E),X) = 1.6 Hz, 5J(A,M(Z)) = 1.1 Hz, J(A,N(E)) = 0.8
5
5
5
Hz, J(B,M(Z)) = 0.8 Hz, J(B,N(E)) = 1.3 Hz, 9 H; CHAHBCHX
C(C(HM(Z))3)C(HN(E))3), 3.610 and 3.612 (AB system, 2J(A,B) = 14.0
Hz, 2 H; CHAHBO), 7.37−7.40 (m, 3 H; H-3/H-4/H-5, C6H5), 7.60−
7.58 (m, 2 H; H-2/H-6, C6H5). 13C NMR (125.8 MHz, CD2Cl2): δ
−6.7 (SiCH3), 14.7 (CH2CHC(CH3)2), 17.7 (CH2CH
C(C(HM(Z))3)(C(HN(E))3)), 25.8 (CH2CHC(C(HM(Z))3)-
(C(HN(E))3)), 54.2 (CH2O), 119.0 (CH2CHC(CH3)2), 128.2 (C-
3/C-5, C6H5), 129.7 (C-4, C6H5), 130.5 (CH2CHC(CH3)2), 134.5
(C-2/C-6, C6H5), 136.6 (C-1, C6H5). 29Si NMR (99.4 MHz, CD2Cl2):
δ −6.5. Anal. Calcd for C13H20OSi: C, 70.85; H, 9.15. Found: C,
70.77; H, 9.34.
1
as a colorless liquid (10.5 g, 44.0 mmol; yield 80%). H NMR (500.1
MHz, CD2Cl2): δ 0.41 (s, 3 H; SiCH3), 1.55 (δM(Z)), 1.70 (δN(E)), 1.82
2
(δA), 1.86 (δB), and 5.18 (δX) (ABM3N3X system, J(A,B) = 14.1 Hz,
3J(A,X) = 8.3 Hz, 3J(B,X) = 8.5 Hz, 4J(M(Z),X) = 1.4 Hz, 4J(N(E),X)
AUTHOR INFORMATION
5
5
5
■
= 1.4 Hz, J(A,M(Z)) = 0.7 Hz, J(A,N(E)) = 1.1 Hz, J(B,M(Z)) =
5
Corresponding Author
*E-mail: r.tacke@uni-wuerzburg.de.
0.7 Hz, J(B,N(E)) = 1.1 Hz, 9 H; CHAHBCHXC(C(H(M(Z))3)C-
2
(HN(E))3), 3.02 (δA) and 3.45 (δB) (AB system, J(A,B) = 13.7 Hz, 2
H; CHAHBCl), 7.37−7.44 (m, 3 H; H-3/H-4/H-5, C6H5), 7.56−7.58
(m, 2 H; H-2/H-6, C6H5). 13C NMR (125.8 MHz, CD2Cl2): δ −6.3
(SiCH3), 14.7 (CH2CHC(CH3)2), 17.8 (CH2CHC(C(HM(Z))3)-
(C(HN(E))3)), 25.8 (CH2CHC(C(HM(Z))3)(C(HN(E))3)), 29.4
(CH2Cl), 118.2 (CH2CHC(CH3)2), 128.2 (C-3/C-5, C6H5),
130.0 (C-4, C6H5), 131.2 (CH2CHC(CH3)2), 134.4 (C-2/C-6,
C6H5), 135.6 (C-1, C6H5). 29Si NMR (99.4 MHz, CD2Cl2): δ −4.1.
Anal. Calcd for C13H19ClSi: C, 65.38; H, 8.02. Found: C, 65.54; H,
8.06.
Notes
The authors declare no competing financial interest.
REFERENCES
■
(1) (a) van der Weerdt, A. J. A.; Plomp, R.; Willem, A. (Inventors;
Naarden International N.V., The Netherlands). Eur. Pat. Appl. EP
0049543 A1; April 14, 1982. (b) Hochstetler, A. R. (Inventor;
Givaudan Corp., NJ, USA). US Pat. 4549029; October 22, 1985.
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2000, 112, 3106−3138; Angew. Chem., Int. Ed. 2000, 39, 2980−3010.
(3) (a) Abate, A.; Brenna, E.; Fronza, G.; Fuganti, C.; Gatti, F. G.;
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A.; Brenna, E.; Fuganti, C.; Gatti, F. G.; Serra, S. Chem. Biodiversity
2004, 1, 1888−1898.
Preparation of rac-(Acetoxymethyl)methyl(3-methylbut-2-
en-1-yl)phenylsilane (rac-18). Compound rac-17 (3.00 g, 12.6
mmol) was added at 20 °C in a single portion to a stirred mixture of
sodium acetate (3.10 g, 37.8 mmol), tetra-n-butylphosphonium
chloride (370 mg, 1.25 mmol), and N,N-dimethylformamide (40
mL). The resulting mixture was heated under reflux for 17 h and was
then cooled to 20 °C. The solvent was removed under reduced
pressure, followed by sequential addition of water (25 mL) and diethyl
ether (25 mL). The organic layer was separated, the aqueous layer was
extracted with diethyl ether (3 × 20 mL) and discarded, the combined
organic extracts were dried (Na2SO4), and the solvent was removed
under reduced pressure. The residue was purified by column
chromatography on silica gel (eluent, n-hexane/ethyl acetate (98:2
v/v)) to furnish rac-18 as a colorless liquid (2.47 g, 9.41 mmol; 75%
(4) Recent publications dealing with silicon-based odorants:
(a) Natscher, J. B.; Laskowski, N.; Kraft, P.; Tacke, R. ChemBioChem
̈
2010, 11, 315−319. (b) Sunderkotter, A.; Lorenzen, S.; Tacke, R.;
̈
Kraft, P. Chem.−Eur. J. 2010, 16, 7404−7421. (c) Geyer, M.; Bauer, J.;
Burschka, C.; Kraft, P.; Tacke, R. Eur. J. Inorg. Chem. 2011, 2769−
2776. (d) Dorrich, S.; Bauer, J. B.; Lorenzen, S.; Mahler, C.;
̈
Schweeberg, S.; Burschka, C.; Baus, J. A.; Tacke, R.; Kraft, P. Chem.−
1
Eur. J. 2013, 19, 11396−11408.
yield). H NMR (500.1 MHz, CD2Cl2): δ 0.35 (s, 3 H; SiCH3), 1.54
(δM(Z)), 1.69 (δN(E)), 1.77 (δA), 1.81 (δB), and 5.18 (δX) (ABM3N3X
(5) Review dealing with silicon-based odorants: Tacke, R.; Metz, S.
Chem. Biodiversity 2008, 5, 920−941.
system, 2J(A,B) = 14.2 Hz, 3J(A,X) = 8.3 Hz, 3J(B,X) = 8.4 Hz,
H
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(6) Coulombel, L.; Rajzmann, M.; Pons, J.-M.; Olivero, S.; Dunach,
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(12) Although the SiCH3 moiety does not contribute to the spin
system of this diastereomer, we have used identical numbering
schemes for the spins of both diastereomers for reasons of comparison.
(13) The silica gel was treated with 25% aqueous ammonia solution
(7% by weight related to the silica gel), and the resulting mixture was
shaken until a homogeneous powder was obtained.
I
dx.doi.org/10.1021/om401070c | Organometallics XXXX, XXX, XXX−XXX