Article pubs.acs.org/Organometallics
Sila-rhubafuran and Derivatives: Synthesis and Olfactory Characterization of Novel Silicon-Containing Odorants Bettina Förster,† Rüdiger Bertermann,† Philip Kraft,‡ and Reinhold Tacke*,† †
Institut für Anorganische Chemie, Universität Würzburg, Am Hubland, D-97074 Würzburg, Germany Givaudan Schweiz AG, Fragrance Research, Ü berlandstrasse 138, CH-8600 Dübendorf, 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.
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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 silarhubafuran (1b), a silicon analogue of 1a. In addition, we have prepared the related C/Si pairs 2a/2b and 3a/3b. Silarhubafuran (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.
Scheme 1. Synthesis of (3SR,5SR)-1b/(3SR,5RS)-1b
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,δunsaturated 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-2phenylpropanal (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
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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) © XXXX American Chemical Society
Received: November 4, 2013
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dx.doi.org/10.1021/om401070c | Organometallics XXXX, XXX, XXX−XXX
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Scheme 2. Synthesis of rac-2a
[(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-methylpropionitrile) (AIBN), finally afforded the target compound rac-2b in 42% yield. 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-2phenylpent-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-2phenylhex-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 rac3a in 43% yield. 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)magnesium 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 3. Synthesis of rac-2b
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(2methylprop-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 chlorophenylselane,7 in the presence of triethylamine, furnished a 1:1 mixture of (3SR,5SR)- and (3SR,5RS)-3,5-dimethyl-3-phenyl-5B
dx.doi.org/10.1021/om401070c | Organometallics XXXX, XXX, XXX−XXX
Organometallics
Article
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 compound (3SR/5SR)-1a/ (3SR/5RS)-1aa (3SR/5SR)-1b/ (3SR/5RS)-1ba rac-2a rac-2b rac-3a rac-3b a
odor threshold value [ng L−1 air]
olfactory properties intense rhubarb and citrus character, with a green eucalyptus heart
0.68
green-fruity, fatty odor, with bergamot and linalyl acetate connotation and grapefruit as well as cassis facets in front of a floralpowdery, magnolan-type background intense citrus and grapefruit odor, pleasant bloomy and honey-like 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) green, bitter citrus-grapefruit-type odor, with slightly animalic and slightly dry, woody facets
18.1 11.8 7.58 18.9 2.50
Studied as a 1:1 mixture.
agrestic (i.e., “rural-Provençal” 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-2ene). 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 silaanalogue 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-trimethyl1,2,3,4,4a,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.
sodium acetate, in the presence of tetra-n-butylphosphonium chloride, furnished rac-(acetoxymethyl)methyl(3-methylbut-2en-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 3silatetrahydropyran 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, rac2b, 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 silarhubafuran (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 greenminty 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
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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, silarhubafuran (1b) and its derivatives 2b and 3b represent the first silicon-based grapefruit odorants. For the construction of the 3silatetrahydrofuran skeleton of 1b and the 3-silatetrahydropyran skeleton of 3b, a new synthetic method has been used, an aluminum(III) trifluoromethane sulfonate-catalyzed intramolecular 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 unlikeenantiomers (2R,4S)-1a and (2S,4R)-1a to represent the odor C
dx.doi.org/10.1021/om401070c | Organometallics XXXX, XXX, XXX−XXX
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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 etheroxygen 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.
Article
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 of the 1H NMR spectroscopic data were supported by 1H,1H COSY, 13 1 C, H HMQC, 13C,1H HMBC, and 29Si,1H HMQC (optimized for 2 J(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)-3,5Dimethyl-3-phenyl-3-silatetrahydrofuran ((3SR,5SR)-1b/ (3SR,5RS)-1b; Sila-rhubafuran). Aluminum(III) trifluoromethanesulfonate (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). 1 H NMR (500.1 MHz, CD2Cl2; data for two diastereomers (molar 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) = 14.4 Hz, 2J(X,Y) = 13.6 Hz, 3J(F,Z) = 10.3 Hz, 3J(M,Z) = 5.1 Hz, 3 J(N,Z) = 6.0 Hz, 4J(F,Y) = 0.4 Hz, 4J(M,Y) = 0.3 Hz, 4J(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 system, 2J(M,F) = 14.4 Hz, 2J(X,Y) = 13.7 Hz, 3J(F,Z) = 10.1 Hz, 3 J(M,Z) = 5.2 Hz, 3J(N,Z) = 6.0 Hz, 4J(A,X) = 0.5 Hz, 4J(F,Y) = 0.4 Hz, 4J(M,Y) = 0.3 Hz, 4J(Y,Z) = 0.6 Hz, 11 H; C(HA)3SiCHXHYOCHZ(C(HN)3)CHFHM), 7.38−7.42 (m, 6 H; H3/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
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 enlargement to be powerful tools for odorant design by fine-tuning molecular geometries. D
dx.doi.org/10.1021/om401070c | Organometallics XXXX, XXX, XXX−XXX
Organometallics
Article
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. 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 (691 mg, 3.63 mmol; 46% yield). 1H 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, 2 J(M,N) = 12.6 Hz, 2J(X,Y) = 8.6 Hz, 4J(A,N) = 0.6 Hz, 4J(A,Y) = 0.6 Hz, 4J(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 (CH 3 C(C 6 H 5 )), 52.8 (C(CH 3 ) 2 CH 2 ), 77.2 (CH 2 O), 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. Preparation of rac-3,5,5-Trimethyl-3-phenyl-3-silatetrahydrofuran (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 trin-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, 4.07 mmol; 42% yield). 1H 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; C(CH3)CH3), 3.49 (δA) and 3.58 (δB) (AB system, 2J(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). 29 Si 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-phenyltetrahydropyran (rac-3a). Aluminum(III) trifluoromethanesulfonate (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
system, 2J(A,B) = 13.6 Hz, 2J(M,N) = 13.6 Hz, 2J(X,Y) = 11.9 Hz, 3 J(A,M) = 8.3 Hz, 3J(A,N) = 4.3 Hz, 3J(B,M) = 4.1 Hz, 3J(B,N) = 8.8 Hz, 4J(M,X) = 1.3 Hz, 4J(N,Y) = 1.4 Hz, 6 H; 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). 13 C NMR (125.8 MHz, CD2Cl2): δ 25.9 (CH3C(C6H5)), 26.2 (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-silatetrahydropyran (rac-3b). Aluminum(III) trifluoromethanesulfonate (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% yield). 1H NMR (500.1 MHz, CD2Cl2): δ 0.37 (s, 3 H; SiCH3), 0.92 (δA), 1.07 (δB), 1.77 (δM), 1.79 (δN), 3.50 (δX), and 3.63 (δY) (ABMNXY system, 2J(A,B) = 14.9 Hz, 2J(M,N) = 14.2 Hz, 2J(X,Y) = 15.2 Hz, 3J(A,M) = 4.3 Hz, 3J(A,N) = 9.0 Hz, 3J(B,M) = 9.9 Hz, 3 J(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-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 CH2CHCH2MgCl) 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% yield). 1H 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, 3 J(B,X) = 8.1 Hz, 3J(M(E),X) = 10.1 Hz, 3J(N(Z),X) = 17.0 Hz, 4 J(A,M(E)) = 1.0 Hz, 4J(A,N(Z)) = 1.4 Hz, 4J(B,M(E)) = 1.0 Hz, 4 J(B,N(Z)) = 1.4 Hz, 5 H; CHAHBCHXCHM(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 (CH2CHCH2), 28.7 (CH2Cl), 114.8 (CH2CHCH2), 128.1 (C-3/ C-5, C6H5), 130.0 (C-4, C6H5), 133.3 (CH2CHCH2), 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. 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-dimethylformamide (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, 31.2 mmol; 92% yield). 1H 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 (δX) (ABMNX system, 2J(A,B) = 12.6 Hz, 2J(M(E),N(Z)) = 2.1 Hz, 3 J(A,X) = 8.0 Hz, 3J(B,X) = 8.1 Hz, 3J(M(E),X) = 10.1 Hz, 3 J(N(Z),X) = 17.0 Hz, 4J(A,M(E)) = 1.0 Hz, 4J(A,N(Z)) = 1.4 Hz, 4 J(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 (CH2CHCH2), 20.9 (C(O)CH3), 55.4 (CH2O), 114.4 (CH2CHCH2), 128.2 (C-3/C-5, C6H5), 130.0 (C-4, C6H5), 134.0 (CH2CHCH2), 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. 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 bulbto-bulb distillation (oven temperature 100 °C, 0.03 mbar) to furnish rac-7 as a colorless liquid (3.89 g, 20.2 mmol; 79% yield). 1H 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, 3 J(A,X) = 8.0 Hz, 3J(B,X) = 8.1 Hz, 3J(M(E),X) = 10.1 Hz, 3 J(N(Z),X) = 17.0 Hz, 4J(A,M(E)) = 1.0 Hz, 4J(A,N(Z)) = 1.4 Hz, 4 J(B,M(E)) = 1.0 Hz, 4J(B,N(Z)) = 1.4 Hz, 5 H; CHAHBCHX CHM(E)HN(Z)), 3.639 and 3.641 (AB system, 2J(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 (CH2CHCH2), 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 (CH2CHCH2), 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 (rac9). A mixture of rac-8 (3.00 g, 22.4 mmol) and 3-chloro-2-methylprop1-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
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), 4.68 (δX(Z)), and 4.86 (δY(E)) (ABF3XY system, 2J(A,B) = 13.9 Hz, 2 J(X(Z),Y(E)) = 2.2 Hz, 4J(A,X(Z)) = 0.9 Hz, 4J(B,X(Z)) = 1.0 Hz, 4 J(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, 2 J(A,B) = 13.5 Hz, 2J(X(Z),Y(E)) = 2.5 Hz, 4J(A,X(Z)) = 0.9 Hz, 4 J(B,X(Z)) = 1.1 Hz, 4J(B,F) = 0.3 Hz, 4J(F,X(Z)) = 0.9 Hz, 4 J(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): δ 21.9 (CH 3 C(C 6 H 5 )), 24.6 (CH 2 C(CH 3 )CH 2 ), 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. Preparation of rac-(Chloromethyl)methyl(2-methylprop-2en-1-yl)phenylsilane (rac-11). A 1.8 M solution of phenylmagnesium 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-2methylprop-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, 2 J(X(Z),Y(E)) = 2.2 Hz, 4J(A,X(Z)) = 1.1 Hz, 4J(B,X(Z)) = 1.0 Hz, 4 J(F,X(Z)) = 0.8 Hz, 4J(F,Y(E)) = 1.5 Hz, 7 H; CHAHBC(C(HF)3) CHX(Z)HY(E)), 3.065 (δA) and 3.08 (δB) (AB system, 2J(A,B) = 13.7 F
dx.doi.org/10.1021/om401070c | Organometallics XXXX, XXX, XXX−XXX
Organometallics
Article
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. Preparation of rac-(Acetoxymethyl)methyl(2-methylprop-2en-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% yield). 1H 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 system, 2J(A,B) = 13.7 Hz, 2J(X(Z),Y(E)) = 2.3 Hz, 4J(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 (δA) and 4.03 (δB) (AB system, 2J(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-(Hydroxymethyl)methyl(2-methylprop-2en-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, 2 J(A,B) = 13.5 Hz, 2J(X(Z),Y(E)) = 2.3 Hz, 4J(A,X(Z)) = 1.1 Hz, 4 J(B,X(Z)) = 1.0 Hz, 4J(F,X(Z)) = 0.8 Hz, 4J(F,Y(E)) = 1.4 Hz, 7 H; 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)-3,5Dimethyl-3-phenyl-5-[(phenylseleno)methyl]-3-silatetrahydrofuran ((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
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/ (3SR,5RS)-14 as a yellow liquid (2.20 g, 6.09 mmol; 63% yield). 1H 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 3.69 (δB) (AB system, 2J(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. Preparation of rac-2,5-Dimethyl-2-phenylhex-4-enal (rac15). 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 chromatography 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 colorless liquid (2.61 g, 12.9 mmol; 68%). 1H NMR (500.1 MHz, C6D6): δ 1.36 (s, 3 H; CH3C(C6H5)), 1.49 (δM(Z)), 1.61 (δN(E)), 2.66 (δA), 2.67 (δB), and 5.11 (δX) (ABM3N3X system, 2J(A,B) = 14.7 Hz, 3 J(A,X) = 7.4 Hz, 3J(B,X) = 7.5 Hz, 4J(M(Z),X) = 1.4 Hz, 4J(N(E),X) = 1.5 Hz, 5J(A,M(Z)) = 0.6 Hz, 5J(A,N(E)) = 1.1 Hz, 5J(B,M(Z)) = 0.8 Hz, 5J(B,N(E)) = 1.3 Hz, 9 H; CHAHBCHXC(C(HN(E))3)C(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 (CH2CHC(C(HM(Z))3)(C(HN(E))3)), 19.1 (CH3C(C 6 H 5 )), 25.8 (CH 2 CHC(C(H M(Z) ) 3 )(C(H N(E) ) 3 )), 34.9 (CH2CHC(CH3)2), 54.4 (CH3C(C6H5)), 119.4 (CH 2CH 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 (CH2CHC(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. Preparation of rac-2,5-Dimethyl-2-phenylhex-4-en-1-ol (rac16). 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
a colorless liquid (1.80 g, 8.81 mmol; 76% yield). 1H NMR (500.1 MHz, C6D6): δ 0.95 (δX), 3.56 (δA), and 3.66 (δB) (ABX system, 2 J(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, 4 J(N(E),X) = 1.5 Hz, 5J(A,M(Z)) = 0.6 Hz, 5J(A,N(E)) = 1.1 Hz, 5 J(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 (CH2CHC(C(HM(Z))3)(C(HN(E))3), 22.1 (CH3C(C6H5)), 25.9 (CH2CHC(C(HM(Z))3)(C(HN(E))3)), 37.0 (CH2CHC(CH3)2), 44.0 (CH3C(C6H5)), 71.7 (CH2O), 120.9 (CH2CHC(CH3)2), 126.2 (C-4, C6H5), 127.1 (C-2/ C-6, C6H5), 128.3 (C-3/C-5, C6H5), 133.3 (CH2CHC(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-(Chloromethyl)methyl(3-methylbut-2en-1-yl)phenylsilane (rac-17). A 1.8 M solution of phenylmagnesium 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 1chloro-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 as a colorless liquid (10.5 g, 44.0 mmol; yield 80%). 1H NMR (500.1 MHz, CD2Cl2): δ 0.41 (s, 3 H; SiCH3), 1.55 (δM(Z)), 1.70 (δN(E)), 1.82 (δA), 1.86 (δB), and 5.18 (δX) (ABM3N3X system, 2J(A,B) = 14.1 Hz, 3 J(A,X) = 8.3 Hz, 3J(B,X) = 8.5 Hz, 4J(M(Z),X) = 1.4 Hz, 4J(N(E),X) = 1.4 Hz, 5J(A,M(Z)) = 0.7 Hz, 5J(A,N(E)) = 1.1 Hz, 5J(B,M(Z)) = 0.7 Hz, 5J(B,N(E)) = 1.1 Hz, 9 H; CHAHBCHXC(C(H(M(Z))3)C(HN(E))3), 3.02 (δA) and 3.45 (δB) (AB system, 2J(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 (CH2CHC(CH3)2), 17.8 (CH2CHC(C(HM(Z))3)(C(HN(E))3)), 25.8 (CH2CHC(C(HM(Z))3)(C(HN(E))3)), 29.4 (CH2Cl), 118.2 (CH2CHC(CH3)2), 128.2 (C-3/C-5, C6H5), 130.0 (C-4, C6H5), 131.2 (CH2CHC(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. Preparation of rac-(Acetoxymethyl)methyl(3-methylbut-2en-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% yield). 1H 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 system, 2J(A,B) = 14.2 Hz, 3J(A,X) = 8.3 Hz, 3J(B,X) = 8.4 Hz,
4
J(M(Z),X) = 1.4 Hz, 4J(N(E),X) = 1.5 Hz, 5J(A,M(Z)) = 0.8 Hz, J(A,N(E)) = 0.8 Hz, 5J(B,M(Z)) = 0.8 Hz, 5J(B,N(E)) = 1.2 Hz, 9 H; CHAHBCHXC(C(HM(Z))3)C(HN(E))3), 2.00 (s, 3 H; C(O)CH3), 3.988 and 3.990 (AB system, 2J(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 (CH2CHC(CH3)2), 17.7 (CH2CHC(C(HM(Z))3)(C(HN(E))3)), 20.9 (C(O)CH3), 25.8 (CH2CHC(C(HM(Z))3)(C(HN(E))3)), 55.6 (CH2O), 118.4 (CH2CHC(CH3)2), 128.2 (C-3/C-5, C6H5), 129.8 (C-4, C6H5), 130.8 (CH2CHC(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. Preparation of rac-(Hydroxymethyl)methyl(3-methylbut-2en-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, 2 J(A,B) = 14.2 Hz, 3J(A,X) = 8.4 Hz, 3J(B,X) = 8.5 Hz, 4J(M(Z),X) = 1.4 Hz, 4J(N(E),X) = 1.6 Hz, 5J(A,M(Z)) = 1.1 Hz, 5J(A,N(E)) = 0.8 Hz, 5J(B,M(Z)) = 0.8 Hz, 5J(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 (SiCH 3 ), 14.7 (CH 2 CHC(CH 3 ) 2 ), 17.7 (CH 2 CH C(C(H M(Z) ) 3 )(C(H N(E) ) 3 )), 25.8 (CH 2 CHC(C(H M(Z) ) 3 )(C(HN(E))3)), 54.2 (CH2O), 119.0 (CH2CHC(CH3)2), 128.2 (C3/C-5, C6H5), 129.7 (C-4, C6H5), 130.5 (CH2CHC(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. 5
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[email protected]. Notes
The authors declare no competing financial interest.
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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. (2) Kraft, P.; Bajgrowicz, J. A.; Denis, C.; Frater, G. Angew. Chem. 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.; Serra, S.; Zardoni, E. Helv. Chim. Acta 2004, 87, 765−780. (b) Abate, A.; Brenna, E.; Fuganti, C.; Gatti, F. G.; Serra, S. Chem. Biodiversity 2004, 1, 1888−1898. (4) Recent publications dealing with silicon-based odorants: (a) Nätscher, J. B.; Laskowski, N.; Kraft, P.; Tacke, R. ChemBioChem 2010, 11, 315−319. (b) Sunderkötter, 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) Dörrich, S.; Bauer, J. B.; Lorenzen, S.; Mahler, C.; Schweeberg, S.; Burschka, C.; Baus, J. A.; Tacke, R.; Kraft, P. Chem.− Eur. J. 2013, 19, 11396−11408. (5) Review dealing with silicon-based odorants: Tacke, R.; Metz, S. Chem. Biodiversity 2008, 5, 920−941.
H
dx.doi.org/10.1021/om401070c | Organometallics XXXX, XXX, XXX−XXX
Organometallics
Article
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dx.doi.org/10.1021/om401070c | Organometallics XXXX, XXX, XXX−XXX
