Synthesis and Olfactory Characterization of Sila-Methyl

Article pubs.acs.org/Organometallics

Synthesis and Olfactory Characterization of Sila-Methyl Pamplemousse and Related Odorants with a 2,2,5-Trimethyl-2silahex-4-ene Skeleton Julian Friedrich,† Steffen Dörrich,† André Berkefeld,† Philip Kraft,‡ and Reinhold Tacke*,† †

Institut für Anorganische Chemie, Universität Würzburg, Am Hubland, D-97074 Würzburg, Germany Fragrance Research, Givaudan Schweiz AG, Ü berlandstrasse 138, CH-8600 Dübendorf, Switzerland

‡

ABSTRACT: The synthetic grapefruit odorant methyl pamplemousse (1a) has lately become an important trend odorant, and the related 2,2,5-trimethylhex-4-enes 2a−4a also possess interesting olfactory properties of fresh hesperidic and fruity-agrestic character. On the basis of the carbon/silicon switch strategy, the silicon-containing analogues silamethyl pamplemousse (1b) and 2b−4b were synthesized and studied for their olfactory properties (olfactory evaluation of the C/Si pairs 1a/1b−4a/4b). Sila substitution (C/Si exchange) was demonstrated to affect the olfactory properties substantially. The C/Si analogues 1a and 1b were found to be genuine grapefruit odorants, with the silicon compound 1b showing additional agrestic facets. As a proof of principle, it was demonstrated that C/Si analogues can display a different mechanism and rate of degradation (degradation studies with 1a and 1b under acidic conditions).

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INTRODUCTION Citrus notes, referred to in perfumery as hesperidic notes, are indispensable for the creation of fresh and radiant top notes.1 They comprise the essential oils of sweet and bitter oranges, mandarin, lemon, grapefruit, bergamot, lime, and most recently also yuzu fruit, which are commonly produced by cold pressing of the peeling waste of the foodstuff and beverage industry.2 Thus, they are relatively inexpensive as compared to essential oils of plants exclusively cultivated for the perfumery use. Their use is by far not limited to Eaux de Cologne themes or perfumes with prominent citrus character. They are in fact extensively employed across all fragrance families to provide freshness and lift, even if a hesperidic character per se is not desired. As the odor character in the hesperidic family is somewhat limited to the mentioned commercial citrus fruits, there is a high demand for alternative synthetic hesperidic odorants. Since the pricing pressure of the oils produced from peeling waste is high, only very few synthetic hesperidic odorants have been introduced to perfumery so far. Methyl pamplemousse (1a),3 also known as amarocit, pomelocite, or grapefruit acetal, is probably the most successful citrus odorant. It possesses a fresh hesperidic-floral grapefruit peel odor with slightly bitter and woody accents and has lately become a real trendsetter in perfumery. While 1−1.5% is rather commonly used, as for instance in “Amor Amor” (Cacharel, 2003; 1.5% of 1a) by Laurent Bruyere and Dominique Ropion, “Un Jardin sur le Nil” (Hermès, 2005; 1.3%) by Jean-Claude Ellena, “Unforgivable” (Sean John, 2006; 1%) by David Apel, Pierre Negrin, Aurelian Guichard, and Caroline Sabas, and “Bleu de Chanel” (Chanel, 2010; 1%) by Jacques Polge, we have even seen dosages of 2.9% of 1a in “Terre d’Hermès” (Hermès, 2006) by Jean-Claude Ellena, 3.8% in “CH Sport Men” (Carolina Herrera, 2012), 7.4% in “Good Life” (Davidoff, 1998) by Pierre Bourdon, and even 7.7% of 1a in “Cologne © 2014 American Chemical Society

Bigarade” (Frederic Malle, 2001) again by Jean-Claude Ellena. It is therefore not surprising that related alcohols, formats, and acetates, such as compounds 2a−4a, were also investigated and indeed were found to also display interesting olfactory properties, mainly of fresh hesperidic, fruity-agrestic odor quality.4 Agrestic, derived from the French “agreste” (meaning “bucolic”, “rural”) is an odor classification combining the common olfactory attributes of French Provençal herbs such as rosemary, lavender, and thyme.

In continuation of our systematic studies on silicon-based odorants,5,6 we have synthesized the silicon analogues of 1a− 4a, compounds 1b−4b, and have studied their olfactory properties. In a previous study on the synthesis and olfactory characterization of sila-rhubafuran and derivatives,5n we have found that gem-dimethyl-substituted systems display a methyl Received: December 9, 2013 Published: January 24, 2014 796

dx.doi.org/10.1021/om401181h | Organometallics 2014, 33, 796−803

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pamplemousse character rather than a rhubarb-citrus note and that this fresh hesperidic-floral grapefruit peel character was indeed intensified upon sila-substitution. As this could be due to the elongation of the molecule by sila-substitution and consequently to the different distance between the hydrophobic tail and the osmophoric ether oxygen atom, it seemed interesting to study silicon-containing derivatives of methyl pamplemousse (1a). We report here on the preparation of 2a− 4a (syntheses developed on the basis of the patent literature)4 and 1b−4b and the olfactory characterization of the C/Si pairs 1a/1b−4a/4b. In addition, we report on the stability of the C/ Si analogues 1a and 1b under acidic conditions.

Scheme 2. Synthesis of 2a−4a

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RESULTS AND DISCUSSION Syntheses. Sila-methyl pamplemousse (1b) was synthesized according to Scheme 1, starting from (chloromethyl)Scheme 1. Synthesis of Sila-Methyl Pamplemousse (1b) Scheme 3. Synthesis of 2b−4b

trimethoxysilane (5). Thus, treatment of 5 with sodium methoxide furnished trimethoxy(methoxymethyl)silane (6; 87% yield), which upon bromination with N-bromosuccinimde (NBS), in the presence of 2,2′-azobis(isobutyronitrile) (AIBN), afforded (bromo(methoxy)methyl)trimethoxysilane (7; 38% yield). Subsequent reaction of 7 with methanol, in the presence of triethylamine, furnished (dimethoxymethyl)trimethoxysilane (8). To increase the yield of 8, this compound was prepared from 6 in a one-pot synthesis (60% yield), without isolation of the intermediate 7. Sequential treatment of 8 with (3methylbut-2-en-1-yl)magnesium chloride and methylmagnesium bromide finally afforded (dimethoxymethyl)dimethyl(3methylbut-2-en-1-yl)silane (sila-methyl pamplemousse, 1b; 42% yield). The carbon compounds 2a−4a were synthesized according to Scheme 2, starting from methyl isobutyrate (9). Thus, deprotonation of 9 with lithium diisopropylamide (LDA) and subsequent reaction with 1-bromo-3-methylbut-2-ene afforded methyl 2,2,5-trimethylhex-4-enoate (10; 89% yield), which upon reduction with lithium aluminum hydride and subsequent aqueous workup furnished 2,2,5-trimethylhex-4-en-1-ol (2a; 86% yield). Reaction of 2a with formic acid, in the presence of sodium sulfate, afforded 2,2,5-trimethylhex-4-en-1-yl formate (3a; 83% yield), and treatment of 2a with acetic anhydride and sodium acetate furnished 2,2,5-trimethylhex-4-en-1-yl acetate (4a; 77% yield). The silicon compounds 2b−4b were synthesized according to Scheme 3, starting from chloro(chloromethyl)dimethylsilane

(11). Thus, treatment of 11 with (3-methylbut-2-en-1-yl)magnesium chloride afforded (chloromethyl)dimethyl(3-methylbut-2-en-1-yl)silane (12; 84% yield), which upon reaction with sodium formate, in the presence of tetra-n-butylphosphonium chloride, furnished (formyloxymethyl)dimethyl(3-methylbut-2-en-1-yl)silane (3b; 65% yield). The analogous reaction of 12 with sodium acetate, in the presence of tetra-nbutylphosphonium chloride, afforded (acetoxymethyl)dimethyl(3-methylbut-2-en-1-yl)silane (4b; 76% yield), which upon reduction with lithium aluminum hydride and subsequent aqueous workup furnished (hydroxymethyl)dimethyl(3-methylbut-2-en-1-yl)silane (2b; 91% yield). For reasons of comparison (see Stability Studies), we have also synthesized the silanol 13 according to Scheme 4, starting from dimethoxydimethylsilane (14) (Scheme 4). Thus, treatment of 14 with (3-methylbut-2-en-1-yl)magnesium chloride afforded methoxydimethyl(3-methylbut-2-en-1-yl)silane (15; 92% yield), which upon reaction with lithium aluminum hydride furnished dimethyl(3-methylbut-2-en-1-yl)silane (16; 82% yield). Treatment of 16 with potassium hydroxide and 797


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spectroscopy).7 The silicon compound 1b was found to decompose somewhat faster (Figure 1); however, in this case the formation of a product mixture was observed that did not contain the analogous aldehyde 17b. One of the degradation products was identified to be the silanol 13 (Si−C bond cleavage), the identity of which was established by NMR spectroscopic studies (comparison with an authentic sample synthesized according to Scheme 4). The formation of 13 can be explained by a two-step process involving an acetal cleavage to give the formylsilane 17b and its subsequent spontaneous decomposition to form the silanol 13 (formylsilanes are known to be very reactive).8,9 Although the experimental conditions in these studies do not reflect typical environmental conditions, the results obtained demonstrate that the carbon/silicon switch strategy in certain cases may have some potential to affect both the mechanism and the rate of odorant degradation.

Scheme 4. Synthesis of 13

water finally afforded dimethyl(3-methylbut-2-en-1-yl)silanol (13; 79% yield). Compounds 1b−4b, 2a−4a, 6−8, 10, 12, 13, 15, and 16 were isolated as colorless liquids. Their identities were established by elemental analyses (C, H) and NMR spectroscopic studies (1H, 13C, 29Si). Stability Studies. The bioaccumulation of odorants in the environment is an increasingly important issue in the fragrance industry. In this context, the carbon/silicon switch strategy may offer interesting possibilities to affect the chemical stability of a given odorant by creating reactive silicon−element bonds. As a proof of principle, we have studied the chemical stability of the C/Si analogues 1a and 1b under acidic conditions. For this purpose, the decomposition kinetics of these compounds were investigated at 23 °C in an acidic mixture of CD3CN and D2O (5/1 v/v) using DCl as the proton source and 1H NMR spectroscopy as the analytical tool. Compounds 1a and 1b were found to be stable at pD 4−7; however, under more acidic conditions degradation was observed. As can be seen from Figure 1, at pD 2.5 the carbon compound 1a decomposes completely within ca. 400 min to give the corresponding aldehyde 17a (identity established by NMR

Olfactory Studies. The C/Si pairs 1a/1b−4a/4b were evaluated for their olfactory properties (Table 1). While there Table 1. Olfactory Properties of Compounds 1a−4a, 1b−4b, and 13 compound 1a 1b 2a 2b 3a 3b 4a 4b 1310

olfactory properties fresh, citrusy, hesperidic-floral grapefruit peel odor, with slightly bitter and woody accents agrestic grapefruit odor, reminiscent of methyl pamplemousse (1a) fatty, oily, weak, with a slightly citrusy connotation in the direction of limonene floral-green odor, with a slightly technical character fruity, fatty-metallic odor of aldehydic tonality, in the direction of grapefruit peel, with slightly sweet, floral facets floral-fruity, rosy odor, recalling geranyl (sweet, rosy, lavender) and citronellyl acetate (rose, geranium) fruity-agrestic odor, slightly reminiscent of linalyl acetate (bergamot, lavender), with green-fatty, slightly straw-type facets natural lavender-type odor, recalling linalyl acetate and bergamot oil, with slightly sweet, floral facets floral, agrestic-herbaceous odor in the direction of linalool, with a slightly dull aquatic aspect

odor threshold (ng L−1 air) 18 24 330 126 151 199 181 250 62

are slightly bitter and woody accents in the olfactory profile of methyl pamplemousse (1a), the odor of the silicon analogue 1b is very clean and fresh, hesperidic-floral, and typically reminiscent of grapefruit peel. The odor threshold for 1a (18 ng L−1 air) is not outstanding, but the low molecular mass and an accordingly high vapor pressure compensate for that. The odor threshold for the silicon analogue 1b (24 ng L−1 air) is comparable to that of 1a, but on blotter it appears weaker due to its lower volatility. The odor character of sila-methyl pamplemousse (1b) is clearly reminiscent of methyl pamplemousse (1a) but has distinct agrestic facets. Though not very pronounced, the Provençal herbaceous facets

Figure 1. (a) Kinetics of the decomposition of compounds 1a (El = C (▲)) and 1b (El = Si (●)) in CD3CN/D2O (5/1 v/v) at 23 °C: [1a] = [1b] = 0.1 mol L−1; [DCl] = 1 × 10−3 mol L−1; pD value 2.5. (b) Determination of the kexp values as the gradient of the linear functions. 798


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odor into the agrestic or floral-fruity rosy odor direction. However, the molecular dimensions of the compounds studied seem of equal importance as the functional groups, by which they bind to the receptor. Already the slight change in the molecular dimensions from methyl pamplemousse (1a) to its silicon analogue 1b introduces agrestic facets, once again indicating that the carbon/silicon switch strategy is a powerful tool for the evaluation of structure−odor relationships. However, further close analogues of methyl pamplemousse (1a) with low odor thresholds will be necessary to gain insight into the molecular parameters that control the hesperidic grapefruit note of 1a. Silanol 13 also constitutes an agresticherbaceous odorant, with floral facets in the direction of linalool but significantly weaker. As a proof of principle, we have also demonstrated for methyl pamplemousse (1a) and sila-methyl pamplemousse (1b) that C/Si analogues can display a different mechanism and rate of degradation.

accompany the grapefruit note of 1b and thereby make it less clean and less desirable from a perfumery point of view. In terms of the odor threshold, compounds 2a−4a and 2b− 4b were found to be significantly weaker than methyl pamplemousse (1a) and its silicon analogue 1b, roughly by about a factor of 10. With 330 ng L−1 air, compound 2a had the highest odor threshold of the compounds investigated and was also weak on the blotter. The character was only fatty oily, with a slightly citrusy connotation in the direction of limonene. The silicon analogue 2b (odor threshold 126 ng L−1 air) was stronger in smell and possessed a floral-green odor, with a slightly technical, solvent-like character. Citrus or grapefruit facets were absent. Compound 3a (odor threshold 151 ng L−1 air) was comparable in intensity but possessed a fruity, fatty-metallic odor of aldehydic character, with slightly sweet-floral facets recalling grapefruit peel. The corresponding silicon analogue 3b (odor threshold 199 ng L−1 air) was slightly weaker yet had no reminiscence to grapefruit. Instead, it smelled floral-fruity with a distinct rose note and had some agrestic facets, again recalling the sweet rosy, lavender scent of geranyl acetate and the rosegeranium note of citronellyl acetate. The C/Si analogues 4a and 4b strongly inclined toward the agrestic side, with the parent carbon compound 4a smelling fruity-agrestic, with some slight reminiscence to the bergamotlavender odor of linalyl acetate, and having green-fatty, slightly straw-type facets. The silicon analogue 4b possessed a natural, lavender-type odor that recalls bergamot oil and linalyl acetate, with slightly sweet and floral facets, and so has to be considered as completely belonging to the agrestic family. However, with an odor threshold of 250 ng L−1 air, the silicon compound 4b is not powerful enough to be of use in perfumery. The same is true for the carbon analogue 4a (odor threshold 181 ng L−1 air), but here the odor profile is not uniform enough, and the green-fatty facets are undesirable. Despite the grapefruit facets of compound 3a, only the C/Si analogues 1a and 1b can be considered as genuine grapefruit odorants. Silanol 13 as well has no grapefruit character but constitutes an agrestic-herbaceous odorant with floral facets in the direction of linalool, accompanied by a slightly dull aquatic aspect. Although, with an odor threshold of 62.0 ng L−1 air, silanol 13 is significantly stronger than compounds 2a−4b, it is still weak for this odor family, much weaker for instance than linalool. In conclusion, sila-substitution of the grapefruit odorant methyl pamplemousse (1a → 1b) shifts the odor to an agrestic, herbaceous tonality. In the case of the alcohol 2a, carbon/ silicon exchange (→2b) induces a floral-green character, while sila-substitution of the formate 3a (→3b) introduces a rosyagrestic note. The acetate 4a is already agrestic, but this note is further pronounced upon carbon/silicon exchange (→4b).

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EXPERIMENTAL SECTION

General. All syntheses in organic solvents were carried out under dry argon. The organic solvents used were dried and purified according to standard procedures and stored under dry argon. Starting materials and reagents were purchased from ABCR, Acros, or Aldrich and were used without further purification. Bulb-to-bulb distillations were accomplished by using a Büchi GKR-50 Glass Oven apparatus. The 1H, 13C, and 29Si NMR spectra were recorded at 23 °C on a Bruker DRX-300 (1H, 300.1 MHz; 13C, 75.5 MHz; 29Si, 59.6 MHz) or a Bruker Avance 500 NMR spectrometer (1H, 500.1 MHz; 13C, 125.8 MHz; 29Si, 99.4 MHz) using C6D6 as the solvent. Chemical shifts (ppm) were determined relative to internal C6HD5 (1H, δ 7.28 ppm), internal C6D6 (13C, δ 128.0 ppm), or external TMS (29Si, δ 0 ppm). Analysis and assignment of the 1H and 13C NMR spectroscopic data was supported by 1H,1H gradient selected COSY along with 13C,1H gradient selected HMQC and HMBC experiments. Assignment of the 13 C NMR spectroscopic data was additionally supported by DEPT 135 experiments. The spin systems were analyzed by using the WINDAISY software package (version 4.05, Bruker).11 Coupling constants are given as their absolute values. Elemental analyses were performed by using a VarioMicro apparatus (Elementar Analysensysteme GmbH) or a EURO EA Elemental Analyzer (EuroVector). 1,1-Dimethoxy-2,2,5-trimethyl-4-hexene (Methyl Pamplemousse, 1a). This compound was commercially available. Synthesis of (Dimethoxymethyl)dimethyl(3-methylbut-2en-1-yl)silane (Sila-Methyl Pamplemousse, 1b). A solution of 1-chloro-3-methylbut-2-ene (3.02 g, 28.9 mmol) in tetrahydrofuran (70 mL) was added dropwise at −30 °C within 2 h to a stirred suspension of magnesium turnings (2.87 g, 118 mmol) in tetrahydrofuran (10 mL). The mixture was warmed to 0 °C, stirred at this temperature for 1 h, and then added dropwise at −20 °C within 1.5 h to a stirred solution of 8 (5.53 g, 28.2 mmol) in tetrahydrofuran (40 mL). The resulting mixture was warmed to 20 °C and stirred at this temperature for 16 h, followed by dropwise addition of a 3 M solution of methylmagnesium bromide in diethyl ether (30 mL, 90 mmol of MeMgBr) at 20 °C within 30 min. The resulting mixture was stirred for a further 30 min, water (50 mL) was added, the organic phase was separated, the aqueous phase was extracted with diethyl ether (3 × 50 mL) and discarded, and the combined organic solutions were dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by 3-fold column chromatography on silica gel (35−70 μm; eluent, n-hexane/ethyl acetate (98/2 v/v)) to furnish 1b (2.39 g, 11.8 mmol; 42% yield) as a colorless liquid. 1H NMR (500.1 MHz, C6D6): δ 0.28 (s, 6 H; Si(CH3)2), 1.69 (δA(Z)), 1.75 (δM), 1.83 (δF(E)), and 5.41 (δX) (A3F3M2X system, 3JMX = 8.5 Hz, 4JA(Z)F(E) = 0.4 Hz, 4JA(Z)X = 1.4 Hz, 4 JF(E)X = 1.4 Hz, 5JA(Z)M = 0.7 Hz, 5JF(E)M = 1.1 Hz, 9 H; C(HM)2CHXC(C(HA(Z))3)C(HF(E))3), 3.39 (s, 6 H; OCH3), 4.36 ppm (s, 1 H; SiCH). 13C NMR (125.8 MHz, C6D6): δ −5.0 (Si(CH3)2), 15.7 (CH2CHC), 17.7 (CHCC(Z)), 25.9 (CH

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CONCLUSION Only the C/Si analogues 1a and 1b possess a typical fresh, citrusy hesperidic-floral grapefruit peel odor, and already the silicon compound 1b shows additional agrestic facets. In the case of the formate 3a, the grapefruit peel note is only an aspect of an overall metallic aldehydic character. The C/Si analogues 2a and 2b are weak and untypical. Thus, the functional group of the compounds studied seems to be of utmost importance with respect to the grapefruit character, and the acetal function of 1a and 1b is not easily exchangeable by other hydrogen-bond acceptors, such as the carbonyloxy oxygen, without drifting the 799


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Hz, 4JA(Z)F(E) = 0.4 Hz, 4JA(Z)X = 1.4 Hz, 4JF(E)X = 1.5 Hz, 5JA(Z)M = 0.7 Hz, 5JF(E)M = 1.1 Hz, 9 H; C(HM)2CHXC(C(HA(Z))3)C(HF(E))3), 3.89 (δA) and 7.75 ppm (δX) (A2X system, 4JAX = 0.9 Hz, 3 H; C(HA)2OC(O)HX). 13C NMR (125.8 MHz, C6D6): δ 17.8 (CH CC ( Z ) ), 24.1 (CH 2 C(CH 3 ) 2 ), 26.0 (CHCC ( E ) ), 34.8 (CH 2 C(CH 3 ) 2 ), 37.3 (CH 2 CHC), 71.2 (CH 2 O), 120.3 (CH2CHC), 133.8 (CH2CHC), 160.5 ppm (C(O)H). Anal. Calcd for C10H18O2: C, 70.55; H 10.66. Found: C, 70.25; H, 10.67. Odor description: fruity, fatty-metallic odor of aldehydic tonality, in the direction of grapefruit peel, with slightly sweet, floral facets. Odor threshold: 151 ng L−1 air. Synthesis of (Formyloxymethyl)dimethyl(3-methylbut-2-en1-yl)silane (3b). Compound 12 (786 mg, 4.45 mmol) was added at 20 °C in a single portion to a stirred mixture of sodium formate (911 mg, 13.4 mmol), tetra-n-butylphosphonium chloride (132 mg, 448 μmol), and N,N-dimethylformamide (20 mL), and the resulting mixture was then heated under reflux for 16 h. The mixture was cooled to 20 °C within 45 min, and the solvent was removed under reduced pressure. Diethyl ether (25 mL) and water (25 mL) were added to the residue, and the resulting mixture was stirred at 20 °C for 20 min. The organic phase was separated, the aqueous phase was extracted with diethyl ether (3 × 10 mL) and discarded, the combined organic solutions were dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (35−70 μm; eluent, n-hexane/ ethyl acetate (98/2 v/v)) to furnish 3b (538 mg, 2.89 mmol; 65% yield) as a colorless liquid. 1H NMR (500.1 MHz, C6D6): δ 0.06 (s, 6 H; Si(CH3)3), 1.51 (δM), 1.60 (δA(Z)), 1.78 (δF(E)), and 5.25 (δX) (A3F3M2X system, 3JMX = 8.5 Hz, 4JA(Z)F(E) = 0.4 Hz, 4JA(Z)X = 1.4 Hz, 4 JF(E)X = 1.5 Hz, 5JA(Z)M = 0.7 Hz, 5JF(E)M = 1.1 Hz, 9 H; C(HM)2CHXC(C(HA(Z))3)C(HF(E))3), 3.88 (δA) and 7.80 ppm (δX) (A2X system, 4JAX = 1.0 Hz, 3 H; C(HA)2OC(O)HX). 13C NMR (125.8 MHz, C6D6): δ −4.9 (Si(CH3)2), 15.7 (CH2CHC), 17.6 (CHCC(Z)), 25.8 (CHCC(E)), 55.6 (CH2O), 118.9 (CH2CH C), 129.8 (CH2CHC), 161.1 ppm (C(O)H). 29Si NMR (99.4 MHz, C6D6): δ 0.2 ppm. Anal. Calcd for C9H18O2Si: C, 58.02; H, 9.74. Found: C, 57.73; H, 9.90. Odor description: floral-fruity, rosy odor recalling geranyl and citronelyl acetate. Odor threshold: 199 ng L−1 air. Synthesis of 2,2,5-Trimethylhex-4-en-1-yl Acetate (4a). This procedure follows a general protocol described in ref 4: compound 2a (2.00 g, 14.1 mmol) was added at 20 °C in a single portion to a stirred mixture of acetic anhydride (2.06 g, 20.2 mmol) and sodium acetate (622 mg, 7.58 mmol), and the resulting mixture was then heated under reflux for 4 h. The mixture was cooled to 20 °C within 15 min and stirred at this temperature for 16 h. Water (10 mL) and methyl tert-butyl ether (10 mL) were added, the organic phase was separated, the aqueous phase was extracted with methyl tert-butyl ether (3 × 5 mL) and discarded, the combined organic solutions were dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (35−70 μm; eluent, n-hexane/ethyl acetate (98/2 v/v)) to furnish 4a (1.99 g, 10.8 mmol; 77% yield) as a colorless liquid. 1H NMR (500.1 MHz, C6D6): δ 0.96 (s, 6 H; CH2C(CH3)2), 1.62 (δA(Z)), 1.76 (δF(E)), 2.06 (δM), and 5.31 (δX) (A3F3M2X system, 3JMX = 7.8 Hz, 4JA(Z)F(E) = 0.4 Hz, 4JA(Z)X = 1.4 Hz, 4JF(E)X = 1.4 Hz, 5JA(Z)M = 0.7 Hz, 5JF(E)M = 1.1 Hz, 9 H; C(HM)2CHXC(C(HA(Z))3)C(HF(E))3), 1.82 (s, 3 H; C(O)CH3), 3.97 ppm (s, 2 H; CH2O). 13C NMR (125.8 MHz, C6D6): δ 17.8 (CHCC(Z)), 20.4 (C(O)CH3), 24.2 (CH2C (CH3)2), 26.1 (CHCC(E)), 34.9 (CH2C(CH3)2), 37.5 (CH2 CHC), 72.0 (CH2O), 120.6 (CH2CHC), 133.6 (CH2CHC), 170.1 ppm (C(O)CH3). Anal. Calcd for C11H20O2: C, 71.70; H, 10.94. Found: C, 71.88; H, 11.11. Odor description: fruity-agrestic odor, slightly reminiscent of linalyl acetate, with green-fatty, slightly strawtype facets. Odor threshold: 181 ng L−1 air. Synthesis of (Acetoxymethyl)dimethyl(3-methylbut-2-en-1yl)silane (4b). Compound 12 (10.0 g, 56.6 mmol) was added at 20 °C in a single portion to a stirred mixture of sodium acetate (13.9 g, 169 mmol), tetra-n-butylphosphonium chloride (1.67 g, 5.66 mmol), and N,N-dimethylformamide (250 mL), and the resulting mixture was then heated under reflux for 16 h. The mixture was cooled to 20 °C

CC(E)), 57.1 (C(OCH3)2), 106.7 (SiCH), 119.7 (CH2CHC), 129.2 ppm (CH2CHC). 29Si NMR (99.4 MHz, C6D6): δ −1.9 ppm. Anal. Calcd for C10H22O2Si: C, 59.35; H, 10.96. Found: C, 59.15; H, 10.93. Odor description: agrestic grapefruit odor, reminiscent of methyl pamplemousse (1a). Odor threshold: 24 ng L−1 air. Synthesis of 2,2,5-Trimethylhex-4-en-1-ol (2a). A solution of 10 (3.23 g, 19.0 mmol) in diethyl ether (90 mL) was added at 0 °C within 1 h to a stirred suspension of lithium aluminum hydride (720 mg, 19.0 mmol) in diethyl ether (30 mL). The reaction mixture was warmed to 20 °C within 1 h, and stirring was continued for 1 h. Subsequently, a saturated aqueous solution of sodium sulfate (6 mL) was added carefully at 0 °C, and the insoluble components were filtered off, washed with diethyl ether (3 × 10 mL), and discarded. The filtrate and the wash solutions were combined and dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (35−70 μm; eluent, n-hexane/ethyl acetate (9/1 v/v)) to furnish 2a (2.55 g, 17.9 mmol; 94% yield) as a colorless liquid. 1H NMR (500.1 MHz, C6D6): δ 0.90 (br s, 1 H; CH2OH), 0.96 (s, 6 H; CH2C(CH3)2), 1.67 (δA(Z)), 1.79 (δF(E)), 2.08 (δM), and 5.37 (δX) (A3F3M2X system, 3JMX = 7.8 Hz, 4JA(Z)F(E) = 0.4 Hz, 4JA(Z)X = 1.4 Hz, 4 JF(E)X = 1.4 Hz, 5JA(Z)M = 0.7 Hz, 5JF(E)M = 1.1 Hz, 9 H; C(HM)2CHXC(C(HA(Z))3)C(HF(E))3), 3.25 ppm (br s, 2 H; CH2OH). 13C NMR (125.8 MHz, C6D6): δ 17.8 (CHCC(Z)), 24.0 (OCH2C(CH3)2), 26.1 (CHCC(E)), 36.4 (OCH2C(CH3)2), 37.2 (CH2CHC), 71.5 (CH2OH), 121.4 (CH2CHC), 133.0 ppm (CH2CHC). Anal. Calcd for C9H18O: C, 76.00; H, 12.76. Found: C, 76.04; H, 12.84. Odor description: fatty, oily, weak, with a slightly citrusy connotation in the direction of limonene. Odor threshold: 330 ng L−1 air. Synthesis of (Hydroxymethyl)dimethyl(3-methylbut-2-en-1yl)silane (2b). A solution of 4b (1.84 g, 9.18 mmol) in diethyl ether (50 mL) was added at 0 °C within 1 h to a stirred suspension of lithium aluminum hydride (391 mg, 10.3 mmol) in diethyl ether (20 mL). The reaction mixture was warmed to 20 °C within 1 h and stirring was continued for 1 h. Subsequently, a saturated aqueous solution of sodium sulfate (5 mL) was added carefully at 0 °C, and the insoluble components were filtered off, washed with diethyl ether (3 × 10 mL), and discarded. The filtrate and the wash solutions were combined and dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (35−70 μm; eluent, n-hexane/ ethyl acetate (1/1 v/v)) to furnish 2b (1.32 g, 8.34 mmol; 91% yield) as a colorless liquid. 1H NMR (500.1 MHz, C6D6): δ 0.15 (s, 6 H; Si(CH3)2), 0.49 (br s, 1 H; CH2OH), 1.62 (δM), 1.66 (δA(Z)), 1.81 (δF(E)), and 5.37 (δX) (A3F3M2X system, 3JMX = 8.5 Hz, 4JA(Z)F(E) = 0.4 Hz, 4JA(Z)X = 1.4 Hz, 4JF(E)X = 1.5 Hz, 5JA(Z)M = 0.7 Hz, 5JF(E)M = 1.1 Hz, 9 H; C(HM)2CHXC(C(HA(Z))3)C(HF(E))3), 3.30 ppm (br s, 2 H; CH2OH). 13C NMR (125.8 MHz, C6D6): δ 5.1 (Si(CH3)2), 15.8 (CH 2 CHC), 17.6 (CHCC (Z) ), 25.9 (CHCC (E) ), 54.6 (CH2OH), 120.0 (CH2CHC), 129.1 ppm (CH2CHC). 29Si NMR (99.4 MHz, C6D6): δ −0.1 ppm. Anal. Calcd for C8H18OSi: C, 60.69; H, 11.46. Found: C, 60.62; H, 11.62. Odor description: floralgreen odor, with a slightly technical character. Odor threshold: 126 ng L−1 air. Synthesis of 2,2,5-Trimethylhex-4-en-1-yl Formate (3a). This compound was synthesized according to ref 4, with slight modifications of the protocol: compound 2a (1.02 g, 7.17 mmol) was added at 20 °C in a single portion to a stirred mixture of formic acid (1.45 g, 31.5 mmol) and sodium sulfate (200 mg, 1.41 mmol), and the resulting mixture was then stirred at this temperature for 24 h. Water (5 mL) and diethyl ether (5 mL) were added, the organic phase was separated, the aqueous phase was extracted with diethyl ether (3 × 2 mL) and discarded, the combined organic solutions were dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (35−70 μm; eluent, n-hexane/ethyl acetate (98/2 v/v)) to furnish 3a (1.01 g, 5.93 mmol; 83% yield) as a colorless liquid. 1H NMR (500.1 MHz, C6D6): δ 0.89 (s, 6 H; CH2C(CH3)2), 1.60 (δA(Z)), 1.75 (δF(E)), 2.00 (δM), and 5.25 (δX) (A3F3M2X system, 3JMX = 7.8 800


Organometallics

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within 45 min, and the solvent was removed under reduced pressure. Diethyl ether (200 mL) and water (200 mL) were added, and the resulting mixture was stirred at 20 °C for 20 min. The organic phase was separated, the aqueous phase was extracted with diethyl ether (3 × 90 mL) and discarded, the combined organic solutions were dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by distillation in vacuo to furnish 4b (8.62 g, 43.0 mmol; 76% yield) as a colorless liquid. Bp: 74−75 °C/15 mbar. 1H NMR (500.1 MHz, C6D6): δ 0.12 (s, 6 H; Si(CH3)2), 1.57 (δM), 1.63 (δA(Z)), 1.79 (δF(E)), and 5.30 (δX) (A3F3M2X system, 3JMX = 8.5 Hz, 4JA(Z)F(E) = 0.4 Hz, 4JA(Z)X = 1.4 Hz, 4JF(E)X = 1.4 Hz, 5JA(Z)M = 0.7 Hz, 5JF(E)M = 1.1 Hz, 9 H; C(HM)2CHXC(C(HA(Z))3) C(HF(E))3), 1.83 (s, 3 H; C(O)CH3), 3.94 ppm (s, 2 H; CH2O). 13C NMR (125.8 MHz, C6D6): δ −4.8 (Si(CH3)2), 15.9 (CH2CHC), 17.6 (CHCC(Z)), 20.3 (C(O)CH3), 25.8 (CHCC(E)), 56.4 (CH2O), 119.2 (CH2CHC), 129.6 (CH2CHC), 170.7 ppm (C(O)CH3). 29Si NMR (99.4 MHz, C6D6): δ 0.3 ppm. Anal. Calcd for C10H20O2Si: C, 59.95; H, 10.06; Found: C, 59.94; H, 10.22. Odor description: natural lavender-type odor, recalling linalyl acetate and bergamot oil, with slightly sweet, floral facets. Odor threshold: 250 ng L−1 air. (Chloromethyl)trimethoxysilane (5). This compound was commercially available. Synthesis of Trimethoxy(methoxymethyl)silane (6). This compound was synthesized according to ref 12, with slight modifications of the protocol: compound 5 (50.0 g, 293 mmol) was added dropwise within 1 h to a boiling solution of sodium methoxide in methanol (freshly prepared from sodium (7.40 g, 322 mmol) and methanol (140 mL)). The resulting mixture was stirred under reflux for a further 1 h, cooled to 20 °C within 1 h, and then stirred at this temperature for 17 h. The insoluble components were filtered off, washed with methanol (3 × 15 mL), and discarded. The filtrate and the wash solutions were combined, the solvent was removed by distillation at atmospheric pressure (formation of a white precipitate), and diethyl ether (40 mL) was added to the mixture. The insoluble components were filtered off, washed with diethyl ether (2 × 20 mL), and discarded. The filtrate and the wash solutions were combined, the solvent was removed by distillation at atmospheric pressure, and the residue was purified by distillation in vacuo to furnish 6 (42.4 g, 255 mmol; 87% yield) as a colorless liquid. Bp: 79−80 °C/90 mbar. 1H NMR (500.1 MHz, C6D6): δ 3.23 (s, 3 H; COCH3), 3.30 (s, 2 H; CH2), 3.64 ppm (s, 9 H; Si(OCH3)3). 13C NMR (125.8 MHz, C6D6): δ 50.6 (Si(OCH3)3), 60.8 (CH2), 62.8 ppm (COCH3). 29Si NMR (99.4 MHz, C6D6): δ −52.4 ppm. Anal. Calcd for C5H14O4Si: C, 36.12; H, 8.49. Found: C, 36.12; H, 8.47. Synthesis of (Bromo(methoxy)methyl)trimethoxysilane (7). Compound 6 (10.0 g, 60.2 mmol) was added at 20 °C in a single portion to a stirred mixture of N-bromosuccinimide (12.3 g, 69.1 mmol), 2,2′-azobis(isobutyronitrile) (319 mg, 1.94 mmol), and tetrachloromethane (60 mL). The resulting mixture was stirred under reflux for 1 h and then cooled to 20 °C within 1 h. The insoluble components were filtered off, washed with tetrachloromethane (2 × 10 mL), and discarded. The filtrate and the wash solutions were combined, the solvent was removed by distillation at atmospheric pressure, and the residue was purified by distillation in vacuo to furnish 7 (5.61 g, 22.9 mmol; 38% yield) as a colorless liquid. Bp: 91−92 °C/15 mbar. 1H NMR (300.1 MHz, C6D6): δ 3.17 (s, 3 H; COCH3), 3.68 (s, 9 H; Si(OCH3)3), 5.66 ppm (s, 1 H; CH). 13C NMR (75.5 MHz, C6D6): δ 51.7 (Si(OCH3)3), 60.7 (COCH3), 89.2 ppm (CH). 29Si NMR (59.6 MHz, C6D6): δ −68.2 ppm. Anal. Calcd for C5H13BrO4Si: C, 24.50; H, 5.35. Found: C, 24.16; H, 5.26. Synthesis of (Dimethoxymethyl)trimethoxysilane (8). Compound 6 (12.5 g, 75.2 mmol) was added at 20 °C in a single portion to a stirred mixture of N-bromosuccinimide (14.9 g, 83.7 mmol), 2,2′azobis(isobutyronitrile) (391 mg, 2.38 mmol), and tetrachloromethane (75 mL). The resulting mixture was stirred under reflux for 1 h and then cooled to 20 °C within 1 h. The insoluble components were filtered off, washed with diethyl ether (3 × 15 mL), and discarded. The filtrate and the wash solutions were combined, and the resulting solution was added at 20 °C in a single portion to a stirred

solution of methanol (2.89 g, 90.2 mmol) and triethylamine (9.13 g, 90.2 mmol) in diethyl ether (75 mL). The resulting mixture was stirred under reflux for 1 h and then cooled to 20 °C within 1 h. The insoluble components were filtered off, washed with diethyl ether (3 × 15 mL), and discarded. The filtrate and the wash solutions were combined, the solvent was removed by distillation at atmospheric pressure, and the residue was purified by distillation in vacuo to furnish 8 (8.85 g, 45.1 mmol; 60% yield) as a colorless liquid. Bp: 65−66 °C/ 20 mbar. 1H NMR (300.1 MHz, C6D6): δ 3.44 (s, 6 H; COCH3), 3.67 (s, 9 H; Si(OCH3)3), 4.60 ppm (s, 1 H; CH). 13C NMR (75.5 MHz, C6D6): δ 50.8 (Si(OCH3)3), 56.2 (C(OCH3)2). 102.5 ppm (CH). 29Si NMR (59.6 MHz, C6D6): δ −62.1 ppm. Anal. Calcd for C6H16O5Si: C, 36.72; H, 8.22. Found: C, 36.92; H, 8.10. Methyl Isobutyrate (9). This compound was commercially available. Synthesis of Methyl 2,2,5-Trimethylhex-4-enoate (10). This compound was synthesized according to ref 13: a 2.5 M solution of nbutyllithium in hexanes (32.0 mL, 80.0 mmol of n-BuLi) was added at −78 °C within 1 h to a stirred solution of diisopropylamine (8.10 g, 80.0 mmol) in tetrahydrofuran (25 mL). The resulting mixture was stirred at −78 °C for 30 min, followed by dropwise addition of a solution of 9 (7.38 g, 72.3 mmol) in tetrahydrofuran (25 mL) over a period of 30 min. The mixture was stirred at −78 °C for 1 h, followed by dropwise addition of a solution of 1-bromo-3-methylbut-2-ene (12.0 g, 80.5 mmol) in tetrahydrofuran (25 mL) within 30 min, and the mixture was stirred at −78 °C for 1 h. The cooling bath was removed, a saturated aqueous solution of ammonium chloride (100 mL) was added dropwise within 20 min, diethyl ether (50 mL) was added in a single portion, and the resulting mixture was warmed to 20 °C over a period of 15 min. The organic phase was separated and washed with a saturated aqueous solution of sodium chloride (50 mL), and the aqueous phase and the wash solution were combined and then extracted with diethyl ether (2 × 50 mL). The combined organic solutions were dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure, and the residue was distilled in vacuo to furnish 10 (11.1 g, 65.2 mmol; 90% yield) as a colorless liquid. Bp: 70−71 °C/15 mbar. 1H NMR (500.1 MHz, C6D6): δ 1.31 (s, 6 H; CH2(CH3)2), 1.62 (δA(Z)), 1.74 (δF(E)), 2.41 (δM), and 5.36 (δX) (A3F3M2X system, 3JMX = 7.6 Hz, 4JA(Z)F(E) = 0.4 Hz, 4JA(Z)X = 1.4 Hz, 4JF(E)X = 1.4 Hz, 5JA(Z)M = 0.7 Hz, 5JF(E)M = 1.1 Hz, 9 H; C(HM)2CHXC(C(HA(Z))3)C(HF(E))3), 3.47 ppm (s, 3 H; OCH3). 13 C NMR (125.8 MHz, C 6D6): δ 17.8 (CHCC(Z)), 25.0 (CH2C(CH3)2), 26.0 (CHCC(E)), 39.1 (CH2CHC), 43.0 (CH 2 C(CH 3 ) 2 ), 51.2 (OCH 3 ), 120.6 (CH 2 CHC), 134.0 (CH2CHC), 177.4 ppm (C(O)CH3). Anal. Calcd for C10H18O2: C, 70.55; H, 10.66; Found: C, 70.20; H, 10.68. Chloro(chloromethyl)dimethylsilane (11). This compound was commercially available. Synthesis of (Chloromethyl)dimethyl(3-methylbut-2-en-1yl)silane (12). A solution of 1-chloro-3-methylbut-2-ene (10.7 g, 102 mmol) in tetrahydrofuran (230 mL) was added dropwise at −30 °C within 2 h to a stirred suspension of magnesium turnings (10.0 g, 411 mmol) in tetrahydrofuran (40 mL). The mixture was warmed to 0 °C, stirred at this temperature for 1 h, and then added dropwise at 0 °C within 1 h to a stirred solution of 11 (15.1 g, 106 mmol) in diethyl ether (100 mL). The resulting mixture was warmed to 20 °C and stirred at this temperature for 16 h. A saturated aqueous solution of ammonium chloride (300 mL) was added, the organic phase was separated, the aqueous phase was extracted with diethyl ether (3 × 125 mL) and discarded, and the combined organic solutions were dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by distillation in vacuo to furnish 12 (15.1 g, 85.4 mmol; 84% yield) as a colorless liquid. Bp: 68−69 °C/10 mbar. 1H NMR (300.1 MHz, C6D6): δ 0.11 (s, 6 H; Si(CH3)2), 1.44 (δM), 1.50 (δA(Z)), 1.67 (δF(E)), and 5.12 (δX) (A3F3M2X system, 3JMX = 8.5 Hz, 4JA(Z)F(E) = 0.4 Hz, 4JA(Z)X = 1.4 Hz, 4 JF(E)X = 1.4 Hz, 5JA(Z)M = 0.7 Hz, 5JF(E)M = 1.1 Hz, 9 H; C(HM)2CHXC(C(HA(Z))3C(HF(E))3), 2.64 ppm (s, 2 H; CH2Cl). 13 C NMR (75.5 MHz, C6D6): δ −4.8 (Si(CH3)2), 15.7 (CH2CHC), 17.6 (CHCC(Z)), 25.8 (CHCC(E)), 29.8 (CH2Cl), 118.9 801


Organometallics

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was warmed to 20 °C within 2 h, and stirring was continued for 17 h. Subsequently, water (35 mL) was added carefully at 0 °C, and the insoluble components were filtered off, washed with diethyl ether (3 × 75 mL), and discarded. The filtrate and the wash solutions were combined and dried over anhydrous sodium sulfate, and the solvent was removed by distillation at atmospheric pressure. The residue was purified by distillation at atmospheric pressure to furnish 16 (12.0 g, 93.5 mmol; 82% yield) as a colorless liquid. Bp: 143−145 °C. 1H NMR (500.1 MHz, C6D6): δ 0.15 (δA), 1.57 (δD), 1.65 (δG(Z)), 1.81 (δM(E)), 4.25 (δP), and 5.36 ppm (δX) (A6D2G3M2PX system, 3JAP = 3.6 Hz, 3JDP = 3.1 Hz, 3JDX = 8.4 Hz, 4JG(Z)M(E) = 0.4 Hz, 4JG(Z)X = 1.4 Hz, 4JM(E)X = 1.4 Hz, 5JDG(Z) = 0.7 Hz, 5JDM(E) = 1.1 Hz, 16 H; HPSi[C(HA)3)2]C(HD)2CHXC(C(HG(Z))3)C(HM(E))3). 13C NMR (125.8 MHz, C6D6): δ −4.5 (Si(CH3)2), 16.2 (CH2CHC), 17.6 (CHCC(Z)), 25.9 (CHCC(E)), 119.9 (CH2CHC), 129.4 ppm (CH2CHC). 29Si NMR (99.4 MHz, C6D6): δ −14.5 ppm. Anal. Calcd for C7H16Si: C, 65.54; H, 12.57. Found: C, 65.57; H, 12.59. Kinetic Studies. The 1H NMR spectra for the kinetic studies were recorded at 23 °C using a Bruker DRX-300 NMR spectrometer (1H, 300.1 MHz). The CD3CN/D2O mixture (5/1 v/v; 1.0 mL; [DCl] = 1 × 10−3 mol L−1) was added to a mixture of 1a (18.6 mg, 100 μmol) and 1b (20.2 mg, 100 μmol) in a 5 mm screw-cap NMR tube (Wilmad). After tuning and matching the probe to this CD3CN/D2O mixture, we also shimmed the spectrometer with this standard sample. Subsequently, the NMR tube was replaced by a freshly identically prepared sample for the hydrolysis reactions, and the 1H NMR measurement of the locked sample was started using an aquisition time of 10 s and a sweep width of 4194.6 Hz. Four scans per spectrum were recorded with a 30° pulse width and a delay D1 of 30 s. The starting points of acquisition were extracted automatically from the audit files and were used as values on the time axis. The pD values of the reaction mixture were measured at the starting point of the hydrolysis reactions and after complete hydrolysis using the two available samples. For the measurement of the pD values, a combination of a Mettler Toledo MP 220 pH meter and a Mettler Toledo InLab Science Pro instrument was used. The glass electrode was conditioned for 7 days in D2O prior to use. The pH meter was standardized with conventional buffer mixtures with a pD close to the range of the pD measurements.14,15 Olfactory Characterization. Compounds 1a−4a, 1b−4b, and 13 were olfactorily evaluated on smelling blotters by a panel of at least two expert perfumers as 10% solutions in dipropylene glycol (DPG) and in ethanol, respectively. The blotters were dipped 4 and 8 h in advance and compared with the freshly dipped samples for top, middle, and dry down odor character. The compounds investigated proved to be olfactorily pure and linear in smell. They were mainly top-note odorants and so showed little to no dry down contribution. The detection odor thresholds were determined by GC− olfactometry: different dilutions of the sample substance were injected into a gas chromatograph in descending order of concentration until the panelist failed to detect the respective substance at the sniffing port. The panelist smelled in blind and pressed a button upon perceiving an odor. If the recorded time matched the retention time, the sample was further diluted. The last concentration detected at the correct retention time is the individual odor threshold. The reported threshold values are the geometrical means of the individual odor thresholds of at least three different panelists.

(CH2CHC), 129.9 ppm (CH2CHC). 29Si NMR (59.6 MHz, C6D6): δ 2.9 ppm. Anal. Calcd for C8H17ClSi: C, 54.36; H, 9.69. Found: C, 54.32; H, 9.74. Dimethyl(3-methylbut-2-en-1-yl)silanol (13). Potassium hydroxide (9.10 g, 162 mmol) was added in a single portion at 20 °C to a vigorously stirred mixture of 16 (10.0 g, 77.9 mmol), water (150 mL), and tetrahydrofuran (30 mL), and stirring was continued at this temperature for 4 days. Diethyl ether (250 mL) was added, the organic phase was separated, the aqueous phase was extracted with diethyl ether (3 × 75 mL) and discarded, and the combined organic solutions were dried over anhydrous sodium sulfate. The solvent was removed by distillation at atmospheric pressure, and the residue was purified by distillation in vacuo to furnish 13 (8.90 g, 61.7 mmol; 79% yield) as a colorless liquid. Bp: 89−91 °C/43 mbar. 1H NMR (500.1 MHz, C6D6): δ 0.21 (s, 6 H; Si(CH3)2), 1.61 (δM), 1.67 (δA(Z)), 1.82 (δF(E)), and 5.37 (δX) (A3F3M2X system, 3JMX = 8.4 Hz, 4JA(Z)F(E) = 0.4 Hz, 4 JA(Z)X = 1.4 Hz, 4JF(E)X = 1.4 Hz, 5JA(Z)M = 0.7 Hz, 5JF(E)M = 1.1 Hz, 9 H; C(HM)2CHXC(C(HA(Z))3)C(HF(E))3), 1.85 ppm (s, 1 H; OH). 13 C NMR (125.8 MHz, C6D6): δ −0.3 (Si(CH3)2), 17.7 (CH CC(Z)), 20.3 (CH2CHC), 25.9 (CHCC(E)), 119.4 (CH2CHC), 129.4 ppm (CH2CHC). 29Si NMR (99.4 MHz, C6D6): δ 13.7 ppm. 1 H NMR (500.1 MHz, CD3CN/D2O mixture (5/1 v/v; [13] = 2.1 × 10−1 mol L−1; [DCl] = 1 × 10−3 mol L−1)): δ 0.21 (s, 6 H; Si(CH3)2), 1.41 (δM), 1.52 (δA(Z)), 1.63 (δF(E)), and 5.11 ppm (δX) (A3F3M2X system, 3JMX = 8.5 Hz, 4JA(Z)F(E) = 0.4 Hz, 4JA(Z)X = 1.4 Hz, 4JF(E)X = 1.5 Hz, 5JA(Z)M = 0.5 Hz, 5JF(E)M = 0.7 Hz, 9 H; C(HM)2CHX C(C(HA(Z))3)C(HF(E))3), OH not detected (H/D exchange). 13C NMR (125.8 MHz, CD3CN/D2O mixture (5/1 v/v; [13] = 2.1 × 10−1 mol L−1; [DCl] = 1 × 10−3 mol L−1)): δ −0.5 (Si(CH3)2), 17.7 (CHCC(Z)), 20.4 (CH2CHC), 25.9 (CHCC(E)), 120.4 (CH2CHC), 130.1 ppm (CH2CHC). 29Si NMR (99.4 MHz, CD3CN/D2O mixture (5/1 v/v; [13] = 2.1 × 10−1 mol L−1; [DCl] = 1 × 10−3 mol L−1)): δ 13.2 ppm. Anal. Calcd for C7H16OSi: C, 58.27; H, 11.18. Found: C, 58.50; H, 11.25. Odor description: floral, agresticherbaceous odor in the direction of linalool, with a slightly dull aquatic aspect. Odor threshold: 62.0 ng L−1 air. Dimethoxydimethylsilane (14). This compound was commercially available. Synthesis of Methoxydimethyl(3-methylbut-2-en-1-yl)silane (15). A solution of 1-chloro-3-methylbut-2-ene (15.0 g, 143 mmol) in tetrahydrofuran (350 mL) was added dropwise at −30 °C within 3 h to a stirred suspension of magnesium turnings (14.0 g, 576 mmol) in tetrahydrofuran (130 mL). The mixture was warmed to 0 °C, stirred at this temperature for 1 h, and then added dropwise at −20 °C within 2 h to a stirred solution of 14 (35.0 g, 291 mmol) in tetrahydrofuran (300 mL). The resulting mixture was warmed to 20 °C and was then stirred at this temperature for 17 h. Subsequently, approximately 600 mL of tetrahydrofuran were removed by distillation, n-pentane (300 mL) was added, and the resulting precipitate was filtered off, washed with n-pentane (3 × 150 mL), and discarded. The filtrate (including the wash solutions) was added to ice−water (100 mL), the organic phase was separated, the aqueous phase was extracted with diethyl ether (3 × 100 mL) and discarded, and the combined organic solutions were dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by distillation in vacuo to furnish 15 (20.8 g, 131 mmol; 92% yield) as a colorless liquid. Bp: 107−109 °C/200 mbar. 1H NMR (500.1 MHz, C6D6): δ 0.21 (s, 6 H; Si(CH3)2), 1.66 (δM), 1.67 (δA(Z)), 1.81 (δF(E)), and 5.39 (δX) (A3F3M2X system, 3JMX = 8.4 Hz, 4JA(Z)F(E) = 0.4 Hz, 4 JA(Z)X = 1.4 Hz, 4JF(E)X = 1.4 Hz, 5JA(Z)M = 0.7 Hz, 5JF(E)M = 1.1 Hz, 9 H; C(HM)2CHXC(C(HA(Z))3)C(HF(E))3), 3.40 ppm (s, 3 H; OCH3). 13C NMR (125.8 MHz, C6D6): δ −2.6 (Si(CH3)2), 17.6 (CHCC(Z)), 18.5 (CH2CHC), 25.9 (CHCC(E)), 50.1 (OCH3), 119.3 (CH2CHC), 129.3 ppm (CH2CHC). 29Si NMR (99.4 MHz, C6D6): δ 15.8 ppm. Anal. Calcd for C8H18OSi: C, 60.69; H, 11.46. Found: C, 60.58; H, 11.60. Dimethyl(3-methylbut-2-en-1-yl)silane (16). A solution of 15 (18.0 g, 114 mmol) in diethyl ether (100 mL) was added dropwise at −78 °C within 1 h to a stirred suspension of lithium aluminum hydride (2.50 g, 65.9 mmol) in diethyl ether (200 mL). The reaction mixture

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REFERENCES

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Synthesis and Olfactory Characterization of Sila-Methyl

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