ORGANIC COMPOUNDS

The present invention relates to substituted spiro[bornyl-2,4'-(1,3-dioxanes)]. This invention relates furthermore to a method for their production and to fragrance compositions comprising them.

In the fragrance industry there is a constant demand for new compounds that enhance or improve on odour, or impart new odour notes. Particularly preferred are those compounds possessing a low odour threshold and that thus may be used in fragranced products at lower concentration than compounds of similar odour profile having a higher odour threshold without essentially influencing the character of a fragrance composition comprising it.

EP 0 761 664 refers to spiro[bornyl-2,4'-(1,3-dioxane)] derivatives substituted at 2' position of the dioxane ring optionally substituted with a methyl group at 6' position of the dioxane ring. The compounds described therein possess woody and ambery notes, often accompanied with camphoraceous, patchouli aspects.

It has now been found that the odour threshold can positively be influenced if the compounds described in EP 0761 664 are substituted at C5' of the dioxane ring. This class of compounds has not been described in the literature and thus is novel in its own right. Accordingly, the present invention refers in one of its aspects to a compound of formula (1)

wherein R ¹ to R ⁶ independently represent hydrogen; C _1-4 alky!, e.g. methyl, ethyl, n- propyl, /-propyl, and i-butyl; or C _2-4 alkenyl, e.g. vinyl, allyl, propenyl and i-propenyl; or C _3-4 cycloalkyl, e.g. cyclopropyl; or at least one of the residues R ¹ and R ² , R ³ and R ⁴ ,

and/or R ⁵ and R ⁶ form together with the carbon atom to which they are attached a C ₃ _ ₅ cycloalkyl ring; with the proviso that R ¹ is C _1-4 alkyl, C ₂ _ ₄ alkenyl or ; or C3- ₄ cycloalkyl if R ² is hydrogen; and the number of carbon atoms of R ¹ +R ² +R ³ +R ⁴ +R ⁵ +R ⁶ is between 1 and 6, preferably between 2 and 5, most preferably between 2 and 4.

The compounds of formula (1) comprise several chiral centres and as such may exist as a mixture of stereoisomers, or they may be resolved as isomerically pure forms. Resolving stereoisomers adds to the complexity of manufacture and purification of these compounds and so it is preferred to use the compounds as mixtures of their stereoisomers simply for economic reasons. However, if it is desired to prepare individual stereoisomers, this may be achieved according to methods known in the art, e.g. preparative HPLC and GC, crystallization or stereoselective synthesis.

Preferred are compounds of formula (1 ) wherein R ¹ is methyl or ethyl, or compounds wherein R ¹ is methyl or ethyl and R ³ and/or R ⁴ is methyl. Most preferred are compounds wherein R ¹ is methyl and R ² , R ³ and R ⁴ is hydrogen, or compounds wherein R ¹ and R ³ is methyl and R ² and R ⁴ is hydrogen, or compounds wherein R ¹ , R ⁴ and R ³ is methyl and R ² is hydrogen.

Particularly preferred are compounds selected from the list comprising

(1R,2S,2 ^I S,4R,5 ^I S)-1 _I 2 ^I ,5 ^I ,7 _> 7-pentamethylspiro[bicycloI2.2.1]heptane-2,4 ¹ - [1 ,3]dioxane], (1R _I 2S _I 2 ^I R,4R,5 ^f S)-1 _I 2' _l 5',7 _I 7-pentamethylspiro[bicyclo[2.2.1]heptane- 2,4'-[1 ,3]dioxane], (1 R,2S,2'S,4R,5'R)-1 ,2',5',7,7- pentamethylspiro[bicyclo[2.2.1]heptane-2,4'-[1 ,3]dioxane], (1 R,2S,2'S,4R,5'S)-2'-ethyl- 1.δ'.Z^-tetramethylspiroCbicyclop^.iJheptane^^'-II ,3]dioxane], (1 R,2S,2'R,4R,5'S)- 2'-ethyl-1 ,5',7,7-tetramethylspiro[bicyclo[2.2.1]heptane-2,4'-[1 ,3]dioxane], (I R^S^'S^R.δ'S^'-isopropyl-i .δ'yj-tetramethylspiroIbicyclop^.ilheptane^^'- [1 ,3]dioxane], (1 R^S^'R^R.δ'S^'-isopropyM ,5',7,7- tetramethylspiro[bicyclo[2.2.1]heptane-2,4'-[1 ,3]dioxane], (1 R,2S,2'S,4R,5'R)-2'- isopropyl-1 ,5',7,7-tetramethylspiro[bicyclo[2.2.1]heptane-2,4'-[1 ,3]dioxane],

(1 R,2S,4R,5'S)-1.Z^'.δ'JJ-hexamethylspirotbicyclop^.ilheptane ^^'-ti ,3]dioxane], (I R^S^R.δ'R^I^'^'.δ'jy-hexamethylspirofbicycloβ^.ilheptane^ ^'-fi .SJdioxane], (1 RS^SR^RS/SR^RS.δ'RS/SR.e'RS/SRH ,2',5',6\7,7- hexamethylspiro[bicyclo[2.2.1]heptane-2,4'-[1 ,3]dioxane], (1 RS,2SR,4RS,5'RS/SR,6'RS/SR)-1 ,2',2\5',6\7,7-

heptamethylspiro[bicyclo[2.2.1]heptane-2,4'-[1 ,3]dioxane], (1 RS,2SR,2'RS/SR,4RS,5'RS/SR,6'RS/SR)-6'-Ethyl-1 ,2',5',7,7- pentamethylspiro[bicyclo[2.2.1]heptane-2,4'-[1,3]dioxane], (1 RS,2SR,4RS,5'RS/SR,6'RS/SR)-6'-ethyl-1 ,2', 2', 5' JJ- hexamethylspirolbicycloβ^.^heptane^^'-π ^dioxane] and (1 RS^SR^'RS/SR^RS.δ'RS/SRJ-δ'-Ethyl-i ,2 ¹ JJ- tetramethylspiro[bicyclo[2.2.1]heptane-2,4'-[1 ,3]dioxane].

Compounds of formula (1 ) wherein R ¹ and R ⁵ is not hydrogen and R ² and R ⁶ is hydrogen are preferred from an olfactive point of view, if the mixture of stereoisomers is enriched in (1 R,2S,2'S,5'S)-stereoisomer, e.g. diastereomer mixture of (IRS^SR^'RS/SR^RS.δ'RS/SRVI^'.δ'.Z.Z-pentamethylspiroIbicy clop^.ilheptane- 2,4'-[1 ,3]dioxane] enriched in (1R,2S,2'S,4R,5'S)-1 ,2',5',7,7- pentamethylspiro[bicyclo[2.2.1]heptane-2,4'-[1 ,3]dioxane], is preferred. Thus, in a further aspect, the present invention refers to the use of a compound of formula (1 ) enriched in a compound of formula (1')

wherein R ¹ and R ³ to R ⁵ have the same meaning as given above.

The term "enriched" is used herein to describe a compound containing more than 25 weight % of the (1R,2S,2'S,5'S)-stereoisomer. Compounds are preferred containing 50 weight % or more of the (1R,2S,2'S,5'S)-stereoisomer. Particularly preferred are compounds having a diastereomeric purity of 75 weight %, or greater.

The compounds according to the present invention may be used alone or in combination with a.base material. As used herein, the "base material" includes all known odourant molecules selected from the extensive range of natural products and

synthetic molecules currently available, such as essential oils, alcohols, aldehydes and ketones, ethers and acetals, esters and lactones, macrocycles and heterocycles, and/or in admixture with one or more ingredients or excipients conventionally used in conjunction with odourants in fragrance compositions, for example, carrier materials, and other auxiliary agents commonly used in the art.

The following list comprises examples of known odourant molecules, which may be combined with the compounds of the present invention:

- ethereal oils and extracts, e.g. tree moss absolute, basil oil, fruit oils such as bergamot oil and mandarine oil, myrtle oil, palmarose oil, patchouli oil, petitgrain oil, jasmine oil, rose oil, sandalwood oil, wormwood oil, lavender oil or ylang-ylang oil;

- alcohols, e.g. cinnamic alcohol, cis-3-hexenol, citronellol, Ebanol™, eugenol, farnesol, geraniol, Super Muguet™, linalool, menthol, nerol, phenylethyl alcohol, rhodinol, Sandalore™, terpineol or Timberol™.

- aldehydes and ketones, e.g. anisaldehyde, α-amylcinnamaldehyde, Georgywood™, hydroxycitronellal, lso E Super ^® , Isoraldeine ^® , Hedione ^® , Lilial ^® , maltol, Methyl cedryl ketone, methylionone, verbenone or vanillin;

- ethers and acetals, e.g. Ambrox™, geranyl methyl ether, rose oxide or Spirambrene™.

- esters and lactones, e.g. benzyl acetate, Cedryl acetate, γ-decalactone, Helvetolide ^® , γ-undecalactone or Vetivenyl acetate.

- macrocycles, e.g. Ambrettolide, Ethylene brassylate or Exaltolide ^® .

- heterocycles, e.g. isobutylchinoline.

The compounds according to formula (1) may be used in a broad range of fragrance applications, e.g. in any field of fine and functional perfumery, such as perfumes, household products, laundry products, body care products and cosmetics. The compounds can be employed in widely varying amounts, depending upon the specific

application and on the nature and quantity of other odourant ingredients. The proportion is typically from 0.001 to 20 weight percent of the application. In one embodiment, compounds of the present invention may be employed in a fabric softener in an amount of from 0.001 to 0.05 weight percent. In another embodiment, compounds of the present invention may be used in fine perfumery in amounts of from 0.1 to 20 weight percent, more preferably between 0.1 and 5 weight percent. However, these values are given only by way of example, since the experienced perfumer may also achieve effects or may create novel accords with lower or higher concentrations.

The compounds of the present invention may be employed into the fragrance application simply by directly mixing the fragrance composition with the fragrance application, or they may, in an earlier step, be entrapped with an entrapment material, for example, polymers, capsules, microcapsules and nanocapsules, liposomes, film formers, absorbents such as carbon or zeolites, cyclic oligosaccharides and mixtures thereof, or they may be chemically bonded to substrates, which are adapted to release the fragrance molecule upon application of an external stimulus such as light, enzyme, or the like, and then mixed with the application.

Thus, the invention additionally provides a method of manufacturing a fragrance application, comprising the incorporation of a compound of the present invention, as a fragrance ingredient, either by directly admixing the compound to the application or by admixing a fragrance composition comprising a compound of formula (1), which may then be mixed to a fragrance application, using conventional techniques and methods.

As used herein, "fragrance application" means any product, such as fine perfumery, e.g. perfume and eau de toilette; household products, e.g. detergents for dishwasher, surface cleaner; laundry products, e.g. softener, bleach, detergent; body care products, e.g. shampoo, shower gel; and cosmetics, e.g. deodorant, vanishing creme, comprising an odourant. This list of products is given by way of illustration and is not to be regarded as being in any way limiting.

The compounds of the present invention may be prepared by reaction of the corresponding diol of the general formula (2)

with a carbonyl compound of the formula R ⁵ R ⁶ C=O, or an acetal or ketal of the formula R ⁵ R ⁶ C(OR'") ₂ , wherein R ¹ to R ⁶ have the same meaning as defined for the compound of formula (1 ), and R'" is methyl, ethyl or propyl, under conditions known in the art.

The diol of the general formula (2) may be obtained either via substituted vinylisobomeol 4 (route I) or allylisoborneol 5 (route Il and III) as depicted in Scheme 1. Both isoborneols may be prepared by addidion of a corresponding organometallic reagent, preferably Grignard reagent, to camphor. In route Il and III, the allylisoborneol 5 undergoes either epoxidation or ozonolysis, both followed by reduction or addition of an organometallic reagent. In route I ₁ the vinylisobomeol 4 is hydroborated and oxidized, to give the diol of formula (2).

a) R ³ R ⁴ C=CR ¹ MgX; b) 1. NaBH ₄ , BF ₃ -Et ₂ O; 2. H ₂ O ₂ ; c) R ¹ R ² C=CR ³ CRR ¹ MgX; d) MCPBA (m-chloroperbenzoic acid), NaHCO ₃ ; e) LAH; f) R"Li/Cul; h) O ₃ ; i) NaBH ₄ ; j) R ⁴ MgX, wherein R ¹ to R ⁴ has the same meaning as given in the specification above, -CRR' results in R ⁴ , R" is alkyl, e.g. methyl or ethyl, and X is Cl, Br or I.

Whereas the procedure according to route Il and III are generally known, route I has not been described in literature.

Accordingly, the present invention refers in a further aspect to a method of producing a compound of formula (2)

wherein

R ¹ , R ³ and R ⁴ independently represent hydrogen; or Ci^alkyl, e.g. methyl, ethyl, n-propyl, /-propyl, and /-butyl; or C ₃ - ₄ cycloalkyl, e.g. cycloporpyl; and R ² is hydrogen; comprising the steps of a) reacting an organometallic reagent with camphor giving a compound of formula 4, followed by b) hydroboration and oxidation giving a compound of formula (2).

Surprisingly, it has been found that the compounds of the present invention wherein the mixture of stereoisomers is enriched in those of configuration (1 R,2S,2'S,5'S) is obtained if the diol of formula (2) has been prepared following the procedure according to route I, as described above.

Thus, in another embodiment the present invention refers to a method of producing a compound of formula (1) enriched in a compound of formula (1') comprising the steps of a) reacting an organometallic reagent with camphor giving a compound of formula 4, followed by b) hydroboration and oxidation giving a compound of formula (2), followed by c) reaction of the resulting compound of step b) with a carbonyl compound of the formula R ⁵ R ⁶ C=O, or an acetal or ketal of the formula R ⁵ R ⁶ C(OR"') ₂ ,

wherein R ⁵ and R ⁶ independently represent hydrogen; C _1-4 alkyl, e.g. methyl, ethyl, n-propyl, i-propyl, and /-butyl; or C _2-4 alkenyl, e.g. vinyl, allyl, propenyl and /- propenyl; ; or C _3-4 cycloalkyl, e.g. cyclopropyl; or R ⁵ and R ⁶ form together with the carbon atom to which they are attached a C ₃ _ ₅ cycloalkyl ring; and R'" is methyl, ethyl or propyl.

Further particulars as to reaction conditions are provided in the examples.

The invention is now further described with reference to the following non-limiting examples.

The reported NMR data were measured under the following general conditions: ¹ H at 400 and ¹³ C at 100 MHz; in CDCI ₃ , if not otherwise stated; chemical shifts (δ) in ppm downfield from TMS; coupling constants J in Hz; NOESY, and GRASP COSY-DQF, HMBC and HMQC data were used in signal attributions. The reported MS and GC/MS data refer to the intensities (in brackets) in % rel. to the base peak. GC: DB™-1701. Flash chromatography: Merck silica gel 60 (230 - 400 mesh), if not otherwise stated. The new products were obtained as colourless oils, except where otherwise stated. The yields were not optimised.

Example 1 : (1R.2S.2'R/S.4R.5'S)-1.2'.5'.7.7-Pentamethvlspirorbicvclor2. 2.11heDtane- 2,4'-[1 ,3]dioxane] (1a)

a) (1 R,2S,4R)-2-lsopropenyl-1 ,7,7-trimethylbicyclo[2.2.1]heptan-2-ol (4a)

A small amount of 2-bromopropene was added to magnesium turnings (6.0 g, 0.25 mol) covered with minimum of THF. After starting the reaction, a solution of 2-bromopropene (total amount 27 ml, 0.30 mol) in THF (200 ml) was added dropwise in a rate to maintain gentle reflux of the reaction mixture. After additional 30 min. of reflux, a suspension prepared by 2 h stirring of (1 R)-(+)-camphor (20 g, 0.13 mol) and dried cerium (III) chloride (10 g, 41 mmol) in THF (100 ml) was added at room temperature. Stirring at rt continued for 4 h, then the reaction mixture was poured into aqueous solution of ammonium chloride (300 ml) and extracted with MTBE (2 x 200 ml). After washing with brine, drying (MgSO ₄ ), evaporation of solvents in vacuo and sublimation of the unreacted camphor, crude (1 R,2S,4R)-2-isopropenyl-1 ,7,7-

trimethylbicyclo[2.2.1]heptan-2-ol (4a, 24 g, quantitative yield, 95% GC pure) was obtained. It was engaged in the next step without further purification.

¹ H-NMR: δ0.85 (s, 3H), 0.99 (s, 3H), 1.03 (ddd, J=12.3, 8.8, 5.3, 1H), 1.14 (s, 3H), 1.27 (ddd, J=13.1, 8.8, 4.1, 1H), 1.34 (ddd, J=13.1, 11.2, 5.3, 1H), 1.57 (s, 1H), 1.61-1.70 (m, 1H), 1.74 (t, J=4.3, 1H), 1.88 (dd, J=1A, 0.5, 3H), 1.92 (ddd, J=13.6, 4.3, 3.3, 1H), 2.08 (d, J=13.6, 1H), 4.90 (qi, J=1.4, 1H), 5.06 (sb, 1H); ¹³ C-NMR: δ 11.6 (q), 21.4 (q), 21.5 (q), 21.8 (q), 26.7 (t), 30.8 (t), 42.9 (t), 45.1 (d), 50.0 (s), 52.3 (s), 83.9 (s), 112.1 (t), 149.8 (s); MS: 195 (0.5), 194 (4, M ⁺ ), 179 (3), 161 (3), 133 (5), 123 (4), 110 (18), 109 (30), 108 (10), 95 (100), 85 (11), 84 (15), 69 (15), 67 (8), 55 (9), 43 (10), 41 (20); [α] _D ²² -54.9 (c 1.0, EtOH).

b) (1 R,2S,2'S,4R)- 2-(2-Hydroxy-1-methylethyl)-1 ,7,7-trimethylbicyclo[2.2.1]heptan-2-ol (2a) and (1 R,2S,2'R,4R)- 2-(2-hydroxy-1-methylethyl)-1 ,7,7- trimethylbicyclo[2.2.1]heptan-2-ol (2b)

A solution of (1R,2S,4R)-2-isopropenyl-1 ,7,7-trimethylbicyclo[2.2.1]heptan-2-ol (4a, 23 g, 0.12 mol) in diglyme (46 ml) was added to a suspension of sodium borohydride (6.7 g, 0.18 mol) in the same solvent (46 ml). Boron trifluoride diethyl etherate (23 ml, 0.18 mol) was added to the reaction mixture cooled with an ice bath and stirring continued for 1 h. 4N sodium hydroxide (53 ml, 0.21 mol) and 30% aqueous hydrogen peroxide (21 ml, 0.21 mmol) solutions were added successively while maintaing the temperature below 20°C. After further 45 min. stirring at room temperature, the reaction mixture was diluted with water (100 ml) and extracted with MTBE (2 x 300 ml). The combined organic layers were washed with water (300 ml), aqueous sodium bicarbonate solution (100 ml) and again with water (2 x 200 ml). After drying (MgSO ₄ ) and evaporation of solvents in vacuo, the residue was purified by flash chromatography (n-hexane/MTBE 2:1) to give (1R,2S,2'S,4R)- 2-(2-hydroxy-1-methylethyl)-1 ,7,7- trimethylbicyclo[2.2.1]heptan~2-ol (2a, 17.1 g, 68%), its epimer (1 R,2S,2'R,4R)- 2-(2- hydroxy-1-methylethyl)-1 ,7,7-trimethylbicyclo[2.2.1]heptan-2-ol (2b, 3.3 g, 13%), and a 9:10 mixture of 2a and 2b (3.8 g, 15%).

c) (1 R,2S,2'R/S,4R,5'S)-1 ,2'5',7,7-Pentamethylspiro[bicyclo[2.2.1]heptane-2,4'- [1 ,3]dioxane] (1a)

A solution of diol 2a (3.0 g, 14 mmol), acetaldehyde (2.2 g, 50 mmol) and p- toluenesulfonic acid monohydrate (0.20 g, 1.1 mmol) in anhydrous THF (45 ml) was stirred overnight under nitrogen at room temperature, then poured into ice-cold 10 % NaHCO ₃ solution (100 ml) and extracted with MTBE (2 x 100 ml). The combined organic phases were washed with brine (150 ml), dried (MgSO ₄ ) and concentrated in vacuo. The residue (3.3 g) was purified by flash chromatography (n-hexane/MTBE 20:1 ) to give a 1 :1.1 mixture of (1 R,2S,2'S,4R,5'S)- and (1 R,2S,2'R,4R,5'S)-1 ,2',5',7,7- pentamethylspiro[bicyclo[2.2.1]heptane-2,4'-[1 ,3]dioxane] (1a, 2.6 g, 77%). [α] _D ²² -49.0 (c 1.1 , EtOH).

For the analytical data of single epimers see Example 2, compounds 1b and 1c.

Odour description (mixture of epimers): woody, ambery, fruity, rich, sweet.

Example 2: (1 R,2S,2'S,4R,5'S)-1 ,2',5',7,7-Pentamethylspiro[bicyclo[2.2.1]heptane-2,4'- [1,3]dioxane] (1b) and (1R,2S,2'R,4R,5'S)-1,2',5',7,7- pentamethylspiro[bicyclo[2.2.1]heptane-2,4'-[1 ,3]dioxane] (1c)

Samples of single stereoisomer 1b (first eluted) and 1c were obtained by flash chromatography separation (n-hexane/MTBE 40:1 ) of the epimeric mixture 1a obtained in Example 1.

1b: ¹ H NMR: δ0.86 (s, 3H), 0.87 (d, J=6.6, 3H), 0.88 (s, 3H), 0.99 (s, 3H), 0.99-1.09 (m, 1H), 1.20 (d, J=5.1, 3H), 1.36 (ddd, J=13.9, 11.9, 5.6, 1H), 1.48 (d, J=13.4, 1H), 1.58 (ddd, J=13.9, 9.0, 3.3, 1H), 1.62-1.72 (m, 1H), 1.76 (t, J=4.5, 1H), 1.95 (ddd, J=13.4, 4.5, 3.0, 1H), 2.10 (ddq, J=11.6, 6.6, 5.1, 1H), 3.20 (t, J=11.6, 1H), 3.67 (dd, J=11.6, 5.1, 1H), 4.72 (q, J=5.1, 1H); ¹³ C NMR: δ 10.9 (q), 15.4 (q), 20.8 (q), 21.3 (q), 21.8 (q), 26.3 (t), 29.8 (t), 31.4 (d), 33.6 (t), 45.1 (d), 49.8 (s), 54.9 (s), 71.2 (t), 86.6 (s), 90.7 (d); MS: 239 (0.3), 238 (2, M ⁺ ), 194 (7), 179 (11), 164 (6), 152 (29), 137 (11), 123 (14), 121 (22), 110 (20), 109 (53), 108 (100), 95 (59), 93 (23), 81 (31), 69 (20), 55 (27), 43 (38), 41 (52); [α] _D ²² -47.6 (c 1.0, EtOH).

Odour description: ambery, woody, dry, sweet, animalic.

1c: ¹ HNMR: δ0.82 (s, 3H), 0.93-1.01 (m, 1H), 1.09 (d, J=6.7, 3H), 1.09 (s, 3H), 1.11 (s, 3H), 1.18 (d, J=5.1, 3H), 1.24-1.34 (m, 1H), 1.49 (ddd, J=14.0, 9.5, 3.4, 1H), 1.61-1.69 (m, 2H), 1.64

(d, J=13.9, 1H), 1.82 (ddd, J=13.9, 4.0, 3.5, 1H), 2.29 (qid, J=6.7, 3.3 1H), 3.55 (dd, J=10.6, 6.8 1H), 3.90 (dd, J=10.6, 3.0, 1H), 5.32 (q, J=5.1, 1H); ¹³ C NMR: δ 15.4 (q), 17.1 (q), 21.1 (q), 21.2 (q), 21.6 (q), 26.9 (t), 30.8 (t), 31.2 (d), 42.0 (t), 44.2 (d), 50.0 (s), 54.8 (s), 68.6 (t), 86.1 (s), 92.2 (d); MS: 239 (0.5), 238 (3, M ⁺ ), 194 (8), 179 (14), 164 (6), 152 (12), 137 (13), 123 (18), 121 (21), 110 (19), 109 (61), 108 (100), 95 (67), 93 (25), 81 (25), 69 (21), 55 (30), 43 (45), 41 (57); [α] _D ²² -49.5 (c 1.1, EtOH).

Odour description: dry, woody, cedarwood, ambery, warm, powdery, weaker than 1b.

Example 3: (1R.2S.2'S,4R.5'R)-1.2',5'.7.7-Pentamethvlspiro[bicvclo[2.2. 1]heptane-2.4'- [1,3]dioxane] (1d)

Prepared according to Example 1c starting from diol 2b, described in Example 1b. The evaluated sample contained about 4% of tentatively (1 R,2S,2'R,4R,5'R) epimer.

¹ H NMR: δ0.82 (s, 3H), 0.93 (s, 3H), 0.94 (s, 3H), 0.94-1.03 (m, 1H), 1.24 (d, J=5.1, 3H), 1.245 (d, J=6.1, 3H), 1.25 (d, J=13.0, 1H), 1.28-1.35 (m, 1H), 1.35-1.42 (m, 1H), 1.49 (ddd, J=13.2, 9.5, 3.4, 1H), 1.67-1.76 (m, 2H), 2.33 (ddd, J=13.0, 3.9, 3.7, 1H) 3.66 (dd, J=11.2, 1.7, 1H) 4.02 (dd, J=11.2, 1.7, 1H), 4.88 (q, J=5.1, 1H); ¹³ C NMR: δ 11.8 (q), 15.9 (q), 20.8 (q), 20.9 (q), 21.4 (q), 27.4 (t), 28.3 (t), 37.9 (d), 42.1 (t), 44.7 (d), 50.3 (s), 52.3 (s), 71.6 (t), 83.9 (s), 91.3 (d); MS: 239 (1), 238 (7, M ⁺ ), 194 (18), 179 (12), 152 (37), 137 (12), 123 (16), 121 (15), 110 (27), 109 (62), 108 (100), 95 (80), 93 (26), 81 (52), 69 (36), 55 (34), 45 (27), 43 (40), 41 (62); [α] _D ²² -65.3 (c 0.6, EtOH).

Odour description: ambery, woody, balsamic, green.

Example 4: (1 RS,2SR,2'RS/SR,4RS,5'RS/SR)-1 ,2',5',7,7- Pentamethylspiro[bicyclo[2.2.1]heptane-2,4'-[1,3]dioxane] (1e and 1f)

a) Starting from rac-camphor and according to the experimental procedure of Example 1a-c, except for the separation of the intermediate diols 2c, a 1 :14:10 (sorted by GC elution order) racemic mixture 1e of (1 R*,2S ^* ,2'S*,4R*,5'R*)-, (1R*,2S*,2'S*,4R*,5'S*)- and (1R*,2S*;2'R*,4'R*,5,S*)-diastereOmersOf-1 ,2'75',7,7-- pentamethylspiro[bicyclo[2.2.1]heptane-2,4'-[1 ,3]dioxane] was obtained in 82% overall yield.

Odour description: ambery, woody, earthy/mossy, fruity.

b) A 6:2:1 racemic mixture 1f of diastereomers of (1 R*,2S*,2'S*,4R*,5'R*)-, (1 R*,2S ^* ,2'S*,4R*,5'S*)- and (1 R*,2S*,2'R*,4R* ₁ 5'S*)-1 ,2',5',7J- pentamethylspiro[bicyclo[2.2.1]heptane-2,4'-[1 ,3]dioxane] was obtained in 38% overall yield following the experimental procedure of Example 1c, starting from the diol mixture 2d obtained from rac-camphor via 2-(1-methylallyl)-1 ,7,7-trimethylbicyclo[2.2.1]heptan- 2-ol (5a), applying the methodology of Kostova et al (HeIv. Chim. Acta 1999, 82, 1385), i.e. route III. The epimeric intermediate enols and diols were not separated.

(1 R ^* ,2S*,2'S*,4R*,5'S*)- and (1 R*,2S*,2'S*,4R*,5'R*)- enatiomeric pairs are the strongest constituents of the mixture. Their relative odour threshold, compared to the whole stereoisomer mixture, were 1 :50:4 (rac-1b : rac-1d : 1f).

Odour description (1f): woody, fruity, ambery.

Example 5 (compounds 1g - 1n):

The following dioxanes were obtained starting from diols 2a, 2b, 2c or 2d described in Examples 1b and 4, following the experimental procedures of Example 1c and 2:

a) (1 R,2S,2'S,4R,5'S)-2'-Ethyl-1 ,5',7,7-tetramethylspiro[bicyclo[2.2.1]heptane-2,4'- [1 ,3]dioxane] (1g)

¹ H NMR (C ₆ D ₆ ): δ0.55 (d, J=6.6, 3H), 0.85 (s, 3H), 0.88-0.93 (m, 1H), 0.97 (t, J= 7.6, 3H), 1.02 (s, 3H), 1.14 (s, 3H), 1.23-1.30 (m, 1H), 1.26 (d, J=I 3.4, 1H), 1.45 (ddd, J=13.9, 9.0, 3.3, 1H), 1.53-1.75 (m, 4H), 1.80 (ddd, J=13.4, 4.5, 3.0, 1H), 2.00 (ddq, J=11.4, 6.6, 5.1, 1H), 3.01 (t, J=I 1.4, 1H), 3.59 (dd, J=I 1.4, 5.1, 1H), 4.44 (t, J=4.8, 1H); ¹³ C NMR (C ₆ D ₆ ): δ8.3 (q), 10.9 (q), 15.2 (q), 20.7 (q), 22.2 (q), 26.2 (t), 28.6 (t), 29.8 (t), 31.5 (d), 33.5 (t), 45.2 (d), 49.7 (s), 54.9 (s), 70.8 (t), 86.4 (s), 94.6 (d); MS: 253 (0.3), 252 (2, M ⁺ ), 194 (5), 179 (10), 164 (44), 152 (12), 149 (27), 135 (24), 122 (20), 121 (100), 109 (44), 108 (87), 107 (61), 95 (42), 93 (96), 79 (39), 58 (38), 55 (34), 41 (73), 29 (68); [α] _D ²² -53.7 (c 1.0, EtOH).

Odour description: woody, ambery, green, sweet, floral.

b) (1 R,2S,2'R,4R,5 ^, S)-2'-Ethyl-1 ,5',7,7-tetramethylspiro[bicyclo[2.2.1]heptane-2,4'- [1 ,3]dioxane] (1h)

¹ H NMR (C ₆ D ₆ ): δ0.76-0.86 (m, 1H), 0.78 (s, 3H), 0.95 (d, J=6.6, 3H), 0.99 (t, J= 7.6, 3H), 1.02 (s, 3H), 1.10-1.20 (m, 1H), 1.26 (s, 3H), 1.28 (ddd, J=13.9, 9.4, 3.5, 1H), 1.49-1.58 (m, 2H), 1.52 (d, J=13.6, 1H), 1.68 (m, 2H), 1.90-1.98 (m, 2H), 3.48 (dd, J=10.6, 6.3, 1H), 3.75 (dd, J=10.6, 3.0, 1H), 5.12 (t, J=4.8, 1H); ¹³ C NMR (C ₆ D ₆ ): δ8.3 (q), 15.5 (q), 17.1 (q), 21.1 (q), 21.5 (q), 27.0 (t), 29.4 (t), 31.0 (t), 31.5 (d), 42.5 (t), 44.4 (d), 50.1 (s), 54.7 (s), 68.3 (t), 85.8 (s), 96.4 (d); MS: 253 (0.5), 252 (3, M ⁺ ), 194 (7), 179 (14), 164 (45), 149 (27), 135 (24), 122 (22), 121 (100), 109 (53), 108 (95), 107 (63), 95 (53), 93 (100), 91 (46), 79 (41), 77 (31), 67 (28), 58 (41), 55 (39), 41 (81), 29 (73); [α] _D ²² +22.9 (c 0.9, EtOH).

Odour description: woody, green, weaker than compound 1g.

c) (1R,2S,2'S,4R,5'S)-2'-lsopropyl-1,5',7,7-tetramethylspiro[bi cyc[o[2.2.1]heptane-2,4'- [1 ,3]dioxane] (1i)

¹ H NMR (C ₆ D ₆ ): δ0.55 (d, J=6.6, 3H), 0.85 (s, 3H), 0.85-0.98 (m, 1H), 1.00 (s, 3H), 1.045 (d, J=7.1, 3H), 1.05 (d, J=7.1, 3H), 1.14 (s, 3H), 1.22-1.30 (m, 1H), 1.26 (d, J=13.4, 1H), 1.44 (ddd, J=13.9, 9.1, 3.3, 1H), 1.53-1.61 (m, 1H), 1.65 (t, J=4.5, 1H), 1.80 (ddd, J=13.4, 4.5, 3.3, 1H), 1.86 (qid, J=6.8, 4.0, 1H), 1.97 (ddq, J=11.4, 6.6, 5.1, 1H), 3.00 (t, J=11.4, 1H), 3.60 (dd, J=11.4, 5.1, 1H), 4.28 (d, J=4.0, 1H); ¹³ C NMR (C ₆ D ₆ ): δ 10.9 (q), 15.3 (q), 17.1 (q), 17.3 (q), 20.8 (q), 22.6 (q), 26.2 (t), 30.0 (t), 31.6 (d), 33.3 (d), 33.6 (t), 45.3 (d), 49.7 (s), 55.2 (s), 70.8 (t), 86.4 (s), 97.2 (d); MS: 267 (0.4), 266 (2, M ⁺ ), 194 (7), 179 (15), 177 (26), 164 (24), 152 (16), 149 (16), 135 (17), 121 (67), 109 (45), 108 (97), 107 (43), 95 (53), 93 (65), 81 (34), 79 (28), 69 (30), 55 (38), 43 (84), 41 (100); [α] _D ²² -52.5 (c 0.7, EtOH).

Odour description: woody, ambery, sweet, dry, cedarwood, creamy.

d) (1 R,2S,2'R,4R,5'S)-2'-lsopropyl-1 ,5',7,7-tetramethylspiro[bicyclo[2.2.1]heptane-2,4'- [1 ,3]dioxane] (1j)

¹ H NMR (C ₆ D ₆ ):δ0.78(s, 3H), 0.80-87 (m,1H), 0.95 (d, J=6.6, 3H), 1.04 (s,3H), 1.05 (d, J=6.8, 3H), 1.08 (d, J=6.8, 3H), 1.10-1.18 (m, 1H), 1.22-1.32 (m, 1H), 1.25 (s, 3H), 1.49-1.57

(m, 2H), 1.52 (d, J=13.9, 1H), 1.86 (qid, J=6.8, 4.5, 1H), 1.87-1.96 (m, 2H), 3.46 (dd, ./=10.6, 6.3, 1H), 3.76 (dd, J=10.6, 2.8, 1H), 4.96 (d, J=4.5, 1H); ¹³ C NMR (C ₆ D ₆ ): δ 15.7 (q), 16.7 (q), 17.1 (q), 17.2 (q), 21.2 (q), 21.7 (q), 27.0 (t), 31.1 (t), 31.5 (d), 34.0 (d), 42.6 (t), 44.4 (d), 50.1 (s), 54.8 (s), 68.4 (t), 85.8 (s), 98.8 (d); MS: 267 (0.7), 266 (4, M ⁺ ), 194 (9), 179 (19), 177 (17), 164 (24), 152 (8), 149 (14), 135 (15), 121 (59), 109 (49), 108 (100), 107 (39), 95 (59), 93 (62), 81 (29), 79 (27), 69 (27), 55 (37), 43 (79), 41 (92); [α] _D ²² +18.4 (c 1.1, EtOH).

Odour description: ambery, woody, green, floral, weaker than compound 1i.

e) (1R,2S,2'S,4R,5'R)-2'-lsopropyl-1 ,5',7,7-tetramethylspiro[bicyclo[2.2.1]heptane-2,4'- [1 ,3]dioxane] (1k)

¹ H NMR (C ₆ D ₆ ): δ0.81 (s, 3H), 0.81-0.93 (m, 2H), 0.95 (d, J=13.1, 1H), 1.03 (d, J=7.1, 3H), 1.04 (s, 3H), 1.05 (s, 3H), 1.06 (d, J=7.1, 3H), 1.22 (d, J=7.1, 3H), 1.24-1.39 (m, 2H), 1.57-1.67 (m, 2H), 1.89 (qid, J=7.1, 4.1, 1H), 2.15 (dt, J=13.1, 3.8, 1H), 3.49 (dd, J=I Ll, 1.5, 1H), 3.72 (dd, J=ILl, 1.5, 1H), 4.39 (d, J=4.1, 1H); ¹³ C NMR: δ 11.7 (q), 15.8 (q), 16.5 (q), 17.5 (q), 20.9 (q), 21.2 (q), 27.4 (t), 28.4 (t), 32.9 (d), 38.2 (d), 42.0 (t), 44.6 (d), 50.2 (s), 52.7 (s), 71.4 (t), 83.6 (s), 97.7 (d); MS: 267 (1), 266 (5, M ⁺ ), 194 (17), 179 (13), 177 (29), 153 (12), 152 (30), 137 (10), 123 (14), 121 (28), 109 (51), 108 (100), 95 (63), 93 (33), 81 (44), 69 (32), 69 (30), 55 (38), 43 (54), 41 (68); [α] _D ²² -62.5 (c 0.7, EtOH).

Odour description: fruity, animalic, woody, touch ambrette seeds.

f) (1 RS,2SR,2'RS/SR,4RS,5'RS/SR)-2'-Ethyl-1 ,5',7,7~tetramethylspiro[bicyclo[2.2.1]- heptane-2,4'-[1 ,3]dioxane] (11)

1 :1.6:1.7 (GC elution order) racemic mixture of diastereomers.

Odour description: woody, ambery, fruity, carrot, sweet.

g) (1 RS,2SR,2'RS/SR,4RS,5'SR)-2'-lsopropyl-1 ,5',7,7-tetramethylspiro[bicyclo[2.2.1]- heptane-2,4'-[1 ,3]dioxane] (1m) 1 :1.2 (1R*,2S*,2'S*, 4R*,5'S*)/(1 R*,2S*,2'R*,4R*,5'S*) racemic mixture of epimers.

Odour description: ambery, woody, fruity, rich.

h) (1 RS,2SR,2'RS/SR _l 4RS,5'RS/SR)-2'-lsopropyI-1 ,5',7,7-tetramethylspiro [bicyclo[2.2.1]heptane-2,4'-[1 ,3]dioxane] (1n) 2.3:27:1.2:1 (GC elution order) racemic mixture of diastereomers.

Odour description: fruity, woody, green.

Example 6: (1 R.2S.4R.5'S)-1.2'.2'.5'.7.7-Hexamethvlspirorbicvclor2.2.1lhe ptane-2.4'- [1 ,3]dioxane] (1o)

A solution of diol 2a from Example 1b (3.0 g, 14 mmol), 2,2-dimethoxypropane (2.35 g, 23 mmol), PTSA monohydrate (0.20 g, 1.1 mmol) and lithium bromide (0.20 g, 2.3 mmol) in THF (45 ml) was stirred overnight at room temperature. The reaction mixture was poured into ice-cold aqueous sodium bicarbonate solution (100 ml), and extracted with MTBE (2 x 100 ml). After washing with brine (100 ml), drying (MgSO ₄ ) and evaporation of solvents in vacuo, the residue was purified by flash chromatography (neutral aluminum oxide; n-hexane/MTBE 15:1 ) to give (1 R,2S,4R,5'S)-1 ,2',2',5',7,7- hexamethylspiro[bicyclo[2.2.1]heptane-2,4'-[1 ,3]dioxane] (1o, 0.99 g, 28%).

¹ H NMR: δ0.84 (s, 3H), 0.845 (s, 3H), 0.98 (d, J=6.8, 3H), 0.99-1.06 (m, 1H), 1.07 (s, 3H), 1.26 (s, 3H), 1.32 (ddd, J=13.9, 11.6, 5.1, 1H), 1.43 (s, 3H), 1.46 (ddd, J=13.9, 9.1, 3.5, 1H), 1.57- 1.67 (m, 1H), 1.66 (d, J=13.6, 1H), 1.69 (t, J=4.5, 1H), 2.02-2.12 (m, 1H), 2.09 (ddd, J=13.6, 4.5, 3.0, 1H), 3.40 (dd, J=11.8, 7.6, 1H), 3.65 (dd, J=11.8, 5.3, 1H); ¹³ C NMR: δ 10.9 (q), 17.5 (q), 21.0 (q), 21.7 (q), 24.9 (q), 26.3 (t), 29.2 (q), 29.4 (t), 30.9 (d), 37.9 (t), 45.8 (d), 49.3 (s), 55.6 (s), 64.9 (t), 84.7 (s), 97.4 (s); MS: 253 (0.1), 252 (1, M ⁺ ), 194 (15), 179 (21), 164 (21), 149 (13), 137 (10), 135 (13), 123 (13), 121 (55), 109 (45), 108 (100), 107 (36), 95 (78), 93 (58), 81 (40), 69 (29), 59 (40), 55 (34), 43 (100), 41 (67); [α] _D ²² -43.5 (c 1.0, EtOH).

Odour description: woody, ambery, camphoraceous, earthy/mossy.

Example 7: (1 R,2S,4R,5'R)-1 ,2',2',5',7,7-Hexamethylspiro[bicyclo[2.2.1]heptane-2,4'- [1 ,3]dioxane] (1p)

Prepared according to the experimental procedure of Example 6 starting from diol 2b of Example 1b.

¹ HNMR: δ0.81 (s, 3H), 0.89 (s, 3H), 0.94-1.00 (m, 1H), 1.01 (s, 3H), 1.23 (d, J=6.6, 3H), 1.31- 1.38 (m, 2H), 1.33 (s, 3H), 1.38 (d, J=12.6, 1H), 1.47 (s, 3H), 1.54 (ddd, J=12.9, 9.3, 3.5, 1H), 1.62-1.73 (m, 1H), 1.65 (t, J=4.5, 1H), 2.54 (ddd, J=12.6, 4.5, 3.3, 1H), 3.49 (dd, ./=11.6, 2.3, 1H), 4.28 (dd, J=I 1.6, 1.6, 1H); ¹³ C NMR: δ 12.1 (q), 16.2 (q), 20.9 (q), 24.1 (q), 27.2 (t), 28.4 (t), 31.3 (q), 31.3 (q), 37.6 (d), 45.0 (d), 45.4 (t), 50.4 (s), 52.9 (s), 65.2 (t), 83.4 (s), 98.0 (s); MS: 253 (0.1), 252 (1, M ⁺ ), 194 (28), 179 (18), 177 (12); 164 (15), 152 (9), 149 (10), 137 (10), 135 (11), 125 (17), 121 (45), 109 (48), 108 (100), 107 (30), 95 (82), 93 (48), 81 (46), 69 (35), 59 (44), 55 (34), 43 (83), 41 (64); [α] _D ²² -68.1 (c 1.0, EtOH).

Odour description: woody, agrestic, ambery, earthy/mossy, dry, cedarwood aspect.

Example 8: (1 RS,2SR,4RS,5'RS/SR)-1 ,2\2',5',7,7-Hexamethylspiro[bicyclo[2.2.1] heptane-2,4'-[1 ,3]dioxane] (1q)

Prepared according to the experimental procedure of Example 6 starting from diols 2d of Example 4b as a 1 :1.8 (1 R*,2S*,4R*,5'S*)/(1 R*,2S*,4R*,5'R*) racemic mixture of epimers.

Odour description: earthy/mossy, woody, vetiver aspect.

Example 9: (1 RS,2SR,2'RS/SR,4RS,5'RS/SR,6'RS/SR)-1 ,2',5\6',7,7- Hexamethylspiro[bicyclo[2.2.1]heptane-2,4'-[1 ,3]dioxane] (1r)

a) (1RS,2SR,1'RS/SR,2'RS/SR,4RS)- 2-(2-Hydroxy-1-methylpropyl)-1 ,7,7- trimethylbicyclo[2.2.1]heptan-2-ol (2e)

A diastereoisomer mixture of (1 RS,2SR,4RS)-2-(1 -oxiranylethyl)-1 ,7,7- trimethylbicyclo[2.2.1]heptan-2-ols was prepared according to the procedure described by Dimitrov, V.; Philipova, I. and Simova, S. {Tetrahedron: Asymmetry 1996, 7, 1493), i.e. route II, by MCPBA oxidation of (IRS^SR.I'RS/SR/lRS^-Cl-methylallyO-IJJ- trimethylbicyclo[2.2.1]heptan-2-ol (5a) cited in Example 4b. A solution of this mixture (2Q g _J _89jτmrioQ lidi _. ethyLether (60 ml) was added_dropw[se to lithium aluminum hydride (3.4 g, 89 mmol) suspended in the same solvent (200 ml), at t <10°C. The reaction mixture was stirred at room temperature for 2.5 h, then more LAH (3.4 g, 89

mmol) was added and stirring continued for 0.5 h. An aqueous 2M solution of sodium hydroxide (17 ml, 34 mmol) was added under ice bath cooling, the solid filtered off and the filtrate washed with brine (200 ml), dried (MgSO ₄ ) and concentrated in vacuo to give crude racemic mixture of diastereomers of (1 RS,2SR,1'RS/SR,2'RS/SR,4RS)-2-(2- hydroxy-1-methylpropyl)-1 ,7,7-trimethylbicyclo[2.2.1]heptan-2-ol (2e, 17.5 g, 87%, waxy white solid) used in the next step without further purification.

b) (1 RS,2SR,2'RS/SR,4RS,5'RS/SR,6'RS/SR)-1 ,2',5',6',7,7- hexamethylspiro[bicyclo[2.2.1]heptane-2,4'-[1 ,3]dioxane] (1r)

Prepared as a 3.2:13.6:1 :1.3 (GC elution order) racemic mixture of diastereoisomers starting from the above described diol, according to the experimental procedure of Example 1c.

¹ H NMR (main racemic diastereoisomer): δ0.82 (s, 3H), 0.94 (s, 3H), 0.94-1.20 (m, 1H), 0.95 (s, 3H), 1.01 (d, J=6.6, 3H), 1.13-1.19 (m, 1H), 1.14 (d, J=6.6, 3H), 1.22 (d,-J=13.7, 1H), 1.25 (d, J=5.1, 3H), 1.33-1.43 (m, 1H), 1.47-1.55 (m, 1H), 1.67-1.76 (m, 1H), 1.69 (t, J=4.5, 1H), 2.30 (dt, J=12.9, 3.8, 1H), 3.98 (qd, J=6.6, 2.0, 1H), 4.90 (q, J= 5.1, 1H); ¹³ C NMR (main racemic diastereoisomer): δ9.4 (q), 12.1 (q), 19.0 (q), 20.9 (q), 21.0 (q), 21.4 (q), 27.5 (t), 28.2 (t), 41.8 (d), 41.9 (t), 44.6 (d), 50.0 (s), 52.5 (s), 72.5 (d), 84.9 (s), 91.2 (d); MS (main racemic diastereoisomer): 253 (0.5), 252 (2, M ⁺ ), 208 (23), 193 (10), 153 (30), 152 (21), 137 (7), 121 (11), 110 (28), 109 (59), 108 (98), 95 (100), 93 (29), 91 (25), 83 (31), 81 (81), 79 (28), 69 (39), 67 (31), 56 (45), 55 (48), 43 (35), 41 (61).

Odour description: Woody, fruity, ambery, sweet, cedarwood.

Example 10: (1 RS,2SR,4RS,5'RS/SR,6'RS/SR)-1 ,2',2',5',6',7,7- Heptamethylspiro[bicyclo[2.2.1]heptane-2,4'-[1 ,3]dioxane] (1s)

Prepared as a 1 :5.5 (GC elution order) racemic mixture of epimers starting from diol 2e described in Example 9a, following the experimental procedure of Example 6.

¹ H NMR (main racemic epimer): δ0.81 (s, 3H), 0.82 (s, 3H), 0.94-1.02 (m, 1H), 0.99 (d, J=6.6, 3H), 1.02 (s, 3H), 1.12-1.18 (m, 1H), 1.14 (d, J=6.6, 3H), 1.31-1.40 (m, 1H), 1.33 (s, 3H), 1.36 (d, J=12.6, 1H), 1.46 (s, 3H), 1.55 (ddd, J=13.4, 9.3, 3.5, 1H), 1.63-173 (m, 1H), 1.64 (t, J=4.4,

1H), 2.51 (ddd, J=12.6, 4.4, 3.3, 1H), 4.27 (qd, J=6.4, 1.4, 1H); ¹³ C NMR: (main racemic diastereoisomer): δ9.5 (q), 12.4 (q), 19.3 (q), 20.9 (q), 21.0 (q), 24.6 (q), 27.4 (t), 28.3 (t), 31.4 (q), 41.8 (d), 44.9 (d), 45.2 (t), 50.5 (s), 52.9 (s), 65.6 (d), 84.9 (s), 98.5 (s); MS (main racemic diastereoisomer): 266 (0.1, M ⁺ ), 251 (1), 208 (24), 191 (11), 153 (10), 152 (19), 135 (10), 121 (16), 110 (27), 109 (57), 108 (93), 95 (100), 93 (34), 83 (32), 81 (76), 67 (27), 59 (43), 55 (48), 43 (64), 41 (57).

Odour description: Woody, earthy/mossy, cedarwood.

Example 11 : (1 RS,2SR,2'RS/SR,4RS,5'RS/SR,6'RS/SR)-6'-Ethyl-1 ,2',5',7,7- pentamethylspiro[bicyclo[2.2.1]heptane-2,4'-[1 ,3]dioxane] (1t)

a) (1 RS,2SR,1'RS/SR,2'RS/SR,4RS)- 2-(2-Hydroxy-1-methylbutyl)-1 ,7,7- trimethylbicyclo[2.2.1]heptan-2-ol (2f)

1.6 M solution of methyl iodide in diethyl ether (223 ml, 0.36 mol) was added to a suspension of copper (I) iodide (34 g, 0.18 mol) in diethyl ether (100 ml) at t <-20°C and stirring continued at this temperature for 35 min. The clear yellow reaction mixture was cooled to -40°C and the crude 2-(1-oxiranylethyl)-1 ,7,7- trimethylbicyclo[2.2.1]heptan-2-ol from Example 9a (5.0 g, 22 mmol) dissolved in diethyl ether (25 ml) was added. After stirring for 1h at -40°C and 2 h at -20°C, the reaction mixture was poured into an ice-cold solution of ammonium chloride (300 ml), acidified with 2M HCI and filtered through Celite ^® . The filtrate was extracted with MTBE (2 x 200 ml), washed with brine (2 x 200 ml) dried (MgSO ₄ ) and concentrated in vacuo to give crude (1RS,2SR,1'RS/SR,2'RS/SR,4RS)- 2-(2-hydroxy-1-methylbutyl)-1 ,7,7- trimethylbicyclo[2.2.1]heptan-2-ol (2f, 4.2 g, 79%, waxy white solid), used in the next ketalisation steps without further purification.

b) (1 RS,2SR,2'RS/SR,4RS,5'RS/SR,6'RS/SR)-6'-Ethyl-1 ,2',5',7,7- pentamethylspiro[bicyclo[2.2.1]heptane-2,4'-[1 ,3]dioxane] (1t)

Prepared as a 1.6:3.8:1 (GC elution order) racemic mixture of diastereoisomers starting from the above described diol (2f), according to the experimental procedure of Example 1c.

¹³ C NMR (main racemic diastereoisomer): δ 9.6 (q), 10.0 (q), 12.2 (q), 20.9 (q), 21.0 (q), 21.4 (q), 25.7 (t), 27.6 (t), 28.2 (t), 40.1 (d), 42.0 (t), 44.6 (d), 50.5 (s), 52.5 (s), 78.7 (d), 84.9 (s), 91.3 (d); MS (main racemic diastereoisomer): 267 (0.4), 266 (2, M ⁺ ), 237 (2), 222 (18), 193 (28), 153 (51), 152 (18), 135 (7), 121 (12), 110 (29), 109 (64), 108 (100), 95 (98), 93 (32), 81 (78), 70 (38), 69 (55), 55 (58), 43 (32), 41 (61).

Odour description: woody, fruity, green, pine, eucalyptus, cedarwood.

Example 12; (1 RS,2SR,4RS,5'RS/SR,6'RS/SR)-6'-Ethyl-1 ,2',2\5',7,7- hexamethylspiro[bicyclo[2.2.1]heptane-2,4'-[1 ,3]dioxane] (1u)

Prepared as a 1 :2 racemic mixture of diastereoisomers starting from diol 2f described in Example 11a, following the experimental procedure of Example 6.

¹ H NMR (main racemic epimer, C ₆ D ₆ ): δ0.85 (s, 3H), 0.86-0.95 (m, 1H), 0.90 (t, J=7.4, 3H), 1.06-1.09 (m, 4H), 1.08 (s, 3H), 1.18 (s, 3H), 1.18-1.27 (m, 1H), 1.19 (d, J=12.7, 1H), 1.28-1.35 (m, 1H), 1.40 (s, 3H), 1.45 (s, 3H), 1.47-1.54 (m, 1H), 1.59 (t, J=4.6, 1H), 1.59-1.68 (m, 2H), 2.45 (ddd, J=12.7, 4.6, 3.0, 1H), 3.85 (dd, J=8.2, 5.1, 1H); ¹³ C NMR: (main racemic diastereoisomer, C ₆ D ₆ ): δ 10.3 (q), 10.4 (q), 12.9 (q), 21.2 (q), 21.5 (q), 24.6 (q), 26.2 (t), 27.7 (t), 28.6 (t), 31.7 (q), 40.6 (d), 45.2 (d), 45.6 (t), 50.8 (s), 53.2 (s), 71.8 (d), 85.1 (s), 98.8 (s); MS: 280 (0.1, M ⁺ ), 265 (1), 222 (14), 205 (10), 193 (15), 153 (28), 152 (20), 135 (8), 121 (14), 110 (29), 109 (66), 108 (99), 95 (100), 93 (31), 83 (26), 81 (80), 80 (25), 69 (55), 67 (29), 59 (53), 55 (52), 43 (56), 41 (57).

Odour description: floral, sweet, woody, cedarwood aspect.

Example 13: (1 RS,2SR,2'RS/SR,4RS,5'RS/SR)-5'-Ethyl-1 ,2',7,7- tetramethylspiro[bicyclo[2.2.1]heptane-2,4'-[1 ,3]dioxane] (1v)

a) (1RS,2SR,4RS)-2-(1-Methylenepropyl)-1 ,7,7-trimethylbicyclo[2.2.1]heptan-2-ol (4b)

Prepared following the experimental procedure of Example 1a starting from racemic camphor and-2-bromobutd-ene.

¹ H-NMR: δ0.85 (s, 3H), 0.97 (s, 3H), 1.04 (ddd, J=12.2, 9.0, 5.1, 1H), 1.08 (t, J=7.3, 3H), 1.15 (s, 3H), 1.22 (ddd, J=13.1, 9.0, 4.1, 1H), 1.31 (ddd, J=13.1, 11.4, 5.1, 1H), 1.57 (s, 1H), 1.61- 1.69 (m, 1H), 1.74 (t, j=4.4, 1H), 1.93 (ddd, J=13.6, 4.3, 3.3, 1H), 2.08 (d, ,/=13.6, 1H), 2.05- 2.16 (m, 1H), 2.20-2.30 (m, 1H), 4.94 (sb, 1H), 5.18 (sb, 1H). ¹³ C-NMR: δ 11.4 (q), 13.7 (q), 21.4 (q), 21.5 (q), 25.9 (t), 26.8 (t), 30.8 (t), 43.1 (t), 45.0 (d), 50.0 (s), 52.6 (s), 84.4 (s), 109.6 (t), 155.8 (s); MS: 209 (0.2), 208 (1, M ⁺ ), 193 (2), 190 (11), 175 (12), 147 (20), 133 (14), 119 (14), 110 (14), 109 (25), 108 (10), 99 (16), 95 (100), 91 (16), 83 (27), 69 (10), 55 (32), 43 (16), 41 (26).

b) (1RS,2SR,1'RS/SR,4RS/SR)-2-(1-Hydroxymethylpropyl)-1 ,7,7-trimethyl- bicyclo[2.2.1]heptan-2-ol (2g)

Prepared as a racemic mixture of epimers following the experimental procedure of Example 1b starting from 4b. The crude (1RS,2SR,1'RS/SR,4RS/SR)-2-(1- hydroxymethylpropyl)-1 ,7,7-trimethyl-bicyclo[2.2.1]heptan-2-ol (2g, waxy solid) was used in the next step without further purification.

c) (1 RS,2SR,2'RS/SR,4RS,5'RS/SR)-5'-Ethyl-1 ,2',7,7- tetramethylspiro[bicyclo[2.2.1]heptane-2,4'-[1,3]dioxane] (1v)

Prepared as a 1 :1.3:1.2 (GC elution order) racemic mixture of diastereoisomers starting from (1RS,2SR,1'RS/SR,4RS/SR)-2-(1-hydroxymethylpropyl)-1,7,7-tri methyl- bicyclo[2.2.1]heptan-2-ol (2g), according to the experimental procedure of Example 1c.

¹ H NMR (main racemic diastereoisomer (1R*,2S*,2'S*,4R*,5'S*), C ₆ D ₆ ): δ0.48 (sp, J=7.4, 1H), 0.72 (t, J=7.4, 3H), 0.86 (s, 3H), 0.92-1.01 (m, 1H), 1.03 (s, 3H), 1.13 (s, 3H), 1.18 (d, J=13.4, 1H), 1.27-1.39 (m, 3H), 1.28 (d, J=5.1, 3H), 1.58-1.71 (m, 2H), 1.66 (t, J=4.6, 1H), 1.88 (ddd, J=13.4, 4.6, 3.0, 1H), 3.08 (dd, J=11.4, 0.8, 1H), 3.87 (dd, J=11.4, 5.3, 1H), 4.66 (q, J=5.1, 1H); ¹³ C NMR (main racemic diastereoisomer, C ₆ D ₆ ): δ 11.3 (q), 13.5 (q), 20.9 (q), 21.6 (q), 22.3 (q), 22.6 (t), 27.2 (t), 29.7 (t), 34.7 (t), 39.8 (d), 45.4 (d), 50.1 (s), 55.1 (s), 69.4 (t), 85.9 (s), 91.2 (d); MS (main racemic diastereoisomer): 253 (0.4), 252 (2, M ⁺ ), 208 (5), 179 (12), 164 (6), 153 (15), 152 (34), 135 (25), 125 (23), 121 (19), 110 (21), 109 (59), 108 (100), 107 (23), 95 -(66), 93 (33), 81 (41), 69 (29), 56 (39), 55 (53),43-(58), 41- (76), 29-(35).

Odour description: woody, ambery, fruity, slightly carrot-like.

Example 14: Determination of GC-odour threshold concentration

According to standard procedures known to the person skilled in the art, threshold concentrations for volatile perfumery compounds are determined on a gas chromatograph equipped with a sniff port by a panel of trained evaluators. The lowest concentration smelled by each panellist is recorded as the individual threshold concentration expressed in ng (absolute amount of compound delivered at the sniff port).

Under identical conditions the odour threshold concentration for racemic mixture of compounds A, B and C respectively was measured and compared by a group of 4 panelists. The results are given below.

odour threshold concentration [ng]

Compound geometric mean

A (Example Ia of EP 0 761 664) 22 B (Example Is of EP 0 761 664) 68

C (compound according to the present invention wherein 3 R ¹ and R ⁵ is methyl and R ² , R ³ , R ⁴ and R ⁶ is hydrogen)

It can be seen from the results that the compounds of the present invention which is substituted at C5' position has an odour threshold value which is more than 22 times lower compared to the compound substituted at C6' position and more than 7 times lower-compared to the-compound-which is substituted at 02' position only-With other- words, whereas the substitution at C6' position (prior art) negatively influence the odour threshold, the substitution at C5' position influence it positively compared to the

compound which is substituted neither at C5' nor at C6' position (prior art). Based on this, a significant advance is achieved because much smaller amounts of the claimed compounds is required to impart the same odour.

Example 15: Feminine fine fragrance composition

In this feminine accord, the presence of the compound 1b enhances the woody amber notes and makes the whole composition richer, more dynamic and more elegant.