Organic compounds

Abstract

Disclosed are 3-alkylcyclopent-2-en-1-one and 3-alkylcyclopentan-1-one derivatives of formula (I) that possess strong spicy and woody notes.

Description

[Technical field]

[0001] The present invention relates to flavor and fragrance ingredients and compositions containing them useful for flavor and fragrance applications. It also relates to methods for making them. In particular, the present invention relates to 3-alkylcyclopent-2-en-1-one derivatives of formula (I) that possess strong spicy and woody notes. [Background technology]

[0002] In the flavor and fragrance industry, perfumers and flavorists are constantly searching for new compounds that possess unique olfactory properties. For example, there is a need for ingredients that are suitable for the flavor and fragrance industry and possess spicy and woody notes. Woody and spicy notes are fundamental olfactive families, such as jasmine and floral, for example. They can not only be key attributes of a perfume, but also support and complement the overall harmony of the perfume.

[0003] Surprisingly, the inventors have found that a new class of ingredients, represented by formula (I) as defined herein below, possesses the highly sought-after spicy and woody notes, which in particular support and promote the harmony of spicy and woody fragrances. Summary of the Invention

[0004] According to a first aspect of the present invention, a compound of formula (I) [ka] During the ceremony R 1 is selected from C1-C3 alkyl (e.g., ethyl, n-propyl, iso-propyl); R2 is a hydrocarbon residue containing up to 10 carbon atoms, R 3 and R 4 is independently selected from hydrogen and methyl, with the proviso that R 3 or R 4 is methyl; and the dotted line, together with the carbon-carbon bond, forms a single or double bond. The compound represented by the formula: is provided in the form of any one of its stereoisomers or a mixture thereof.

[0005] According to a second aspect of the present invention there is provided a fragranced article comprising a compound of formula (I) of the first aspect as an odorant. According to a third aspect of the invention there is provided a method of improving, enhancing and / or modifying a consumer product base or consumable product base by addition thereto of an olfactory acceptable amount of a compound of formula (I) of the first aspect.

[0006] According to a fourth aspect of the present invention there is provided a flavoured product comprising a compound of formula (I) according to the first aspect. According to a fifth aspect of the present invention there is provided a fragrance or flavour composition comprising a compound of formula (I) according to the first aspect. According to a sixth aspect of the present invention there is provided the use of a compound of formula (I) according to the first aspect as a flavour or fragrance.

[0007] Certain embodiments of any aspect of the invention may provide one or more of the following advantages: Providing novel flavor and fragrance compounds with spicy and woody notes; - Providing highly performing compounds with low odor thresholds.

[0008] The details, examples, and preferences provided with respect to any particular one or more of the defined aspects of the invention are described further herein and will apply equally to all aspects of the invention. Any combination of the embodiments, examples, and preferences described herein in all their possible variations is covered by the present invention unless otherwise indicated herein or otherwise clearly contradicted by context. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0009] Detailed Description The present invention is based on the surprising finding that 3-alkylcyclopent-2-en-1-one derivatives as defined herein possess strong spicy and woody notes.

[0010] In a first aspect of the present invention, a compound of formula (I) [ka] During the ceremony R 1 is selected from C1-C3 alkyl (e.g., ethyl, n-propyl, iso-propyl); R 2 is a hydrocarbon residue containing up to 10 carbon atoms, R 3 and R 4 is independently selected from hydrogen and methyl, with the proviso that R 3 or R 4 is methyl; and The dotted lines, together with the carbon-carbon bond, form a single or double bond. The compound represented by the formula: is provided in the form of any one of its stereoisomers or a mixture thereof.

[0011] In one particular embodiment, the compound of formula (II) [ka] During the ceremony R 1 is selected from C1-C3 alkyl (e.g., ethyl, n-propyl, iso-propyl); R 6 is selected from hydrogen, and C1-C3 alkyl (e.g., ethyl, n-propyl, iso-propyl); R 3 and R 4 is independently selected from hydrogen and methyl, with the proviso that R 3 or R 4 is methyl; R 5 is selected from hydrogen and C1-C3 alkyl (e.g., ethyl, n-propyl, iso-propyl); and Each of the dotted lines, together with the carbon-carbon bond, forms a single bond or a double bond. The compound represented by the formula: is provided in the form of any one of its stereoisomers or a mixture thereof.

[0012] In another specific embodiment, the 3-alkylcyclopent-2-en-1-one derivative is represented by formula (III): [ka] During the ceremony R 1 is methyl or ethyl, and R 6 is methyl or ethyl, R 3 and R 4 is independently selected from hydrogen and methyl, with the proviso that R 3 or R 4 is methyl, and The dotted lines, together with the carbon-carbon bond, form a single or double bond. in the form of any one of its stereoisomers or a mixture thereof.

[0013] In a further specific embodiment, the 3-alkylcyclopent-2-en-1-one derivative is represented by formula (IV): [ka] During the ceremony R 1 is methyl or ethyl, and R 7 is methyl or ethyl, R 3 and R 4 is independently selected from hydrogen and methyl; in the form of any one of its stereoisomers or a mixture thereof.

[0014] In one specific embodiment, the compound of formula (I), which encompasses the compounds of formulas (II), (III), and (IV), comprises R 3 and R 4 is methyl. In one specific embodiment, the compound of formula (I), which encompasses the compounds of formulas (II), (III), and (IV), comprises R 1 , R 3 , and R 4 is methyl.

[0015] In another specific embodiment, the compound of formula (I) is 2-(3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one, (3-(but-2-en-1-yl)-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one, 2-(2,2-dimethyl-3-(pent-2-en-1-yl)cyclopropyl)-3-methylcyclopent-2-en-1-one, 2-(2,2-dimethyl-3-pentylcyclopropyl)-3-methylcyclopent-2-en-1-one, 2-(3-butyl-2,2-dimethylcyclopropyl)-3-propylcyclopent-2-en-1-one, 2-(3-butyl-2,2-dimethylcyclopropyl)-3-ethylcyclopent-2-en-1-one, 2-(3-(but-2-en-1-yl)-2,2-dimethylcyclopropyl)-3-ethylcyclopent-2-en-1-one, 2-(3-(hex-2-en-1-yl)-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one, 2-(3-hexyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one, 3-methyl-2-(2,2,3-trimethylcyclopropyl)cyclopent-2-en-1-one, 2-(3-ethyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one, 2-(2,2-dimethyl-3-propylcyclopropyl)-3-methylcyclopent-2-en-1-one, 2-(3-allyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one, and 2-(3-(but-2-en-1-yl)-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one is selected from the group consisting of:

[0016] The compounds according to the present invention contain one or more chiral centers, and therefore may be present as a mixture of stereoisomers or may be resolved as isomerically pure forms.Resolving stereoisomers increases the complexity of the preparation and purification of these compounds, so it is preferred, for economic reasons only, to use the compounds as a mixture of their stereoisomers.However, if it is desired to prepare individual stereoisomers, this may be achieved according to methodologies known in the art, such as preparative HPLC and GC, or by stereoselective synthesis.

[0017] As one particular example, 2-(3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one may be cited, which contains two asymmetric centers and therefore may exist as a mixture of up to four stereoisomers (Va to Vd as shown below), in their diastereomerically pure or even enantiomerically pure forms. Some of the individual isomers have different odor qualities, both in terms of performance as well as olfactory properties. [ka]

[0018] For example, one may cite 2-((1S,3R)-3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one (Va), which, in addition to its overall spicy and woody odor notes, also possesses green, orris, rooty and vetiver aspects. 2-((1S,3R)-3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one has a remarkably low odor threshold concentration (below 1 pg), which is about 50,000 times lower than 2-((1R,3S)-3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one (Vb) and about 5,000 times lower than rel-2-((1S,3S)-3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one.

[0019] As a further example, 2-((1S,3R)-3-(but-2-en-1-yl)-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one may be cited, which also has a significantly lower odor threshold, about 6 times higher than 2-((1S,3R)-3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one (Va).

[0020] Thus, in another embodiment, there is provided a compound of formula (I) (which encompasses compounds of formulas (II) and (III)), wherein the relative configuration is as shown in formula (Ia): [ka] R in the formula 1 , R 2 , R 3 , and R 4 has the same meaning as given for the compounds of formula (I), As shown, it is in 1S, 3R.

[0021] In a further embodiment, there is provided a compound of formula (II) (which encompasses compounds of formulas (III) and (IV)), wherein the relative configuration is as shown in formula (IIa): [ka] R in the formula 1 , R 3 , R 4 , R 5 , and R 6 has the same meaning as given for the compounds of formula (II), As shown, it is in 1S, 3R.

[0022] As used herein, a "hydrocarbon residue" means a monovalent residue containing 1 to 10 carbon atoms (e.g., 2 to 9 C atoms, 3 to 8 C atoms, 4 to 7 C atoms, 4 to 6 C atoms), including C1 to C6, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl, isopentyl, 2-methylbutyl, n-pentyl, 4-methylpentyl, n-hexyl, n-heptyl, and n-octyl. 10Alkyl (linear or branched) and C2-C containing at least one double bond (e.g., up to three double bonds), such as 3-methyl-but-2-en-1-yl, 2-methylprop-1-en-1-yl, prop-1-en-1-yl, vinyl, but-1-en-1-yl, but-2-en-1-yl, but-3-en-1-yl, penta-1-en-1-yl, buta-1,3-dien-1-yl, and penta-1,3-dien-1-yl. 10 Includes alkenyl (linear or branched).

[0023] The compounds of formula (I), which encompasses the compounds of formulas (II), (III) and (IV), may be used alone, as mixtures of their isomers, or in combination with known odorant molecules selected from a wide range of natural products and currently available synthetic molecules (essential oils, alcohols, aldehydes and ketones, ethers and acetals, esters and lactones, macrocycles and heterocycles, etc.) and / or admixed with one or more ingredients or excipients (e.g. carrier materials and other auxiliaries commonly used in the art) conventionally used in conjunction with odorants in fragrance compositions.

[0024] As used herein, "carrier material" means a material that is practically neutral from the odorant's point of view, ie, a material that does not significantly alter the organoleptic properties of the odorant.

[0025] The term "auxiliary agent" refers to an ingredient that may be employed in a fragrance composition because it is not particularly related to the olfactory performance of the composition. For example, an auxiliary agent may be an ingredient that acts as an aid for processing the fragrance ingredient(s) or the composition containing the ingredient(s), or it may improve the handling or storage of the fragrance ingredient or the composition containing the ingredient. It may also be an ingredient that provides additional benefits, such as imparting color or texture. It may also be an ingredient that imparts lightfastness or chemical stability to one or more ingredients contained in the fragrance composition. A detailed description of the nature and type of adjuvants commonly used in fragrance compositions containing the ingredient cannot be exhaustive, but it should be mentioned that the ingredients are well known to those skilled in the art.

[0026] As used herein, "fragrance composition" refers to any composition comprising a compound represented by formula (I) (which encompasses compounds represented by formulas (II) and (III)), or a mixture thereof, and a diluent conventionally used in conjunction with odorants, such as base materials, e.g., diethyl phthalate (DEP), dipropylene glycol (DPG), isopropyl myristate (IPM), pentane-1,2-diol, triethyl citrate (TEC), and alcohol (e.g., ethanol). Optionally, the composition may contain an antioxidant adjuvant. The antioxidant may be selected from Tinogard® TT (BASF), Tinogard® Q (BASF), tocopherol (including its isomers, CAS 59-02-9; 364-49-8; 18920-62-2; 121854-78-2), 2,6-bis(1,1-dimethylethyl)-4-methylphenol (BHT, CAS 128-37-0), and the related phenol, hydroquinone (CAS 121-31-9).

[0027] The following list includes examples of known odorant molecules, which may be combined with the compounds of formula (I) (which encompasses the compounds of formula (Ia)), or mixtures thereof: essential oils and extracts, such as, for example, bead onion, costus root oil, oak moss absolute, geranium oil, tree moss absolute, basil oil, fruit oils such as bergamot oil and mandarin oil, myrtle oil, palmarosa oil, patchouli oil, petitgrain oil, jasmine oil, rose oil, sandalwood oil, absinthe oil, gruyun balsam oil, lavender oil and / or ylang-ylang oil;

[0028] alcohols, such as cinnamic alcohol ((E)-3-phenylprop-2-en-1-ol); cis-3-hexenol ((Z)-hex-3-en-1-ol); citronellol (3,7-dimethyloct-6-en-1-ol); dihydromyrcenol (2,6-dimethyloct-7-en-2-ol); Ebanol (trademark) ((E)-3-methyl-5-(2,2,3-trimethylcyclopenta[1,2-diphenylphosphine]-2,4-diol); -3-en-1-yl)pent-4-en-2-ol;Eugenol (4-allyl-2-methoxyphenol);Ethylinalool ((E)-3,7-dimethylnona-1,6-dien-3-ol);Farnesol ((2E,6Z)-3,7,11-trimethyldodeca-2,6,10-trien-1-ol);Geraniol ((E)-3,7-dimethylocta-2,6-dien-1-ol);Super Lily of the Valley (Super Muguet™ ((E)-6-ethyl-3-methyloct-6-en-1-ol); Linalool (3,7-dimethylocta-1,6-dien-3-ol); Menthol (2-isopropyl-5-methylcyclohexanol); Nerol (3,7-dimethyl-2,6-octadien-1-ol); Phenylethyl alcohol (2-phenylethanol); Rhodinol™ (3,7-dimethyloct-6-en-1-ol); Sandalore™ (3 -methyl-5-(2,2,3-trimethylcyclopent-3-en-1-yl)pentan-2-ol; terpineol (2-(4-methylcyclohex-3-en-1-yl)propan-2-ol); or Timberol™ (1-(2,2,6-trimethylcyclohexyl)hexan-3-ol); 2,4,7-trimethylocta-2,6-dien-1-ol, and / or [1-methyl-2(5-methylhex-4-en-2-yl)cyclopropyl]-methanol;

[0029] - aldehydes and ketones, such as anisaldehyde (4-methoxybenzaldehyde); alpha-amyl cinnamaldehyde (2-benzylideneheptanal); Georgywood™ (1-(1,2,8,8-tetramethyl-1,2,3,4,5,6,7,8-octahydronaphthalen-2-yl)ethanone); Hydroxycitronellal (7-hydroxy-3,7-dimethyloctanal); Iso E Super Super)® (1-(2,3,8,8-tetramethyl-1,2,3,4,5,6,7,8-octahydronaphthalen-2-yl)ethanone); Isoraldeine® ((E)-3-methyl-4-(2,6,6-trimethylcyclohex-2-en-1-yl)but-3-en-2-one); Hedione® (methyl 3-oxo-2-pentyl cyclopentane acetate); 3-(4-isobutyl-2-methylphenyl)propanal; maltol; methyl cedryl ketone; methyl ionone; verbenone; and / or vanillin;

[0030] ethers and acetals, such as, for example, Ambrox® (3a,6,6,9a-tetramethyl-2,4,5,5a,7,8,9,9b-octahydro-1H-benzo[e][1]benzofuran); geranyl methyl ether ((2E)-1-methoxy-3,7-dimethylocta-2,6-diene); and / or Spirambrene® (2',2',3,7,7-pentamethylspiro[bicyclo[4.1.0]heptane-2,5'-[1,3]dioxane]);

[0031] esters and lactones, such as, for example, benzyl acetate; cedryl acetate ((1S,6R,8aR)-1,4,4,6-tetramethyloctahydro-1H-5,8a-methanoazulen-6-yl acetate); delta-decalactone (6-pentyltetrahydro-2H-pyran-2-one); Helvetolide® (2-(1-(3,3-dimethylcyclohexyl)ethoxy)-2-methylpropylpropionate); delta-undecalactone (5-heptyloxolan-2-one); and / or vetiberyl acetate ((4,8-dimethyl-2-propan-2-ylidene-3,3a,4,5,6,8a-hexahydro-1H-azulen-6-yl)acetate);

[0032] macrocycles, such as, for example, ambrettolide ((Z)-oxacycloheptadecan-10-en-2-one); ethylene brassylate (1,4-dioxacycloheptadecane-5,17-dione); and / or Exaltolide® (16-oxacyclohexadecane-1-one); and - Heterocycles, for example isobutylquinoline (2-isobutylquinoline).

[0033] Thus, in a further aspect of the present invention, there is provided a fragrance composition comprising a compound of formula (I) (which encompasses compounds of formulae (II), (III) and (IV)).

[0034] The compounds of formula (I), which encompasses the compounds of formulas (II), (III), and (IV), may be used in a wide range of perfumed articles, including, for example, in the fields of fine and functional perfumery (perfumes, air care products, household products, laundry products, body care products, and cosmetics). The compounds may be employed in widely varying amounts, depending on the particular article and the nature and amount of other odorant ingredients. The proportion is typically from 0.00001 to 3 weight percent of the article. In one embodiment, the compounds may be employed in an amount of 0.0001 to 1 weight percent (e.g., 0.001 to 0.1 weight percent, including 0.05 weight percent and 0.03 weight percent) in a fabric softener. In another embodiment, the compounds may be used in fine perfumes in amounts of 0.00001 to 30 weight percent (e.g., up to about 10 weight percent or up to 20 weight percent), more preferably between 0.01 and 5 weight percent (e.g., 0.01-0.1 weight percent). However, these values ​​are given by way of example only, since a skilled perfumer can achieve effects or create new harmonies at lower or higher concentrations.

[0035] In another embodiment, the compounds of formula (I) (which encompasses the compounds of formulas (II), (III), and (IV)) may be used in a wide range of flavored products, including alcoholic and non-alcoholic beverages (e.g., tea), frozen dairy desserts, confectionery and bakery products, gelatin, puddings, meat and meat products, and tobacco. The compounds of formula (I) (which encompasses the compounds of formulas (II), (III), and (IV)) may also be used for flavor compositions, such as grape flavors, plum flavors, dried fruit flavors, red berry flavors (such as raspberry, blackberry, or gooseberry flavors). They may also be used as flavor enhancers, such as pepper, ginger, basil, rosemary, cardamom, nutmeg, cinnamon, peppermint, grapes (such as Shiraz grapes), juniper, and grapefruit.

[0036] When used in flavored products, the compounds of the present invention have a concentration of 0.01 ppb (10 ppb) by weight on a consumable basis. -11 ) to 10ppb(10 -8 ) by weight, more preferably up to 0.1 ppb (10 -10 ) to 1 ppb (10 -9 ), however, these values ​​should not be limiting for the present invention, since a skilled flavorist can achieve effects or create new combinations at lower or higher concentrations.

[0037] The compound of formula (I) (which encompasses compounds of formulae (II), (III) and (IV)) may be incorporated into a consumer product base by simply directly mixing the compound, or a fragrance composition comprising a compound of formula (I) (which encompasses compounds of formulae (II), (III) and (IV)), or mixtures thereof, with the consumer product base, or it may be encapsulated in a previous step with an encapsulating material (e.g. polymers, capsules, microcapsules and nanocapsules, liposomes, film formers, absorbents such as carbon or zeolites, cyclic oligosaccharides, and mixtures thereof) and then mixed with the consumer product base.

[0038] Thus, the present invention additionally provides a method for producing a perfumed article or flavored product, said method comprising the incorporation of a compound of formula (I) (which encompasses compounds of formulae (II), (III), and (IV)) or mixtures thereof as a flavor and / or fragrance ingredient either directly into a consumer product base or by incorporation of a fragrance / flavor composition comprising a compound of formula (I) (which encompasses compounds of formulae (II), (III), and (IV)) or mixtures thereof, which may then be mixed with the consumer product base using conventional techniques and methods. Through the addition of an olfactory acceptable amount of a compound of formula (I) (which encompasses compounds of formulae (II), (III), and (IV)) or mixtures thereof, the odor notes of the consumer product base will be improved, enhanced, or modified.

[0039] Thus, the present invention also provides a method of improving, enhancing or modifying a consumer product base by adding thereto an olfactory acceptable amount of a compound of formula (I) (which covers compounds of formulas (II), (III) and (IV)) or a mixture thereof.

[0040] In a further aspect of the present invention, there is provided a perfumed article comprising: a) Formula (I) [ka] During the ceremony R 1 is selected from C1-C3 alkyl (e.g., ethyl, n-propyl, iso-propyl); R 2 is a hydrocarbon residue containing up to 10 carbon atoms, R 3 and R 4 is independently selected from hydrogen and methyl, with the proviso that R 3 or R 4 is methyl; and The dotted lines, together with the carbon-carbon bond, form a single or double bond. Compounds represented by the formula: b) Consumer product based.

[0041] As used herein, "consumer product base" refers to a composition for use as a consumer product that performs a specific function, such as cleaning, softening, and care. Examples of such products include fine perfumes, such as perfumes and eau de toilette; fabric care, household products, and personal care products, such as cosmetics, laundry care detergents, rinse conditioners, personal cleansing compositions, dishwasher cleaners, surface cleaners; laundry products, such as fabric softeners, bleaches, cleaning agents; body care products, such as shampoos, shower gels; air care products (including products that preferably contain volatile and often fragrant compounds, which can advantageously mask unpleasant odors even in very small amounts). Air fresheners for living areas contain, inter alia, natural and synthetic essential oils, such as pine oil, citrus oil, eucalyptus oil, lavender oil, etc., in amounts of, for example, up to 50% by weight. As aerosols, they tend to contain smaller amounts of such essential oils, for example less than 5% or less than 2% by weight, but additionally include compounds such as acetaldehyde (especially <0.5% by weight), isopropyl alcohol (especially <5% by weight), mineral oil (especially <5% by weight), and propellants.

[0042] Cosmetic products include: (a) Cosmetic skin care products, in particular bath products, products for washing and cleansing the skin, skin care products, eye make-up, lip care products, nail care products, intimate care products and foot care products; (b) Cosmetic products with specific functions, in particular sunscreens, tanning products, depigmenting products, deodorants, antiperspirants, depilatories and shaving products; (c) Cosmetic dental care products, in particular dental and oral care products, tooth care products, cleaners for dental prostheses, adhesives for dental prostheses; and (d) Cosmetic hair products, in particular hair shampoos, hair care products, hair setting products, hair shaping products and hair colouring products.

[0043] This list of products is given by way of example and should not be considered limiting in any way. In one particular embodiment, the consumer product base is selected from fine fragrances and personal care products including deodorants, hair care products, soaps, and the like. In further specific embodiments, the consumer product base is selected from fabric care products, including fabric softeners, and home care products, including air fresheners, dishwashers, and the like.

[0044] In a further aspect, there is provided a flavored product comprising: a) Formula (I) [ka] During the ceremony R 1 is selected from C1-C3 alkyl (e.g., ethyl, n-propyl, iso-propyl); R 2 is a hydrocarbon residue containing up to 10 carbon atoms, R 3 and R 4 is independently selected from hydrogen and methyl, with the proviso that R 3 or R 4 is methyl; and The dotted lines, together with the carbon-carbon bond, form a single or double bond. Compounds represented by the formula: b) Consumables-based.

[0045] As used herein, "consumable base" means a composition for use as a consumable, such as a foodstuff and beverage, or a personal care product that is intended to be introduced into the oral cavity of a human or animal and remain there for a period of time before being ingested or removed from the mouth. Such products encompass the composition in a processed, partially processed, or raw state.

[0046] R 2 The compounds of formula (I) (which encompasses compounds of formula (II), (III), and (IV)), wherein is selected from alkyl and alkenyl, may be synthesized, for example, by ozonolysis of delta-3-carene followed by Wittig reaction, hydrogenation, alkylation, and ring closure, or by cyclopropanation reaction of an alkene, or by the Stetter reaction of an aldehyde with an alpha,beta-unsaturated ketone followed by ring closure.

[0047] R 2 The compound of formula (I) (which encompasses compounds of formulas (II), (III), and (IV)), wherein is selected from alkoxy, may be synthesized, for example, by ozonolysis of delta-3-carene, followed by etherification, followed by alkylation and ring closure. The invention will now be further described with reference to the following non-limiting examples, it will be understood that these examples are for the purpose of illustration only, and that variations and modifications may be made by those skilled in the art.

[0048] Example 1: 2-((1S,3R)-3-Butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one a) Synthesis of 2-((1R,3S)-2,2-dimethyl-3-(2-oxopropyl)cyclopropyl)acetaldehyde (1S,6R)-3,7,7-trimethylbicyclo[4.1.0]hept-3-ene ((+)-3-carene, [α] D 24= +21.4° [c = 1.3, EtOH]) (20.0 g, 147 mmol, 1.0 equiv) was ozonized at -78 °C until the color of the solution changed to light blue. The reaction mixture was then purged with nitrogen and triphenylphosphine (47.4 g, 181 mmol, 1.2 equiv) was added slowly in several portions at 0 °C. After stirring at 23 °C for 1 h, the reaction mixture was concentrated under reduced pressure. The crude was diluted with heptane / MTBE (3:1), mixed and the formed precipitate was filtered off. The filtrate was concentrated under reduced pressure and purified by column chromatography to provide 2-((1R,3S)-2,2-dimethyl-3-(2-oxopropyl)cyclopropyl)acetaldehyde (19.6 g, 79% yield) as a colorless liquid.

[0049] 1 H NMR (400 MHz, CDCl3, δ / ppm): 9.73 (t, J = 1.8 Hz, 1H), 2.39 - 2.21 (m, 4H), 2.12 (s, 3H), 1.10 (s, 3H), 0.97 - 0.90 (m, 2H), 0.87 (s, 3H). 13 C NMR (101 MHz, CDCl3, δ / ppm): 208.1, 201.7, 39.5, 39.2, 29.5, 28.4, 21.1, 19.2, 17.0, 15.0. GC / MS (EI): m / z (%):153 (1, [M] +· - ·CH3), 139 (12), 111 (19), 82 (11), 81 (14), 79 (12), 67 (13), 55 (27), 43 (100), 41 (20), 39 (12). [α] D 24 = -17.9°[c = 0.99, EtOH]. IR (neat, ν / cm -1): 2946, 2868, 1713s, 1454, 1413, 1357, 1321, 1302, 1234, 1165, 1030, 967, 921, 539. HRMS (ESI): C 10 H 17 O2[M + H] + Calculated m / z: 169.1223, Found: 169.1226.

[0050] b) Synthesis of 1-((1S,3R)-3-(but-2-en-1-yl)-2,2-dimethylcyclopropyl)propan-2-one To a solution of ethyltriphenylphosphonium bromide (38.8 g, 105 mmol, 1.1 equiv) in THF (160 mL) was added KOtBu (11.7 g, 105 mmol, 1.1 equiv) in portions at 0° C., and the reaction mixture was stirred at 0° C. for 30 min. The deprotonated Wittig salt mixture was then added dropwise to a solution of 2-((1R,3S)-2,2-dimethyl-3-(2-oxopropyl)cyclopropyl)acetaldehyde (16.0 g, 95 mmol, 1.0 equiv) in THF (160 mL) at 0° C. After stirring for 1 h at 0° C. and 14 h at room temperature, the reaction mixture was quenched with water and extracted with MTBE. The combined organic extracts were washed with brine, dried over MgSO4, and concentrated under reduced pressure. The crude material was purified by column chromatography to give 1-((1S,3R)-3-(but-2-en-1-yl)-2,2-dimethylcyclopropyl)propan-2-one (7.80 g, 46% yield, mixture of Z / E isomers in 88:12 ratio) as a colorless liquid.

[0051] 1 H NMR (400 MHz, CDCl3, δ / ppm, mixture of isomers): 5.49 - 5.26 (m, 2H), 2.43-2.25 (m, 2H), 2.15 (s, 3H), 1.98-1.88 (m, 2H), 1.64 - 1.55 (m, 3H), 1.07 (s, 3H), 0.92 (s, 3H), 0.86 - 0.75 (m, 1H), 0.62 (td, J = 7.5, 9.0 Hz, 1H). 13 C NMR (101 MHz, CDCl3, δ / ppm, Z isomers): 209.1, 129.8, 123.5, 39.4, 29.5, 28.9, 26.1, 22.0, 21.2, 17.0, 14.9, 12.8. Characteristic signals for the minor E isomer: 13 C NMR (101 MHz, δ / ppm): 130.4, 124.6, 25.5. GC / MS (EI), major Z isomer: m / z (%): 180 (0, [M] +· ), 123 (29), 107 (22), 95 (22), 81 (25), 79 (12), 69 (17), 67 (16), 55 (21), 43 (100), 41 (17). GC / MS (EI), minor E isomer: m / z (%):165 (5, [M] +· - ·CH3), 123 (21), 107 (19), 95 (20), 81 (24), 79 (11), 69 (15), 67 (16), 55 (24), 43 (100), 41 (17). [α] D 24 = -14.8°[c = 1.00, EtOH]. IR (neat, ν / cm -1 ): 3014, 2978, 2922, 2864, 1716s, 1669, 1453, 1406, 1354, 1320, 1302, 1256, 1234, 1163, 968, 696, 590, 546. HRMS (ESI): C 12 H 21 O [M + H] + Calculated m / z: 181.1587, Found: 181.1591.

[0052] Odour description: Peppery, pink peppercorn, black pepper, white pepper, green, slightly metallic.

[0053] c) Synthesis of 1-((1S,3R)-3-butyl-2,2-dimethylcyclopropyl)propan-2-one A suspension of 1-((1S,3R)-3-(but-2-en-1-yl)-2,2-dimethylcyclopropyl)propan-2-one (7.0 g, 38.8 mmol, 1.0 equiv) and Pd / C (5%, 0.41 g, 0.5 mol%) in EtOH (140 mL) was purged with argon (3x) and hydrogenated with a H2 balloon (1 bar) at room temperature for 3 h. The reaction mixture was filtered and concentrated under reduced pressure. The crude was purified by column chromatography to give 1-((1S,3R)-3-butyl-2,2-dimethylcyclopropyl)propan-2-one (6.80 g, 96% yield) as a colorless liquid.

[0054] 1 H NMR (400 MHz, CDCl3, δ / ppm): 2.38 - 2.23 (m, 2H), 2.14 (s, 3H), 1.32 - 1.10 (m, 6H), 1.05 (s, 3H), 0.93-0.84 (m, 6H), 0.76 (td, J = 7.3, 8.9 Hz, 1H), 0.52 (ddd, J = 6.6, 7.5, 8.9 Hz, 1H). 13 C NMR (101 MHz, CDCl3, δ / ppm): 209.4, 39.5, 32.2, 29.5, 28.9, 26.3, 24.2, 22.6, 21.3, 16.9, 14.9, 14.1. GC / MS (EI): m / z (%): 182 (1, [M] +· ), 125 (82), 95 (18), 83 (49), 82 (11), 81 (12), 69 (87), 67 (15), 55 (37), 43 (100), 41 (31). [α] D 24 = -14.2°[c = 1.01, EtOH]. IR (neat, ν / cm -1): 2956, 2927, 2860, 1715s, 1459, 1412, 1375, 1355, 1164. HRMS (ESI): C 12 H 23 O [M + H] + Calculated m / z: 183.1743, Found: 183.1747.

[0055] Odour description: Green, barky, vegetable, oily, fatty.

[0056] d) Synthesis of 1-((1S,3R)-3-butyl-2,2-dimethylcyclopropyl)hexane-2,5-dione To a solution of diisopropylamine (5.95 mL, 42.1 mmol, 1.6 equiv) in THF, n-BuLi (24.7 mL, 39.5 mmol, 1.5 equiv, 1.6 M in hexane) was added dropwise at -60°C, and the reaction mixture was stirred at that temperature for 30 min. Then, a solution of 1-((1S,3R)-3-butyl-2,2-dimethylcyclopropyl)propan-2-one (4.8 g, 26.3 mmol, 1.0 equiv) in THF (10 mL) was added dropwise at -60°C. After stirring at -60°C for 30 min, 1-chloropropan-2-one (3.1 mL, 39.5 mmol, 1.5 equiv) was added dropwise at -60°C. After stirring at -60°C for 30 min and 0°C for 30 min, the reaction mixture was stirred for 2 h while allowing to warm to room temperature. After quenching with brine, the reaction mixture was extracted with MTBE (2x). The combined organic extracts were washed with brine, dried over MgSO4, and the solvent was concentrated under reduced pressure. The crude was purified by column chromatography to give 1-((1S,3R)-3-butyl-2,2-dimethylcyclopropyl)hexane-2,5-dione (2.7 g, 11.3 mmol, 43%) as a colorless oil.

[0057] 1H NMR (400 MHz, CDCl3, δ / ppm): 2.74-2.63 (m, 4H), 2.46 - 2.22 (m, 2H), 2.16 (s, 3H), 1.39 - 1.08 (m, 6H), 1.04 (s, 3H), 0.91 - 0.83 (m, 6H), 0.76 (td, J = 7.2, 9.0 Hz, 1H), 0.56 - 0.45 (m, 1H). 13 C NMR (101 MHz, CDCl3, δ / ppm): 209.7, 207.2, 38.6, 36.9, 35.6, 32.2, 29.9, 28.9, 26.3, 24.2, 22.6, 21.2, 16.9, 14.9, 14.1. GC / MS (EI): m / z (%): 238 (2, [M] +· ), 125 (28), 99 (100), 95 (11), 83 (16), 71 (16), 69 (52), 67 (8), 55 (22), 43 (47), 41 (19). [α] D 24 = -14.5°[c = 1.32, EtOH]. IR (neat, ν / cm -1 ): 2955, 2925, 2861, 1711s, 1458, 1401, 1357, 1180, 1162, 1095. HRMS (ESI): C 15 H 27 O2[M + H] + Calculated m / z: 239.2006, Found: 239.2009.

[0058] e) Synthesis of 2-((1S,3R)-3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one To a solution of 1-((1S,3R)-3-butyl-2,2-dimethylcyclopropyl)hexane-2,5-dione (2.70 g, 11.3 mmol, 1.1 equiv) in EtOH (60 mL) was added dropwise at room temperature with aqueous 0.5 M NaOH (20 mL, 10.0 mmol, 1.0 equiv). After stirring at 30 °C for 24 h, the reaction mixture was extracted with MTBE (2x). The combined organic extracts were washed with water and brine, dried over MgSO4, and the solvent was removed under reduced pressure. The crude was purified by column chromatography and Kugelrohr distillation (130 °C, 0.05 mbar) to give 2-((1S,3R)-3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one (compound of formula Va) (1.27 g, 52%, >99% ee) as a colorless oil.

[0059] 1 H NMR (400 MHz, CDCl3, δ / ppm): 2.49 - 2.44 (m, 2H), 2.38 - 2.31 (m, 2H), 2.06 (s, 3H), 1.63 - 1.49 (m, 1H), 1.41 - 1.21 (m, 4H), 1.18 (s, 3H), 1.02 - 0.95 (m, 1H), 0.88 - 0.82 (m, 6H), 0.82 - 0.68 (m, 2H). 13 C NMR (101 MHz, CDCl3, δ / ppm): 209.7, 174.5, 138.1, 34.7, 32.3, 31.5, 29.2, 26.9, 26.4, 22.8, 21.7, 19.0, 17.9, 16.5, 14.2. GC / MS (EI): m / z (%): 220 (16, [M] +· ), 163 (54), 145 (82), 135 (44), 110 (100), 91 (61), 79 (41), 77 (41), 69 (89), 55 (60), 41 (75). [α] D 24 = +69.3°[c = 1.00, EtOH]. IR (neat, ν / cm -1 ): 2955, 2928, 2860, 1701s, 1635, 1440, 1410, 1382, 1285, 1184, 1124, 1076, 997. HRMS (ESI): C 15 H 25 O [M + H] + Calculated m / z: 221.1900, Found: 221.1904.

[0060] Odour description: spicy, peppery, black pepper, woody, acet guayil, cephalis, green, rooty, vetiver-fruity, jasmone. Taste description (@3ppb in water): Woody, peppery, floral, citrus-grapefruit-like, slightly resinous.

[0061] Example 2: rel-2-((1S,3R)-3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one a) Synthesis of 2-(hex-1-yn-1-yl)-3-methylcyclopent-2-en-1-one A solution of 2-iodo-3-methylcyclopent-2-en-1-one (5.00 g, 22.5 mmol, 1.0 equiv, prepared according to WO2016044558A1), copper iodide (0.39 g, 2.0 mmol, 0.09 equiv), bis(triphenylphosphine)palladium(II) dichloride (0.63 g, 0.90 mmol, 0.04 equiv), and diisopropylamine (19 mL, 0.14 mol, 6.0 equiv) in THF (120 mL) was heated to 50° C. and a solution of 1-hexyne (5.20 mL, 45 mmol, 2.0 equiv) was added dropwise over 2 h. After stirring at 50° C. overnight, the reaction mixture was diluted with water and extracted with MTBE (2×). The combined organic extracts were washed with brine, dried over MgSO4, and the solvent was removed under reduced pressure. The crude material was purified by column chromatography to give 2-(hex-1-yn-1-yl)-3-methylcyclopent-2-en-1-one (3.50 g, 88%) as a colorless oil.

[0062] 1 H NMR (400 MHz, CDCl3, δ / ppm): 2.59 - 2.54 (m, 2H), 2.45 - 2.33 (m, 4H), 2.17 (s, 3H), 1.58 - 1.48 (m, 2H), 1.46 - 1.33 (m, 2H), 0.88 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, CDCl3, δ / ppm): 206.1, 178.3, 126.4, 99.1, 70.7, 34.5, 31.6, 30.7, 21.8, 19.3, 18.7, 13.5. GC / MS (EI): m / z (%): 176 (14, [M] +· ), 147 (28), 134 (100), 133 (55), 119 (36), 110 (27), 105 (45), 92 (49), 91 (92), 79 (25), 77 (37). IR (neat, ν / cm -1 ): 2931, 1704s, 1621, 1430, 1381, 1339, 1293, 1198, 1112, 682, 614. HRMS (ESI): C 12 H 17 O [M + H] + Calculated m / z: 177.1274, Found: 177.1278.

[0063] b) Synthesis of (Z)-2-(hex-1-en-1-yl)-3-methylcyclopent-2-en-1-one A suspension of 2-(hex-1-yn-1-yl)-3-methylcyclopent-2-en-1-one (2.90 g, 16.5 mmol, 1.0 equiv) and Lindlar catalyst (50 mg) in toluene (50 mL) and pyridine (5 mL) in a round-bottom flask was purged with argon and hydrogenated at 1 atm H2 (balloon) for 7 h. After complete conversion, the reaction mixture was filtered and concentrated under reduced pressure. The crude was purified by column chromatography to give (Z)-2-(hex-1-en-1-yl)-3-methylcyclopent-2-en-1-one (2.70 g, 92%) as a colorless oil.

[0064] 1 H NMR (400 MHz, CDCl3, δ / ppm): 5.80 - 5.66 (m, 2H), 2.58-2.51 (m, 2H), 2.45 - 2.36 (m, 2H), 1.99 (s, 3H), 1.90 - 1.82 (m, 2H), 1.37 - 1.18 (m, 4H), 0.88 - 0.74 (m, 3H). 13 C NMR (101 MHz, CDCl3, δ / ppm): 208.3, 171.5, 138.0, 136.6, 118.2, 34.6, 31.7, 31.3, 29.4, 22.2, 18.4, 13.8. GC / MS (EI): m / z (%):178 (50, [M] +· ), 149 (52), 135 (50), 122 (76), 121 (47), 110 (100), 93 (54), 91 (89), 79 (80), 77 (64). IR (neat, ν / cm -1 ): 2956, 2926, 2871, 2858, 1697s, 1625, 1438, 1406, 1377, 1284, 1173, 725. HRMS (ESI): C 12 H 19 O [M + H] + Calculated m / z: 179.1430, Found: 179.1433.

[0065] Odor description: Green, jasmon, carvone, celery ketone, floral, jasmine.

[0066] c) Synthesis of rel-2-((1S,3R)-3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one 1,1'-(pyridine-2,6-diyl)bis(N-(2-(tert-butyl)phenyl)ethan-1-imine) (0.20 g, 0.47 mmol, 10 mol%, 2-t-Bu A suspension of PDI (prepared according to Werth, J.; Uyeda, C. Angew. Chem. Int. Ed. 2018, 57, 13902) and CoBr2 (0.10 g, 0.47 mmol, 10 mol%) was stirred at room temperature for 20 h. Then a solution of (Z)-2-(hex-1-en-1-yl)-3-methylcyclopent-2-en-1-one (0.84 g, 4.71 mmol, 1.0 equiv) in THF (15 mL) was added, followed by Zn (0.62 g, 9.48 mmol, 2.0 equiv) and ZnBr2 (1.10 g, 4.71 mmol, 1.0 equiv). The color slowly changed from yellow to violet. After stirring for 15 min, dichloropropane (0.98 mL, 9.48 mmol, 2.0 equiv) was added dropwise and stirring was continued at room temperature for 16 h (10% conversion, 5% product peak by GC, 85% starting material). The reaction mixture was filtered over silica and concentrated under reduced pressure. The crude was purified twice by column chromatography to give rel-2-((1S,3R)-3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one (16 mg, 83% purity with 17% starting material, <2% yield) as a colorless oil. Analytical data were identical to those reported for 2-((1S,3R)-3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one (Example 1).

[0067] Odor description of rel-2-((1S,3R)-3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one: green (rooty, vetiver, slightly metallic), fruity (jasmone), spicy (peppery), woody (cedarwood bark, acetoguayl)

[0068] Example 3: Separation of 2-((1R,3S)-3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one from rel-2-((1S,3R)-3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one by chiral preparative HPLC A hexane solution (10 mg / mL solvent) of rel-2-((1S,3R)-3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one (prepared as described in Example 2) was separated by chiral preparative HPLC using a Regis(R,R)-Whelk-O 1 column (21 injections, 20 μL per injection). A total volume of 15 mL was collected and concentrated using a nitrogen stream to ca. 1.5 mL solvent to provide 2-((1R,3S)-3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one with a purity of 98.2% (>99% ee).

[0069] [α] D 24 = Optical rotation (OR) negative sign according to HPLC detector. Odor description: Woody, wood fiber, cedarwood, peppery, black pepper, green, rooty, vetiver root, slightly dusty, earthy.

[0070] Example 4: 2-(2-butylcyclopropyl)-3-methylcyclopent-2-en-1-one To freshly distilled CH2Cl2 (20 mL) was added diethylzinc (416 mg, 0.43 mL, 3.37 mmol, 2.0 equiv) under N2. The solution was cooled in an ice bath and a solution of trifluoroacetic acid (384 mg, 0.26 mL, 3.37 mmol, 2.0 equiv) in CH2Cl2 (5 mL) was added dropwise very slowly via syringe to the reaction mixture. After stirring for 20 min, a solution of methyl iodide (901 mg, 0.27 mL, 3.37 mmol, 2.0 equiv) in CH2Cl2 (5 mL) was added. After an additional 20 min of stirring, a solution of (E)-2-(hex-1-en-1-yl)-3-methylcyclopent-2-en-1-one (0.30 g, 1.68 mmol, 1.0 equiv) (CAS: 137097-83-7, prepared according to Tetrahedron Lett. 1991, 32, 4453) in CHCl (5 mL) was added and the ice bath was removed. After 30 min of stirring, the reaction mixture was quenched with 0.1 N HCl (50 mL) and hexanes (25 mL) and the layers were separated. The aqueous layer was extracted with hexanes. The combined organic layers were washed with saturated NaHCO, H0, and brine, dried (NaSO), filtered, and concentrated. The crude material was purified by column chromatography (hexane:MTBE=50:1) to give 2-(2-butylcyclopropyl)-3-methylcyclopent-2-en-1-one (100 mg, 31%).

[0071] 1 H NMR (400 MHz, CDCl3, δ / ppm): 2.48-2.38 (m, 2H), 2.33-2.25 (m, 2H), 2.09 (s, 3H), 1.50-1.22 (m, 7H), 1.20-1.06 (m, 2H), 0.89 (t, J = 7.1 Hz, 3H), 0.49-0.45 (m, 1H). 13 C NMR (400 MHz, CDCl3, δ / ppm): 209.0, 169.6, 139.1, 34.6, 34.3, 31.5, 31.2, 22.5, 17.9, 17.2, 14.5, 14.1, 11.5. GC / MS (EI): m / z (%): 192 (40) [M+], 177 (20), 163 (18), 149 (45), 135 (45), 122 (98), 110 (65), 91 (70), 79 (100), 65 (28), 55 (40).

[0072] Odour description: green, jasmon, jasmine, spicy, aniseed, celery, fenugreek.

[0073] Example 5: rel-2-((1S,3S)-3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one 1,1'-(pyridine-2,6-diyl)bis(N-(2-(tert-butyl)phenyl)ethan-1-imine) (0.24 g, 0.56 mmol, 10 mol%, 2-t-Bu A suspension of PDI (prepared according to Werth, J.; Uyeda, C. Angew. Chem. Int. Ed. 2018, 57, 13902) and CoBr2 (0.12 g, 0.56 mmol, 10 mol%) was stirred at room temperature for 20 h (green suspension). Then, a solution of (E)-2-(hex-1-en-1-yl)-3-methylcyclopent-2-en-1-one (1.0 g, 5.61 mmol, 1.0 equiv, prepared according to Pecunioso, A.; Menicagli, R. J. Org. Chem. 1988, 53, 11, 2614) in THF (8 mL) was added, followed by Zn (0.73 g, 11.2 mmol, 2.0 equiv) and ZnBr2 (1.30 g, 5.77 mmol, 1.0 equiv). After stirring for 15 min, dichloropropane (1.2 mL, 11.5 mmol, 2.0 equiv) was added dropwise. After stirring at room temperature for 16 h (29% conversion, 26% product peak by GC, 71% starting material), the reaction mixture was filtered over silica and concentrated under reduced pressure. The crude was purified three times by column chromatography to provide the enriched fraction of rel-2-((1S,3S)-3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one (90 mg, 95% purity with 5% starting material, 8% yield) as a yellow oil.

[0074] 1 H NMR (400 MHz, CDCl3, δ / ppm): 2.49 - 2.42 (m, 2H), 2.34 - 2.27 (m, 2H), 2.06 (s, 2H), 1.48 - 1.28 (m, 6H), 1.16 (s, 3H), 1.12 - 1.07 (m, 1H), 0.94 - 0.85 (m, 3H), 0.78 (s, 3H), 0.76 - 0.70 (m, 1H). 13 C NMR (101 MHz, CDCl3, δ / ppm): 209.8, 172.4, 138.4, 34.6, 32.2, 31.4, 29.6, 28.6, 25.7, 22.9, 22.7, 21.0, 21.0, 17.8, 14.1. GC / MS (EI): m / z (%): 220 (20, [M] +· ), 163 (55), 145 (84), 110 (100), 91 (65), 77 (45), 69 (93), 55 (50), 41 (85). IR (neat, ν / cm -1 ): 2956, 2921, 2858, 1697s, 1637, 1457, 1441, 1379, 1119, 1083. HRMS (EI): C 15 H 24 O [M] + Calculated m / z: 220.1822, Found: 220.1821.

[0075] Odor description: warm wood, patchouli, spicy, peppery, fresh ground pepper, green, metallic, rooty, fruity, jasmone.

[0076] Example 6: Separation of (+)-trans-2-(3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one by preparative HPLC A hexane solution (10 mg / mL solvent) of rel-2-((1S,3S)-3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one (prepared as described in Example 5) was separated by chiral preparative HPLC using a Regis(R,R)-Whelk-O 1 column (2 μL per injection). The collected fractions were concentrated using a nitrogen stream to a 1500 ng / μL solution of (+)-trans-2-(3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one with a purity of 99.9% (>99% ee).

[0077] [α] D 24 = Optical rotation (OR) positive sign according to HPLC detector. Odor description: woody, spicy, peppery, warm, round, soft.

[0078] Chiral GC (Macherey-Nagel, Hydrodex-beta-3P, 2min@50℃~1℃ / min~2min@230℃, H2): t R = 92.7min.; Chiral HPLC (Regis (R,R)-Whelk-O 1 column, isocratic elution with n-hexane / iPrOH 90:10, 1ml / min, 30°C, DAD@220nm, 250nm&280nm and ORD detector): t R = 4.97min.

[0079] Example 7: Separation of (-)-trans-2-(3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one by preparative HPLC A hexane solution (10 mg / mL solvent) of rel-2-((1S,3S)-3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one (prepared as described in Example 5) was separated by chiral preparative HPLC using a Regis(R,R)-Whelk-O 1 column (2 μL per injection). The collected fractions were concentrated using a nitrogen stream to a 1000 ng / μL solution of (−)-trans-2-(3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one with a purity of 99.9% (>99% ee).

[0080] [α] D 24 = Optical rotation (OR) negative sign according to HPLC detector. Odor description: Woody, spicy, peppery, green, metallic, rooty, ground pepper.

[0081] Chiral GC (Macherey-Nagel, Hydrodex-beta-3P, 2min@50℃~1℃ / min~2min@230℃, H2): t R = 93.1 min.; Chiral HPLC (Regis (R,R)-Whelk-O 1 column, isocratic elution with n-hexane / iPrOH 90:10, 1 ml / min, 30°C, DAD@220 nm, 250 nm & 280 nm and ORD detector): t R = 5.58min.

[0082] Example 8: 2-((1S,3R)-3-(but-2-en-1-yl)-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one a) 1-((1S,3R)-3-(but-2-en-1-yl)-2,2-dimethylcyclopropyl)hexane-2,5-dione To a solution of diisopropylamine (6.4 mL, 45 mmol, 1.4 equiv) in THF (10 mL), n-BuLi (26 mL, 45 mmol, 1.3 equiv, 1.6 M in hexane) was added dropwise at -60°C, and the reaction mixture was stirred at that temperature for 30 min. Then, a solution of 1-((1S,3R)-3-(but-2-en-1-yl)-2,2-dimethylcyclopropyl)propan-2-one (5.8 g, 32 mmol, 1.0 equiv, prepared according to Example 1b) in THF (10 mL) was added dropwise at -60°C. After stirring at -60°C for 30 min, 1-chloropropan-2-one (3.3 mL, 42 mmol, 1.3 equiv) was added dropwise at -60°C. After stirring at -60°C for 30 min and at 0°C for 30 min, the reaction mixture was stirred for 2 h while allowing to warm to room temperature. After quenching with brine, the reaction mixture was extracted with MTBE (2x). The combined organic extracts were washed with brine, dried over MgSO4, and the solvent was concentrated under reduced pressure. The crude was purified by column chromatography to give 1-((1S,3R)-3-(but-2-en-1-yl)-2,2-dimethylcyclopropyl)-hexane-2,5-dione (2.5 g, 32 mmol, 33%, mixture of Z / E isomers, 93:7 ratio) as a colorless oil.

[0083] 1 H NMR (400 MHz, CDCl3, mixture of isomers, δ / ppm): 5.46 - 5.27 (m, 2H), 2.75 - 2.63 (m, 4H), 2.47 - 2.31 (m, 2H), 2.17 (s, 3H), 1.95 - 1.85 (m, 2H), 1.63 - 1.55 (m, 3H), 1.07 - 1.04 (m, 3H), 0.91 - 0.86 (m, 3H), 0.85 - 0.75 (m, 1H), 0.60 (td, J = 7.6, 9.0 Hz, 1H). 13C NMR (101 MHz, CDCl3, main Z isomer δ / ppm): 209.6, 207.2, 129.8, 123.5, 38.5, 36.8, 35.5, 29.9, 28.8, 26.0, 22.0, 21.0, 17.0, 14.9, 12.8. GC / MS (EI, main Z isomer): m / z (%): 236 (1, [M] +· ), 151 (9), 123 (22), 107 (13), 99 (100), 81 (18), 71 (15), 55 (20), 43 (56), 41 (16).

[0084] [α] D 24 = -10.0°[c = 1.15, EtOH]. IR (neat, ν / cm -1 ): 2919, 1710s, 1402, 1364, 1096, 970, 694, 586. HRMS (EI): C 15 H 24 O2[M] + Calculated m / z: 236.1771, Found: 236.1771. Odor description: Metallic, hot iron, slightly peppery.

[0085] b) 2-((1S,3R)-3-(but-2-en-1-yl)-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one To a solution of 1-((1S,3R)-3-(but-2-en-1-yl)-2,2-dimethylcyclopropyl)hexane-2,5-dione (2.2 g, 9.3 mmol, 1.2 equiv) in EtOH (25 mL) was added dropwise 0.5 M aqueous NaOH (16 mL, 8.0 mmol, 1.0 equiv) at room temperature. After stirring at 50° C. for 16 h, the reaction mixture was extracted with MTBE (2×). The combined organic extracts were washed with water and brine, dried over MgSO4, and the solvent was removed under reduced pressure. The crude material was purified by column chromatography and Kugelrohr distillation (130 °C, 0.05 mbar) to give 2-((1S,3R)-3-(but-2-en-1-yl)-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one (1.50 g, 73%, mixture of Z / E isomers, 9:1 ratio) as a colorless solid.

[0086] 1 H NMR (400 MHz, CDCl3, δ / ppm): 5.43 - 5.32 (m, 2H), 2.53 - 2.43 (m, 2H), 2.40 - 2.32 (m, 3H), 2.07 - 2.05 (m, 3H), 1.63 - 1.51 (m, 3H), 1.47 - 1.36 (m, 1H), 1.19 - 1.16 (m, 3H), 1.04 - 0.97 (m, 1H), 0.92 - 0.83 (m, 1H), 0.86 (s, 3H). 13 C NMR (101 MHz, CDCl3, main Z isomer, δ / ppm): 209.7, 175.1, 137.7, 130.4, 123.3, 34.7, 31.5, 29.0, 26.5, 24.2, 21.5, 18.9, 17.9, 16.6, 12.9. GC / MS (EI, main Z isomer): m / z (%): 218 (2, [M] +· ), 163 (100), 145 (88), 135 (35), 105 (32), 91 (50), 79 (30), 77 (33), 55 (34), 41 (29).

[0087] [α] D 24 = +59.3°[c = 1.04, EtOH]. IR (neat, ν / cm -1 ): 2915, 1699, 1635, 1439, 1381, 1289, 1123, 1009, 671. HRMS (EI): C 15 H 22 O [M] + Calculated m / z: 218.1665, Found: 218.1666. Odor description: Creamy, woody, aromatic, spicy, peppery, slightly green, metallic.

[0088] Example 9: Fragrance Composition [Table 1-1]

[0089] [Table 1-2]

[0090] 1) Mixture of 2-(2,2,7,7-tetramethyltricyclo[6.2.1.0((1,6)]undec-5(4)-en-5-yl)propan-1-ol 2) 1-Methyl-2-(1,2,2-trimethylbicyclo(3.1.0)-hex-3-ylmethyl)cyclopropyl)methanol 3) 8-Methyl-1-oxaspiro[4.5]decan-2-one

[0091] The fragrance composition is suitable for incorporation into candles @ eg 4wt% or as a freshener in e.g. rattan sticks. The fragrance harmony represents a woody and floral harmony with iris and vetiver as the main attributes. By replacing ISOPAR™ M with 5 parts 2-((1S,3R)-3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one @ 10% in TEC, the diffusion is clearly enhanced and the character improves in terms of depth and naturalness, with the orris and sandalwood aspects becoming richer.

[0092] Example 10: Raspberry flavour formulation for consumable products (e.g. @0.06% beverages) [Table 2-1]

[0093] [Table 2-2]

[0094] The above flavour composition represents a typical raspberry flavour suitable for beverages as an example, at 0.06% in water containing 1% citric acid and sweetened with 7% sugar.

[0095] By replacing 0.00008 parts of DPG with 0.00008 parts of 2-((1S,3R)-3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one (resulting in a composition containing 80 ppb of the compound of formula (I)), the flavor was perceived as more natural in its profile with reduced candy notes and more fruity, ionon seedy notes produced, resulting in a more authentic fruit-like and fresh fruit juice character, compared to a flavor composition without 2-((1S,3R)-3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopent-2-en-1-one.

Claims

1. Equation (I) 【Chemistry 1】 During the ceremony R 1 C 1 ~C 3 Selected from alkyl groups; R 2 This is a hydrocarbon residue containing up to 10 carbon atoms; R 3 and R 4 R is independently selected from hydrogen and methyl, however R 3 or R 4 is methyl; and The dotted lines indicate single or double bonds, along with carbon-carbon bonds. A compound represented by , wherein the compound exists in the form of one of its stereoisomers or a mixture thereof.

2. The relative spatial arrangement is given by equation (Ia) 【Chemistry 2】 During the ceremony R 1 is selected from C 1 to C 3 alkyl; R 2 This is a hydrocarbon residue containing up to 10 carbon atoms; R 3 and R 4 R is independently selected from hydrogen and methyl, however R 3 or R 4 is methyl; and The dotted lines indicate single or double bonds, along with carbon-carbon bonds. The compound according to claim 1, located at 1S,3R as shown by...

3. Next: 2-(3-butyl-2,2-dimethylcyclopropyl)-3-methylcyclopenta-2-en-1-one, (3-(buta-2-en-1-yl)-2,2-dimethylcyclopropyl)-3-methylcyclopenta-2-en-1-one, 2-(2,2-dimethyl-3-(penta-2-en-1-yl)cyclopropyl)-3-methylcyclopenta-2-en-1-one, 2-(2,2-dimethyl-3-pentylcyclopropyl)-3-methylcyclopenta-2-en-1-one, 2-(3-butyl-2,2-dimethylcyclopropyl)-3-propylcyclopenta-2-en-1-one, 2-(3-butyl-2,2-dimethylcyclopropyl)-3-ethylcyclopenta-2-en-1-one, 2-(3-(buta-2-en-1-yl)-2,2-dimethylcyclopropyl)-3-ethylcyclopenta-2-en-1-one, 2-(3-(hexa-2-en-1-yl)-2,2-dimethylcyclopropyl)-3-methylcyclopenta-2-en-1-one, 2-(3-hexyl-2,2-dimethylcyclopropyl)-3-methylcyclopenta-2-en-1-one, 3-Methyl-2-(2,2,3-trimethylcyclopropyl)cyclopenta-2-en-1-one, 2-(3-ethyl-2,2-dimethylcyclopropyl)-3-methylcyclopenta-2-en-1-one, 2-(2,2-dimethyl-3-propylcyclopropyl)-3-methylcyclopenta-2-en-1-one, 2-(3-allyl-2,2-dimethylcyclopropyl)-3-methylcyclopenta-2-en-1-one, and 2-(3-(buta-2-en-1-yl)-2,2-dimethylcyclopropyl)-3-methylcyclopenta-2-en-1-one A compound according to claim 1, selected from a list comprising:

4. Equation (I) 【Transformation 3】 During the ceremony R 1 C 1 ~C 3 Selected from alkyl groups; R 2 This is a hydrocarbon residue containing up to 10 carbon atoms; R 3 and R 4 R is independently selected from hydrogen and methyl, however R 3 or R 4 is methyl; and The dotted lines indicate single or double bonds, along with carbon-carbon bonds. A flavor composition or fragrance composition comprising a compound represented by in the form of one of its stereoisomers or a mixture thereof.

5. Equation (I) 【Chemistry 4】 During the ceremony R 1 C 1 ~C 3 Selected from alkyl groups; R 2 This is a hydrocarbon residue containing up to 10 carbon atoms; R 3 and R 4 R is independently selected from hydrogen and methyl, however R 3 or R 4 is methyl; and The dotted lines indicate single or double bonds, along with carbon-carbon bonds. A flavored article comprising a compound represented by in the form of one of its stereoisomers or a mixture thereof.

6. Equation (I) 【Transformation 5】 During the ceremony R 1 C 1 ~C 3 Selected from alkyl groups; R 2 This is a hydrocarbon residue containing up to 10 carbon atoms; R 3 and R 4 R is independently selected from hydrogen and methyl, however R 3 or R 4 is methyl; and The dotted lines indicate single or double bonds, along with carbon-carbon bonds. A flavored product containing a compound represented by in the form of one of its stereoisomers or a mixture thereof.

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