Sabinene derivatives, synthesis, and uses thereof

Abstract

Derivatives of Sabinene (1-isopropyl-4-methylenebicyclo[3.1.0]hexane, CAS No. 3387-41-5), as well as their synthesis and use in organoleptic applications, are described herein. The Sabinene derivatives include a compound having a general Formula (I), wherein --- is a single or a double bond; wherein if --- is a single bond, then Y is selected from the group consisting of CH2R1, CH=C(R2)R3, and (CH2)xCHR3R4; and OR5; wherein if --- is a double bond, then Y is O, N-OMe, or N-OEt; R is selected from the group consisting of H, C(O)-R6, and CH(R6)-OR5; R1 is selected from the group consisting of 1,3-dioxepan, 5-methyl-1,3-dioxolan-4-one, (CH=CH)x(CH2)nOH, (CH=CH)x(CH2)nCHO, CH(CH3)CO2Et, and CH(CH3)OH; R2 = H or Me; R3 is selected from the group consisting of CHO, CO2Et, (CH2)nOH, (CH2)nCHO, (CH2)nCN, and (CH2)nCO2Bu; and R4 is CHO or CH2OH; or R3 and R4 in combination form a dihydropyran, a tetrahydropyran, a tetrahydropyranol, a tetrahydropyranone, a dimethylcyclohexenone, or a dimethylcyclohexenol; R5 is selected from the group consisting of CH(CH3), CH(CH2CH3), C(CH3)CH3, and C(CH3)CH2CH3; R6 is selected from the group consisting of OMe and Me; x is an integer selected from 0 or 1; and n is an integer selected from 2 to 7; with the proviso that when --- is a double bond and Y is O, then R and R6 are not H.

Description

SABINENE DERIVATIVES, SYNTHESIS, AND USES THEREOFFIELD OF THE INVENTION

[0001] The present invention relates generally to novel Sabinene (1 -isopropyl-4-methylenebicyclo[3.1.0]hexane, CAS No. 3387-41-5) derivatives and their use in organoleptic applications.BACKGROUND OF THE INVENTION

[0002] To increase the range of notes available to perfumers and flavorists in their creations, the perfume and flavor industry is constantly looking for new organoleptic compounds to meet increasing regulatory requirements, such as replacing compounds identified by regulatory bodies as undesirable or even unacceptable. Additionally, cost constraints are increasingly important.

[0003] Amongst the organoleptic molecules, compounds with spicy, aromatic and I or herbal notes are known, but many have disadvantages, such as a poor stability, a tendency to color the finish product, or are subject to regulatory restrictions. Amongst the most commonly used compounds are eugenol, cinnamaldehyde, anisaldehyde or estragol. Each of the foregoing is regulated and / or its use restricted. Eugenol and cinnamaldehyde are also chromophorous, meaning that they may color the finish product under the effect of light. Anisaldehyde may cause irritation on skin contact. Estragol is restricted due to its potential genotoxicity. Few herbal compounds are available. One can cite Herboxane™, described as spicy, herbal, basil. But this compound shows medium to poor stability in applications such as antiperspirant or powder detergent, and a poor substantivity.

[0004] Accordingly, in order to meet the constant needs of the perfume and flavor industry, and to expand the palette of perfumers and flavorists, there is a need for new compounds having spicy, aromatic and I or herbal notes.SUMMARY OF THE INVENTION

[0005] Certain aspects of the present disclosure are described in the appended claims. There are additional features and advantages of the subject matter described herein. They will become apparent as this specification proceeds. In this regard, it isto be understood that the claims serve as a brief summary of varying aspects of the subject matter described herein. The various features described in the claims and below for various embodiments may be used in combination or separately. For example, specified ranges may be inclusive of their recited endpoints, unless explicitly excluded. Any particular embodiment need not provide all features noted above, nor solve all problems or address all issues noted above.

[0006] One object of the invention is a compound having a general Formula (I) is provided:Formula (I),wherein — is a single or a double bond;wherein if — is a single bond, then Y is selected from the group consisting of CH2R1, CH=C(R2)R3, and (CH2)xCHR3R4; and OR5; wherein if — is a double bond, then Y is 0, N-OMe, or N-OEt;R is selected from the group consisting of H, C(O)-R6, CH(R6)-OR5;R1is selected from the group consisting of 1 ,3-dioxepan, 5-methyl-1 ,3-dioxolan-4-one, (CH=CH)x(CH2)nOH, (CH=CH)x(CH2)nCHO, CH(CH3)CO2Et, and CH(CH3)OH;R2= H or Me;R3is selected from the group consisting of CHO, C02Et, (CFhjnOH, (CFhjnCHO, (CH2)nCN and (CH2)nCO2Bu; and R4is CHO or CH2OH; or R3and R4in combination form a dihydropyran, a tetrahydropyran, a tetrahydropyranol, a tetrahydropyranone, a dimethylcyclohexenone, or a dimethylcyclohexenol;R5is selected from the group consisting of CH(CH3), CH(CH2CH3), C(CH3)CH3 and C(CH3)CH2CH3;R6is selected from the group consisting of OMe and Me;x is an integer selected from 0 or 1 ; andn is an integer selected from 2 to 7;with the proviso that when — is a double bond and Y is 0, then R and R6are not H.

[0007] Another object of the invention is a fragrance composition, a flavor composition, a pharmaceutical composition, a cosmetic composition, a cleaning composition, a food composition, or an intermediate composition for the preparation ofone of said compositions, is provided, wherein the composition comprises one or more compounds having a general Formula (I).

[0008] Another object of the invention is a use of at least one compound of general Formula (I) is provided, said use is to confer, modify, or enhance the olfactory properties of a substance, composition, or article.BRIEF DESCRIPTION OF THE DRAWINGS

[0001] The accompanying drawing, which are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and, together with a general description of the invention given above, and the detailed description given below, serve to explain the invention. It will be appreciated that for purposes of clarity and where deemed appropriate, reference numerals have been repeated in the figures to indicate corresponding features.

[0002] FIG. 1 is a schematic showing a retrosynthetic strategy for making one or more compounds of general Formula (I) starting from Sabinene.DETAILED DESCRIPTION

[0009] Unless otherwise explained, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. In case of conflict, the present specification, including explanations of terms, will control. The singular terms "a," "an," "at least one," “one or more”, and "the" include plural referents unless context clearly indicates otherwise. Similarly, the word "or" is intended to include "and" unless the context clearly indicates otherwise. The term "comprising" means "including;" hence, "comprising A or B" means including A or B, as well as A and B together. The term "comprising" further includes the meaning of “consisting of”.

[0010] Objects of the invention relate to new compounds derived from Sabinene ((1-isopropyl-4-methylenebicyclo[3.1.0]hexane, CAS No. 3387-41-5), said compounds having spicy, aromatic and I or herbal notes, their preparation process, as well as their uses in the chemical industry, and in particular in perfumery, cosmetics, parapharmacy, home and personal care applications, as well as in food, said compounds having interesting organoleptic properties and a particular potency and persistence.

[0011] Thus, in accordance with an object of the invention, a compound having a general Formula (I) is provided:Formula (I),wherein — is a single or a double bond;wherein if — is a single bond, then Y is selected from the group consisting of CH2R1, CH=C(R2)R3, and (CH2)xCHR3R4; and OR5; wherein if — is a double bond, then Y is 0, N-OMe, or N-OEt;R is selected from the group consisting of H, C(O)-R6, and CH(R6)-OR5;R1is selected from the group consisting of 1 ,3-dioxepan, 5-methyl-1 ,3-dioxolan-4-one, (CH=CH)x(CH2)nOH, (CH=CH)x(CH2)nCHO, CH(CH3)CO2Et, and CH(CH3)OH; in particular R1is selected from the group consisting of 1 ,3-dioxepan, 5-methyl-1 ,3-dioxolan-4-one, CH(CH3)CO2Et, and CH(CH3)OH; more particularly R1is selected from the group consisting of 1 ,3-dioxepan, 5-methyl-1 ,3-dioxolan-4-one and CH(CH3)CO2Et; even more particularly R1is 5-methyl-1 ,3-dioxolan-4-one;R2= H or Me;R3is selected from the group consisting of CHO, C02Et, (CH2)nOH, (CH2)nCHO, (CH2)nCN, and (CH2)nCO2Bu; and R4is CHO or CH2OH; or R3and R4in combination form a dihydropyran, a tetrahydropyran, a tetrahydropyranol, a tetrahydropyranone, a dimethylcyclohexenone, or a dimethylcyclohexenol;R5is selected from the group consisting of CH(CH3), CH(CH2CH3), C(CH3)CH3, and C(CH3)CH2CH3;R6is selected from the group consisting of OMe and Me;x is an integer selected from 0 or 1 ; andn is an integer selected from 2 to 7;with the proviso that when — is a double bond and Y is 0, then R and R6are not H.

[0012] As used herein the expression “integer selected from 2 to 7” means that the integer may be equal to 2, 3, 4, 5, 6, or 7, or a range between any two of the foregoing. For example, n may be selected from 2 to 7, 3 to 7, 4 to 7, 5 to 7, 6 to 7, 2 to 6, 3 to 6, 4 to 6, etc.

[0013] In an embodiment, the compound having a general Formula (I) is not one, more or all of the following:8-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-oct-6-enal;8-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-oct-6-enol;8-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-octanol; and6-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)hexanol.

[0014] In an embodiment, — is a single bond and Y is selected from the group consisting of CH2R1, CH=C(R2)R3, and (CH2)xCHR3R4; and OR5. In another embodiment, — is a double bond, Y is 0, and R is selected from the group consisting of C(O)-R6and CH(R6)-OR5. In yet another embodiment, — is a double bond, Y is N-OMe or N-OEt, and R is H.

[0015] In an embodiment, the compound having a general Formula (I) is selected from the group consisting of:methyl 1 -isopropyl-4-oxobicyclo[3.1 ,0]hexane-3-carboxylate;8-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)oct-6-enal;3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2-methylacrylaldehyde;8-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)oct-6-en-1 -ol;8-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)octan-1 -ol;7-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)hept-6-en-1 -ol;ethyl 3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2-methylpropanoate;7-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)hept-6-enal;ethyl 3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2-methylacrylate;5-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)pent-4-enenitrile;2-((5-isopropylbicyclo[3.1 ,0]hexan-2-yl)methyl)-5-methyl-1 ,3-dioxolan-4-one; 2-((5-isopropylbicyclo[3.1 ,0]hexan-2-yl)methyl)-1 ,3-dioxepane;ethyl 3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)acrylate;3-(hydroxymethyl)-5-isopropylbicyclo[3.1 ,0]hexan-2-ol;5a-isopropyl-2-methylhexahydro-4h-cyclopropa[4,5]cyclopenta[1 ,2-d][1 ,3]dioxine;3-acetyl-5-isopropylbicyclo[3.1 ,0]hexan-2-one;2-ethyl-5a-isopropylhexahydro-4h-cyclopropa[4,5]cyclopenta[1 ,2-d][1 ,3]dioxine; 5a-isopropyl-2,4-dimethylhexahydro-4h-cyclopropa[4,5]cyclopenta[1 ,2-d][1 ,3]dioxine;3-(1 -hydroxyethyl)-5-isopropylbicyclo[3.1 ,0]hexan-2-ol;5a-isopropyl-2,2-dimethylhexahydro-4h-cyclopropa[4,5]cyclopenta[1 ,2-d][1 ,3]dioxine;2-ethyl-5a-isopropyl-2-methylhexahydro-4h-cyclopropa[4,5]cyclopenta[1 ,2-d][1 ,3]dioxine;6-((5-isopropylbicyclo[3.1.0]hexan-2-yl)methyl)-4-methyl-3,6-dihydro-2h-pyran; 2-((5-isopropylbicyclo[3.1 ,0]hexan-2-yl)methyl)-4-methylenetetrahydro-2h-pyran; 2-((5-isopropylbicyclo[3.1.0]hexan-2-yl)methyl)-4-methyl-3,6-dihydro-2h-pyran; 4-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2,6-dimethylcyclohex-2-en-1 -ol;4-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2,6-dimethylcyclohex-2-en-1 -one;2-((5-isopropylbicyclo[3.1 ,0]hexan-2-yl)methyl)-4-methyltetrahydro-2h-pyran-4-ol;butyl 4-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-5-oxopentanoate;2-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)pentane-1 ,5-diol;3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)tetrahydro-2h-pyran;butyl 5-hydroxy-4-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)pentanoate;5-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)tetrahydro-2h-pyran-2-one;5-isopropylbicyclo[3.1 ,0]hexan-2-one o-ethyl oxime; and5-isopropylbicyclo[3.1 ,0]hexan-2-one o-methyl oxime.

[0016] In another embodiment, the compound having a general Formula (I) is selected from the group consisting of:3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2-methylacrylaldehyde;7-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)hept-6-en-1 -ol;7-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)hept-6-enal;ethyl 3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2-methylacrylate;5-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)pent-4-enenitrile;ethyl 3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)acrylate;3-(hydroxymethyl)-5-isopropylbicyclo[3.1 ,0]hexan-2-ol;3-acetyl-5-isopropylbicyclo[3.1 ,0]hexan-2-one;2-ethyl-5a-isopropylhexahydro-4h-cyclopropa[4,5]cyclopenta[1 ,2-d][1 ,3]dioxine; 3-(1-hydroxyethyl)-5-isopropylbicyclo[3.1 ,0]hexan-2-ol;6-((5-isopropylbicyclo[3.1 ,0]hexan-2-yl)methyl)-4-methyl-3,6-dihydro-2h-pyran; 2-((5-isopropylbicyclo[3.1.0]hexan-2-yl)methyl)-4-methylenetetrahydro-2h-pyran;2-((5-isopropylbicyclo[3.1 ,0]hexan-2-yl)methyl)-4-methyl-3,6-dihydro-2h-pyran;4-(5-isopropylbicyclo[3.1.0]hexan-2-yl)-2,6-dimethylcyclohex-2-en-1 -one; and butyl 4-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-5-oxopentanoate.

[0017] According to embodiments of the present invention, use of one or more compounds having a general chemical Formula (I) as a perfuming agent, a flavoring agent, an odor neutralizing agent, or a taste-masking agent is provided.

[0018] According to embodiments of the present invention, a composition comprising one or more compound of general Formula (I) is provided. Said composition can be for instance a fragrance composition, a flavoring composition, a pharmaceutical composition, a cosmetic composition, a cleaning composition, a food composition, or an intermediate composition for the preparation of one of said compositions.

[0019] In accordance with another object of the invention, a fragrant composition is provided, which comprises at least one compound of general Formula (I) and a solvent.

[0020] In accordance with another object of the invention, a fragrant composition is provided, which comprises a solvent, and at least one compound of general Formula (I) selected from the group consisting of:methyl 1-isopropyl-4-oxobicyclo[3.1 ,0]hexane-3-carboxylate;8-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)oct-6-enal;3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2-methylacrylaldehyde;8-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)oct-6-en-1 -ol;8-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)octan-1 -ol;7-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)hept-6-en-1 -ol;ethyl 3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2-methylpropanoate;7-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)hept-6-enal;ethyl 3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2-methylacrylate;5-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)pent-4-enenitrile;2-((5-isopropylbicyclo[3.1 ,0]hexan-2-yl)methyl)-5-methyl-1 ,3-dioxolan-4-one;2-((5-isopropylbicyclo[3.1 ,0]hexan-2-yl)methyl)-1 ,3-dioxepane;ethyl 3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)acrylate;3-(hydroxymethyl)-5-isopropylbicyclo[3.1 ,0]hexan-2-ol;5a-isopropyl-2-methylhexahydro-4h-cyclopropa[4,5]cyclopenta[1 ,2-d][1 ,3]dioxine; 3-acetyl-5-isopropylbicyclo[3.1 ,0]hexan-2-one;2-ethyl-5a-isopropylhexahydro-4h-cyclopropa[4,5]cyclopenta[1 ,2-d][1 ,3]dioxine; 5a-isopropyl-2,4-dimethylhexahydro-4h-cyclopropa[4,5]cyclopenta[1,2-d][1 ,3]dioxine;3-(1-hydroxyethyl)-5-isopropylbicyclo[3.1 ,0]hexan-2-ol;5a-isopropyl-2,2-dimethylhexahydro-4h-cyclopropa[4,5]cyclopenta[1,2-d][1 ,3]dioxine;2-ethyl-5a-isopropyl-2-methylhexahydro-4h-cyclopropa[4,5]cyclopenta[1 ,2-d][1 ,3]dioxine;6-((5-isopropylbicyclo[3.1.0]hexan-2-yl)methyl)-4-methyl-3,6-dihydro-2h-pyran; 2-((5-isopropylbicyclo[3.1 ,0]hexan-2-yl)methyl)-4-methylenetetrahydro-2h-pyran; 2-((5-isopropylbicyclo[3.1.0]hexan-2-yl)methyl)-4-methyl-3,6-dihydro-2h-pyran;m 4-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2,6-dimethylcyclohex-2-en-1 -ol;4-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2,6-dimethylcyclohex-2-en-1 -one;2-((5-isopropylbicyclo[3.1 ,0]hexan-2-yl)methyl)-4-methyltetrahydro-2h-pyran-4-ol; butyl 4-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-5-oxopentanoate;2-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)pentane-1 ,5-diol;3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)tetrahydro-2h-pyran;butyl 5-hydroxy-4-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)pentanoate;5-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)tetrahydro-2h-pyran-2-one;5-isopropylbicyclo[3.1.0]hexan-2-one o-ethyl oxime; and5-isopropylbicyclo[3.1.0]hexan-2-one o-methyl oxime.

[0021] The effective amount of the compounds of the invention to be incorporated into these compositions depends on the nature of said compositions, the desired odorous or flavoring effect and the nature of other odorous or flavoring compounds possibly present. It is easily determined by those skilled in the art, and can vary in a very wide range, from 100 ppb to 50%. For example, in an embodiment, the at least one compound of general Formula (I) may be incorporated into composition in an amount from 100 ppb to 50%, or from 0.001 to 50%, in particular 0.01 to 30%. The preceding percentages are expressed in total weight of the composition.

[0022] In one embodiment of the invention, the composition is a perfume composition comprising: at least one compound of general Formula (I), preferably selected from the group consisting of:3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2-methylacrylaldehyde;7-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)hept-6-en-1 -ol;7-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)hept-6-enal;ethyl 3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2-methylacrylate;5-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)pent-4-enenitrile;ethyl 3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)acrylate;3-(hydroxymethyl)-5-isopropylbicyclo[3.1 ,0]hexan-2-ol;3-acetyl-5-isopropylbicyclo[3.1 ,0]hexan-2-one;2-ethyl-5a-isopropylhexahydro-4h-cyclopropa[4,5]cyclopenta[1 ,2-d][1 ,3]dioxine; 3-(1-hydroxyethyl)-5-isopropylbicyclo[3.1 ,0]hexan-2-ol;6-((5-isopropylbicyclo[3.1.0]hexan-2-yl)methyl)-4-methyl-3,6-dihydro-2h-pyran; 2-((5-isopropylbicyclo[3.1 ,0]hexan-2-yl)methyl)-4-methylenetetrahydro-2h-pyran;2-((5-isopropylbicyclo[3.1.0]hexan-2-yl)methyl)-4-methyl-3,6-dihydro-2h-pyran; 4-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2,6-dimethylcyclohex-2-en-1 -one; butyl 4-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-5-oxopentanoate; and5-isopropylbicyclo[3.1.0]hexan-2-one o-methyl oxime andat least one other odorous substance.

[0023] Other odorous substances that can be used in combination with the compounds of the present invention may be natural products such as extracts, essential oils, absolutes, resinoids, resins, concretes etc., but also synthetic products such as hydrocarbons, alcohols, aldehydes, ketones, ethers, acids, esters, acetals, nitriles etc., including saturated or unsaturated, aliphatic, heterocyclic, or carbocyclic compounds. Such odorous substances are mentioned, for example, in S. Arctander, "Perfume and Flavor Chemicals" (Montclair, N.J., 1969), or in "Common Fragrance and Flavor Materials", Wiley-VCH, Weinheim, 2006. Finally, a plurality of compounds of general Formula (I) can also be used in combination in the same composition.

[0024] Because of the pleasant smell they emit, the compounds of general Formula (I) find many applications in perfumery. The term "perfumery" is used here in its general sense; it refers not only to traditional perfumery (alcoholic or not), but also to other areas in which the smell / fragrance of products is important. Reference may thus be made to perfumery compositions in the usual and traditional sense (such as perfume bases and concentrates, perfumes, colognes, eau de toilette, indoor air fresheners, home fragrances, scented candles and similar products), to topical compositions including cosmetic compositions (such as face and I or body creams, talcum powders, hair oils, shampoos, hair lotions, bath salts and oils, shower and / or bath gels, toilet soaps, antiperspirants and body deodorants, shaving lotions and creams, soaps, toothpastes, mouthwashes, ointments, and similar products), as well as cleaningproducts, in particular household cleaning products (such as detergents, fabric softeners, home air fresheners, home fragrances and similar products).

[0025] Thus, embodiments of the invention extend to a perfume composition comprising at least one compound of general Formula (I), preferably selected from the group consisting of:3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2-methylacrylaldehyde;7-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)hept-6-en-1 -ol;7-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)hept-6-enal;ethyl 3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2-methylacrylate;5-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)pent-4-enenitrile;ethyl 3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)acrylate;3-(hydroxymethyl)-5-isopropylbicyclo[3.1 ,0]hexan-2-ol;3-acetyl-5-isopropylbicyclo[3.1 ,0]hexan-2-one;2-ethyl-5a-isopropylhexahydro-4h-cyclopropa[4,5]cyclopenta[1 ,2-d][1 ,3]dioxine; 3-(1-hydroxyethyl)-5-isopropylbicyclo[3.1 ,0]hexan-2-ol;6-((5-isopropylbicyclo[3.1.0]hexan-2-yl)methyl)-4-methyl-3,6-dihydro-2h-pyran; 2-((5-isopropylbicyclo[3.1.0]hexan-2-yl)methyl)-4-methylenetetrahydro-2h-pyran;2-((5-isopropylbicyclo[3.1.0]hexan-2-yl)methyl)-4-methyl-3,6-dihydro-2h-pyran; 4-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2,6-dimethylcyclohex-2-en-1 -one; butyl 4-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-5-oxopentanoate; and5-isopropylbicyclo[3.1.0]hexan-2-one o-methyl oxime.

[0026] It may, in particular, be a composition of the traditional perfumery, a cosmetic composition, cleaning product, or a so-called "intermediate composition", intended to be used for the preparation of compositions or finished products (including perfumes, cosmetics, cleaning products).

[0027] Such a perfume composition is generally prepared from a basic product, in which the compound or compounds of the invention are found to be incorporated. The basic product will be easily determined by those skilled in the art according to the composition envisaged and therefore the intended use. The composition of these basic products and the nature of their usual components, such as perfuming ingredient(s), flavoring ingredient(s), solvent(s), additive(s), fixative(s), and I or adjuvant(s), are well known to those skilled in the art.

[0028] A fixative is a base ingredient or blend that is utilized in perfumes to help the scent last longer. For example, fixatives can reduce the rate of evaporation of the more volatile materials in fragrance composition. A non-limiting list of fixatives includes resinoids such as benzoin, labdanum, myrrh, olibanum, storax, and tolu balsam; terpenoids such as ambroxide ((3aR,5aS,9aS,9bR)-3a,6,6,9a-tetramethyldodecahydronaphtho[2,1-b]furan); polycyclic ketones such as civetone ((9Z)-cycloheptadec-9-en-1 -one) and muscone ((3R)-3-methylcyclopentadecan-1-one); glycerin; Galaxolide (4,6,6,7,8,8-hexamethyl-1 , 3, 4, 6,7,8-hexahydrocyclopenta[g]isochromene); Iso E Super (1-(1,2,3,4,5,6,7,8-octahydro-2,3,8,8,-tetramethyl-2-naphthyl)ethan-1-one); orris root (Rhizoma iridis)', benzyl benzoate; triethyl citrate; dipropylene glycol (DPG); ethyl hexyl glycerin; and oud base.

[0029] The compounds used in these perfume compositions, in particular the compounds of the invention, may be incorporated into or on an inert support material. The carrier materials that can be used are many and varied, for example polar solvents, oils, greases, finely divided solids, cyclodextrins, maltodextrins, gums, resins, and any other carrier material known for such compositions (for example, soaps, candles, ointments, textiles, wipes, scented gels, or the like).

[0030] According to another embodiment of the invention, the composition is a flavor composition comprising: at least one compound of Formula (I), preferably selected from the group consisting of:3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2-methylacrylaldehyde;7-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)hept-6-en-1 -ol;7-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)hept-6-enal;ethyl 3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2-methylacrylate;5-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)pent-4-enenitrile;ethyl 3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)acrylate;3-(hydroxymethyl)-5-isopropylbicyclo[3.1 ,0]hexan-2-ol;3-acetyl-5-isopropylbicyclo[3.1 ,0]hexan-2-one;2-ethyl-5a-isopropylhexahydro-4h-cyclopropa[4,5]cyclopenta[1 ,2-d][1 ,3]dioxine; 3-(1-hydroxyethyl)-5-isopropylbicyclo[3.1 ,0]hexan-2-ol;6-((5-isopropylbicyclo[3.1 ,0]hexan-2-yl)methyl)-4-methyl-3,6-dihydro-2h-pyran; 2-((5-isopropylbicyclo[3.1 ,0]hexan-2-yl)methyl)-4-methylenetetrahydro-2h-pyran;2-((5-isopropylbicyclo[3.1 ,0]hexan-2-yl)methyl)-4-methyl-3,6-dihydro-2h-pyran;4-(5-isopropylbicyclo[3.1.0]hexan-2-yl)-2,6-dimethylcyclohex-2-en-1 -one; butyl 4-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-5-oxopentanoate, and5-isopropylbicyclo[3.1.0]hexan-2-one o-methyl oxime; andat least one other flavoring substance.

[0031] For example, in one aspect, the flavor composition may be an ingestible product, which refers to a "beverage", "food", an "edible composition", and / or a "food product". Said ingestible product preferentially relates, but is not limited to, products intended for human consumption, intended for animal feed (pets) or pharmaceutical compositions. Examples of food products may include, but are not limited to, snacks, confectionery, plant materials, and meals that may or may not provide essential nutrients. Plant materials include cocoa, cocoa beans, coffee, coffee beans, and tea leaves or powder. Examples of food products include salad dressings, sauces, marinades, sticks, nutrition bars, pastries, breads, caramel, cooked cereals, meat products, poultry products, meat, poultry, fish, marine protein sources, beans, pasta, confectionery products, salty snacks, dairy products, cheeses, yogurt, butter, margarine, ready-to-eat cereals, condiments and sauces and beverages. In particular, the term "beverage" includes mixtures and concentrates, including, but not limited to, ready-to-drink alcoholic and non-alcoholic beverages and dry powdered beverages. Non-limiting examples of beverages include, but are not limited to, soft drinks, brewed beverages, dairy products, drinking yogurt, milk, coffee, whitening agents, nutritional drinks, and the like. Non-limiting examples of animal feed may include, but are not limited to, pet food, such as dogs and cats; rodent food; livestock feed; cattle feed; horse feed; and the like. Other applications for the compounds of general Formula (I) may also include tobacco products or tobacco-related products.

[0032] In accordance with yet another embodiment of the invention, the use of at least one compound of general Formula (I), in a form of a stereoisomer or a mixture of stereoisomers, or a racemic mixture, to confer, modify, or enhance the organoleptic properties of a substance, a composition, or an article is provided.

[0033] The present invention also relates to a process for modifying the organoleptic properties of a substance, a composition or an article comprising at least one of the following steps: adding a compound of general Formula (I) to said substance, composition, or article, or applying a compound of Formula (I) to the surface of said article.

[0034] As used herein, "organoleptic properties" means any property likely to modify, improve or enhance the organoleptic perception of a substance, composition or article by a user (e.g., olfactory or gustatory perception)

[0035] In an embodiment, at least one compound of Formula (I) is used as a fragrant agent, alone or in combination with at least one other odorant substance, and I or at least one solvent, and I or at least one adjuvant. The additional odorant agent(s), solvent(s) and adjuvant(s) are known to those skilled in the art who will be able to choose the most appropriate or the most appropriate according to the desired effect.

[0036] As used herein, the term "fragrant" is used here to refer to any organoleptic compound that pleasantly stimulates the sense of smell. The terms “fragrant” or “perfume” are used interchangeably in the present disclosure. Thus, the expressions “fragrant composition” and “perfume composition” refer to the same objects.

[0037] The compounds according to the invention may particularly be used as a masking agent or as an odor neutralizing agent. As used herein, the term "masking agent" or "odor neutralizing agent" is meant to identify a characteristic of the compounds within the scope of the invention to reduce or eliminate the perception of a bad odor generated by one or more other molecules present in a composition or a product.

[0038] In particular, the compounds according to the invention can be used alone or in combination with taste-modulating compounds. “Taste-modulating compound” refers to a compound which can modify taste and sensory perceptions. In any case, the specificity of such taste-modulating compounds is that they do not exhibit noticeable taste and flavor properties (without taste and flavor). Such flavor-altering compounds can be of synthetic or natural origin.

[0039] In accordance with embodiments of the present invention, compounds of general Formula (I) are Sabinene derivatives, which are particularly derived from Sabinene carbaldehyde (Compound A), Sabinene carboxaldehyde (Compound B), and I or Sabina ketone (Compound C) (see FIG. 1 ). Sabinene, which may be synthetic or obtained from natural sources, may be a single compound, a single enantiomer, an enriched enantiomer, or a racemic mixture. In an embodiment, Sabinene may be a mixture containing other monoterpenes comprising an exocyclic methylene group, such as beta-pinene. Non-limiting natural sources of Sabinene include essential oils of a variety of plants including, but not limited to, orange, nutmeg, holm oak, or Norway spruce.

[0040] The presence and I or creation of asymmetric centers in the structure of the compounds of Formula (I) according to the invention causes the existence, for each of them, of several enantiomeric and I or diastereomeric forms. The invention also covers the compounds represented by the general Formula (I) in the form of mixtures of enantiomers and I or diastereomers, in varying proportions, in particular racemic mixtures. The invention also comprises compounds of general Formula (I) in the form of a single enantiomer and I or diastereomer. Enantiomer I diastereomer mixtures or pure forms may be obtained by synthesis from optically enriched or optically pure starting materials, or by crystallization or chromatographic separation methods. The invention also covers the compounds represented by the general Formula (I), which may be stereoisomers, such as cis or trans isomers.

[0041] In an embodiment, Sabinene carbaldehyde (Compound A, 5-isopropylbicyclo[3.1 ,0]hexane-2 -carbaldehyde, CAS No. 57129-54-1) is modified (derivatized) to prepare one or more compounds having the general Formula (I). In an embodiment, Sabinene carbaldehyde (Compound A) may be prepared in two steps. First, hydroboration of Sabinene, followed by an oxidative work up produces the desired alcohol intermediate (5-(1-isopropyl)bicyclo[3.1 ,0]hexane-2-methanol), which contains a hydroxyl functional group. The hydroxyl functional group of 5-(1-isopropyl)bicyclo[3.1 ,0]hexane-2-methanol may be oxidized (e.g., TEMPO ((2, 2,6,6-tetramethylpiperidin-1-yl)oxyl) oxidation) to the corresponding Sabinene carbaldehyde (Compound A).

[0042] In an aspect, Sabinene carbaldehyde (Compound A) is modified (derivatized) via an aldol condensation reaction to form one or more compound of general Formula (I). Other approaches involve derivatizing Sabinene carbaldehyde by reacting Sabinene carbaldehyde with a phosphorus ylide, or deprotonated phosphonate to form one or more compound of general Formula (I). The compounds thus formed can be again modified (derivatized) via hydrogenation and I or reduction and I or oxidation reactions to form one or more compound of general Formula (I). In an embodiment, the derivatizing reaction may be one or more of the following named or well-known reactions: Wittig, Wittig-Horner, aldolization, optionally followed by reduction, hydrogenation, and I or oxidation.

[0043] In another embodiment, Sabinene carboxaldehyde (Compound B, 2-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)acetaldehyde), is modified (derivatized) to prepare one or more compounds having the general Formula (I). Sabinene carboxaldehyde(Compound B) may be prepared in a single step, where sabinene is hydroformylated in the presence of a Ruthenium catalyst. In a preferred embodiment, Sabinene is hydroformylated in the presence of triphenylphosphine and (acetylacetonato)dicarbonylrhodium(l) in toluene solvent under an atmosphere of a 50:50 mixture of hydrogen and carbon monoxide.

[0044] In an aspect, Sabinene carboxaldehyde (Compound B) is modified (derivatized) by reacting Sabinene carboxaldehyde with an aliphatic diol, glycolic acid, a phosphorus ylide, and I or an alpha-beta unsaturated ester, alcohol, or aldehyde to form one or more compound of general Formula (I). The compounds thus formed can be again modified (derivatized) via hydrogenation and I or reduction and I or cyclization reactions to form one or more compound of general Formula (I). In an embodiment, the derivatizing reaction may be one or more of the following named or well-known reactions: acetalization, Wittig, Prins, Robinson annulation, Michael addition, and optionally followed by hydrogenation, reduction, and I or cyclisation.

[0045] In yet another embodiment, Sabina ketone (Compound C, 5-isopropylbicyclo(3.1 ,0)hexan-2-one, CAS No. 513-20-2) is modified (derivatized) to prepare one or more compounds having the general Formula (I). Sabinene may be readily ozonized to form Sabina ketone (Compound C), which comprises a ketone functional group.

[0046] In an aspect, Sabina ketone (Compound C) is modified (derivatized) via an oximation reaction or via an alpha alkylation or acylation reaction to form one or more compound of general Formula (I). The compounds thus formed can be again modified (derivatized) via a reduction reaction, optionally followed by an acetalization reaction to form one or more compound of general Formula (I).EXAMPLES

[0047] The following examples illustrate a particular way of preparing the compounds of the invention, as well as the olfactory I aromatic profile of each of the exemplified compounds (1-14). These examples are for illustrative purposes only and should not be understood as limiting the general scope of the invention.

[0048] Compound A: Sabinene carbaldehyde (5-isopropylbicyclo[3.1 ,0]hexane-2-carbaldehyde): Step 1 : In a 3-necked flask fitted with a thermometer, a condenser and an addition funnel were placed 100 g of Sabinene (Treatt Pic (Suffolk, UK), 78% Sabinene, 22% beta-pinene) in 150 mL of tetrahydrofuran (THF). The resulting solutionwas cooled at 0 °C and 34.8 mL of borane dimethyl sulfide complex was added dropwise. At the end of the addition, the reaction mixture was stirred for 30 minutes at room temperature (RT). The resulting solution was cooled at 0 °C and a solution of 32.3 g of sodium hydroxide in 100 mL of water was added dropwise. Then, 78 mL of 32 wt% hydrogen peroxide in water were added dropwise. At the end of the addition, the reaction mixture was stirred for 30 minutes at RT. The reaction mixture was poured over 200 mL of 10% aqueous HCI and 200 mL of methyl te / t-butyl ether (MTBE). The layers were separated. The aqueous phase was extracted once with 100 mL of MTBE. The combined organic phases were washed twice with a 100 mL of a saturated aqueous solution of sodium thiosulfate, then washed with water, dried, and concentrated under vacuum. The crude product was distilled under reduced pressure (boiling point: 70 °C at 0.3 Torr) to provide (5-isopropylbicyclo[3.1 ,0]hexan-2-yl)methanol.

[0049] Step 2: To a round-bottom flask equipped with a stirring bar, a condenser, and a thermometer, were charged 50 g of (5-isopropylbicyclo[3.1 ,0]hexan-2-yl)methanol (from Step 1) and 2.53 g of TEMPO ((2,2,6,6-tetramethylpiperidin-1-yl)oxyl) in 200 mL of dichloromethane followed by 100 mL of deionized water. The mixture was stirred and cooled down below 5 °C. 115 g of BAIB ((Bisacetoxyiodo)benzene) was added portionwise (10 portions in 10 minutes) at 0 °C. After addition, the reaction mixture was brought to room temperature and stirred until full conversion of the starting alcohol was observed. The reaction mixture was quenched with 5 volumes (5V) of Na2S20s (saturated aqueous solution). After decantation, the organic phase was washed with 3 volumes (3V) of deionized water (pH = 2) and 3V of NaHCOs (saturated aqueous solution) until neutral before being dried over MgSCk and concentrated under vacuum. The crude product was distilled under reduced pressure (boiling point: 37 °C at 0.7 Torr) to provide Compound A (Sabinene carbaldehyde).

[0050] Compound B: Sabinene carboxaldehyde (2-(5-isopropylbicyclo[3.1.0]hexan-2-yl)acetaldehyde): In an autoclave reactor, 80 g of Sabinene, 15.40 g of triphenylphosphine and 0.45 g of (acetylacetonato)dicarbonylrhodium(l) were solubilized into 225 mL of toluene. After closing the reactor, 3 nitrogen purges and one purge with a 50:50 mixture of hydrogen and carbon monoxide were carried out. The reaction medium was heated to 130 °C and placed under a continuous pressure of 20 bar of 50:50 mixture of hydrogen and carbon monoxide. After 24 hours, the reaction medium was cooled, the autoclave was purged with nitrogen 3 times, then the reactionmedium was concentrated under vacuum and finally distilled under 6.6 Torr at 85-87 °C. 43 g of Compound B were obtained as a mixture of isomers. Olfactory description: aldehyde, green, citrus, slightly lemony, watery, powerful. The resulting Compound B (Sabinene carboxaldehyde) has the following spectral characteristics:1H-NMR (300 MHz, CDCh): 5 (ppm) 9.81-9.64 (m, 1H), 2.66-2.14 (m, 3H), 1.99-1.12 (m, 5H), 1.16-0.82 (m, 5H), 0.83 (t, J = 1.0 Hz, 1H), 0.40-0.10 (m, 1H).13C-NMR (75 MHz, CDCh): 5 (ppm) 204.80, 203.24, 203.00, 202.91, 202.67, 54.75, 54.65, 51.99, 51.01, 50.58, 49.87, 48.26, 46.22, 45.57, 41.01, 40.45, 39.49, 38.64, 36.48, 36.31, 36.25, 34.97, 34.61, 34.34, 34.21, 34.15, 33.37, 32.47, 32.42, 32.26, 29.90, 29.58, 28.61, 27.89, 27.69, 27.49, 27.44, 26.74, 26.62, 26.32, 26.10, 24.76, 24.29, 23.19, 23.15, 21.97, 21.92, 20.26, 20.03, 19.92, 19.85, 19.81, 19.75, 17.93, 17.72, 16.99, 16.50, 12.65, 10.07, 8.81.

[0051] Compound C: Sabina ketone (5-isopropylbicyclo[3.1.0]hexan-2-one): 20 g of Sabinene material (Treatt Pic (Suffolk, UK), 78% Sabinene, 22% beta-pinene) and 100 mL of ethyl acetate were added to a 3-necked flask fitted with a thermometer, a stopper and a bubbler. The resulting solution was cooled to -50 °C, and a flow of ozone was bubbled subsurface (ozone parameters: 1.2 L / min - 145 g / Nm3; theoretical reaction time: 40.5 min). When the reaction mixture turned blue, the ozone flow was discontinued, and the mixture was degassed with air until turning a pale yellow color. The reaction mixture was poured over 46.2 g of triphenylphosphine, stirred, and allowed to reach the ambient temperature. The process was repeated 8 times and combined into a single mixture, which was filtered and concentrated under vacuum. The resulting residue was diluted with 3 volumes (v / m) of pentane and stored overnight at 4 °C. The resulting solution was filtered and the filtrate was concentrated under vacuum. The resulting residue was diluted with 1 volume (v / m) of polypropylene glycol and vacuum distilled (2.3 mbar at 55 °C) to provide 134.2 g of Compound C (78% Sabina ketone, 22% nopinone).The resulting Compound B (Sabina ketone) has the following spectral characteristics:1H NMR (300 MHz, CDCh): 52.20 - 2.04 (m, 2H), 2.03 - 1.94 (m, 2H), 1.67 - 1.54 (m, 2H), 1.18 (ddt, J = 9.1, 4.6, 1.1, 1.1 Hz, 1H), 1.12 - 1.05 (m, 1H), 0.97 (dd, J = 13.2, 6.8 Hz, 6H).13C NMR (75 MHz, CDCh): 5214.65, 40.40, 39.47, 33.70, 33.15, 32.21, 23.56, 19.50, 19.23, 19.13.MS [El+] (m / z) (%): 138 (M+, 12), 123 (21), 97 (19), 96 (75), 95 (82), 83 (14), 82 (20), 81 (100), 79 (25), 77 (12), 68 (17), 67 (49), 65 (13), 55 (52), 54 (11), 53 (23), 51 (12), 43 (32), 41 (54), 39 (42).Nopinone: MS [El+] (m / z) (%): 138 (M+, 10), 123 (20), 110 (14), 109 (28), 97 (13), 96 (30), 95 (53), 83 (100), 82 (18), 81 (47), 79 (16), 69 (15), 68 (14), 67 (32), 55 (67), 53 (21), 43 (13), 41 (52), 39 (43).

[0052] Compound 1 (3-(5-lsopropylbicyclo[3.1 ,0]hexan-2-yl)-2-methylacryl-aldehyde): In a 3-necked flask fitted with a thermometer, a condenser and an addition funnel was placed a solution of 0.7 g of sodium hydroxide in 10 mL of methanol. The resulting solution was heated under reflux and a mixture of 7.54 mL of propionaldehyde and 8 g of Compound A (preparation described above) were added dropwise via the addition funnel. At the end of the addition, the reaction mixture was stirred for 2 hours and was then allowed to cool down to room temperature. The reaction mixture was poured over a mixture of 50 mL of water and 50 mL of MTBE and the layers were then separated. The aqueous phase was extracted once with 50 mL of MTBE. The combined organic phases were washed with water, dried over MgSCM, and concentrated under vacuum. The crude product was distilled under reduced pressure (boiling point: 80 °C at 0.58 Torr) to provide Compound 1. Olfactory description: anisic, cinnamon, violet, raspberry. Compound 1 has the following spectral characteristics:1H-NMR (300 MHz, CDCh): 5 (ppm) 9.45 (m, 1H), 5.29 - 5.23 (m, 1H), 3.28-2.78 (m, 1H), 2.60 - 2.14 (m, 1H), 2.19 - 2.02 (m, 1H), 2.02 - 1.57 (m, 4H), 1.62 - 1.02 (m, 3H), 1.06 - 0.73 (m, 7H), 0.67 - 0.20 (m, 1 H).13C-NMR (75 MHz, CDCh): 5 (ppm) 196.10, 195.85, 195.73, 176.67, 173.58, 173.29, 164.49, 159.71, 159.18, 158.87, 149.70, 149.35, 148.90, 137.98, 125.60, 77.25, 48.09, 45.03, 40.14, 39.65, 39.57, 39.31, 36.68, 35.99, 34.98, 34.92, 34.69, 34.45, 34.27, 32.51, 32.41, 32.39, 32.36, 30.29, 28.00, 27.93, 27.62, 27.52, 27.41, 27.38, 27.36, 27.10, 27.03, 26.58, 26.54, 26.43, 25.70, 25.64, 25.01, 24.28, 23.40, 20.73, 20.24, 20.18, 20.02, 19.92, 19.90, 19.84, 12.54, 12.37, 12.25, 12.09, 9.92, 9.41, 9.06, 8.99, 8.67

[0053] Compound 2 (7-(5-lsopropylbicyclo[3.1 ,0]hexan-2-yl)hept-6-en-1-ol): 175 g of (6-hydroxyhexyl)(triphenyl)phosphonium bromide and 500 mL of toluene were charged in a 3-necked flask fitted with a thermometer, a condenser, an addition funnel and a mechanical stirrer. 74 g of potassium fe / Y-butoxide were added under stirring and the resulting red reaction mixture was heated at 70 °C for 3 hours. 50 g ofCompound A (preparation described above) were charged in the addition funnel and then added dropwise under stirring at 70 °C. The reaction was continued until the conversion of the carbaldehyde was complete (reaction progress was followed by gas chromatography). After the completion of the reaction, the reaction mixture was cooled down to room temperature, poured over 250 mL of a 10 wt% aqueous HCI solution, stirred for a few minutes and then partitioned into two layers. The organic phase was washed with water, dried over MgSCk, and concentrated under vacuum. The crude product was distilled under reduced pressure (boiling point: 71 °C at 1.0 Torr) to provide Compound 2. Olfactory description: herbal, green, aldehydic, algae. Compound 2 has the following spectral characteristics:1H-NMR (300 MHz, CDCh): 5 (ppm) 5.50 - 5.43 (m, 2H), 3.57 (q, J = 5.8 Hz, 2H), 2.62 (t, J = 5.9 Hz, 1 H), 2.51 - 2.42 (m, 1 H), 2.05 - 1.91 (m, 3H), 1.75 - 1.62 (m, 3H), 1.62 - 1.51 (m, 3H), 1.50 - 1.34 (m, 6H), 0.93 (d, J = 5.3 Hz, 3H), 0.89 (d, J = 5.3 Hz, 3H).13C-NMR (75 MHz, CDCh): 5 (ppm) 135.57, 135.21, 133.59, 132.17, 132.03, 128.63, 128.46, 127.22, 77.47, 77.05, 76.62, 66.21, 62.92, 46.46, 43.40, 42.94, 40.26, 39.32, 37.78, 37.76, 34.24, 33.98, 33.90, 32.95, 32.65, 32.62, 32.50, 29.78, 29.71, 29.60, 29.44, 28.51, 28.46, 28.44, 27.95, 27.82, 27.59, 27.40, 27.31, 26.69, 25.37, 25.32, 24.79, 24.57, 24.22, 24.06, 23.29, 21.96, 20.36, 20.19, 20.02, 19.99, 19.94, 19.87, 19.80, 19.73, 12.56, 8.80, 8.63.

[0054] Notably, the same Wittig reaction conditions applied on Compound B instead of Compound A provided 8-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)oct-6-en-1-ol. An oxidation reaction of the latter using (Bisacetoxyiodo)benzene and TEMPO provided 8-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)oct-6-enal, whereas an hydrogenation reaction catalyzed by Palladium on charcoal of the latter provided 8-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)octan-1 -ol.

[0055] Compound 3 (7-(5-lsopropylbicyclo[3.1 ,0]hexan-2-yl)hept-6-enal): To a round-bottom flask equipped with a stirring bar, a condenser, and a thermometer, was charged 28 g of 7-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)hept-6-en-1-ol (Compound 2) and 0.37 g of TEMPO ((2,2,6,6-tetramethylpiperidin-1-yl)-oxyl), followed by in 200 mL of butyronitrile and 100 mL of water. The mixture was stirred and cooled down below 5 °C. 38.3 g of BAIB ((Bisacetoxyiodo)benzene) was added portion wise (10 portions in 10 minutes) at 0 °C. At the end of the addition, the reaction mixture was brought to room temperature and stirred until full conversion of the starting alcohol was observed. The reaction mixture was quenched with 5V of Na2S20s (saturated aqueous solution).After decantation, the organic phase was washed with 3V of deionized water (pH =2) and 3V of NaHCOs (saturated aqueous solution) until neutral before being dried over MgSCk and concentrated under vacuum. The crude product was distilled under reduced pressure (boiling point: 80 °C at 0.5 Torr) to provide Compound 3.Olfactory description: herbal, green, parsley, cumin, coriander. Compound 3 has the following spectral characteristics:1H-NMR (300 MHz, CDCh): 5 (ppm) 9.77 (d, J = 2.1 Hz, 1 H), 5.48 - 5.11 (m, 2H), 3.63 (s, 1 H), 3.74 - 3.35 (m, 1 H), 3.07 - 2.72 (m, 1 H), 2.44 (td, J = 7.3, 2.0 Hz, 1 H), 2.08 (dq, J = 12.4, 6.2 Hz, 2H), 1.93 - 1.21 (m, 5H), 1.31 (s, 1 H), 1.26 - 0.71 (m, 9H), 0.47 - 0.02 (m, 2H).13C-NMR (75 MHz, CDCh): 5 (ppm) 202.76, 135.97, 135.61, 134.04, 127.97, 126.57, 77.47, 77.05, 76.62, 46.42, 43.78, 40.25, 39.31, 37.81, 37.78, 34.25, 34.00, 32.99, 32.60, 32.49, 31.50, 29.41, 29.25, 28.45, 28.40, 28.10, 27.94, 27.78, 27.65, 27.57, 27.31, 27.02, 26.91, 26.86, 26.67, 25.37, 25.16, 24.55, 23.28, 21.92, 21.66, 20.34, 20.18, 20.01, 19.93, 19.88, 19.79, 12.56, 9.88, 8.63.

[0056] Compound 4 (Ethyl 3-(5-isopropylbicyclo[3.1.0]hexan-2-yl)-2-methylacrylate): To a 3-necked flask, fitted with a thermometer, a condenser, and an addition funnel, was charged 48.2 g of triethyl phosphonopropionate and 150 mL of THF. Under vigorous stirring, the mixture was heated to reflux, then 75 mL of sodium ethoxide in ethanol (21%wt.) was introduced into the addition funnel and added dropwise. The mixture was stirred for 1 hour under reflux and 22 g of Compound A (preparation described above) was added dropwise over 30 minutes. After stirring the reaction medium overnight under reflux, the mixture was cooled down to room temperature and poured into an aqueous solution of 10% sulfuric acid under stirring. The layers were separated, and the organic phase was washed with water and dried over MgSCk. The solvent was removed under vacuum. The crude product was distilled under reduced pressure (boiling point: 81 °C at 0.5 Torr) to provide Compound 4. Olfactory description: green, anisic, fennel, violet. Compound 4 has the following spectral characteristics:1H-NMR (300 MHz, CDCh): 5 (ppm) 6.79 - 6.58 (m, 1H), 4.26 - 4.03 (m, 2H), 3.03 (dqt, J = 14.1, 9.9, 5.3 Hz, 1H), 1.92 - 1.15 (m, 10H), 1.14 - 0.97 (m, 1H), 1.01 - 0.80 (m, 7H), 0.56 - 0.11 (m, 2H).13C-NMR (75 MHz, CDCh): 5 (ppm) 168.39, 146.91, 146.74, 146.46, 145.68, 126.52, 126.01, 125.56, 124.98, 77.46, 77.04, 76.62, 60.33, 59.99, 45.77, 45.16, 40.22, 40.11,39.91, 39.62, 39.35, 39.26, 34.61, 34.51, 34.39, 34.15, 32.48, 32.42, 32.37, 28.26, 28.01, 27.88, 27.84, 27.70, 27.55, 27.50, 27.45, 27.08, 26.57, 25.68, 25.53, 24.35, 23.46, 23.12, 21.03, 20.66, 20.39, 20.24, 20.15, 20.00, 19.87, 19.79, 14.30, 14.24, 12.61, 12.44, 12.33, 9.04, 8.67.

[0057] Notably, a hydrogenation reaction catalyzed by Palladium on charcoal of Compound 4 provided ethyl 3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2-methylpropanoate.

[0058] Compound 5 (5-(5-lsopropylbicyclo[3.1.0]hexan-2-yl)pent-4-enenitrile): In a 3-necked flask fitted with a thermometer, a dropping funnel and a condenser, were placed 63 g of (3-cyanopropyl)triphenylphosphonium chloride and 300 mL of toluene.32.4 g of potassium te / t-butoxide were then added under stirring. The mixture was stirred and heated at 70 °C for 1 hour. Then, 22 g of Compound B (preparation described above) was added dropwise over 1 hour. The mixture was heated at 70 °C overnight. The medium was cooled down to room temperature and poured over a 10% HCI aqueous solution, the organic phase was washed with water, dried, and then concentrated under vacuum. The crude product was diluted in 300 mL of te / Y-butyl methyl ether. This solution was cooled at 4 °C overnight to precipitate triphenylphosphine oxide formed during the reaction. The solid was filtered off and the filtrate was concentrated under vacuum. The crude product obtained as a mixture of isomers, was distilled under reduced pressure: its boiling point is 67 °C under 0.8 Torr to provide Compound 5. Olfactory description: spicy, lemon, woody, smoked. Compound 5 has the following spectral characteristics:1H-NMR (300 MHz, CDCh): 5 (ppm) 7.41-7.16 (m, 1H), 6.88-6.80 (m, 1H), 3.62 -3.30 (m, 2H), 2.36 (s, 1 H), 2.47 - 2.08 (m, 1 H), 1.74 - 1.60 (m, 1 H), 1.65 - 1.53 (m, 1 H), 1.59 - 1.42 (m, 1H), 1.46 - 1.33 (m, 1H), 1.39 - 1.16 (m, 1H), 1.21 - 1.01 (m, 1H), 1.06 - 0.68 (m, 6H), 0.39 - 0.26 (m, 2H), 0.16 (dd, J = 8.0, 4.9 Hz, 1 H).13C-NMR (75 MHz, CDCh): 5 (ppm) 129.44, 129.15, 119.81, 115.40, 66.42, 66.14, 47.80, 47.61, 43.38, 42.92, 33.89, 33.69, 32.61, 32.51, 27.39, 25.05, 24.79, 24.24, 24.09, 23.67, 23.62, 20.29, 19.97, 19.85, 19.71, 12.50, 8.78.

[0059] Compound 6 (Ethyl 3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)acrylate): To a 3-necked flask, fitted with a thermometer, a condenser, and an addition funnel, were charged 51 g of triethyl phosphonoacetate and 150 mL of THF. Under vigorous stirring, the mixture was heated to reflux, then 85 mL of sodium ethoxide in ethanol (21wt%) were added to the reaction medium. The reaction mixture was stirred for 1 hour and25 g of Compound A (preparation described above) were added dropwise over 30 minutes. After stirring the reaction medium under reflux overnight, the mixture was poured into an aqueous solution of 10% sulfuric acid under stirring. The layers were separated, and the organic phase was washed with water and dried over MgSCh. The solvent was removed under vacuum. The crude product was distilled under reduced pressure (boiling point: 56 °C at 0.5 Torr) to provide Compound 6. Olfactory description: green, anisic, fennel, citrus. Compound 6 has the following spectral characteristics:1H-NMR (300 MHz, CDCh): 5 (ppm) 6.99-6.78, 6.07-5.61 (m, 1H), 5.34-5.04 (m, 1H) 4.10 - 3.97 (m, 2H), 3.16-2.81 (m, 1H), 2.07 - 1.80 (m, 4H), 1.85 - 1.25 (m, 3H), 1.22-1.13 (m, 3H), 0.89 - 0.78 (m, 6H), 0.64 - 0.44 (m, 1H).13C-NMR (75 MHz, CDCh): 5 (ppm) 172.73, 172.49, 153.16, 152.15, 148.59, 148.24, 146.17, 119.66, 119.12, 112.56, 112.51, 108.76, 108.48, 77.24, 71.63, 63.66, 63.58, 60.41, 60.10, 52.34, 47.86, 47.75, 45.27, 43.00, 42.71, 41.79, 40.88, 40.70, 40.65, 39.04, 37.60, 36.58, 34.95, 34.90, 34.37, 33.12, 32.83, 32.75, 32.45, 32.41, 32.15, 30.50, 29.42, 27.73, 27.67, 27.59, 27.29, 26.75, 26.60, 26.24, 26.15, 26.01, 25.94, 25.84, 25.03, 24.71, 24.22, 23.75, 23.60, 21.92, 21.52, 20.72, 20.17, 20.03, 19.97, 19.84, 19.79, 19.70, 19.65, 16.18, 16.08, 14.29, 14.22, 11.77, 9.28.

[0060] Compound 7 (3-Acetyl-5-isopropylbicyclo[3.1 ,0]hexan-2-one): 64.95 g of potassium te / t-butoxide and 300 mL of THF were charged to a 3-necked flask fitted with a thermometer, a condenser, and an addition funnel. Under stirring, a mixture of 40 g of Compound C (preparation described above) and 76.5 g of ethyl acetate were added dropwise over 30 minutes. After the addition was complete, the mixture was stirred 2 h at RT. GC analysis confirmed a total conversion of the Sabina ketone. The reaction mixture was poured into 150 mL of cold water, and stirred for 30 minutes, before being transferred into a separatory funnel. The layers were separated, the aqueous phase was extracted twice with 100 mL of MTBE. The combined organic phases were washed with brine, then water and finally dried over MgSCh. The solvent was removed under vacuum, and the crude product was distilled under reduced pressure (boiling point: 75 °C at 0.23 Torr) to provide Compound 7. Olfactory description: spicy, saffron, aromatic, anisic, thyme, herbal, celery. Compound 7 has the following spectral characteristics:1H-NMR (300 MHz, CDCh): 5 (ppm) 3.46 - 3.27 (m, 1H), 2.61 - 2.41 (m, 1H), 2.27-2.21 (m, 1H), 2.04 - 1.84 (s, 3H), 1.70 (m, 1H), 1.65 - 1.40 (m, 1H), 1.31 - 1.10 (m,1 H), 1.15 - 0.95 (m, 1 H), 0.92 (m, 5H), 0.67 (m, 1 H).13C-NMR (75 MHz, CDCh): 5 (ppm) 208.15, 206.78, 206.62, 202.92, 201.76, 170.96, 107.17, 77.52, 77.10, 76.67, 61.49, 56.84, 53.80, 39.66, 39.40, 38.14, 37.95, 34.45, 33.72, 33.66, 32.54, 31.99, 31.90, 31.84, 31.11, 29.04, 28.71, 27.90, 26.91, 26.76, 25.83, 25.63, 24.92, 21.30, 20.71, 20.69, 19.64, 19.49, 19.39, 19.26, 19.24, 19.06, 19.00, 17.34.

[0061] Notably, the same procedure using dimethyl carbonate instead of ethyl acetate provided methyl 1-isopropyl-4-oxobicyclo[3.1 ,0]hexane-3-carboxylate.

[0062] Compound 8 (3-(Hydroxymethyl)-5-isopropylbicyclo[3.1 ,0]hexan-2-ol): 64.95 g of potassium te / Y-butoxide and 300 mL of THF were charged into a 3-necked flask fitted with a thermometer, a condenser, and an addition funnel. Under stirring, a mixture of 40 g of Compound C (preparation described above) and 64.32 g of ethyl formate were added dropwise over 30 minutes. After the addition was complete, the mixture was stirred 2 h at RT. GC analysis confirmed a total conversion of the Sabina ketone. The reaction mixture was poured into 150 mL of cold water, and stirred for 30 minutes, then transferred to a separatory funnel. The layers were separated, the aqueous phase was extracted twice with 100 mL of MTBE. The combined organic phases were washed with brine, then water and finally dried over MgSCh. The solvent was removed under vacuum, and the crude product, containing 99.2% of formylated Sabina ketone intermediate in GC analysis, was used without any further purification in the next step.

[0063] In a 3-necked flask fitted with a thermometer, a dropping funnel and a condenser, 14 g of sodium borohydride and 90 mL of water were placed. The reaction medium was cooled to 15 °C. Then, a solution of 41 g of formylated Sabina ketone intermediate in 90 mL of MTBE was added dropwise. The mixture was stirred at room temperature and after 2 hours, gas chromatography analysis indicated that the conversion of formylated Sabina ketone intermediate was complete. The medium was poured over a 50:50 mixture of a 1% aqueous solution of HCI and fe / Y-butyl methyl ether, the organic phase was washed with water, dried over MgSO4, and then concentrated under vacuum. The 39.8 g of Compound 8 was finally isolated with 98% purity. Olfactory description: aromatic, animalic, spicy. The resulting Compound 8 has the following spectral characteristics:1H-NMR (300 MHz, CDCh): 5 (ppm) 4.22 (dd, J = 7.8, 4.5 Hz, 1H), 3.69 - 3.32 (m, 1 H), 3.13 (s, 2H), 2.32 - 2.03 (m, 1 H), 2.01 - 1.70 (m, 1 H), 1.47 - 1.26 (m, 2H), 1.29- 1.11 (m, 1 H), 1.11 - 0.92 (m, 1 H), 0.96 - 0.79 (m, 4H), 0.79 - 0.72 (m, 1 H), 0.35 (ddd, J = 8.1, 5.0, 1.2 Hz, 1H).13C-NMR (75 MHz, CDCh): 5 (ppm) 78.37, 78.20, 77.47, 77.05, 76.63, 74.14, 69.41, 66.49, 66.32, 65.62, 64.06, 53.91, 48.04, 47.33, 43.90, 41.47, 41.07, 40.51, 40.18, 38.22, 37.74, 36.51, 34.40, 32.44, 32.35, 32.07, 31.23, 30.61, 29.19, 29.05, 29.01, 27.95, 27.66, 27.46, 27.32, 25.65, 22.39, 22.24, 20.01, 19.89, 19.67, 19.49, 19.41, 15.61, 10.66.

[0064] Compound 9 (2-Ethyl-5a-isopropylhexahydro-4h-cyclopropa[4,5]cyclopenta [1 ,2-d][1 ,3]dioxine): 1.1 g of para-toluenesulfonic acid monohydrate and 5 mL of MTBE were charged to a 3-necked flask fitted with a thermometer, a condenser, and an addition funnel. Under vigorous stirring, at -5 °C, a mixture of 42 mL of propionaldehyde and 10 g of Compound 8 was added dropwise to the reaction medium. The reaction mixture was stirred for 1 hour at -5 °C. Then, 1 g of sodium carbonate was added to the reaction medium while stirring and warming to room temperature. The reaction mixture was filtered and the filtrate was concentrated under vacuum. The crude product was distilled under reduced pressure (boiling point: 95 °C at 0.25 Torr). Olfactory description: herbal, green, anisic, fennel, celery, spicy. The resulting Compound 9 has the following spectral characteristics:1H-NMR (300 MHz, CDCh): 5 (ppm) 4.55 - 4.23 (m, 1 H), 4.16 - 3.83 (m, 1 H), 3.83 -3.42 (m, 1H), 2.31 - 1.74 (m, 2H), 1.78 - 1.15 (m, 6H), 1.12 (s, 1H), 1.07 - 0.63 (m, 9H), 0.47 - 0.26 (m, 1H).13C-NMR (75 MHz, CDCh): 5 (ppm) 109.82, 103.93, 101.68, 100.84, 100.55, 84.98, 77.46, 77.04, 76.90, 76.62, 72.16, 69.09, 46.13, 45.47, 43.91, 41.08, 39.20, 38.07, 34.74, 33.75, 33.47, 32.69, 32.37, 31.87, 30.08, 29.81, 29.56, 28.87, 28.33, 28.09, 27.88, 27.71, 27.35, 24.56, 24.25, 23.19, 22.68, 20.14, 19.65, 19.63, 19.41, 11.21, 10.52, 9.08, 8.69, 8.17.

[0065] Notably, the same acetalization procedure using acetaldehyde instead of propionaldehyde on Compound 8 provided 5a-isopropyl-2-methylhexahydro-4h-cyclopropa[4,5]cyclopenta[1 ,2-d][1 ,3]dioxine. The same acetalization procedure using acetone instead of propionaldehyde on Compound 8 provided 5a-isopropyl-2,2-dimethylhexahydro-4h-cyclopropa[4,5]cyclopenta[1 ,2-d][1 ,3]dioxine. The same acetalization procedure using methyl ethyl ketone instead of propionaldehyde on Compound 8 provided 2-ethyl-5a-isopropyl-2-methylhexahydro-4h-cyclopropa[4,5]cyclopenta[1 ,2-d][1 ,3]dioxine. The same acetalization procedure usingacetaldehyde instead of propionaldehyde on Compound 10 provided 5a-isopropyl-2,4-dimethylhexahydro-4h-cyclopropa[4,5]cyclopenta[1 ,2-d][1 ,3]dioxine.

[0066] Compound 10 (3-(1-Hydroxyethyl)-5-isopropylbicyclo[3.1 ,0]hexan-2-ol): In a 3-necked flask fitted with a thermometer, a dropping funnel and a condenser, 6.3 g of sodium borohydride and 50 mL of water were placed. The reaction medium was cooled to 15 °C. Then, a solution of 20 g of Compound 7 in 50 mL of MTBE was added dropwise into the reaction medium stirred at room temperature. After 2 hours, gas chromatography analysis indicated that the conversion of Compound 7 was complete. The medium was poured over a 50:50 mixture of a 1% aqueous solution of HCI and te / t-buty I methyl ether. The organic phase was then separated and washed with water, dried over MgSCk, and then concentrated under vacuum. 20.2 g of Compound 10 were finally isolated with 99% purity. Olfactory description: aromatic, anisic, green, spicy. The resulting Compound 10 has the following spectral characteristics:1H-NMR (300 MHz, CDCh): 5 (ppm) 4.28 (dt, J = 8.1 , 4.3 Hz, 1 H), 3.89 - 3.56 (m, 1 H), 2.88 (s, 3H), 1.78 - 1.63 (m, 1 H), 1.62 - 1.04 (m, 6H), 1.04 - 0.71 (m, 5H), 0.42 - 0.24 (m, 1H).13C-NMR (75 MHz, CDCh): 5 (ppm) 79.34, 77.48, 77.06, 76.64, 74.78, 73.31, 67.81, 48.66, 48.54, 36.56, 34.64, 32.42, 32.34, 32.17, 31.78, 31.61, 31.50, 31.09, 29.50, 29.37, 29.14, 28.08, 27.54, 27.20, 22.55, 21.38, 19.97, 19.86, 19.68, 19.64, 19.41, 19.37, 12.59, 10.72, 10.27.

[0067] Compound 11 (6-((5-lsopropylbicyclo[3.1.0]hexan-2-yl)methyl)-4-methyl-3,6-dihydro-2h-pyran, 2-((5-isopropylbicyclo[3.1.0]hexan-2-yl)methyl)-4-methylenetetra-hydro-2h-pyran and 2-((5-isopropylbicyclo[3.1.0]hexan-2-yl)methyl)-4-methyl-3,6-dihydro-2h-pyran mixture): To a 3-necked flask fitted with a thermometer, a Dean-Stark apparatus fitted with a condenser, and an addition funnel, were charged 0.57 g of para-toluenesulfonic acid, 150 mL of methylcyclohexane and 10 g of Compound B (preparation described above). Under vigorous stirring, the mixture was heated under reflux, and then 6.1 mL of 3-methyl-3-buten-1-ol were added. The mixture was stirred at reflux until there was no more water to distill. The reaction medium was allowed to cool down to RT and was then poured into a saturated aqueous solution of sodium bicarbonate under stirring. The layers were separated, and the organic phase was washed with water and dried over MgSCk. The solvent was removed under vacuum. The crude product was distilled under reduced pressure (boiling point: 98 °C at 1.8 Torr). Olfactory description: green, herbal, leaves, dill, petitgrain. The resultingCompound 11 has the following spectral characteristics:1H-NMR (300 MHz, CDCh): 5 (ppm) 4.85 - 4.63 (m, 2H), 4.24 - 3.78 (m, 1 H), 3.45 -3.17 (m, 1H), 2.42 - 2.07 (m, 2H), 2.12 - 1.86 (m, 1H), 1.90 - 1.45 (m, 3H), 1.50 -1.14 (m, 4H), 1.14 - 0.66 (m, 8H), 0.39 - 0.13 (m, 2H).13C-NMR (75 MHz, CDCh): 5 (ppm) 144.95, 144.86, 131.95, 131.88, 131.40, 124.38, 119.75, 108.30, 108.25, 108.18, 108.03, 94.95, 94.86, 78.26, 78.24, 77.49, 77.42, 77.25, 77.06, 76.64, 72.41, 72.29, 71.31, 71.25, 68.69, 68.67, 65.89, 63.55, 63.45, 63.30, 63.15, 63.11, 44.20, 43.92, 42.79, 42.43, 42.10, 42.04, 41.79, 41.66, 41.57, 41.50, 41.27, 41.22, 40.52, 39.78, 38.69, 36.39, 36.28, 36.26, 36.21, 36.18, 36.13, 36.04, 35.90, 35.86, 35.56, 35.50, 35.29, 35.25, 33.87, 33.80, 33.75, 33.71, 32.74, 32.71, 32.65, 31.78, 30.11, 28.45, 28.27, 28.19, 28.10, 28.06, 27.97, 27.87, 27.78, 27.71, 27.57, 27.36, 27.16, 27.09, 26.93, 26.71, 26.65, 26.46, 26.36, 24.71, 24.67, 24.61, 24.51, 23.24, 23.06, 21.61, 20.45, 20.41, 20.06, 19.91, 19.86, 19.84, 17.83, 16.68, 12.84, 12.78, 12.73, 12.69, 12.65, 8.75, 8.53.

[0068] Notably, the same Prins procedure on Compound B using formic acid at room temperature instead of para-toluenesulfonic acid at reflux provided 2-((5-isopropylbicyclo[3.1 ,0]hexan-2-yl)methyl)-4-methyltetrahydro-2h-pyran-4-ol.

[0069] Compound 12 (4-(5-lsopropylbicyclo[3.1 ,0]hexan-2-yl)-2,6-dimethylcyclohex-2-en-1-one): In a 3-necked flask fitted with a thermometer, a dropping funnel and a condenser were placed 140 mL of 37wt% aqueous formaldehyde solution. 13.3 g of pyrrolidine were added dropwise over this solution at room temperature over 30 minutes, then 14 g of propionic acid were added dropwise over 30 minutes. The mixture was heated at 50 °C. Finally, 312 g of Compound B (preparation described above) were added dropwise over 2 hours and the reaction mixture was stirred at 50 °C overnight. The medium was cooled to room temperature and poured over a 50:50 mixture of water and fe / t-butyl methyl ether. The organic phase was separated, washed with water, dried over MgSCM, and then concentrated under vacuum. The crude product, obtained as a mixture of isomers, was distilled under reduced pressure (55-58 °C under 1 mbar) to provide methylene Sabinene carboxaldehyde intermediate.

[0070] To a 3-necked flask fitted with a thermometer, a condenser, and an addition funnel, were charged 6 g of potassium hydroxide and 89 mL of ethanol. Under vigorous stirring, the mixture was cooled down to 0 °C and then 75 mL of 3-pentanone followed by 90 g of methylene Sabinene carboxaldehyde intermediate were added dropwisesuccessively. After the addition, the reaction mixture was allowed to warm up to RT under stirring. After 1 hour of reaction, the mixture was poured into a mixture of 100 mL of water and 100 mL of MTBE. The layers were separated, and the organic phase was washed with water and dried over MgSCk. The solvent was removed under vacuum. The crude product was distilled under reduced pressure (boiling point: 102 °C at 0.2 Torr). Olfactory description: anisic, herbal, green, leathery. The resulting Compound 12 has the following spectral characteristics:1H-NMR (300 MHz, CDCh): 5 (ppm) 6.61 (s, 1 H), 2.77 - 2.46 (m, 1 H), 2.36 (ddddd, J = 15.7, 13.4, 6.5, 4.2, 2.1 Hz, 1H), 2.27 - 1.83 (m, 2H), 1.87 - 1.72 (m, 4H), 1.76 -1.59 (m, 1H), 1.59 (ddd, J= 7.0, 4.6, 1.9 Hz, 1H), 1.57 - 1.36 (m, 2H), 1.40 - 1.18 (m, 1H), 1.18 - 1.10 (m, 3H), 1.15 - 0.98 (m, 1H), 1.03 - 0.77 (m, 6H), 0.44 - 0.31 (m, 1 H), 0.25 (tdt, J = 7.8, 4.8, 2.6 Hz, 1 H).13C-NMR (75 MHz, CDCh): 5 (ppm) 202.80, 149.14, 148.71, 148.60, 148.34, 135.11, 134.96, 133.76, 127.04, 126.84, 77.49, 77.27, 77.07, 76.64, 45.59, 45.47, 45.36, 44.41, 44.30, 43.20, 41.87, 41.51, 41.45, 41.39, 39.28, 38.74, 38.13, 37.42, 37.29, 36.82, 36.35, 36.03, 35.34, 35.27, 35.08, 34.95, 34.20, 33.89, 33.73, 32.93, 32.67, 32.56, 32.52, 32.34, 32.24, 30.36, 29.68, 29.09, 27.70, 27.59, 27.53, 26.83, 26.61, 26.12, 26.03, 25.79, 25.22, 25.17, 25.11, 25.06, 24.75, 20.29, 20.23, 20.20, 20.06, 20.04, 19.86, 18.17, 17.75, 16.56, 16.41, 16.06, 15.94, 15.53, 15.40, 13.33, 12.63, 12.42, 9.44, 9.02.

[0071] Notably, a reduction reaction on Compound 12 using sodium borohydride in ethanol at RT provided 4-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2,6-dimethylcyclohex-2-en-1-ol.

[0072] Compound 13 (Butyl 4-(5-isopropylbicyclo[3.1.0]hexan-2-yl)-5-oxopentanoate): To a 3-necked flask fitted with a thermometer, a condenser, and an addition funnel, were charged 90 mL of butyl acrylate, 9.3 mL of diethylamine and 200 mL of ethanol. Under vigorous stirring at RT, 30 g of Compound B (preparation described above) were added dropwise. The mixture was then stirred under reflux overnight. After cooling down to RT, the reaction medium was poured into a mixture of 100 mL of water and 100 mL of MTBE under stirring. The layers were separated, and the organic phase was washed with water and dried over MgSCh. The solvent was removed under vacuum. The crude product was distilled under reduced pressure (boiling point: 90 °C at 0.5 Torr). Olfactory description: herbal, green, parsley, citrus, woody. The resulting Compound 13 has the following spectral characteristics:T11H-NMR (300 MHz, CDCI3): 6 (ppm) 9.60 (dd, J = 6.4, 3.4 Hz, 1 H), 4.06 (tq, J = 6.7, 1.4 Hz, 2H), 2.47 - 2.06 (m, 3H), 2.06 - 1.74 (m, 2H), 1.79 - 1.60 (m, 1 H), 1.66 - 1.49 (m, 3H), 1.41 (dtdd, J = 16.1 , 14.4, 9.7, 6.8 Hz, 4H), 1.27 - 1.00 (m, 1 H), 0.93 (ddd, J = 7.1 , 5.0, 2.7 Hz, 7H), 0.91 - 0.78 (m, 4H), 0.43 - 0.18 (m, 2H).13C-NMR (75 MHz, CDCI3): 5 (ppm) 205.37, 205.05, 204.97, 173.29, 173.25, 173.19, 173.16, 77.48, 77.26, 77.06, 76.63, 64.45, 56.09, 56.03, 55.89, 55.60, 40.97, 40.93, 40.84, 40.61, 35.10, 35.03, 34.36, 33.53, 32.53, 32.21, 31.96, 31.90, 31.82, 30.60, 27.43, 26.80, 26.58, 26.20, 25.79, 25.62, 25.36, 24.97, 24.79, 24.44, 23.74, 23.06, 22.38, 22.18, 20.18, 20.04, 19.98, 19.94, 19.85, 19.14, 13.76, 12.71, 12.55, 9.62, 9.44.

[0073] Notably, a reduction reaction on Compound 13 using sodium borohydride in isopropanol at 30 °C provided 2-(5-isopropylbicyclo[3.1.0]hexan-2-yl)pentane-1,5-diol. The latter can be cyclized in the presence of a catalytic amount of phosphoric acid to provide 3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)tetrahydro-2h-pyran. A hydrogenation reaction on Compound 13 catalyzed by Raney Nickel under 50 bar of hydrogen at 120 °C in butanol provided butyl 5-hydroxy-4-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)pentanoate. The latter can be cyclized in the presence of a catalytic amount of para-toluenesulfonic acid to provide 5-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)tetrahydro-2h-pyran-2-one.

[0074] Compound 14 (5-isopropylbicyclo[3.1 ,0]hexan-2-one o-methyl oxime): In a 3-necked round bottomed flask equipped with a condenser were added 5 g of Compound C, 120 mL of Methanol, 5.9 g of Sodium Acetate and then 3.63 g of O-methoxylamine hydrochloride under stirring. The reaction mixture was stirred under reflux for 1 h30, the GC analysis then featured a full conversion of Compound C. The reaction mixture was cooled down to room temperature, and then poured into a mixture of 50 mL of ethyl acetate and 30 mL of saturated aqueous sodium bicarbonate solution. The aqueous phase was extracted twice with EtOAc. Combined organic phases were then washed with brine and dried over MgSCk. After concentration of the organic phase in vacuo, the crude product was distilled under reduced pressure (boiling point: 38 °C at 0.4 Torr). 4.26g of pure Compound 14 was finally obtained with 99.5% purity.Olfactory description: herbal, green, ripe fruit, lychee. The resulting Compound 14 has the following spectral characteristics:1H-NMR (300 MHz, CDCI3): 5 (ppm) 3.82 (dd, J = 8.5, 1.5 Hz, 3H), 2.84 - 2.63 (m, 1H), 2.62 - 2.25 (m, 1H), 2.24 - 2.00 (m, 1H), 2.00 - 1.71 (m, 3H), 1.52 (dt, J = 13.5, 6.8 Hz, 1 H), 1.41 - 1.24 (m, 1 H), 1.05 - 0.63 (m, 6H).13C-NMR (75 MHz, CDCh): 5 (ppm) 166.86, 165.91, 164.37, 77.60, 77.38, 77.18, 76.75, 61.28, 61.22, 61.13, 60.89, 48.12, 42.99, 41.39, 40.78, 40.63, 40.46, 38.35, 36.75, 32.41, 32.29, 30.89, 27.29, 26.85, 26.48, 26.05, 25.75, 25.60, 25.16, 24.61, 23.28, 23.21, 22.40, 22.32, 22.15, 22.13, 21.81, 19.68, 19.50, 19.45, 18.43, 17.13, 16.98.

[0075] Notably, the same oximation procedure on Compound C using O-ethoxylamine hydrochloride instead of O-methoxylamine hydrochloride provided 5-isopropylbicyclo[3.1 ,0]hexan-2-one O-ethyl oxime.

[0076] Example 1: Perfume Composition with Compound 12.

[0077] Exemplary comparative and inventive perfume compositions were prepared in accordance with the materials listed in Table 1. The comparative example Comp Ex A was evaluated by trained perfumers in comparison to the inventive example Ex A, where a portion of the solvent (dipropylene glycol) was replaced with an equivalent amount (by mass) of Compound 12, which is one of the inventive compounds within the general Formula (I) described above.

[0078] Table 1: Perfume Compositions.

[0079] An accord Ex A was obtained from a Lavender cologne accord Comp Ex A, by replacing 1.5% of DPG by 1.5% of the Compound 12. The two different accordswere compared at 5% in alcohol. Adding Compound 12 to the accord gives warmth to the note and adds complexity. It pushes the anisic and spicy tonalities and delivers an interesting strong woody signature.

[0080] Example 2: Perfume Composition with Compound 12.

[0081] Exemplary comparative and inventive perfume compositions were prepared in accordance with the materials listed in Table 2. The comparative example Comp Ex B was evaluated by trained perfumers in comparison to the inventive example Ex B, where a portion of the solvent (dipropylene glycol) was replaced with an equivalent amount (by mass) of Compound 12, which is one of the inventive compounds within the general Formula (I) described above.

[0082] Table 2: Perfume Compositions.

[0083] An accord Ex B was obtained from a Spicy woody fougere accord Comp Ex B, by replacing 2% of DPG by 2% of the Compound 12. The two different accords were compared at 5% in alcohol. Adding Compound 12 to the accord boosts the woody note and gives warmth and complexity to the note. It pushes the anisic and spicy tonalities and delivers an interesting strong woody signature.

[0084] Example 3: Perfume Composition with Compound 12.

[0085] Exemplary comparative and inventive perfume compositions were prepared in accordance with the materials listed in Table 3. The comparative example Comp Ex C was evaluated by trained perfumers in comparison to the inventive example Ex C, where a portion of the solvent (dipropylene glycol) was replaced with an equivalent amount (by mass) of Compound 12, which is one of the inventive compounds within the general Formula (I) described above.

[0086] Table 3: Perfume Compositions.

[0087] An accord Ex C was obtained from a floral chypre accord Comp Ex C, by replacing 1.5% of DPG by 1.5% of the Compound 12. The two different accords were compared at 0.6% in a shampoo base. Adding Compound 12 to this white floral opulent chypre accord changes the note: the accord is much more woody and round, however less chypre. The volume is enhanced, with more fruitiness.

[0088] While the invention has been illustrated by the description of one or more embodiments thereof, and while the embodiments have been described in considerable detail, they are not intended to restrict or in any way limit the scope of the appended claims to such detail. Additional advantages and modifications will readily appear to those skilled in the art. The invention in its broader aspects is therefore not limited to the specific details, representative product and / or method and examples shown and described. The various features of exemplary embodiments described herein may be used in any combination. Accordingly, departures may be made from such details without departing from the scope of the general inventive concept.

Claims

1. Claims1. A compound having a general Formula (I):Formula (I),wherein — is a single or a double bond;wherein if — is a single bond, then Y is selected from the group consisting of CH2R1, CH=C(R2)R3, and (CH2)xCHR3R4; and OR5; wherein if — is a double bond, then Y is 0, N-OMe, or N-OEt;R is selected from the group consisting of H, C(O)-R6, and CH(R6)-OR5;R1is selected from the group consisting of 1 ,3-dioxepan, 5-methyl-1 ,3-dioxolan-4-one, CH(CH3)CO2Et, and CH(CH3)OH;R2= H or Me;R3is selected from the group consisting of CHO, C02Et, (CH2)nOH, (CH2)nCH0, (CH2)nCN and (CH2)nCO2Bu; and R4is CHO or CH2OH; or R3and R4in combination form a dihydropyran, a tetrahydropyran, a tetrahydropyranol, a tetrahydropyranone, a dimethylcyclohexenone, or a dimethylcyclohexenol;R5is selected from the group consisting of CH(CH3), CH(CH2CH3), C(CH3)CH3and C(CH3)CH2CH3;R6is selected from the group consisting of OMe and Me;x is an integer selected from 0 or 1 ; andn is an integer selected from 2 to 7;with the proviso that when — is a double bond and Y is 0, then R and R6are not H.

2. The compound of claim 1 , wherein — is a single bond and Y is selected from the group consisting of CH2R1, CH=C(R2)R3, and (CH2)xCHR3R4; and OR5.

3. The compound of claim 1, wherein — is a double bond and Y is 0, N-OMe, or N-OEt.

4. The compound of any one of claims 1 to 3, wherein R is selected from the group consisting of C(O)-R6and CH(R6)-OR5.

5. The compound of claim 1 , selected from the group consisting of:methyl 1 -isopropyl-4-oxobicyclo[3.1 ,0]hexane-3-carboxylate;3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2-methylacrylaldehyde;7-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)hept-6-en-1 -ol;ethyl 3-(5-isopropylbicyclo[3.1.0]hexan-2-yl)-2-methylpropanoate;7-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)hept-6-enal;ethyl 3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2-methylacrylate;5-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)pent-4-enenitrile;2-((5-isopropylbicyclo[3.1.0]hexan-2-yl)methyl)-5-methyl-1 ,3-dioxolan-4-one; 2-((5-isopropylbicyclo[3.1 ,0]hexan-2-yl)methyl)-1 ,3-dioxepane;ethyl 3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)acrylate;3-(hydroxymethyl)-5-isopropylbicyclo[3.1 ,0]hexan-2-ol;5a-isopropyl-2-methylhexahydro-4h-cyclopropa[4,5]cyclopenta[1 ,2-d][1 ,3]dioxine; 3-acetyl-5-isopropylbicyclo[3.1 ,0]hexan-2-one;2-ethyl-5a-isopropylhexahydro-4h-cyclopropa[4,5]cyclopenta[1 ,2-d][1 ,3]dioxine; 5a-isopropyl-2,4-dimethylhexahydro-4h-cyclopropa[4,5]cyclopenta[1 ,2-d][1 ,3]dioxine;3-(1 -hydroxyethyl)-5-isopropylbicyclo[3.1 ,0]hexan-2-ol;5a-isopropyl-2,2-dimethylhexahydro-4h-cyclopropa[4,5]cyclopenta[1 ,2-d][1 ,3]dioxine;2-ethyl-5a-isopropyl-2-methylhexahydro-4h-cyclopropa[4,5]cyclopenta[1 ,2-d][1 ,3]dioxine;6-((5-isopropylbicyclo[3.1.0]hexan-2-yl)methyl)-4-methyl-3,6-dihydro-2h-pyran; 2-((5-isopropylbicyclo[3.1.0]hexan-2-yl)methyl)-4-methylenetetrahydro-2h-pyran; 2-((5-isopropylbicyclo[3.1.0]hexan-2-yl)methyl)-4-methyl-3,6-dihydro-2h-pyran; 4-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2,6-dimethylcyclohex-2-en-1 -ol;4-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2,6-dimethylcyclohex-2-en-1 -one;2-((5-isopropylbicyclo[3.1 ,0]hexan-2-yl)methyl)-4-methyltetrahydro-2h-pyran-4-ol; butyl 4-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-5-oxopentanoate;2-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)pentane-1 ,5-diol;3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)tetrahydro-2h-pyran;butyl 5-hydroxy-4-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)pentanoate; 5-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)tetrahydro-2h-pyran-2-one;5-isopropylbicyclo[3.1 ,0]hexan-2-one o-ethyl oxime; and5-isopropylbicyclo[3.1 ,0]hexan-2-one o-methyl oxime.

6. The compound of claim 1 , selected from the group consisting of:3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2-methylacrylaldehyde;7-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)hept-6-en-1 -ol;7-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)hept-6-enal;Ethyl 3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2-methylacrylate;5-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)pent-4-enenitrile;Ethyl 3-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)acrylate;3-(hydroxymethyl)-5-isopropylbicyclo[3.1 ,0]hexan-2-ol;3-acetyl-5-isopropylbicyclo[3.1 ,0]hexan-2-one;2-ethyl-5a-isopropylhexahydro-4h-cyclopropa[4,5]cyclopenta[1 ,2-d][1 ,3]dioxine; 3-(1 -hydroxyethyl)-5-isopropylbicyclo[3.1 ,0]hexan-2-ol;6-((5-isopropylbicyclo[3.1.0]hexan-2-yl)methyl)-4-methyl-3,6-dihydro-2h-pyran; 2-((5-isopropylbicyclo[3.1.0]hexan-2-yl)methyl)-4-methylenetetrahydro-2h-pyran;2-((5-isopropylbicyclo[3.1.0]hexan-2-yl)methyl)-4-methyl-3,6-dihydro-2h-pyran; 4-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-2,6-dimethylcyclohex-2-en-1 -one;Butyl 4-(5-isopropylbicyclo[3.1 ,0]hexan-2-yl)-5-oxopentanoate; and5-isopropylbicyclo[3.1 ,0]hexan-2-one o-methyl oxime.

7. A composition comprising one or more compounds according to any one of claims 1 to 6, said composition being in particular a fragrance composition, a flavor composition, a pharmaceutical composition, a cosmetic composition, a cleaning composition, a food composition, or an intermediate composition for the preparation of one of said compositions.

8. Use of at least one compound according to any one of claims 1 to 6 to confer, modify, or enhance the organoleptic properties of a substance, composition, or article.

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