CYCLOPROPYL RING OPENING BY ALPHA ALKYLATION OF AN ALDEHYDE WITH A POLYCYCLIC OLEFIN

Abstract

Described herein is a process including alpha alkylation of an aldehyde with a polycyclic olefin followed by a ring opening step in order to provide a compound of formula

##STR00001##

in a form of any one of its stereoisomers or a mixture thereof and where n represents 1 to 4 and R.sup.2 to R.sup.5 represent independently of each other, a hydrogen atom or a C.sub.1-6 linear alkyl group or a C.sub.3-6 branched alkyl group; and R.sup.3 and R.sup.4 or R.sup.5 or, alternatively, R.sup.2 and R.sup.3 when taken together form a saturated or unsaturated optionally substituted 5 or 6 membered carbocyclic ring.

Claims

1. A process for the preparation of a compound of formula ##STR00009## in a form of any one of its stereoisomers or a mixture thereof and wherein n represents 1 to 4, R.sup.1 represents a hydrogen or a C.sub.1-8 linear alkyl group; R.sup.2 to R.sup.5 represent independently of each other, a hydrogen atom or a C.sub.1-6 linear alkyl group or a C.sub.3-6 branched alkyl group; and R.sup.3 and R.sup.4 or R.sup.5 or, alternatively, R.sup.2 and R.sup.3 when taken together form a saturated or unsaturated optionally substituted 5 or 6 membered carbocyclic ring; comprising the step of an alpha alkylation of an aldehyde of formula R.sup.1—CH.sub.2—CHO wherein R.sup.1 has the same meaning as described above with an olefin compound being a fused or bridged bicyclic or tricyclic compound with a methylene group in alpha position of a cyclopropyl ring junction; said step being performed in the presence of a photoredox catalyst, a hydrogen atom transfer donor, a secondary amine and light.

2. The process according to claim 1, wherein the aldehyde is propanal.

3. The process according to claim 1, wherein the olefin is a compound of formula ##STR00010## in a form of any one of its stereoisomers or a mixture thereof; and wherein n represents 1 to 4 and R.sup.2 to R.sup.5 represent independently of each other, a hydrogen atom or a C.sub.1-6 linear alkyl group or a C.sub.3-6 branched alkyl group; and R.sup.3 and R.sup.4 or R.sup.5 or, alternatively, R.sup.2 and R.sup.3 when taken together form a saturated or unsaturated optionally substituted 5 or 6 membered carbocyclic ring.

4. The process according to claim 1, wherein the photoredox catalyst is an organic photocatalyst, an iridium complex, or a ruthenium complex.

5. The process according to claim 1, wherein the hydrogen atom transfer donor is a thiophenol of formula ##STR00011## wherein each R.sup.a represents, independently from each other, a hydrogen atom, a halogen atom, a C.sub.1-2 linear alkyl group, a C.sub.3-4 linear or branched alkyl group, a phenyl group optionally substituted by one to five halogen atoms and/or C.sub.1-4 alkyl or alkoxyl groups or a silyl group trisubstituted with C.sub.1-4 alkyl groups or an aryl group; provided that at most two R.sup.a group represent a hydrogen atom.

6. The process according to claim 1, wherein the compound of formula (I) is selected from the group consisting of 2-methyl-3-(2,3,4,4-tetramethylcyclohex-1-en-1-yl)prop anal, 2-methyl-3-(3-methyl-2-pentylcyclopent-1-en-1-yl)propanal, 3-(3-isopropyl-3-methylcyclopent-1-en-1-yl)-2-methylpropanal, and 3 -((R)-3-isopropyl-3-methylcyclopent-1-en-1-yl)-2-methylpropanal.

7. A compound of formula ##STR00012## in a form of any one of its stereoisomers or a mixture thereof and wherein n represents 1 to 4; R.sup.1 represents a hydrogen or a C.sub.1-8 linear alkyl group and R.sup.2 to R.sup.5 represent independently of each other, a hydrogen atom or a C.sub.1-6 linear alkyl group or a C.sub.3-6 branched alkyl group; and R.sup.3 and R.sup.4 or R.sup.5 or, alternatively, R.sup.2 and R.sup.3 when taken together form a saturated or unsaturated optionally substituted 5 or 6 membered carbocyclic ring.

8. A method to confer, enhance, improve or modify the odor properties of a perfuming composition or of a perfumed article, which method comprises adding to said composition or article an effective amount of the compound of formula (I) as defined in claim 7.

9. A method of using the compound of formula (I) as defined in claim 7, the method comprising using the compound of formula (I) as a perfuming ingredient.

10. A perfuming composition comprising i) at least one compound of formula (I) as defined in claim 7; ii) at least one ingredient selected from the group consisting of a perfumery carrier and a perfumery base; and iii) optionally at least one perfumery adjuvant.

11. A perfumed consumer product comprising at least one compound of formula (I) as defined in claim 7.

12. The perfumed consumer product according to claim 11, wherein the product is a perfume, a fabric care product, a body-care product, a cosmetic preparation, a skin-care product, an air care product or a home care product.

13. The perfumed consumer product according to claim 12, wherein the perfumed consumer product is a fine perfume, a splash or eau de perfume, a cologne, an shave or after-shave lotion, a liquid or solid detergent, a fabric softener, a fabric refresher, an ironing water, a paper, a bleach, a carpet cleaner, a curtaincare product, a shampoo, a coloring preparation, a color care product, a hair shaping product, a dental care product, a disinfectant, an intimate care product, a hair spray, a vanishing cream, a deodorant or antiperspirant, a hair remover, a tanning or sun product, a nail product, a skin cleansing, a makeup, a perfumed soap, shower or bath mousse, oil or gel, or a foot/hand care products, a hygiene product, an air freshener, a “ready to use” powdered air freshener, a mold remover, a furnisher care, a wipe, a dish detergent or hard-surface detergent, a leather care product, or a car care product.

14. The process according to claim 1, wherein the photoredox catalyst is an iridium complex.

15. The process according to claim 1, wherein the compound of formula (I) is 3-((R)-3-isopropyl-3-methylcyclopent-1-en-1-yl)-2-methylpropanal.

16. A perfumed consumer product comprising a perfuming composition as defined in claim 10.

16. The perfumed consumer product according to claim 16, wherein the product is a perfume, a fabric care product, a body-care product, a cosmetic preparation, a skin-care product, an air care product, or a home care product.

17. The perfumed consumer product according to claim 17, wherein the perfumed consumer product is a fine perfume, a splash or eau de perfume, a cologne, an shave or after-shave lotion, a liquid or solid detergent, a fabric softener, a fabric refresher, an ironing water, a paper, a bleach, a carpet cleaner, a curtaincare product, a shampoo, a coloring preparation, a color care product, a hair shaping product, a dental care product, a disinfectant, an intimate care product, a hair spray, a vanishing cream, a deodorant or antiperspirant, a hair remover, a tanning or sun product, a nail product, a skin cleansing, a makeup, a perfumed soap, shower or bath mousse, oil or gel, or a foot/hand care products, a hygiene product, an air freshener, a “ready to use” powdered air freshener, a mold remover, a furnisher care, a wipe, a dish detergent or hard-surface detergent, a leather care product, or a car care product.

Description

EXAMPLES

[0105] The invention will now be described in further detail by way of the following examples, wherein the abbreviations have the usual meaning in the art, the temperatures are indicated in degrees centigrade (° C.). NMR spectra were acquired using either a Bruker Avance II Ultrashield 400 plus operating at 400 MHz, (.sup.1H) and 100 MHz (.sup.13C) or a Bruker Avance III 500 operating at 500 MHz (.sup.1H) and 125 MHz (.sup.13C) or a Bruker Avance III 600 cryoprobe operating at 600 MHz (.sup.1H) and 150 MHz (.sup.13C). Spectra were internally referenced relative to tetramethyl silane 0.0 ppm. .sup.1H NMR signal shifts are expressed in δ ppm, coupling constants (J) are expressed in Hz with the following multiplicities: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; b, broad (indicating unresolved couplings) and were interpreted using Bruker Topspin software. .sup.13C NMR data are expressed in chemical shift 8 ppm and hybridization from DEPT 90 and DEPT 135 experiments, C, quaternary; CH, methine; CH.sub.2, methylene; CH.sub.3, methyl.

Preparation of Compounds Using the Invention's Process

Example 1

[0106] A glass tube with water jacket was charged with 2-methylene-1-pentylbicyclo[3.1.0]hexane (3.28 g, 20 mmol), [4,4′-Bis(1,1-dimethylethyl)-2,2′-bipyridine-N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]Iridium.sup.(III) hexafluorophosphate (0.011 g, 0.01 mmol), 2,4,6-tri-tert-butylbenzenethiol (0.070 g, 0.25 mmol), HCl (0.08 ml, 0.5 mmol), H.sub.2O (0.54 ml, 30 mmol), DME (5 mL). Finally, propionaldehyde (0.58 g, 10 mmol) and 2,2,2-trifluoro-N-methylethanamine (0.11 g, 1.0 mmol) were added.

[0107] The mixture was irradiated with a blue LED lamp and stirred at RT for 24 h. The aqueous layer was decanted, then extracted with diethyl ether then the organic phase was washed twice with water, dried over magnesium sulfate, and the solvents were evaporated under vacuum. The crude product was purified by Kügelrohr bulb to bulb distillation (0.1 mbar, 120° C.) to afford 2-methyl-3-(3-methyl-2-pentylcyclopent-1-en-1-yl)propanal as a colorless oil (1.51 g, 6.1 mmol, 58% yield). Compared to all the similar processes describe in the literature, this aldehyde was obtained in a surprisingly, selectivity manner (selectivity higher than 95%) as a result of the kinetically favored exo ring cyclopropyl opening of the 2-methylene-1-pentylbicyclo[3.1.0]hexane.

[0108] An olfactive evaluation of the compound has shown an interesting watery olfactive note.

[0109] .sup.1H NMR (CDCl.sub.3, 500 MHz), mixture diastereoisomers: 0.88 (t, J=7.2 Hz, 6H), 0.97 (d, J=6.7 Hz, 3H), 0.98 (d, J=7.0 Hz, 3H), 1.02 (d, J=7.0 Hz, 3H), 1.03 (d, J=6.7 Hz, 3H), 1.18-1.35 (m, 12H), 1.36-1.44 (m, 2H), 1.88-1.95 (m, 2H), 1.97-2.18 (m, 8H), 2.19-2.29 (m, 2H), 2.37-2.52 (m, 4H), 2.63-2.71 (m, 2H), 9.63 (d, J=1.9 Hz, 1H), 9.64 (d, J=1.9 Hz, 1H) ppm.

[0110] .sup.13C NMR (CDCl.sub.3, 125 MHz), mixture of diastereoisomers: 205.35 (CH), 205.31 (CH), 143.33 (C), 143.23 (C), 130.98 (C), 130.95 (C), 45.06 (CH), 45.00 (CH), 41.40 (CH), 41.38 (CH), 33.98 (CH.sub.2), 33.94 (CH.sub.2), 32.07 (CH.sub.2), 32.02 (CH.sub.2), 31.25 (2CH.sub.2), 29.87 (CH.sub.2), 29.64 (CH.sub.2), 27.79 (CH.sub.2), 27.74 (CH.sub.2), 26.21 (CH.sub.2), 26.20 (CH.sub.2), 22.59 (2CH.sub.2), 19.47 (CH.sub.3), 19.39 (CH.sub.3), 14.06 (2CH.sub.3), 13.33 (CH.sub.3), 13.09 (CH.sub.3) ppm.

Example 2

[0111] A glass tube equipped with a water jacket was charged with (1S,5S)-1-isopropyl-4-methylenebicyclo[3.1.0]hexane (20.44 g, 150 mmol), [4,4′-Bis(1,1-dimethylethyl)-2,2′-bipyridine-N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]Iridium.sup.(III) hexafluorophosphate (0.056 g, 0.05 mmol), 2,4,6-tri-tert-butylbenzenethiol (0.35 g, 1.25 mmol), HCl (0.42 ml, 2.5 mmol), H.sub.2O (2.7 ml, 150 mmol), DME (25 mL). Finally propionaldehyde (2.90 g, 50 mmol) and 2,2,2-trifluoro-N-methylethanamine (0.56 g, 5 mmol) were added.

[0112] The mixture was stirred at RT and placed under Blue LED lamp irradiation for 24 h. The aqueous layer was decanted, diethyl ether was added and the organic phase was washed twice with water, dried over magnesium sulfate, and the solvents evaporated in vacuo. The crude product was purified by Fisher distillation (0.5 mbar, 120° C.) to afford 3-[(3S)-3-isopropyl-3-methyl-1-cyclopenten-1-yl]-2-methylpropanal as a colorless oil (2.90 g, 14.6 mmol, 29% yield). The compound resulting from the endo ring cyclopropyl opening (i.e. thermodynamically favored compound) was not observed.

[0113] The compound obtained was olfactively evaluated and described as having an aldehydic and watery note.

[0114] .sup.1H NMR (CDCl.sub.3, 500 MHz), mixture diastereoisomers: 0.81 (d, J=7.0 Hz, 6H), 0.83 (d, J=6.9 Hz, 6H), 0.93 (s, 3H), 0.94 (s, 3H), 1.07 (d, J=6.9 Hz, 6H), 1.46-1.51 (m, 2H), 1.52-1.57 (m, 2H), 1.76-1.82 (m, 2H), 2.08-2.30 (m, 6H), 2.41-2.48 (m, 2H), 2.48-2.55 (m, 2H), 5.22-5.24 (m, 2H), 9.63 (d, J=1.6 Hz, 1H), 9.64 (d, J=1.6 Hz, 1H) ppm.

[0115] .sup.13C NMR (CDCl.sub.3, 125 MHz), mixture of diastereoisomers: 205.12 (CH), 205.11 (CH), 138.42 (C), 138.39 (C), 135.48 (CH), 135.45 (CH), 51.95 (C), 51.93 (C), 44.68 (CH), 36.41 (CH), 34.63 (CH.sub.2), 34.57 (CH.sub.2), 34.28 (CH.sub.2), 32.43 (CH.sub.2), 32.40 (CH.sub.2), 23.55 (CH.sub.3), 23.47 (CH.sub.3), 18.42 (CH.sub.3), 18.39 (CH.sub.3), 18.15 (CH.sub.3), 13.50 (CH.sub.3), 13.45 (CH.sub.3) ppm.

Example 3

[0116] A glass tube equipped with a water jacket was charged with 1,5,5-trimethyl-2-methylenebicyclo[4.1.0]heptane (0.9 g, 6 mmol), [4,4′-Bis(1,1-dimethylethyl)-2,2′-bipyridine-N1,N1′]bis[3,5-difluoro-2-[5-(trifluoromethyl)-2-pyridinyl-N]phenyl-C]Iridium.sup.(III) hexafluorophosphate (0.011 g, 0.01 mmol), 2,4,6-tri-tert-butylbenzenethiol (0.070 g, 0.25 mmol), HCl (0.08 ml, 0.5 mmol), H.sub.2O (0.54 ml, 30 mmol), DME (25 mL). Finally propionaldehyde (0.58 g, 10 mmol) and 2,2,2-trifluoro-N-methylethanamine (0.11 g, 1.0 mmol) were added.

[0117] The mixture was irradiated with blue LED light and stirred at RT for 24 h. The aqueous layer was decanted, diethylether was added and the organic phase was washed twice with water, dried over magnesium sulfate, and the solvents were evaporated under vacuum. The crude product was purified by column chromatography (heptane/EtOAc 9/1) and then by Kügelrohr bulb to bulb distillation (0.1 mbar, 120° C.) to afford 2-methyl-3-(2,3,4,4-tetramethylcyclohex-1-en-1-yl)propanal as a colorless oil (0.25 g, 1.2 mmol, 40% yield). The compound resulting from the endo ring cyclopropyl opening (i.e. thermodynamically favored compound) was not observed.

[0118] The olfactive profile of the compound was evaluated as showing an interesting watery olfactive note.

[0119] .sup.1H NMR (CDCl.sub.3, 500 MHz), mixture of diastereoisomers: 0.84 (s, 3H), 0.84 (s, 3H), 0.86 (s, 3H), 0.86 (s, 3H), 0.90 (d, J=7.0 Hz, 3H), 0.91 (d, J=6.9 Hz, 3H), 1.05 (d, J=6.8 Hz, 6H), 1.14-1.18 (m, 2H), 1.24-1.31 (m, 4H), 1.46-1.53 (m, 2H), 1.64 (m, 6H), 1.83-1.99 (m, 2H), 2.09-2.14 (m, 2H), 2.30-2.36 (m, 2H), 2.49-2.57 (m, 2H), 9.6 (d, J=2.3 Hz, 2H) ppm.

[0120] .sup.13C NMR (CDCl.sub.3, 125 MHz), mixture of diastereoisomers : 205.43 (2×CH), 133.11 (C), 133.08 (C), 124.54 (C), 124.47 (C), 45.96 (CH), 45.91 (CH), 45.52 (CH), 45.41 (CH), 34.32 (CH.sub.2), 34.26 (CH.sub.2), 31.65 (C), 31.63 (C), 31.34 (CH2), 31.18 (CH.sub.2), 27.46 (CH.sub.2), 27.40 (CH.sub.2), 27.14 (2×CH.sub.3), 27.03 (2×CH.sub.3), 18.88 (CH.sub.3), 18.85 (CH.sub.3), 15.36 (CH.sub.3), 15.31 (CH.sub.3), 13.25 (CH.sub.3), 13.12 (CH.sub.3)ppm.