The present invention refers to a novel process for the preparation of linear and cyclic homoallylic ester and amides, which constitutes a valuable class of organic compounds.

Prior art

Such compounds can be prepared by multistage syntheses which are essentially based on five basic methods known in the art: a) By addition of an allyl metal species to a carbonyl compound and imino groups resulting in homoallyl alcohols or amines, followed by esterification or amide formation. b) By carbonyl ene or Conia ene reactions to homoallylic alcohols, followed bv esterification, c) By imino ene reactions to homoallyl amine derivatives, followed bv subsequent

transformation which lead to amide formation. d) By metal hydride catalyzed addition of dienes to carbonyl compounds, followed by

esterification. e) By 2,3-Wtttig rearrangements of allyl benzyl or diallyl ethers and aza-Wittig rearrangements resulting in homoallyl alcohols and amines respectively, followed bv esterification and amide formation.

All the prior art syntheses have in common that the preparation of the esters and amides respectively take place in two sub-sequential steps, this means that in a first step a homoallylic alcohol or amine is formed which is subsequently transformed into an ester or amide derivative, respectively.

Description of the Invention

One object of the present invention is a simple and cost-effective method for producing linear and cyclic homoallylic ester and amides as herein below described. One embodiment of the present invention is the direct acid catalyzed intermolecular electrocyclic rearrangement of β,γ-unsaturated aldehydes or ketones with another aldehyde to afford esters or lactones of homoaliylic alcohols in one process step. The β,γ-unsaturation is not part of an aromatic ring.

A further embodiment of the present invention is the direct acid catalyzed intermolecular electrocyclic rearrangement of β,γ-unsaturated aldehydes or ketones with secondary aldimines to form amides or lactames of homoaliylic amines in one process step. The β,γ- unsaturation is not part of an aromatic ring.

Surprisingly it was found that, in the presence of a catalyst, β,γ -unsaturated carbonyl compounds (A) react with another carbonyl compound (B wherein X = O) or a derivative like an imine or oxime ether (B wherein X = NR ⁷ ) to homoaliylic compounds (I). It is believed, without to be bound by theory that this reaction proceeds via an intermolecular electrocyclic rearrangement that involves an activated homoaliylic aldehyde / Lewis acid (LA) complex C which rearranges via intermediate of formula (C") to form a compound of formula (I), as depicted in Scheme 1 below. The stabilization of positive charge by substituents in the intermediate (C") is beneficial for a smooth conversion of the starting compound of formula (A) to the rearranged compound of formula (I).

Scheme 1 : rearrangement reaction

(A) (B) (C)

As used herein, the term "secondary aldimines" denotes for imines in analogy to aldehydes wherein the carbonyl oxygen atom is replaced by RN= group with R is not hydrogen (i.e. R is aikyl). Non limiting examples are secondary aldimines selected from acetaldehyde O-methyl oxime, acetaldehyde O-ethyl oxime , hexanal O-methyi oxime, hexanal O-ethyl oxime, 3-methylbut- 2-enal O-ethyl oxime, benzaldehyde O-methyl oxime, 2,3,4, 5-tetrahyd ropyrid i ne, indole, 3,4- dihydro2H-pyrrole, N-butylidenebutan-1-amine, and 3-(methyleneamino) propanoates, such as ethyl 3-(methleneamino)propanoate.

In another embodiment there is provided a method of producing homoallylic compounds of formula (I)

by an intermolecular electrocyclic rearrangement of a beta, gamma-unsaturated carbonyl compound of formula (A)

with a compound of formula (B)

X e (B) wherein

X is oxygen or

X is NR. ⁷ , wherein R ⁷ is selected from Ci~G _B alkyl (e.g. butyl, isoamyl), C ₆ -C _e aryl, C _r C ₂ alkoxy, d-Cg alkyl comprising one carbonyloxy group (-C(O)O-) ; or

R ⁶ and R ⁷ may form together with the atoms to which they are attached a 5 - 10 membered mono- or bi-cyclic ring (e.g. compound B is selected from 3,4-dihydro2H- pyrrole, 3H-indole, or 2,3,4, 5-tetrahydropyridine);

R ¹ is selected from hydrogen, methyl and phenyl; R ² is selected from hydrogen, a hydrocarbon group selected from C-i-C ₈ alkyl (e.g. methyl), C ₂ -C _B alkenyl (e.g. 3-methyl-pent-4-enyl) , C ₆ -C ₈ aryl, and C C ₃ alkyl C ₆ -C ₈ aryl (e.g. benzyl), wherein the hydrocarbon group optionally comprises one functional group selected from methoxy, -C(O) - and -OC(O) -;

R ³ is selected from hydrogen and methyl; or

R ¹ and R ² or R ¹ and R ³ form together a bivalent linear C ₃ - C ₁₆ alkyl or alkenyl (e.g. -(CH ₂ ) ₃ ~, -(CH ₂ ) ₄ -, ~(CH ₂ ) _S - -(CH ₂ ) ₆ -, -iCH ₂ ) ₇ ~, -(CH _? ) ₁₀ -, -CH=CH-CH ₂ -), wherein the alkyl / alkenyl chain may be optionally substituted with one or more methyl or ethyl groups; or

R ² and R ³ form together with the carbon atom to which they are attached a C ₅ ~C ₈ cycloalkyl ring or C ₅ -C ₈ cycloalkenyl ring (e.g. C ₆ cycloalkenyl), the ring is optionally substituted with one or more Ci - C ₄ alkyl or alkenyl groups (e.g. with two alkyl groups);

R ⁴ is selected from hydrogen, methyl and ethyl;

R ^s is selected from hydrogen, d-C ₅ alkyl or alkenyl (e.g. methyl, ethyl) and C ₂ -C ₅ alkenyl (e.g. 1-propenyl); or

R ⁴ and R ⁵ form together a bivalent C ₃ - C ₆ alkyl or alkenyl (e.g. -(CH ₂ ) ₃ -, -(CH ₂ ) ₄ -, and -(CH ₂ )s-, -Ch CH-CHH; or

R ^s and R ² or R ⁵ and R ³ form together with the carbon atoms to which they are attached a 5-12 membered hydrocarbon ring (e.g. a 6-membered ring);

R ⁶ is selected from H, C,-C _e alkyl (e.g. iso-butyl, tert-butyl, n-butyl, n-propyl, iso-propyl, hexyl), C ₂ -C ₈ alkenyl (e.g. isobutenyl) and C ₆ -C _B aryl wherein the aryl is optionally substituted with one or more groups selected from methyl, methoxy, ethoxy, acetoxy, hydroxy, and 1 ,3-dioxol;

in the presence of a Lewis acid or Bransted acid,

Non limiting examples are compounds of formula (B) wherein X is oxygen selected from acetaldehyde, propionaldehyde, isobutyraldehyde, butyraldehyde, pivalaldehyde, hexanal, heptanal, and 3-methylbutanal, anisaldehyde, heliotropin (benzo[d}[1 ,3]dioxo!e-5- carbaldehyde) and vanillin.

As used in relation to compounds of formula (I) and formula (A) respectively, unless otherwise indicated, "hydrocarbon ring" refers to cycloakly rings comprising none, one or more double bonds, the ring being optionally substituted with one or more C _t - C ₄ alkyl groups, such as methyl, ethyl, and iso-propyl. For example, hydrocarbon rings comprising 5, 6, 7, 8, 9, 10, or 11 ring members, the ring may be further substituted with one ethyl group, or one, two or three methyl groups.

As used in relation to the compounds of formula (I), (A) and (B), unless otherwise indicated, "alkyl" and "alkenyl" refers to linear and branched alkyl and linear and branched alkenyl.

Non limiting examples are beta, gamma-unsaturated carbonyl compounds of formula (A) selected from 2,4-dimethyl-1-(prop-1-en-2-yl)cyclohex-3-enecarbaldehyde,

1- (prop-1-en-2-yl)cyc!ohex-3-enecarbaldehyde, 1-vinylcyclohex-3-enecarbaldehyde, 6-methyl-3-(prop-1-en-2-yl)oct-7-en-2-one, 5-acetyl-6-methylhept-6-en-2-yl acetate,

2- (prop-1-en-2-yl)cyclopentanone, [1 , 1 '-bi(cyclopentan)]-1 '-en-2-one,

1-methyl-[1 , 1'-bi(cyclopentan)]-1 '-en-2-one, 2-(prop-1-en-2-yl)cyc!ododecanone,

1- (4,7,7-trimethylbicyclo[4.1.0]hept-4-en-3-yl)ethanone,

3,3, -tri methylpent-4-en-2-one , 2-(prop-1-en-2-yl)cyclohexanone,

2- (prop-1-en-2-yl)cycloheptanone, 2-(prop-1-en-2-yl)cyclooctanone,

2-(prop-1-en-2-yl)cyclododecanone, 2-benzyl-2-methylpent-3-enal,

2,5-dimethyl-2-(prop-1-en-2-yl)cyclohexanone, 2-(prop-1-en-2-yl)cyclononanone,

2,6,6-trimethylcyclohex-2-enecarbaldehyde, and 4-ethyl-2-(prop-1-en-2-yl)cyclohexanone.

Non limiting examples are homoallylic esters and amides of formula (I) selected from

4-(2,4-dimethylcyclohex-3-en-1-ylidene)pentan-2-yl formate, 5-(cyclohex-3-en-1-ylidene)-2-methylhexan-3-yl formate,

4-(cyclohex-3-en-1-ylidene)butan-2-yl formate,

4,8-dimethyldeca-4,9-dien-2-yl acetate,

(E)-4-methylnon-4-ene-2,8-diyl diacetate,

rac-(Z)-7,9-dimet yl-4,5,8,9-tetrahydrooxonin-2(3H)-one,

rac-{Z)-1 ,7-Dimethyl-5,6,8,9,10,10a-hexahydro-1 H-cyclopenta[c]oxonin-3(4H)-one, rac-(E)- 14,16-Dimethyloxacyclohexadec- 13-en-2-one,

(S)-1-((1 R,2S,6R)-3,7,7-Trimethylbicyclo[4.1.0]hept-3-en-2-yl)ethyl acetate,

2,3-Dimethylundec-2-en-5-yl acetate,

/\/-(4,5-dimet ylhex-4-en-2-yl)-/V-methoxyacetamide,

/V-(2,3-dimethyldec-2-en-5-yl)-A/-methoxyacetamide,

/V-(4,5-dimethylhex-4-en-2-yl)-/V-ethoxyacetamide,

N-methoxy-N-(2,6,7-trtmethylocta-2 ₎ 6-dien-4-y!)acetamide,

/V-(3,4-dimethyl-1 -phenyl pent-3-en-1-yl)-A -rnethoxyacetamide,

1-(2-(2,3-dimethylbut-2-en-1-yl)indolin-1 -yl)ethanone,

f-E -1-methoxy-8,10-dimethyl-3,4,5,6,9,10-hexahydroazecin-2(1H)- one,

(E)-1-ethoxy-8,10-dimethyl-3,4,5,6,9, 10-hexahydroazecin-2(1H)-one,

(E)- 1 -meth oxy-8-m ethyl-10-pentyl-3,4,5,6,9 , 10-hexahydroazect n~2{ 1 H)-one,

(E -12-methyl-7,8,9, 10, 13a,14-hexahydroazecino[1 ,2-a]indol-6(13H)-one,

(EJ- 1-methoxy-9, 11 -dimethylazacycloundec-8-en-2-one,

f ^* EJ-1-ethoxy-9, 1 1-dimethylazacycloundec-8-en-2-one,

(E -1-methoxy-10-methyl-12-pentylazacyclododec-9-en-2-one,

(E)-1-methoxy-10, 12-dimethylazacyclododec-9-en-2-one,

CE^-1-ethoxy-10,12-dimethylazacyclododec-9-en-2-one,

fE -1-methoxy-14, 16-dimethylazacyclohexadec-13-en-2-one,

E -1-ethoxy-14, 16-dimethylazacyclohexadec-13-en-2-one,

/V-(2,4-dimethyl-1-phenyldec-2-en-5-yl)-/V-methoxyformamide

f4S,E)-1-butyl-4,7,8-trimethyl-10-propyl-3, 4,5,6,9, 10-hexahydroazecin-2(1H)-one,

('E -12-methyl-3,4,7,8,9, 10, 13, 13a-octahydro-1H-pyrido[1 ,2-a]azecin-6(2H)-one,

1-(2-(2,3-dimethylbut-2-en-1-yl)piperidin-1-yl)ethanone, and

ethyl 3-(1 1 -methyl-2-oxoazacyclotridec- 10-en- 1 -yl)propanoate. Lewis acids may be selected from all types of Lewis acids, well known to the skilled person. Suitable acids are, for example, BF ₃ Et ₂ 0, SnCI _4» TiC . AICIj, EtAICI ₂ , FeCI ₃ , ZnBr ₂ and H ^® . Bronsted acids are well known to the skilled person. Examples are p-TsOH, H ₂ S0 ₄ , and CF ₃ SO ₃ H.

The concentration of the acid is not critical and may vary from about 0.5 mol% to about 120 mol%. However it was observed that the reaction described herein above is a catalytic reaction when esters or lactones are formed (i.e. for compounds of formula (I) wherein X is oxygen). By catalytic reaction is meant, that about 0.5 mol % to about 20 mol % of an acid (e.g. about 10 mol %) is sufficient enough to drive the conversion to completion. Even though low concentrations of acid are sufficient enough, higher concentrations may have an influence on the reaction rate and thus be preferred. The optimum concentration may be easily established by routine experimentation in every case.

The reaction temperature applied is not really critical either. The intermolecular electrocyclic rearrangement takes place in a broad temperature range, e.g. from -80°C to 120°C, such as from -10°C to about 80°C, (for example about 0°C to room temperature (i.e. about 20 - 25°C), or 50°C to about 80°C).

Beta substituted beta, gamma-unsaturated carbonyl compound, i.e. compounds of formula (A) wherein R ⁴ is not hydrogen, were found to undergo the reaction described hereinabove much faster and with higher yields compared to compounds of formula (A) wherein R ⁴ is hydrogen.

Using the method described hereinabove it was possible to produce not only known compounds, such as derivatives of 1 ,3-dimethyl-but-3-en-1-yl formate, e.g. 1 ,3-dimethyl-but- 3-en-1-yl isobutyrate = 4-methylpent-4-en-2-yl i sob uty rate (CAS 80118-06-5) or 1 -(3,7,7- trimethylbicyclo[4.1.0]hept-3-en-2-yl)ethyi acetate (CAS 29583-31-1) but also compounds not described in the literature such as 4-(2,4-dimethylcyclohex-3-en-1-ylidene)pentan-2-yl formate, 5-(cyclohex-3-en-1-ylidene)-2-methylhexan-3-yl formate, 4,8-dimethyldeca-4,9-dien- 2-yl acetate, 1-(3,7,7-Trimethylbicyclo[4.1.0]hept-3-en-2-yl)ethyl acetate and 1 -methoxy-8, 10- dimethyl-3,4,5,6,9, 10-hexahydroazecin-2(1 H)-one. In a particular embodiment there is provided a method of preparing lactones starting from compounds of formula (A) wherein X is oxygen and R ¹ and R ² or R ³ form together a bivalent C ₃ - C,6 alkyl or alkenyl group, resulting in a ring-enlargement [n+4] lactone (I), as depicted in Scheme 2 below.

(A) (B) (C") (I)

In a further embodiment there is provided a method of preparing lactames starting from compounds of formula (A) wherein X is NR ⁷ , and R ¹ and R ² or R ³ form together a bivalent C ₃ - C ₁₆ alkyl or alkenyl group, resulting in a ring-enlargement [n+4] lactam, as depicted in Scheme 3 below.

(A) (B) (G'J (C ) (I)

Using the method described herein there is provided a new process for medium size {8 - 12 membered ring, e.g. 9, 10, or 11 membered ring) to macro size (13- 20 membered rings) lactones and lactames. In particular medium sized lactones are difficult to prepare with methods known to the skilled person and thus the process described herein constitutes a real alternative for the preparation of medium to macro size lactones.

In a further embodiment there is provided a method of producing homoallylic compounds of formula (I) wherein R ¹ is selected from hydrogen, methyl and phenyl, and R ² and R ³ form together with the carbon atom to which they are attached a C ₃ -C ₈ cycloalkyl ring or C ₅ -C ₃ cycloalkenyl ring (e.g. C ₆ cycloalkenyl), the ring is optionally substituted with one or more C, - C ₄ alkyl or alkenyl groups (e.g. with two alkyi groups), R ⁴ is selected from hydrogen, methyl and ethyl, and R ⁵ is hydrogen or methyl.

In a further embodiment there is provided a method of producing homoallylic compounds of formula (I) wherein R ³ is hydrogen, R ⁴ is selected from hydrogen, methyl and ethyl, R ⁵ is hydrogen or methyl, and R ¹ and R ² form together a bivalent C ₃ - C ₆ alkyl (R ¹ and R ² form together -(CH ₂ ) ₃ -, -(CH ₂ )4-,-(CH ₂ ) ₅ -,-(CH ₂ ) _B -, or -(CH ₂ ) ₁₀ -,)

The beta, gamma-unsaturated carbonyl compound of formula (A) may be easily prepared by art-recognized methods.

The linear and cyclic homoallylic ester and amides of formula (I) produced in accordance with the invention may be odorant compounds as such. They are also valuable intermediates or precursors for the preparation of other chemical compounds suitable as fragrance, pharmaceutical and/or agrochemical.

The invention is now further described with reference to the following non-limiting examples. These examples are for the purpose of illustration only and it is understood that variations and modifications can be made by one skilled in the art.

Example 1 ; 4r^4-dimetrwlcvclohex-^n-1-vlidene)pentan-2-vl formate

An argon flushed three-necked flask which was cooled by an ice-water bath was charged with β,γ-unsaturated carbonyl compound A (2 ,4-dimethyl-1 -(prop- 1 -en-2-yl)cyclohex-3- enecarbaldehyde, mixture of syn and anti in a ratio of 4 : 1 ; 1.78 g, 10 mmol), aldehyde B (acetaldehyde, 0.53 g, 12 mmol) and 1 ,2-dichloroethane (20 mL), Boron trifluoride etherate (0.14 g, 1.0 mmol) were added dropwise under argon. After completion of the addition the ice-water bath was removed and the mixture was stirred for 2 hours at room temperature. The completion of reaction was checked by GC analysis of reaction aliquots quenched with a solution of saturated NaHC0 ₃ in water. After complete conversion (>95%), the reaction mixture was quenched with sat. aqueous NaHC0 ₃ solution (10 mL). The organic phase was separated and the aqueous layer was extracted with MTBE three times. The combined organic layers were washed with brine (20 mL), dried (MgS0 ₄ ) and evaporated in vacuo. The residue was purified by column chromatography on silica gel (MTBE / hexane = 1 : 20) to yield the title product (1.55 g, 70%) as colorless liquid. Mixture of four isomers in a ratio of 1

; 2 ; 3 I 16. H NMR (300 MHz, CDCI ₃ ): δ = 7.99 (s, 1 H. -OCHO), 5.32-5.26 (m, 1 H), 5.21 -5.10 (m, 1H), 3.10-2.95 (m, 1H), 2.65-2.57 (m, 1 H), 2.50 {dd, J = 7.5, 13.5 Hz, 1H), 2.18 (dd, J = 7.5, 13.5

Hz, 1H), 2.09-1.86 (m, 3H), 1.70 (s, 3H, CHS), 1.66 (s, 3H, CHS), 1.25 (d, J = 6.3 Hz, 3H), 0.98 (d, J = 7.0 Hz, 3H) ppm. Major isomer: ¹³ C NMR (75 MHz, CDCI ₃ ); δ = 160.6 (d), 137.2 (S), 133.3 (s), 126.9 (d), 121.1 {$}, 69.9 (d), 40.3 (t), 33.5 (d), 31.7 (t), 23.3 (q), 23.3 (t), 20.4 (q), 19.9 (q), 18.4 (q) ppm. GC/MS (El): 222 (M\ 27), 176 (14), 161 (100), 147 (7), 135 (51), 119 (71), 107 (59), 91 (41), 77 (18), 41 (22). IR (neat, v/crrf ¹ ): 2961 , 2903, 1721 , 1451 , 1378, 1177. HRMS (ESI): m/z: calcd. for C ₁₄ H ₂₂ 0 ₂ (M + Na) ^* 245.1517: Found: 245.1510.

Odour description: lactonic, slight milk, sweet, very metallic

Example 2: 5-(cvclohex-3-en-1-vlidene)-2-methvlhexan-3-vl formate

Following the general procedure as described in Example 1 , 1 -{prop-1 -en-2-yl)cyclohex-3- enecarbaldehyde (1.50 g, 10 mmol), isobutyraldehyde (0.86 g, 12 mmol) and boron trifluoride etherate (0.14 g, 1.0 mmol) in 1 ,2-dichloroethane (10 mL) were reacted to give the title product as a colorless liquid (1.55 g. 70 % yield). Mixture of E / Z isomers in a ratio 2 : 1.

¹ H NMR (300 MHz, CDCi ₃ ): δ = 8.03, 7.99 (s. 1 H, -OCHO), 5.80-5.60 (m, 2H), 5.02-4.89 (m, 1H), 2.92-2.65 (m, 2H), 2.60-2.45 (m, 1H), 2.43-1.99 (m, 5H), 1.92-1.75 (m, 1H), 1.71 , 1.68 (s, 3H, CH3), 0.95 (d, J = 6.7 Hz, 6H, -CH(CH3)2) ppm. ³ C NMR (75 MHz, CDCI ₃ ): δ = 160.8, 160.7 (d), 132.0, 131.7 (s), 127.2, 126.9 (d), 126.9, 126.6 (d), 121.9, 121.6 (s), 77.3, 76.9 (d), 36.2, 35.7 (t), 31.8, 31.5 (d), 29.9, 29.8 (t), 27.1 , 26.8 (t), 26.9, 26.6 (t), 18 9, 18.8 (q), 18.7, 18.0 (q), 17.5, 17.4 (q) ppm. GC/MS (El): 222 (M ⁺ , 1), 176 (26), 161 (15), 147 (1), 133 (100), 120 (18), 105 (67), 91 (59), 79 (46), 67 (9), 55 (26), 41 (21). IR (neat, v/crn ^'1 ): 3025, 2965, 2913, 1721 , 1467, 1388, 1169. HRMS (ESI): m/z: calcd for C ₁₄ H ₂₂ 0 ₂ (M + Na) ⁺ 245.1517: Found: 245.1501.

Odour description: green geranium, slightly floral cinnamic fruity. Example 3: 4-(cyclohex-3-en-1-vlidene)butan-2-yl formate

Following the general procedure as described in Example 1 , 1-vinylcyclohex-3- enecarbaldehyde (1.50 g, 10 mmol), acetaldehyde (0.53 g, 12 mmol) and boron trifluoride etherate (0.14 g, 1 ,0 mmol) in 1 ,2-dichloroethane (10 ml_) were reacted to give the title product as a colorless liquid (0.72 g, 40 % yield). Mixture of E / Z isomers in a ratio 1 : 1.

Ή NMR (300 MHz, CDCI ₃ ): δ = 8.03, (s, 1 H, -OCHO), 5 78-5.58 (m, 2H), 5.27-5.11 (m, 1H), 5.07-4.95 (m, 1 H), 2.80-2.68 (m, 2H), 2.46-2.22 (m, 4H), 2.17-2.05 (m, 2H), 1.25 (d, J = 6.2 Hz, 3H, CH3) ppm. ³ C NMR (75 MHz, CDCI ₃ ): δ = 160.7 (d), 138.9, 138.8 (s), 127.3, 126.8 (d), 126.7, 125.6 (d), 117.0, 1 16.2 (d), 71.0, 70.9 (d), 35.4, 33.7 (t), 33 2, 33.0 (t), 28.1 , 27.2 (t), 27.0, 25.4 (t), 19.5, 19.4 (q) ppm. GC/MS (El): 180 (M\ 1), 162 (1), 134 (73), 119 (54), 105 (51), 91 (92), 79 (100), 65 (12), 45 (23). IR (neat, v/cm ¹ ): 3026, 2911 , 1719, 1448, 1 176 HRMS (ESI): m/z: calcd. for C ₁₁ H ₁₆ 0 ₂ (M + Na) ⁺ 203.1048: Found: 203.1039.

Example 4: 4,8-dimethyldeca-4 -dien-2-yj acetate

Following the general procedure as described in Example 1 , 6-methyl-3-(prop-1-en-2-yl)oct-7- en-2-one (1.80 g, 10 mmol), acetaldehyde (0.53 g, 12 mmol) and boron trifluoride etherate (0.14 g, 1.0 mmol) in 1 ,2-dichloroethane (10 mL) were reacted to give the title product as a colorless liquid (1.90 g, 85 % yield). Mixture of 2 isomers in a ratio 1 : 5.

Ή NMR (300 MHz, CDCi ₃ ): δ = 5 78-5.60 (m, 1 H), 5,27-5.12 (m, 1 H), 5.04 (dd, J = 6.5, 12.9 Hz, 1H). 5 00-4.87 (m, 2H), 2.45-2.22 (m, 1H), 2.18-1.92 (m, 7H), 1.70, 1.61 (s, 3H, CHS), 1.37-1.26 (m, 2H), 1.18 (d, J = 6.2 Hz, 3H), 0.98 (d, J - 6.7 Hz, 3H) ppm. Major E-isomer: ¹³ C NMR (75 MHz, CDCI ₃ ): δ = 170.4 (s), 144.5 (d), 130.9 (s), 127.9 (d), 1 12.6 (t), 69.1 (d), 46.3 (t), 37.3 (d), 36.5 (t), 25.6 (t), 21.2 (q), 20.1 (q), 19.7 (q), 16.1 (q) ppm. GC/MS (El): 224 (M\ 1), 164 (5), 149 (20), 135 (10), 121 (14), 109 (22), 95 (57), 81 (33), 67 (33), 55 (23), 43 (100). IR (neat, v/cm ¹ ): 2969, 1734, 1453, 1373, 1242.

Odour description: floral, fruity, myraldyl violet. Example 5: (E)-4-met ylnon-4-ene-2,8-diyl diaeetate

Following the general procedure as described in Example 1 , 5-acetyl-6-methylhept-6-en-2-yl acetate (2.12 g, 10 mmol), acetaldehyde (0.53 g, 12 mmol) and boron trifluoride etherate (0.14 g, 1.0 mmol) in 1 ,2-dichloroethane (10 mL) were reacted to give the title product as a colorless liquid (2.41 g, 94 % yield). Mixture of 4 isomers in a ratio of 1 : 1 : 3 : 3. H NMR (300 MHz, CDCI ₃ ): δ = 5.23-5.1 1 (m, 1 H), 5 09-4.98 (m, 1H), 4.94-4.80 (m, 1 H), 2.45-2.20 (m, 1 H), 2.16-1 98 (m, 9H), 1.73-1.43 (m, 5H), 1.26-1.13 (m, 6H) ppm. Two major isomers: ¹³ C NMR (75 MHz, CDCI ₃ ): δ = 170.6 (s), 170.4 (s) _» 131.9, 131.8 (s), 126.7, 126.6 (d), 70.4 (d), 69.0 (d). 46.2 (t), 35.7, 35.6 (t), 23.9, 23.8 (t), 21.3 (q), 21.2 (q), 19.9 (q). 19.7 (q), 16.0 (q) ppm. GC/MS (El): 256 (M ⁺ , 1), 136 (38). 121 (43), 107 (100), 95 (24), 79 (13), 68 (16), 55 (8), 43 (84). IR (neat, v/crrf ¹ ); 2977, 1732, 1449, 1371 , 1238. HRMS (ESI): m/z: calcd. for C ₁₄ H ₂₄ 0 _<t (M + Naf 279.1572: Found: 279.1577.

Example 6: rac-(Z)-7.9-dimethvl-4.5.8.9-tetrahvdrooxonin-2(3H)-one

Following the general procedure as described in Example 1 , 2-(prop-1-en-2- yl)cyclopentanone (1.24 g, 10 mmol), acetaldehyde (0.53 g, 12 mmol) and boron trifluoride etherate (0. 4 g, 1.0 mmol) in 1 ,2-dichloroethane (10 mL) were reacted to give the title product as a colorless liquid (0.59 g, 35 % yield). Single Z-isomer.

¹ H NMR (300 MHz, CDCI ₃ ): 6 = 5.23-5.13 (m, 1 H), 5.07-4.94 (m, 1 H), 2 52 (dd, J = 12.5. 12.5 Hz, 1 H), 2.46-2.35 (m. 1H), 2.34-2.16 (m, 2H), 2.10-1.96 (m, 2H), 1.85-1 75 (m, 1 H), 1.76 (d, J = 12.5 Hz, 1 H), 1.71 (s, 3H, CHS), 1.31 (d, J = 6.4 Hz, 3H, CH3) ppm. ¹³ C NMR (75 MHz, CDC ): δ = 174.6 (s), 132.0 (s), 128.8 (d), 68.6 (d), 41.3 (t), 33 4 (t), 27.1 (t). 25.8 (t), 25.3 (q), 20.4 (q) ppm. GC/MS (El): 168 (M ⁺ , 13), 124 (22), 109 (8), 96 (100), 81 (33), 68 (32), 55 (26), 41 (16).

Example 7: rac-(Z)-1.7-Dimethyl-5.6.8.9.10. 0a-hexahvdro-1H-cyclopentafcloxonin-3(4H)- one

Following the general procedure as described in Example 1 , [1 , 1 '-bi(cyclopentan)]-1'-en-2- one (1.64 g, 10 mmol), acetaldehyde (0.53 g, 12 mmol) and boron trifluoride etherate (0.14 g. 1.0 mmol) in 1 ,2-dichloroethane (10 mL) were reacted to give the title product as a colorless liquid (1.73 g, 83 % yield). Single Z-isomer. ¹ H NMR (300 MHz, CDCI ₃ ): δ = 4.78-4.65 (m, 1 H), 2.85-2.57 (m, 2H), 2.41-2.08 (m, 5H), 2.05-1.88 (m, 3H), 1.73-1.60 (m, 3H), 1 .58 (s, 3H), 1 .27 (d, J = 6.1 Hz, 3H) ppm. Two diastereomers: Major isomer: ¹³ C NMR (75 MHz, CDCI ₃ ): δ = 173.9 (s), 138.8 (s), 128.0 (s), 71.2 (d), 49.3 (d), 32.8 (t), 32.7 (t). 30.5 (t), 29.8 (t), 23.6 (t), 23.0 (t), 19.3 (q), 18.5 (q) ppm. GC/MS (El): 208 (M ⁺ , 23), 164 (28), 146 (52), 135 (17), 121 (58), 108 (94), 93 (100), 79 (36), 67 (18). 55 (16), 41 (21 ). IR (neat, v/cm ^' ): 2948, 2871 , 1736, 1448, 1 143, 1073. HRMS (ESI): m/z: calcd. for C ₁₃ H _?0 O ₂ (M + Naf 231.1361 : Found: 231.1359.

Example 8: rac-(E)- 4.16-Dimethyloxacyclohexadec-13-en-2-one

Following the general procedure as described in Example 1 , 2-(prop-1-en-2- yl)cyclododecanone (2.22 g, 10 mmol), acetaldehyde (0.53 g, 12 mmol) and boron trifluoride etherate (0.14 g, 1 .0 mmol) in 1 ,2-dtchloroethane (10 mL) were reacted to give the title product as a colorless liquid (2.34 g, 88 % yield. Mixture of E / Z isomers in a ratio of 8 : 1.

¹ H NMR (300 MHz, CDCI ₃ ): δ = 5.23-5.02 (m, 2H), 2.34-2.18 (m, 3H), 2.17-2.03 (m, 1 H), 2.01 -1.88 (m, 1 H), 1 79-1.50 (m, 2H), 1 .61 (s, 3H), 1.46-1.17 (m, 18H) ppm. Major isomer: ¹³ C NMR (75 MHz, CDCI ₃ ): δ = 173.5 (s), 131.1 (s), 127.9 (d), 68.5 (d), 46.5 (t), 33.6 (t), 28.9 (t), 27.2 (t), 26.6 (t), 26.5 (d), 26 4 (t), 26.3 (t). 25.3 (t), 24.8 (t), 23.1 (t), 20.7 (q), 16.9 (q) ppm. GC/MS (El): 266 (M 28), 251 (4), 237 (3), 223 (6), 195 (2), 182 (3), 164 (4), 137 (4), 123 (18), 109 (25), 95 (100), 82 (75), 67 (37), 55 (43), 41 (34). IR (neat, v/cm ¹ ): 2927, 2856, 1730, 1459, 1375, 1 172, 1 130. HRMS (ESI): m/z: calcd. for C ₁₇ H ₃₀ O ₂ (M + Na) ⁺ 289 2143: Found: 289.2 14.

Example 9: (S)-1-((1 R.2S.6R)-3.7.7-Trimethvlbicvclo[4.1.0lhept-3-en-2-vl)ethvl acetate Following the general procedure as described in Example 1 , 1 -(4,7,7- tri methyl bicyc!o[4.1 .0]hept-4-en-3-yl)ethanone (1.78 g, 10 mmol), acetaldehyde (0.53 g, 12 mmol) and boron trifluoride etherate (0.14 g, 1.0 mmol) in 1 ,2-dichloroethane (10 mL) were reacted to give the title product as a colorless liquid (1.82 g, 82 % yield).

¹ H NMR (300 MHz, CDCI ₃ ): δ = 5 44-5.36 (m, 1 H), 5.31-5.20 (m, 1H), 2.41-2.27 (m, 1 H), 2.25-2.17 (m, 1 H), 2.1 1-2.05 (m, 1 H), 2.02 (s, 3H, acetyl-CH3), 1.66 (s, 3H, CH3), 1.22 (d. J = 6.5 Hz, 3H), 1.02 (s, 3H, CH3), 0.86 (s, 3H, CH3), 0.71 (dd, J = 8.7, 8.7 Hz, 1 H), 0 58 (d, J = 9.1 Hz, 1 H) ppm. ¹³ C NMR (75 MHz, CDCI ₃ ): δ = 170.4 (s), 131.2 (s), 120.4 (d), 73.5 (d), 39.9 (d), 29.2 (q), 23.5 (q), 23.2 (t), 21 .8 (t), 21 .3 (q), 18.0 (d), 16.4 (q), 16.3 (s), 13.6 (q) ppm. GC/MS (El): 222 { ⁺ , 1), 162 (13), 147 (23), 133 (8), 119 (78), 105 (18), 93 (100), 77 (14), 65 (4), 43 (75). IR (neat, v/cm ¹ ): 2938, 2866, 1735, 1450, 1370, 1237. HRMS (ESI); m/z: calcd. for C ₁₄ H ₂₂ 0 ₂ (M + HaY 245.1517: Found: 245,1498.

Odour description: floral, agrestic, a bit woody, Nopyl Acetate -like, slight piny Example 10: 2,3-Dimethylundec-2-eo-5-¥l acetate

Following the general procedure as described in Example 1, 3,3,4-trimethylpent-4-en-2-one (126 g, 10 mmoi), heptanal (1.37 g, 12 mmol) and boron trifluoride etherate (0.14 g, 1.0 mmol) in 1 ,2-dichloroethane (10 mL) were reacted to give the title product as a colorless liquid (2.18 g, 91 % yield).

¹ H NMR (300 MHz, CDCI ₃ ): δ = 5.04-4.93 (m, 1 H), 2.38 (dd, J = 8.0, 13.6 Hz, 1 H), 2.13 (dd, J = 5.6, 13.6 Hz, 1H), 1.99 (s, 3H, acetyl-CH3), 1 ,67 (s, 3H, CHS), 1.66 (s, 3H, CHS), 1.63 (s, 3H, CH3), 1.57-1.45 (m, 2H), 1.38-1.20 (m, 8H), 0.88 (t, J = 6.2 Hz, 3H, -CH2CH3) ppm. ¹³ C NMR (75 MHz, CDCI ₃ ): δ = 170.6 (s), 127.0 (s), 123.8 (s), 73.4 (d), 39.4 (t), 34.2 (t), 31.7 (t), 29.2 (t), 25.5 (t), 22.5 (t), 21.1 (q), 20.6 (q), 20.5 (q), 19.0 (q), 14.0 (q) ppm. GC/MS (El): 240 <M\ 1), 180 (53), 165 (8), 151 (2), 37 (18), 123 (14), 109 (64), 95 (38), 83 (40), 67 (28), 55 (32), 43 (100). IR (neat, v/cm ^"1 ): 2928, 2359, 2914, 1736, 1458, 1374, 1240. HRMS (ESi): m/z: calcd. for C ₁₅ H ₂₈ 0 ₂ (M + Naf 263.1987: Found: 263.1975.

Example 11 : N-f4.5-dimethvlhex-4-en-2-vn-A/-methoxvacetamide

An argon flushed three-necked flask which was cooled by an ice-water bath was charged with 3,3,4-trimethylpent-4-en-2-one (0.50 g, 3.96 mmol), acetaldehyde O-methyl oxime (0.35 g, 4.75 mmol), and SnC (1.24 g, 4.75 mmol) in 1 ,2-dichloroethane (40 ml). The mixture was stirred for 48 hours at room temperature. The completion of reaction was checked by GC analysis of reaction aliquots quenched with a solution of saturated NaHC0 ₃ in water. After complete conversion, the reaction mixture was quenched with sat, aqueous NaHC0 ₃ solution (10 mL), The organic phase was separated and the aqueous layer was extracted with MTBE three times. The combined organic layers were washed with brine (20 mL), dried (MgS0 ₄ ) and evaporated in vacuo. The crude product was purified by distillation under reduced pressure to yield 0.76 g of the title product as colorless liquid (97%), ¹ H NMR (300 MHz, CDCt ₃ ): δ = 4,72-4.52 (m, 1H), 3.76 (s, 3H), 2.41 (dd, J = 13.2Hz, 7.2Hz, 1H), 2.20 (dd, J = 13.2Hz, 7.2Hz, 1H), 2.09 (s, 3H), 1.68 (s, 3H), 1.64 (s, 3H), 1.63 (s, 3H), 1.23 (d, J = 6.9Hz, 3H); ¹³ C NMR (75 MHz, CDCI ₃ ): δ = 173.5 (s), 127.1 (s), 124.4 (s), 64 5 (q), 52.6 (d), 38.5 (t), 20.6 (q), 20.6(q), 20.5 (q), 18.6 (q), 17.7 (q); IR (neat, v/cm ^"1 ): 2980, 2921 , 1671 , 1444, 1372, 1316, 1032 cm ^" '; GC/MS (El): mlz (%): 199 (1) [M ^* ], 110 (32), 95 (11), 74 (100), 55 (9), 43 (20); HRMS (ESI): mlz calcd for C _n H ₂₁ NO _z +H ⁺ : 200.1645; [ +H ⁺ ]; found: 200.1640.

Example 12. A -(2,3-dimethvldec-2-en-5-vl)-/V-methoxvacetarnide

Following the general procedure as described in Example 11 , 3,3,4-trimethylpent-4-en-2-one (0.50 g, 3.96 mmol), hexanal O-methyl oxime (0.62 g, 4.75 mmol), and SnCI ₄ (1.24 g, 4.75 mmol) in 1,2-dichloroethane (40 ml) were reacted to give the title product as a colorless liquid (0.47 g, 47% yield).

¹ H NMR (300 MHz, CDCI ₃ ): δ = 4.50-4.35 (m, 1H), 3.72 (s, 3H), 2.46 (dd, J = 13.2Hz, 7.8Hz, 1 H), 2.17 (dd, J = 13.2Hz, 6.6Hz, 1H), 2.10 (s, 3H), 1.66 (s, 3H), 1.62 (s, 6H), 1 48-1.31 (m, 8H), 0.88 (t, J = 6.0Hz, 3H); ¹³ C NMR (75 MHz, CDCI ₃ ): δ = 173.8 (s), 127.0 (s), 124 7 (s), 64.1 (q), 57.7 (d), 37.7 (t), 32.0 (t), 31.8 (t), 26.5 (t), 22.6 (t), 20.8 (q), 20.6 (q), 20.6 (q), 18.7 (q), 14.1 (q); IR (neat, v/cm ¹ ): 2928, 2860, 1670, 1372 cm ^""1 ; GC/MS (El): mlz {%): 255 (1) [M ^* ], 166 (25), 142 (3), 130 (100), 100 (12), 83 (5), 67 (3), 55 (10), 43 (20); HRMS (ESI): mlz calcd for C ₁₅ H ₂₉ N0 ₂ +H ⁺ : 256.2271 ; [ +H ^* ]; found: 256.2288.

Example 13: N-(4,5-dimethvlhex-4-en-2-vl)-/V-ethoxyacetamide

Following the general procedure as described in Example 11, 3,3,4-trimethylpent-4-en-2-one (0.50 g, 3.96 mmol), acetaldehyde O-ethyl oxime (0.41 g, 4.75 mmol), and SnCU (1.24 g, 4.75 mmol) in 1 ,2-dichloroethane (40 ml) were reacted to give the title product as a colorless liquid (0.75 g, 89% yield).

Ή NMR (300 MHz, CDCI ₃ ): δ = 4.70-4.50 (m, 1 H), 3.92 (q, J = 6.3Hz, 2H), 2 42 (dd, J = 13.2Hz, 7.2Hz, 1H), 2.20 (dd, J = 13.2Hz, 7.5Hz, 1H), 2.08 (s, 3H), 1.68 (s, 3H), 1.63 (s, 6H), 1.26 (t, J = 7.2Hz, 3H), 1.21 (d. J = 6.9Hz, 3H); ¹³ C NMR (75 MHz, CDCI ₃ ): δ = 173.4 (s), 127.0 (s), 124.4 (s), 72.4 (t), 52 6 (d), 38.6 (t), 20.7 (q), 20.6(q), 20.5 (q), 18.6 (q), 17.7 (q), 13.4 (q); IR (neat, v/cm ^"1 ): 2980, 2932, 1669, 1373, 1033 cm ^"1 ; GC/MS (El): mlz (%): 213(1) [M ^* l, 130 (11), 110 (24), 88 (100), 60 (9), 43 (17). Example 14: /V-methoxy-/\/-(2.6,7-trirnethvlocta-2.6-dien-4-vl)acetamide

Following the general procedure as described in Example 11 , 3, 3,4-trimethylpent-4-en-2-one (0.50 g, 3.96 mmol), 3-methylbut-2-enal O-ethyl oxime (0.54 g, 4.75 mmol), and EtAICI ₂ (0.60 g, 4.75 mmol) in 1 ,2-dichloroethane (40 ml) were reacted to give the title product as a colorless liquid (0.30 g, 32% yield).

¹ H MR (300 MHz, CDCI ₃ ): δ = 5.30 (d, J = 9.0Hz, 1 H), 5.23-5.08 (m, 1 H). 3.72 (s, 3H), 2.55 (dd, J = 13.2Hz, 7.5Hz, 1 H), 2.18 (dd, J = 13.2Hz, 6.9Hz, 1 H), 2.06 (s, 3H), 1.73 (s, 3H), 1.67 (s, 6H), 1.63 (s, 3H), 1.60 (s, 3H); ¹³ C NMR (75 MHz, CDCI ₃ ). δ = 172.0 (s), 135.5 (s), 127.1 (s), 123.8 (s), 122.8 (d), 64.2 (q), 54.2 (d), 37.7 (t), 25.5 (q), 20.5 (q), 20.3 (q), 20.3 (q), 18.8 (q), 18.6 (q); IR (neat, v/cm ^'1 ):_2970, 2914. 2862, 1665, 1375, 986 cm ^{" 1} ; GC/MS (El): mlz (%): 239(1) [M 156 (42), 135 (6), 114 (100), 83 (15), 67 (6), 55 (12), 44 (18); HRMS (ESI): mlz caicd for CH^NC H ^* : 240.1958; [ +Hl; found: 240.1962.

Example 15: /V-(3.4-dimethvl-1-phenvlpent-3-en-1-yl)-/V-methoxvacetamide

Following the general procedure as described in Example 11 , 3,3,4-trimethylpent-4-en-2-one (0.50 g, 3.96 mmol), benzaldehyde O-methyl oxime (0.64 g, 4.75 mmol), and SnCI« (1.24 g, 4.75 mmol) in 1 ,2-dichloroethane (40 ml) were reacted to give the title product as a colorless liquid (0.40 g, 39% yield). H NMR (300 MHz, CDCI ₃ ): δ ^" = 7.46 (d, J = 6.6Hz _» 2H), 7.36-7.28 (m, 3H), 5.80-5.50 (m, 1 H), 3.28 (s, 3H), 3, 13 (dd, J = 13.5Hz, 6.6Hz, 1 H), 2.45 {dd, J = 13.5Hz, 5.4Hz, 1 H), 2.08 (s, 3H), 1.69 (s, 3H), 1 64 (s, 3H), 1.61 (s, 3H); ³ C NMR (75 MHz, CDCI ₃ ): 6 = 172.8 (s), 139.7 (s), 128.5 (d), 128.5 (d), 128.3 (d), 128.3 (d), 127.9 (s), 127.7 (d), 123.8 (s), 64.3 (q), 58.4 (d), 35.0(t), 20.8 (q), 20.5(q), 20.5(q), 18.6 (q); IR (neat, v/cffl ^"1 ): 2916, 1667, 1372, 988, 708 cm ^"1 ; GC/MS (El): mlz (%): 261 (1 ) [M ^* ], 130 (100), 109 (6), 100 (19), 91 (2), 81 (12), 67 (13), 55 (23), 41 (13).

Example 16: 1-{2-(2.3-dimethvlbut-2-en-1-vl)indolin-1-vl)ethanone

Following the general procedure as described in Example 11 , 3,3,4-trimethylpent-4-en-2-one (0.50 g, 3.96 mmol), 1 H-indole (0.56 g, 4.75 mmol) which was in situ isomerized to 3H-indole, and SnCI ₄ (1.24 g, 4.75 mmol) in 1 ,2-dichloroethane (40 ml) were reacted to give the title product as a white solid (0.56 g, 58%). ¹ H NMR (300 MHz, DMSO-d ₆ ): δ = 7 98 (d, J = 7.8Hz, 1H), 7.25 (d, J = 7.2Hz, 1 H), 7.16 (t, = 7.5Hz, 1 H), 7.01 (t, J = 7.5Hz, 1 H), 4.61 (q, J = 7.5Hz, 1 H), 3.19 (dd, J ~ 15.6Hz, 8.1 Hz, 1 H), 2.62 (d, J ~ 15.6Hz, 1 H), 2.36-2.08 (m, 5H), 1.69 (s, 3H), 1.63 (s, 3H), 1.49 (s, 3H); ¹³ C NMR (75 MHz, DMSO-d ₆ ): δ = 167.7 (s), 141.8 (s), 131.1 (s), 127.7 (s), 126.8 (d), 124.9 (d), 123.4 (d), 123.3 (s), 1 17.1 (d), 59.0 (d), 38.5 (t), 33.1 (t), 22.9 (q), 20.5 (q), 20.2 (q), 18.5 (q); IR (neat, v/cm ¹ ): 2918, 1651 , 1403, 769 cm ^"1 ; GC/MS (El): m/z (%): 243(8) [M ^* ], 160 (22), 130 (2), 1 18 (100), 106 (1), 91 (7), 77 (1), 65 (1 ), 55 (2), 43 (5); HRMS (ESI): m/z calcd for C ₁₆ H _z1 NO+H ⁺ : 244.1696; [ +H ⁺ ]; found: 244.1694.

Example 17: <EJ-1-methoxy-8 0-dimethyl-3,4.5,6,9.10-hexahvdroazecin-2(1ti)-one

An argon flushed three-necked flask which was cooled by an ice-water bath was charged with 2-(prop-1-en-2-yl)cyclohexanone (0.88 g, 6.38 mmol), acetaldehyde O-methyl oxime (0.56 g, 7.65 mmol), and SnCI (1.66 g, 6.38 mmol) in 1 ,2-dichloroethane (65 ml). The mixture was stirred for 48 hours at room temperature. The completion of reaction was checked by GC analysis of reaction aliquots quenched with a solution of saturated NaHC0 ₃ in water. The reaction mixture was quenched with sat. aqueous NaHC0 ₃ solution (50 mL). The organic phase was separated and the aqueous layer was extracted with MTBE three times. The combined organic layers were washed with brine (30 mL), dried (MgS0 ) and evaporated in vacuo. The crude product was purified by distillation under reduced pressure to yield the title product as a colorless liquid (1.13 g, 84%).

¹ H NMR (300 MHz, CDCI ₃ ): δ = 5.08 (t, J = 8.9 Hz, 1 H), 4.76-4.69 (m, 1 H), 3.66 (s, 3H), 2.92- 2 83 (m, 1 H), 2.32-2.04 (m, 5H), 1.86-1.76 (m, 4H), 1.56 (s, 3H), 1.33 (d, J = 17.7Hz, 3H); ¹³ C NMR (75 MHz, CDCl ₃ ): δ = 179.8 (s), 134.4 (s), 128.1 (d), 64.3 (q), 56.6 (d), 44.2 (t), 31.4 (t), 29.5 (t), 28 5 (t), 23.7 (t), 18.1 (q), 17.3 (q); IR (neat, v/cm ¹ ): 2923, 2850. 1669, 1442, 1368, 1045 cm ^'1 ; GC/MS (El): m/z (%): 211 (8) [ΛΓ], 180 (4), 130 (2), 165 (40, 138(23), 123 (15), 109 (100), 94 (1 1). 74 (37), 55 (11), 41 (15); HRMS (ESI): m/z calcd for C _l2 H ₂₁ N0 ₂ +H ⁺ : 212.1645; [M+H ⁺ J; found: 212.1639.

Odour description: verbena fresh citrus grapefruit herbal, slightly bergamot, musky, agrumex aspect.

Example 18: ^-1-ethoxy-8, 10-dimethyl-3,4.5^9, 10-hexa

Following the general procedure as described in Example 17, 2-(prop-1-en-2- yl)cyclohexanone (0.88 g, 6.38 mmol), acetaldehyde O-ethyl oxime (0.67 g, 7.65 mmol), and SnCU (1.66 g, 6.38 mmol) in 1 ,2-dichloroethane (65 ml) were reacted to give the title product as a colorless liquid (1.14 g, 80% yield).

¹ H NMR (300 MHz, CDCI ₃ ): δ = 5.11 (t, J = 6.9Hz, 1 H), 4.77-4.70 (m, 1 H), 3.85-3.77 (m, 2H), 2.93-2.84 (m, 1H), 2.30 (t, J = 12.0Hz, 1H), 2.22-2.04 (m, 4H), 1.87-1.76 (m, 4H), 1.56 (s, 3H), 1.28-1.23 (m, 6H); "C NMR (75 MHz, CDCI ₃ ): «5 = 179.8 (s), 134.2 (s), 128.0 (d), 72.2 (t), 56.4 (d), 44.3 (t), 31.6 (t), 29.4 (t), 28.4 (t), 23.7 (t), 18.1 (q), 17.2 (q), 13.3 (q); IR (neat, v/cnf ¹ ): 2977, 2922, 1669, 1443, 1368, 1042 cm ^'1 ; GC/MS (El): m/z (%): 225(5) [Af ], 165 (4), 138 (22), 123 (17), 109 (100), 88 (52), 67 (23), 55 (14), 40 (25).

Example 19:^-1 -met oxv-8-methvl-10-pentvl-3.4.5.6.9.10-hexahvdroazecin-2(1H)-on e

Following the general procedure as described in Example 17, 2-(prop-1-en-2- yl)cyclohexanone (0.88 g, 6.38 mmol), hexanal O-ethyl oxime (0.99 g, 7.65 mmol), and SnCI {1.66 g, 6.38 mmol) in 1 ,2-dichloroethane (65 mi) were reacted to give the title product as a colorless liquid (1.00 g, 59% yield). E isomer >98%.

¾ NMR (300 MHz, CDCI ₃ ): <5 = 5.03(dd, J = 9.0Hz, 4.5Hz, 1 H), 4.49-4.43 (m, 1H), 3.58 (s, 3H), 2.84-2.75 (m, 1 H), 2.23-1.96 (m, 5H), 1.75-1.71 (m, 4H), 1.48 (s, 3H), 1.38-1.25 (m, 8H), 0.83 (t, J = 6.6Hz, 3H); ¹³ C NMR (75 MHz, CDC! ₃ ): <5 = 180.4 (s), 134.0 (s), 128.0 (d), 63.9 (q), 61.8 (d), 42.5 (t), 32.2 (t), 31.9 (t), 31.6 (t), 29.5 (t), 28.6 (t), 26.9 (t), 23.8 (t), 22.6 (t), 17.3 (q), 14.0 (q); IR (neat, v/cm ^'1 ): 2928, 2858, 1671 , 1444, 1364,1206, 1011 cm ^"1 ; GC/MS (El): m/z (%): 267 (5) [f f], 236 (3), 130 (69), 109 (100), 94 (1 ), 79 (21), 67 (23), 55 (18), 41 (22).

Example 20. E)-12-methvl-7.8,9.10,13a.14-hexahvdroazecino[1.2-alindol-6( 13W-one

Following the general procedure as described in Example 17, 2-(prop-1-en-2- yl)cyclohexanone (0.88 g, 6.38 mmol), 1 H-indole (0.90 g, 7.65 mmol) which was in situ isomerized to 3H-indole, and EtAICI ₂ (0.81 g, 6.38 mmol) in 1 ,2-dichloroethane (65 ml) were reacted to give the title product as a white solid (1.25 g, 77% yield).

Ή NMR {300 MHz, CDCI ₃ ): δ = 8.23 (d, J = 7.8Hz, 1 H), 7.19-7.11 (m, 2H), 6.96 (t, J = 7.5Hz, 1 H), 4.98-4.95 (m, 1H), 4.22 (t, J = 9.6Hz, 1 H), 3.32 (dd, J = 15.3Hz, 9,6Hz, 1 H), 2.55 (d, J = 9.6Hz, 1 H), 2.42-2.38 (m, 1 H), 2.19-2.05 (m, 4H), 1.84 (d, J ~ 12.9Hz, 1 H), 1.73 (s, 3H), 1.66- 1.48 (m, 4H); ³ C NMR (75 MHz, CDCI ₃ ): 5 = 172.0 (s), 142.0 (s), 131.3 (d), 130.6 (s), 129.2

(s), 127.4 (d), 124.6 (d), 123.7 (d), 119.0 (d), 57.7 (d), 45.9 (t), 36.1 (t), 31.9 (t), 28.1 (t), 25.1 (t), 23.9 (t), 17.6 (q); IR (neat, v/cm ¹ ): 2915, 2857, 1642, 1396, 1269 cm ^"1 ; GC/MS (El): m/z (%): 255(11} [ftf], 138 (4), 118 (100), 109 (11), 90 (9), 79 (7), 67 (7), 55 (4), 44 (6); HRMS (ESI); m/z calcd for C ₁₇ H ₂₁ NO+H ⁺ : 256.1696; [M+hfj; found: 256.1685.

Example 21 : fEJ-1-methoxy-9,11-dimefhylazacvcloundec-8-en-2-one

Following the general procedure as described in Example 17, 2-(prop-1-en-2- yl)cycloheptanone (0.97 g, 6.38 mmol), acetaldehyde O-methyl oxime (0.56 g, 7.65 mmol), and SnCI ₄ (1.66 g, 6.38 mmol) in 1 ,2-dichloroethane (65 ml) were reacted to give the title product as a colorless liquid (1.29 g, 90% yield).

¹ H N R (300 MHz, CDCI ₃ ): 6 = 5.13 (dd, J = 1 1 ,1 Hz, 3.9Hz, 1 H), 4.87-4.81 (m, 1 H), 3.72 (s, 3H), 2.96 (dt, J = 12.3Hz, 3.3Hz, 1 H), 2 41 (t, J = 12.3Hz, 1 H), 2.06-1 , 61 (m, 7H), 1.61 (s, 3H), 1.44-1.33 (m, 1H), 1.29 (d, J = 6.9Hz, 3H), 1.04-0.98 (m, 2H); ³ C NMR (75 MHz, CDCI ₃ ): 5 = 177.3 (s), 132.8 (s), 128.8 (d), 64.8 (q), 52.9 (d), 44.1 (t), 28.9 (t), 28.8 (t), 25.4 (t), 24.5 (t), 23.3 (t), 19.2 (q), 16.4 (q); IR (neat, v/cm ^"1 ): 2974, 2933, 2857, 1667, 1378, 1044 cm ^-1 ;

GC/MS (El): m/z (%): 225(6) [AT], 152 (16), 137 (15), 123 (14), 109 (94), 74 (67), 55 (22), 44 (100), 32 (53).

Example 22: fEH -ethoxv-9.11-dimethvlazacvcloundec-8-en-2-one

Following the general procedure as described in Example 17, 2-(prop-1-en-2- yl)cycloheptanone (0.97 g, 6.38 mmol), acetaldehyde O-ethyl oxime (0.66 g, 7.65 mmol), and SnCI ₄ (1.66 g, 6.38 mmol) in 1 ,2-dichloroethane (65 ml) were reacted to give the title product as a colorless liquid (1.11 g, 73% yield).

¹ H NMR (300 MHz, CDCl ₃ ): δ = 5.16 (dd, J = 11.1Hz, 4.5Hz, 1 H), 4,87-4.81 (m, 1 H), 3.92- 3.82 (m, 2H), 3.01-2.92 (m, 1 H), 2.44 (t, J = 12.6Hz, 1 H), 2.05-1.54(m, 8H), 1.61 (s, 3H), 1.28-1 24 (m, 6H), 1.07-1.04 (m, 2H); ¹³ C NMR (75 MHz, CDCI ₃ ): δ = 177.3 (s), 132.6 (s), 128.7 (d), 72.7 (t), 52.7 (d), 44.1 (t), 28.9 (t), 28.7 (t), 25.4 (t), 24.5 (t), 23.3 (t). 19.2 (q), 16.3 (q), 13.4 (q); IR (neat, v/cm ^"1 ): 2976, 2933, 1666, 1382, 1040 cm ^{" 1} ; GC/MS (El): m/z (%): 239(9) [Af], 152 (11), 137 (8), 123 (12), 109 (79), 88 (100), 67 (19), 55 (17), 41 (17).

Example 23: fEJ-1-methoxy-10-methyl-12-pentylazacvclododec-9-en-2-one

An argon flushed three-necked flask which was cooled by an ice-water bath was charged with

2-(prop-1-erv2-yl)cyclooctanone (1.50 g, 9.02 mmol), hexanal O-methy! oxime (1.56 g, 13.53 mmol), and SnCU (2,35 g, 9,02 mmol) in 1 ,2-dichloroethane (90 ml). The mixture was stirred for 2 days at room temperature. The completion of reaction was checked by GC analysis of reaction aliquots quenched with a solution of saturated NaHC0 ₃ in water. The reaction mixture was quenched with sat. aqueous NaHC0 ₃ solution (50 ml_). The organic phase was separated and the aqueous layer was extracted with MTBE three times. The combined organic layers were washed with brine (30 mL), dried (MgS0 ₄ ) and evaporated in vacuo. The crude product was purified by distillation to give the title product as a yellow oily liquid (2.38 g, 89%). E isomers > 98%.

¹ H MR (300 MHz, CDCI ₃ ): δ = 5.05 (d, J = 11.1 Hz, 1 H), 4.82-4.74 (m, 1 H), 3.74 (s, 3H), 2.98-2.88 (m, 1H), 2.40 (t, J « 12.6Hz, 1 H), 2.16-1.92 (m, 5H), 1.60 (s, 3H), 1.60-1.31 (m, 12H), 1.20-1.04 (m, 3H), 0.89(t, J = 6.6Hz, 3H); ³ C NMR (75 MHz, CDCI ₃ ): δ = 175.3 (s), 131.2 (s), 128.0 (d), 65.1 (q), 54.8 (d), 42.7 (t), 33 9 (t), 31.9 (t), 28.9 (t), 26.6 (t), 25.1 (t), 25.0 (t), 24.4 (t), 23.5 (t), 22.8 (t), 22.7 (t), 16.1 (q), 14.2 (q); IR (neat, v/crn ¹ ): 2927, 2857, 1658, 1445, 1386 cm ^"1 ; GC/MS (El): m/z (%): 295 (13) [M ^* ], 264 (2), 166 (5), 130 (100), 109 (13), 95 (8), 81 (8), 67 (10), 55 (1 1), 41 (9); HRMS (ESI): m/z calcd for C ₁₈ H ₃₃ N0 ₂ +H ⁺ : 296.2584; [M+H*J; found: 296.2585.

Example 24: iEM-methoxv-10.12-dimethvlazacyclododec-9-en-2-one

Following the general procedure as described in Example 23, 2-(prop-1-en-2- yl)cyclooctanone (1 ,50 g, 9.02 mmol), acetaldehyde O-methyl oxime (0.99 g, 13.53 mmol), and SnCI ₄ (2.35 g, 9.02 mmol) in 1 ,2-dichloroethane (90 ml) were reacted to give the title product as a colorless liquid (1.91 g, 89% yield). E isomer > 95%.

Ή NMR (300 MHz, CDCI ₃ ): δ = 5.06-4.96 (m, 2H), 3.76 (s, 3H), 2.98-2.88 (m, 1 H), 2.41 (t, J = 12.6Hz, 1 H), 2.20-1.89(m, 5H), 1.63-1.44 (m, 7H), 1.29 (d, J = 3.6Hz, 3H), 1.30-1.07 (m, 3H); ¹³ C NMR (75 MHz, CDCI ₃ ): 6 = 174.4 (s), 131 2 (s), 127.9 (d). 65.5 (q), 49.7 (d), 44.4 (t), 28.6 (t), 24.9 (t), 24.8 (t), 24.1 (t), 23.2 (t), 22.6 (t), 19.9 (q), 15.9 (q); IR (neat, v/cm ¹ ): 2938. 2855, 1656, 1447, 1387 cm ^{" 1} ; GC/MS (El): mlz (%): 239(20) [M'] _: 192 (12), 166 (15), 151 (15), 123 (37), 109 (40), 74 (100), 55 (27), 41 (25).

Exa m pie 25 : (E)A -ethoxy- 10.12-dimethvlazacvclododec-9-en-2-one

Following the general procedure as described in Example 23, 2-(prop-1-en-2- yl)cyclooctanone (1.50 g, 9.02 mmol), acetaldehyde O-ethyl oxime (1.18 g, 13.53 mmol), and SnCI (2.35 g, 9.02 mmol) in 1 ,2-dichloroethane (90 ml) were reacted to give the title product as a colorless liquid (1.98 g, 87% yield). E isomer >96%.

Ή NMR (300 MHz, CDCI ₃ ): δ = 5.09-4.98 (m, 2H), 3.98-3.84 (m, 2H), 2 97-2.88 (m, 1 H), 2.43 (t, J = 12.6Hz, 1H), 2.17-1.78 (m, 6H), 1.61 (s, 3H), 1.56-1.44 (m, 4H), 1.29-1.25 (m, 6H), 1.71-1.08 (m, 2H); ¹³ C NMR (75 MHz, CDCi ₃ ): 5 = 1 4.5 (s), 131.2 (s), 127.9 (d), 73.3 (t), 49.6 (d), 44.4 (t), 28.7 (t), 24 9 (t), 24.8 (t), 24.0 (t), 23.3 (t), 22 6 (t), 20.0 (q), 15.9 (q), 13.4 (q); IR (neat, v/cm ¹ ): 2977, 2935, 2856, 1656, 1440, 1385 cm ^"1 ; GC/MS (El): mlz (%):

253(14) [M\ 192 (9), 151 (8), 123 (20), 109 (23), 88 (100), 67 (19), 55 (17), 41 (16).

Example 26; fS-1 -methoxv-14.16-dimethvlazacvclohexadec- 13-en-2-one

Following the general procedure as described in Example 23, 2-(prop-1-en-2- yi)cyclododecanone (2.00 g, 9.02 mmol), acetaldehyde O-m ethyl oxime (0.99 g, 13.53 mmol), and SnCU (2.35 g, 9.02 mmol) in 1 ,2-dichloroethane (90 ml) were reacted to give the title product as a colorless liquid (2.33 g, 88% yield). Mixture of E / Z isomers in a ratio of 3 ; 1.

¹ H NMR (300 MHz, CDCI ₃ ): δ = 5.25-5.15 (m, 1 H), 4.78-4.59 (m, 1H), 3.75 (s, 3H). 2.58-2.44 (m, 2H), 2.23-1.92 (m, 4H), 1.72-1.60 (m, 5H), 1.31-1.26 (m, 17H); ¹³ C NMR (75 MHz, CDCI ₃ ): (5 = 175.5(S), 131.7 (s), 128.3 (d), 64.6 (q), 51.2 (d), 43 8 (t), 35.9 (t), 31.3 (t), 28.6 (t), 27.6 (t), 26.7 (t), 26.3 (t), 26.2 (t), 26.0 (t), 25.5 (t), 23.5 (t), 19 7 (q), 15.6 (q); IR (neat, v/cm ^{' 1} ): 2926, 2855, 1664, 1443, 1383 cm ^{- 1} ; GC/MS (El); mlz (%): 295 (25) [M ^* ], 265 (15), 222 (14), 207 (47), 109 (24), 95 (52), 74 (97), 55 (70), 44 (100).

Example 27; (E)A -ethoxy- 14. 6-dimethvlazacvclo hexadec- 13-en-2-one

Following the general procedure as described in Example 23, 2-(prop-1-en-2- yl)cyclododecanone (2.00 g, 9.02 mmol), acetaldehyde O-ethyl oxime (1.18 g, 13.53 mmol), and SnCI ₄ (2.35 g, 9.02 mmol) in 1 ,2-dichloroethane (90 ml) were reacted to give the title product as a colorless liquid (2.45 g, 88% yield). ixture of E / Z isomers in a ratio of 2 : 1. H NMR (300 MHz, CDCI ₃ ): δ = 5.25-5.16 <m, 1 H), 4.75-4.61 (m, 1 H), 4.02-3.88 (s, 2H), 2.63- 2.45 (m, 2H), 2.21-1.93(m, 4H), 1.71-1.46 (m, 5H). 1.33-1.28 (m, 17H); ¹³ C NMR (75 MHz, CDCI ₃ ): δ = 175.6 (s), 131.8 (s), 128.3 (d), 72.5 (t), 51.4 (d), 43.9 (t), 36.1 (t), 31.5 (t), 28.7 (t), 27.6 (t), 26.8 (t), 26.4 (t), 26.4 (t), 26.1 (t), 25.6 (t), 23.7 (t), 19.9 (q), 15.9 (q), 13.6 (q); IR (neat, v/crrf ¹ ): 2926, 2856, 1664, 1443, 1384, 1030 cm ^"1 ; GC/MS (El): m/z (%): 309(1) [AT], 222 (7), 207 (7), 164 (5), 109 (10), 88 (100), 67 (20), 55 (29), 41 (20),

Example 28: /V-(2.4-dimethyl-1-phenvldec-2-en-5-vl)-/V-methoxyformamide

Following the general procedure as described in Example 11 , 2-benzyl-2-methylpent-3-enal (0.74 g, 3.96 mmol), hexanal O-methyl oxime (0.62 g, 4.75 mmol), and SnCI (1.24 g, 4.75 mmol) in 1 ,2-dichloroethane (40 ml) were reacted to give the title product as a yellow liquid (0.70 g, 56% yield). Mixture of 4 isomers in a ratio of 2 : 2 : 3 : 3.

Ή NMR (300 MHz, CDCI ₃ ): 6 = 8.53-7.83 (m, 1 H), 7.29-7.13 (m, 5H), 5.24-4.98 (m, 1 H), 4.07-3.48 (m, 4H), 3.30-3.11 (m, 2H), 2.90-2.65 (m, 1H), 1.66-1 29 (m, 1 1 H), 1.06-0.89 (m, 6H); ¹³ C NMR (75 MHz, CDCI ₃ ): 6 = 158.7 (d), 139.8 (s), 136.2 (s), 128.9 (d), 128.6 (d), 128.3 (d), 128.3 (d), 128.1 (d), 126.0 (d), 65.8 (d), 62.8 (q), 37.9 (t), 35.2 (d), 31.6 (t), 28.7 (t), 26.2 (t), 22.5 (t), 18.6 (q), 16.3 (q), 14.0 (q); IR (neat, v/em ^"1 ): 2930, 1681 , 1494, 1007, 699 cm ^"1 ; GC/MS (El): m/z (%): 317 (1) [ ^* ], 242 (7), 207 (7), 158 (100), 128 (16), 117 (21), 98 (36), 71 (25), 55 (13), 43 (30).

Example 29: ^S.EH -butvl-4.7.8-trimethvl-10-propyl-3.4.5.6.9.10- hexa d roazeci n-2( 1 H)- one

Following the general procedure as described in Example 17, 2,5-dimethyl-2-(prop-1-en-2- yl)cyclohexanone (1.06 g, 6.38 mmol), N-butylidenebutan-1 -amine (0.97 g, 7.65 mmol), and SnC (1.66 g, 6.38 mmol) in 1 ,2-dichloroethane (65 ml) were reacted to give the title product as a colorless liquid (1.28 g, 76% yield). 3 isomers in a ratio of 1 : 2 : 8.

¹ H NMR (300 MHz, CDCI ₃ ): δ = 3.57-3.40 (m, 2H), 2.73-2.66 (m, 1H), 2.60-2.40 (m, 3H), 1.91-1.62 (m, 10H), 1.50 (s, 3H), 1.47-1.20(m, 9H), 1.04-0.89 (m, 7H); ¹³ C NMR (75 MHz, CDCI ₃ ): δ = 173.2 (s), 132.3 (s), 123.9(s), 56.1 (d), 43.0 (t), 38.6 (t), 36.1 (t), 34.3 (t), 33.6 (t), 33.4 (t), 31.5 (d), 29.8 (t), 25.7 (q), 20 9 (t). 20.9 (t). 20.2 (q), 19.0 (q), 14.0 (q), 14.0 (q); IR (neat, v/crrf ¹ ): 2956, 2869, 1631 , 1454, 105. 730 cm ^"1 , GC/MS (El): m/z (%): 293 (8) [/VT], 264 (5), 250 (6), 128 (100), 107 (4), 84 (10), 67 (6), 55 (7). 41 (8).

Example 30: ra-12-methvl-3.4.7.8.9.10.13.13a-octahvdro-1 H-pvridori .2-a1azecin-6(2H)-one Following the general procedure as described in Example 17, 2~(prop-1-en-2- yl)cyclohexanone (0.88 g, 6.38 mmol), 2,3,4,5-tetrahydropyridine (0.64 g, 7 65 mmol), and SnCI ₄ (1.66 g, 6.38 mmol) in 1 ,2-dichloroethane (65 ml) were reacted to give the title product as a colorless liquid (0.97 g, 69% yield).

¹ H MMR (300 MHz, CDCI ₃ ): <5 = 4,93-4.67 (m, 2H), 3.12 (dt, J = 12.6Hz, 3.0Hz, 1 H), 2.64-2.01 (m, 7H), 1.82-1.32 (m, 13H); ¹³ C NMR (75 MHz, CDCI ₃ ): <5 = 174.1 (s), 134.9 (s), 125.8 (d), 49.1 (d), 41.5 (t), 40.5(t), 34.2 (t), 28.5 (t), 27 9 (t), 25.9 (t), 25.4 (t), 25.0(t), 19.4 (t), 17.8 (q); IR (neat, v/cnY ¹ ): 2937, 2917, 2852, 1638, 1407, 1245 cm ^{" 1} ; GC/MS (El): mlz (%): 221 (16) [ *], 206 (2), 178 (4), 138 (5), 109 (7), 84 (100), 67 (8), 55 (12), 41 (8).

Example 31 : 1-(2-(2.3-dimethvlbut-2-en-1-yl)piperidin-1-vl)ethanone

Following the general procedure as described in Example 11 , 3,3,4-trimethylpent-4-en-2-one (0.50 g, 3.96 mmol), 2,3,4,5-tetrahydropyridine (0.39 g, 4.75 mmol), and SnCU (1.24 g, 4.75 mmol) in ,2-dichloroethane (40 ml) were reacted to give the title product as a colorless liquid (0.24 g, 29%).

¹ H NMR (300 MHz, CDCI ₃ ): <5 = 4.87-4.55 (m, 1 H), 3.96-3.58 (m, 1H), 3.20-2.63 (m. 1H), 2.49-2.04 (m, 6H), 1.81-1.37 (m, 13H); ¹³ C NMR (75 MHz, CDCI ₃ ): δ = 169.0 (s), 127.3 (s), 124.4 (s), 53.0 (d), 36.7 (t), 35.2 (t), 29 1 (t), 25.4 (t), 21.1 (q), 20.5 (q), 20.5 (q), 19.4 (t), 19.1 (q); IR (neat, v/cnf ¹ ): 2930, 2860, 1635, 1421 , 265, 997 cm ^{" 1} ; GC/MS (El); mlz (%): 209 (1) [M*], 126 (48), 84 (100), 55 (7), 43 (7).

Example 32: ethyl 3-(11-methyl-2-oxoazacvclotridec-10-en-1-vl)propanoate

An argon flushed flask was charged with 2-(prop-1 -en-2-yl)cyclononanone (1.44 g, 8.0 mmol), imine ethyl 3-(methyleneamino)propanoate (2.58 g, 20.0 mmol) and 1 ,2-dichloroethane (40 mL). Ethylaluminum dichloride (8.89 ml, 1.8 M in toluene, 16 mmol) was added dropwise at room temperature. The mixture was stirred for 24 hours. The reaction mixture was quenched with sat. aqueous NaHC03 solution (50 mL). The organic phase was separated and the aqueous layer was extracted with MTBE (50 mL ^* 2). The combined organic layers were washed with brine (50 mL), dried (MgS04) and evaporated in vacuo. The residue was purified by column chromatography on silica gel (MTBE / hexane = 1 : 5) and give ethyl 3-(11- methyl-2-oxoazacyclotridec-10-en-1-yl)propanoate as a colorless liquid (2.15 g, 87 % yield), E:Z=1 :1. E isomer: a pair of rotamers (-1 : 1 ratio). ¹ H N R (mixture of rotamers, 300 MHz, CDCI3): δ = 5.19-5.14 (m, 1 H), 4.64-4,55 and 2.59- 2.52 (m, 1H), 4.19-4.10 (m, 2H), 3.88-3.35 (m, 3H). 2.67-2.52 (m, 3H), 2.28-2.07 (m, 5H), 1.91-1.62 (m, 5H), 1.44-1.20 (m, 1 1H); ¹³ C NMR (mixture of rotamers, 75 MHz, CDCI3): δ = 173.3 (s), 173.3 (s), 172.3 (s). 171.2 (s), 132.4 (s), 131.4 (s), 129.7 (d), 127.8 (d), 60.9 (t),

60.5 (t), 46.5 (t), 41.6 (t), 41.5 (t), 40.2 (t), 38.3 (t), 37.5 (t), 33 3 (t), 32.7 (t), 32.6 (t), 29 8 (t),

27.6 (t), 27.6 (t), 27.1 (t), 27.0 (t), 26.7 (t), 26.5 (t), 26.1 (t), 26.0 (t), 25.1 (t), 25 0 (t), 24.3 (t), 23.1 (t), 17.0 (q), 15.7 (q), 14.2 (q), 14.1 (q); IR (neat): v ^' = 2926, 2855, 1732, 1642, 1421 , 1373, 1180 cm-1 ; GC/MS (El): m/z (%): 309 (1 ) [M ⁺ ], 294 (1), 264 (7), 222 (7), 130 (100), 84 (11 ), 55 (16), 42 (13); HRMS (ESI): m/z calcd. for C ₁₈ H ₃₁ M0 ₃ +Wa ⁺ : 332.2196; [M+Na ^* ]: Found: 332 2212.

Example 33: Catalyst screening

Following the general procedure as described in Example 1 , several catalysts have been used. Further details are given in Table 1 , below. Yields are not optimized.

(A) (I)

Table 1. Catalyst screening for the intermolecular electrocyclic rearrangement

Example 34: Catalyst screening

Following the general procedure as described in Example 11 , several catalysts have been used. Further details are given in Table 2, below. Yields are not optimized.

Table 2. Catalyst screening for the intermolecular electrocyclic rearrangement entry Catalyst amount of catalyst (mol%) conversion [%] yield (%)

2-1 BF ₃ Et _z O 00 99 96

2-2 SnGf ₄ 100 > 99 97

2-3 SnCI« 50 93 91

2-4 SnCl ₄ 20 68 65

2-5 TiCU 100 > 99 81

2-6 EtAICI ₂ 100 80 78

2-7 AIC 100 82 80

2-8 FeCI ₃ 100 97 92

2-9 CF ₃ SO ₃ H 100 > 99 59