The present invention is concerned with p,Y-unsatui-ated-y,y-disubstituted esters and with methods of synthesizing same.

P,y-unsaturated-y,y-disubstituted esters 1 can be prepared by vaiious methods known in the ait.

1

Such methods include (a) isomerization of α,β-unsaturated esters, (b) selective reduction of α,β,γ,δ-unsaturated esters, (c) cyanation of allylic halides, followed by hydrolysis and esterification, (d) carbonylation of allylic halides or (activated) allylic alcohols in the presence ofPd- or Ru-catalysts and (e) by other methods such as cross metathesis.

High E/Z-ratios of 1, however, are usually not obtained through these methods, unless stereopure E-allylic alcohols or halides are used as precursors (in case ofc or d), whose synthesis is difficult. WO 2007096791 describes the transesterification / decarboxylation of conjugated malonate 3a for the E-selective synthesis of la, using a salt MX _n (with n = 1-3, X being a halide or an anion of an acid HX and M being a group I, Π or III metal) in the presence of a carboxylic acid of the type R'C0 ₂ H with R' representing a hydrocarbon group.

Although high E/Z-ratios and β,γ / α,β ratios were reported from this method, these results were only obtained with substoichiometric amounts of the relatively expensive calcium 2- ethylhexanoate in combination with stoichiometric amounts of 2-ethylhexanoic acid, which after transesterification to alkyl 2-ethylhexanoate has to be separated from product la. Other MX ₃ / R'C0 ₂ H combinations claimed in this patent are less efficient

There remains a need to provide synthetic procedures into p,y-unsaturated-y,Y-disubstituted esters, which procedures are carried out relatively inexpensively and which provide 1 with high purity, in particular with high EIZ Ratios.

The invention provides in one of its aspects a process for the preparation of ,Y-unsaturated-y,Y- disubstituted esters 1,

R ¹

^ γ ^ν a C0 ₂ R

1

said process comprising the step of reacting at a temperature of between about 100 to about 350, more particularly about 130 to about 170 degrees centigrade the conjugated malonate

R ¹ co ₂ R

R ₂ - ^J ^ _C02R

3 with a MX„ , in the presence of an inorganic proton source and optionally a polar solvent, wherein MX _n is an inorganic salt or an organic cation/halide anion pair, X is a halide and n is an integer of 1 to 3, and M is a group I, II or III metal when MX _n is an inorganic salt, or M is selected from the group consisting of pyrridinium, piperidinium, pyiTolidinium, imidazolium, ammonium, phophonium and sulphonium, when MX _n is an organic cation/halide anion air; and wherein the groups R ¹ , R ² and R are organic residues. The skilled person will appreciate that the compound 1 is an interesting intermediate, which may be employed in synthetic routes to many interesting end products in the chemical arts and the nature of the ¹ , R ² and R will depend on the desired end product. In particular, the substituents R , R and R can be chosen lrom substituents useful in the fragrance art. More particularly, the substituents may be independently selected from hydrogen; linear, branched or (poly)cyclic C MS alkyl, aryl or arylalkyl groups, which optionally contain unsaturated bonds and/or 1 to 4 heteroatoms independently selected from O, S, N and Si. The groups R on the malonate 3 can be the same or different or together can form a (poly)cyclic group, optionally containing unsaturation or substituents as hereinabove defined.

Particularly preferred substituents R include methyl and ethyl.

Particularly preferred substituents R ¹ include methyl, phenyl, 2-(2,6,6-trimethylcyclohex-l- enyl)-ethyl, 4, 8 -dimethylnona-3 , 7-dien- 1 -yl.

Particularly preferred substituents R ² include methyl, phenyl, 2-(2,6,6-trimethylcyclohex-l- enyl)-ethyl, 4, 8 -dimethylnona-3 ,7-dien- 1 -yl .

Compound 1 formed by a process of the present invention can exist as an isomer mixture, with the double bond located in the β,γ-position or in the α,β-position, and if R≠R i the p,y- isomer, ElZ isomers are possible. The present invention provides a process for the preparation of 1 with high β,γ / ,β ratio, in particular of at least 95 : 5. The compounds 1 can also be formed with high E/Z-ratio, in particular of at least 75:25, more particularly at least 80:20. Compounds 1 formed by a process of the present invention are usefial compounds and may be used as reagents in all manner of organic syntheses.

Examples of 1 are cyclohomofamesic ester la and homofamesic ester lb, whose E-isomers are valuable precursors for the synthesis of (3ai?,5aiS',9a5',9bi?)-3a,6,6,9a-tetramethyl-dodecahydro- naphlho[2,l-b]furan 2 (Ambrox), which can be prepared from la or lb for example as described in WO 2006010287 (Givaudan). The stereochemical descriptors 3aR,5aS,9aS,9bR refer to the relative as well as to the absolute configuration, which means that 2 can be prepared as racemate or enantiomeric ally enriched, as desired.

Ambrox 2 is an important fragrance ingredient whose olfactory profile is, apart from its enantiopurity, determined by its diastereopurity, which in turn depends on the E/Z-iatios of the cyclization precursors, e.g. the compounds la and lb. Processes are desired, which provide these precursors with high E/Z-selectivity.

Accordingly, in another aspect of the present invention there is provided a process of preparing (Sa -jSa^^a^^b^^Sa^^^a-tetramethyl-dodecahydro-naphthof , 1 -b]furan, said process comprising the step of reacting at a temperature of between about 100 to about 350, more particularly about 130 to about 170 degrees centigrade the conjugated malonate 3

R ¹ C0 ₂ R

3 with a MX _n in the presence of an inorganic proton source and optionally a polar solvent, wherein MX _n is an inorganic salt or an organic cation halide anion pair, X is a halide and n is an integer of 1 to 3, and M is a group I, II or ΠΙ metal when MX _n is an inorganic salt, or M is selected from the group consisting of pyrridinium, piperidinium, pyrrolidinium, imidazolium, ammonium, phophonium and sulphonium, when MX _n is an organic cation/halide anion pair; and wherein the group R ¹ is 2-(2,6,6-trimethylcyclohex-l -enyl)-ethyl or 4,8-dimethylnona-3,7- dien-l -yl, R ² is methyl and R is selected from the groups as hereinabove defined.

In yet another aspect of the present invention there is provided (3a ?,5aS',9aS',9bi?)-3a,6,6,9a- tetrame&yl-dodecahydro-naphtho[2,l-b]furan obtainable by a process as hereinabove described.

In yet another aspect of the present invention there is provided a perfume composition comprising (3 aif^a^ _j ai ^b -J-Sa^^^a-tetramethyl-dodecahydro- a hthof , 1 -b]furan obtainable by a process as hereinabove described.

In yet another aspect of the invention there is provided a consumer product comprising

(3a/?,5a5' _J 9aiS,9bi?)-3a,6,6 _> 9a-tetramemyl-dodecahydro-naphmo[2,l-b]furan obtainable by a process as hereinabove described. The MX _n inorganic salt may be, in particular a group la, Ila or Illb halide, including lanthanide halides such as CeCl ₃ . Preferred inorganic salts are magnesium chloride and lithium chloride.

The MX _n organic cation / halide anion pair may be any of those materials referred to

hereinabove. Optionally, the organic cations are substituted with 1 -4 alkyl and / or aryl groups, which themselves can be substituted by any functional group. The organic cations can be linked among each other, thus forming a solid phase.

Salt mixtures of low melting points, which are liquid between about 100 °C and 200 °C can be used in the presence or absence of a polar solvent.

The salts may be used singularly or as mixtures. The amount of salt employed may be 0.2 mol% to 200 mol%, more particularly 1 mol% to 20 mol%.

The inorganic proton source can be any inorganic proton donor with a pK. _A between about 0 and about 17. Suitable inorganic proton sources include water (PK _A 15.6) or boric acid (JJK _A 9.2), which are soluble or partially soluble in the polar solvent. Mixtures of inorganic proton donors such as water / boric acid mixtures may be employed. Other mixtures include boric

acid/metaboric acid mixtures. Examples of boric acid proton donors include metaboric acid (HB0 ₂ ), monoalkyl or monoaryl boric esters (ROB(OH) ₂ with R = alkyl, aryl and substituted analogs thereof; bisalkyl or bisaryl boric esters (HOB(OR) ₂ with R = alkyl, aryl and substituted analogs thereof; as well as alkylidene, arylidene or arylalkylidene bridged borates, whose bridges can carry any kind of substituent, including linkers to other borate units.

The amount of inorganic proton source employed will depend upon the nature of the source and how many protons it can provide. In particular, the amount of proton source employed is in the range of about 0.25 to about 2.5 mol equiv, more particularly about 0.5 to about 1.5 equiv. At least 1 mol equivalent of protons will be required to affect transesterification or hydrolysis. In the case of boric acid, 3 protons can be delivered per entity ¾B0 ₃ , this proton source could be employed at about 0.35 mol equiv, more preferably about 0.5 mol equiv.

The polar solvent may be any suitable solvent that can dissolve completely or partially the conjugated malonate starting material, the inorganic proton source and the MX _n salt. In particular, polar solvents employed in the present invention are solvents which are partially or completely miscible with water. The polar solvents may be polar aprotic solvents. Polar solvents, which may be mentioned include alcohols, alkyl sulfoxides, sulfolanes, substituted amides, N-substituted pyrrolidones, N-substituted caprolactams and N-substituted ureas. Water- insoluble N-substituted pyrrolidones carrying substituents with more than 4 carbon atoms are included in this invention, as well as organic cation / halide anion pairs, which form ionic liquids at the reaction temperature, which are polar but often not miscible with water. Included are also mixtures of molten salts, which are liquid between about 100 °C and 200 °C. Mixtures of all these solvents can be used.

Whereas alkylsulfoxides and sulfolanes can be employed, it is preferable not to use these materials when compound 1 is to be employed in a synthesis of a fragrance material because of their rather strong and unpleasant odour, which can be rather difficult to remove.

N-substituted pyrrolidones such as N-Methyl-pyrrolidone (NMP) or N-ethyl-pyrrolidone (NEP) are preferred polar aprotic solvents.

The polar solvent can be also used in low amounts, preferably with 1 - 2 weight equivalents (w/w) based on the amount of conjugated malonate 3. In case of the N-substituted pyrrolidones such as NMP or NEP the solvent can be separated from the salt / water phase after aqueous work-up and is recycled or discarded as such.

The process of the present invention has the advantage that relatively inexpensive reagent combinations, e.g. MgCl ₂ / boric acid, LiCl / boric acid, MgCl ₂ / water or LiCl / water can be used in low amounts, which remain after aqueous work-up of the reaction in the water phase. A particular preparation of the p,y-unsaturated-y,Y-disubstituted esters by the decarboxylation of the conjugated malonate 3 is described in more detail herein below, wherein = Me or Et. However, the conditions described below apply to the process of the present invention as a generality. The conjugated malonate starting material may be obtained from commonly available starting materials using routine syntheses. A suitably substituted aldehyde (by way of example, aldehyde 4 shown above) may be reacted with a bisalkyl malonate under noevenagel conditions, for which a variety of methods and reagents are known in the art, to provide the conjugated

5 malonate 3, the starting material in a process according to the present invention.

It is preferred to employ as a proton donor one or more of the boric acid proton donors referred to hereinabove (e.g. boric acid) either alone or in admixture with other proton donors.

10 Water may be employed as the proton donor, but this is not preferred. If the decarboxylation of conjugated malonate 3 to β,γ-ester la is to be carried out in the presence of water (or any source of nucleophilic OH ^" ) a reiro-Knoevenagel-reaction of 3 to aldehyde 4 can occur as a side- reaction. This is disadvantageous as the aldehyde 4 would have to be removed from the desired material la.

15

Reagent systems employing water as the proton donor have been developed that reduce this side reaction particular examples of which include LiCl, MgCl ₂ or CaCl ₂ in polar aprotic solvents such as NMP, DMF, DMAA, NEP or in ionic liquids such as [BMEVTJBr (see examples). Such reagent systems can reduce the side reaction to a large extent, in particular limiting it to 5 to 20 10%. These combinations give ester la with E/Z-ratios between of 80:20 or more; and good β,γ / α,β ratios, for example 96:4 to 99:1.

With some other water-containing systems the back-reaction to aldehyde 4 may be substantially completely suppressed. In water-containing systems, it is preferred to use N-substituted

25 pyrrolidones such as NOP or NCP with, for example, LiCl or NaCl at 130 to 160 degrees

centigrade, la can be thus obtained with good E/Z-ratios, for example up to 83 :17 and good β,γ / α,β ratios. After aqueous work-up the polar solvent such as NOP or NCP remains in the organic phase. Particularly good EIZ ratios, in particular up to 86:14 may be obtained with boric acid as a trans esterification reagent. Boric acid may be used in combination with (earth)alkali halide catalysts such as Li CI, MgCl ₂ or CaCl ₂ . The solvent may be an N-substituted pyrrolidone such as NMP. Group III metal halides such as ScCl ₃ or CeCl ₃ can catalyze this reaction with similar efficiency. Ionic liquid catalysts such as [EM ] CI are also effective. Using these catalysts under water-free conditions can avoid formation of byproduct 4.

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

Example 1: Dimethyl 2-(2-methyl-4-(2,6,6-trimethylcyclohex-l-enyl)butylidene)mal onate 3a: Under water-free conditions titanium(IV) chloride (91 g, 0.5 mol) in tetrachloro methane (120 ml) are added dropwise within 45 min to tetrahydrofuran at 0 °C. The mixture is stirred for another 30 min at this temperature, then 2-Methyl-4"(2,6,6-trimethylcyclohex-l-enyl)butanal 4 (50 g, 0.24 mol) (M. Matsui et al., Agric. Biol. Chem. 50, 1475 - 1480, 1986) and dimethyl malonate (31.7 g, 0.24 mol) in tetrahydrofuran (50 ml) are added within 15 min at 0 °C followed by dropwise addition of pyridine (76 g) in tetrahydiOfuran (240 ml) over 90 min at 0 °C. The orange-brown suspension is stin'ed for 18 h at 25 °C, then poured upon ice / water and extracted with tert-butyl methyl ether. The combined organic layers are washed with water and cone. NaCl and dried over MgS0 ₄ . After filtration and evaporation of the solvents the crude product

(75 g) is short-path-distilled giving 62.5 g (81%) of 3a at 170 °C / 0.07 mbar. Analytical data: Ή- NM (400 MHz, CDCI3): 5 0.95 (s, 6 H), 1.1 (d, 3 H), 1.4 - 1.5 (4H), 1.5 - 1.6 (2 H), 1.58 (s, 3 H), 1.8 - 2.0 (2 H), 2.5 (m, 1 H), 3.8 (s, 3 H), 3.85 (s, 3 H), 6.85 (d, 1 H) ppm. ¹³ C-NMR (400 MHz, CDCI3): δ 19.45 (t), 19.55 (q), 19.75 (q), 26.4 (t), 28.5 (q), 32.7 (t), 34.8 (s), 35.7 (d), 36.8 (t), 39.7 (t), 52.1 (q), 52.2 (q), 126.7 (s), 127.1 (s), 136.8 (s), 154.9 (d), 164.4 (s), 166.0 (s). MS (El): m/z (%) 322 (Μ ⁺ , 10), 307 ([M - 15] ⁺ , 2), 275 (6), 259 (7), 243 (16), 215 (11), 200 (18), 187 (19), 175 (20), 173 (16), 172 (100), 153 (22), 145 (28), 140 (70), 137 (27), 135 (34), 123 (60), 122 (28), 121 (42), 109 (35), 108 (34), 95 (62), 93 (36), 81 (44), 79 (33), 55 (36), 41 (35). ffi. (film): 2950 (m), 2926 (m), 2865 (m), 1725 (s), 1642 (w), 1454 (w), 1433 (m), 1363 (w), 1327 (w), 1246 (s), 1221 (s), 1204 (s), 1168 (w), 1104 (w), 1054 (m), 991 (w), 945 (w), 925 (w), 833 (w), 762 (w).

Example 2: Diethyl 2-(2-methyl-4-(2,6,6-trimethylcyclohex-l-enyl)butylidene)mal onate 3b:

Under the conditions described in example 1, titanium(IV) chloride ( 1 g, 0.5 mol), 2-methyl-4- (2,6,6-trimethylcyclohex-l-enyl)butanaI 4 (50 g, 0.24 mol) and diethyl malonate (39.7 g, 0.24 mol) in tetrahydrofuran and tetrachloromethane are reacted which each other to give after workup and short- ath-distillation 70.1 g (83%) of 3b. Analytical data: Ή- NMR (400 MHz, CDC1 ₃ ): δ 0.97 (s, 6 H), 1.1 (d, 3 H), 1.25 - 1.6 (6 H), 1.3 (2 t, 6 H), 1.58 (s, 3 H) _; 1.8 - 2.0 (2 H), 2.55 (m, 1 H), 4.15 - 4.35 (2 q, 4 H), 6.8 (d, 1 H) ppm. ^,3 C-NMR (400 MHz, CDC1 ₃ ): 6 14.0 (q), 14.15 (q), 19. 5 (t), 19.6 (q), 19.8 (q), 26.5 (t), 28.5 (q), 32.7 (t), 34.85 (s), 35.6 (d), 36.9 (t), 39.8 (t), 61.1 (t), 61.15 (t), 127.0 (s), 127.5 (s), 136.9 (s), 153.9 (d), 164.0 (s), 165.7 (s). MS (EI): m/z (%) 350 (M ⁺ , 4), 335 ([M - 15] ⁺ , 3), 305 (4), 289 (5), 259 (9), 243 (11), 215 (8), 200 (98), 190 (18), 187 (11), 175 (16), 173 (27), 167 (18), 154 (100), 135 (30), 123 (42), 122 (30), 121 (39), 109 (19), 108 (60), 107 (32), 105 (19), 95 (52), 93 (34), 91 (25), 81 (40), 79 (30), 77 (15), 69 (21), 67 (26), 55 (36), 41 (32), 29 (28). ffi. (film): 2950 (m), 2960 (m), 2930 (m), 2862 (m), 1725 (s), 1645 (w), 1455 (m), 1375 (m), 1325 (w), 1250 (s), 1222 (s), 1205 (s), 1180 (m), 1170 (m), 1100 (m), 1050 (m), 1030 (m), 950 (w), 865 (w), 800 (w), 765 (w). Example 3: (E)-methyl 4-me1hyl-6-(2,6,6-n'imethylcyclohex-l-enyl)hex-3-enoate la-Me (la with R = Me): Conjugated malonate 3a (0.5 g, 1.5 mmol), anhydrous lithium chloride (93 mg, 2.2 mmol) and water (53 mg, 3 mmol) in N-methyl-pyrrolidone (2.9 g, 29 mmol) are heated under stirring to 130 °C. After 4 h at this temperature the mixture is poured upon 2 M HCl and extracted with ieri-butyl methyl ether. The combined organic layers are washed with cone. NaHC(¾, cone. NaCl and dried over MgS0 ₄ . After filtration and evaporation of the solvent the crude product (0.64 g) is bulb-to-bulb-distilled to give 0.4 g of la-Me at 120 °C / 0.1 mbar. E/Z ratio 82:18. Retention times (GC): 9.47 (Z), 9.56 (α,β), 9.62 (E) min. Analytical data of the E-isomer: Ή- NMR (400 MHz, CDC1 ₃ ): 6 1.0 (s, 6 H), 1.4 (m, 2 H), 1.55 (m, 2 H), 1.6 (s, 3 H), 1.7 (s, 3 H), 1.9 (m, 2 H), 2.1 (4 H), 3.05 (d, 2 H), 3.7 (s, 3 H), 5.35 (t, 1 H) ppm. ¹³ C-NMR (400 MHz, CDCI3): δ 16.35 (t), 19.5 (t), 19.8 (q), 27.5 (t), 28.6 (q, 2 C), 32.8 (t), 33.5 (t), 34.95 (s), 39.8 (t), 40.0 (t), 51.6 (q), 115.0 (d), 127.1 (s), 136.9 (s), 139.9 (s), 172.9 (s). MS (EI): m/z (%) 264 (M ⁺ , 4), 249 ([M - 15] ⁺ , 1), 190 (3), 175 (3), 138 (10), 137 (100), 136 (21), 121 (12), 106 (11), 95 (73), 81 (45), 55 (19), 41 (21). The mass spectra of the E- and Z-isomers are identical. IR (film): 2972 (m), 2865 (m), 1738 (s), 1434 (m), 1258 (m), 1199 (m), 1 148 (m). Table 1 : Variation of some reaction parameters of example 3 :

run 3 equiv ^c equiv ^c solvent ^a T t [h] subst" aid ⁰ prod " EIZ

R = MX _n H ₂ 0 w/w [°C] 3a 4 la α,β

1 Me 1.5 LiCl 2 6 NMP 130 4 h 11% 79% 82:18 99:1

2 Me 1.5 LiCI 2 13 [BMIMJBr 130 3 h 11% 9% 73% 71 :29 96:4

3 Me 1.5 LiCI 2 4 DMF 130 4 h 4% 11% 78% 81 :19 96:4

4 Me 1.5 LiCl 2 7 NEP 130 3 h 10% 90% 80:20 99:1

5 Me 1.5 LiCl 2 5 DMAA 130 3 h 8% 90% 78:22 99:1

6 Me 1 CaCl ₂ 2 10 NMP 130 3 h 6% 92% 78:22 98:2 7 Me 1 CaCl ₂ 2 6 DMAA 130 3 h 10% 90% 79:21 97:3

9 Et 0.1 MgCl ₂ 0.7 + 03 ⁶ 2 MP 160 6 h 6% 93% " 81:19 97:3

Decarboxylation of conjugated malonate 3: a) w/w = weight equiv. MP = N-methyl-pyrroIidone, [BMlM]Br = 1- butyl-3-methyl-imidazolium bromide, DMF = dimethyl formamide, NEP = N-ethyl-pyrrolodone, DMAA = dimethyl acetamide. b) GC-conversions: Subst = substrate, aid = aldehyde, prod = product, c) equiv =molar equivalents, d) The product is the ethylester of la. e) Reaction started with 0.7 equiv water, 0.3 equiv water added after 70 % conversion .

Table 2: Variation of some reaction parameters of example 3 (giving no back-reaction to aldehyde 4):

Decarboxylation of conjugated malonate 3: a) w/w = weight equivalents. NCP =N-cyclohexyI-pyrroIidone, NOP N-octyl-pyrrolidone. b) GC-conversions. c) equiv = molar equivalents, d) The product is the ethylester of la.

Example 4: Preparation of ( TJ-ethyl 4-methyl-6-(2,6,6-trimethylcyclohex-l-enyl)hi

la-Et (ethyl ester of la) by LiCl-catalyzed decarboxylation:

Under stirring and nitrogen conjugated diethyl malonate 3b (500 g, 1.39 mol), anhydrous lithium chloride (5.6 g, 0.13 mol) and anhydrous boric acid 41 g, 0.65 mol) in water- free N- methyl-pyrrolidone (880 ml, 8.9 mol) are heated to 160 - 170 °C for 10 h. After cooling the mixture is poured upon 2M HC1. After phase separation the organic phase is washed with cone. NaHC0 ₃ and cone. NaCl. The combined water phases are extracted with toluene. The combined organic layers are evaporated under reduced pressure to give 412 g of crude residue. Short-path- distillation at 150 °C / 0.06 mbar gives 352 g (91%) of ester la-Et. E/Z-ratio: 86:14. The analytical data of this compound are identical with the ones described for the isomers by M. Matsui et al. Agric. Biol. Chem. 50, 1475 - 1480, 1986.

Example 5: Preparation of la-Et by MgCl ₂ -catalyzed Decarboxylation:

Under stirring and nitrogen conjugated diethyl malonate 3b (52 g, 149 mmol), anhydrous magnesium chloride (0.56 g, 5.93 mmol) and anhydrous boric acid (4.5 g, 73 mmol) in water- free N-methyl-pyrrolidone (67 ml, 0.81 mol) are heated to 160 - 170 °C for 3 h. After cooling to 120 °C water is added and the mixture is acidified to pH 3 with 2 M H ₂ S0 ₄ . After extraction with hexane the combined organic layers are washed with water, cone. Na ₂ C0 ₃ , 10% HOAc, water and cone. NaCl. The organic phase is dried over MgS0 ₄ , filtered and evaporated under reduced pressure giving 42 g of a crude residue, which is bulb-to-bulb-distilled to give 36.6 g (88%) of la-Et. is/Z-ratio: 84:16. The analytical data of this compound are identical with the ones described for the isomers by M. Matsui et al. Agric. Biol. Chem. 50, 1475 - 1480, 1986.

Table 3: Variation of some reaction parameters of examples 4 and 5: run equiv* equiv' NMP T subst ^b product" EIZ ratio β,γ / α,β Yield ^d

MX„ ¾B0 ₃ w/w [h] 3b la-Et ratio

1 0.1 LiCl 0.5 1.8 6 h 99% 86.14 98:2 96%

2 1.5 LiCl 2 1.8 4 h 99% 82:18 98:2 90%

3 ^h 2 CaCl ₂ 2 4 2 h 3% 84% 82:18 98:2 79%

3 1.5 LiBr 2 6 4 h 99% 82:18 98:2 80%

4 0.04 MgC¾ 0.5 1.3 3 h 1% 96% 84:16 99:1 88%

5 o.i tEMUvqcr 0.5 1.8 44 h 3% 85% 78:22 92:8 n.d.

6 0.1 ScCl ₃ 0.5 1.8 10 h 99% 84:16 94:6 quant."

7 0.1 CeCl ₃ 0.5 1.8 24 h 3% 94% 84:16 99:1 quant. ⁶ Decarboxylation of conjugated malonate 3 b (R = Et) in the presence of boric acid and group Ι,Π or ΙΠ MX„ catalysts (x = 1-3, M = group 1,11 or IH metal, X = halide) in NMP at 160-165 °C under water-free conditions: a) w/w = weight equiv b) GC-conversions. Sub = substrate, c) [EMM]CI = l-ethyI-3 -methyl- imidazolium chloride, d) chemical yield after aqueous work-up and distillation, e) crude, f) equiv = molar equivalents, g) n.d. = not determined, h) Conjugated malonate 3 (R = Me), 130 °C, 4 w/w NMP

Example 6: Preparation of (E)-ethyl 4-metl yl-6-(2,6,6-rrimetliylcyclohex-l-enyl)hex-3-enoate la-Et (ethyl ester of la) in the presence of metaboric acid (HB0 ₂ ):

According to the procedure of example 4, conjugated diethyl malonate 3b (10 g, 28 mmol), anhydrous lithium chloride (0.12 g, 2.8 mol) and metaboric acid 99% (1.25 g, 28 mmol) in water-free N-methyl-pyrrolidone (19 g, 0.19 mol) gave after 23 h at 160 °C, standard work-up and bulb-to-bulb distillation 6.6 g (84%) of la-Et (93% purity, E/Z 82:18). The analytical data of this compound are identical with the ones described for the isomers by M. Matsui et al. Agrtc. Biol. Chem. 50, 1475 - 1480, 1986.