Process Involving Cross Metathesis of Olefins

Abstract

A method of forming a macrocyclic musk compound comprising the steps of: i) cross-metathesizing a first olefin and a second olefin in the presence of a homogeneous transition metal catalyst comprising an alkylidene ligand, to form a statistical mixture of a hetero-dimer intermediate of said first and second terminal olefin, and homo-dimers ii) separating the hetero-dimer from the statistical mixture of hetero- and homo-dimers iii) and cyclizing the hetero-dimer intermediate to form the macrocyclic musk compound.

Claims

1. A method of forming a macrocyclic musk compound comprising the steps of: i) cross-metathesizing a first olefin and a second olefin in the presence of a homogeneous transition metal catalyst comprising an alkylidene ligand, to form a statistical mixture of a hetero-dimer intermediate of said first and second terminal olefin, and homo-dimers ii) separating the hetero-dimer from the statistical mixture of hetero- and homo-dimers iii) and cyclizing the hetero-dimer intermediate to form the macrocyclic musk compound.

2. A method according to claim 1 wherein the first olefin has the formula (I) ##STR00028## wherein OR.sub.2 is a protected hydroxyl group, which is selected from: an alkyl ether group; an ester group; a silyl ether group; and a carbonate group; R.sub.3 is H or methyl; and, n is an integer from 1-8

3. A method according to claim 1, wherein the second olefin has the formula ##STR00029## wherein: R.sub.7 is branched or non-branched alkyl moiety containing 1 to 5 carbon atoms, and m is an integer from 1 to 10.

4. A method according to claim 1, wherein the hetero-dimer has the formula ##STR00030##

5. A method according to claim 1, wherein the hetero-dimer has the formula ##STR00031##

6. A method according to claim 1, wherein the hetero-dimer has the formula ##STR00032##

7. A method according to claim 1, wherein the first olefin and second olefin are reacted in a 1:x molar ratio to produce a ratio of hetero-dimer:first homo-dimer:second homo-dimer of 2x:1:1x.sup.2.

8. A method according to claim 1, wherein the hetero-dimer is formed in admixture with a protected alcohol homo-dimer and a carboxylic acid ester homo-dimer.

9. A method according to claim 8 wherein the mixture of protected alcohol hetero-dimer and each carboxylic acid ester homo-dimer is formed in a molar ratio of 2:1:1.

10. A method according to claim 1, wherein the hetero-dimer is separated from the homo-dimers by distillation at a temperature of 100 to 220 degrees centigrade and a pressure of 1 to 10 mbar.

11. A method according to claim 1, wherein the homo-dimers are recycled by metathesis with ethylene to regenerate the first and second olefins.

12. A method according to claim 11 wherein the homo-dimers are treated with ethylene gas at a pressure of 1 bar to 20 bar.

13. A method according to claim 1, wherein the hetero-dimer is cyclised by trans-esterification.

14. A method according to claim 13 wherein, if the hetero-dimer contains a protected alcohol group, it is first de-protected by hydrolysis before being subjected to cyclisation by tran-esterification.

15. A method of forming E/Z 9-ambrettolide according to the method according to claim 1.

16. A method of forming E/Z 9-ambrettolide according to claim 15, wherein the E/Z ratio is from 80.20 to 90:10.

17. A method according to claim 16 wherein the E/Z ratio is 85:15.

18. A method according to claim 1, wherein the catalyst is a molybdenum or tungsten catalyst containing an alkylidene ligand.

19. A method according to claim 1, wherein the catalyst is a compound according to the formula: ##STR00033## wherein M=Mo or W; R.sup.1 is aryl, heteroaryl, alkyl, or heteroalkyl; which may be substituted; R.sup.2 and R.sup.3 can be the same or different and each is hydrogen, alkyl, alkenyl, heteroalkyl, heteroalkenyl, aryl, or heteroaryl; which may be substituted; R.sup.5 is alkyl, alkoxy, heteroalkyl, aryl, aryloxy, heteroaryl, silylalkyl, silyloxy, which may be substituted; and R.sup.4 is a residue R.sup.6X, wherein X?O and R.sup.6 is aryl, which may be substituted; or X?S and R.sup.6 is aryl, which may be substituted; or X?O and R.sup.6 is (R.sup.7, R.sup.8, R.sup.9)Si; wherein R.sup.7, R.sup.8, R.sup.9 are alkyl or phenyl, which may be substituted; or X?O and R.sup.6 is (R.sup.10, R.sup.11, R.sup.12)C, wherein R.sup.10, R.sup.11, R.sup.12 are independently selected from phenyl, alkyl; which may be substituted; or, R.sup.4 and R.sup.5 are linked together and are bound to M via oxygen.

20. E/Z 9-ambrettolide formed according to a method according to claim 1.

21. The hetero-dimer of the formula: ##STR00034## wherein: OR.sub.2 is a protected hydroxyl group, selected from: an alkyl ether group; an ester group; a silyl ether group; or a carbonate group; R.sub.3 is H or methyl; n is an integer from 1-8; and, R.sup.7 is a branched or non-branched alkyl moiety containing 1 to 5 carbon atoms

22. The hetero-dimer according to claim 21 having the formula: ##STR00035##

23. The hetero-dimer according to claim 21 or claim 22 having the formula: ##STR00036##

24. E/Z Nirvanolide formed according to a method according to claim 1.

25. The hetero-dimer according to claim 21 having the formula: ##STR00037##

26. The hetero-dimer according to claim 25 having the formula: ##STR00038##

27. A method according to claim 3, wherein: R.sub.7 is methyl or ethyl.

28. A method according to claim 3, wherein: m is 7.

Description

EXAMPLE 1

[0113] In an open screw cap vial the 0.1 M solution of X052 in dry benzene (10.9 ?L, 50 ppm) was added to the mixture of purified methyl decenoate (11a) (2.00 g, 10.9 mmol, 2.28 mL) and purified tert-butyl ether (3i) (2.00 g, 10.9 mmol, 2.52 mL) and the reaction mixture was stirred at rt for 20 h, then it was quenched with 0.2 mL of diethyl ether (Analysis: ca. 100 ?L of reaction mixture was filtered through silica pad (ca. 4-5 mL) and washed with the mixture of n-heptane and EtOAc (7:3, 15 mL) and the filtrate was analyzed by GC-MS.). The CM reaction of 11a with 3i afforded a statistical mixture of 14i, 16ai and 18a (1:2:1) with 95% conversion for both starting olefins and E/Z ratios were found to be 85/15 for all three compounds.

EXAMPLE 2

[0114] In an open screw cap vial 0.5 mol % of trioctylaluminum (25 w % in hexane) (80 mg, 5.45*10.sup.?2 mmol, 114 ?L) was added to the mixture of methyl decenoate (11a) (2.00 g, 10.9 mmol, 2.28 mL) and tert-butyl ether (3i) (2.00 g, 10.9 mmol, 2.52 mL) and the reaction mixture was stirred at rt for 1 h, then the 0.1 M solution of X190 in dry benzene (5.45 ?L, 25 ppm) was also added to the reaction mixture and stirring was continued for 20 h, then it was quenched with 0.2 mL of diethyl ether (Analysis: ca. 100 ?L of the reaction mixture was filtered through silica pad (ca. 4-5 mL) and washed with the mixture of n-heptane and EtOAc (7:3, 15 mL) and the filtrate was analyzed by GC-MS.). The CM reaction of 11a with 3i afforded a statistical mixture of 14i, 16ai and 18a (1:2:1) with 95% conversion for both starting olefins and E/Z ratios were found to be 84/16 for all three compounds.

EXAMPLE 3

[0115] Methyl decenoate (11a) (51.2 g, 278 mmol, 58.0 mL) and tert-butyl octenyl ether (3i) (50.4 g, 273 mmol, 63.0 mL) were charged in a 500 mL round-bottom flask and the mixture was stirred for ten minutes, then 0.1 M solution of X039 in dry benzene (560 ?L, 100 ppm) was added in one portion. The reaction vessel was connected to a vacuum pump and the reaction mixture was stirred at room temperature under 50 mbar dynamic vacuum for 4 hours. GC-MS analysis of the crude product found 90% conversion for both starting olefins. Non-anhydrous ethyl acetate (10 mL) was added to the reaction mixture to quench the metathesis reaction. The quenched mixture was passed through a pad of silica (approx. 20 mL) using 500 mL ethyl acetate as eluent. Volatiles were removed in vacuo to afford the crude product as a practically colourless oil (92.4 g). Metathesis products 14i, 16ai and 18a were formed in the statistical (1:2:1) ratio and E/Z ratios were found to be 9/91 for all three compounds.

EXAMPLE 4

[0116] Methyl decenoate (11a) (0.675 g, 3.66 mmol, 765 ?L) and octenyl acetate (3m) (0.623 g, 3.66 mmol, 700 ?L) were charged in a 30 mL glass vial and the mixture was homogenized, then 0.1 M solution of X054 in dry benzene (74 ?L, 1000 ppm) was added in one portion. The vial was connected to a vacuum pump and the reaction mixture was stirred under 50 mbar dynamic vacuum at room temperature for 6 hours (90% conversion for both starting olefins according to GC-MS). Non-anhydrous diethyl ether (10 mL) was added to it to quench the metathesis reaction. The mixture was passed through a silica pad (10 mL) using n-HeptaneEthyl acetate; 1:1 solvent mixture as eluent. Approximately 75 mL filtrate was collected. Solvent was removed in vacuo to afford the metathesis product mixture as a slightly brownish oil (1.18 g). Metathesis products 14m, 16am and 18a were formed in the statistical (1:2:1) ratio and E/Z ratios were found to be 11/89 for all three compounds.

EXAMPLE 5

[0117] Methyl decenoate (11a) (21.4 mg, 0.116 mmol, 24.2 ?L) and octenyl acetate (3m) (19.6 mg, 0.115 mmol, 22.0 ?L) were charged in a 4 mL glass vial and the mixture was homogenized, then 0.1 M solution of X038 in dry benzene (11.5 ?L, 5000 ppm) was added in one portion. The vial was closed with a pierced cap and the reaction mixture was stirred under atmospheric pressure at room temperature. (Analysis: 20 ?L of the reaction mixture was mixed with 200 ?L of non-anhydrous diethyl ether within the glovebox to quench the metathesis reaction, then the quenched sample was passed through a silica plug (approx. 2 cm thick layer in a Pasteur-pipette) using 4 mL n-HeptaneEthyl acetate; 1:1 solvent mixture as eluent and the filtrate was analyzed by GC-MS. Sample taken after 2 hours showed 57% conversion for both starting olefins (11a, 3m) and cross metathesis products 14m, 16am and 18a were formed in the statistical (1:2:1) ratio. E/Z ratios were found to equal to 3/97 for all three cross metathesis products. A sample was taken after 2.5 days to find only 68% conversion of both starting olefins and E/Z=4/96 ratios for all three metathesis products.

##STR00024##

EXAMPLE 6

[0118] In an open screw cap vial the 0.1 M solution of X190 in dry benzene (26.2 ?L, 400 ppm) was added to the mixture of purified methyl decenoate (11a) (600 mg, 3.27 mmol, 683 ?L) and purified carbonate (3l) (609 mg, 3.27 mmol) and the reaction mixture was stirred at rt for 20 h, then it was quenched with 0.2 mL of diethyl ether (Analysis: ca. 100 ?L of reaction mixture was dissolved in methanol (1 mL) and a small amount sodium methoxide was added to the solution and it was stirred at rt for 4 h. After that it was diluted with water (0.5 mL) and extracted with dichloromethane (2?2 mL), dried over magnesium sulphate and evaporated. The sample was analyzed by GC-MS.). The CM reaction of 11a with 3l afforded a statistical mixture of 14l, 16al and 18a (1:2:1) with 95% conversion.

EXAMPLE 7

[0119] In an open screw cap vial 0.5 mol % of trioctylaluminum (25 w % in hexane) (40 mg, 2.72*10.sup.?2 mmol, 57 ?L) was added to the mixture of methyl decenoate (11a) (1.00 g, 5.43 mmol, 1.13 mL) and carbonate (3l) (1.00 g, 5.43 mmol) and the reaction mixture was stirred at rt for 1 h, then the 0.1 M solution of X190 in dry benzene (21.7 ?L, 200 ppm) was also added to the reaction mixture and stirring was continued for 20 h, then it was quenched with 0.2 mL of diethyl ether (Analysis: ca. 100 ?L of reaction mixture was dissolved in methanol (1 mL) and a small amount sodium methoxide was added to the solution and it was stirred at rt for 4 h. After that it was diluted with water (0.5 mL) and extracted with dichloromethane (2?2 mL), dried over magnesium sulphate and evaporated. The sample was analyzed by GC-MS.). The CM reaction of 11a with 3l afforded a statistical mixture of 14l, 16al and 18a (1:2:1) with 35% conversion.

EXAMPLE 8

[0120] Methyl decenoate (11a) (0.098 g, 0.50 mmol, 104 ?L) and 3-methylhex-5-enyl acetate (13) (0.078 g, 0.50 mmol, 85 ?L) were measured into a 4 mL vial, 0.1 M solution of X054 in dry benzene (5.0 ?L, 500 ppm) was added in one portion, then the vial was connected to a vacuum pump and the reaction was stirred at room temperature under 50 mbar dynamic vacuum (Analysis: 5.0 ?L of the reaction mixture was mixed with 200 ?L non-anhydrous diethyl ether to quench the metathesis reaction, then the quenched sample was passed through a silica plug (approx. 2 cm thick layer in a Pasteur-pipette) using 4 mL n-Heptane Ethyl acetate; 1:1 solvent and the filtrate was analyzed by GC-MS. Sample taken after 19 hours showed 97% conversion for both starting olefins (11a, 13) and cross metathesis products 15, 17 and 18a were formed in the statistical (1:2:1) ratio. Since E- and Z-isomers of the acetate compound 17 separate less readily in GC-MS than isomers of deprotected alcohol 22, the acetate moiety was selectively cleaved via trans-esterification of 20 ?L reaction mixture samples with dry methanol/NaOMe (1.0 mL methanol, approx. 5 mg NaOMe) following a protocol analogous to that described in Example 9. The resulting material was analyzed by GC-MS to determine E/Z ratio of compound 17. It was found that the more branched the chain is (2, 1 or no methyl groups in homoallylic position(s) of the double bond, the higher the Z-selectivity is. E/Z ratios for cross metathesis products: 15 (2/98); 17 (5/95); 18a (7/93). A sample taken only after 4 hours showed 89% conversion for 13 and 95% conversion 11a, indicating that the more branched substrate undergoes metathesis less readily. E/Z ratios were the same as those reported for the sample taken after 19 hours.

EXAMPLE 9

[0121] The experiment described in Example 8 was repeated using catalyst X039. In this case 96% conversion of both starting olefins was achieved within 4 hours. Cross metathesis products 15, 17 and 18a were again formed in the statistical (1:2:1) ratio. E/Z ratios: 15 (2/98); 17 (7/93); 18a (12/88).

EXAMPLE 10

[0122] Cleavage of a tBu-Ether Protecting Group

[0123] Crude product obtained in Example 3 was charged in a 500 mL two-necked round-bottom flask and dissolved in dry dichloromethane (200 mL, freshly distilled from CaH.sub.2). The flask was flushed with nitrogen and cooled to 0? C. by applying an ice/water bath. Titanium tetrachloride was added in small portions over 15 minutes and the mixture was stirred for additional 15 minutes. Still at 0? C., under constant cooling, saturated aqueous solution of NH.sub.4Cl solution (20 mL) was added dropwise. The mixture was allowed to warm to room temperature and brine was added to ease phase separation (1?100 mL). Phases were separated and the organic phase was washed with brine (2?50 mL) and dried over MgSO4. Volatiles were removed in vacuo. Column chromatographic purification of the resulting oil using silica and n-heptanediethyl ether; 2:1 as eluent afforded the desired product (21a) as a colorless oil (31.0 g, 109 mmol, 79% overall yield for the cross metathesis and tert-butyl cleavage steps). The E/Z isomer ratio was invariably 9/91.

[0124] Synthesis of Ambrettolide Intermediate w-Hydroxy Esters (21a-c, 22) Via Selective Alcohol Deprotection:

##STR00025##

EXAMPLE 11

[0125] Cleavage of an Ester Protecting Group

[0126] The crude product obtained in Example 4 was dissolved in 3 mL dry methanol, 20 mg sodium methylate was added and the mixture was stirred at room temperature for 2 hours. The mixture was passed through a silica pad (7 mL silica) and the pad was washed with ethyl acetate (75 mL). The filtrate was evaporated to afford 1013 mg crude transesterification product. The desired product was isolated by flash column chromatography using n-heptanediethyl ether; 2:1. The desired product (21a, R.sub.1=Me) was obtained as a yellowish oil (355 mg, 1.25 mmol, 68% overall yield for the cross metathesis and acetate cleavages). The E/Z isomer ratio was invariably 11/89.

[0127] GC-MS Analytical Method for Product Identification (Method A):

[0128] GC analyses were run using a flame ionization detector (FID). Column: ZB-35HT Inferno (35% Phenyl 65% Dimethylpolysiloxane) from Phenomenex; 30 m?0.25 mm (i.d.)?0.25 mm film thickness. GC and column conditions: injector temperature 370? C.; detector temperature 240? C.; oven temperature, starting temperature 50? C., hold time 5 min, ramp rate 25? C./min to 340? C., hold time 12 min; carrier gas nitrogen.

[0129] GC-MS Analytical Method for Product Identification (Method B):

[0130] GC analyses were run using a flame ionization detector (FID). Column: ZB-35HT Inferno (35% Phenyl 65% Dimethylpolysiloxane) from Phenomenex; 30 m?0.25 mm (i.d.)?0.25 mm film thickness. GC and column conditions: injector temperature 370? C.; detector temperature 240? C.; oven temperature, starting temperature 55? C., hold time 2 min, ramp rate 25? C./min to 200? C., hold time 0 min; ramp rate 4? C./min to 260? C., hold time 0 min, ramp rate 40? C./min to 340? C., hold time 3.2 min carrier gas nitrogen.

TABLE-US-00001 TABLE 1 Cross metathesis of decenoic acid esters and protected oct-7-enol derivatives. Cat- Loading Con- E/Z Entry Substrates alyst (ppm (mol)) version ratio Procedure 1 11a and 3m X007 2000 ppm 80% 82/18 A 2 11a and 3m X007 1000 ppm 15% 80/20 A 3 11a and 3m X008 2000 ppm 25% 81/19 A 4 11a and 3m X001 2500 ppm 85% 85/15 A 5 11a and 3m X030 2000 ppm 50% 83/17 A 6 11a and 3m X041 2000 ppm 50% 83/17 A 7 11a and 3m X042 2000 ppm 90% 84/16 A 8 11a and 3m X046 2000 ppm 90% 81/19 A 9 11a and 3m X040 2000 ppm 95% 85/15 A 10 11a and 3m X042 1000 ppm 80% 83/17 A 11 11a and 3m X052 1000 ppm 85% 84/16 A 12 11a and 3m X051 1000 ppm 35% 85/15 A 13 11a and 3m X004 1000 ppm 60% 86/14 A 14 11a and 3m X042 500 ppm 15% 85/15 A 15 11a and 3m X123 200 ppm 10% 85/15 B 16 11a and 3m X054 1000 ppm 90% 11/89 Example 4 17 11a and 3m X038 5000 ppm 68% 4/96 Example 5 18 11a and 3h X042 1000 ppm 95% 84/16 A 19 11a and 3h X052 1000 ppm 95% 85/15 A 20 11a and 3h X052 250 ppm 95% 84/16 A 21 11a and 3h X042 250 ppm 95% 85/15 A 22 11a and 3h X052 100 ppm 95% 84/16 A 23 11a and 3h X042 100 ppm 95% 85/15 A 24 11a and 3h X052 50 ppm 85% 85/15 A 25 11a and 3h X042 50 ppm 40% 84/16 A 26 11a and 3h X051 50 ppm 75% 85/15 A 27 11a and 3h X061 50 ppm 85% 84/16 A 28 11a and 3h X062 50 ppm 65% 84/16 A 29 11a and 3h X063 50 ppm 40% 70/30 A 30 11a and 3g X052 100 ppm 95% 84/16 A 31 11a and 3g X042 100 ppm 70% 85/15 A 32 11a and 3i X052 100 ppm 90% 83/17 A 33 11b and 3i X052 100 ppm 95% 85/15 A 34 11c and 3i X052 100 ppm 95% 84/16 A 35 11a and 3i X039 100 ppm 90% 9/91 Example 3 36 11a and 3i X052 50 ppm 90% 84/16 A 37 11a and 3i X061 50 ppm 20% 83/17 A 38 11a and 3i X059 50 ppm 20% 84/16 A 39 11a and 3i X004 50 ppm 20% 85/15 A 40 11a and 3i X076 50 ppm 90% 60/40 A 41 11a and 3i X114 50 ppm 15% 80/20 A 42 11a and 3i X123 50 ppm 85% 85/15 A 43 11a and 3i X123 25 ppm 90% 85/15 B 44 11a and 3i X149 25 ppm 10% 84/16 B 45 11a and 3i X154 25 ppm 85% 85/16 B 46 11a and 3i X123 17 ppm 75% 84/16 B 47 11a and 3i X123 12 ppm 55% 84/16 B 48 11a and 3l X190 400 95% n/a Example 6 49 11a and 3l X190 200 32% n/a A 50 11a and 3l X190 200 35% n/a Example 7 51 11a and 3l X190 100 10% n/a A

TABLE-US-00002 TABLE 2 Cross metathesis of decenoic acid esters and protected oct-7-enol derivatives. Loading Con- E/Z Entry Substrates Catalyst (ppm (mol)) version ratio Procedure 48 11a and 3i X190 25 ppm 85% 85/15 B 49 11a and 3f X052 50 ppm 60% 84/16 B 50 11a and 3f X123 50 ppm 90% 85/15 B 51 11a and 3f X123 25 ppm 80% 84/16 B 52 11a and 3o X123 50 ppm 50% 84/16 B 53 11a and 3n X123 50 ppm 45% 85/15 B 54 11a and 3c X052 250 ppm 50% 84/16 A 55 11a and 3c X123 250 ppm 80% 85/15 A 56 11a and 3d X052 500 ppm 90% 84/16 A 57 11a and 3d X123 500 ppm 90% 85/15 A

TABLE-US-00003 TABLE 3 Cross metathesis of methyl dec-9-enoate (11a) and 3-methylhex-5-enyl acetate (13). Loading E/Z Entry Substrates Catalyst (ppm (mol)) Conversion ratio Procedure 1 11a and 13 X054 500 ppm 97% (19 h) 5/95 Example 6 2 11a and 13 X039 500 ppm 96% (4 h) 7/93 Example 7

TABLE-US-00004 TABLE 4 Characterization of cross metathesis products. CM Entry products GC-MS Retention MS (mw) 1 16aa Method A 15.82 min 368 [M].sup.+ 2 16ab Method A 16.44 min 368 [M].sup.+ 3 16ac Method A 16.74 min 382 [M].sup.+ 4 16ad Method A 17.10 min 396 [M].sup.+ 5 16ae Method A 18.25 min 438 [M].sup.+ 6 16af Method A 15.02 min 356 [M].sup.+ 7 16ag Method A 15.72 min 399 [M].sup.+ 8 16ah Method A 14.60 min 298[M].sup.+ 9 16ai Method A 15.31 min 284 [M ? CCH.sub.3].sup.+ 10 16aj Method A 15.52 min 355 [M].sup.+ 11 16ak Method A 15.98 min 346, 348 [M].sup.+ 12.sup.a 16al Method A 14.98 min 284 [M].sup.+ 13 16an Method A 15.43 min 326 [M].sup.+ 14 16ao Method A 15.83 min 340 [M].sup.+ 15 16ap Method A 15.94 min 354 [M].sup.+ 16 16ar Method A 16.03 min 325 [M].sup.+ 17 16bi Method A 15.27 min 355 [M].sup.+ 18 16bj Method A 15.72 min 298 [M ? CH(CH.sub.3)OC.sub.2H.sub.5].sup.+ 19 16bn Method A 15.68 min 340 [M].sup.+ 20 16ci Method A 15.30 min 312 [M ? CCH.sub.3].sup.+ 21 16cj Method A 15.75 min 385 [M].sup.+ 22 17 Method B 15.74 min 312 [M].sup.+, 252 [M ? AcOH].sup.+ .sup.aBefore the product identification the protective group was cleaved by sodium methoxide in methanol.

[0131] Recycling of Homodimeric Side Product(s) Via Cross Metathesis:

##STR00026##

EXAMPLE 12

[0132] (Scenario 1):

[0133] The homodimer of tert-butyl octenyl ether (14i) (0.085 g, 0.25 mmol, 100 ?L, E/Z=85/15) and the homodimer of methyl dec-9-enoate (18a) (0.086 g, 0.25 mmol, 92 ?L, E/Z=85/15) were charged in a 4 mL screw cap vial and the mixture was homogenized. Metathesis catalyst X190, (1.0*10.sup.?4 mmol, 10 ?L, 0.01 M in benzene) was added in one portion. The vial was closed with a septum cap and the reaction mixture was stirred at room temperature overnight. The reaction mixture was subjected to air and mixed with 1 mL non-anhydrous ethyl acetate to quench the reaction. The sample was then passed through a silica pad using pure ethyl acetate as eluent (5 mL) and the filtrate was analyzed by GC-MS. The reaction afforded 14i, 16ai and 18a with 95% recycling efficiency. In case of compound 16ai the ratio of E- and Z-isomers was found to correspond to the thermodynamical equilibrium value (E/Z=85/15).

EXAMPLE 13

[0134] (Scenario 2):

[0135] 8-(tert-Butoxy)oct-1-ene (3i) (0.092 g, 0.50 mmol, 114 ?L) and methyl dec-9-enoate (11a) (0.092 g, 0.50 mmol, 104 ?L) along with the homodimer of tert-butyl octenyl ether (14i) (0.086 g, 0.25 mmol, 100 ?L, E/Z=85/15) and the homodimer of methyl dec-9-enoate (18a) (0.086 g, 0.25 mmol, 92 ?L, E/Z=85/15) were charged in a 4 mL screw cap vial and the mixture was homogenized. Metathesis catalyst X052 (2.0*10.sup.?4 mmol, 20 ?L, 0.01 M in benzene) was added in one portion. The vial was closed with a pierced cap and the reaction mixture was stirred at room temperature. Samples (10 ?L) taken from the reaction mixture after 2 h and 18 h reaction times were subjected to air and mixed with 0.2 mL non-anhydrous diethyl ether to quench the reaction. The samples were then passed through a silica pad using pure EtOAc as eluent (5 mL) and the filtrate was analyzed by GC-MS. For the sample taken at 2 hours reaction time GC-MS analysis found 90% recycling efficiency and in case of compound 16ai the ratio of E- and Z-isomers was found to correspond to the thermodynamical equilibrium value (E/Z=85/15). The sample taken after 18 hours showed identical values regarding both recycling efficiency and E/Z ratio.

EXAMPLE 14

[0136] (Scenario 3):

[0137] Methyl dec-9-enoate (11a) (0.184 g, 1.0 mmol, 208 ?L) and the homodimer of tert-butyl octenyl ether (14i) (0.170 g, 0.5 mmol, 200 ?L, E/Z=85/15) were charged in a 4 mL screw cap vial along with trioctylaluminum (4.0*10.sup.?4 mmol, 16.8 ?L, 0.024 M in benzene) and the mixture was stirred at room temperature for 3.5 hours, then metathesis catalyst X190 (4.0*10.sup.?4 mmol, 40 ?L, 0.01 M in benzene) was added in one portion. The vial was closed tightly and the reaction mixture was stirred at room temperature for 1.5 hours. The vial was connected to a 50 mbar dynamic vacuum source and its content was stirred for further 2.5 hours. The reaction mixture was subjected to air and mixed with 1 mL non-anhydrous ethyl acetate to quench the reaction. The sample was then passed through a silica pad using pure ethyl acetate as eluent (5 mL) and the filtrate was analyzed by GC-MS. GC-MS analysis found 95% recycling efficiency and in case of compound 16ai the ratio of E- and Z-isomers was found to correspond to the thermodynamical equilibrium value (E/Z=85/15).

EXAMPLE 15

[0138] (Scenario 4):

[0139] 8-(tert-Butoxy)oct-1-ene (3i) (0.186 g, 1.0 mmol, 235 ?L) and the homodimeric olefin (18a) (0.170 g, 0.5 mmol, 183 ?L, E/Z=85/15) were charged in a 4 mL screw cap vial along with trioctylaluminum (2.0*10.sup.?4 mmol, 8.4 ?L, 0.024 M in benzene) and the mixture was stirred at ca. 30? C. for 3.5 hours, then metathesis catalyst X190 (2.0*10.sup.?4 mmol, 20 ?L, 0.01 M in benzene) was added in one portion. The vial was closed tightly and the reaction mixture was stirred at ca. 30? C. for 1.0 hours. The vial was connected to a 50 mbar dynamic vacuum source and its content was stirred for further 1.5 hours. The reaction mixture was subjected to air and mixed with 1 mL non-anhydrous ethyl acetate to quench the reaction. The sample was then passed through a silica pad using pure ethyl acetate as eluent (5 mL) and the filtrate was analyzed by GC-MS. GC-MS analysis found 95% recycling efficiency and in case of compound 16ai the ratio of E- and Z-isomers was found to correspond to the thermodynamical equilibrium value (E/Z=85/15).

TABLE-US-00005 TABLE 5 Selected examples of recycling experiments based on various strategies outlined in Scheme Substrates, Loading (ppm (mol)) Recycling molar in monomer efficiency E/Z ratio Entry ratios Catalyst equivalents.sup.a %.sup.b (16ai) Procedure 1 14i, 18a X190 100 ppm 95% 85/15 Example 10 2 1:1 X052 100 ppm 40% 85/15 Conditions of Example 10 3 3i, 11a, 14i, X052 100 ppm 90% 85/15 Example 11 4 18a X190 100 ppm 70% 85/15 Conditions of 2:2:1:1 Example 11 5 11a, 14i X190 200 ppm 95% 85/15 Example 12 2:1 6 3i, 18a X190 100 ppm 95% 85/15 Example 13 2:1 .sup.aMonomeric olefins (3i, 11a) equal to 1, while homodimeric olefins (14i, 18a) equal to 2 equivalents of monomeric units. Loadings are given with respect to the sum of all olefinic starting materials. .sup.bRecycling efficiency is calculated in the following way: rec. efficiency % = [n(octenyl units in 16ai/?n(octenyl units in any form) + n(octenyl units in 16ai/?n(octenyl units in any form)]*100. Its value is 0% for all starting mixtures and equals to 100% for a statistical mixture of 14i, 16ai, 18a.

[0140] Experimental Details on the Recycling of Homodimeric Side Product(s) Via Ethenolysis:

##STR00027##

TABLE-US-00006 TABLE 6 Ethenolysis of tert-butyl ether dimer (14i)..sup.a Entry Substrate Catalyst Loading (ppm (mol)) Conversion 1 14i X041 400 ppm 65% 2 14i X042 400 ppm 60% 3 14i X052 400 ppm 75% 4 14i X076 400 ppm 60% 5 14i X041 200 ppm 57% 6 14i X042 200 ppm 41% 7 14i X052 200 ppm 52% 8 14i X076 200 ppm 33% .sup.9.sup.b 14i X041 200 ppm 91% 10.sup.b.sup. 14i X052 200 ppm 62% .sup.aAll reactions were carried out at 0.73 mmol scale, reaction mixtures were stirred at room temperature for 16 h under 11.5 bar ethylene pressure. .sup.bn-Heptane was used as solvent to increase the solubility of ethylene.

EXAMPLE 16

[0141] General Procedure of Ethenolysis (for Results in Table 6.):

[0142] In an open screw cap vial the 0.1 M solution of metathesis catalyst (in dry benzene) (200-400 ppm) was added to 14i or 18a (0.73 mmol) and the reaction mixture was stirred at rt under 11.5 bar ethylene for 20 h, then it was quenched with 0.2 mL diethyl ether (Analysis: ca. 100 ?L of the reaction mixture was filtered through a silica pad (ca. 4-5 mL) the pad was washed with a mixture of n-heptane and EtOAc (7:3, 15 mL) and the filtrate was analyzed by GC-MS.).

TABLE-US-00007 TABLE 7 Results of ethenolysis experiments. Loading Conversion Entry Substrate Catalyst (ppm (mol)).sup.a Conditions %.sup.b 1 14i X061 1000 ppm Example 16 80% (isolated) 2.sup.c X008 400 ppm 4x volume of 80% 3.sup.c 200 ppm pentane, r.t., 50% 11.5 bar, 12 h 4 18a X008 1000 ppm Example 17 86% (isolated) 5.sup.c 400 ppm 4x volume of 50% pentane, r.t., 11.5 bar, 12 h 6.sup.c 400 ppm 4x volume of 55% 7.sup.c 200 ppm pentane, 2.5 30% mol % Et.sub.3Al, r.t. 1.5 h then catalyst X008, r.t., 11.5 bar, 12 h .sup.aCatalyst loadings given with respect to starting homodimers (14i and 18a). .sup.bGC conversions unless indicated otherwise. .sup.cReactions were carried out on 0.5 mmol scale. Work-up analogous to that described for experiments listed in Table 6.

EXAMPLE 17

[0143] Diether (14i) (2.47 g; 7.25 mmol) was dissolved in 12.0 mL pentane in a 30 mL oven-dried glass vial equipped with a stir bar, stock solution of catalyst X061 (0.1 M in benzene; 72.6 ?L; 0.1 mol %) was added to the reaction mixture and the vial was placed into an autoclave (250 mL inner volume). The autoclave was closed and pressurized to 11.5 bar for 30 minutes. Ethylene source was disconnected and the autoclave was chambered out from the glovebox. The reaction mixture was allowed to stir at room temperature for 12 hours. Ethylene was carefully released, the autoclave lid was removed and 1 mL heptane:EtOAc (non-anhydrous solvents) 1:1 solvent mixture was added subsequently to quench the reaction. The quenched reaction mixture was passed through a silica plug (ca. 10 cm silica layer in a 20 mL syringe barrel) using 150 mL heptane:EtOAc 1:1 solvent mixture as eluent. The filtrate was concentrated in vacuo and the oily residue was distilled bulb-to-bulb (3.0-3.3?10.sup.?2 mbar; 52-55? C.) to afford recovered tert-butyl octenyl ether (3i) as a colorless oil (2.13 g; 11.56 mmol; yield: 80%).

EXAMPLE 18

[0144] Procedure and workup were identical to those describe in Example A but catalyst X008 was used. Diester (18a) (2.27 g; 6.67 mmol) dissolved in 9.6 mL n-pentane was ethenolyzed in the presence of catalyst X008 (0.1 M in benzene; 66.4 ?L; 0.1 mol %). Bulb-to-bulb distillation (8.5-9.0?10.sup.?2 mbar; 60-61? C.) afforded the title compound as a colorless oil (2.10 g; 11.40 mmol; yield: 86%).

[0145] .sup.1H-NMR analysis of the crude products before bulb-to-bulb distillation both for Example 16 and Example 17 showed that crude products consisted of ca. 95% monomer (3i; 11a) and residues of unreacted homodimer (14i; 18a). No signs of undesired side reactions during the ethenolysis or workup were observed. NMR spectra of bulb-to-bulb distilled materials correspond to those of pure 3i and 11a.