Syntheses of Z-olefin-containing lepidopteran insect pheromones

Patent metadata

Field	Value
Publication number	US-8987531-B2
Application number	US-201313785101-A
Country	US
Kind code	B2
Filing date	Mar 5, 2013
Priority date	Mar 5, 2012
Publication date	Mar 24, 2015
Grant date	Mar 24, 2015

Abstract

The present invention is directed to methods of synthesizing insect pheromones, particularly lepidopteran insect pheromones, their precursors and derivatives from inexpensive, readily available starting materials using olefin metathesis catalysis.

First claim

What is claimed:

1. A method of synthesizing a lepidopteran insect pheromone containing a Z-olefin metathesis product, said method comprising:
(a) cross-metathesizing (i) a terminal olefin and an internal olefin or (ii) two terminal olefins in the presence of a hindered ruthenium metathesis catalyst to form the insect pheromone containing Z-olefin metathesis product and a side product;
the hindered metathesis catalyst comprising a C—H activated olefin metathesis catalyst compound having a structure of Formula I:

wherein
X 1 is a t-butyl carboxylate or a nitrate;
L 1 is a carbene ligand having the structure of Formula (II):

wherein,
Q is ethylene (—CH 2 —CH 2 —);
R 1 is an adamantylene group, where R 1 links L 1 and M and, together with L 1 and M, form one or more cyclic groups, and wherein M, L 1 and R 1 form an M-R 1 -L 1 chelating ligand ring structure having a ring size of 5 atoms;
R 2 is 2,4,6-trimethyl phenyl (mesityl), 2,6-methylisopropylphenyl (MIPP), or 2,6-diisopropylphenyl (DIPP);
Y is O;
R 3 , R 4 , R 5 , and R 6 are each hydrogen;
n is 1; and
Z is alkyl.

2. The method of claim 1 , wherein R 2 is 2,4,6-trimethyl phenyl (mesityl) or 2,6-di-isopropylphenyl (DIPP); X 1 is nitrate or pivalate; and (Z) n is isopropyl.

3. The method of claim 1 , the C—H activated olefin metathesis catalyst compound comprising at least one of the following:

4. The method of claim 1 , wherein the C—H activated olefin metathesis catalyst compound comprises:

5. The method of claim 1 , further comprising (b) applying conditions sufficient to remove the side product from the metathesis product the conditions comprising (a) providing sufficiently high temperature or sufficiently low pressure, or both, so as to preferentially volatilize the side product from the metathesis product or vice versa; (b) extracting the side product from the metathesis product with a solvent or (c) chromatographic methods.

6. The method of claim 1 , the method comprising cross-metathesizing a terminal olefin and an internal olefin.

7. The method of claim 1 , the method comprising cross-metathesizing two terminal olefins.

8. The method of claim 5 , the method comprising applying the conditions sufficient to remove the side product from the metathesis product during the cross-metathesis reaction.

9. The method of claim 1 , wherein at least one of the starting olefins comprises an alkenyl ester which contains 2 to 22 carbons; alkenyl halide which contains 2 to 22 carbons; alpha, omega-alkenyl diester which contains 4 to 40 carbons; alpha, omega-alkenyl dihalide which contains 4 to 40 carbons; alkene which contains 2 to 44 carbons; alkenol which contains 2 to 22 carbons; alkene diol of which contains 4 to 40 carbons; or a derivative thereof.

10. The method of claim 1 , wherein the terminal olefin has a —CH═CH 2 motif and the internal olefin has a —CH═CH— motif.

11. The method of claim 1 , wherein at least one of the starting olefins comprises a terminal or internal olefin optionally comprising at least one aldehyde, amino, amide, hydroxyl or protected hydroxyl, branched alkyl, alkylaryl, alkylheteroaryl, C 1-6 alkenyl, C 1-6 alkynyl, C 1-6 alkoxy, azide, —N—C(O)—C 1-6 alkyl, —O—C(O)—C 1-6 alkyl, —N—C(O)—O—C 1-6 alkyl, —O—C(O)—O—C 1-6 alkyl, aryl, carboxylic acid, carboxy ester, cyano, epoxide, fluorinated or perfluorinated alkyl, halo (fluorine, chloro, bromo, iodo), heterocyclyl, heteroaryl, or ketone.

12. The method of claim 1 , wherein at least one of the starting olefins comprises allyl acetate, 2-(allyloxy)ethanol, 1-propene, 1-butene, 1-pentene, 1-hexene, 3-hexene, trans-1,4-hexadiene, 1-heptene, 1-octene, 1-nonene, 5-decene, 2-buten-1-ol, 2-butenylacetate, 2-butenylbromide, 2-butenylchloride, 2-butenyliodide, 4-pentenol, 4-pentenyl acetate, 4-pentenyl bromide, 4-pentenyl chloride, 4-pentenyl iodide, 5-hexen-1-ol, 5-hexenyl acetate, 5-hexenyl bromide, 5-hexenyl chloride, 5-hexenyl iodide, 3-hexenol, 3-hexenyl acetate, 1-bromo-3-hexene, 1-chloro-3-hexene, 8-nonen-1-ol, 8-nonen-1-yl acetate, 8-nonen-1-yl bromide, 8-nonen-1-yl chloride, 8-nonen-1-yl iodide, 1-dodecene, oleyl alcohol (cis-9-octadecen-1-ol), oleyl acetate (cis-9-octadecen-1-yl acetate), oleyl bromide (cis-9-octadecen-1-yl bromide), oleyl chloride (cis-9-octadecen-1-yl chloride), oleyl iodide (cis-9-octadecen-1-yl iodide), elaidyl alcohol (9E-octadecen-1-ol), elaidyl acetate (9E-octadecen-1-yl acetate), 11-docosene, 10-methyl undecenoate, 11-eicosenol, methyl 5-eicosenoate, 5-eicosneyl acetate, methyl 11-eicosenoate, 11-eicosenyl acetate, palmitoleyl alcohol (cis-9-hexadecen-1-ol), erucyl alcohol (cis-13-docosen-1-ol), erucyl acetate, erucyl bromide, or erucyl chloride.

13. The method of claim 1 , wherein the side product comprises a C 2 -C 10 olefin.

14. The method of claim 1 , wherein the metathesis product comprises a compound having the formula: 3, 5, 5-Ac, 6-10, 12-13, 15-17, 19-22, or 24:

15. The method of claim 5 , wherein the metathesis product is further purified by distillation or chromatography.

16. The method of claim 1 , wherein the cross-metathesis reaction is conducted at at least one temperature in a range of from about 18° C. to about 200° C.

17. The method of claim 1 , wherein the cis:trans isomeric ratio of the Z-olefin metathesis product is greater than 90:10.

18. The method of claim 5 , the low pressure being less than about 50 mm Hg.

19. The method of claim 1 , with the proviso that the reaction does not comprise the cross-metathesis of 1-hexene and 8-nonenyl acetate to form (Z)-tridec-8-en-1-yl acetate (17).

20. The method of claim 1 , said method comprising:
(a) cross-metathesizing oleyl alcohol and 1-hexene in the presence of the hindered ruthenium metathesis catalyst to form (Z)-tetradec-9-en-1-ol (3) and 1-decene; or
(b) cross-metathesizing 11-eicosenol and and 1-hexene in the presence of the hindered ruthenium metathesis catalyst to form (Z)-hexadec-11-en-1-ol (5) and 1-decene; and optionally further comprising (1) optionally separating the (Z)-hexadec-11-en-1-ol (5) from the 1-decene, and acetylating the the (Z)-hexadec-11-en-1-ol (5) to form (Z)-hexadec-11-en-1-yl acetate (5-Ac); or (2) optionally separating the (Z)-hexadec-11-en-1-ol (5) from the 1-decene, and oxidizing the (Z)-hexadec-11-en-1-ol (5) to form (Z)-hexadec-11-enal (6); or
(c) cross-metathesizing oleyl alcohol and and 1-butene in the presence of the hindered ruthenium metathesis catalyst to form (Z)-dodec-9-en-1-ol (7) and 1-decene; and optionally further comprising optionally separating the (Z)-dodec-9-en-1-ol (7) from the 1-decene, and acetylating the (Z)-dodec-9-en-1-ol (7) to form (Z)-dodec-9-en-1-yl acetate (8); or
(d) cross-metathesizing 11-eicosenol and and 1-butene in the presence of the hindered ruthenium metathesis catalyst to form (Z)-tetradec-11-en-1-ol (9) and 1-de

Assignees

• California Inst Of Techn

Inventors

• Grubbs Robert H
• Herbert Myles B
• Wickens Zachary K
• Marx Vanessa M
• Keitz Benjamin K
• Endo Koji

Classifications

• C07C67/08

  by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds · CPC title

• C07C67/293

  by isomerisation; by change of size of the carbon skeleton · CPC title

• C07C29/00 Primary

  Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring · CPC title

• C07C29/32

  increasing the number of carbon atoms by reactions without formation of -OH groups · CPC title

• C07C67/28

  by modifying the hydroxylic moiety of the ester, such modification not being an introduction of an ester group · CPC title