Claims
- 1. A method of synthesizing aliphatic acids containing 1,5-isoprenoid diene moieties comprising the steps of:
- a. forming a dicopper(I) dienolate of an aliphatic .alpha.,.beta.-unsaturated acid by reaction of the .alpha.,.beta.-unsaturated acid or sodium salt thereof first with lithium dialkyl amide and then with cuprous iodide;
- b. selectively alkylating the dicopper(I) dienolate at the gamma position with an allylic electrophile having the general formula ##STR26## where X .dbd. halide or sulfonate and R.sub.1 -R.sub.5 are hydrogen or C.sub.1 -C.sub.10 aliphatic or cycloaliphatic groups; and
- c. isolalating the alkylation production from the reaction mixture of step (b).
- 2. The method of claim 1 wherein the dicopper(I) dienolate of an aliphatic .alpha.,.beta.-unsaturated acid is formed in the steps comprising:
- a. reacting at a temperature of about 0.degree. a molar equivalent of lithium dialkyl amide with a one-half molar equivalent of the aliphatic .alpha.,.beta.-unsaturated acid or one molar equivalent of the sodium salt thereof;
- b. adding at a temperature of about -80.degree. cuprous iodide in the amount of two molar equivalents relative to the dienolate product of step (a); and
- c. maintaining the reaction mixture of step (b) at -80.degree. for 1 hour with rapid stirring.
- 3. The method of claim 1 wherein the aliphatic .alpha.,.beta.-unsaturated acid has the general formula ##STR27## where R.sub.1, R.sub.2, R.sub.3 are hydrogen or a C.sub.1 - C.sub.5 aliphatic group.
- 4. The method of claim 1 wherein the aliphatic .alpha.,.beta.-unsaturated acid is selected from the group consisting of cis- and trans-3-methyl-2-hexenoic acid, crotonic acid, senecioic acid, tiglic acid and angelic acid.
- 5. The method of claim 3 wherein the allylic electrophile is selected from the group consisting of allyl bromide, 3,3-dimethallyl bromide, trans-1-bromo-2-methyl-2-butene, 2-methyl-2-propenyl chloride, geranyl bromide and 2-(1'-methylcyclohexen-4'-yl)-2-propenyl bromide.
- 6. In the method of claim 3 wherein the reaction mixture from the alkylation step contains acid products of C.sub.10 or less, the additional steps comprising:
- a. quenching the reaction mixture with water and removing precipitated copper salts;
- b. adjusting the reaction mixture to about pH 12 and removing additional precipitated copper salts;
- c. extracting the mixture with ether to remove non-acidic organic residues;
- d. acidifying the reaction mixture to about pH 3 and extracting the product acid with ether; and
- e. isolating the product acid by drying the ether extract and by evaporating the ether.
- 7. In the method of claim 3 wherein the reaction mixture from the alkylation step contains acid products of C.sub.11 - C.sub.14, the additional steps comprising:
- a. quenching the alkylation reaction mixture with dilute hydrochloric acid and adjusting to about pH 3 and removing precipitated copper salts;
- b. extracting the product acid with ether; and
- c. isolating the product acid by drying the ether extract and removing ether by evaporation.
- 8. In the method of claim 3 wherein the reaction mixture from the alkylation step contains acid products of C.sub.15 and higher, the additional steps comprising:
- a. quenching the alkylation reaction mixture with dilute hydrochloric acid and adding saturated ammonium chloride solution to dissolve all of the copper salts;
- b. extracting product acid with ether; and
- c. isolating the product acid by drying the ether extract and by removing ether by evaporation.
- 9. The method of synthesizing farnesoic acid comprising the steps of:
- a. forming the dicopper(I) dienolate of senecioic acid;
- b. selectively alkylating the dicopper(I) at the gamma position with geranyl bromide; and
- c. isolating farnesoic acid from the reaction mixture of step (b).
- 10. The method of synthesizing geranoic acid comprising the steps of:
- a. forming the dicopper(I) dienolate of senecioic acid;
- b. selectively alkylating the dicopper(I) dienolate at the gamma position with 3,3-dimethallyl bromide; and
- c. isolating geranoic acid from the reaction mixture of step (b).
- 11. The compound 2-(1'-penten-2'-yl)-4-penetenoic acid having the formula ##STR28##
- 12. The compound 3-propyl-2,6-heptadienoic acid having the formula ##STR29##
- 13. The compound 2,5-dimethyl-2-vinyl-4-hexenoic acid having the formula ##STR30##
- 14. The compound (E)-2,5,6-trimethyl-2,6-heptadienoic acid having the formula ##STR31##
- 15. The compound (E,E)-2,6-dimethyl-2,6-octadienoic acid having the formula ##STR32##
- 16. The compound (E,Z)-2,6-dimethyl-2,6-Octadienoic acid having the formula ##STR33##
- 17. The compound (E,E)-2,6-dimethyl-2,6-undecadienoic acid having the formula ##STR34##
- 18. The compound 2,4-dimethyl-2-vinyl-4-pentenoic acid having the formula ##STR35##
Government Interests
The invention described herein was made in the course of work under a grant from the Department of Health, Education, and Welfare, and the Government has rights in this invention pursuant to Grant No. MPS-73-08691 awarded by the National Science Foundation.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
3971827 |
Baran et al. |
Jul 1976 |
|
Non-Patent Literature Citations (1)
Entry |
Katzenellenbogen, J., Journal of the American Chemical Society, vol. 96, pp. 5662-5663, (1974). |