FUNCTIONALISATION OF 1,3-ALPHA-DIENES (II)

Abstract

The present invention relates to the functionalisation of specific 1,3-alpha-dienes (by hydroboration). These functionalized 1,3-alpha-dienes are important intermediates in organic synthesis (especially in the synthesis of carotenoids, vitamin A and/or vitamin A derivatives).

Claims

1. A process, wherein a compound of formula (I) ##STR00016## wherein R is ##STR00017## (wherein the asterix shows the connecting bond) is reacted with a borane tetrahydrofuran complex and then oxidized to the corresponding alcohol.

2. Process according to claim 1, wherein the process is carried out in an inert solvent.

3. Process according to claim 1, wherein the process is carried out in THF and optionally at least one other solvent.

4. Process according to claim 1, wherein the compound of formula (Ia) ##STR00018## is used as starting material.

5. Process according to claim 1, wherein the compound of formula (Ib) ##STR00019## is used as starting material.

6. Process according to claim 1, wherein the compound of formula (Ic) ##STR00020## is used as starting material.

7. Process according to claim 1, wherein the borane tetrahydrofuran complex is added to the reaction mixture in an equimolar amount in regard to the compound of formula (I).

8. Process according to claim 1, wherein the borane tetrahydrofuran complex is added in a slight excess (between 1.1-2 eq) in regard to the compound of formula (I).

9. Process according to claim 1, wherein the process is carried out at temperature range of from −10° C.-30° C.

10. Process according to claim 1, wherein the process is carried out at temperature range of from −5° C. to 25° C.

11. Process according to claim 1, wherein the process is carried out under an inert gas atmosphere (usually N.sub.2 gas).

12. Process according to claim 1, wherein in a second step the reaction product is converted into the alcohols via an oxidative cleavage in the presence of hydrogen peroxide and a base.

13. Compound of formula (IIb) ##STR00021##

Description

EXAMPLES

Example 1

[0050] In a 25-ml flask under inert gas atmosphere, borane tetrahydrofuran complex (1M, 1.666 ml, 1.666 mmol) was cooled to 0° C. Cyclohexene (0.169 ml, 1.666 mmol) in THF dry (4.00 ml) was added within 5 min. After 10 min a turbid white reaction mixture was obtained and stirring was continued for 1 h at 0° C. Then, cyclo-α-farnesene (compound of formula (Ia)) (200 mg, 0.833 mmol) in THF dry (2.00 ml) was added. The reaction mixture was allowed to warm to room temperature and was monitored by HPLC. After 1 h 15 min full conversion was observed. Subsequently sodium hydroxide (5.00 ml, 9.99 mmol) and hydrogen peroxide (30%, 0.595 ml, 5.83 mmol) were added and stirring was continued for another hour. Then, the reaction mixture was diluted with diethyl ether (20 mi), transferred to a separation funnel and washed with deionized water. The layers were separated, and the organic layer was washed with brine. The aqueous layers were re-extracted with diethyl ether. The combined organic layers were dried over magnesium sulfate, filtered and evaporated under reduced pressure. The crude product (compound of formula (IIa)) was obtained as colorless oil (263 mg, content by qNMR: 56.4 wt %, 100% conversion, 80.0% yield).

Example 2

[0051] In a 25-ml flask under inert gas atmosphere, borane tetrahydrofuran complex (1M, 1.869 ml, 1.869 mmol) was cooled to 0° C. Cyclohexene (0.190 ml, 1.869 mmol) in THF dry (4.50 ml) was added within 5 min. After 10 min a turbid white reaction mixture was obtained and stirring was continued for 1 h at 0° C. Then, α-farnesene (compound of formula (Ic)) (200 mg, 0.935 mmol) in THF dry (2.25 ml) was added. The reaction mixture was allowed to warm to room temperature. After 2.5 hours, subsequently sodium hydroxide (5.61 ml, 11.22 mmol) and hydrogen peroxide (30%, 0.668 ml, 6.54 mmol) were added and stirring was continued for another hour. Then, the reaction mixture was diluted with diethyl ether (20 ml), transferred to a separation funnel and washed with deionized water. The layers were separated, and the organic layer was washed with brine. The aqueous layers were re-extracted with diethyl ether. The combined organic layers were dried over magnesium sulfate, filtered and evaporated under reduced pressure. The crude product (compound of formula (IIc)) was obtained as colorless oil (416 mg, content by qNMR: 42.0 wt %, 91.9% conversion, 84.0% yield).

Example 3

[0052] In a 25-ml flask under inert gas atmosphere, borane tetrahydrofuran complex (1M, 2.433 ml, 2.433 mmol) was cooled to 0° C. Cyclohexene (0.345 ml, 3.41 mmol) in THF dry (6.25 ml) was added within 5 min. After 15 min a turbid white reaction mixture was obtained and stirring was continued for 1 h at 0° C. Then, 1,3-diene (compound or formula (Ib)) (500 mg, 1.703 mmol) in THF dry (2.50 ml) was added. The reaction mixture was allowed to warm to room temperature. After 1.5 hours, subsequently sodium hydroxide (5.11 ml, 10.22 mmol) and hydrogen peroxide (30%, 0.609 ml, 5.96 mmol) were added and stirring was continued for another hour. Then, the reaction mixture was diluted with diethyl ether (20 ml), transferred to a separation funnel and washed with deionized water. The layers were separated, and the organic layer was washed with brine. The aqueous layers were re-extracted with diethyl ether. The combined organic layers were dried over magnesium sulfate, filtered and evaporated under reduced pressure. The crude product (compound of formula (IIb) was obtained as colorless oil (892 mg, content by qNMR: 36.4 wt %, 90.3% conversion, 66.4% yield).