Process for preparing cyclic alpha-keto alcohols from cyclic alpha-keto enols

Patent metadata

Field	Value
Publication number	US-10017464-B2
Application number	US-201515502816-A
Country	US
Kind code	B2
Filing date	Jul 31, 2015
Priority date	Aug 12, 2014
Publication date	Jul 10, 2018
Grant date	Jul 10, 2018

Abstract

The invention relates to a method for preparing a cyclic α-ketoalcohol, particularly a 6-hydroxycyclohexenone from a cyclic α-ketoenol, particularly a 6-hydroxycyclohexadienone, using a reducing agent. This reducing agent is selected from hydrogen gas; a secondary alcohol, formic acid and the salts of formic acid or a mixture of at least two representatives of these compound classes. The invention further comprises the use of an α-ketoenol, in particular a 6-hydroxycyclohexadienone, as intermediate for preparing astaxanthin.

First claim

The invention claimed is:

1. A method for preparing a 6-hydroxycyclohexenone selected from the group consisting of 6-hydroxy-3-[(1E/Z)-3-hydroxy-3-methylpenta-1,4-dienyl]-2,4,4-trimethylcyclohex-2-en-1-one of the formula (1a) and 6-hydroxy-3-[(1E/Z,3E/Z)-5-hydroxy-3-methylpenta-1,3-dienyl]-2,4,4-trimethylcyclohex-2-en-1-one of the formula (1b)

in which the asymmetric center in position 6 is racemic or has (S) or (R) configuration, wherein a 6-hydroxycyclohexadienone selected from the group consisting of 6-hydroxy-3-[(1E/Z)-3-hydroxy-3-methylpenta-1,4-dienyl]-2,4,4-trimethylcyclohexa-2,5-dien-1-one of the formula (2a) and 6-hydroxy-3-[(1E/Z,3E/Z)-5-hydroxy-3-methylpenta-1,3-dienyl]-2,4,4-trimethylcyclohexa-2,5-dien-1-one of the formula (2b)

is reacted non-stereoselectively or stereoselectively with a reducing agent.

2. The method according to claim 1 , wherein the reducing agent is at least one compound selected from the group consisting of hydrogen gas; a secondary alcohol; formic acid and the salts of formic acid.

3. The method according to claim 1 , wherein the reducing agent is at least one compound selected from the group consisting of hydrogen gas; isopropanol or butan-2-ol; formic acid, an alkali metal, alkaline earth metal or ammonium formate or a mono-, di-, tri- or tetra(C1-C4)-alkylammonium formate.

4. The method according to claim 1 , wherein the 6-hydroxycyclohexadienone is reacted non-stereoselectively or stereoselectively with the reducing agent in the presence of a transition metal catalyst.

5. The method according to claim 1 , wherein the 6-hydroxycyclohexadienone is reacted non-stereoselectively or stereoselectively with the reducing agent in the presence of an achiral or optically active transition metal catalyst.

6. The method according to claim 3 , wherein the transition metal catalyst comprises a transition metal selected from the group consisting of Ti, Zr, Hf, V, Nb, Ta, Cr, Mo, W, Mn, Re, Fe, Ru, Os, Co, Rh, Ir, Ni, Pd, Pt, Cu, Ag and Au.

7. The method according to claim 3 , wherein the transition metal catalyst comprises a transition metal selected from the group consisting of Ru, Ir, Ni and Pd.

8. The method according to claim 3 , wherein the transition metal catalyst comprises at least one ligand selected from amines and/or phosphanes.

9. The method according to claim 5 , wherein the ligand is a phosphane of the general formula (3),

where R, R′ and R″ are each independently selected from the group consisting of at least one of the residues C1-C4-alkyl, phenyl, mono- up to tri-C1-C4-alkyl-substituted aryl and a triarylphosphane.

10. The method according to claim 5 , wherein the ligand is a phosphane of the general formula (3),

where R, R′ and R″ are each independently selected from the group consisting of a triphenylphosphane.

11. The method according to claim 3 , wherein the transition metal catalyst comprises at least one ligand selected from the group consisting of H 2 N—CH 2 —CH 2 —OH, MeHN—CH 2 —CH 2 —OH, H 2 N—CH 2 —CH 2 —NH 2 , TsNH—CH 2 —CH 2 —NH 2 , TsNH—CH 2 —CH 2 —NH—(CH 2 ) n —O m —(CH 2 ) o -aryl where n=1-4, m=0 or 1 and o=1-4 and aryl=phenyl or mono-, di-, tri-C1-C4-alkylphenyl, optically active compound.

12. The method according to claim 3 , wherein the transition metal catalyst comprises at least one ligand selected from the group consisting of an optically active amine.

13. The method according to claim 3 , wherein the transition metal catalyst comprises at least one ligand selected from the group consisting of H 2 N—CHPh-CHPh-OH, H 2 N—CHMe-CHPh-OH, MeHN—CHMe-CHPh-OH, TsNH—CHPh-CHPh-NH 2 , (1S,2S)—N-p-toluenesulfonyl-1,2-diphenylethylenediamine, (1R,2R)—N-p-toluenesulfonyl-1,2-diphenylethylenediamine, N-[(1S,2S)-1,2-diphenyl-2-(2-(4-methylbenzyloxy)ethylamino)ethyl]-4-methylbenzene sulfonamide, N-[(1R,2R)-1,2-diphenyl.

14. The method according to claim 5 , wherein the ligand is deprotonated.

15. The method according to claim 4 , wherein the transition metal is applied to a solid support comprising at least one substance selected from the group consisting of carbon, aluminum oxide and silicon dioxide.

16. The method according to claim 1 , wherein the 6-hydroxycyclohexadienone is reacted non-stereoselectively or stereoselectively with a reducing agent under basic conditions.

17. The method according to claim 1 , wherein the 6-hydroxycyclohexadienone is reacted non-stereoselectively or stereoselectively with a reducing agent in a liquid medium.

18. The method according to claim 17 , wherein said liquid medium comprising more than 50% by volume of at least one organic solvent and said organic solvent comprises at least one compound selected from the group consisting of dichloromethane, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran, ethylene carbonate, propylene carbonate, dimethylformamide, dimethyl sulfoxide, ethyl acetate, n-propyl acetate, toluene, xylene, heptane, hexane, pentane, N-methyl-2-pyrrolidone, dioxane, 2-methyltetrahydrofuran, methyl tert-butyl ether, diisopropyl ether, diethyl ether, di-n-butyl ether, acetonitrile and preferably from the group consisting of dichloromethane, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, tetrahydrofuran, acetonitrile, ethylene carbonate and propylene carbonate.

19. The method according to claim 1 , wherein the 6-hydroxycyclohexadienone is reacted non-stereoselectively or stereoselectively with a reducing agent at a temperature of 10° C. to 85° C.

20. An intermediate for preparing (3R/S, 3′R/S))-astaxanthin (4a), (3S, 3′S)-astaxanthin (4b), and/or (3R, 3′R)-astaxanthin (4c)

which comprises 6-hydroxy-3-[(1E/Z)-3-hydroxy-3-methylpenta-1,4-dienyl]-2,4,4-trimethylcyclohexa-2,5-dien-1-one of the formula (2a).

21. A process for preparing (3R/S, 3′R/S))-astaxanthin (4a), (3S,3′S)-astaxanthin (4b), and/or (3R, 3′R)-astaxanthin (4c)

which comprises utilizing the intermediate comprising 6-hydroxy-3-[(1E/Z)-3-hydroxy-3-methylpenta-1,4-dienyl]-2,4,4-trimethylcyclohexa-2,5-dien-1-one of the formula (2a) or 6-hydroxy-3-[(1E/Z,3E/Z)-5-hydroxy-3-methylpenta-1,3-dienyl]-2,4,4-trimethylcyclohexa-2,5-dien-1-one of the formula (2b).

22. The process as claimed in claim 21 , wherein the compound of formula (2b) is used.

Assignees

• Basf Se

Inventors

• Schäfer Bernd
• Siegel Wolfgang

Classifications

• C07C2601/16

  the ring being unsaturated · CPC title

• C07B2200/07

  Optical isomers · CPC title

• C07C403/24 Primary

  having side-chains substituted by six-membered non-aromatic rings, e.g. beta-carotene · CPC title

• C07C403/08 Primary

  by hydroxy groups · CPC title