A METHOD FOR PREPARING OPTICALLY ACTIVE CARBONYL COMPOUND

Abstract

The present invention discloses a method for preparing optically active carbonyl compound, comprising the following steps: under the catalysis of chiral amine salt and transition metal catalysts, with hydrogen and catalytic amount of dihydropyridine compound as hydrogen source, use , -unsaturated aldehydes or , -unsaturated troponoid compounds to conduct asymmetric catalytic reaction to obtain the optically active carbonyl compound. This method comes in moderate reaction condition, simple operation, and catalytic amount of dihydropyridine compounds usage, the target product is easy to be separated and purified from the reaction system, and the metal catalyst can be recycled, it is economical.

Claims

1. A method for preparing an optically active carbonyl compound, the method being characterized by and comprising the following steps: conducting asymmetric catalytic reaction to obtain the optically active carbonyl compound under catalysis of chiral amine salt and transition metal catalysts, with hydrogen and catalytic amount of dihydropyridine compound as hydrogen source, using , -unsaturated aldehydes or , -unsaturated troponoid compounds; wherein the structures of the , -unsaturated aldehydes or , -unsaturated troponoid compounds are as shown in formula (I): ##STR00030## the structure of the optically active carbonyl compound is as shown in formula (II): ##STR00031## wherein in formulas (I)(II), R.sup.1, R.sup.2 and R.sup.3 are independently selected from hydrogen, halogen, alkyl, heteroaryl, alkoxy or acylamino, wherein acylamino refers to substituents containing CONH or NHCO, and R.sup.1 is different from R.sup.2; the structures of the chiral amine salt are as shown in formula (IV) or (V): ##STR00032## R.sup.4 is selected from substituted or unsubstituted alkyl, the alkyl refers to alkyl containing ether or polyether, alkyl containing ester or polyester, alkyl containing acylamino or polyamide, or polymer chain alkyl containing mixture of ether, ester and acylamino, wherein acylamino refers to substituents containing CONH or NHCO; X means solidified acid; * means asymmetric carbon atom.

2. The method for preparing an optically active carbonyl compound according to claim 1, which is characterized in that: in the R.sup.1, R.sup.2 and R.sup.3, alkyl is alkyl containing 1 to 30 carbon atoms; heteroaryl is aromatic heterocyclic aryls containing 3 to 9 carbon atoms; alkoxy is cyclo-alkoxy or linear or branched alkoxys containing 1 to 30 carbon atoms, and these alkoxys can be substituted by fluorine, chlorine, bromine, iodine, hydroxy or aryl; acylaminos are acylaminos containing 1 to 20 carbon atoms.

3. The method for preparing an optically active carbonyl compound according to claim 2, which is characterized in that: the heteroaryl is: 2-furyl, 2-pyrryl, 2-thienyl, 2-pyridyl, 2-indolyl, 3-furyl, 3-pyrryl, 3-thienyl, 3-pyridyl, or 3-indolyl; the alkoxies are: methoxyl, ethyoxyl, n-propoxyethyl, isopropoxy, n-butoxy, isobutoxy, 2-butoxy, tert-butoxy, n-pentyloxy, 2-pentyloxy, 2-pentyloxy, tert-pentyloxy, n-hexyloxy, cyclopropoxy, cyclobutoxy, cyclopentyloxy, cyclohexyloxy, heptyloxy, octyloxy, nonyloxy, decyloxy, undecyloxy, dodecyloxy, tridecyloxy, tetradecyloxy, pentadecyloxy, hexadecyloxy, heptadecyloxy, octadecyloxy, nonadecyloxy, eicosyloxy, phenylmethoxy, 1-phenylethoxy, or 2-phenylethoxy; the acylaminos can be: formamido-, acetamido-, propionamido-, butyrylamino, valeramide-amino, hexanamide-amino, cyclopentylcarboxyl amine, cyclo-hexanamide-amino, or phenyl-formamido-, phenyl-acetamido- or naphthalene carboxamide amino.

4. The method for preparing an optically active carbonyl compound according to claim 1, which is characterized in that: the R.sup.1 and R.sup.2 form 5-15-member ring together with atoms connected with them, or R.sup.1 and R.sup.3 form 5-15-member ring together with atoms connected with them, or R.sup.2 and R.sup.3 form 5-15-member ring together with atoms connected with them.

5. The method for preparing an optically active carbonyl compound according to claim 1, which is characterized in that: the compound (I) is selected from compounds with the following structures: ##STR00033## ##STR00034## ##STR00035## ##STR00036##

6. The method for preparing an optically active carbonyl compound according to claim 1, which is characterized in that: the R.sup.4 is substituted or unsubstituted C.sub.1C.sub.20 alkyls; the substituents on the C.sub.1C.sub.20 alkyls include fluorine, chlorine, bromine, iodine, alkoxy, hydroxy or aryl.

7. The method for preparing an optically active carbonyl compound according to claim 6, which is characterized in that: the R.sup.4 is methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl, 2-butyl, tertiary butyl, n-amyl, 2-pentyl, 3-pentyl, tertiary pentyl, n-hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, heptyl, octyl, nonyl, decyl, 1-indanyl, 2-indanyl, 1-1,2,3,4-tetralyl, or 2-1,2,3,4-tetralyl.

8. The method for preparing an optically active carbonyl compound according to claim 1, which is characterized in that: the alkyl represented by the R.sup.4 is interrupted by one or more of the following radicals: O, COO and CONH; wherein the alkyl interrupted by O is alkyl containing ether or polyether, the alkyl interrupted by COO is alkyl containing ester or polyester, and the alkyl interrupted by CONH is alkyl containing acylamino or polyamide.

9. The method for preparing an optically active carbonyl compound according to claim 1, which is characterized in that: the X is selected from one of formic acid, acetic acid, propionic acid, trifluoroacetic acid, trichloroacetic acid, substituted or unsubstituted benzoic acid, mandelic acid, citric acid, substituted or unsubstituted 1,1-binaphthyl-2,2-diyl hydrogen-phosphate or from mixture of two or more of them.

10. The method for preparing an optically active carbonyl compound according to claim 1, which is characterized in that: the transition metal catalyst contains ruthenium compound, rhodium compound and indium compound.

11. The method for preparing an optically active carbonyl compound according to claim 1, which is characterized in that: the transition metal catalyst is selected from RuCl.sub.2(PPh.sub.3).sub.3, [Ru(p-cymene)Cl.sub.2], [Ru(p-cymene)I.sub.2].sub.2, RhCl.sub.3, Rh.sub.2(OAc).sub.4, Rh(CO).sub.2acac, Rh(cod)Cl.sub.2, Rh.sub.4(CO).sub.12, Ir.sub.4(CO).sub.12, Ir(cod)Cl.sub.2 or [Ir(cod)OMe].sub.2.

12. The method for preparing an optically active carbonyl compound according to claim 1, which is characterized in that: the dihydropyridine compound is selected from one of the following compounds: ##STR00037##

13. The method for preparing an optically active carbonyl compound according to claim 1, which is characterized in that: the solvent of the asymmetric catalytic hydrogenation reaction is methyl tertiary butyl ether, isopropyl ether, cyclopentylmethylether, ethylene glycol dimethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, methylbenzene, n-hexane, dichloromethane, 1,2-dichloroethane, methanol, ethanol, tertiary butanol, tert-amyl alcohol, isopropanol, water or mixture of these solvents.

14. The method for preparing an optically active carbonyl compound according to claim 1, which is characterized in that: the temperature of the asymmetric catalytic hydrogenation reaction is 20120 C.

15. The method for preparing an optically active carbonyl compound according to claim 1, which is characterized in that: the hydrogen pressure in the asymmetric catalytic hydrogenation reaction is 10600 bar.

16. The method for preparing an optically active carbonyl compound according to claim 1, which is characterized in that: the dosage of the transition metal catalyst is 0.01 mol % to 20 mol % of , -unsaturated aldehydes or , -unsaturated troponoid reagents.

17. The method for preparing an optically active carbonyl compound according to claim 1, which is characterized in that: the dosage of the chiral amine salt is 0.1 mol % to 20 mol % of , -unsaturated aldehydes or , -unsaturated troponoid reagents.

18. The method for preparing an optically active carbonyl compound according to claim 1, which is characterized in that: the dosage of the dihydropyridine compound is 0.2 mol % to 40 mol % of , -unsaturated aldehydes or , -unsaturated troponoid reagents.

Description

SPECIFIC EMBODIMENTS OF THE INVENTION

[0046] Described below is the implementation process of the method for preparing optically active carbonyl compounds provided by the present invention as illustrated by specific embodiments, however, the present invention is not limited to these embodiments only, to technicians in this filed, any equivalent replacement and modification etc. shall fall within the scope of protection of the present invention.

Embodiments 116

[0047] Common method for preparing optically active citronellal (results listed in Table 1) are as follows: in the pressure reactor of 250 mL, under nitrogen protection condition, metal catalyst [Ru(p-cymene)I.sub.2].sub.2 (4.8 mg, 0.005 mol), chiral amine salt (0.01 mol), dihydropyridine compound (0.05 mol), a mixture of geranial and neral (totally 15.2 g, 0.1 mol) and reactive solvant (110 mL) were added, the reaction mixture was stirred for 20 minutes under room temperature condition, then the system was heated up to 55 C., and the hydrogen in the reactor was replaced with 3 bar hydrogen, such hydrogen replacements were repeated, then hydrogen was quickly charged to the reactor to 100 bar pressure reaction, after 46 hours, after the material reaction is completed as proved by gas chromatography analysis, the reaction was stopped and cooled down to room temperature, the hydrogen in the reactor was slowly discharged, and the residual hydrogen in the reactor was replaced with nitrogen. The optical purity (i.e., enantiomeric excess value, ee value) of the product was analyzed by gas chromatography.

TABLE-US-00001 TABLE 1 Reaction results of embodiments 1~16 Main config- Chiral amine salt uration Embodi- Geranial: Chiral Dihydropyridine of Yield ee ment neral amine Acid compound Solvent citronellal (%) (%) 1 95:5 31a CF.sub.3COOH [00013] THF S 12 42 2 95:5 31b CF.sub.3COOH [00014] CH.sub.2Cl.sub.2 S 19 38 3 95:5 31c CF.sub.3COOH [00015] THF:CH.sub.2Cl.sub.2 (1:5) S 81 18 4 95:5 31d CF.sub.3COOH [00016] THF:CH.sub.2Cl.sub.2 (1:3) S 83 30 5 95:5 31e CF.sub.3COOH [00017] THF:CH.sub.2Cl.sub.2 (1:3) S 82 35 6 95:5 31f CF.sub.3COOH [00018] THF:CH.sub.2Cl.sub.2 (1:3) S 81 32 7 90:10 31g CF.sub.3COOH [00019] THF:CH.sub.2Cl.sub.2 (1:3) S 89 55 8 10:90 31j CF.sub.3COOH [00020] THF:CH.sub.2Cl.sub.2 (1:3) R 82 80 9 5:95 31j CF.sub.3COOH [00021] THF:CH.sub.2Cl.sub.2 (1:3) R 82 90 10 95:5 31h CF.sub.3COOH [00022] THF:CH.sub.2Cl.sub.2 (1:3) S 80 72 11 95:5 31i CF.sub.3COOH [00023] THF:CH.sub.2Cl.sub.2 (1:3) S 78 73 12 95:5 31j CF.sub.3COOH [00024] THF:CH.sub.2Cl.sub.2 (1:3) S 81 90 13 95:5 31k CF.sub.3COOH [00025] THF:CH.sub.2Cl.sub.2 (1:3) S 81 65 14 95:5 31l CF.sub.3COOH [00026] THF:CH.sub.2Cl.sub.2 (1:3) S 81 80 15 95:5 31m CF.sub.3COOH [00027] THF:CH.sub.2Cl.sub.2 (1:3) S 81 44 16 95:5 31n CF.sub.3COOH [00028] THF:CH.sub.2Cl.sub.2 (1:3) S 72 21

Embodiments 1720

[0048] Embodiments 1720 were implemented in the same way as Embodiment 9, the difference was the different metal catalyst, and the results are listed in Table 2:

TABLE-US-00002 TABLE 2 Reaction results of embodiments 17~20 Main configuration Yield ee Embodiment Metal catalyst of citronellal (%) (%) 17 [Ru(p-cymene)Cl.sub.2] R 35 81 18 Rh(CO).sub.2acac R 16 28 19 [Ir(cod)OMe].sub.2 R 86 60 20 RuCl.sub.2(PPh.sub.3).sub.3 R 5 0

Embodiments 2126

[0049] Embodiments 2126 were implemented in the same way as Embodiment 9, the difference was the different acid used by the chiral amine salt, and the results were listed in Table 3:

TABLE-US-00003 TABLE 3 Reaction results of embodiments 21~26 Main configuration of Yield ee Embodiment Acid citronellal (%) (%) 21 HCl R 75 11 22 Mandelic acid R 77 78 23 Tartaric acid R 61 45 24 Citric acid R 80 73 25 Parachlorobenzoic- R 80 65 acid 26 1,1-binaphthyl-2, R 75 66 2-diyl hydrogen-phosphate

Embodiments 2730

[0050] Embodiments 2730 were implemented in the same way as Embodiment 9, the difference was the dosage of the chiral amine salt, and the results were listed in Table 4:

TABLE-US-00004 TABLE 4 Reaction results of embodiments 27~30 Trifluoroacetic Main 32j, acid, configuration Yield ee Embodiment mol % mol % of citronellal (%) (%) 27 1 1 R 63 88 28 5 5 R 72 90 29 15 15 R 82 90 30 20 20 R 82 90

Embodiments 3134

[0051] Embodiments 3134 were implemented in the same way as Embodiment 9, the difference was the different dosage of dihydropyridine compound, and the results were listed in Table 5:

TABLE-US-00005 TABLE 5 Reaction results of embodiments 31~34 Embodiment [00029] Main configuration of citronellal Yield (%) ee (%) 31 1 R 55 78 32 10 R 72 90 33 15 R 71 90 34 20 R 72 89

Embodiments 3540

[0052] Embodiments 3540 were implemented in the same way as Embodiment 9, the difference was the different metal catalyst dosage or different reaction hydrogen pressure, and the results are listed in Table 6:

TABLE-US-00006 TABLE 6 Reaction results of embodiments 35~40 Hydrogen Main [Ru(p-cymene)I.sub.2] pressure configuration Yield ee Embodiment mol % bar of citronellal (%) (%) 35 1.25 400 R 85 89 36 2.5 200 R 79 88 37 10 80 R 88 88 38 2.5 100 R 66 90 39 5 80 R 79 90 40 5 300 R 95 90

Embodiments 4143

[0053] Embodiments 4143 were embodiments of metal catalyst recycling experiments, the experimental conditions were the same as Embodiment 9.

[0054] The operation process was as follows: after the reaction of Embodiment 9 was stopped, the reaction was cooled down to room temperature, the hydrogen in the reactor was slowly discharged, and the residual hydrogen in the reactor was replaced with nitrogen. The optical purity (i.e., enantiomeric excess value, ee value) of the product was analyzed by gas chromatography. The solvent was removed through reduced pressure distillation and the product was obtained through rectification, n-heptane was added to the residual, filtered, leached with cold n-heptane and methyl alcohol sequentially, and finally vacuum-dried to obtain recycled catalyst. The recycling data are listed in Table 7:

TABLE-US-00007 TABLE 7 Recycling Main configuration of Yield ee Embodiment times citronellal (%) (%) 41 1st time R 82 90 42 2nd time R 81 90 43 3rd time R 82 88

[0055] It can be seen from Table 7 that the yield and ee value of the recycled catalyst through simple recycling processing have no obvious decrease.