Method for preparing optically active carbonyl compound

Patent metadata

Field	Value
Publication number	US-10065901-B2
Application number	US-201615565133-A
Country	US
Kind code	B2
Filing date	Nov 29, 2016
Priority date	Dec 30, 2015
Publication date	Sep 4, 2018
Grant date	Sep 4, 2018

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 α, β-unsaturated aldehydes or α, β-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.

First claim

The invention claimed is:

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 α, β-unsaturated aldehydes or α, β-unsaturated troponoid compounds;
wherein the structures of the α, β-unsaturated aldehydes or α, β-unsaturated troponoid compounds are as shown in formula (I):

the structure of the optically active carbonyl compound is as shown in formula (II):

wherein in formulas (I)˜(II), R 1 , R 2 and R 3 are independently selected from hydrogen, halogen, alkyl, heteroaryl, alkoxy or acylamino, wherein acylamino refers to substituents containing —CONH— or —NHCO—, and R 1 is different from R 2 ;
the structures of the chiral amine salt are as shown in formula (IV) or (V):

R 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 1 , R 2 and R 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 1 and R 2 form 5-15-member ring together with atoms connected with them, or R 1 and R 3 form 5-15-member ring together with atoms connected with them, or R 2 and R 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:

6. The method for preparing an optically active carbonyl compound according to claim 1 , which is characterized in that: the R 4 is substituted or unsubstituted C 1 ˜C 20 alkyls;
the substituents on the C 1 ˜C 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 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 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 2 (PPh 3 ) 3 , [Ru(p-cymene)Cl 2 ], [Ru(p-cymene)I 2 ] 2 , RhCl 3 , Rh 2 (OAc) 4 , Rh(CO) 2 acac, Rh(cod)Cl 2 , Rh 4 (CO) 12 , Ir 4 (CO) 12 , Ir(cod)Cl 2 or [Ir(cod)OMe] 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:

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 20˜120° 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 10˜600 bar.

16. The method for preparing an optically active carbonyl compound according to claim 1 , which is characterized in th

Assignees

• Zhejiang Nhu Co Ltd
• Shandong Nhu Pharmaceutical Co Ltd
• Univ Zhejiang

Inventors

• Zhou Yougui
• Yu Ming
• Yuan Jintao
• Zhao Lei
• Zhu Xiandong
• Yu Guangxiong
• Su Weiwei
• Shao Weikang
• Shi Xingxing
• Zhang Yin
• Feng Ming
• Chen Zhirong
• Li Haoran
• Zhang Yuhong

Classifications

• C07D333/22

  Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom · CPC title

• C07C201/12

  by reactions not involving the formation of nitro groups · CPC title

• C07C45/62 Primary

  by hydrogenation of carbon-to-carbon double or triple bonds · CPC title

• C07C2601/14

  The ring being saturated · CPC title

• B01J2531/827

  Iridium · CPC title