Method for preparing chiral alpha-hydroxy-beta-dicarbonyl compound with lappaconitine as catalyst

Abstract

The invention discloses a method for preparing chiral alpha- hydroxyl- beta- dicarbonyl compound by taking lappaconitine as catalyst, belonging to the technical field of organic synthesis. The method is characterized in that beta- dicarbonyl compound, the lappaconitine and oxidizing agent are mixed and stirred in inert solvents for thin layer chromatography trace reaction. After the reaction, the chiral alpha- hydroxyl- beta- dicarbonyl compound is obtained by separation. The inert solvents comprise halogenated hydrocarbon, aromatic hydrocarbon, alkane or the like. The dosage mol ratio between organic peroxide which is taken as the oxidizing agent and the beta- dicarbonyl compound is 1-20, the dosage of the lappaconitine taken as catalyst is 0.5-50mol%, and the reaction temperature is -78 DEG C to 25 DEG C. The lappaconitine is extracted from aconitum sinomontanum in the Middle West part of China, is taken as anodyne and local anaesthetics clinically, and has high safety and no addiction. The new method develops the lappaconitine as organic catalyst, so as to prepare the chiral alpha- hydroxyl- beta- dicarbonyl compound by the anisomerous organic catalyst.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, and relates to a method for preparing chiral α-hydroxyl-β-dicarbonyl compounds using quinine as a catalyst. technical background [0002] The optically active α-hydroxyl β-dicarbonyl structure is ubiquitous in natural products and some drug molecules and pesticide molecular structures; at the same time, this structure is also a synthon for the synthesis of other important functional molecular structure intermediates, such as chiral diol compounds. The most ideal way to synthesize chiral α-hydroxy-β-dicarbonyl compounds is chiral catalytic oxidation of β-dicarbonyl compounds. [0003] In recent years, there have been several methods for the preparation of chiral α-hydroxy-β-dicarbonyl compounds. [0004] It has been reported in the literature that the use of Davis reagents to obtain chiral α-hydroxy-β-dicarbonyl compounds (Chem.Rev.1992,92,919-934, J.Am.Chem.Soc.2000,122,8453-8463, Org...

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Problems solved by technology

[0004] It has been reported in the literature that the use of Davis reagents to obtain chiral α-hydroxy-β-dicarbonyl compounds (Chem.Rev.1992,92,919-934, J.Am.Chem.Soc.2000,122,8453-8463, Org.React.2003, 62, 1-356.), this method is more cumbersome to operate, and the reaction conditions are harsher (-78 ° C ~ 0 ° C, NaHMDS is an alkali), and the oxidant used is an equal or excess chiral oxidant , high cost, not suitable for production application

[0005] Literature (Proc.Natl.Acad.Sci.U.S.A.2004,101,5810-5814, Pure App1.Chem.2006,78,391-396 and J.Am.Chem.Soc.2006,128,16488-16489) reported The Lewis acid that utilizes chiral ligand and metal ion coordination is the method for catalyst asymmetric catalysis to prepare chiral α-hydroxyl-β-dicarbonyl compound, although high enantioselective product (>90%ee can be obtained by this method ), but the chiral ligands and oxidants used are expensive and the operation is more complicated

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