Synthesis method of chiral 3,4-dihydrocoumarin derivative compound

Abstract

The invention discloses a synthesis method of a chiral 3,4-dihydrocoumarin derivative compound. The method specifically comprises steps as follows: 2-hydroxychalcone and azlactone are taken as reactants, and a product is synthesized in a solvent under the catalysis of multifunctional chiral quinine thiourea. According to the method, raw materials are simple and easy to obtain, reaction conditions are mild, post-treatment is simple and convenient, the applicable substrate range is wide, the yield is high, and the enantioselectivity is high; the synthesized product can be used for synthesizing intermediates of drugs and insecticides.

Description

technical field [0001] The invention relates to the synthesis of chiral quaternary carbon compounds, in particular to a catalytic synthesis method of chiral 3,4-dihydrocoumarin derivative compounds. Background technique [0002] Chiral quaternary carbon compounds have a wide range of biological activities such as anti-tumor, anti-plant virus, plant growth regulation, weeding, sterilization, inhibition of enzyme activity, anti-oxidation and radiation protection, and destruction of biological cell membranes, and have attracted the attention of many scientists. Chiral 3,4-dihydrocoumarin-derived compounds, as chiral quaternary carbon compounds, also have similar potential application values, so choosing an efficient method to synthesize chiral oxygen-containing aminal compounds has attracted many chemists Of great interest, many synthetic methods have recently emerged. [0003] In the field of organic synthesis, the reaction catalyzed by asymmetric small molecules has become t...

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Problems solved by technology

Hayashi's group reported in 2005 the asymmetric 1,4-addition reaction of coumarin and arylboronic acid catalyzed by rhodium metal using (R)-Segphos as a ligand, which can be 45% The yield of 94% and the enantioselectivity of 99.1%-99.7% obtain 3, the target product of 4-dihydrocoumarin, but because of using metal, add ligand more expensive, so cost is higher (G . Chen, N. Tokunaga, T. Hayashi, Rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to coumarins: Asymmetric synthesis of (R)-Tolterodine. Org. Lett. 2005, 7, 2285.); Ye Song’s research group also reported the cycloaddition reaction of unsaturated ketone QM-1a and enone in 2009, the catalyst used was azacarbene, The yield of 30%-96%, the cis-trans ratio of 2 / 1-9 / 1, and the enantioselectivity of 51%-99% and 86%-96% can be used to obtain cis and trans 3,4-di Hydrocoumarins, but the substrate and catalysis are relatively difficult to synthesize (H. Lv, L. You, S. Ye, Enantioselective synthesis of dihydrocoumarins via n-heterocyclic carbene-catalyzed cycloloaddition of ketenesand o- Quinone methides. Adv. Synth. Catal. 2009, 351, 2822.)

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