Application of chiral taddol ligands combined with rare earth metal amides to catalyze asymmetric reactions

Abstract

The present invention relates to the application of chiral TADDOL ligands and rare earth metal amides to jointly catalyze the asymmetric epoxidation reaction of chalcone compounds: in anhydrous, oxygen-free and protective atmosphere, the α represented by formula (1) , β-unsaturated ketone and peroxy tert-butanol are reacted under the combined catalysis of chiral TADDOL ligand shown in formula (3) and rare earth metal amidide, under the presence of organic base simultaneously, after the reaction is complete, obtain Chiral epoxy compounds shown in formula (2): wherein, R 1 selected from hydrogen, alkyl, halogen, alkoxy, trifluoromethyl, nitro or cyano; R 2 Be selected from phenyl, substituted phenyl, naphthyl, furyl or thienyl; R 3 and R 4 independently selected from alkyl, phenyl or R 3 , R 4 And the carbon atom connected to the two forms a cycloalkyl group; Ar is phenyl, substituted phenyl, biphenyl or naphthyl; the molecular formula of rare earth metal amides is RE[N(SiMe 3 ) 2 ] 3 . The method has a wide range of substrates and high yield and enantioselectivity.

Description

technical field [0001] The invention relates to the field of catalysts for synthesizing chalcone compounds, in particular to the application of a chiral TADDOL ligand and a rare earth metal amide to jointly catalyze an asymmetric reaction. Background technique [0002] Optically active epoxy compounds are important organic synthesis intermediates for the synthesis of many natural products and optically active raw materials. The most direct, economical and green way to epoxy compounds. There are relatively many asymmetric epoxidation substrates reported in the literature, among which the asymmetric epoxidation of α,β-unsaturated ketones is particularly important, and the catalysts involved in such reactions are small organic molecules and some metal catalysts. [0003] Currently, the reports on the asymmetric epoxidation of α,β-unsaturated ketones catalyzed by small organic molecules are as follows: [0004] (1) In 2005, Lattanzi et al. reported a kind of asymmetric epoxida...

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Problems solved by technology

But its catalyst consumption is higher, reaches 30mol%, and reaction time is 27-87h (referring to: Lattanzi, A.Org.Lett.2005,7,2579.)

[0005] (2) In 2007, Zhao Gang et al. used S-diphenylprolinol as the chiral raw material on the basis of Lattanzi et al., and made some modifications to it. The amount of catalyst was still 30mol%. In α, β-unsaturated In the asymmetric epoxidation of ketones, the ee value can reach up to 96%, but the reaction time is longer, requiring 144h (see: Li, W.; Liu, X.; Yang, Y.; Zhao, G.J.Org.Chem. 2007, 72, 288.)

[0010] (6) In 2012, Feng Xiaoming and others used Sc(OTf) 3 And chiral dinitrogen oxide ligands as catalysts have achieved very good results for the asymmetric epoxidation of α, β-unsaturated ketones, the ee value can reach up to 99%, and the catalyst dosage is low, which can be reduced to 1mol% , but the system requires a longer reaction time of 48h (see: Chun, Y.; Liu, X.; Li, W.; Hu, X.; Feng, X.Chem.Sci.2012,3,1996.)

[0012] In summary, for the asymmetric epoxidation of α, β-unsaturated ketones, organic small molecule catalysts and some metal catalysts are currently mainly used, but there are still many problems in these systems, such as: high catalyst dosage, long reaction time, bottom The scope of expansion of the compound is small, and there is still room for improvement in the enantioselectivity of the product, etc.

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