Syntheses Of Ligands With C2 Symmetry Based On Amino Alcohol And Their Chiral Catalysis In Henry Reaction

The asymmetric Henry reaction is a very effective reaction for building C-C bonds.The reaction product can be used to synthesize a variety of natural products and biologically active drugs.At present,the asymmetric Henry reaction has the problems of chiral catalyst synthesis difficulty,high price and low utilization rate.Therefore,it is very important to design and synthesize new and cheap chiral catalysts.This article mainly uses amino acids and amino alcohols as chiral sources to synthesize a variety of ligands through structural adjustment,and studies the chiral catalytic efficiency in Henry reaction by coordination with copper acetate monohydrate.First,three amino acids C2-symmetric chiral ligands(L1-L3)with two coordination centers were synthesized by the condensations of L-valine,L-phenylalanine or Lphenylglycine with terephthalaldehyde and then the aminations by reduction.Second,L-phenylalaninol was used as a chiral source,two diamine chiral ligands(L4 and L5)with single coordination centers were synthesized through the amino protection,the chlorination of the hydroxyl group,further coupling with tetrahydropyrrole or piperidine,and then the deprotection on amino group.The ligand L4 or L5 was respectively condensed with terephthalaldehyde and then the intermediates were successively subjected to reduction.Two diamine C2-symmetric chiral ligands(L6 and L7)with two coordination centers were synthesized.Finally,three aminoalcohol C2-symmetric chiral ligands(L8-L10)were synthesized by using L-phenylalaninol as a chiral source,which was condensed with 2,5-dihydroxyterephthalaldehyde or 2,6-dihydroxynaphthalene-1,5-dicarbaldehyde and successively subjected to the reduction into amines.All structures of ligands and intermediates were characterized by IR,MS and NMR.The ligands were coordinated with the copper salts,and the catalytic tests were performed in Henry reaction of benzaldehyde with nitromethane.First,the ligands were screened,and ligand L7 was determined as the optimum ligand.Secondly,the catalytic conditions of ligand L7 were optimized.Factors were explored,including the source of copper salt,temperature,the amount of catalyst,solvent and alkaline additive.The results show that in ethanol solvent,the amount of ligand is 5 mol%,the addition of copper acetate monohydrate,and the reaction at 5°C for 24 h can give a catalytic result with a yield of 87.5% and an ee value of 91.3%.Subsequently,the reaction substrate was expanded under optimal conditions.After testing seven different aldehydes,the yield was found to be 78.2%-89.6%,and the ee value was 84.3%-92.1%.