The Synthesis Of New Chiral Ligands And The Application In The Henry Reaction

Much attention has been paid to the design and development of effective asymmetric catalyst which is one of the most important aspects of modem organic chemsity.The bifuntional catalytic system incorporates two active center to work together for simultaneous activation of both the electrophilic and nucleophilic reaction partners.Therefore,high efficiency and selectivity are much more easily obtained in this dual activation mode which takes great advantage over the traditional mono activation mode.In recent years,this concept of synergistic effect was applied in the area of asymmetric catalysis and some successful novel bifunctional catalysts were reported by some research groups.Owing to the intrinsic features of bifunctional catalysis and some successful examples,it is promising to development some new catalyst for excellent transformations based on the synergistic effect.Design and preparation of new ligand plays a key role in the development of a novel bifunctional catalyst.5-methyl-3-(bromomethyl)-2-hydroxybenzaldehyde was prepared in this paper which could work as a platform for access to numerous novel chiral ligands.The four substituents on the benzene moiety are all synthetically useful,among which the bromomethyl and aldehyde group could be tethered to diverse coordinating groups:the 2-hydroxy group is coordinating actively itself;the 5-methyl group could affect the reaction pattern of the benzene moiety.11 new ligands were prepared starting with the compound 5-methyl-3-(bromomethyl) -2-hydroxybenzaldehyde in term of the concept of bifunctional catalysis and all the structures were confirmed by the ¹H NMR spectrum.All the ligands were investigated for the asymmetric Henry reaction between m-nitrobenzaldehyde and nitromethane.After screening a new ligand with the best catalytic activity was selected for further optimization.Further research revealed that the ligand/Et₂Zn complex could effectively promote the asymmetric Henry reaction and the additive 2-aminophenol has a dramatic influence on the enatiomeric excess of the product.The best reaction condition was obtained after further investigation—ligand/Et₂Zn/2-aminophenol=2/3/1,THF as solvent,at 0℃for 4-7d.Under the optimized condition,the scope of the substrate was investigated affording the corresponding products in 72-95%yield and ee up to 90%.