Study On The Catalytic Effect Of Bisoxazoline Metal Complexes On The Reactions Of Nitrone And Nitrile Imine

The 1,3-dipolar cycloaddition reaction is a common method for the construction of 5-membered hetereocyclic rings. Due to often high degree of regioselectivity of the 1,3-dipolar cycloaddition reactions, the attempt to control the stereoselectivity have attracted more attention recently. By using chiral metal complexes as catalysts, the optically active products are directly synthesized from the achiral 1, 3-dipolar reagents and achiral alkenes.In this paper, a series of chiral bisoxazolines, S-35a-d and R-35a are synthesized from chiral amino alcohols and diethyl malonate via acylation, chloration and cyclyzation. Then, ten chiral metal complexe catalysts (five different bisoxazolines derivatives with Cu(II), Zn(II) and Co(II)), are tested to catalyze the 1,3-dipolar cycloaddition reactions of electron-deficient alkenes 50a-c, 51 with C,N-diphenylnitrone 41 and pyridine 45, 49 with methyl acrylate.Presents the attempts to apply Cu(OTf)₂-, Zn(OTf)₂- and Co(CH₃COO)₂-bisoxazolines in the 1,3-dipolar cycloaddition reaction between electron-deficient alkenes 50a-c, 51 with nitrones 41 and investigate the influence of catalysts on the reaction rate, diastereoselectivity and enantioselectivity. At the same time, this paper also presents the attempts to apply firstly chiral catalysts in the 1,3-dipolar cycloaddition reaction between pyridine 45, 49 with methyl acrylate, giving lots of significative results. These reactions have been investigated under various conditions with different chiral ligands, the metal salts, different reactants, solvents, molecular sieves, temperature and catalyst amount. The present results have shown that ligands,Chrial ligands of the metal complexs have an important effect on the diastereo- and enantioselectivity of the 1,3-dipolar cycloaddition reaction course and 35a can lead to induced the most excellent chirality ,such as S-57a and S-58a. The 1,3-dipolar cycloaddition reactions between 50a, 50b and 41 catalyzed proceed with a high of enantioselectivity, up to 76% and 80% respectively.Metal salts are crucial for both reaction rate and stereoselectivity of the catalyzed reaction of 50 and 41. When the metal was Cu(II) in catalysts, the reactions proceed with faster reaction rate and better stereoselectivity. When the Cu(II) was insteaded by Zn(II), a moderate reaction rate and stereoselectivity was obtained. However, the result is similar with blank reaction if the metal was Co(II).The reactants also have an important effect on the stereoselectivity of the 1,3-dipolar cycloaddition reactions. In the catalyzed reaction of 41 and 50, a better enantioselectivity can often be observed. But a lack of enantioselectivity is obtained in the reactions of 45, 49 and methyl acrylate.The diastereo- and enantioselectivity of the reaction between 50 and 41 is very solvent dependent. It is appeared that too higher or too lower polarity than CH₂Cl₂ has bad effect on the diastereoselectivity, especially enantioselectivity, and CH₂Cl₂ is a better solvent for those reactions.Temperature has an interesting effect on the diastereo- and enantioselectivity. The diastereo- and enantioselectivity change following different catalysts at low temperature.