The Development Of Novel Tertiary Amine-Phosphoramide Bifunctional Catalysts And Their Applications In Stereodivergent Synthesis

This thesis focus on the development of two types of novel chiral tertiary aminephosphoramide bifunctional catalysts,and the exploration of switching the diastereoselectivity of the reactions simply by varying the H-bond donors.Accordingly,two types of stereodivergent reactions of ?-substituted-?-azido ketones to Michael receptors have been developed,which includes following research work:1)Two types of tertiary amine-phosphoramide bifunctional catalysts were designed and synthesized: chiral ?-amino acid-derived open-chained phosphoramides with structural flexibility and substituents diversity;cinchona alkaloides-derived phosphoramides contain two types of H-bond donors(C6' OH group and C9 phosphoramide).2)In the stereodivergent Michael addition reaction of ?-azido ketones to nitroolefins,phenylalanine-derived phosphoramide afforded syn-selective tertiary azides with high yield and excellent stereoselectivity,an analogous squaramide catalyst selectively gave anti-adducts with excellent enantioselectivity and diastereoselectivity.Thus,all stereoisomers of products could be obtained by using two catalysts and their enantiomers respectively.Theoretical calculations showed that the different catalystsubstrate recognition models is the key to the successful regulation of diastereoselectivity.3)Using quinine-derived phosphoramide,the stereodivergent conjugate addition of ?-azido ketones to ?,?-unsaturated-?-ketoesters was achieved with the addition of hexafluoroisopropanol(HFIP),affording syn-products with up to 99% yield and 99.5% ee value;anti-products were obtained by using quinidine-derived bifunctional thiourea.Thus obtained chiral tertiary azides can be transformed into multi-substituted spiropyrrole derivatives.