Study On Asymmetric Pseudo-allylation Of ?-Ketophosphonate

Many natural products and active pharmaceutical molecules often exhibit special physical and chemical properties and biological activities due to the presence of chiral quaternary carbon center.Therefore,more and more researchers are devoting on the synthesis of chiral quaternary carbon compounds,although there are challenges in the construction of chiral quaternary center due to the high steric hinderance around it.Phosphonate is a key structure in various natural products and drug molecules.It plays an important role in enhancing the activity or efficacy of these copmpounds.The configuration of phosphonate is tetrahedron,which is different from that of the planary ester.Because of that,replacement of ester with phosphonate can enhance the metabolic stability.?-Ketophosphonate is very active nucleophile and can undergo nucleophilic addition reaction with electrophiles to give multifunctional compounds.In this thesis,?-substituted ?-ketophosphonate was used as nucleophile to conduct pseudoallylation reaction with allyl sulfone,which is easy to obtain and has high reactivity,to give phosphonate bearing chiral quaternary carbon.Here,in the presence of chiral ammonium or chiral phosphonium,conjugate substitution reaction,the pseudo-allylation,between ?-ketophosphonate and allylaryl sulfone was investigated.The factors affecting the reaction,such as the kinds and the amount of alkali,solvent,temperature,concentration,catalyst loading etc.were studied.And finanly the best combination was fonud,under which the product can be obtained with up to 92% yield and up to 94% ee.