Catalytic Enantioselective ?-Fluorination,Chlorination,and Allylation Of ?-Substituted ?-Keto Phosphine Oxides

Organophosphorus compounds as important functional molecules,have been widely used in the fields of medicinal chemistry,organic synthesis,coordination chemistry and materials science.Therefore,the investigation of organophosphorus compounds has been a hot topic in the past decades.?-substituted ?-keto phosphine oxides,one of the subunit of organophosphorus compounds,have been received the extensive attention from chemical communications.For example,they have been used as the precursor of Horner-Wadsworth-Emmons reaction,and as the extracting agents of precious metals,and they have been served as organophosphorus ligands.However,the investigation of organic transformation involving ?-substituted ?-keto phosphine oxides was relatively rare,especially the relative catalytic asymmetric reactions were unexplored.Meanwhile,the construction of chiral quaternary carbon centers has always been one of challenging topic in the field of asymmetric synthesis.In particular,the exploration of enantiodivergent construction of chiral quaternary stereocenters is highly needed,but is synthetically challenging.In this thesis,Some the asymmetric transformations involving ?-substituted ?-keto phosphine oxides have been investigate.This thesis includes the following four chapters:Chapter 1: We classified and summarized the synthetic methods and outlined the reactions involving ?-substituted ?-keto phosphine oxide compounds in detail.Chapter 2: The fluorine atom has unique physical,chemical,and biology properties,hence,introduction of fluorine atoms into molecules has always been one of the hot topics in organic synthesis,especially enantiodivergent preparation of two chiral compounds with enantiotopic fluorine-containing stereocenters has not been perfectly solved.In this chapter,an enantiodivergent fluorination of ?-substituted ?-keto diarylphosphonate oxides catalyzed by commercially available cinchona alkaloid derivatives has been developed for the first time,and two desired enantioisomers with a fluorine-containing quaternary stereocentre were conveniently obtained in excellent enantioselectivities(up to 98% ee)with moderate to excellent yields(up to 95%).The current transformation features a wide structure scope,switchable enantioselectivity controlled by commercially available catalysts,and a scalable procedure.Finally,the further derivatization of product and the reaction mechanism are also investigated.Chapter 3: The asymmetric ?-chlorination reaction of the ?-keto phosphine oxide has been preliminarily studied using cinchona alkaloid derivatives as a catalyst for the first time.Under the optimal reaction conditions,module reaction was performed with a yield of 86% and 90% ee and the range of substrates was further expanded.The further investigation is underway in our group.Chapter 4: The asymmetric allylation reaction of ?-keto phosphine oxides has been explored.After the screening of reaction conditions,the palladium-catalyzed racemic allylation was first realized,and the scope of substrates was also expanded(up to 91%yield).Subsequently,chiral ligands have been design and synthesised,and catalytic asymmetric allylation reactions has been explored(up to 91% yield,54%ee).Up to now,no ideal reaction result was obtained and this subject is under developing in our group.