Studies On P?NMe₂?₃-Mediated Chemoselective Epoxidation Between Two Different Carbonyl Electrophiles

As a common cyclic structure unit,epoxides exist in a broad range of natural products and bioactive molecules,and also serve as important synthons in organic synthesis.Due to their inherent ring tension,epoxides can easily undergo ring-opening-functionalization,and thus results in the formation of many valuable molecules.Over the past three decades,significant advances have been achieved for catalytic epoxidations.Among them,alkene epoxidation such as Sharpless epoxidation has been demonstrated to be a powerful tool in both industrial-and academic-scale synthesis of epoxides.Furthermore,the cyclization of sulfur ylides or?-haloenolates with carbonyl compounds provides alternative valuable approaches to epoxides.Despite the efficiency of the existing methods,the development of other new,efficient and selective epoxidation strategies,especially with the aim of synthesis of structurally diverse epoxides from readily available precursors,is still of significant importance.On the basis of the 1,1-dipolar reactivity pattern of the Kukhtin-Ramirez adduct generated in situ from three-coordinate phosphorus reagent and1,2-dicarbonyl compound,this thesis has explored a chemoselective P?NMe₂?₃-mediated epoxidation of 1,2-dicarbonyl compounds with aldehydes and ketones,leading to an efficient synthesis of highly functionalized epoxides.Results from this study show that the epoxidation reaction has a broad substrate scope.Different types of 1,2-dicarbonyl compounds such as isatin,?-keto ester and?-diketone can proceed well with aromatic and heteroaromatic aldehydes,aliphatic aldehydes,?,?-unsaturated aldehydes,and ynones to give the corresponding highly functionalized epoxides in moderate to excellent yields and good diastereoselectivities.Meanwhile,the mechanism of this epoxidation reaction has been discussed.The reaction is believed to be initiated with the in situ formation of the Kukhtin-Ramirez adduct from three coordinate phosphorus reagent and 1,2-dicarbonyl compound,and most likely proceeds in a cascade nucleophilic addition-intramolecular S_N2 sequence.The chemoselectivity of this epoxidation originates from the exclusive Kukhtin-Ramirez addition of three-coordinate phosphorus reagent to 1,2-dicarbonyl compounds,and the aldehydes or ketones only serve as Michael acceptors.It represents the first chemoselective epoxidation between two different carbonyl compounds and also provides a highly efficient and selective synthesis of functionalized epoxides.