Copper Catalyzed NHPI Involved CDC Reaction And The Application Of Cu/NHPI System Catalyzed Allylic Oxidation Reaction In The Synthesis Of 25-hydroxy-provitamin D₃

This thesis aims at the research on copper catalyzed N-hydroxyphthalimide?NHPI?involved cross-dehydrogenative-coupling?CDC?reaction and the application of Cu/NHPI system catalyzed allylic oxidation reaction in the synthesis of 25-hydroxy-provitamin D₃.Details are as follows:The first chapter is a mini review on N-hydroxyphthalimide or sp³C-Hbonds involved CDC reactions.We also discussed the previous work from several aspects,such as catalyst system,composition,reaction selectivity,reaction scope,and reaction mechanism.The second chapter is about a convenient protocol for the synthesis of O-substituted NHPI derivatives by the CDC reaction of NHPI with alkanes and ethers under the action of Cu?OAc?₂·H₂O and Selectfluor.In my opinion,it is an interesting transformation,exhibiting a good scope with respect to various ethers and cycloalkanes in synthetically useful yields of O-substituted NHPI derivatives,and the highest yield was up to89%.Several control experiments have been carried out to probe the reaction was a free radiacl process and a plausible catalytic cycle has been proposed.This method not only provided a simple and atom-economic route for the syntheses of O-substituted NHPI derivatives,but also represented a new strategy for functionalization of simple alkanes and ethers.The third chapter has developed a copper-catalyzed highly efficient esterification of aldehydes with N-hydroxyphthalimide via cross dehydrogenative coupling in water at room temperature in the presence of PhI?OAc?₂as an oxidant and Selectfluor as an additive,offering a convenient and eco-friendly protocol for the synthesis of NHPI esters.A wide range of aldehydes were good coupling partners,and the highest yield was up to 91%.Several control experiments have been carried out to probe the reaction was a free radical process,and two plausible catalytic cycles have been proposed.This CDC reaction could be effective in water at room temperature,the short reaction time and the use of the inexpensive copper powder as the catalyst would make this efficient process attractive.The forth chapter introduced the pharmacological activity of 25-OH-VD₃and presented the synthetical methods of 25-OH-VD₃from two aspects:total-chemical synthesis and semi-chemical synthesis.The fifth chapter mainly research on Cu/NHPI system catalyzed allylic oxidation reaction of 25-hydroxycholesterol diacetate ester.Moreover,the synthesizing process of 7-keton-25-hydroxycholesterol diacetate ester from 7-keton-25-hydroxycholesterol diacetate ester is also studied in this chapter.In addition,the mechanisms of allylic oxidation and dehydrazonation have been investigated:allylic oxidation reaction was a free radical process,mechanism of de-hydrazone reaction was similar to the Bamford-Stevens reaction,a diazonium compound was formed in an aprotic solvent under strong alkaline conditions,then became a carbene after removal of N₂,and finally generated the thermo-dynamically stable multi-substituted olefins.