Studies On Copper-Catalyzed Ring-Opening Defluoroalkylations Of Gem-Difluorocyclopropanol Silyl Ethers

As homoenolate precursors,the ring-opening and conversion reactions of cyclopropanols have a wide range of applications in the synthesis,especially in the research of transition metal-catalyzed ring-opening cross-coupling reaction of cyclopropanols,fruitful results have been achieved.Based on the importance and particularity of fluorine-containing organic compounds,the development of synthetic application of gem-difluoroyclopropanols has important theoretical research significance and practical application value.Difluorocyclopropanol silyl ethers are one of difluorocyclopropanol derivatives with relatively stability.Recently,research on the synthetic application of this kind of fluorine-containing intermediates has attracted attention of chemists.Our research group has carried out continuous exploration in this field,and has developed gem-difluorocyclopropanol silyl ethers into highly reactive,highly selective fluorinated organic synthons,thus establishing new synthetic methods for various types of fluorine-containing organic compounds.This dissertation mainly studies the ring-opening defluorinative alkylations of siloxydifluorocyclopropanes under copper catalysis,including the following three parts:In part one,firstly,the ring-opening cross-coupling reactions of cyclopropanols catalyzed by different transition metals were summarized.Secondly,the research progress of ring-opening reactions of gem-difluorocyclopropanol derivatives was reviewed.In part two,we elaborated the basis and strategy of this dissertation.Base on the importance of developing the synthetic application of difluorocyclopropanols and the current research progress in this research area,we selected siloxydifluorocyclopropanes with thermal stability as the research object,and explored their ring-opening defluoroalkylation under the catalysis of Cu.In part three,we have reported a new copper-catalyzed ring-opening coupling reaction of siloxydifluorocyclopropanes.Firstly,by the use of Cu?OAc?₂ as catalyst and1,10-phenanthroline as ligand,ring-opening defluorination coupling of gem-difluorocyclopropanol silyl ethers with?-bromo carboxylic esters was realized in THF in the presence of KI and Et₃N leading to?-fluoroketoesters effectively via a Cu^?/Cu^? catalytic cycle.Subsequently,under similar reaction conditions,we have also realized the ring-opening defluorination coupling of siloxydifluorocyclopropanes with?-bromoamides.Notably,the coupling reaction is also accompanied by a unique intramolecular C-N oxidative coupling,defluorination,hydrolyzation,ring opening,and dehydration cascade reaction,and a series of important?,?-diketonitrile derivatives were efficiently synthesized.The mechanistic studies suggested that the reaction went through a free radical process involving?-fluoroenone intermediate.The research results provided guidance for expanding the synthesis and application of gem-difluorocyclopropanol silyl ethers,and offered a simple and efficient new strategy for the synthesis of?-fluoroketoesters and diketonitriles.Through this dissertation,we have synthesized 41 new compounds,all of which were characterized by ¹H NMR,¹³C NMR,¹⁹F NMR,and HRMS.