Visible-light Photoredox Catalytic Radical Fluorination Of Tertiary Ethers

Organic fluorine compounds are widely used in all fields of science,due to their unique physical and biological properties.Therefore,the development of new strategies for the construction of C-F bond has long been a research field of great interest in synthetic chemistry.Radical fluorination is one of the most important strategy for the synthesis of organic fluorine compounds.In recent decades,a series of radical precursors have been successfully developed for radical fluorination reactions.However,most of these strategies still require the use of transition metals.Moreover,there are still challenges in the late-stage fluorination of complex molecules.Generally,alkyl ethers are widely used reagents or intermediates in synthetic chemistry.In this paper,we have developed a new radical deoxygenative fluorination method using alkyl ethers as radical precursor via C-O bond cleavage.The main work contains the following two parts:Part Ⅰ:This part consists of optimization of reaction conditions,substrates scope and reaction applications.Selective conversion is achieved through a synergistic strategy of photocatalysis and organocatalysis,using commercially available Selectfluor~?as fluorination reagent.The protocol has a good functional group compatibility,and can be used for the late-stage fluorination of drug-like molecules.The deoxygenative fluorination of complex alcohols has been successfully achieved through consecutive procedures.Part Ⅱ:A series of mechanistic experiments have been done,such as the conditions control experiments,radical trapping experiments,and fluorescence quenching.Based on these experiments,a possible catalytic cycle is proposed.It is speculated that under the synergistic catalysis of photo-redox catalyst and hydrogen atom transfer catalyst,the C-O bond enables homolytic cleavage to form alkyl radical,which then constructs the C-F bond with Selectfluor~?through the transfer of fluorine atom.