N-Heterocyclic Carbenes And Photoredox Co-Catalyzed 1,4-Difluoromethylative Acylation Of 1,3-Enynes

Difluoromethyl（CF₂H）group could act as a metabolically stable bioisostere of lipophilic hydrogen bond donors,playing a vital role in drug discovery.The direct introduction of the CF₂H group into organic molecules represents a challenging and attractive task in organic chemistry.Despite the significance,radical difluoromethylation was an emerging area,and transformations focused on arene（heteroarene）or olefins.Development of the three-component radical difluoromethylation system of other unsaturated molecules would be extraordinarily attractive to access the molecular complexity and diversity.1,3-enynes sever as versatile building blocks in organic synthesis.Radical difluoromethylation of 1,3-enynes provides direct access to value-added difluoromethy-containing allenes.However,to the best of our knowledge,the radical difluoromethylation strategy was rarely employed in the transformation of 1,3-enynes.In this thesis,we reviewed the recent development of radical difluoromethylation and radical 1,4-difunctionalization of 1,3-enynes.We described visible light-mediated N-Heterocyclic Carbene catalysis（NHCs）and photoredox co-catalyzed1,4-difluoromethylative acylation of 1,3-enynes via radical relay.Bench-stable and cost-effective sodium difluoromethyl sulfite and easily-accessing benzoyl fluoride could react with 1,3-enynes,providing direct access to value-added HCF₂-containing allene ketones.This protocol represents a rare example of the installation of the CF₂H or CFH₂ group into1,3-enyne units,providing a modulized platform for the synthesis of fluoromethyl-containing allene ketones.