Copper Difluorocarbene Involved Catalytic gem-Difluoropropargylation

The use of metal for catalytic difluorocarbene transfer reactions has long been hindered by the lack of understanding of metal difluorocarbene chemistry, despite the prospect of a new dimension to create novel fluorine structures for medicinal chemistry and advanced materials science. Here, we report a new mode of copper catalyzed difluorocarbene transfer reaction via 1,2-migration of copper difluorocarbene, in sharp contrast to the previous nucleophilic addition of copper difluorocarbene pathway. This innovative reaction enables the development of a modular catalytic gem -difluoropropargylation reaction using a variety of simple and widely available potassium propiolates, terminal alkynes, and allyl/propargyl electrophiles to couple difluorocarbene, opening a new avenue to precise synthesis of organofluorine compounds without tedious synthetic procedure. The impact of this protocol has been demonstrated by the efficient synthesis of complex fluorinated skeletons and the rapid synthesis of the key intermediates of pheromone derivative and PGF _2a agonist. Mechanistic studies reveal that the migratory insertion of difluorocarbene into the C-Cu bond of the alkynylcopper species is involved in the reaction.