Metal-Catalyzed Cyclization Of Gem-Dihaloolefins And Its Application In The Synthesis Of Fused Heterocycles

Isocoumarin is an important class of organic compounds.Many natural products with important biological activities contain this unit structure.In addition,isocoumarin has rich synthetic applications and can be used as a key precursor to construct target molecules with complex structures.We have developed an efficient method to construct 3-alkynyl isocoumarins via a PdCl₂/CuI-catalyzed tandem Sonogashira coupling/lactonization of methyl 2-?2',2'-dibromovinyl?benzoate with terminal alkynes.Furthermore,a concise synthesis of natural products 3-hydroxycorfin and gymnopalyne A was also achieved using this approach as a key step.Fluorine is a unique element.The introduction of a fluorine atom or a fluorine-containing functional group can often cause the target molecule to exhibit special physical and chemical properties and reactivity.Therefore,organic fluorine compounds are widely used in medicine,pesticides,and functional materials.According to statistics,about20%of the marketed chemical drugs are fluorine-containing drugs.Gem-difluoroolefins are an important class of synthons that can be converted into the corresponding monofluoroolefins and organic fluorine compounds with trifluoromethyl or difluoromethylene.3,4-Dihydroquinoline-2?1H?-one is a kind of dominant skeleton existing in many active molecules and natural products.We have developed a novel silver-promoted decarboxylative radical addition/annulation of oxamic acids with gem-difluoroolefins,thereby enabling efficient access to various CF₂-containing 3,4-dihydroquinolin-2-ones under mild reaction conditions.This reaction presents a new strategy for introduction of the CF₂ moiety to organic molecules through a radical cyclization process of gem-difluoroolefins.In the past decade,visible light-induced redox catalysis has stimulated the great research interest of chemists due to its environmental friendliness,mild reaction conditions,and the need for high-energy ultraviolet light irradiation,and has achieved many breakthrough research advances.Using N-heterocarbene borane as a substrate,we have developed a visible light-induced defluorination for synthesis gem-difluoroallylborames.