Study On The Construction Of Fluoroquinoline Derivatives From O-alkenyl Aromatic Asocyanides

Isocyanides are highly active compounds that have served as extraordinarily valuable building blocks in organic chemistry.Recently,o-functionalized aromatic isocyanides have been well-established for the construction of N-heterocycles.Among them,the radical cyclization for o-alkenyl aromatic isocyanides usually delivered fivemembered indole ring than than six-membered quinoline ring.In this thesis,a variety of cyano-containing o-vinyl aromatic isocyanides were prepared by introducing a cyano group on C1 position of o-vinyl group.Then,we studied trifluoromethyl and difluoromethyl radical promoted cyclization of the cyano-containing o-vinyl aromatic isocyanides to construct 4-CN-2-CF₃/CF₂H-containing quinolines under mild conditions.The main work includes the following two parts:Part I:A radical cascade cyclization of cyano-containing o-vinyl aromatic isocyanides with Togni’s reagent catalyzed by Bu₄NI or copper has been developed.The reaction showed a broad substrate scope and good functional group tolerance.Mechanism demonstrated that CF₃ radical chemoselectively attacks the isonitrile afford the imidoyl radical intermediate.The quinoline ring is formed by two ring formation pathways:1)Radical intermediate undergoes direct 6-endo-trig cycloaddition followed by one-electron oxidation and deprotonation.2)Imidoyl radical intermediate undergoes 5-endo-trig/3-endo-trig/3-exo-trig process to construct quinoline ring.Part Ⅱ:We disclosed a visible-light photoredox catalyzed cyclization between o-alkenyl aryl isonitrile and（difluoromethyl）triphenylphosphonium bromide.This protocol offers an efficient approach to obtain 4-cyano-2-difluoromethylquinoline derivatives with high yields via a radical pathway.