Copper-catalyzed Cascade Reaction Initiated By Trifluoromethyl Radical

Trifluoromethylated compounds have been becoming widely used in the fields of pharmaceuticals,agrochemicals,and special materials in recent years due to their unique characteristics of the excellent lipophilicity,metabolic stability,and bioavailability.Therefore,it is of great importance to develop efficient,mild and convenient methods for the preparation of trifluoromethylated compounds in order to support the development of new drugs and materials.Among the methods of introducing trifluoromethyl group into molecules,trifluoromethylation thought radical relay has great prospects and has become a hot spot in current research.As excellent radical acceptors,unsaturated compounds are widely used in radical cascade reactions,and the synthesis of trifluoromethylated compounds with specific skeletons can be achieved through reasonable substrate design.This dissertation is based on the radical trifluoromethylation reactions,with Togni's reagent used to generate trifluoromethyl radical in situ,the trifluoromethylation of specific alkenes(alkynes)is achieved through copper catalysis.The dissertation includes four parts:Chapter 1:Application and Research Progress of CF3-containing CompoundsIn this chapter,we gave examples of the applications of trifluoromethylated compounds in the fields of pharmaceuticals,agrochemicals,and special materials.Meanwhile,we systematically introduced the currently known synthesis methods and commonly used reagents of trifluoromethylated compounds,focusing on the research progress of various trifluoromethylating reagents in the application of radical trifluoromethylation reactions.Chapter 2:Enantioselective Copper-Catalyzed 1,5-Cyanotrifluoromethylation of VinylcyclopropanesWe have developed a copper-catalyzed enantioselective 1,5-cyanotrifluoromethylation of vinylcyclopropanes via radical addition/ring-opening strategy.With chiral bisoxazoline used as the ligand and TMSCN used as the cyano source,this method has demonstrated high enantioselective control,broad substrate scope,and mild conditions.Chapter 3:Copper-Catalyzed Trifluoromethylation/Cyclization of Alkynes forSynthesis of DioxodibenzothiazepinesWe have developed an efficient approach for the synthesis of dioxodibenzothiazepines via copper-catalyzed trifluoromethyl radical addition/cyclization of o-alkynylbenzenesulfonamides utilizing bipyridine as the ligand.This method features low catalyst loading,high regiocontrol and broad scope under mild conditionsChapter 4:Copper-Catalyzed Synthesis of CF3-containing tetrahydroquinolines via 1,6-HATWe have demonstrated a novel method for the preparation of the CF3-containing tetrahydroquinoline compounds via copper-catalyzed trifluoromethyl radical addition/1,6-HAT/6-exo-trig cyclization of o-alkynylbenzamides using triphenylphosphine as the ligand.This method has showed the good diastereoselectivity.