Fluoroalkylation And Amidation Of Heteroarenes And Decarboxylative Coupling Reactions Of Alkynyl Carboxylic Acids

In this thesis,direct C-H fluoroalkylation and amidation of heteroarenes were explored.In addition,the palladium-catalyzed decarboxylative coupling reactions of alkynyl carboxylic acids or?,?-unsaturated carboxylic acids and N-Boc-3-iodoazetidine were also invetigated.The results are shown as follows:1.Transition-metal-freedirectC-Htrifluoromethylationand perfluoroalkylation of imidazo[1,2-a]pyridines with TMSC_nF_2n+1?n=1,2,3?The first transition-metal-free protocol to C-H trifluoromethylation and perfluoroalkylation of imidazo[1,2-a]pyridine derivatives with readily available TMSC_nF_2n+1?n=1,2,3?.A variety of novel perfluoroalkylated imidazo[1,2-a]pyridines were obtained in moderate to good yields.In addition,notable advantages of this method include mild conditions,easy operation,high-efficiency and wide substrate scope.Scheme 1 Transition-metal-free direct C-H trifluoromethylation and perfluoroalkylation ofimidazo[1,2-a]pyridines2.Copper-catalyzed C5-selective C-H difluoroalkylation of quinoline amides with fluoroalkyl bromides and iodinesAn efficient approach to C5-difluoroalkylated 8-aminoquinoline derivatives was discovered and developed via the copper-catalyzed direct C-H difluoroalkylation of 8-aminoquinoline scaffolds with functionalized difluoromethyl bromides and iodines.This reaction features mild conditions and good substrate tolerance.In addition,a variety of novel C4-difluoromethylated naphthalenes were firstly obtained through our reaction systems.Scheme 2 Copper-catalyzed C5-selective C-H difluoroalkylation of quinoline amides3.Copper-catalyzed C5-selective C-H monofluoroalkylation of quinoline amides with BrCHFCO₂EtAn efficient copper-catalyzed monofluoroalkylation of quinoline amides was developed.The method provides convienient access to the synthesis of C5-monofluoroalkylated 8-aminoquinoline derivatives using BrCHFCO₂Et as the material.This catalytic system features easy operation and good substrate tolerance.Scheme 3 Copper-catalyzed C5-selective C-H monofluoroalkylation of quinoline amides4.Nickel-promoted C?2?-H amidation of quinoline N-oxides with N-fluorobenzenesulfonimideA novel highly efficient nickel-promoted C-H amidation has been developed for the preparation of 1,2-dihydro-2-iminoquinolines from the reaction of quinoline N-oxides and NFSI under mild conditions.The protocol provides convienient access to a variety of useful 1,2-dihydro-2-iminoquinolines in moderate to good yields.Notable advantages of this method include synthetic convenience,mild reaction conditions and high-efficiency.Scheme 4 Nickel-promoted C?2?-H amidation of quinoline N-oxides withN-fluorobenzenesulfonimide5.Preparation of 2-alkynylazetidines,3-alkynylazetidines and 3-vinylazetidines from N-Boc-3-iodoazetidine through palladium-catalyzed decarboxylative coupling reactionsThe facile and efficient methods for palladium-catalyzed decarboxylative coupling reactions of alkynyl carboxylic acids or?,?-unsaturated carboxylic acids with N-Boc-3-iodoazetidine has been developed.A convenient strategy to the regioselective synthesis of 2-alkynylazetidines and 3-alkynylazetidines through efficiently regulating the?-hydride elimination/migratory insertion sequence was provided.In addition,a series of novel 3-vinylazetidines were firstly obtained via the palladium-catalyzed decarboxylative coupling reactions.Scheme 5 Strategies toward selective preparation of azetidines.