Study On Bifunctionalization Of Alkenes Via Radical Migration/[4~++2] Polar Cycloaddition Strategies

Alkenes are a kind of easily accessible organic compounds containing carbon-carbon double bonds with a wide range of sources,and its diverse transformations play indispensable roles in organic chemistry.Among them,the vicinal difunctionalization of alkene by the construction of carbon-carbon bonds and carbon-heteroatom bonds is one of the most representative conversion methods of olefins.It not only plays a part in the synthesis of organic intermediates and functional materials but also provides a crucial means for the modification of drug molecules and natural products.In view of the significance of alkenes difunctionalization,chemists have shown a keen interest in the research of this transformation,meanwhile,a variety of alkenes difunctionalization modes based on different reaction types,strategies and different olefin structures have been developed.In consideration of the background,this thesis reports the studies on the vicinal oxyhalogenation/aminohalogenation of olefin via radical 1,2-halogen migration,pyridinyl dicyanomethylation by radical 1,4-pyridine migration strategies as well as aminoarylation of alkenes through[4⁺+2]polar cycloaddition strategies.As a result,a series of structurally important skeletons containing biologically active heterocycles such as isoxazole,pyrroline-N-oxide,1,2,3,4-tetrahydrocinoline,and pyridine have been successfully synthesized.The content of this thesis includes the following three parts.1.Synthesis of Halomethyl Isoxazoles/Cyclic Nitrones via Cascade Sequence:1,2-Halogen Radical Shift as a Key LinkThis study offers an intramolecular oxyhalogenation and aminohalogenation strategy of alkenes through 1,2-halogen radical migration reaction.In this way,a variety of halomethyl isoxazoles/pyrroline-N-oxide were prepared by using?-halo-?,?-and?-halo-?,?-unsaturated ketoximes as the starting materials and iodobenzene diacetate(Ph I(OAc)₂)/2,2,6,6-tetra-methylpiperidine-1-oxyl(TEMPO)as the commercially available oxidation system.This reaction involves a tandem iminoxyl radical-promoted dichotomous regioselective 5-exo-trig cyclization/1,2-halogen migration sequence.Furthermore,DFT theoretical calculations also reveal the mechanism of the migration reaction:the 1,2-Cl/Br-atom migration undergoes a three-membered ring transition state bridged by halogen,while the shift of 1,2-I atoms can be explained with an elimination/readdition process.Meanwhile,the theoretical calculations also provide the migration ability of halogen which is ranked in the order:I>Br>Cl.2.Visible-Light-Induced Dicyanomethylpyridation of Alkenes via Free Radical 1,4-Pyridine MigrationIn this study,a visible-light-induced intermolecular dicyanomethylpyridation method of alkenes via a radical mediated 1,4-pyridine rearrangement reaction is developed for the synthesis of a series of significant organic molecules containing pyridinyl and dicyanomethyl using dicyanomethylpyridine ylide and various alkenes as the substrates and[Ir(d F(CF₃)ppy)₂(5,5'-d CF₃bpy)]PF₆ as the photocatalyst.The reaction mechanism is revealed by Stern-Volmer fluorescence quenching experiments,cyclic voltammetry(CV)experiments and control experiments.3.Aminoarylation of Unactivated Alkenes by[4⁺+2]Polar Cycloaddition of Alkenes with In-Situ Generated Conjugated Heterodienes:Synthesis of N-Containing HeterocyclesThis study provides a synthetic strategy for the intramolecular aminoarylation of alkenes through[4⁺+2]polar cycloaddition reaction.With this protocol,various of potentially biologically active fused heterocyclic compounds bearing a 1,2,3,4-tetrahydrocinnoline moiety were efficiently synthesized through the polar cycloaddition between carbon-carbon double bond and in situ generated conjugated heterodienes which is produced by an oxidation reaction of 2,2,6,6-Tetramethylpiperidine-1-oxoammonium tetrafluoroborate(TEMPO⁺BF₄^-)and?,?-unsaturated hydrazides/?,?-unsaturated hydrazides.