Copper-catalyzed Intramolecular Difunctionalization Of Alkenes For The Synthesis Of Heterocyclic Compounds

Heterocyclic compounds are a class of important structural units,which widely existed in biologically active natural products,pharmaceuticals,pesticides and functional materials,and are also important synthetic intermediates in chemical and drug synthesis.Therefore,the development of convenient and efficient ways to synthesize heterocyclic compounds is the goal and pursuit for synthetic chemist.Among them,the construction of heterocyclic compounds catalyzed by copper has become the focus of scientific research.By controllable adjustment of the oxidation states of Cu（0）,Cu（I）,Cu（II）and Cu（III）,they can exhibit By controlling the oxidation states of Cu（0）,Cu（I）,Cu（II）and Cu（III）,they can exhibit variable catalytic properties,thus realizing a variety of free radical or oxidative coupling reactions.Moreover,copper also can be used as an alternative catalyst to highly toxic and expensive transition metals,which covers the shortage of environmental pollution and high cost of synthesis.This thesis aims to develop green and efficient methods using the copper catalysis for the synthesis of heterocyclic compounds featuring simple,environmental friendly,highly step-/atom-economy.In this thesis,a series of copper-catalyzed intramolecular difunctionalization of alkenes are developed,which mainly including the following three aspects:1.A new copper-catalyzed two-component amino-benzoyloxylation of unactivated alkenes of unsaturated ketoximes with O-benzoylhydroxylamines as the benzoyloxy sources is developed.Chemoselectivity of this method toward amino-benzoyloxylation or oxy-benzoyloxylation of alkenyl ketoximes relies on the position of the tethered olefins,and provides an external-oxidant-free alkene difunctionalization route that directly utilizes O-benzoylhydroxylamines as the benzoyloxy radical precursors and internal oxidants,Cu Cl as the catalyst and phosphoric acid（BNAP）L1 acts as ligand.A series of cyclic nitrones and isoxazolines were synthesized divergently under the standard condition.Control experiments show that this reaction is a copper-catalyzed radical difunction of olefins initiated by oxime,and chemselectively delivers amin-oxidation or dioxidation products.2.A copper-catalyzed chemically selective radical difunctional cyclization ofγ,δ-unsaturated ketoximes with benzoylhydroxylamine is presented.By using Cu Cl₂as catalyst and DIPEA as the additive,a series of heterocyclic compounds with potential medicinal value were selectively synthesized in argon.The reaction conditions are mild and a wide range of functional groups are well tolerated.The mechanism study shows that the intramolecular diamination of alkenes is initiated by the oxime radicals,and the catalytic cycle of the reaction is driven by the active Cu（II）species.3.A copper-catalyzed enantioselective aryl boration of activated olefin is reported.Using Cu OAC as catalyst,（R）-（CHTFPO*）L1 as ligand and ^tBu OK as base,chiral 3,3’-disubstituted indoline-oxidized derivatives were efficiently prepared at 50^oC.The enantioselective arylboration of the C=C double bond tethered to o-iodoacrylamide was achieved by tuning the chiral ligands,and then the enantioselective difunctionalization reaction was achieved to obtain the arylboration products of alkenes in high enantiomeric excess.