Studies On Difunctionalization Of Olefins Via Visible-Light-Induced Atom Transfer Pathway

Olefins can be used as receptors to realize functionalization in visible light induced reactions.It is an effective method to use the free-radical addition route to realize the functionalization of olefins for the synthesis of biological and pharmaceutical intermediates.Difunctionalization of olefins is one of the important methods to construct complex organic compounds,which can complete the functionalization at both ends of olefins in one step.The currently reported difunctionalization of olefins generally have problems such as high energy consumption,high cost,low atomic utilization and environmental friendliness.Hence,in this paper three kinds of atom transfer pathways,proton-coupled electron transfer（PCET）,hydrogen atom transfer（HAT）and halogen atom transfer（XAT）for visible-light-induced difunctionalization of olefins have been studied.The visible light induced method was used to promote the conversion of diazocarboxylates to carbene radicals via the PCET pathway.Thenγ-amino acid esters was synthesized by the reaction of 1,2-difunctional alkenes with carbene radical and diarylamine.Using 30 W blue LEDs（450-490 nm）as light sources and Ir[d F（CF₃）ppy]₂（dtbbpy）PF₆ as photocatalysts,three-component reactions were carried out at room temperature with 14 kinds of diarylamines,2 kinds of diazocarboxylates and12 kinds of arylolefin and alkylolefin substrates.A series ofγ-amino acid esters were synthesized in one step with a yield of 19%-88%.This method avoids the steps of pre-functionalization.Theγ-amino acid ester（58%）was obtained by the gram scale-up experiment.The reaction mechanism was studied by fluorescence quenching experiment,deuterium generation experiment,etc.It was confirmed that the reaction system was a reduction quenching cycle,and proved that the carbene radical was obtained via the PCET（proton-coupled electron transfer）pathway.A diazonium derivative,4-methoxyphenyl diazonium salt（PMPN₂BF₄）was used as a HAT（hydrogen atom transfer）reagent to activate hydrogen donors such as malonates and halogenated hydrocarbons.Pyrrole[3,2-c]quinolines and indole[2,1-α]isoquinolines were prepared by using two kinds of olefins as substrates in the 1,2-difunctional cyclization of olefins.Under the illumination of 10 W 455 nm LED,34 kinds of ring-closing products were obtained at room temperature,and the yield was 30%-91%.The yield of indole[2,1-α]isoquinoline was 70%in gram scale-up experiment.The mechanism of the reaction was investigated by kinetic experiments,which proved the dehydrogenation process of hydrogen donors participated in the decisive step of the reaction.The oxidative quenching cycle XAT dehalogenation process was designed and indole[2,1-α]isoquinolines were prepared by 1,2-difunctional cyclization of olefins.Using 10 W 455 nm LED lamp as light sources,TBHP（tert-butyl peroxide）as HAT reagents,diisopropylethylamine as XAT reagents,indole[2,1-α]isoquinoline derivatives were obtained at room temperature via 1,2-olefin difunctionalization with 9 kinds of 2-aryl indolene substrates,18 kinds of halogenated hydrocarbons.What is more,9 kinds of ring-closing substrates involved inα-amino carbon radicals were extended.The yield of indole[2,1-α]isoquinolines was 31%-92%.The indole[2,1-α]isoquinoline was obtained in gram scale-up reaction（yield 85%）.The mechanism of the reaction was studied by the free radical trapping control experiment and the isotope effect experiment.The difference in kinetic mechanism of the ring closure reaction between XAT pathway and HAT pathway was made clear.In this reaction,the formation of carbon radicals by dehalogenation was not the decisive step（KIE=1.0）.