Visible Light Induced Radical Cascade Reactions Of Alkenes For The Synthesis Of Hydrazine Compounds

Organic hydrazine compounds have been widely used in the synthesis of pesticides,dyes and drugs.They are often used for the synthesis of heterocyclic compounds such as pyrazole and pyridazine as well.Hydrazine-containing heterocyclic compounds with special functional groups inβorγpositions have also been widely used in the development of pharmaceutical molecules.In this dissertation,organic hydrazine compounds with special functional groups were efficiently constructed through the three-component radical cascade reactions of an alkene,a nucleophile and an electrophilic radical acceptor under the irradiation of visible light with organic photosensitizers.1)Under visible light,9-fluorenone was used as photosensitizer to catalyze the three-component radical cascade reactions of an corresponding unactivated alkene,TMSN₃ and di-tert-butyl azodicarboxylate.The reaction exhibited a wide range of substrates.Various types of alkenes,such as conjugated,non-conjugated,di-substituted or tri-substituted ones were well-tolerated.The products could also be effectively derived into 1,2-diamines and corresponding heterocyclic compounds in good yields.In addition,the methodology had also been successfully applied to the total synthesis of ibrutinib,which is used as an anticancer drug.Mechanistic and kinetic studies revealed that azide radical can be efficiently generated by 9-fluorenone under visible light irradiation.Although each step in the tandem reaction is fast,the addition of azide radical to alkenes is a reversible process.So the structure of alkenes has a significant impact on overall reaction rate,as it determines the concentration of the alkyl radical intermediate.Substituents such as arenes or hetero atoms are able to stabilize the alkyl radical adducts and lead to faster reactions,while simple alkyl substituents show inferior stablization effect and thus resulted in slower reactions.2)Under visible light,Mes Acr⁺ClO₄^-was used as a photosensitizer to catalyze the three-component radical cascade reaction of an unactivated alkenes,CF₃SO₂Na and di-tert-butyl azodicarboxylate.This method renders an efficient approach toβ-trifluoromethyl hydrazines with readily available reagents and is applicable to a broad range of alkenes.In addition,correspondingβ-trifluoromethylamino compounds,β-trifluoromethylated pyrazoles or pyridazine-based heterocyclic compounds can also be synthesized from the products.A series of mechanistic studies unveiled that the behaveior of trifluoromethyl radical and azide radical are quite different.In this cascade,the addition of trifluoromethyl radical to an alkene is a fast and irreversible process,while the capturing of alkyl radical intermediate by di-tert-butyl azodicarboxylate is relatively slow.3)Under visible light,Mes Acr⁺ClO₄^-was used as the photosensitizer to catalyze the three-component radical cascade reaction of an unactivated alkenes,CF₃SO₂Na and acylhydrazone compounds.This transformation produced a series ofγ-trifluoromethyl hydrazines and the experimental results suggested that the acylhydrazone shows different reactivity compared to azodicarbonate,in terms of electrophilicity.This reaction is applicable to various types of non-conjugated olefins and enol ether substrates while styrene-based conjugated olefins can not be converted to the desired products.