Application Of Hantzsch Ester In Visible-light-indcued Hydrodifluoroalkylation Of Alkenes

Hantzsch esters,has been widely used in organic synthesis as a multifunctional reagent.Since first reported in 1881,it has been applied in transfer hydrogenation reactions through various pathways as hydride donor.In addition,via a hydrogen atom transfer process,Hantzsch ester could be converted to radical intermediate which was highly potent electron donor drived by aromatization.Therefore,Hantzsch ester plays an important role in reductive reaction via electron transfer pathway.This thesis focused on the reducing potency of Hantzsch ester's radical,includinga)Thiyl-radcial-catalyzed hydrodifluoroacetamidation of alkene with Hantzsch ester as electron-donor and hydrogen atom donor.b)Hydrodifluoromethanephosphonylation of alkene via a synegestic catalysis of thiyl radical/fac-Ir(ppy)3 with Hantzsch ester as terminal reductant.These two sections were introduced as:1.Thiyl-Radical-Catalyzed Photoreductive Hydrodifluoroacetamidation of Alkenes with a Hantzsch Ester as a Multifunctional ReagenIn this chapter,hydrodifluoroacetamidation of alkenes with readily available?-bromodifluoroacetamide was achieved with Hantzsch ester as electron donor and hydrogen atom source using phenyl thiyl radical catalysis at room temperature under visible light irradiation in MeCN.The reaction condition was mild and had good tolerability for various non-activated olefin,alkenes containing heterocycles and alkenes incorporating a variety of functional groups.It was also suitable to progesterone derivatives.With this approach,a derivative containing difluoroalkyl high serine was synthesized.Mechanism studies show that thiyl radicals may first capture the C4 hydrogen atom of Hantzsch ester,then the generated Hantzsch ester free radical intermmediates reducing a-bromodifluoroacetamides giving difluoroacetamides radicals.The difluoroacetamide radicals attacked olefin with following hydrogenation addition.2.Photocatalytic Hydrophosphonodifluoromethylation of Alkenes Prompted by Electron Transfer from Excited Hantzsch Ester to PhotocatalystIn this chapter,we reported a protocol for visible-light-induced catalytic hydrophosphonodifluoromethylation of mono-and disubstituted alkenes using bromodifluoromethanephosphonate with Hantzsch ester as electron donor and hydrogen atom donor,HSAcOMe as hydrogen transfer reagents,fae-Ir(ppy)3 as the photosensitizer and K2CO3 as base in CH3CN.The reaction conditions were mild and compatible with a number of fucnationalities.Single or double substituted olefins were effective substrates in this transformation.Compared with the traditional 7-step synthesis of PNP inhibitor intermediate(1,1-difluorophosphate-5-hydroxy hexane),this pharmaceutical compound was achieved with in one step with 57%increase of yield.Mechanism study revealed that the reaction may occurred in multiple pathways.At first excited fac-Ir(ppy)3 is reduced by Hantzsch ester or its readical derivative.giving Ir? species.This species then transfers one erlectron to bromodifluoromethanephosphonate and generates difluorocarbon radical adding to alkenes.