Intermolecular Heck-type Reaction Of Fluorosulfonamides And Unactivated Alkenes Enabled By Directing-group-based Strategy

The Mizoroki-Heck reaction is considered as one of the most effective ways for constructing carbon-carbon bonds,which is widely used in many fields,such as the synthesis of pharmaceutical active molecules and fine material preparation.For this reason,its discoverer R.F.Heck won the 2010 Nobel Prize in Chemistry.In this type of reaction,the substrate is often limited to activated olefins（such as styrene,acrylate,vinyl ether,etc.）and aryl/vinyl halides to build C_sp2-C_sp2 bonds.In recent years,it has been discovered that the single electron transfer（SET）process between alkyl electrophiles and transition metals is more energy-efficient than the oxidative addition process.On this basis,the Heck-type reaction between alkyl electrophiles and olefins has been greatly developed for the construction of C_sp2-C_sp3 bonds.This type of reaction generally generates alkyl radicals through the SET process between transition metal and alkyl electrophiles,avoiding the problem of slow oxidation and addition of the alkyl electrophile,and at the same time inhibiting theβ-H elimination of the alkyl metal intermediate.However,this type of reaction is often aimed at activated olefin substrates.For non-activated olefins with low reactivity,the coupling reaction with alkyl electrophiles is still a problem.Current research mainly uses trifluoromethyl-stable carbon radical precursors for intermolecular coupling with non-activated olefins,while studies on unstable alkyl radicals with non-activated olefins are very rare.In this paper,N-fluorosulfonamide is used as the precursor of alkyl radicals.Under the catalysis of transition metal copper,nitrogen radicals are generated through the SET process,and then alkyl radical intermediates are generated through the1,5-hydrogen atom transfer（HAT）process,subsequently reacted with non-activated olefins tethered with a directing group.The intermolecular Heck-type coupling of unstable alkyl radicals and non-activated olefins was realized,and the C_sp2-C_sp3 bond was constructed,the long chain internal olefin with sulfonamide group was synthesized at the same time.This method is suitable for variousα-substituted non-activated olefins and N-fluorosulfonamides that can generate secondary and tertiary alkyl radicals,at the same time,excellent regioselectivity and good stereoselectivity are maintained.The content of this paper could be divided into the following two parts:The first part summarized the development of Heck-type reactions involving alkyl electrophiles and non-activated olefins,and the functionalization reaction of remote C_sp3-H initiated by nitrogen radicals is also briefly described.The second part focuses on the introduction of the research background,optimization of experimental conditions,substrates scope and mechanism.This protocol features wide functional group compatibility and broad substrate scope,which could efficiently synthesize the long-chain internal olefins containing amide groups.