Directing-group-based Strategy Enabling Intermolecular Heck-type Reaction Of Cycloketone Oxime Esters And Unactivated Alkenes

The Mizoroki-Heck reaction of aryl/vinyl(pseudo)halides and alkenes is considered as one of the most powerful methods in constructing Csp~2-Csp~2 bonds.Recent research advances show that alkyl electrophiles can service as good partners to undergo Heck-type reactions with olefins to form Csp~2-Csp~3 bonds.This type of Heck-like reaction usually relies in a single electron transfer(SET)process betwwen alkyl electrophiles and transition metal species to generate alkyl radical intermediates,which can avoid both slow oxidative addition and?-H elimination.Current research on alkyl-Heck-type reactions mainly focuses on the reaction between activated olefins and alkyl electrophiles,while less attention has been paid to the intermolecular Heck-type reactions of non-activated olefins and alkyl electrophiles with only a few cases,wherein the non-activated olefins are performed to couple with alkyl radical intermediates stabilized by adjacent functional groups.However,the intermolecular Heck-type reactions of non-activated olefins and unstable alkyl radical intermediates without adjacent functional groups have not been studied.In this case,exploring a new strategy to realize the Heck-type reaction of non-activated olefin and unstable alkyl radical intermediate can not only expand the research scope of the Heck-type reactions,but also enrich the alkyl radical chemistry.In this paper,a combination of non-activated olefins tethered with a directing group and cycloketone oxime esters is used to realize the first intermolecular Heck-type reaction between an unactivated olefin and an unstable alkyl radical intermediate.This protocol provided an efficient cyanide-free synthesis of internal cyanoalkenes,and was compatible with a variety of non-activated olefins as well as cyclobutanone,cyclopentanone,and cyclohexanone-derived oxime esters.Furthermore,density functional theory(DFT)calculations showed that the2-butanol-assisted concerted H-OBz elimination of conformationally strained metallacyclic transition state is the main reason for the reaction to obtain excellent regioselectivity and good diastereoselectivity.The content of this paper could be devided into the following two parts:The first part summarized the development of Heck-type reactions involving alkyl electrophiles and briefly described the transition metal-catalyzed and photo-induced ring-opening reactions of cycloketone oxime esters.In the second part,the research background of this paper was introduced.The intermolecular Heck-type reaction between non-activated olefins and cycloketone oxime esters was realized for the first time.This reaction provided an efficient method for the synthesis of internal cyanoalkenes without the need of additional cyanide source.High regioselectivities,good stereoselectivities,and compatibility with various functional groups were observed for these reactions.