Hydrogen Atom Transfer Promoted Addition Of Alkenyl Radicals To Aldehydes

Alcohols are versatile building blocks and serve as important synthetic intermediates for preparation of complex molecules.As such,the development of efficient methods for constructing these compounds is of significant importance.As compared to ionic reactions,radical reactions are featured with mild conditions and excellent functional group tolerance,thus providing an efficient method for the synthesis of alcohols.Radical addition to carbonyls constitutes a formidable challenge,due to the formation of thermodynamically unfavorable alkoxy radicals.In this respect,the reductive radical addition to carbonyls is a common strategy,which suffers from the use of stoichiometric reductants,highly toxic reagents,and poor functional group compatibility.With hydrogen atom transfer（HAT）of alkoxy radicals as the key step,two novel reductive radical addition of alkenyl radicals to aldehydes have been developed here,thus providing facile access to cyclic alcohols or ethers with high efficiency under mild reaction conditions.The main contents are summarized as follows:1.Investigations on the intermolecular HAT-promoted the addition of alkenyl radicals to aldehydes.Using fac-Ir（ppy）₃as the photocatalyst,K₃PO₄as the base,and THF as the solvent,a visible light photocatalytic coupling of alkynyl aldehydes with fluoroalkyl halides is realized,in which fluoroalkylated cyclic alcohols are synthesized in moderate to high yields.It is believed to proceed via a mechanism consisting of fluoroalkylation of C-C triple bonds,5-exo cyclization of aldehyde,and HAT between the in situ form alkoxy radicals and tetrahydrofuran.This work is highlighted by the use of environmentally friendly tetrahydrofuran,instead of the traditional toxic n-Bu₃Sn H,as the hydrogen atom source,thus making it a highly appealing method for synthetic application.2.Investigations on the intramolecular HAT-promoted the addition of alkenyl radicals to aldehydes.Using fac-Ir（ppy）₃as the photocatalyst,Na HCO₃as the base,acetonitrile as the solvent,a remote C-H etherization triggered by radical addition to thioalkyne benzylether has been achieved for the first time,providing a direct access to cyclic ethers at room temperature in medium to high yields.Various functional groups such as fluorine,chlorine,bromine,trifluoromethyl,methyl,cyano,and ester groups are compatible for this reaction.It is worth mentioning that this reaction displays excellent diastereoselectivity and represents one of the rare examples of diastereoselective radical-mediated transformations.Mechanistic studies suggest a mechanism comprising sulfur-directedβ-addition,5-exo cyclization of carbonyls,intramolecular 1,5-HAT,single electron transfer oxidation,and C-O bond formation.Our work represents one of the rare examples of diastereoselective remote C-H functionalization,thus providing new opportunities for the development of selective functionalization of inert C-H bonds.