An Umpolung Strategy Enabled α-C-H Functionalization Of Oxazolines

α-C-H functionalization of carbonyl compounds repersents a main research direction of synthetic chemistry.The conventional α-functionalization relies on the use of strong bases to remove α-proton to form enolates that can react with electrophilic species.With the help of this model,a series of name reactions including Aldol reaction,Claisen condensation and Dieckmann condensation have been developed.In contrast,in past few years,an umpolung protocol via coordination/oxidation of carbonyls with hypervalent iodine has been validated which makes the original nucleophilic α-carbon to be electrophilic.Thus,it can be coupled with nucleophilic species.However,the instability of the iodane/carbonyl intermediates and hypervalent iodine itself often leads to poor functional group compatibility and limites the substrate scope,eventually restricting the adoption of the reaction.Recently,our research group developed an asymmetric [3,3] rearrangement reaction between aryl iodanes and chiral oxazolines.Mechanistic studies revealed that oxazolines exhibit more effective interaction with iodanes than that of other carbonyl compounds,thus enabling the rearrangement that cannot occur with other carbonyl compounds.It can be expected that the effective interation between oxazolines and iodanes might be used to solve the poor stability issue in the field of iodane-induced umpolung of carbonyls.On the basis of this consideration,an arrary of iodine(III)and sulfur(IV)species were screened.As a result,an aryl sulfoxide appears to be the most effective oxidant which can be readily assembled with oxazolines in presence of electrophilic reagent(TFAA).Subsequent deprotonation by mild base(DBU)leads to an enamine sulfonium intermediate,which can be trapped by a nucleophile to giveα-C-H functionalized oxazolines.It was found that a wide variety of nucleophiles such as aniline,alkyl amine,thiophenol,phenol and malonic ester are suitable for the process.In addition,the reaction featrues mild conditions,excellent functional group compatibility,and broad substrate scope for both oxazolines and nucleophiles.In short,this study not only offers an important synthetic method for α-C-H functionalization of oxazolines,but also provides a more effective protocol for the umpolung chemistry of carbonyl compounds.