Radical Alkylation Of Para C(sp~2)–OMe Bond In Aniline

One of most useful synthesis strategies for preparing functional aromatic compounds both in the laboratory and in industry is the cross coupling of aryl halides and organic nuclephiles.However,most aryl halides are derived from petroleum products,such as benzene,toluene,and xylenes.In addition,highly functionalized aryl halides aren’t convinient to obtain.Therefore,easily obtained aryl ethers can be used as powerful and pratical subtitutes for aryl halides.Despite the advances in nucleophilic functionalization of aryl ethers,the direct reaction of C(sp~2)–OMe group with electrophile still poses a challenge to date.Herein,a protocol for direct alkylation of inert Ar-OMe bond in anilines with electrophilicα-bromo esters and amides is reported with photoredox catalysis at room temperature via a radical pathway.The chemoselectivity is studied with Fukui indices for radical attack.A number of functional groups,including epoxide,imidate,alkene,alkyne and heterocycles,were well-tolerated.Straightforward syntheses of several pharmaceutical compounds are achieved with this approach.