Difunctionalisation of Arenes and Heteroarenes by Directed Metallation and Sulfoxide–Magnesium Exchange

Abstract

The aryl sulfoxide moiety allows an expedient two‐step difunctionalisation of readily available diaryl sulfoxides. Highly functionalised 1,2,4‐trisubstituted arenes and difunctionalised heteroarenes (furans, thiophenes, benzofurans and pyridines) were prepared in a two‐step sequence, triggered by an aryl sulfoxide group. In the first step, the sulfoxide moiety acts as a metallation‐directing group, allowing smooth ortho‐magnesiation with TMPMgCl⋅LiCl (TMP=tetramethylpiperidine). After a quenching reaction with an electrophile, the resulting sulfoxide is converted into a second magnesium reagent with iPrMgCl⋅LiCl (sulfoxide–magnesium exchange), which can be trapped with various electrophiles. Highly chemoselective TMPMgCl⋅LiCl and iPrMgCl⋅LiCl are compatible with a broad range of functional groups (e.g., F, Cl, CF₃, CN, CO₂tBu, alkynyl, ethers, thioethers). Large‐scale reactions (25–40 mmol) and the preparation of fully functionalised furans and thiophenes are also reported.