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

作者：Melzig Laurin; Rauhut Christian B; Naredi Rainer Nikolaus; Knochel Paul^*

来源：Chemistry - A European Journal, 2011, 17(19): 5362-5372.

DOI：10.1002/chem.201003657

• arenes
• heterocycles
• magnesium
• metalation
• sulfoxide-magnesium exchange

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 center dot LiCl (TMP=tetramethylpiperidine). After a quenching reaction with an electrophile, the resulting sulfoxide is converted into a second magnesium reagent with iPrMgCl center dot LiCl (sulfoxide-magnesium exchange), which can be trapped with various electrophiles. Highly chemoselective TMPMgCl center dot LiCl and iPrMgCl center dot LiCl are compatible with a broad range of functional groups (e.g., F, Cl, CF3, CN, CO(2)tBu, alkynyl, ethers, thioethers). Large-scale reactions (25-40 mmol) and the preparation of fully functionalised furans and thiophenes are also reported.

• 出版日期2011-5