[3,3]-Sigmatropic Rearrangement Of Aryl Fluoroalkyl Sulfoxides With Alkyl Nitriles

Aromatic[3,3]-σrearrangement is a powerful synthetic protocol for accessing valuable arene derivatives.In the past few years,[3,3]-σrearrangement of aryl sulfoxides with certain nucleophiles via constructing unstable rearrangement precursors has attracted great attentions from synthetic community.This type of reactions proceeding under catalyst-and metal-free conditions features remarkable selectivity and excellent functional group compatibility and has become a practical synthetic tool.In this context,we serendipitously discovered the[3,3]-σrearrangement of aryl sulfoxides with alkyl nitriles.The reaction involves the assembly of both reaction partners,deprotonation by base,and rearrangement process.As such,we developed an“assembly/deprotonation”strategy for triggering[3,3]-σrearrangement.On the other hand,the difluoromethylthio group is generally considered as a highly lipophilic weak hydrogen bonding donor and thus plays critical roles in many pharmaceuticals,agrochemicals and bioactive compounds.This project aims to apply the“assembly/deprotonation”protocol for developing[3,3]-σrearrangement of aryl fluoroalkyl sulfoxides with alkyl nitriles.The reaction consists of three steps including the Tf₂O initiated assembly of both coupling partners,deprotonation of in situ generated imine sulfonium intermediates giving ketenimine sulfonium species,and final[3,3]-σrearrangement producing ortho-cyanoalkylated difluoromethylthio arenes.The project not only incorporates valuable cyano groups into arens but also produces important bioactive difluoromethylthio group.It is worthy to note that the introduction of fluoroalkyl groups improves the electrophilicity of aryl sulfoxides and thus make the reaction system applicable to some electron-rich aryl sulfoxides,which cannot be tolerated by the reaction of normal aryl sulfoxides we developed before.Thus,the study also provides a new insight into the aryl sulfoxide-rearrangement chemistry.