Pummerer chemistry of benzothiophene S-oxides: Metal-free alkylation and arylation of benzothiophenes

Abstract

Functionalized benzothiophenes are important constructs found in molecules with wide ranging biological activity and in organic materials. An efficient, metal-free approach to C3 and C2 arylated and alkylated benzothiophenes is summarized in this review. The strategy utilizes synthetically unexplored yet readily accessible benzothiophene S-oxides in an interrupted Pummerer/charge accelerated [3,3]-sigmatropic rearrangement cascade process to regioselectively install aryl, allyl or propargyl groups at C3 of benzothiophenes at the expense of C–H bonds. The intermediate sulfonium salts generated after the interrupted Pummerer reaction lack aromaticity and therefore allow the [3,3]-sigmatropic rearrangement, the key C–C bond-forming event, to occur under mild conditions. In addition, a previously unexplored 1,2-migration of substituents in benzothiophenium salts, generated during the cascade process, can be used to access C2 functionalized benzothiophenes.

Graphical Abstract

Keywords:

• Pummerer reactions
• sulfoxides
• sigmatropic rearrangement
• sulfur heterocycles
• cascades