Synthesis of Thiophenes from Pyridines Using Elemental Sulfur.

Abstract

We describe a skeletal editing of pyridines to afford thiophenes through a formal [4 + 1] reaction using elemental sulfur. 2-Arylpyridines are converted to ring-opened aza-triene Zincke ketone structures, followed by simple treatment with sulfur to give 2-aroylthiophene products directly. The amphiphilic character of octasulfur enables smooth reaction with the Zincke dienamine, affording the cyclized products under mild and neutral conditions. We illustrate this new disconnection with a synthesis of the anti-inflammatory drug suprofen from a pyridine starting material.