PIFA-mediated cyclization of methyl(2-(1-phenylvinyl)phenyl)sulfane for the concise, flexible, and scalable de novo synthesis of C3-arylated benzo[b]thiophenes

Abstract

The well-decorated arylated benzo[b]thiophene scaffold is a pivotal structural motif with diverse applications in medicinal chemistry. This paper outlines a de novo synthesis of C3-arylated benzo[b]thiophenes, showcasing its flexibility and efficiency. The methodology involves Pd-catalyzed coupling of N-tosylhydrazones with (2-bromophenyl)(methyl)sulfane derivatives, followed by cyclization under mild conditions using [bis-(trifluoroacetoxy)iodo]benzene (PIFA) to yield the desired C3-arylated benzo[b]thiophenes. Substrate scope investigations and a gram-scale reaction underscore this protocol's synthetic potential and scalability. The developed approach offers a concise and versatile strategy for accessing this important class of compounds, providing a valuable tool for medicinal chemistry and pharmaceutical research.