Benzo<b>thiophenes are an important class of sulfur-containing heterocycles that are found in pharmaceuticals such as raloxifene, sertaconazole, or zileuton, and used as building blocks for synthesis of agrochemicals, and materials. New drug candidates are being actively developed, and for some compounds, presence of sulfur can be the determining factor in biological activity. Continued development of new methods for synthesis of this important molecular scaffold is warranted because current methods either use stoichiometric reagents or metal catalysts that are costly or require air- and moisture-free reaction conditions. Here we report an efficient method for gold(I)–IPr hydroxide-catalyzed synthesis of benzo<b>thiophenes from 2-alkynyl thioanisoles. For our model substrate, the reaction proceeds efficiently in presence of 1 mol % of Au(IPr)Cl or Au(IPr)OH. Notably, the reaction only occurs in presence of a Brønsted acid of sufficient strength. We will present our investigation of the effect of the catalyst, solvent, reaction conditions, and additives on the reaction. We will also discuss the mechanistic hypotheses and experimental evidence that support it.

Synthesis of 2-substituted benzothiophenes via gold(I)–IPr hydroxide-catalyzed cyclization of 2-alkynyl thioanisoles

2019 Spring National Meeting

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