Silver-Catalyzed Direct Selenylation of Indoles

The functionalization of indole core has received considerable attention since this heterocycle is an important structural unit in many bioactive compounds and organic materials with technological interest.1 Among them, 3-chalcogenylindoles are an emergent class of synthetic structures due their potential therapeutic values in the treatment of different diseases such cancer, cardiovascular, and bacterial diseases.2 The methodologies reported for the preparation of 3-selenylindoles commonly involve the direct chalcogenylation of indole nucleus with various electrophilic organochalcogen reagents, then catalytic versions of these reactions employing safe diorganoyl dichalcogenides attracted interest. In the other hand, Ag-catalyzed reactions appeared as important synthetic tool for a variety of organic transformation.3 This fact prompted us to explore a Ag-catalyzed regioselective C3 direct selenylation of indole. The suitable reaction conditions were developed with 1H-indole and diphenyl diselenide with Ag(I) salts and dimethyl sulfoxide as solvent. First, we use 10 mol% of AgNO3 due low cost and availability, at a temperature of 100°C for 24 hours (GC yield = 35%, anthracene as internal standard). Then, another silver salts were investigated in the same conditions, affording the follow GC yields: Ag2CO3 (21%), Ag2O (82%) (Scheme 1) and Ag2SO4 (77%). The effects temperature, solvent, catalyst source and catalyst amount are under evaluation. The regioselective direct selenylation on C3 position of 1H-indoles was developed with use of silver salts as catalysts and the effect of each condition such as temperature, solvent effect and reaction is still been evaluated.