4196681

Expanding the scope of carbon-nucleophiles for nucleophilic aromatic substitutions of halopyridinium ketene hemiaminals | Poster Board #1185

Date
March 24, 2025

Nucleophilic aromatic substitution (SNAr) is one of the most frequently employed reactions in drug discovery, and it is estimated that between 15-20% of all C-N, C-O, and C-S bonds in pharmaceutical synthesis are prepared by this method. In contrast, C-C bond formation to aromatic and heteroaromatic ring systems are more often installed via metal-catalyzed cross coupling reactions. However, these reactions may involve more complex procedures, expensive catalysts, and metal-contamination that can interfere with critical bioassays. Recently, we have discovered that halopyridinium ketene hemiaminals are highly reactive in nucleophilic aromatic substitutions with nitrogen and sulfur nucleophiles. This presentation will detail our expansion into more challenging carbon nucleophiles such as electron-rich aromatics (e.g., indoles and anilines) and carbanions (e.g., enolates).

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