Overcoming Challenges in O‐Nitration: Selective Alcohol Nitration Deploying N,6‐Dinitrosaccharin and Lewis Acid Catalysis

• Published in: Angewandte Chemie International Edition 2024-10, Vol.63 (40), p.e202411073-n/a
• Main Authors: Fernandes, Anthony J., Valsamidou, Vasiliki, Katayev, Dmitry
• Format: Article
• Language: English
• Subjects: Alcohol; Alcohols; Alkenes; Alkynes; Carbonyl compounds; Carbonyls; Catalysis; Catalysts; Chemical synthesis; Density Functional Theory; Energetic materials; Environmental chemistry; Esters; Functional groups; Lewis acid; Magnesium; Materials science; Mechanism; Nitrate esters; Nitrates; Nitration; Reagents; Substrates
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202411073

Nitrate esters hold pivotal roles in pharmaceuticals, energetic materials, and atmospheric processes, motivating the development of efficient synthesis routes. Here, we present a novel catalytic method for the synthesis of nitrates via the direct O‐nitration of alcohols, addressing limitations of current traditional methods. Leveraging bench‐stable and recoverable N,6‐dinitrosaccharin reagent, our catalytic strategy employs magnesium triflate to achieve mild and selective O‐nitration of alcohols, offering broad substrate scope and unprecedentedly large functional group tolerance (e.g. alkenes, alkynes, carbonyls). DFT mechanistic studies reveal a dual role of the magnesium catalyst in the activation of both the nitrating reagent and the alcohol substrate. They also unveil a barrierless proton transfer upon formation of a widely‐accepted – yet elusive in solution – nitrooxonium ion intermediate. Overall, our work contributes to the development of mild, selective, and sustainable approaches to nitrates synthesis, with potential applications in drug discovery, materials science, and environmental chemistry. We present a novel catalytic approach for the mild and selective synthesis of nitrate esters by direct O‐nitration of alcohols and diols. Using stable N,6‐dinitrosaccharin and magnesium triflate, this method tolerates a broad diversity of functional groups and is amenable to late‐stage functionalization. DFT studies reveal a dual role of magnesium catalyst. This innovative method advances the synthesis of versatile nitrates for drug discovery.