New Sulfinylamine Reagent

Sulfonamides are found in many pharmaceutically active compounds and several widely used drugs. Primary sulfonamides are also useful intermediates in organic synthesis. Usually, primary sulfonamides are prepared via a reaction of sulfonyl chlorides or similar activated species with ammonia, followed by a deprotection step. However, this synthesis involves harsh conditions and hard-to-handle reagents. Alternative approaches suffer from, e.g., limited substrate scopes or a need for harmful reagents.

Michael C. Willis, University of Oxford, UK, and colleagues have developed a new sulfinylamine reagent, N-sulfinyl-O-(tert-butyl)hydroxylamine (t-BuONSO, pictured), that can be used for the synthesis of primary sulfonamides. The t-BuONSO reagent was prepared on a 15 g scale from commercially available O-tert-butylhydroxylamine hydrochloride via a reaction with thionyl chloride and triethylamine. The reagent is a stable, colorless liquid.

The team then converted a variety of (hetero)aryl or alkyl Grignard reagents or organolithiums to the corresponding primary sulfonamides by reacting them with t-BuONSO in tetrahydrofuran (THF) at –78 °C. The desired products were obtained in good to excellent yields, and the reaction shows good functional group tolerance. Overall, the new reagent allows for a convenient one-step synthesis of primary sulfonamides.

• Primary Sulfonamide Synthesis Using the Sulfinylamine Reagent N-Sulfinyl-O-(tert-butyl)hydroxylamine, t-BuONSO,
  Thomas Q. Davies, Michael J. Tilby, David Skolc, Adrian Hall, Michael C. Willis,
  Org. Lett. 2020.
  https://doi.org/10.1021/acs.orglett.0c03505

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