One-Pot Synthesis of Sulfonamides from Unactivated Acids and Amines via Aromatic Decarboxylative Halosulfonylation

P. Scott Pedersen, David C. Blakemore, Gary M. Chinigo, Thomas Knauber, David W.C. MacMillan

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The coupling of carboxylic acids and amines to form amide linkages is the most commonly performed reaction in the pharmaceutical industry. Herein, we report a new strategy that merges these traditional amide coupling partners to generate sulfonamides, important amide bioisosteres. This method leverages copper ligand-to-metal charge transfer (LMCT) to convert aromatic acids to sulfonyl chlorides, followed by one-pot amination to form the corresponding sulfonamide. This process requires no prefunctionalization of the native acid or amine and extends to a diverse set of aryl, heteroaryl, and s-rich aliphatic substrates. Further, we extend this strategy to the synthesis of (hetero)aryl sulfonyl fluorides, which have found utility as “click” handles in chemical probes and programmable bifunctional reagents. Finally, we demonstrate the utility of these protocols in pharmaceutical analogue synthesis.

Original languageEnglish (US)
Pages (from-to)21189-21196
Number of pages8
JournalJournal of the American Chemical Society
Volume145
Issue number39
DOIs
StatePublished - Oct 4 2023

All Science Journal Classification (ASJC) codes

  • Catalysis
  • General Chemistry
  • Biochemistry
  • Colloid and Surface Chemistry

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