Mechanistic insight enables practical, scalable, room temperature Chan–Lam N-arylation of N-aryl sulfonamides

Julien C. Vantourout, Ling Li, Enrique Bendito-Moll, Sonia Chabbra, Kenneth Arrington, Bela E. Bode, Albert Isidro-Llobet, John A. Kowalski, Mark G. Nilson, Katherine M. P. Wheelhouse, John L. Woodard, Shiping Xie, David C. Leitch, Allan J. B. Watson

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)
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Abstract

Sulfonamides are profoundly important in pharmaceutical design. C–N cross-coupling of sulfonamides is an effective method for fragment coupling and structure–activity relationship (SAR) mining. However, cross-coupling of the important N-arylsulfonamide pharmacophore has been notably unsuccessful. Here, we present a solution to this problem via oxidative Cu-catalysis (Chan–Lam cross-coupling). Mechanistic insight has allowed the discovery and refinement of an effective cationic Cu catalyst to facilitate the practical and scalable Chan–Lam N-arylation of primary and secondary N-arylsulfonamides at room temperature. We also demonstrate utility in the large scale synthesis of a key intermediate to a clinical hepatitis C virus treatment.
Original languageEnglish
Pages (from-to)9560-9566
Number of pages7
JournalACS Catalysis
Volume8
Early online date6 Sept 2018
DOIs
Publication statusE-pub ahead of print - 6 Sept 2018

Keywords

  • Boronic acid
  • Boronic ester
  • Catalysis
  • Chan-Lam
  • Copper
  • Sulfonamide

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