Nms-Amides: An Amine Protecting Group with Unique Stability and Selectivity

Philipp Spieß, Ana Sirvent Verdú, Irmgard Tiefenbrunner, Jules Sargueil, Anthony Julien Fernandes-Goodall, Ana Arroyo-Bondía, Ricardo José Cruz Meyrelles, David Just, Alexander Prado-Roller, Saad Shaaban, Daniel Kaiser, Nuno Maulide (Corresponding author)

Publications: Contribution to journalArticlePeer Reviewed

Abstract

p-Toluenesulfonyl (Tosyl) and nitrobenzenesulfonyl (Nosyl) are two of the most common sulfonyl protecting groups for amines in contemporary organic synthesis. While p-toluenesulfonamides are known for their high stability/robustness, their use in multistep synthesis is plagued by difficult removal. Nitrobenzenesulfonamides, on the other hand, are easily cleaved but display limited stability to various reaction conditions. In an effort to resolve this predicament, we herein present a new sulfonamide protecting group, which we term Nms. Initially developed through in silico studies, Nms-amides overcome these previous limitations and leave no room for compromise. We have investigated the incorporation, robustness and cleavability of this group and found it to be superior to traditional sulfonamide protecting groups in a broad range of case studies.

Original languageEnglish
Article numbere202301312
JournalChemistry - A European Journal
Volume29
Issue number41
DOIs
Publication statusPublished - 20 Jul 2023

Austrian Fields of Science 2012

  • 104015 Organic chemistry

Keywords

  • amines
  • density functional theory calculations
  • orthogonal deprotection
  • protecting groups
  • sulfonamides

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