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

• Published in: Chemistry : a European journal Vol. 29; no. 41; pp. e202301312 - n/a
• Main Authors: Spieß, Philipp, Sirvent, Ana, Tiefenbrunner, Irmgard, Sargueil, Jules, Fernandes, Anthony J., Arroyo‐Bondía, Ana, Meyrelles, Ricardo, Just, David, Prado‐Roller, Alexander, Shaaban, Saad, Kaiser, Daniel, Maulide, Nuno
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 20.07.2023; Wiley Subscription Services, Inc; John Wiley and Sons Inc
• Subjects: Amides; Amines; Chemistry; Chemistry, Multidisciplinary; density functional theory calculations; orthogonal deprotection; Physical Sciences; Protecting groups; Robustness; Science & Technology; Stability; Sulfonamides; protecting groups; CINACALCET; amines; density functional theory calculations; orthogonal deprotection; sulfonamides; BASIS-SETS; CLEAVAGE; STRATEGIES
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202301312

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. 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 and 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 conundrum, we herein present Nms‐amides, initially developed through in silico studies, which overcome these previous limitations and leave no room for compromise, enabling a range of transformations that are not possible with traditional sulfonamide protecting groups.