TY - JOUR
T1 - Nms-Amides: An Amine Protecting Group with Unique Stability and Selectivity
AU - Spieß, Philipp
AU - Sirvent Verdú, Ana
AU - Tiefenbrunner, Irmgard
AU - Sargueil, Jules
AU - Fernandes-Goodall, Anthony Julien
AU - Arroyo-Bondía, Ana
AU - Cruz Meyrelles, Ricardo José
AU - Just, David
AU - Prado-Roller, Alexander
AU - Shaaban, Saad
AU - Kaiser, Daniel
AU - Maulide, Nuno
N1 - Publisher Copyright:
© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.
PY - 2023/7/20
Y1 - 2023/7/20
N2 - 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.
AB - 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.
KW - amines
KW - density functional theory calculations
KW - orthogonal deprotection
KW - protecting groups
KW - sulfonamides
UR - http://www.scopus.com/inward/record.url?scp=85161059590&partnerID=8YFLogxK
U2 - 10.1002/chem.202301312
DO - 10.1002/chem.202301312
M3 - Article
AN - SCOPUS:85161059590
VL - 29
JO - Chemistry: A European Journal
JF - Chemistry: A European Journal
SN - 0947-6539
IS - 41
M1 - e202301312
ER -