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

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.

Entschützende Funktionalisierung: eine direkte Umwandlung von Nms‐Amiden in Carbonsäureamide

“…Herkömmliche Benchmark‐Sulfonamide wie Ns(nosyl)‐ Amide und Ts(tosyl)‐Amide zwangen Chemiker jedoch in der Vergangenheit dazu, Kompromisse zwischen chemischer Stabilität und einer zuverlässigen und milden Entschützung einzugehen. Um dieses Problem anzugehen, haben unsere Gruppe und Yokoshimas Team kürzlich neu entwickelte Sulfonamid‐Schutzgruppen eingeführt: Nms‐Amide [14] und f Xs‐Amide [15] (Schema 1B).…”

“…B. Natriumsulfide) hergestellt werden müssen (Schema 3B). Darüber hinaus schränkt die relativ geringe chemische Stabilität von Dinitrobenzolsulfonamiden ihre Verwendung ein und macht sie zu einer ansonsten selten verwendeten Schutzgruppe [14,27] …”

Deprotective Functionalization: A Direct Conversion of Nms‐Amides to Carboxamides Using Carboxylic Acids

“…Conventional benchmark sulfonamides such as Ns(nosyl)‐amides and Ts(tosyl)‐amides, however, have historically forced chemists to compromise between chemical stability and a reliable and mild deprotection. To address this issue, our group and Yokoshima's team have recently introduced newly developed sulfonamide protecting groups: Nms‐amides [14] and f Xs‐amides [15] (Scheme 1B), respectively.…”

“…sodium sulfides) (Scheme 3B) [26] . Moreover, the comparatively low chemical stability of dinitrobenzenesulfonamides, restricts their use and renders them an otherwise rare protecting group [14,27] …”

Synthesis of Complex Tetracyclic Fused Scaffolds Enabled by (3 + 2) Cycloaddition

“…Additionally, the scope of the (3 + 2) cycloaddition was examined using various protected amines to allow for milder deprotection conditions. Good results were obtained with both Nms 26 and Boc protecting groups, which provided products 5l and 5m , respectively.…”