Fluorosulfuryl Isocyanate Enabled SuFEx Ligation of Alcohols and Amines. (18th August 2021)

• Record Type: Journal Article
• Authors: Sun, Shoujun; Gao, Bing; Chen, Junyu; Sharpless, K. Barry; Dong, Jiajia
• Is Part Of: Angewandte Chemie. Volume 133:Number 39(2021)
• Page Start: 21365
• Page End: 21369
• Publication Date: 2021-08-18
• Subjects: carbamates -- click chemistry -- fluorosulfuryl isocyanate -- on water -- SuFEx reaction -- urea; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202105583
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Fluorosulfuryl isocyanate (FSI, FSO2 NCO) is established as a reliable bis‐electrophilic linker for stepwise attachment of an alcohol bearing module to an amine bearing module and thence a new module RO‐C(=O)‐NH‐SO2 ‐NR′R′′ is created. FSI's isocyanate motif fuses directly and quickly with alcohols and phenols, affording fluorosulfuryl carbamates in nearly quantitative yield. A new reagent and process to deliver the FSI‐derived fluorosulfuryl carbamate fragment to amines are also developed. The resulting S VI −F motifs from step‐1 are remarkably stable, given the great structural complexities in diverse products. In the step‐2 reaction with amines, the best yield of the S−N linked products arise with water alone. This "on water" interfacial reactivity phenomenon is crucial, revealing the latent reactivity of S VI −F probe for potential covalent capture of proteins in vivo which is important in today's drug discovery. The scope of the SuFEx chemistry is largely expanded thereby and the facile entry to these phosphate‐like connections should prove useful to click chemistry across diverse fields. Abstract : Fluorosulfuryl isocyanate (FSI, FSO2 ‐NCO) is established as a reliable bis‐electrophilic linker for stepwise attachment of alcohol and amine bearing modules. In step‐1, FSI's isocyanate fuses directly and quickly with alcohols and phenols, and aliphatic amines are attached through the sulfuryl carbamate transfer strategy, both with remarkable selectivity. In step‐2, best yields of S−N linked products arise with a unique on water process. The scope of SuFEx ligation is greatly expanded in directions which would be especially interesting for drug discovery and chemical biology.