Fluorosulfuryl Isocyanate Enabled SuFEx Ligation of Alcohols and Amines.

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.

SUBMITTER: Sun S 

PROVIDER: S-EPMC9881234 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature