Late-Stage Radical (Radio)fluorosulfonylation of Amines with [19F]fluoride and [18F]fluoride

Abstract

Abstract Late-stage labeling with fluorine-18 serves to advance clinical care and drug discovery via positron emission tomography (PET). This goal motivates efforts to expand the accessible chemical space with tailored 18F-containing groups. Sulfamoyl fluorides are promising because of their potential physiological stability. Existing synthetic routes largely depend on group-transfer protocols from preformed fluorosulfonyl reagents. As a result, synthetic methods for [18F]sulfamoyl fluorides are fundamentally based on isotope exchange. None of the methods have enabled a no-carrier-added (NCA) protocol for radiofluorosulfonylation of amines. Herein, we provide nitrogen-centered radical-mediated assembling fluorosulfonylation reactions, enabling conversion of abundant NH-containing substrates into sulfamoyl fluorides with [19F]fluoride and [18F]fluoride as an exclusive fluorine source. Our method features high functional group tolerance, broad NH-substrates, and an NCA radiochemical technique. The initial preclinical evaluation of the freshly synthesized [18F]SUFA-flurpiridaz and its in vivo myocardial perfusion PET imaging collectively highlights the potential physiological stability of sulfamoyl [18F]fluoride groups and the potential application of our radical radiofluorosulfonylation strategy.

The authors' abstract, as published at the source. ACS Central Science, 2026 · DOI ↗