TY - JOUR
T1 - A modular flow platform for sulfur(VI) fluoride exchange ligation of small molecules, peptides and proteins
AU - Bernús, Miguel
AU - Mazzarella, Daniele
AU - Stanić, Jelena
AU - Zhai, Ziran
AU - Yeste-Vázquez, Alejandro
AU - Boutureira, Omar
AU - Gargano, Andrea F. G.
AU - Grossmann, Tom N.
AU - Noël, Timothy
PY - 2024/2
Y1 - 2024/2
N2 - Sulfur(VI) fluoride exchange click chemistry is a formidable tool to rapidly and effectively link chemical structures. Despite advances in the field in recent years, the installation of the sulfonyl fluoride handle still requires the use of purpose-designed, expensive and non-atom-economic reagents. The use of the SO2F2 for sulfonyl fluoride synthesis has been thwarted by the difficulties associated with the manipulation and dosage of this toxic gas, and by its apparent low reactivity with amino functionalities. Here we report a modular flow platform that can generate on demand, and efficiently dose, gaseous SO2F2. The use of flow technologies allows many lingering limitations of this transformation to be overcome, resulting in reduced reaction times, efficient reactivity and broad substrate scope. The effectiveness of the process was demonstrated by the successful synthesis of a diverse set of fluorosulfates and sulfamoyl fluorides, including those derived from biorelevant compounds, peptides and proteins.
AB - Sulfur(VI) fluoride exchange click chemistry is a formidable tool to rapidly and effectively link chemical structures. Despite advances in the field in recent years, the installation of the sulfonyl fluoride handle still requires the use of purpose-designed, expensive and non-atom-economic reagents. The use of the SO2F2 for sulfonyl fluoride synthesis has been thwarted by the difficulties associated with the manipulation and dosage of this toxic gas, and by its apparent low reactivity with amino functionalities. Here we report a modular flow platform that can generate on demand, and efficiently dose, gaseous SO2F2. The use of flow technologies allows many lingering limitations of this transformation to be overcome, resulting in reduced reaction times, efficient reactivity and broad substrate scope. The effectiveness of the process was demonstrated by the successful synthesis of a diverse set of fluorosulfates and sulfamoyl fluorides, including those derived from biorelevant compounds, peptides and proteins.
U2 - 10.1038/s44160-023-00441-0
DO - 10.1038/s44160-023-00441-0
M3 - Article
SN - 2731-0582
VL - 3
SP - 185
EP - 191
JO - Nature Synthesis
JF - Nature Synthesis
IS - 2
ER -