Desmethyl SuFEx-IT: SO2F2-Free Synthesis and Evaluation as a Fluorosulfurylating Agent
Jan Bertram, Felix Neumaier, Boris D. Zlatopolskiy, Bernd Neumaier*
*Forschungszentrum Jülich GmbH, Institute of Neuroscience and Medicine, Nuclear Chemistry (INM-5), Wilhelm-Johnen-Straße,
Jülich 52425, Germany, Email: b.neumaier
fz-juelich.de
J. Bertram, F. Neumaier, B. D. Zlatopolskiy, B. Neumaier, J. Org. Chem., 2024, 89, 3821-3833.
DOI: 10.1021/acs.joc.3c02643
see article for more reactions
Abstract
Access to SuFExable compounds was remarkably simplified using the solid FO2S-donor SuFEx-IT. A hectogram-scale and SO2F2-free preparation of the analogous desmethyl SuFEx-IT from inexpensive starting materials in high yield and without chromatographic purification is possible. The use of this reagent enables the preparation of a series of fluorosulfates and sulfamoyl fluorides in very high yields.
see article for more examples
SO2F2-Free Synthesis of Desmethyl SuFEx-IT
Details
The article discusses the development of a new, efficient method for synthesizing desmethyl SuFEx-IT, a fluorosulfurylating agent, without using the toxic and hard-to-obtain sulfuryl fluoride (SO2F2). The new protocol uses inexpensive starting materials and achieves an 85% total yield without chromatographic purification. Desmethyl SuFEx-IT was successfully used to prepare various fluorosulfates and sulfamoyl fluorides in high yields, demonstrating its utility as a valuable alternative to common FO2S-donors. The reagent showed excellent stability, with minimal decomposition when stored at low temperatures. This advancement simplifies access to SuFExable compounds, making the process safer and more cost-efficient, and broadens the applicability of SuFEx click chemistry in organic synthesis, material sciences, drug discovery, and radiochemistry. The study was supported by Deutsche Forschungsgemeinschaft (DFG) and involved contributions from researchers at Forschungszentrum Jülich GmbH and the University of Cologne. The findings highlight the potential of desmethyl SuFEx-IT as a practical and scalable reagent for various chemical applications.
General Procedure for Preparation of Fluorosulfates
Desmethyl SuFEx-IT (1.3 equiv) was added to a solution of the phenol substrate (0.1 - 5 mmol, 1.0 equiv) and Et3N (1.6 equiv) in MeCN (2-5 mL), and the mixture was stirred until TLC showed full conversion (30-90 min). The products were purified by dry load column chromatography or filtration over a silica plug with an appropriate solvent unless stated otherwise.
General Procedure for Preparation of Sulfamoyl Fluorides
Desmethyl SuFEx-IT (1.1 equiv) was added to a solution of the amine substrate (0.6 - 2 mmol, 1.0 equiv) in MeCN (2-5 mL), and the mixture was stirred until TLC or HPLC showed full conversion (15-90 min). The products were purified by dry load column chromatography or filtration over a silica plug with an appropriate solvent unless stated otherwise.
Key Words
fluorosulfates, sulfamoyl fluorides
ID: J42-Y2024
