Late-Stage Fluorosulfurylation using Sulfuryl Fluoride Bound within a Metal-Organic Framework
Year: 2026
Type: preprint
Abstract: Organic S(VI) fluorides have garnered substantial interest for covalent drug discovery and chemoproteomics due to their ambient stability and unique electrophilic reactivity. Sulfuryl fluoride (SO 2 F 2 ) is the ideal reagent for the synthesis of various S(VI)–F moieties, yet it is a toxic greenhouse gas, often making it incompatible with laboratory settings. Developing a strategy for handling SO 2 F 2 that is amenable to high-throughput reaction discovery would enhance its utility in the laboratory without necessitating specialized equipment or extensive safety measures. Herein, we report a strategy to safely store reactive SO 2 F 2 within a metal–organic framework (MOF) for its facile application to the synthesis of electrophilic, bioactive molecules. The solid SO 2 F 2 –Mg 2 (dobdc) reagent can be stored for at least five months with minimal gas loss due to the strong yet reversible interaction between SO 2 F 2 and Mg 2+ centers in the MOF, as confirmed by single-crystal X-ray diffraction. Using this reagent, we prepare a range of drug-like arylfluorosulfates, saturated N -heterocyclic sulfamoyl fluorides, and N -heteroarene sulfamoyl fluorides. These findings represent the first experimental study of SO 2 F 2 adsorption within a MOF and the first use of MOFs for late-stage fluorosulfurylation, paving the way towards a general approach to carefully handle dangerous, reactive gases as solid reagents.
Source: ChemRxiv
Subfield: Inorganic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Funders: National Science Foundation, U.S. Department of Energy, Massachusetts Institute of Technology, Dartmouth College, Korea Institute of Science and Technology, Korea Institute of Science and Technology Information, KU-KIST Graduate School of Converging Science and Technology, National Institutes of Health, Office of Science, Cornell Center for Materials Research, National Supercomputing Center, Korea Institute of Science and Technology Information, National Institute of General Medical Sciences, Division of Materials Research, Division of Chemistry, Basic Energy Sciences
Awards: G106394233, G1134277896, G2015640770, G3631263731, THE CENTER FOR ENHANCED NANOFLUIDIC TRANSPORT (CENT), G479123316, G5722673456, MRI: Acquisition of a Cryogenic Probe and Modern Console for Outstanding NMR Sensitivity to Benefit Research and Education at Cornell University, THE CENTER FOR ENHANCED NANOFLUIDIC TRANSPORT (CENT), G8389919011, G876993293, G9000026681, Training future leaders at the chemistry-biology interface
OpenAlex ID: W7125530760
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