18FTrifluoroiodomethane - Enabling Photoredox-mediated Radical 18FTrifluoromethylation for Positron Emission Tomography

• Published in: Angewandte Chemie International Edition 2025-01, Vol.64 (4), p.e202416901
• Main Authors: Veth, Lukas, Windhorst, Albert D, Vugts, Danielle J
• Format: Article
• Language: English
• ISSN: 1521-3773; 1521-3773
• DOI: 10.1002/anie.202416901

The development of new tracers for positron emission tomography (PET) is highly dependent on the available synthetic tools for their radiosynthesis. Herein, we present the radiosynthesis and application of [18F]trifluoroiodomethane - the first reagent for broad scope radical [18F]trifluoromethylation chemistry in high molar activity. CF2 18FI can be prepared from [18F]fluoroform with 67±5 % AY and >99 % RCP. Its synthetic utility is demonstrated by the radiosynthesis of previously unprecedented 18F-labeled α-trifluoromethyl ketones and 18F-labeled trifluoromethyl sulfides, important motifs that are present in a range of bioactive compounds. Both protocols are Ru- and photo-mediated and proceed under mild reaction conditions. They show good functional group tolerance evidenced by the respective reaction scopes and make use of easily obtainable starting materials. The products can be isolated in 8.3-11.1 GBq/μmol (starting from ca. 5 GBq [18F]fluoride). The applicability to PET tracer synthesis is shown by the radiolabeling of bioactive compounds, such as derivatives of probenecid and febuxostat. In a broader context, this work opens the door to the utilization of radical [18F]trifluoromethylation chemistry for the radiolabeling of PET tracers in high molar activity.The development of new tracers for positron emission tomography (PET) is highly dependent on the available synthetic tools for their radiosynthesis. Herein, we present the radiosynthesis and application of [18F]trifluoroiodomethane - the first reagent for broad scope radical [18F]trifluoromethylation chemistry in high molar activity. CF2 18FI can be prepared from [18F]fluoroform with 67±5 % AY and >99 % RCP. Its synthetic utility is demonstrated by the radiosynthesis of previously unprecedented 18F-labeled α-trifluoromethyl ketones and 18F-labeled trifluoromethyl sulfides, important motifs that are present in a range of bioactive compounds. Both protocols are Ru- and photo-mediated and proceed under mild reaction conditions. They show good functional group tolerance evidenced by the respective reaction scopes and make use of easily obtainable starting materials. The products can be isolated in 8.3-11.1 GBq/μmol (starting from ca. 5 GBq [18F]fluoride). The applicability to PET tracer synthesis is shown by the radiolabeling of bioactive compounds, such as derivatives of probenecid and febuxostat. In a broader context, this work opens the door to the utilization of radical [18F]trifluoromethylation