Synthesis and Derivatization of 1,1‐[18F]Difluorinated Alkenes

• Published in: Angewandte Chemie International Edition Vol. 58; no. 2; pp. 472 - 476
• Main Authors: Frost, Aileen B., Brambilla, Marta, Exner, Rüdiger M., Tredwell, Matthew
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 08.01.2019; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Alkenes; Chemical synthesis; Chemistry; Chemistry, Multidisciplinary; Fluorides; Fluorination; Fluorine; fluorine-18; Functional groups; Physical Sciences; positron emission tomography; Radiochemistry; Science & Technology; DRUG; DESIGN; ARENES; fluorination; F-18; IODIDES; fluorine-18; POSITRON-EMISSION-TOMOGRAPHY; RADIOSYNTHESIS; ARYL; INHIBITORS; positron emission tomography; BRAIN; fluorine
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201810413

A general method for the synthesis of 1,1‐[18F]difluorinated alkenes from [18F]fluoride is reported. This transformation is highly regioselective giving the desired 18F‐fluoroalkenes with radiochemical purities of up to 77 % within 20 minutes and a molar activity (Am) of 1 GBq μmol−1. The transformations are operationally simple to perform and were readily translated onto a commercial automated synthesis unit. The resultant 1,1‐[18F]difluorinated alkene motif is prevalent in numerous drug molecules, and this is the first general method to synthesize this motif with fluorine‐18. 18F‐fluorinated alkenes are excellent building blocks and participate in a number of post‐labeling transformations to access a range of 18F‐perfluorinated functional groups that have never before been radiolabeled with non‐carrier‐added [18F]fluoride. This method considerably expands the range of 18F‐motifs accessible to radiochemists. Some like it hot: A general method for the radiochemical synthesis of 1,1‐[18F]difluoroalkenes from fluoroalkenyl(aryl)iodonium triflates and [18F]fluoride is reported. The 18F‐fluorination reaction is highly regioselective, giving radiochemical purities (RCP) of up to 77 %. The resultant geminal‐difluoroalkenes are versatile 18F‐building blocks, which allow for the first radiochemical syntheses of a range of 18F‐perfluorinated motifs.