Electrochemical Vicinal Difluorination of Alkenes: Scalable and Amenable to Electron‐Rich Substrates

• Published in: Angewandte Chemie International Edition Vol. 59; no. 3; pp. 1155 - 1160
• Main Authors: Doobary, Sayad, Sedikides, Alexi T., Caldora, Henry P., Poole, Darren L., Lennox, Alastair J. J.
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 13-01-2020; John Wiley and Sons Inc
• Edition: International ed. in English
• Subjects: Alkenes; Bioactive compounds; Communication; Communications; Conformation; Electrochemistry; Electrons; fluorination; green chemistry; hypervalent iodine; Iodine; oxidation; Pharmacokinetics; Substrates; hypervalent iodine; fluorination; oxidation; electrochemistry; green chemistry
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201912119

Fluorinated alkyl groups are important motifs in bioactive compounds, positively influencing pharmacokinetics, potency and conformation. The oxidative difluorination of alkenes represents an important strategy for their preparation, yet current methods are limited in their alkene‐types and tolerance of electron‐rich, readily oxidized functionalities, as well as in their safety and scalability. Herein, we report a method for the difluorination of a number of unactivated alkene‐types that is tolerant of electron‐rich functionality, giving products that are otherwise unattainable. Key to success is the electrochemical generation of a hypervalent iodine mediator using an “ex‐cell” approach, which avoids oxidative substrate decomposition. The more sustainable conditions give good to excellent yields in up to decagram scales.
Fluorination for the nation: A method for the difluorination of unactivated alkenes with electron‐rich functionalities is described. Key to success is the electrochemical generation of a hypervalent iodine mediator using an “ex‐cell” approach, which avoids oxidative substrate decomposition.