Electrochemical Vicinal Difluorination of Alkenes: Scalable and Amenable to Electron‐Rich Substrates. (28th November 2019)

• Record Type: Journal Article
• Authors: Doobary, Sayad; Sedikides, Alexi T.; Caldora, Henry P.; Poole, Darren L.; Lennox, Alastair J. J.
• Is Part Of: Angewandte Chemie. Volume 132:Number 3(2020)
• Page Start: 1171
• Page End: 1176
• Publication Date: 2019-11-28
• Subjects: Elektrochemie -- Fluorierungen -- Grüne Chemie -- Hypervalentes Iod -- Oxidation; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201912119
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: 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. Abstract : Ex und hopp : Ein Verfahren zur Difluorierung von nicht‐aktivierten Alkenen mit elektronenreichen Funktionalitäten wird beschrieben, das Produkte zugänglich macht, die anderwegs unerreichbar sind. Der Schlüssel ist die elektrochemische Erzeugung eines hypervalenten Iod‐Mediators unter Verwendung eines „ex‐cell"‐Ansatzes, der die oxidative Substratzersetzung vermeidet.