Protodefluorinated Selectfluor® Aggregatively Activates Selectfluor® for Efficient Radical C(sp3)-H Fluorination
Shahboz Yakubov1, Bastian Dauth1, Willibald J Stockerl1
1Institute of Organic Chemistry, University of Regensburg, Universitätsstr. 31, 93053, Regensburg, Germany.
Abstract:
Efficient fluorination reactions are key in the late-stage functionalization of complex molecules in medicinal chemistry, in upgrading chemical feedstocks, and in materials science. Radical C(sp3)-H fluorinations using Selectfluor® - one of the most popular fluorination agents - allow to directly engage unactivated precursors under mild photochemical or thermal catalytic conditions. However, H-TEDA(BF4)2 to date is overlooked and discarded as waste, despite comprising 95% of the molecular weight of Selectfluor®. We demonstrate that the addition of H-TEDA(BF4)2 at the start of fluorination reactions markedly promotes their rates and accesses higher overall yields of fluorinated products (~3.3 × higher on average across the cases studied) than unpromoted reactions. Several case studies showcase generality of the promotor, for photochemical, photocatalytic and thermal radical fluorination reactions. Detailed mechanistic investigations reveal the key importance of aggregation changes in Selectfluor® and H-TEDA(BF4)2 to fill gaps of understanding in how radical C(sp3)-H fluorination reactions work. This study exemplifies an overlooked reaction waste product being upcycled for a useful application.
More Related Videos
08:43Protocol for the Synthesis of Ortho-trifluoromethoxylated Aniline Derivatives
Published on: January 19, 2016
09:04Identifying Per- and Polyfluorinated Chemical Species with a Combined Targeted and Non-Targeted-Screening High-Resolution Mass Spectrometry Workflow
Published on: April 18, 2019
Related Concept Videos
Electrophilic Aromatic Substitution: Fluorination and Iodination of Benzene
ortho–para-Directing Deactivators: Halogens
Radical Reactivity: Concentration Effects
Radical Substitution: Allylic Chlorination
Radical Reactivity: Nucleophilic Radicals
Radical Reactivity: Intramolecular vs Intermolecular
