Hydrofluoromethylation of alkenes with fluoroiodomethane and beyond. Issue 36 (18th August 2021)

• Record Type: Journal Article
• Authors: Hell, Sandrine M.; Meyer, Claudio F.; Ortalli, Sebastiano; Sap, Jeroen B. I.; Chen, Xuanxiao; Gouverneur, Véronique
• Is Part Of: Chemical science. Volume 12:Issue 36(2021)
• Page Start: 12149
• Page End: 12155
• Publication Date: 2021-08-18
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d1sc03421a
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : Herein, we report the direct hydro(halo)methylation of alkenes from a variety of (halo)methyl iodides (including F-18, C-13, D-2 isotopologues), enabling the incorporation of a plethora of C-1 fragments into complex biologically active molecules. Abstract : A process for the direct hydrofluoromethylation of alkenes is reported for the first time. This straighforward silyl radical-mediated reaction utilises CH2 FI as a non-ozone depleting reagent, traditionally used in electrophilic, nucleophilic and carbene-type chemistry, but not as a CH2 F radical source. By circumventing the challenges associated with the high reduction potential of CH2 FI being closer to CH3 I than CF3 I, and harnessing instead the favourable bond dissociation energy of the C–I bond, we demonstrate that feedstock electron-deficient alkenes are converted into products resulting from net hydrofluoromethylation with the intervention of (Me3 Si)3 SiH under blue LED activation. This deceptively simple yet powerful methodology was extended to a range of (halo)methyl radical precursors including ICH2 I, ICH2 Br, ICH2 Cl, and CHBr2 F, as well as CH3 I itself; this latter reagent therefore enables direct hydromethylation. This versatile chemistry was applied to 18 F-, 13 C-, and D-labelled reagents as well as complex biologically relevant alkenes, providing facile access to more than fifty products for applications in medicinal chemistry and positron emission tomography.