Zinc-Mediated Radiosynthesis of Unprotected Fluorine-18 Labelled α-Tertiary Amides

Jay S Wright; Richard Ma; E William Webb; Wade P Winton; Jenelle Stauff; Kevin Cheng; Allen F Brooks; Melanie S Sanford; Peter J H Scott

doi:10.1002/anie.202316365

Zinc-Mediated Radiosynthesis of Unprotected Fluorine-18 Labelled α-Tertiary Amides

Angew Chem Int Ed Engl. 2024 Jan 8;63(2):e202316365. doi: 10.1002/anie.202316365. Epub 2023 Dec 8.

Authors

Jay S Wright¹, Richard Ma¹, E William Webb¹, Wade P Winton¹, Jenelle Stauff¹, Kevin Cheng¹, Allen F Brooks¹, Melanie S Sanford², Peter J H Scott¹

Affiliations

¹ Department of Radiology, University of Michigan, Ann Arbor, MI-48109, USA.
² Department of Chemistry, University of Michigan, Ann Arbor, MI-48109, USA.

PMID: 38010255
PMCID: PMC10872995 (available on 2025-01-08)
DOI: 10.1002/anie.202316365

Abstract

This report describes the development of a Zn(OTf)₂ -mediated method for converting α-tertiary haloamides to the corresponding fluorine-18 labelled α-tertiary fluoroamides with no-carrier-added [¹⁸ F]tetramethylammonium fluoride. 1,5,7-Triazabicyclo[4.4.0]dec-5-ene is an essential additive for achieving high radiochemical conversion. Under the optimised conditions, radiofluorination proceeds at sterically hindered tertiary sites in high radiochemical conversions, yields, and purities. This method has been successfully automated and applied to access >200 mCi (>7.4 GBq) of several model radiofluorides. Mechanistic studies led to the development of a new, nucleophilic C-H radiofluorination process using N-sulphonyloxyamide substrates.

Keywords: C−H Radiofluorination; Fluorine-18; Late-Stage Fluorination; Positron Emission Tomography; Radiochemistry.

Abstract

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