A Ni-Mediated Cross-Coupling Approach to Deuterated 18F- Fluoromethylated (Hetero)arenes

Maddison Lovell; Sebastiano Ortalli; Raquel Sánchez-Bento; Matthew Tredwell; Joseph Ford; Véronique Gouverneur

doi:10.1021/jacs.6c09649

A Ni-Mediated Cross-Coupling Approach to Deuterated ¹⁸F- Fluoromethylated (Hetero)arenes

Maddison Lovell
, Sebastiano Ortalli
, Raquel Sánchez-Bento
, Matthew Tredwell
, Joseph Ford
, Véronique Gouverneur

University of Oxford
MSD
Cardiff University School of Medicine
Cardiff University

Research output: Contribution to journal › Article › peer-review

Abstract

Herein, we report a Ni-mediated ¹⁸F,D₂-monofluoromethylation of (hetero)arenes from (pseudo)halide coupling partners. This new approach offers key advantages compared to traditional radiochemistry based on S_N2-type reactivity with [¹⁸F]fluoride. These include increased precursor stability and availability, obviating bespoke precursor syntheses, broad functional group tolerance, and the late-stage introduction of deuterium and fluorine-18 in a single step, all features facilitating early access to PET ligands for discovery campaigns. This novel protocol is applied to over 30 diverse substrates, including complex bioactive molecules, and is amenable to scale-up via a semiautomated protocol on a commercial platform, illustrated by isolation of a ¹⁸F,D₂-labeled PARP radiotracer.

Original language	English
Pages (from-to)	28049-28054
Number of pages	6
Journal	Journal of the American Chemical Society
Volume	148
Issue number	27
DOIs	https://doi.org/10.1021/jacs.6c09649
State	Published - 15 Jul 2026
Externally published	Yes

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title = "A Ni-Mediated Cross-Coupling Approach to Deuterated 18F- Fluoromethylated (Hetero)arenes",

abstract = "Herein, we report a Ni-mediated 18F,D2-monofluoromethylation of (hetero)arenes from (pseudo)halide coupling partners. This new approach offers key advantages compared to traditional radiochemistry based on SN2-type reactivity with [18F]fluoride. These include increased precursor stability and availability, obviating bespoke precursor syntheses, broad functional group tolerance, and the late-stage introduction of deuterium and fluorine-18 in a single step, all features facilitating early access to PET ligands for discovery campaigns. This novel protocol is applied to over 30 diverse substrates, including complex bioactive molecules, and is amenable to scale-up via a semiautomated protocol on a commercial platform, illustrated by isolation of a 18F,D2-labeled PARP radiotracer.",

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AU - Ortalli, Sebastiano

AU - Sánchez-Bento, Raquel

AU - Tredwell, Matthew

AU - Ford, Joseph

AU - Gouverneur, Véronique

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AB - Herein, we report a Ni-mediated 18F,D2-monofluoromethylation of (hetero)arenes from (pseudo)halide coupling partners. This new approach offers key advantages compared to traditional radiochemistry based on SN2-type reactivity with [18F]fluoride. These include increased precursor stability and availability, obviating bespoke precursor syntheses, broad functional group tolerance, and the late-stage introduction of deuterium and fluorine-18 in a single step, all features facilitating early access to PET ligands for discovery campaigns. This novel protocol is applied to over 30 diverse substrates, including complex bioactive molecules, and is amenable to scale-up via a semiautomated protocol on a commercial platform, illustrated by isolation of a 18F,D2-labeled PARP radiotracer.

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A Ni-Mediated Cross-Coupling Approach to Deuterated ¹⁸F- Fluoromethylated (Hetero)arenes

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