title: Synthesis of18F-Arenes from Spirocyclic Iodonium(III) Ylides via Continuous-Flow Microfluidics.
abstract: Spirocyclic hypervalent iodine(III) ylides have proven to be synthetically versatile precursors for efficient radiolabelling of a diverse range of non-activated (hetero)arenes, highly functionalised small molecules, building blocks and radiopharmaceuticals from [18F]fluoride ion. Herein, we report the implementation of these reactions onto a continuous-flow microfluidic platform, thereby offering an alterative and automated synthetic procedure of a radiopharmaceutical, 3-[18F]fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile ([18F]FPEB) and a routinely used building block for click-radiochemistry, 4-[18F]fluorobenzyl azide. This new protocol was applied to the synthesis of [18F]FPEB (radiochemical conversion (RCC) = 68 ± 5%) and 4-[18F]fluorobenzyl azide (RCC=68 ± 5%; isolated radiochemical yield = 24±0%). We anticipate that the high throughput microfluidic platform will accelerate the discovery and applications of18F-labelled building blocks and labelled compounds prepared by iodonium ylide precursors as well as the production of radiotracers for preclinical imaging studies.
authors: University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, Oxford, UK; Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, 55 Fruit Street, Boston, USA.
authors: Samuel
authors: S
authors: Calderwood
authors: Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, 55 Fruit Street, Boston, USA; Department of Radiology, Harvard Medical School, 55 Fruit Street, Boston, USA; Advion BioSystems, 10 Brown Road, Suite 101, Ithaca, New York, USA.
authors: Thomas Lee
authors: TL
authors: Collier
authors: University of Oxford, Chemistry Research Laboratory, 12 Mansfield Road, Oxford, UK.
authors: Véronique
authors: V
authors: Gouverneur
authors: Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, 55 Fruit Street, Boston, USA; Department of Radiology, Harvard Medical School, 55 Fruit Street, Boston, USA.
authors: Steven H
authors: SH
authors: Liang
authors: Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, 55 Fruit Street, Boston, USA; Department of Radiology, Harvard Medical School, 55 Fruit Street, Boston, USA.
authors: Neil
authors: N
authors: Vasdev