Synthesis of 18F-Arenes from Spirocyclic Iodonium(III) Ylides via Continuous-Flow Microfluidics

摘要

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 of ¹⁸F-labelled building blocks and labelled compounds prepared by iodonium ylide precursors as well as the production of radiotracers for preclinical imaging studies.