Синтез гем-дифлуорованих циклобутанових та циклопентанових будівельних блоків

• Date: 2025
• Main Authors: Olifir, Oleksandr S., Liashuk, Oleksandr S.
• Format: Article
• Language: English
• Published: V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine 2025
• Subjects: флуор; циклобутан; циклопентан; флуоровані будівельні блоки
• Online Access: https://bioorganica.com.ua/index.php/journal/article/view/105
• Journal Title: Ukrainica Bioorganica Acta

Herein, we describe a concise and scalable strategy for the preparation of gem-difluorinated cyclobutanes and cyclopentanes from simple, commercially available precursors under mild deoxyfluorination conditions. Optimization of the fluorination step enabled direct access to key intermediates, such as gem-difluorocyclobutyl bromides and boronates in two to three steps and on up to 77 g scale, avoiding the mercury-mediated or high-temperature processes typical of earlier methodologies. The developed protocol exhibits broad functional-group tolerance, allowing the preparation of amino-, hydroxy-, and sulfonyl-substituted derivatives, as (including deoxyfluorination of certainly functionalized cyclobutanones or by rearrangement of methylenecyclopropanes), remain hardly accessible due to lengthy synthetic procedures or limited scalability. Their higher homologues, gem-difluorinated cyclopentanes, are described significantly well as novel cis- and trans-difluorocyclopentane scaffolds including diols, diamines, and carboxylic acid analogues. The operational simplicity, scalability, and structural diversity of the resulting building blocks make this approach a valuable platform for the exploration of CF₂-containing fragments in medicinal and materials chemistry