An efficient one-pot microwave-assisted potassium fluoride-mediated synthesis of 1-fluoroalkyl-3-fluoroisoquinolines and fused fluoroalkylpyridines from N-fluoroalkylated 1,2,3-triazoles was developed. The reaction has a wide scope and allows the preparation of structurally diverse 3-fluoroisoquinolines with a fluoroalkyl group in position 1, a substituent in position 4 and a substituent on the fused benzene (or heteroaromatic) ring. N-Fluoroalkylated ketenimines, which undergo stereoselective formal 1,3-fluorine shift to difluoroazadienes, were identified as intermediates in the reaction sequence. The presence of fluorine in position 3 and a halogen in position 4 of the resulting isoquinolines allowed for further modification by nucleophilic aromatic substitution and cross-coupling reactions, respectively. The developed methodologies were utilized for the synthesis of derivatives of drug candidates.

中文翻译：

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N-氟烷基-1,2,3-三唑一锅多步合成1-氟烷基异喹啉和稠合氟烷基吡啶


开发了一种高效的一锅微波辅助氟化钾介导的从 N-氟烷基化 1,2,3-三唑合成 1-氟烷基-3-氟异喹啉和稠合氟烷基吡啶的方法。该反应范围广泛，可以制备结构多样的3-氟异喹啉，其中1位有氟烷基，4位有取代基，稠合苯（或杂芳族）环上有取代基。 N-氟烷基化烯酮亚胺，其经历立体选择性形式1,3-氟转变为二氟氮杂二烯，被鉴定为反应序列中的中间体。所得异喹啉的 3 位存在氟，4 位存在卤素，可以分别通过亲核芳族取代和交叉偶联反应进行进一步修饰。开发的方法用于候选药物衍生物的合成。