Maruno Koki, Niina Kiyoteru, Nagata Osamu, Shibata Norio
Department of Nanopharmaceutical Sciences and Department of Life Science and Applied Chemistry, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555, Japan.
Pharmaceutical Division, Ube Industries, Ltd., Seavans North Building, 1-2-1 Shibaura, Minato-ku, Tokyo 105-8449, Japan.
Org Lett. 2022 Mar 4;24(8):1722-1726. doi: 10.1021/acs.orglett.2c00358. Epub 2022 Feb 24.
Fluoro-functionalization is now recognized as a critical strategy in drug discovery; however, the accessible fluoro-functional groups are limited. We herein introduce an eccentric, fully fluorinated motif, -tetrafluoro-λ-sulfanyl -difluorocyclopropene . This novel motif is highly lipophilic and polarized, enabling a connection of two independent groups via three continuous atoms with a large angle of pseudo configuration. The target motif was synthesized via a [2+1] cycloaddition of electron-deficient (hetero)aryl-SF-alkynes with an electrophilic difluorocarbene source.
氟官能化现在被认为是药物发现中的一种关键策略；然而，可获得的氟官能团是有限的。我们在此引入一种奇特的全氟取代基，即 - 四氟 - λ - 硫烷基 - 二氟环丙烯。这种新型取代基具有高度亲脂性和极化性，能够通过三个连续原子以较大的假构型角连接两个独立的基团。目标取代基是通过缺电子（杂）芳基 - SF - 炔烃与亲电二氟卡宾源的[2 + 1]环加成反应合成的。
