Ma Tao, Wei Xing-Pin, Wang Xin-Chun, Qiao Xiu-Xiu, Li Ganpeng, He Yonghui, Zhao Xiao-Jing
School of Ethnic Medicine, Yunnan Minzu University, Kunming 650500, China.
Key Laboratory of Chemistry in Ethnic Medicinal Resources, School of Ethnic Medicine, Yunnan Minzu University, Kunming 650500, China.
Org Lett. 2023 Dec 8;25(48):8666-8671. doi: 10.1021/acs.orglett.3c03445. Epub 2023 Nov 28.
Fluoroalkylated compounds are of high interest in drug discovery and have inspired the evolution of diverse C-F bond activation methodologies. However, the selective activation of polyfluorinated compounds remains challenging. Herein, we describe an unprecedented strategy for synthesizing enantioenriched fluorofuro[3,2-]indolines through the organocatalytic aza-Friedel-Crafts reaction coupled with selective C-F bond activation. These reactions feature excellent enantioselectivities (≤96% ee) and yields (≤96%) as well as good functional group compatibility. Mechanistic investigations by means of F nuclear magnetic resonance experiments provided sufficient support for silica gel as the key medium in this transformation.
氟烷基化化合物在药物发现中备受关注，并推动了多种碳-氟键活化方法的发展。然而，多氟化合物的选择性活化仍然具有挑战性。在此，我们描述了一种前所未有的策略，通过有机催化的氮杂傅-克反应与选择性碳-氟键活化相结合，合成对映体富集的氟代呋喃并[3,2-]吲哚啉。这些反应具有优异的对映选择性（≤96% ee）和产率（≤96%）以及良好的官能团兼容性。通过氟核磁共振实验进行的机理研究为硅胶作为该转化中的关键介质提供了充分的支持。
