Highly Enantioselective Synthesis of 3<i>a</i>-Fluorofuro[3,2-<i>b</i>]indolines via Organocatalytic Aza-Friedel–Crafts Reaction/Selective C–F Bond Activation
Tao Ma, Xing‐Pin Wei, Xinchun Wang, Xiu‐Xiu Qiao, Ganpeng Li, Yonghui He, Xiaojing Zhao
Abstract
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- b ]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 19 F nuclear magnetic resonance experiments provided sufficient support for silica gel as the key medium in this transformation.