Sc(OTf)₃-Catalyzed C2-Selective Cyanation/Defluorination Cascade of Perfluoroalkylated 3-Indolylmethanols and Application to the Synthesis of 3-Fluoro(perfluoroalkyl)-β-carbolines

Abstract

An unprecedented Sc(OTf)₃-catalyzed C2-selective cyanation/defluorination cascade of perfluoroalkylated 3-indolylmethanols with TMSCN is described, which provides a novel and practical strategy for the synthesis of structurally diverse 3-(2-cyano)-indolyl substituted <i>gem</i>-difluoroalkenes and β-fluoro-β-perfluoroalkylalkenes. The reaction features excellent regio- and stereoselectivity and broad substrate scope. Notably, the obtained <i>gem</i>-difluoroalkenes and β-fluoro-β-perfluoroalkylalkenes could be easily transformed into 3-fluoro(perfluoroalkyl)-β-carbolines with excellent efficiency simply by treating them with Grignard reagents or DIBAL-H under mild reaction conditions.