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

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 gem-difluoroalkenes and beta-fluoro-beta-perfluoroalkylalkenes. The reaction features excellent regio- and stereoselectivity and broad substrate scope. Notably, the obtained gem-difluoroalkenes and beta-fluoro-beta-perfluoroalkylalkenes could be easily transformed into 3-fluoro(perfluoroalkyl)-beta-carbolines with excellent efficiency simply by treating them with Grignard reagents or DIBAL-H under mild reaction conditions.

Automated summary

This study presents an unprecedented Sc(OTf)(3)-catalyzed C2-selective cyanation/defluorination cascade, which provides a novel and practical strategy for the synthesis of structurally diverse 3-(2-cyano)-indolyl substituted gem-difluoroalkenes and beta-fluoro-beta-perfluoroalkylalkenes. The obtained gem-difluoroalkenes and beta-fluoro-beta-perfluoroalkylalkenes can be easily transformed into 3-fluoro(perfluoroalkyl)-beta-carbolines with excellent efficiency under mild reaction conditions.