Monofluoromethylation of Tetrahydroisoquinolines by Visible‐light Induced Direct C(sp³)H Bond Activation

Abstract

A visible‐light photoredox‐catalyzed reaction of tetrahydroisoquinolines with β‐fluorinated gem‐diols results in the formation of C1‐monofluoromethylated tetrahydroisoquinolines via C(sp3)H bond activation. This protocol provides a new method to introduce a CF group with stable, easily‐prepared monofluorinated gem‐diol as CF source. A mechanistic investigation is presented based on control experiments.magnified image

Visible Light‐Induced C−H Bond Functionalization: A Critical Review

“…In 2014, Zhu and co‐workers achieved the visible light‐induced difluoromethylation of tetrahydroisoquinolines with β,β‐difluorinated gem ‐diols as CF 2 source . As a continuation of their interest in visible light‐promoted C−H bond activation and in consideration of the importance of fluoro‐containing organic compounds, these authors reported the monofluoromethylation of tetrahydroisoquinolines with easily‐prepared trifluoromethyl β‐fluorinated gem ‐diols as CF source (Scheme ) …”

Recent Progress in the in situ Detrifluoro­acetylative Generation of Fluoro Enolates and Their Reactions with Electrophiles

“…It was shown that monofluoro enolates 21 can react with tetrahydroisoquinolines 60 under visible‐light photoredox catalysis conditions in the presence of a catalyst generated from RuCl 2 and 1,10‐phenanthroline (Scheme ) 52a. The additions take place at ambient temperature to afford products 62 with yields ranging from 42 to 88 %.…”

Visible‐Light Photoredox‐Catalyzed Cross‐Dehydrogenative Coupling of Tetrahydroisoquinolines with 3‐Fluorooxindoles

“…Fu and co‐workers have reported the oxidative coupling of tetrahydroisoquinolines with trimethyl(trifluoromethyl)silane using rose bengal as the photocatalyst . Zhu and co‐workers have disclosed mild mono‐ and difluoromethylation of tetrahydroisoquinolines with in‐situ generated fluoroenolate from the corresponding β‐fluorinated gem ‐diols (Scheme a) b) .…”