Visible-light-induced direct C(sp3)–H difluromethylation of tetrahydroisoquinolines with the in situ generated difluoroenolates

Abstract

An effective approach to C1-difluoromethylated tetrahydroisoquinoline derivatives has been developed through C-H functionalization of tertiary amines by visible-light photoredox catalysis. This method uses stable, easily obtained α,α-difluorinated gem-diol as the CF2 source. The corresponding products were obtained in moderate to high yields at ambient temperature.

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 ) …”

Optimized synthesis of a pentafluoro- gem -diol and conversion to a CF2Br -glucopyranose through trifluoroacetate-release and halogenation

“…9 In 2011, we demonstrated that difluoroenolates could be generated by the mild release of trifluoroacetate from pentafluoro- gem -diols using LiBr and Et 3 N. 12 The difluoroenolates react well with aldehydes, 12 imines, 13 and electrophilic halogenation reagents 14 (Figure 1). Subsequent innovations mediated by the release of trifluoroacetate include catalytic asymmetric aldol reactions, 15 integration with light-induced photoredox catalysis, 16 and stereoselective additions to chiral N -sulfinyl imines. 17 Indeed, the major advantage of using trifluoroacetate release is that it is quite mild yet compatible with many types of reagents.…”

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

“…The same group52b has also reported similar reactions with difluoro enolate precursors 20 (Scheme ).…”