Visible‐Light‐Mediated Two‐Fold Unsymmetrical C(sp³)−H Functionalization and Double C−F Substitution

Abstract

A visible-light-mediated [3+3] annulation of tertiary amines with α-trifluoromethyl alkenes was developed. The reaction offers a direct route to fluorinated tetrahydropyridines and azabicyclo[3.m.1] frameworks under very mild conditions. This protocol presents a rare example of dual sp C-H functionalization of tertiary amines with the formation of two different C-C bonds (one sp -sp bond, one sp -sp bond). Moreover, two consecutive C-F substitutions in a trifluoromethyl group were achieved in one pot using visible light photoredox catalysis, which enables an unprecedented ring construction.

Photoredox Generation of Carbon‐Centered Radicals Enables the Construction of 1,1‐Difluoroalkene Carbonyl Mimics

“…Indeed, such a radical process is viable for the addition of acyl and stabilized α-amino radicals to trifluoromethyl styrenes, but a general method for the utilization of 1°, 2°, and 3° radicals does not exist. [12] Moreover, we reasoned that using an array of radical precursors would impart several benefits such as additive-free reactions at near neutral pH, the ability to use inexpensive photocatalysts, and the opportunity to install a wide range of functional groups.…”

Photoredox Generation of Carbon‐Centered Radicals Enables the Construction of 1,1‐Difluoroalkene Carbonyl Mimics

“…Although protonation is viable,w ea nticipated the known propensity for such anions to undergo E1cB-type fluoride elimination [11] to predominate and provide the desired gem-difluoroalkene by ar adical/polar crossover process.I ndeed, such ar adical process is viable for the addition of acyl and stabilized aamino radicals to trifluoromethyl styrenes,b ut ag eneral method for the utilization of primary,secondary,and tertiary radicals does not exist. [12] Moreover,w er easoned that using an array of radical precursors would impart several benefits such as additive-free reactions at near-neutral pH, the ability to use inexpensive photocatalysts,a nd the opportunity to install awide range of functional groups.…”

Photocatalytic C−F Bond Activation of Fluoroarenes, gem‐Difluoroalkenes and Trifluoromethylarenes

“…In 2017, Zhou and co‐workers reported a photocatalytic 3+3 annulation of tertiary amines with α‐trifluoromethylalkenes, which also involved the similar monofluoroalkenylation reaction [57] . In the same year, Fu and co‐workers reported another defluoroalkylation of gem ‐difluoroalkenes via visible light induced decarboxylation of N‐protected α‐amino acids 37 and C−F bond activation utilizing Ir[dF(CF 3 )ppy] 2 (dtbbpy)PF 6 as PC affording the α‐amino monofluoroalkenes 38 a (Scheme 26).…”