Metal-Free Photocatalytic Radical Trifluoromethylation Utilizing Methylene Blue and Visible Light Irradiation

Abstract

The use of organofluorine compounds, especially those with an incorporated trifluoromethyl moiety, has increased dramatically in both the pharmaceutical and agrochemical industry. It has therefore become imperative to develop a mild and efficient synthetic technique for the inclusion of trifluoromethyl groups. Herein, we report the first use of methylene blue as a photosensitizer for the catalytic radical trifluoro-and hydrotrifluoromethylation of electronrich heterocycles as well as terminal alkenes and alkynes under visible light irradiation. These reactions proceed with moderate to good yields at low catalyst concentrations; short irradiation times; and most importantly, without the need for potentially toxic transition-metal catalysts. In this work, considerable emphasis was also placed on understanding the kinetics of the mechanistically key steps through the use of laser flash photolysis techniques to more efficiently optimize the reaction conditions.

Photocatalytic fluoroalkylation reactions of organic compounds

“…Umemoto's reagent is also used to carry out the photocatalytic 62 reaction of 3-methyl indole but the trifluoromethylated product is obtained in low yield (35 %). 105 Scheme 42b. Trifluoromethylation of heterocycles with Methylene Blue as photocatalyst…”

An overview of reductive trifluoromethylation reactions using electrophilic ‘+CF3’ reagents

“…60 These reactions gave the desirable trifluoromethylated products (237,239,241) in moderate to good yields with low catalyst loadings and short irradiation times in the absence of expensive transition-metal complexes. When the reaction was performed with TEMPO radical, TEMPO-CF 3 was obtained in good yield, confirming the formation of CF 3 radicals.…”

Organic Reactions Promoted by Metal-Free Organic Dyes Under Visible Light Irradiation

“…Scaiano's group used MB as a photocatalyst under the visible light irradiation [48]. The radical trifluoromethylation of electron-rich heterocycles was studied by the use of Togni's reagent 39 as a CF 3 radical source (Figure 15).…”