Direct Photoassisted α‐Trifluoromethylation of Aromatic Ketones with Trifluoroacetic Anhydride (TFAA)

Abstract

Direct a-Trifluoromethylation of acetophenone derivatives was achieved by using trifluoroacetic anhydride (TFAA) as the trifluoromethyl source and pyridine-N-oxide (PyÀO) as activator and oxidant under visible light irradiation and tris-(2,2'-bipyridine)ruthenium(II) hexafluorophosphate (Ru(bpy) 3 (PF 6 ) 2 ) as the photocatalyst. Different acetophenone derivatives could be converted to the corresponding a-CF 3 derivatives with high selectivity. Extensive mechanistic investigation revealed the formation of vinyl trifluoroacetate as the key intermediate for this transformation.

Au@ZnO Core–Shell: Scalable Photocatalytic Trifluoromethylation Using CF3CO2Na as an Inexpensive Reagent under Visible Light Irradiation

“…As a result, scalability, broad substrate applicability, and inexpensive methods for trifluromethylation are challenging. A number of efficient methodologies utilizing nucleophilic (CF 3 – ) and electrophilic (CF 3 + ) trifluoromethylation reagents have been reported. − Although these are very important methods, they suffer from one or more disadvantages such as limited substrate scope and generality, expensive catalyst or reagent, and use of harsh reaction conditions (temperature above 100 °C or use of a strong acid or base). − Initially, thermally metal-catalyzed trifluoromethylation reactions generating a trifluoromethyl radical (CF 3 • ) by means of a strong oxidant or photoredox catalyst were developed and highly regarded by organic chemists. − Compared to these traditional methods, visible light photoredox catalytic reactions can improve a wide range of important reactions with advantages such as environmental adaptability, versatility, practical reaction conditions (ambient temperature and pressure), and in many cases high selectivity and scalability. ,− Visible light trifluoromethylation reactions, commonly involving Ru, Ir, and Pt complexes as photocatalysts, allow accomplishment of the reactions under efficient conditions (room temperature, good selectivity, and operation simplicity). ,,, …”

Visible‐Light‐Mediated Trifluoromethylation of Enol Acetates Using Trifluoroacetic Anhydride

“…We believe that the reaction follows the mechanism proposed by the Stephenson [15] and Schaub groups. [17] The involvement of radical intermediates was supported indirectly by experiments in which BHT and TEMPO were found to inhibit the reaction. Pyridine N-oxide reacts with TFAA in-situ to form the intermediate 4 which on interaction with the excited Ru(II) photocatalyst eventually generates the trifluoromethyl radical 6 (Scheme 3).…”

“…Qing's group, [16] respectively. S. Das et al [17] have just reported an interesting method for the direct α-trifluoromethyation of acetophenones (Scheme 1). [18] We have been working towards the trifluoromethylation of acetophenone derived enol-acetates using photoredox catalysis that employs TFAA as the source of the trifluoromethyl group.…”

Scissoring Enaminone C═C Double Bond by Free Radical Process for the Synthesis of α-Trifluoromethyl Ketones with CF3SO2Na

“…Typically, the trifluoromethylation of activated ketones such as silyl enol ethers, enol acetates/triflates, α-haloketones, and α-ketocarboxylic acids has been proven to be applicable methods for α-trifluoromethyl ketone synthesis. In addition, the direct C–H trifluoromethylation of methyl ketones and the difunctionalization of alkynes, alkenes, or their functionalized derivatives have also been developed. Generally, the employment of a noble metal catalyst or expensive or sensitive trifluoromethyl reagent and/or the requirement of prior functionalization to activate the ketone substrates are yet the restrictions in known methods, which implies that more efforts are yet desirable to develop a complementary method for the synthesis of α-trifluoromethyl ketones.…”