Trifluoromethylation of α-Haloketones

Abstract

The C-X bond (X = Br, Cl) of α-haloketones is smoothly trifluoromethylated with the fluoroform-derived CuCF(3) reagent recently developed in our laboratories. This is the first nucleophilic α-trifluoromethylation reaction of carbonyl compounds and a rare example of CF(3)-C(sp(3)) coupling. The transformation employs only low-cost chemicals and cleanly occurs in up to 99% yield at room temperature, thereby providing an unprecedentedly easy entry to valuable 2,2,2-trifluoroethylketones.

Recent advances in the trifluoromethylation methodology and new CF3-containing drugs

“…As pointed out above, nucleophilic reagents such as CF 3 SiMe 3 may not be used for a-trifluoromethylations of carbonyl compounds. However, a CuCF 3 species prepared from fluoroform was suitable for reacting with a-chloro or bromoketones to furnish a-(trifluoromethyl)ketones without affecting the carbonyl group [59]. Similarly, a formal a-trifluoromethylation of esters was accomplished by means of another CuCF 3 reagent, this time prepared from CF 3 SiMe 3 , that served to convert a-diazoesters into a-(trifluoromethyl)esters in a process promoted by water as activating agent [60].…”

Radical Desulfur‐Fragmentation and Reconstruction of Enol Triflates: Facile Access to α‐Trifluoromethyl Ketones

“…[2] a-CF 3 carbonyl compounds have drawn special attention as they serve as valuable building blocks for various CF 3 -containing complex moieties. [4] General strategies to radical trifluoromethylation include using enolates in reactions with trifluoromethylation reagents, such as CF 3 SO 2 Na(Cl), [5] CF 3 I, [6] or Togni reagent [7] (Scheme 1a). [4] General strategies to radical trifluoromethylation include using enolates in reactions with trifluoromethylation reagents, such as CF 3 SO 2 Na(Cl), [5] CF 3 I, [6] or Togni reagent [7] (Scheme 1a).…”

Combining Photoredox‐Catalyzed Trifluoromethylation and Oxidation with DMSO: Facile Synthesis of α‐Trifluoromethylated Ketones from Aromatic Alkenes

“…[3] Trifluoromethylated carbonyl compounds are versatile building blocks for the synthesis of a wide variety of fluorinated compounds. [5] A few other unique methods have also been reported, [6][7][8][9] but examples of the "direct" oxidative trifluoromethylation (keto-trifluoromethylation) of alkenes, which are abundant and commonly used feedstocks, have been limited thus far. [5] A few other unique methods have also been reported, [6][7][8][9] but examples of the "direct" oxidative trifluoromethylation (keto-trifluoromethylation) of alkenes, which are abundant and commonly used feedstocks, have been limited thus far.…”