Advances in the Synthesis of α-Trifluoromethyl Ketones and Their Application via Defluorinative Reactions

doi:10.6023/cjoc202411018

Abstract

α-Trifluoromethyl ketones are a class of useful compounds with versatile applications. Their synthetic application via the transformation of the C—F bonds is of particular interest by allowing the synthesis of organic compounds with diverse structures. Herein, the advances in the research areas of α-trifluoromethyl ketone synthesis and their defluorination reactions are reviewed. Discussion on the mechanisms of the typical reactions has also been provided, in hope of affording some guides to the chemistry of α-trifluoromethyl ketones in the synthetic methods toward themselves and their derivatives.

Key words: α-trifluoromethyl ketone, synthetic method, synthetic application, defluorination, cascade reaction

Cite this article

Sufang Cao, Yunyun Liu, Jieping Wan. Advances in the Synthesis of α-Trifluoromethyl Ketones and Their Application via Defluorinative Reactions[J]. Chinese Journal of Organic Chemistry, 2025, 45(1): 86-103.

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Fig. & Tab. 41

Figure 1. Bioactive molecules featuring α-trifluoromethyl ketone fragment

Scheme 1. Synthesis of α-trifluoromethyl ketones via the reactions of alkenes and CF3SO2Na

Scheme 2. Synthesis of α-trifluoromethyl ketones via the reactions of alkenes and TMSCF3

Scheme 3. Synthesis of α-trifluoromethyl ketones from alkenyl trifluoromethanesulfonates

Scheme 4. Et3B promoted synthesis of α-trifluoromethyl ketones from alkenyl trifluoromethanesulfonate

Scheme 5. Photocatalytic synthesis of α-trifluoromethyl ketones with product as photocatalyst

Scheme 6. Photocatalytic α-trifluoromethyl ketone synthesis with TFAA

Scheme 7. Electrochemical synthesis of α-trifluoromethyl ketones

Scheme 8. α-Trifluoromethyl ketone synthesis with CF3Br

Scheme 9. Photocatalytic synthesis of α-trifluoromethyl ketones with vinyl azides

Scheme 10. Photocatalytic synthesis of α-trifluoromethyl ketones with enol pyridinium salt

Scheme 11. Photocatalysis synthesis of α-trifluoromethyl ketones with alkenes and trifluoromethylsulfonyl pyridinium salt was the source of oxygen atom in the products (Scheme 12).

Scheme 12. Cu(II)-catalyzed synthesis of α-trifluoromethyl ketones with propionic acid and Togni’s reagent

Scheme 13. Ag-catalyzed α-trifluoromethyl ketone synthesis with alkynes and CF3SO2Na

Scheme 14. Photocatalytic synthesis of α-trifluoromethyl ketones with alkynes and Umemoto reagent

Scheme 15. Synthesis of α-trifluoromethyl ketones via alkyne hydration

Scheme 16. Light promoted synthesis of α-trifluoromethyl ketones from terminal alkynes

Scheme 17. Synthesis of α-trifluoromethyl ketones and β-keto esters

Scheme 18. Nucleophilic trifluoromethylation of α-bromoke- tones

Scheme 19. Two-step continuous flow synthesis of α-trifluo- romethyl ketones

Scheme 20. Cu-catalyzed decarboxylative trifluoromethylation of β-keto acids

Scheme 21. Photocatalytic C—H trifluoromethylation of methyl ketones

Scheme 22. Synthesis of α-trifluoromethyl ketones with enaminones

Scheme 23. Synthesis of α-trifluoromethyl ketones with sulfonium ylides and α-bromodifluoromethyl esters

Scheme 24. Ni and light co-catalytic synthesis of α-trifluoromethyl ketones

Scheme 25. NHC and visible light co-catalytic α-trifluorome- thyl ketone synthesis

Scheme 26. Photocatalytic synthesis of α-trifluoromethyl ketones with α-chloroketones

Scheme 27. C—CF3 bond cleavage of α-trifluoromethyl amides

Scheme 28. Synthesis of α-cyanoketones via full defluorination

Scheme 29. Synthesis of amides/ureas via C(O)—C bond cleavage

Scheme 30. Synthesis of sulfenylated alkenyl amides/esters via full C—F functionalization

Scheme 31. Double nucleophilic reactions of α-trifluoromethyl carbonyl compounds

Scheme 32. Three-component synthesis of 5-amino-1,2,3-triazoles

Scheme 33. Selective synthesis of 5-aminocarbonyl and 1-aryl- 5-amino-1,2,3-triazoles

Scheme 34. The three-component synthesis of 5-cyano-1,2,3- trizoles

Scheme 35. Synthesis of 1,3,4-oxadiazoles with α-trifluoro- methyl ketones

Scheme 36. Synthesis of fluorinated enones via double C—F functionalization

Scheme 37. Copper-catalyzed C—F functionalization for the synthesis of fluorinated sulfenyl alkenes

Scheme 38. Pd-catalyzed C—F functionalization for the synthesis of indol-1-yl functionalized fluoroalkenyl amides

Scheme 39. Synthesis of F-functionalized fused benzimidazole polyheterocycle

Scheme 40. Synthesis of fluorine-functionalized indolizines

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