Trifluoroacetic Acid Derivatives as Nucleophilic Trifluoromethylating Reagents

Abstract

Secondary trifluoroacetamides and alkyl trifluoroacetates can be used as nucleophilic trifluoromethylating reagents towards non-enolizable ketones by action of potassium tert-butoxide.

Key words

trifluoromethylation - trifluoroacetamide - fluorinated compounds - trifluoromethylcarbinols - tetrahedral intermediate

References

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Typical Procedure: To a solution of 2a (1 mmol) and the electrophile (1 mmol) in DMF (1 mL) was added a 1 M solution of t-BuOK in THF (1 mL). After 24 h, the crude mixture was hydrolyzed by HCl 1 M (1 mL) overnight and extracted with diethyl ether. The organic phase was dried on Na₂SO₄ and the the solvent removed in vacuo. The crude products were purified by chromatography over silica gel.
Spectral Data: Compound 4b: ¹H NMR (300 MHz, CDCl₃): δ = 8.61-8.63 (massif, 1 H), 7.70-7.78 (m, 3 H), 7.50-7.55 (m, 1 H), 7.32-7.47 (m, 4 H), 7.06 (br s, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 155.3, 147.6, 138.7, 137.9, 129.0, 128.9, 127.4 (q, J = 2.1 Hz), 125.5 (q, J = 286.4 Hz), 124.4, 123.3 (q, J = 1.9 Hz), 78.1 (q, ² J _C-F = 28.9 Hz). ¹⁹F NMR (282 MHz, CDCl₃): δ = -75.19. MS: m/z = 253 (M⁺ ), 184, 176, 106, 78, 77, 69, 51. Compound 4f: ¹H NMR (300 MHz, CDCl₃): δ = 8.61 (d, 2 H, J = 4.7 Hz), 8.13 (d, 2 H, J = 8.1 Hz), 7.75 (td, 2 H, J = 7.8 Hz, J = 7.7 Hz), 7.42 (s, 1 H), 7.30 (dd, J = 7.5 Hz, J = 4.9 Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 155.4, 148.0, 137.5, 124.9 (q, J = 286.4 Hz), 124.2, 123.6 (q, J = 1.7 Hz), 77.5 (q, J = 28.3 Hz). ¹⁹F NMR (282 MHz, CDCl₃): δ = -76.47. MS: m/z = 254 (M⁺ ), 237, 185, 176, 106, 78, 52.

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Inschauspe, D.; Sortais, J.-B.; Billard, T.; Langlois, B. R. Synlett 2002, in press.