Novel Synthesis of (E)-α-Fluorochalcones

Abstract

α-Fluorochalcones 4 can be synthesized by the Wittig reaction via α-fluoro substituted ylide 3, affoding a general method for the stereoselective synthesis of (E)-α-fluoro-α,β-unsaturated compounds 4.

Key words

α-fluorochalcones - Wittig reaction - synthesis

References

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General Procedure for the Stereoseletive Synthesis ofα-Fluorochalcones 4 (Method B): To the solution of benzoylmethylene triphenylphosphorane 1 (0.92 g, 2.0 mmol) in THF (20 mL), was added dropwise the solution of N-fluorodiphenylsulfonamide (0.63 g, 2.0 mmol) in THF (20 mL) at -20 °C. The mixture was stirred at r.t. for 3 h and a lot of precipitate was formed. After LDA (2 mmol) was added dropwise and the reaction mixture was stirred for 30 min, aldehyde (2 mmol) was added and the reaction mixture was stirred at r.t. for 27-40 h (see Table [1] ). After filtration, the filtrate was concentrated and subjected to preparative TLC (silica gel, hexane-ethyl acetate as eluent) to give
α-fluorochalcones 4a-e.

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4a: Mp 100-101 °C. ¹H NMR: δ (ppm) = 8.29 (d, 2 H, J = 8 Hz), 8.04 (d, 2 H, J = 8 Hz), 7.83 (d, 1 H, J = 16 Hz), 7.68-7.60 (m, 3 H), 7.58-7.50 (m, 2 H). MS: m/z (%) = 271(1) [M⁺], 77(100). Compound 4b: mp 89-90 °C. ¹H NMR:
δ (ppm) = 8.03 (d, 2 H, J = 8 Hz), 7.83 (d, 1 H, J = 16 Hz), 7.70-7.61 (m, 2 H), 7.51-7.48 (m, 3 H), 7.45-7.40 (m, 2 H). MS: m/z (%) = 244(4) [M⁺], 57(100). 4c: Mp 79-80 °C (Lit [9] 77 °C). ¹H NMR: δ (ppm) = 8.01 (d, 2 H, J = 8 Hz), 7.76 (d, 1 H, J = 16 Hz), 7.60-7.56(m, 2 H), 7.51-7.46 (m, 3 H), 7.40 (d, 2 H, J = 8 Hz). MS m/z (%) = 260(2) [M⁺], 157(100). 4d: Mp 52-53 °C (Lit [9] 54 °C). ¹H NMR: δ (ppm) = 8.01 (d, 2 H, J = 8 Hz), 7.81 (d, 1 H, J = 16 Hz), 7.65-7.61 (m, 2 H), 7.53-7.49 (m, 3 H), 7.44-7.40 (m, 2 H). MS m/z (%) = 226(13) [M⁺], 57(100). 4e: Mp 69-70 °C (Lit [9] 69 °C). ¹H NMR: δ (ppm) = 8.01(d, 2 H, J = 8 Hz), 7.79(d, 1 H, J = 16 Hz), 7.61-7.45 (m, 5 H), 7.23 (d, 1 H, J = 8 Hz), 2.40 (s, 3 H). MS m/z (%) = 240(2) [M⁺], 207(100).