Asymmetric Fluorination of β-Keto Esters

Aqueous K₃PO₄ or other base (2 M, 2 equivalents, 0.1 mL) was added to a mixture of β-keto ester 9 (0.1 mmol, 24.4 mg, ω = 95%) and organocatalyst I–IX (2 mol%) in toluene or in CH₂Cl₂ (2 mL) under argon atmosphere. The mixture was cooled to −10℃ and NFSI (1.1 equivalents, 34.7 mg) was added in two portions over 2 h. The reaction mixture was stirred for another 12 h at −10 °C. After completion, the reaction was quenched by addition of NH₄Cl (aq. sat, 4 mL) and extracted with CH₂Cl₂ (10 mL). The organic phase was dried over anhydrous Na₂SO₄, filtered, and the volatiles were evaporated in vacuo. The residue was purified by column chromatography (Silica gel 60, EtOAc/n-Heptane = 1:15). Enantiomeric excess (ee) was determined by HPLC (Chiralpak AD-H, n-Hexane/i-PrOH = 200:1, flow rate 0.75 mL/min, λ = 250 nm, 10 °C) after isolation by column chromatography.