Methyl phenylacetate → methyl (2S)-2-hydroxy-2-phenylacetate

Participants

Reaction Steps

Experimental description: 90 mg methyl 2-phenyl acetate was dissolved in 500 μL ethanol and added to 240 mL potassium phosphate buffer pH 8.0. P450BM3 was added to the mixture at a final concentration of 2 μM. The mixture was split in 4 mL aliquots into 15 mL scintillation vials equipped with a stir bar. 500 μL of a 5 mM NADPH solution was added to each vial and stirred for 2 minutes. 500 μL of a cofactor regeneration solution containing 300 mM glucose-6-phosphate and 10 units/mL glucose-6-phosphate dehydrogenase were then added to each vial. The resulting mixtures were stirred at room temperature. After 4 hours, the reaction mixtures were joined together and extracted with chloroform (3×100 mL). The organic phase was then dried over magnesium sulfate (MgSO4) and evaporated in vacuo. Purification of the resulting oil by silica gel chromatography (5% ethyl acetate:95% hexane) afforded the activated product ((S)-methyl 2-hydroxy-2-phenylacetate, 40.5 mg). 40 mg (0.24 mmol) of activated product was dissolved in 2 mL dry dichloromethane (CH2Cl2) and a catalytic amount (4 drops) of ethanol was added to the solution. The solution was cooled to −78° C. (dry ice) and then 41 μL DAST (0.29 mmol) was added. The reaction was stirred in dry ice for 12 hours. The reaction mixture was then added with 5 mL saturated sodium bicarbonate (NaHCO3) and extracted with dichloromethane (3×15 mL). The organic phase was then dried over magnesium sulfate (MgSO4) and evaporated in vacuo. Purification of the resulting oil by silica gel chromatography (5% ethyl acetate:95% hexane) afforded the fluorinated product ((R)-methyl 2-fluoro-2-phenylacetate) (30 mg, 75% yield, pale yellow oil) in 74% ee, as determined by chiral GC analysis. 1H-NMR (300 MHz, CDCl3): δ 3,75 (s, 3H, —OCH3), δ 5.77 (d, J=48 Hz, 1H, —CHF), δ 7.37-7.46 (m, 5H); 13C-NMR (75 MHz, CDCl3): δ2.8, 89.5 (d, J=184.5 Hz), 126.8, 126.9, 129.0, δ 129.9, δ 134.4 (d, J=34.5 Hz), δ 169.0. 19F-NMR (282 MHz, CDCl3): δ −180.29 (d, J=48.7 Hz). HRMS (EI+): exact mass calculated for C9H9FO2 requires m/z 168.0587, found 168.0594.

Provenance & Evidence