Sodium Chloride → [(2R,3R)-3-(3-fluorophenyl)oxiran-2-yl]methanol

Participants

Reaction Conditions

Reaction Steps

An oven-dried, 3-neck, 2-L round bottom flask fitted with two oven-dried addition funnels and a rubber septum was charged with diisopropyl D-tartrate (11.55 g, 49.3 mmol, 0.30 equiv.), 4 Å powdered, activated molecular sieves (40 g) and dry dichloromethane (800 mL) under nitrogen. After being cooled to −25° C., to the reaction mixture was added titanium isopropoxide (9.6 mL, 33 mmol, 0.20 equiv.) slowly via a hypodermic syringe. After stirring for 10 minutes, anhydrous t-butyl hydroperoxide (5.5 M in decane, 75.0 mL, 413 mmol, 2.5 equiv.) was added at a moderate rate via an addition funnel. The resulting mixture was stirred at −25° C. for 30 minutes. trans-3-Fluorocinnamyl alcohol (25.0 g, 164 mmol) in dry dichloromethane (50 mL) was added dropwise via an addition funnel while maintaining the temperature at −25° C. After the addition, the reaction mixture was stirred at −25° C. for 1 hour and at −20° C. for another 3 hours. After the reaction was complete, cooled aqueous sodium hydroxide solution (30%, 20 mL) saturated with sodium chloride was added slowly at −20° C. After diethyl ether (150 mL) was added, the cold bath was removed and the mixture was allowed to warm to ˜5° C. and stirred for 1 hour. Magnesium sulfate (anhydrous, 50 g) was added and the mixture was stirred for 20 minutes, then filtered through a pad of silica gel, and washed with ether (300 mL). The filtrate was concentrated and toluene was used to azeotropically remove excess t-butyl hydroperoxide. The residual oil was purified on silica gel (0-30% ethyl acetate:hexane) to give 24.80 g (90%) of [(2R,3R)-3-(3-fluorophenyl)oxiran-2-yl]methanol as a viscous, colorless oil. Percent ee: >96.5%. MS (ESI) m/z 169.1 ([M+H]+).

Provenance & Evidence