Chlorotrimethylsilane → (5S)-5,6-dihydroxy-3-oxohexanoic tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a suspension of 9.82 g (150 mmol) of zinc dust in 40 mL of tetrahydrofuran was added 1.9 mL (15 mmol) of trimethylsilyl chloride at room temperature, and the mixture was stirred for 30 minutes. To this mixture were added 2.4 mL (10.5 mmol) of tert-butyl α-bromoacetate and 4.27 g (42 mmol) of (S)-β-hydroxy-γ-butyrolactone, and the temperature was increased to 65° C. At the same temperature, 15.3 mL (94.5 mmol) of tert-butyl α-bromoacetate was further added gradually over 30 minutes. After completion of addition, the mixture was further stirred at 65° C. for 30 minutes, at the end of which time the reaction mixture was cooled to room temperature and diluted with 50 mL of water. The reaction mixture was then adjusted to pH 6.8 with 20% aqueous NaOH solution and the precipitated solid was filtered off. The filtrate was extracted with 3 portions of ethyl acetate, 100 mL each, and the organic layers were combined and dehydrated over anhydrous sodium sulfate. The solvent was then distilled off under reduced pressure to give a yellow oil. This residue was purified by silica gel column chromatography (Kieselgel 60, product of Merck; hexane:acetone=5:1) to give 2.66 g of (5S)-5,6-dihydroxy-3-oxohexanoic tert-butyl ester (yellow oil). Yield 29%.

Provenance & Evidence