tert-Butyl hydroperoxide → (2S,3R)-3-(4-chlorophenyl)-2,3-epoxy-1-propanol

Participants

Reaction Conditions

Reaction Steps

To 520 ml of a methylene chloride solution of 10.98 g of titanium tetraisopropoxide cooled to -70° C., 12 ml of a methylene chloride solution of 12.07 g of D-(-)-diethyl tartarate was added dropwise, and the resulting mixture was stirred for 20 minutes. Then, 25 ml of a methylene chloride solution of 12.9 g of p-chlorocinnamyl alcohol was added dropwise, and the resulting mixture was stirred for 20 minutes. Then, 42.0 ml of t-butyl hydroperoxide (3.67 mol/l methylene chloride solution) was added dropwise, and the resulting mixture was stirred at 70° C. for 1.5 hours, at -40° C. for 2 hours and at -20° C. for 1.5 hours, and then brought to -10° C. over 1 hour and stirred at the same temperature for 2 hours. After it was cooled again to -20° C., 150 ml of an aqueous solution of 38.5 g of iron sulfate hexahydrate and 15.4 g of citric acid monohydrate was added dropwise over 0.5 hour below 5° C. The mixture was stirred vigorously at 0° C. for 0.5 hour and filtered through celite. The filtrate was allowed to separate, and the aqueous layer was extracted again with methylene chloride. The organic layers were combined and washed with a saturated sodium hydrogen carbonate aqueous solution, water and a saturated saline solution. After the solvent was distilled off, the residue was dissolved in diethyl ether, and sodium sulfate and activated carbon were added, and the mixture was allowed to stand for 0.5 hour. The mixture was filtered through celite, and the ether solution thus obtained was cooled with ice. 172 ml of 1N sodium hydroxide aqueous solution was added, and then, the resulting mixture was stirred vigorously for 1 hour. After it was allowed to separate, the organic layer was washed with water (twice) and with a saturated saline solution, treated with activated carbon and filtered through celite. After the solvent was distilled off, the residue was purified by silica gel chromatography (eluent; methanol/chloroform=1/99) and crystallized from cyclohexane to obtain 6.35 g of the title compound as white crystals of [α]D25 +39.42° (chloroform, c 1.042).

Provenance & Evidence