(1S,2R)-2-(phenylmethoxymethyl)cyclopent-3-en-1-ol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Cyclopentadiene (39 g., 0.59 mol.) at -20° was added over 35 minutes to a stirred mixture of 31.0 g. of 40% sodium sand in mineral oil (0.54 g. atm.) in 264 ml. of dry tetrahydrofuran at -15°. The mixture was stirred at -10° for 1.5 hours, warmed to 0°, and cannulated to an addition funnel at 0°. The mixture was then added over 30 minutes to a stirred solution of benzyl chloromethyl ether (100 g., 0.64 mol.) in 200 ml. of tetrahydrofuran at -50° to -55°. The mixture was stirred at -55° to -40° for 1 hour and then cooled to -65°. To this was added, by cannula over 5 minutes, the crystalline slurry of (-)-diisopinocampheylborane from step A, which had been cooled to -60°. The reaction was stirred at -60° for 1 hour, warmed to -10° and stored at -20° overnight. The reaction mixture was stirred for 1 hour at 5° and concentrated in vacuo to one half its original volume. Ether (600 ml.) was added, the stirred mixture was cooled to 0°, and 188 ml. of 3N sodium hydroxide was added dropwise keeping the temperature below 5°. Cold 30% hydrogen peroxide (188 ml.) was added dropwise over 1 hour keeping the temperature below 12°, and then the mixture was stirred for 1 hour longer while maintaining the temperature below 12°. The layers were separated, and the aqueous layer was washed with ether. The ether extracts were combined, dried(sodium sulfate), and concentrated in vacuo to a residue (337 g.). Chromatography of this residue on a column of Merck silica gel [2300 g., packed in petroleum ether-ether (2:1)] using petroleum ether-ether (2:1) and then (1:1)]gave fraction A (17.56 g. of impure desired product), fraction B (11.03 g. of pure desired product), and fraction C (3.52 g. of impure desired product). Similar chromatography of fraction A on 800 g. of silica gel, and fraction C on 140 g. of silica gel, gave 8.08 g. and 2.33 g., respectively, of additional pure desired product for a total yield of 21.44 g. of title compound. at -15° warmed to 0° cannulated to an addition funnel at 0° at -50° to -55° The mixture was stirred at -55° to -40° for 1 hour cooled to -65° To this was added, by cannula over 5 minutes The reaction was stirred at -60° for 1 hour warmed to -10° stored at -20° overnight The reaction mixture was stirred for 1 hour at 5° concentrated in vacuo to one half its original volume Ether (600 ml.) was added the stirred mixture was cooled to 0° of 3N sodium hydroxide was added dropwise the temperature below 5° Cold 30% hydrogen peroxide (188 ml.) was added dropwise over 1 hour the temperature below 12° the mixture was stirred for 1 hour longer while maintaining the temperature below 12° The layers were separated the aqueous layer was washed with ether dried(sodium sulfate), and concentrated in vacuo to a residue (337 g.) of silica gel, gave 8.08 g

Conditions: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The known title compound and the title compounds in sections C and D were prepared by modification of the method of K. Biggadike et al., J. Chem. Soc. Perkin Trans. 1, 549 (1988). Cyclopentadiene (28.68 g, 0.434 mol), maintained at -30°, was added over 1 hour to a stirred mixture of 22.5 g of 40% sodium sand in mineral oil (0.391 g atm) in dry tetrahydrofuran (156 ml) at -10° under nitrogen. After the addition, the mixture was cannulated to an addition funnel at 0° C. and added over 1.3 hours to a stirred solution of benzyl chloromethyl ether (65.2 ml, 0,469 mol) in tetrahydrofuran (130 ml) at -50° under nitrogen. After the addition, the reaction was stirred at -45° for 1.3 hours and then cooled to -60°. Tetrahydrofuran (390 ml) was added followed by the above preparation of (-)-diisopinocampheylborane (136 g, 0,477 mol). The reaction was stirred for 1 hour at -60° C., warmed to -10° C. over 1.5 hours and then stirred for 16 hours at +5°. After concentrating the reaction mixture in vacuo to one half of its original volume, ether (390 ml) was added. The stirred mixture was cooled to 0° and then 3N sodium hydroxide (156 ml, 0,469 mol) was added over 45 minutes keeping the temperature at 0°. Then, 30% hydrogen peroxide (156 ml) was added over 1 hour while maintaining the temperature below 12°. After the addition, the reaction was stirred for 1 hour at 10°, and then the layers were separated. The aqueous layer was washed with ether (300 ml) and all ether layers were combined, washed with aqueous sodium chloride, dried (sodium sulfate), and concentrated in vacuo to a residue. Chromatography of the residue on a column of Merck silica gel (5000 ml) using petroleum ether-ether (2:1) gave a 10 g fraction of impure desired product, a 15.72 g fraction of pure desired product, and a 2.7 g fraction of impure desired product. The 10.0 g and 2.7 g fractions were combined with 4.7 g of impure desired product from several other similar reactions, and the mixture was chromatographed over 1500 ml of Merck silica gel, using petroleum ether-ether (2:1 and then 1:1), to give an additional 8.00 g of pure desired product. After the addition the mixture was cannulated to an addition funnel at 0° C. After the addition cooled to -60° The reaction was stirred for 1 hour at -60° C. stirred for 16 hours at +5° After concentrating the reaction mixture in vacuo to one half of its original volume, ether (390 ml) was added The stirred mixture was cooled to 0° at 0° while maintaining the temperature below 12° After the addition the reaction was stirred for 1 hour at 10° the layers were separated The aqueous layer was washed with ether (300 ml) washed with aqueous sodium chloride dried (sodium sulfate) concentrated in vacuo to a residue