CSC.B.[Br:5][C:6]1[CH:11]=[CH:10][C:9]([C@@H:12]([N:14]2[CH2:23][CH2:22][C:17]3([CH2:21][CH:20]=[CH:19][CH2:18]3)[O:16][C:15]2=[O:24])[CH3:13])=[CH:8][CH:7]=1.C([OH:28])(C)C>O1CCCC1>[Br:5][C:6]1[CH:11]=[CH:10][C:9]([C@@H:12]([N:14]2[CH2:23][CH2:22][C:17]3([CH2:21][CH:20]([OH:28])[CH2:19][CH2:18]3)[O:16][C:15]2=[O:24])[CH3:13])=[CH:8][CH:7]=1Borane dimethyl sulfide complex (2 mol/L in diethyl ether, 4.64 mL) is added dropwise to a solution of 8-[(S)-1-(4-bromo-phenyl)-ethyl]-6-oxa-8-aza-spiro[4.5]dec-2-en-7-one (2.60 g) in tetrahydrofuran (30 mL) chilled in an ice bath. The cooling bath is removed and the solution is stirred at room temperature overnight. The solution is then chilled again in an ice bath and 4 M aqueous NaOH solution (2.1 mL) is added followed by the dropwise addition of hydrogen peroxide (35% in water, 6 mL). The cooling bath is removed and the mixture is warmed to 40° C. and stirred at this temperature for 1 h. The mixture is diluted with water and extracted with diethyl ether. The combined extracts are washed with water, dried (Na2SO4), and concentrated. The residue is chromatographed on silica gel (methanol/ethyl acetate 0:1→4:1) to afford a mixture of the four title compounds which is submitted to SFC (Supercritical Fluid Chromatography) on chiral phase (column: phenomenex LUX 2A, 250×20 mm, 5 μM; eluent: isopropanol containing 0.2% diethylamine/sc carbon dioxide 25:75; flow: 60 mL/min) to give the four isomers in separate fractions.
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